Infectious Diseases — High-Yield Notes (PDF)

Sepsis

Life-threatening organ dysfunction caused by a dysregulated host response to infection. Defined by the Sepsis-3 criteria (SOFA score ≥2). Affects ~250,000 people per year in the UK with a mortality of 15–20% overall and up to 40–50% in septic shock.

MRCP Part 1 · MRCP Part 2 · PLAB 1 · UKMLA · MRCGP AKT · MSRA

Key Facts

Sepsis-3 definition: life-threatening organ dysfunction due to dysregulated host response to infection - identified by SOFA score ≥2 (or qSOFA ≥2 for screening)
NICE NG51: recommends using NEWS2 for sepsis screening in UK hospitals - escalate if NEWS2 ≥5 or high-risk criteria met
Sepsis Six (within 1 hour): 3 in (oxygen, IV fluids, IV antibiotics) and 3 out (blood cultures, lactate, urine output monitoring)
Empirical antibiotics within 1 hour: piperacillin-tazobactam 4.5g IV TDS or per local protocol; source-guided once culture results available
IV fluid resuscitation: 500ml 0.9% NaCl bolus over 15 min, repeat up to 30 ml/kg if hypotensive or lactate >2 mmol/L
Lactate >2 mmol/L indicates tissue hypoperfusion - serial measurements guide response to treatment
Surviving Sepsis Campaign 2021: 1-hour bundle (cultures, lactate, antibiotics, fluids, vasopressors if needed)
UK mortality: ~48,000 deaths/year; sepsis accounts for ~1 in 5 hospital deaths

Overview

Key Facts

Sepsis is one of the leading causes of death worldwide and in the UK. Early recognition using structured screening tools (NEWS2) and prompt delivery of the Sepsis Six bundle significantly reduces mortality. The 2016 Sepsis-3 definitions replaced the older SIRS criteria.

Epidemiology

~250,000 cases per year in the UK; ~48,000 deaths annually
Incidence increasing due to ageing population, immunosuppression, antimicrobial resistance
In-hospital mortality: 15–20% for sepsis, 40–50% for septic shock
Leading cause of preventable death in hospitals
Disproportionately affects extremes of age, immunocompromised, and those with chronic disease

Aetiology

Common sources:

Respiratory (~40%): pneumonia
Urinary (~20%): UTI, pyelonephritis
Abdominal (~15%): peritonitis, cholangitis, appendicitis
Skin/soft tissue (~10%): cellulitis, necrotising fasciitis
Line-related (~5%): central venous catheter infections
Other: endocarditis, meningitis, bone/joint infections

Common organisms:

Gram-positive: S. aureus, S. pneumoniae, Enterococcus
Gram-negative: E. coli, Klebsiella, Pseudomonas
Fungi: Candida (especially in ICU, immunocompromised)

Pathophysiology

Infection triggers innate immune response → pattern recognition receptors (TLRs) detect PAMPs
Cytokine storm: TNF-α, IL-1, IL-6 → systemic inflammation

Endothelial dysfunction

increased vascular permeability

distributive shock

Coagulation activation

microvascular thrombosis

DIC

Mitochondrial dysfunction → impaired cellular oxygen utilisation
Organ dysfunction: AKI, ARDS, hepatic dysfunction, encephalopathy, myocardial depression

Clinical Presentation

Typical Presentation

Fever (>38°C) or hypothermia (<36°C)
Tachycardia (HR >90)
Tachypnoea (RR >20)
Altered mental state (new confusion - very sensitive early sign)
Hypotension (SBP <90 or MAP <65)

Source-Specific Features

Respiratory: cough, dyspnoea, pleuritic chest pain, consolidation
Urinary: dysuria, frequency, loin pain
Abdominal: pain, tenderness, rigidity, absent bowel sounds
Skin: erythema, warmth, fluctuance, crepitus (necrotising fasciitis)
CNS: headache, neck stiffness, photophobia, non-blanching rash

Red Flags (NICE NG51 high-risk criteria)

SBP ≤90 mmHg (or drop >40 from baseline)
Heart rate >130
Respiratory rate ≥25
Lactate >2 mmol/L
New need for oxygen to maintain SpO2 >92%
Non-blanching rash, mottled/ashen/cyanotic skin
Not passed urine in 18 hours (or <0.5 ml/kg/hr)
Recent chemotherapy

Differential Diagnosis

Diagnosis	Key Features	Investigation
Cardiogenic shock	History of MI/heart failure, raised JVP, pulmonary oedema	ECG, troponin, echo, BNP
Hypovolaemic shock	Haemorrhage, dehydration, GI losses	FBC, lactate, imaging for bleeding source
Anaphylaxis	Acute onset, urticaria, angioedema, known allergen exposure	Clinical diagnosis, tryptase
Pancreatitis	Epigastric pain radiating to back, vomiting	Amylase/lipase, CT abdomen
Adrenal crisis	Hypotension, hyperkalaemia, hyponatraemia, pigmentation	Cortisol, Synacthen test
PE	Pleuritic pain, sudden dyspnoea, risk factors	CTPA, D-dimer
Drug reaction	Temporal relationship, eosinophilia, rash	Drug history, eosinophil count

Diagnosis / Investigation

Bedside

NEWS2 score: calculate and escalate appropriately
Blood glucose: hypoglycaemia or hyperglycaemia
VBG/ABG: pH, lactate (most important prognostic marker), bicarbonate
Urinalysis: MSU if urinary source suspected
ECG: exclude MI, new arrhythmia

Bloods

Blood cultures: minimum 2 sets (peripheral ± line) BEFORE antibiotics
FBC: leucocytosis or leucopenia, thrombocytopenia
U&Es: AKI
LFTs: hepatic dysfunction
CRP/procalcitonin: inflammation markers
Lactate: >2 mmol/L indicates tissue hypoperfusion; >4 mmol/L associated with >40% mortality
Coagulation screen: DIC (prolonged PT/APTT, low fibrinogen, raised D-dimer)
Blood gas: metabolic acidosis

Imaging

CXR: pneumonia, ARDS
CT abdomen/pelvis: intra-abdominal source (abscess, perforation, cholangitis)
CT head: if CNS source suspected
Echocardiography: if endocarditis suspected or to assess cardiac function in shock

Special Tests

Lumbar puncture: if meningitis suspected (after CT if raised ICP signs)
Joint aspiration: if septic arthritis suspected
Procalcitonin: may guide antibiotic duration (PRORATA, SAPS trials)

Management

Non-pharmacological

Sepsis Six bundle (complete within 1 hour):
1. Give high-flow oxygen (target SpO2 94–98%)
2. Take blood cultures
3. Give IV antibiotics
4. Give IV fluids
5. Measure lactate
6. Measure urine output (catheterise)

Pharmacological

Antibiotics (within 1 hour - NICE NG51):

Empirical: piperacillin-tazobactam 4.5g IV TDS (or per local antimicrobial guidelines)
If penicillin allergy: meropenem 1g IV TDS
Unknown source with septic shock: add gentamicin 5mg/kg IV
Suspected MRSA: add vancomycin 15–20 mg/kg IV BD
Suspected meningitis: ceftriaxone 2g IV BD
Review at 48–72 hours: narrow spectrum based on cultures (antimicrobial stewardship)

IV fluid resuscitation:

500ml 0.9% NaCl bolus over 15 min
Repeat up to 30 ml/kg in first 3 hours if hypotensive/lactate elevated
Reassess fluid status after each bolus (avoid fluid overload)

Vasopressors (if MAP <65 despite fluids):

Noradrenaline: first-line vasopressor (0.05–0.5 mcg/kg/min) - requires ICU/critical care setting
Vasopressin: 0.03 units/min as adjunct to noradrenaline
Hydrocortisone 50mg QDS IV: for refractory septic shock (ADRENAL, APROCCHSS trials support use)

Landmark trials:

PROCESS, ARISE, ProMISe: early goal-directed therapy no better than usual care
ADRENAL/APROCCHSS: hydrocortisone in septic shock - faster shock reversal, possible mortality benefit
Surviving Sepsis Campaign 2021: updated international guidelines

Surgical/Interventional

Source control: drain abscesses, remove infected devices, debride necrotic tissue - within 6–12 hours
Central venous access: for vasopressors, monitoring
Arterial line: for continuous BP monitoring in shock

Referral Criteria

ICU/critical care: septic shock, multi-organ failure, need for vasopressors/ventilation
Surgical team: if source requires operative intervention
Microbiology/infectious diseases: complex infections, unusual organisms, persistent bacteraemia

Prognosis

Overall sepsis mortality: 15–20%
Septic shock mortality: 40–50%
Each hour delay in antibiotics increases mortality by ~4–8%
Lactate >4 mmol/L: ~40% mortality
1-year mortality after sepsis: ~40% (including post-discharge deaths)
Long-term sequelae: cognitive impairment, PTSD, chronic fatigue, functional decline in ~50% of survivors
Re-hospitalisation rate within 90 days: ~40%
Compliance with Sepsis Six bundle reduces mortality by ~20%

Other Relevant Information

Sepsis-3 Definitions

Term	Definition
Sepsis	Life-threatening organ dysfunction (SOFA ≥2) due to infection
Septic shock	Sepsis + vasopressor requirement for MAP ≥65 + lactate >2 despite adequate fluid resuscitation
qSOFA	≥2 of: RR ≥22, altered mentation, SBP ≤100

Sepsis Six Bundle (Within 1 Hour)

Give (3 In)	Take (3 Out)
High-flow oxygen	Blood cultures
IV antibiotics	Serum lactate
IV fluids (500ml bolus)	Urine output measurement

NEWS2 Escalation

NEWS2 Score	Clinical Risk	Response
0–4	Low	Routine monitoring
5–6 (or 3 in single parameter)	Medium	Urgent review
≥7	High	Emergency response, consider ICU

NICE Guidelines / CKS

Septic Shock

A subset of sepsis with circulatory and cellular/metabolic dysfunction characterised by persistent hypotension requiring vasopressors to maintain MAP ≥65 mmHg and lactate >2 mmol/L despite adequate fluid resuscitation. Carries in-hospital mortality of 40–50%.

MRCP Part 1 · MRCP Part 2 · PLAB 1 · UKMLA · MRCGP AKT · MSRA

Key Facts

Sepsis-3 definition: sepsis + need for vasopressors to maintain MAP ≥65 mmHg + lactate >2 mmol/L despite adequate fluid resuscitation
Noradrenaline is the first-line vasopressor - start at 0.05 mcg/kg/min, titrate to MAP ≥65 mmHg
Stress-dose steroids: hydrocortisone 50mg IV QDS if shock refractory to fluids + vasopressors (APROCCHSS trial)
Target MAP ≥65 mmHg - higher targets (80 mmHg) showed no benefit in SEPSISPAM trial (except in chronic hypertension)
30 ml/kg crystalloid within first 3 hours for initial resuscitation; 0.9% NaCl or balanced crystalloid (Hartmann's/Plasmalyte)
Lactate clearance >20% in first 6 hours associated with improved survival - serial monitoring essential
Mortality 40–50% in-hospital; each hour of delayed vasopressor initiation increases mortality
ICU management essential: invasive monitoring (arterial line, CVC), organ support, source control within 6–12 hours

Overview

Key Facts

Septic shock represents the most severe manifestation of sepsis, characterised by profound circulatory, cellular, and metabolic abnormalities that substantially increase mortality beyond sepsis alone. Prompt fluid resuscitation, early antibiotics, and vasopressor support are the cornerstones of management.

Epidemiology

~50,000 cases per year in the UK
In-hospital mortality: 40–50% (despite modern intensive care)
Accounts for 10% of ICU admissions
1-year mortality: ~60%
Most common cause of death in non-cardiac ICU patients

Aetiology

Same infectious sources as sepsis, but with more severe host response
Gram-negative bacteraemia: higher incidence of shock vs Gram-positive
Polymicrobial infections: higher mortality
Fungal sepsis (Candida): increasing incidence in ICU, high mortality (~50%)
Abdominal source: higher rate of shock than other sources

Pathophysiology

Massive cytokine release

systemic vasodilation

distributive shock

Endothelial glycocalyx disruption

capillary leak

tissue oedema and hypovolaemia

Myocardial depression: cytokine-mediated (TNF-α, IL-1β) → reduced cardiac output
Mitochondrial dysfunction → impaired oxygen utilisation despite adequate delivery (cytopathic hypoxia)

Microvascular thrombosis

DIC

multi-organ failure

Relative adrenal insufficiency → impaired vasopressor response

Result: inadequate tissue oxygen delivery and utilisation

anaerobic metabolism

lactic acidosis

cell death

Clinical Presentation

Early (Warm Shock)

Flushed, warm peripheries (vasodilation)
Bounding pulse, wide pulse pressure
Tachycardia, tachypnoea
Hypotension (SBP <90 or MAP <65)
Confusion, agitation
Fever or hypothermia

Late (Cold Shock)

Cool, mottled, clamped peripheries
Weak, thready pulse
Profound hypotension
Oliguria/anuria
Reduced consciousness → obtundation

Multi-Organ Failure

Respiratory: ARDS - bilateral infiltrates, PaO2/FiO2 <300
Renal: AKI - oliguria, rising creatinine
Hepatic: coagulopathy, jaundice, raised transaminases
Haematological: DIC - thrombocytopenia, prolonged PT/APTT
Neurological: septic encephalopathy - confusion, delirium, coma

Red Flags

MAP <65 despite 30 ml/kg fluid resuscitation
Lactate >4 mmol/L (or rising despite treatment)
Vasopressor requirement escalating rapidly
PaO2/FiO2 <200 (severe ARDS)
Anuria >6 hours
Mottled skin, prolonged capillary refill >5 seconds

Differential Diagnosis

Diagnosis	Key Features	Investigation
Cardiogenic shock	Raised JVP, pulmonary oedema, cold peripheries	Echo, troponin, BNP, PA catheter
Hypovolaemic shock	Haemorrhage, dehydration, flat JVP	FBC, group & save, imaging
Obstructive shock (PE/tamponade)	Raised JVP, distended neck veins, pulsus paradoxus	CTPA, echo
Anaphylactic shock	Urticaria, angioedema, wheeze, allergen exposure	Tryptase
Neurogenic shock	Spinal injury, bradycardia + hypotension, warm extremities	History, imaging
Adrenal crisis	Chronic steroid use, pigmentation, hyponatraemia + hyperkalaemia	Cortisol, Synacthen test
Toxic shock syndrome	Desquamating rash, mucosal involvement, S. aureus/GAS	Cultures, toxin testing

Diagnosis / Investigation

Bedside

Arterial blood gas: pH, lactate, PaO2/FiO2 ratio - serial measurements
NEWS2 score: will be high (≥7)
Blood glucose: stress hyperglycaemia or hypoglycaemia
ECG: arrhythmias, new ischaemia
Bladder catheter: hourly urine output monitoring

Bloods

Blood cultures: before antibiotics (peripheral + central line)
FBC: leucocytosis/leucopenia, thrombocytopenia
U&Es: AKI
LFTs: hepatic dysfunction
Lactate: serial (every 2–4 hours) - target clearance >20% in 6 hours
Coagulation: PT, APTT, fibrinogen, D-dimer (DIC screen)
CRP, procalcitonin: inflammation
Cortisol: if adrenal insufficiency suspected

Imaging

CXR: ARDS, pneumonia
CT with contrast: source identification (abdominal collection, perforation)
Echocardiography: assess cardiac function, guide fluid management

Special Tests

Central venous pressure (CVP): guide fluid resuscitation (target 8–12 mmHg)
ScvO2 (central venous oxygen saturation): <70% suggests inadequate oxygen delivery
Point-of-care USS: IVC diameter for volume assessment, lung USS for ARDS
Cardiac output monitoring: PiCCO, LiDCO in complex cases

Management

Non-pharmacological

ICU admission: mandatory for vasopressor therapy
Invasive monitoring: arterial line (continuous BP), CVC (for vasopressors and CVP)
Lung-protective ventilation: if intubated - tidal volume 6 ml/kg IBW, plateau pressure <30 cmH2O
Prone positioning: for severe ARDS (PaO2/FiO2 <150) - PROSEVA trial
Blood glucose control: target 6–10 mmol/L (NICE-SUGAR trial)
VTE prophylaxis: LMWH unless contraindicated
Source control within 6–12 hours: drain collections, remove infected devices, debride necrotic tissue

Pharmacological

Antibiotics:

Administer within 1 hour - broad-spectrum empirical then de-escalate
Same principles as sepsis but with broader cover initially

Fluid resuscitation:

30 ml/kg crystalloid (0.9% NaCl or balanced solution e.g. Plasmalyte) within 3 hours
Reassess with dynamic measures (pulse pressure variation, passive leg raise)
Avoid fluid overload: positive fluid balance associated with worse outcomes
CLASSIC trial: restrictive vs liberal fluids in septic shock - restrictive strategy appears safe

Vasopressors:

Noradrenaline: first-line, 0.05–0.5 mcg/kg/min, titrate to MAP ≥65
Vasopressin: 0.03 units/min as second agent (VASST trial)
Adrenaline: third-line if above insufficient
Dobutamine: if evidence of myocardial dysfunction (low CO despite adequate filling)

Corticosteroids:

Hydrocortisone 50mg IV QDS (200mg/day) if shock refractory to fluids + noradrenaline ≥0.25 mcg/kg/min
APROCCHSS trial: hydrocortisone + fludrocortisone reduced 90-day mortality
ADRENAL trial: faster shock reversal but no significant mortality difference

Organ support:

RRT/CRRT: for AKI with standard indications
Stress ulcer prophylaxis: IV PPI (omeprazole 40mg) - SUP-ICU trial suggests may not be needed in all patients

Surgical/Interventional

Source control: essential within 6–12 hours
Interventional radiology: percutaneous drainage of collections
ECMO: in refractory ARDS or cardiac failure (case-by-case basis)

Referral Criteria

All patients require ICU/critical care
Surgical/IR input for source control
Microbiology for complex infections
Renal team if RRT needed

Prognosis

In-hospital mortality: 40–50%
ICU mortality: 30–40%
90-day mortality: ~45–55%
1-year mortality: ~60%
Lactate >4 mmol/L: mortality >40%
Need for ≥2 vasopressors: mortality >50%
New-onset ARDS: mortality increases to ~50–60%
Survivors: ~30% develop new functional disability; ~25% develop PTSD/depression
Long-term cognitive impairment in ~30–40% of sepsis survivors
Re-hospitalisation within 90 days: ~40%

Other Relevant Information

SOFA Score Components

Organ System	Variable	Score 0–4
Respiration	PaO2/FiO2	>400 to <100
Coagulation	Platelets	>150 to <20
Liver	Bilirubin	<20 to >204 µmol/L
Cardiovascular	MAP/vasopressors	MAP ≥70 to high-dose vasopressors
CNS	GCS	15 to <6
Renal	Creatinine/UO	<110 to >440 µmol/L

Key Landmark Trials in Septic Shock

Trial	Key Finding
APROCCHSS	Hydrocortisone + fludrocortisone reduced 90-day mortality
ADRENAL	Hydrocortisone: faster shock reversal, no significant mortality benefit
VASST	Vasopressin + noradrenaline: no overall mortality benefit but possible benefit in less severe shock
ProMISe/ARISE/PROCESS	Protocolised EGDT no better than usual care
SEPSISPAM	MAP target 65 vs 80: no difference (except fewer arrhythmias with 65)
NICE-SUGAR	Intensive glucose control (4.5–6) increases mortality vs conventional (6–10)

NICE Guidelines / CKS

HIV and AIDS

Human immunodeficiency virus (HIV) is a retrovirus that targets CD4+ T cells, leading to progressive immunodeficiency. AIDS is defined as CD4 count <200 cells/µL or an AIDS-defining illness. Modern antiretroviral therapy (ART) achieves viral suppression in >95% and near-normal life expectancy.

MRCP Part 1 · MRCP Part 2 · PLAB 1 · UKMLA · MRCGP AKT · MSRA

Key Facts

UK prevalence: ~106,000 people living with HIV; estimated 5,150 undiagnosed (2022 data)
BHIVA guidelines: start ART in all patients regardless of CD4 count - as soon as possible after diagnosis (START trial)
First-line ART: typically 2 NRTIs + 1 integrase inhibitor - e.g. tenofovir/emtricitabine + dolutegravir (NICE NG211)
U=U (Undetectable = Untransmittable): patients with sustained viral load <200 copies/mL do not transmit HIV sexually (PARTNER, PARTNER2 trials)
AIDS-defining illnesses: PCP, cerebral toxoplasmosis, CMV retinitis, oesophageal candidiasis, Kaposi sarcoma, TB, cryptococcal meningitis, PML, NHL
CD4 <200: prophylaxis with co-trimoxazole 960mg OD (PCP prevention); CD4 <100 + CMV IgG+: regular fundoscopy
HIV indicator conditions (test for HIV): TB, lymphoma, hepatitis B/C, mononucleosis-like illness, unexplained weight loss, herpes zoster in <65s
PEP (post-exposure prophylaxis): tenofovir/emtricitabine + raltegravir within 72 hours of exposure, for 28 days

Overview

Key Facts

HIV infection remains a major public health concern in the UK. Early diagnosis and treatment with ART is key to achieving viral suppression, preventing transmission, and enabling near-normal life expectancy. The UK has adopted the UNAIDS 95-95-95 targets.

Epidemiology

~106,000 people living with HIV in the UK (PHE/UKHSA data)
New diagnoses: ~3,000–4,000 per year (declining)
Late diagnosis (CD4 <350 at diagnosis): ~42% - associated with 10-fold increased mortality in first year
Men who have sex with men (MSM): largest affected group; heterosexual transmission second
Mother-to-child transmission rate <0.5% with effective interventions
Life expectancy with early ART: near-normal

Aetiology

HIV-1: predominant worldwide (subtypes A–K); HIV-2: West Africa, less pathogenic
Transmission: sexual (vaginal, anal), parenteral (needlestick, IVDU), vertical (pregnancy, delivery, breastfeeding)
NOT transmitted by: casual contact, kissing, sharing utensils, mosquitoes

Pathophysiology

HIV is an RNA retrovirus (Retroviridae, genus Lentivirus)
Binds CD4 receptor + co-receptor (CCR5 or CXCR4) on T-helper cells, macrophages, dendritic cells

Reverse transcriptase converts RNA

DNA

integration into host genome (provirus)

Viral replication destroys CD4+ T cells → progressive immunodeficiency

Acute seroconversion: viraemia peak

immune response

set point viral load

Without treatment: CD4 declines ~50–80 cells/µL per year → AIDS in ~8–10 years
Chronic immune activation drives comorbidities (CVD, neurocognitive decline, malignancy)

Clinical Presentation

Primary HIV Infection (Seroconversion - 2–6 weeks post-exposure)

Occurs in ~60–80% of newly infected; often misdiagnosed as glandular fever
Fever, sore throat, lymphadenopathy, maculopapular rash, myalgia
Oral ulceration, diarrhoea, headache
Rarely: aseptic meningitis, Guillain-Barré syndrome

Asymptomatic Phase (Clinical Latency)

May last years without treatment
Persistent generalised lymphadenopathy
Gradual CD4 decline

Symptomatic HIV (CD4 200–500)

Oral candidiasis, oral hairy leukoplakia
Herpes zoster (multidermatomal)
Seborrhoeic dermatitis, recurrent bacterial infections
Constitutional symptoms: weight loss, night sweats, diarrhoea

AIDS (CD4 <200 or AIDS-defining illness)

PCP (Pneumocystis jirovecii pneumonia): dry cough, dyspnoea, bilateral perihilar infiltrates
Cerebral toxoplasmosis: ring-enhancing lesions, seizures, focal neurology
Cryptococcal meningitis: headache, fever, raised ICP
CMV: retinitis (pizza-pie fundus), colitis, oesophagitis
Kaposi sarcoma: violaceous skin lesions, HHV-8 associated
TB: pulmonary or extrapulmonary (atypical presentations at low CD4)

Red Flags

Fever with new respiratory symptoms in known/suspected HIV
New neurological symptoms (headache, confusion, focal signs)
New visual symptoms (CMV retinitis emergency)
Severe weight loss (>10% body weight)
CD4 <100 with any new symptom

Differential Diagnosis

Diagnosis	Key Features	Investigation
Glandular fever (EBV)	Similar to seroconversion; pharyngitis, splenomegaly	Monospot, EBV serology
CMV primary infection	Fever, lymphocytosis, hepatitis	CMV IgM, PCR
Acute hepatitis B	Jaundice, RUQ pain, risk factors overlap	HBsAg, anti-HBc IgM
Secondary syphilis	Rash (palms/soles), lymphadenopathy, condylomata	RPR/VDRL, TPHA
Lymphoma	Lymphadenopathy, B symptoms, splenomegaly	Biopsy, LDH, imaging
Tuberculosis	Weight loss, night sweats, cough - co-infection common	CXR, sputum AFB/culture, IGRA

Diagnosis / Investigation

Bedside

HIV test: 4th-generation combined antigen/antibody test (detects p24 antigen + HIV-1/2 antibodies)
Window period: 45 days for 4th-gen test
Point-of-care rapid test: fingerprick - result in 20 minutes

Bloods

Confirmatory test: HIV-1/2 differentiation assay
HIV RNA viral load: quantify viraemia (baseline and monitoring)
CD4 count: staging and prophylaxis decisions
HIV resistance genotyping: before starting ART
FBC, U&Es, LFTs, lipids, glucose, HbA1c: baseline metabolic assessment
Hepatitis B/C serology: high co-infection rates
Syphilis serology: RPR/VDRL + TPHA
Toxoplasma IgG: baseline (for future prophylaxis decisions)
CMV IgG: baseline
HLA-B*5701: before abacavir (hypersensitivity risk)

Imaging

CXR: baseline and if respiratory symptoms
CT/MRI brain: if neurological symptoms

Special Tests

Cervical smear: annual (increased HPV/cervical cancer risk)
DEXA scan: if risk factors for osteoporosis
Cardiovascular risk assessment: QRISK3 (HIV increases CV risk)
Neurocognitive screening: for HIV-associated neurocognitive disorder

Management

Non-pharmacological

Partner notification: supported by sexual health services
Barrier contraception advice
Smoking cessation, lifestyle modification: CV risk reduction
Psychological support: high rates of depression, stigma
Adherence support: essential for viral suppression

Pharmacological

Antiretroviral therapy (ART) - start in ALL patients (NICE NG211, BHIVA):

Preferred first-line: tenofovir alafenamide/emtricitabine + dolutegravir (TAF/FTC + DTG)
Alternative: tenofovir disoproxil/emtricitabine + dolutegravir (TDF/FTC + DTG)
Single-tablet regimens available: Triumeq (ABC/3TC/DTG), Biktarvy (TAF/FTC/BIC)
Viral load target: <50 copies/mL by 6 months

Opportunistic infection prophylaxis:

CD4 <200: co-trimoxazole 960mg OD (PCP prophylaxis) - continue until CD4 >200 for 3 months
CD4 <100 + Toxoplasma IgG+: co-trimoxazole also covers toxoplasmosis
CD4 <50 + CMV IgG+: regular fundoscopy; consider valganciclovir if retinitis
Latent TB: treat if IGRA positive (isoniazid 300mg + pyridoxine 10mg for 6 months, or rifampicin + isoniazid for 3 months)

Landmark trials:

START trial: immediate ART (any CD4) superior to deferred (CD4 <350)
PARTNER/PARTNER2: U=U - zero linked transmissions with VL <200
HPTN 052: early ART reduced transmission by 96%

Surgical/Interventional

Not routinely required
Surgical management of complications (lymphoma, Kaposi sarcoma)

Referral Criteria

All newly diagnosed: specialist HIV clinic (GUM/infectious diseases)
Pregnancy: joint HIV/obstetric care
Complex comorbidities: multidisciplinary team
Drug resistance or treatment failure: specialist MDT review

Prognosis

With early ART: near-normal life expectancy (within 5–10 years of HIV-negative population)
Late diagnosis (CD4 <200): 10-fold increased mortality in first year vs early diagnosis
Virological suppression (VL <50): >95% achieve with modern ART
AIDS-related mortality in UK: declining rapidly with widespread ART
Major causes of death in treated HIV: non-AIDS cancers, cardiovascular disease, liver disease (often hepatitis co-infection)
CD4 recovery: most patients achieve CD4 >500 within 2–3 years of ART if started early
U=U: zero sexual transmission risk with sustained viral suppression

Other Relevant Information

WHO Clinical Staging

Stage	Features
1	Asymptomatic, persistent generalised lymphadenopathy
2	Weight loss <10%, minor mucocutaneous, herpes zoster, URTIs
3	Weight loss >10%, chronic diarrhoea, oral candidiasis, pulmonary TB
4 (AIDS)	PCP, toxoplasmosis, cryptococcal meningitis, Kaposi sarcoma, wasting syndrome

CD4-Related Infections

CD4 Count	Opportunistic Infection
<200	PCP, oesophageal candidiasis
<100	Cerebral toxoplasmosis, cryptococcal meningitis
<50	CMV retinitis/colitis, MAC, PML

ART Drug Classes

Class	Examples	Key Side Effects
NRTIs	Tenofovir, emtricitabine, abacavir, lamivudine	Renal (TDF), hypersensitivity (ABC - HLA-B*5701)
NNRTIs	Efavirenz, rilpivirine	Neuropsychiatric (EFV), rash
PIs	Darunavir, atazanavir	GI upset, lipodystrophy, interactions
INSTIs	Dolutegravir, raltegravir, bictegravir	Weight gain, insomnia (DTG)
Entry inhibitors	Maraviroc (CCR5 antagonist)	Hepatotoxicity

NICE Guidelines / CKS

HIV Prophylaxis

Strategies to prevent HIV acquisition including pre-exposure prophylaxis (PrEP) with tenofovir/emtricitabine for at-risk individuals, post-exposure prophylaxis (PEP) following potential exposure, and prevention of mother-to-child transmission (PMTCT).

MRCP Part 1 · MRCP Part 2 · PLAB 1 · UKMLA · MRCGP AKT · MSRA

Key Facts

PrEP (pre-exposure prophylaxis): tenofovir disoproxil/emtricitabine (Truvada) 1 tablet OD - reduces HIV acquisition by >99% when taken consistently (iPrEx, PROUD, DISCOVER trials)
PrEP available free on NHS in England since 2020; Scotland, Wales, and NI have similar schemes
PEP (post-exposure prophylaxis): tenofovir/emtricitabine + raltegravir 400mg BD - start within 72 hours, continue for 28 days
Occupational PEP: after needlestick/mucosal exposure - same regimen; risk of seroconversion ~0.3% (percutaneous) and 0.09% (mucosal)
PMTCT: ART during pregnancy + intrapartum management + neonatal prophylaxis → transmission rate <0.5%
U=U: treatment as prevention - virally suppressed individuals (VL <200) do not transmit sexually
On-demand PrEP (event-based dosing): 2 tablets 2–24h before sex, then 1 tablet at 24h and 48h after first dose (IPERGAY trial) - MSM only
Monitoring on PrEP: HIV test, renal function, STI screen every 3 months

Overview

Key Facts

HIV prophylaxis encompasses pharmacological and non-pharmacological strategies to prevent HIV acquisition. PrEP has transformed HIV prevention and is a cornerstone of the UK's goal to end new HIV transmissions by 2030.

Epidemiology

New HIV diagnoses in UK declining: ~3,118 in 2022 (vs 6,000+ in 2014)
Decline attributed to combination prevention: increased testing, PrEP, U=U
PrEP uptake in UK: >40,000 people accessing PrEP via NHS
Mother-to-child transmission: <0.5% in UK with interventions
Occupational exposure: extremely rare in UK (<1 seroconversion per year with PEP)

Aetiology

Risk factors for HIV acquisition:

Condomless anal intercourse (highest per-act risk: 1.4% receptive)
Multiple sexual partners
STI co-infection (increases risk 2–5 fold)
IV drug use with shared needles
Occupational needlestick injury
Vertical transmission (without interventions: 15–45%)

Pathophysiology

PrEP mechanism:

Tenofovir/emtricitabine (NRTIs): achieve high drug concentrations in genital/rectal tissues
Block reverse transcriptase → prevent proviral DNA integration
Rectal tissue: protective levels in ~7 days; vaginal tissue: ~20 days of daily dosing

PEP mechanism:

ART started after exposure blocks viral replication before systemic dissemination
Must start within 72 hours (ideally within 24 hours) - efficacy decreases with delay
28-day course eliminates virus before chronic infection establishes

Clinical Presentation

PrEP Assessment

Patient presents requesting PrEP - ongoing high-risk exposure
MSM with condomless sex with casual partners
HIV-negative partner of person living with HIV (if partner not virally suppressed)
Heterosexual with partners from high-prevalence areas
IVDU with sharing practices

PEP Assessment

Sexual exposure: unprotected sex with known/suspected HIV+ partner
Occupational exposure: needlestick, sharps injury, mucosal splash
Assess within hours: timeliness is critical

PMTCT Assessment

Antenatal HIV screening (offered to all pregnant women in UK)
Planning delivery method and neonatal prophylaxis

Red Flags

Symptoms suggestive of acute HIV seroconversion (must test and exclude before starting PrEP)
Renal impairment (eGFR <60 - relative contraindication for TDF-based PrEP)
Hepatitis B co-infection (TDF/FTC treats HBV - stopping PrEP can cause HBV flare)
PEP request >72 hours post-exposure (unlikely to be effective)

Differential Diagnosis

Diagnosis	Key Features	Investigation
Acute HIV seroconversion	Fever, rash, sore throat 2–6 weeks post-exposure	4th-gen HIV test, HIV RNA PCR
Other STIs	Discharge, ulcers, rash, dysuria	Full STI screen
Hepatitis B acute	Jaundice, malaise, risk factor overlap	HBsAg, anti-HBc IgM
Non-specific viral illness	Similar symptoms to seroconversion	Monospot, CMV, hepatitis screen

Diagnosis / Investigation

Before Starting PrEP

HIV test (4th-gen): must be NEGATIVE - essential to exclude existing infection
Hepatitis B serology: HBsAg, anti-HBs, anti-HBc (TDF/FTC active against HBV)
Hepatitis C antibody: if risk factors
Renal function: eGFR must be >60 (TDF nephrotoxicity risk)
STI screen: full screen including syphilis, chlamydia, gonorrhoea
Pregnancy test: if applicable

Monitoring on PrEP (every 3 months)

HIV test (4th-gen)
Renal function (eGFR)
STI screen
Hepatitis C if ongoing risk
Adherence assessment

Before Starting PEP

Baseline HIV test: document HIV-negative status
Source patient testing: if available and consenting
Hepatitis B/C serology: co-infection
FBC, U&Es, LFTs: baseline
Pregnancy test: if applicable
STI screen

PEP Follow-up

HIV test at 8–12 weeks post-exposure (to confirm no seroconversion)
Repeat hepatitis B/C at 3 and 6 months

Management

Non-pharmacological

Condom use: remains the cornerstone of combination prevention
Regular STI testing: at least annually, every 3 months for high-risk groups
Partner notification and treatment
Needle exchange programmes: for IVDU
Combination prevention: PrEP + condoms + regular testing + treatment as prevention (U=U)

Pharmacological

Pre-exposure prophylaxis (PrEP):

Daily PrEP: tenofovir disoproxil 245mg/emtricitabine 200mg (Truvada) - 1 tablet OD
On-demand PrEP (MSM only - IPERGAY): 2 tablets 2–24h before sex, 1 tablet 24h later, 1 tablet 48h after first dose
Efficacy: >99% with consistent use (PROUD trial showed 86% reduction in intention-to-treat)
Continue until risk has resolved; if stopping, continue for 7 days after last exposure (28 days for vaginal exposure)

Post-exposure prophylaxis (PEP):

Regimen: tenofovir disoproxil/emtricitabine + raltegravir 400mg BD for 28 days
Must start within 72 hours (preferably within 24 hours)
Available from sexual health clinics and A&E departments
Side effects: nausea, diarrhoea, headache (usually mild and self-limiting)

PMTCT:

Maternal ART: throughout pregnancy, labour, and postpartum - aim for VL <50 copies/mL by 36 weeks
Delivery: vaginal delivery if VL <50; consider elective C-section at 38 weeks if VL >400 at 36 weeks
Neonatal prophylaxis: zidovudine monotherapy (low risk) or triple ART (high risk) for 2–4 weeks
Avoid breastfeeding in UK (formula feeding recommended) - though BHIVA now supports informed choice if VL undetectable

Landmark trials:

iPrEx: first PrEP efficacy trial (MSM) - 44% reduction in ITT, >90% with adherence
PROUD: UK open-label PrEP trial - 86% reduction
DISCOVER: TAF/FTC non-inferior to TDF/FTC for PrEP
IPERGAY: on-demand PrEP - 86% reduction in MSM
HPTN 052: early ART reduced transmission by 96%

Referral Criteria

PrEP: sexual health clinic assessment
PEP: A&E or sexual health clinic within 72 hours
PMTCT: specialist HIV antenatal clinic
Occupational exposure: occupational health + A&E within hours

Prognosis

PrEP: virtually eliminates HIV acquisition risk when taken consistently (>99% efficacy)
PEP: estimated 80% effective if started within 72 hours
PMTCT: reduces transmission from 15–45% to <0.5%
U=U: zero sexual transmissions documented with sustained VL <200 (PARTNER studies: 0 transmissions in >77,000 condomless acts)
UK on track to meet 2030 target of zero new HIV transmissions
Late PEP (>72 hours): not recommended - effectiveness unproven

Other Relevant Information

PEP Risk Assessment

Source HIV Status	Exposure Type	PEP Recommended?
HIV+ (detectable VL)	Receptive anal	Yes
HIV+ (detectable VL)	Insertive anal/vaginal	Yes
HIV+ (undetectable VL)	Any sexual	Not usually (U=U)
Unknown status	High-risk exposure	Consider (risk-benefit)
HIV+	Needlestick (hollow bore)	Yes
HIV+	Mucosal splash	Yes

PrEP Monitoring Schedule

Timepoint	Tests
Baseline	HIV, HBV, HCV, eGFR, STI screen, pregnancy
1 month	HIV, eGFR, tolerability
Every 3 months	HIV, eGFR, STI screen
Annually	HCV (if risk), hepatitis B vaccine response

NICE Guidelines / CKS

Tuberculosis

Infectious disease caused by Mycobacterium tuberculosis, primarily affecting the lungs but capable of involving any organ. The UK has ~4,500 cases/year, predominantly in urban areas and immigrant populations. Standard treatment is 6 months of combination therapy per NICE NG33.

MRCP Part 1 · MRCP Part 2 · PLAB 1 · UKMLA · MRCGP AKT · MSRA

Key Facts

NICE NG33: standard treatment is 2 months RIPE (rifampicin, isoniazid, pyrazinamide, ethambutol) then 4 months RI (rifampicin, isoniazid) = 6 months total
Rifampicin 450mg (<50kg) or 600mg (≥50kg) OD; Isoniazid 300mg OD + pyridoxine 10mg OD (prevent peripheral neuropathy)
Notifiable disease: all cases must be notified to local health protection team within 3 days
UK incidence: ~4,500 cases/year; London accounts for ~35% of cases
Sputum AFB smear and culture: gold standard diagnosis - culture takes 2–8 weeks; GeneXpert MTB/RIF gives results in 2 hours
MDR-TB: resistance to at least rifampicin and isoniazid - requires specialist management with second-line agents for 9–20 months
Contact tracing: screen household and close contacts with symptom enquiry, CXR, and IGRA
HIV co-infection: TB is the leading cause of death in HIV+ individuals globally; always test for HIV in TB patients

Overview

Key Facts

Tuberculosis remains a significant public health concern in the UK, particularly in London and other urban centres. Most cases arise from reactivation of latent infection, especially in immigrant populations. Multi-drug combination therapy is essential to prevent resistance.

Epidemiology

UK: ~4,500 new cases/year (declining trend); London ~35% of cases
73% of UK TB cases are in non-UK-born individuals
Global: ~10.6 million new cases/year; ~1.3 million deaths/year (WHO 2022)
HIV-TB co-infection: ~8% of global TB cases; higher mortality
MDR-TB: ~1.5% of UK cases; globally ~450,000 cases/year

Aetiology

Mycobacterium tuberculosis: acid-fast bacillus (Ziehl-Neelsen stain), slow-growing aerobe
Transmitted via airborne droplet nuclei from pulmonary/laryngeal TB
Risk factors for TB: HIV, immunosuppression, malnutrition, homelessness, imprisonment, IVDU, healthcare workers, close contacts
Risk of progression from latent to active: 5–10% lifetime (50% within first 2 years); much higher with HIV (~10% per year)

Pathophysiology

Inhalation of M. tuberculosis

alveolar macrophage phagocytosis

bacilli survive intracellularly

Granuloma formation: epithelioid cells, Langhans giant cells, caseating necrosis - walled-off infection (primary complex)
Latent TB: contained infection; positive IGRA/Mantoux, no symptoms, not infectious
Active TB: immune failure → caseating necrosis, cavitation, dissemination
Miliary TB: haematogenous spread → disseminated disease (liver, spleen, bone marrow, meninges)
Cell-mediated immunity (CD4+ T cells) is critical - hence increased risk with HIV

Clinical Presentation

Pulmonary TB (most common)

Chronic cough (>3 weeks) - initially dry, then productive
Haemoptysis
Night sweats
Weight loss, anorexia
Low-grade fever
Upper lobe consolidation/cavitation on CXR

Extrapulmonary TB

Lymph node (most common extrapulmonary): painless cervical lymphadenopathy, cold abscess
Pleural: pleuritic chest pain, effusion (lymphocyte-predominant, low glucose)
Bone/joint: Pott's disease (spinal TB) - back pain, kyphosis, psoas abscess
CNS: TB meningitis - headache, cranial nerve palsies, hydrocephalus; TB cerebral abscess
GI: ileocaecal (mimics Crohn's), peritoneal TB (ascites)
Genitourinary: sterile pyuria, epididymo-orchitis, tubal infertility
Miliary TB: disseminated - fever, hepatosplenomegaly, miliary pattern on CXR, pancytopenia

Red Flags

TB meningitis (high mortality - treat empirically if suspected)
Miliary/disseminated TB
Spinal TB with neurological compromise (cord compression)
MDR-TB suspected (previous treatment, travel to high-MDR areas)
Immunosuppressed patient with atypical symptoms

Differential Diagnosis

Diagnosis	Key Features	Investigation
Lung cancer	Older, smoker, weight loss, haemoptysis, mass on CXR	CT chest, biopsy, PET-CT
Pneumonia (bacterial)	Acute onset, productive cough, consolidation	CXR, sputum culture, CRP
Sarcoidosis	Bilateral hilar lymphadenopathy, non-caseating granulomas	ACE, CXR, biopsy
Lymphoma	Lymphadenopathy, B symptoms, mediastinal mass	Biopsy, CT, LDH
NTM infection	Immunocompromised, bronchiectasis, MAC most common	AFB culture with speciation
Fungal infection	Travel to endemic area, immunocompromised	Fungal cultures, serology

Diagnosis / Investigation

Bedside

CXR: upper lobe consolidation, cavitation, miliary pattern, lymphadenopathy, pleural effusion
Sputum collection: 3 early-morning specimens for AFB smear and culture
Observations: weight, temperature

Bloods

FBC: normocytic anaemia, lymphopenia (or lymphocytosis)
CRP/ESR: elevated
LFTs: baseline before treatment (hepatotoxic drugs)
U&Es: baseline
HIV test: MUST be offered to all TB patients (NICE NG33)
Hepatitis B/C: baseline
Vitamin D: commonly deficient in TB patients

Imaging

CXR: first-line
CT chest: if CXR inconclusive or extrapulmonary disease suspected
MRI spine: spinal TB
CT/MRI brain: TB meningitis (basal meningeal enhancement, hydrocephalus, tuberculomas)

Special Tests

Sputum AFB smear (Ziehl-Neelsen): rapid but sensitivity 50–80%
Sputum culture (Löwenstein-Jensen or liquid BACTEC): gold standard - 2–8 weeks; provides sensitivity testing
GeneXpert MTB/RIF: PCR-based, result in 2 hours, detects rifampicin resistance
IGRA (interferon-gamma release assay): for latent TB diagnosis (not affected by BCG)
Mantoux test: intradermal tuberculin injection, read at 48–72 hours (≥5mm positive in immunocompromised, ≥15mm in BCG-vaccinated)
Lymph node biopsy: caseating granulomas, AFB, PCR
CSF: lymphocytic, high protein, low glucose, AFB culture/PCR (TB meningitis)
Pleural biopsy: caseating granulomas (higher yield than fluid culture alone)

Management

Non-pharmacological

Notification: statutory notification to local health protection team
Contact tracing: household and close contacts - symptom screen, CXR, IGRA
Isolation: negative-pressure room if smear-positive pulmonary TB; minimum 2 weeks of treatment before de-isolation
Directly observed therapy (DOT): for non-adherent patients, MDR-TB, homeless, substance misuse
Nutritional support: vitamin D supplementation

Pharmacological

Standard treatment (NICE NG33):

Intensive phase (2 months): Rifampicin + Isoniazid + Pyrazinamide + Ethambutol (RIPE)
Continuation phase (4 months): Rifampicin + Isoniazid (RI)
Total: 6 months for pulmonary TB and most extrapulmonary

Doses (adults):

Rifampicin: 450mg (<50kg) or 600mg (≥50kg) OD
Isoniazid: 300mg OD + pyridoxine 10mg OD (prevent neuropathy)
Pyrazinamide: 1.5g (<50kg) or 2g (≥50kg) OD
Ethambutol: 15mg/kg OD

Extended treatment (12 months):

TB meningitis: 12 months (2 RIPE + 10 RI)
TB meningitis: add dexamethasone (reduces mortality by ~30%)
Bone/joint TB: 12 months

MDR-TB:

Specialist management - second-line agents (fluoroquinolone, amikacin, linezolid, bedaquiline, delamanid)
Duration: minimum 9–20 months

Monitoring:

LFTs at baseline, 2 weeks, then monthly (hepatotoxicity)
Visual acuity: before and monthly during ethambutol (optic neuritis)
Sputum: repeat at 2 months - if still culture-positive, extend intensive phase and review

Drug interactions:

Rifampicin: potent CYP3A4 inducer - reduces efficacy of warfarin, OCP, calcineurin inhibitors, antiretrovirals

Surgical/Interventional

Spinal TB: decompression if cord compression
Abscess drainage: psoas, cold abscesses
Pericardial window: TB pericarditis with effusion

Referral Criteria

All cases: TB specialist/infectious diseases
MDR-TB: regional MDR-TB centre
TB meningitis: neurology + infectious diseases
HIV co-infection: joint HIV-TB MDT
Paediatric TB: specialist paediatric ID

Prognosis

Drug-sensitive pulmonary TB: cure rate >95% with completed treatment
TB meningitis: mortality 15–30% even with treatment; neurological sequelae in 20–50%
Miliary TB: mortality 15–20% with treatment
MDR-TB: treatment success 50–70% (lower with XDR-TB)
HIV-TB co-infection: higher mortality, especially if CD4 <100
Relapse rate with completed 6-month treatment: <5%
Non-adherence is the major risk factor for treatment failure and resistance
UK TB mortality: ~300 deaths/year (~6%)

Other Relevant Information

Standard TB Treatment Regimen

Phase	Duration	Drugs
Intensive	2 months	Rifampicin + Isoniazid + Pyrazinamide + Ethambutol
Continuation	4 months	Rifampicin + Isoniazid
Total	6 months

Key Drug Side Effects

Drug	Major Side Effect	Monitoring
Rifampicin	Hepatotoxicity, orange secretions, drug interactions	LFTs, drug interactions
Isoniazid	Peripheral neuropathy, hepatotoxicity	Pyridoxine prophylaxis, LFTs
Pyrazinamide	Hepatotoxicity, hyperuricaemia, arthralgia	LFTs, uric acid
Ethambutol	Optic neuritis (colour vision loss)	Visual acuity before and monthly

Contact Tracing Approach

Group	Screening
Household contacts	Symptom enquiry + CXR + IGRA
Close contacts (>8 hours)	Symptom enquiry + IGRA (CXR if positive)
Casual contacts	Not routinely screened

NICE Guidelines / CKS

Latent Tuberculosis

Asymptomatic infection with Mycobacterium tuberculosis without active disease, identified by positive IGRA or Mantoux test with normal CXR. Carries a 5–10% lifetime risk of reactivation, reduced to <1% with prophylactic treatment. NICE NG33 recommends screening high-risk groups.

MRCP Part 1 · MRCP Part 2 · PLAB 1 · UKMLA · MRCGP AKT · MSRA

Key Facts

Latent TB: positive IGRA or Mantoux, no symptoms, normal CXR, non-infectious
IGRA (interferon-gamma release assay): QuantiFERON-TB Gold or T-SPOT.TB - preferred in BCG-vaccinated individuals (not affected by BCG)
Lifetime reactivation risk: 5–10% without treatment; 50% of risk in first 2 years; much higher with HIV (5–15% per year)
NICE NG33: screen new entrants from high-incidence countries (≥150/100,000), contacts of active TB, immunosuppressed pre-biologic therapy
Treatment: 3 months isoniazid 300mg + rifampicin 450/600mg OD (preferred) or 6 months isoniazid 300mg OD + pyridoxine 10mg
Before starting anti-TNF therapy (infliximab, adalimumab, etanercept): screen for latent TB with IGRA + CXR - treat if positive
BCG vaccination: offered to neonates in high-risk areas and contacts of active TB; 70–80% effective against severe childhood TB
Active TB must be excluded before starting latent TB treatment (symptoms, CXR, sputum if indicated)

Overview

Key Facts

Latent TB infection (LTBI) represents a state of persistent immune response to M. tuberculosis antigens without clinical evidence of active disease. Identifying and treating LTBI is a key public health strategy to prevent future active TB cases.

Epidemiology

Estimated 1/4 of the world's population has LTBI (WHO)
UK LTBI prevalence: estimated ~500,000–800,000 people
~80% of UK active TB cases arise from reactivation of LTBI
New entrant screening programme identifies thousands of LTBI cases annually
Risk of reactivation: 5–10% lifetime (immunocompetent); 5–15% per year (HIV+)

Aetiology

Prior infection with M. tuberculosis that has been contained by the immune system
High-risk groups for LTBI: immigrants from high-incidence countries, contacts of active TB cases, healthcare workers, prisoners, homeless, IVDU
High-risk for reactivation: HIV, anti-TNF therapy, other immunosuppression (transplant, chemotherapy), diabetes, CKD, malnutrition, silicosis

Pathophysiology

After primary infection, granuloma formation contains M. tuberculosis
Bacilli remain viable but dormant within granulomas (caseous necrosis surrounded by macrophages and T-cells)
Memory T-cells maintain immune surveillance (basis of IGRA and Mantoux tests)

Immunosuppression

granuloma breakdown

reactivation

active TB

Reactivation typically occurs in lung apices (highest oxygen tension) but can affect any organ

Clinical Presentation

Typical Presentation

Asymptomatic - by definition, no clinical features
Identified through screening programmes
Positive IGRA or Mantoux without symptoms or CXR abnormality

Screening Contexts

New entrant screening from high-incidence countries
Contact tracing of active TB case
Pre-immunosuppression screening (before anti-TNF, transplant)
Occupational health screening (healthcare workers)
HIV diagnosis

Red Flags (suggesting active rather than latent TB)

Any respiratory symptoms (cough, haemoptysis)
Systemic symptoms (fever, night sweats, weight loss)
Abnormal CXR
Lymphadenopathy
These require investigation for active TB before treating as LTBI

Differential Diagnosis

Diagnosis	Key Features	Investigation
Active pulmonary TB	Symptoms, CXR abnormality, sputum positive	CXR, sputum AFB/culture, GeneXpert
Extrapulmonary TB	Site-specific symptoms (lymphadenopathy, meningitis)	Biopsy, cultures, imaging
NTM infection	Cross-reactivity with IGRA (rare), immunocompromised	NTM culture, speciation
False-positive IGRA	Borderline result, recent BCG (Mantoux only)	Repeat IGRA, clinical context
Sarcoidosis	Non-caseating granulomas, bilateral hilar lymphadenopathy	CXR, ACE level, biopsy

Diagnosis / Investigation

Screening Tests

IGRA: QuantiFERON-TB Gold Plus or T-SPOT.TB
- Measures interferon-gamma release by T-cells in response to TB-specific antigens (ESAT-6, CFP-10)
- Not affected by BCG vaccination (unlike Mantoux)
- Sensitivity ~90%, specificity ~95%
- Single blood test, result in 24–48 hours
Mantoux test (TST): intradermal injection of 2TU PPD
- Read at 48–72 hours
- Positive: ≥5mm (immunocompromised, close contacts); ≥15mm (BCG-vaccinated)
- Affected by BCG, NTM, immunosuppression

To Exclude Active TB

CXR: must be normal for LTBI diagnosis
Symptom enquiry: cough, fever, night sweats, weight loss
Sputum: only if symptoms or CXR abnormal
HIV test: recommended for all LTBI patients

Before Treatment

LFTs: baseline (hepatotoxic drugs)
Hepatitis B/C serology: increased hepatotoxicity risk
eGFR: dose adjustment if impaired

Management

Non-pharmacological

Patient education: importance of treatment completion, symptoms of active TB, drug side effects
Risk-benefit discussion: individualised decision based on reactivation risk vs treatment toxicity
Contact tracing: if identified through contact screening, ensure index case is managed

Pharmacological

NICE NG33 recommended regimens:

3HR (preferred): isoniazid 300mg OD + rifampicin 450/600mg OD for 3 months + pyridoxine 10mg OD
6H: isoniazid 300mg OD for 6 months + pyridoxine 10mg OD (if rifampicin interactions problematic)
3HP (weekly rifapentine + isoniazid): increasingly used but not yet standard UK practice

Before anti-TNF therapy:

Screen with IGRA + CXR
If LTBI: complete at least 2 months of treatment before starting anti-TNF
If unable to treat: monitor closely for active TB

Monitoring:

LFTs at baseline, 2 weeks, then monthly
Symptom review at each visit
Stop treatment and investigate if: hepatitis symptoms, transaminases >3× ULN with symptoms or >5× ULN without symptoms

Drug interactions:

Rifampicin: potent enzyme inducer - affects warfarin, OCP, immunosuppressants, antiretrovirals
Isoniazid: inhibits CYP2C19, CYP3A4 - interacts with phenytoin, carbamazepine

BCG Vaccination

Neonates: offered in high-incidence areas (≥40/100,000) or with family links to high-incidence countries
Previously unvaccinated contacts of active TB: BCG if Mantoux/IGRA negative and aged <35
Not given if: HIV+ (unless CD4 >200 and on ART), immunosuppressed, previous BCG, positive Mantoux/IGRA

Referral Criteria

TB specialist: all LTBI for treatment decision and monitoring
Specialist advice: HIV co-infection, drug interactions (transplant, rheumatology patients on biologics)
GP: follow-up monitoring for uncomplicated cases on isoniazid monotherapy

Prognosis

LTBI treatment reduces reactivation risk by 60–90%
3HR regimen: completion rates ~80% (better than 6H due to shorter duration)
6H regimen: completion rates ~60%
Untreated LTBI: 5–10% lifetime reactivation risk (immunocompetent)
HIV co-infection without treatment: 5–15% per year reactivation risk
BCG: 70–80% effective against severe childhood TB (miliary, meningitis)
After completed LTBI treatment: reactivation risk <1%
Drug-induced hepatitis: <1% with isoniazid at standard dose (higher in >35 years, alcohol use, hepatitis)

Other Relevant Information

IGRA vs Mantoux Comparison

Feature	IGRA	Mantoux
Affected by BCG	No	Yes
Visits required	1	2 (placement + reading)
Boosting phenomenon	No	Yes
Sensitivity	~90%	~85%
Specificity	~95%	~70% (BCG-vaccinated)
Preferred in	BCG-vaccinated adults	Children <5 years

LTBI Treatment Regimens

Regimen	Duration	Key Points
3HR	3 months	Preferred; isoniazid + rifampicin
6H	6 months	Isoniazid alone; if rifampicin interactions
3HP	3 months (weekly)	Rifapentine + isoniazid; emerging
4R	4 months	Rifampicin alone; alternative

UK LTBI Screening Programme

Group	Screening Approach
New entrants (≥150/100,000 incidence)	IGRA within 6 months of entry
Close contacts of active TB	IGRA (+ CXR if positive)
Pre-anti-TNF therapy	IGRA + CXR
Pre-transplant	IGRA + CXR
HIV+ patients	IGRA at diagnosis

NICE Guidelines / CKS

Malaria

A parasitic infection caused by Plasmodium species transmitted by Anopheles mosquitoes. P. falciparum causes the most severe form with risk of cerebral malaria, severe anaemia, and death. Approximately 1,500–2,000 imported cases occur in the UK annually.

MRCP Part 1 · MRCP Part 2 · PLAB 1 · UKMLA · MRCGP AKT · MSRA

Key Facts

P. falciparum causes >90% of malaria deaths - can cause severe/cerebral malaria; parasitaemia >2% is a marker of severity
UK imported malaria: ~1,500–2,000 cases/year; ~5–10 deaths/year; most acquired in sub-Saharan Africa
Diagnosis: thick and thin blood films (3 films over 48 hours if initial negative); rapid diagnostic test (RDT) for P. falciparum antigen
Severe malaria treatment: IV artesunate 2.4 mg/kg at 0, 12, 24 hours then daily (SEAQUAMAT, AQUAMAT trials) - followed by oral ACT
Uncomplicated P. falciparum: oral artemether-lumefantrine (Riamet) - 4 tablets at 0, 8, 24, 36, 48, 60 hours (24 tablets total)
P. vivax/ovale: chloroquine + primaquine 14 days (to clear liver hypnozoites - check G6PD first)
Chemoprophylaxis: atovaquone-proguanil (Malarone), doxycycline, or mefloquine - depending on destination
Always consider malaria in any febrile returning traveller from an endemic area - medical emergency until excluded

Overview

Key Facts

Malaria is the most important parasitic infection worldwide and a key consideration in the febrile returning traveller in UK practice. P. falciparum malaria is a medical emergency requiring immediate treatment.

Epidemiology

Global: ~247 million cases/year; ~619,000 deaths/year (WHO 2022); >90% in sub-Saharan Africa
UK: ~1,500–2,000 imported cases/year; ~5–10 deaths/year
Most UK cases: visiting friends and relatives (VFR travellers) in West Africa (Nigeria, Ghana)
Peak UK diagnoses: August–October (summer travel season)
UK case-fatality rate: ~0.5% (higher with delayed diagnosis)

Aetiology

Plasmodium falciparum: most virulent, causes severe malaria; sub-Saharan Africa predominant
P. vivax: Asia, Central/South America; causes relapsing malaria (hypnozoites)
P. ovale: West Africa; also causes relapses
P. malariae: widespread but uncommon; can cause nephrotic syndrome
P. knowlesi: Southeast Asia (zoonotic from macaques); can cause severe disease
Transmitted by female Anopheles mosquitoes (dusk to dawn biting)

Pathophysiology

Sporozoites injected by mosquito

liver schizogony (1–2 weeks)

merozoites released into blood

Erythrocytic cycle: merozoite invasion

trophozoite

schizont

RBC lysis

merozoite release (cyclical fever)

P. falciparum: infected RBCs express PfEMP1

cytoadherence to vascular endothelium

microvascular obstruction

organ ischaemia (cerebral malaria, renal failure, ARDS)

P. falciparum infects RBCs of all ages

high parasitaemia

severe haemolysis

P. vivax/ovale: dormant liver stage (hypnozoites) → relapse months to years later

Clinical Presentation

Uncomplicated Malaria

Fever (cyclical or continuous) - paroxysms every 48h (tertian) or 72h (quartan)
Rigors, sweating
Headache, myalgia
Nausea, vomiting, diarrhoea
Hepatosplenomegaly
Jaundice (haemolysis)

Severe/Complicated P. falciparum Malaria

Cerebral malaria: impaired consciousness (GCS <11), seizures
Severe anaemia: Hb <80 g/L
Renal failure: creatinine >265 µmol/L or oliguria
ARDS/pulmonary oedema
Hypoglycaemia: <2.2 mmol/L (quinine-induced or disease-related)
Metabolic acidosis: pH <7.25 or bicarbonate <15
Shock (algid malaria): SBP <80 mmHg
DIC: spontaneous bleeding
Parasitaemia >2% (or >10% = very severe)
Blackwater fever: haemoglobinuria from massive intravascular haemolysis

Red Flags

Any feature of severe malaria (above)
Fever in returning traveller (must exclude malaria)
Non-immune individual (no previous exposure)
Pregnancy (high mortality risk)
Splenectomised patient (overwhelming parasitaemia)

Differential Diagnosis

Diagnosis	Key Features	Investigation
Dengue fever	Tropical travel, retro-orbital pain, thrombocytopenia, rash	Dengue NS1 antigen, IgM/IgG
Typhoid	South Asian travel, relative bradycardia, rose spots	Blood cultures, Widal test
Viral hepatitis	Jaundice, hepatitis risk factors	Hepatitis serology
Influenza	Respiratory symptoms, seasonal	Influenza PCR
Meningitis	Neck stiffness, photophobia, rash	LP, blood cultures
Rickettsial infection	Eschar, rash, tick exposure	Serology
Acute HIV seroconversion	Rash, pharyngitis, risk factors	HIV test

Diagnosis / Investigation

Bedside

Blood glucose: hypoglycaemia (severe malaria, quinine-induced)
Observations: temperature chart, NEWS2
GCS: if altered consciousness

Bloods

Thick and thin blood films: gold standard - thick film detects parasites, thin film identifies species and quantifies parasitaemia. Request 3 films over 48 hours if initial negative
Rapid diagnostic test (RDT): detects P. falciparum HRP-2 antigen - result in 15 minutes; less sensitive for non-falciparum
FBC: thrombocytopenia (very common), anaemia, leucopenia
U&Es: AKI
LFTs: hepatitis, jaundice
LDH, bilirubin, haptoglobin: haemolysis markers
Glucose: hypoglycaemia
Blood gas: metabolic acidosis, lactate
Coagulation screen: DIC
G6PD level: before primaquine
Blood cultures: exclude concurrent bacteraemia

Imaging

CXR: ARDS, pulmonary oedema
CT head: if cerebral malaria suspected (exclude other causes)

Special Tests

Parasitaemia quantification: percentage of infected RBCs on thin film
PCR: for species confirmation if uncertain on microscopy

Management

Non-pharmacological

Medical emergency: admit all confirmed P. falciparum cases
Fluid balance: careful - risk of ARDS with over-resuscitation
Blood glucose monitoring: 4-hourly in severe malaria
Transfusion: if Hb <70 or haemodynamically unstable
Renal support: RRT for AKI
ICU admission: all severe malaria cases

Pharmacological

Severe P. falciparum malaria:

IV artesunate 2.4 mg/kg at 0, 12, 24 hours then daily until oral tolerated (minimum 24 hours IV)
Then complete with oral artemether-lumefantrine (Riamet) for 3-day course
Artesunate superior to IV quinine: SEAQUAMAT trial (35% mortality reduction in adults), AQUAMAT trial (22.5% reduction in children)
If artesunate unavailable: IV quinine loading dose 20mg/kg (max 1.4g) in 5% dextrose over 4 hours, then 10mg/kg TDS (with ECG monitoring)

Uncomplicated P. falciparum:

Artemether-lumefantrine (Riamet): 4 tablets at 0, 8, 24, 36, 48, 60 hours (total 24 tablets over 3 days)
Take with fatty food (improves absorption)
Alternative: atovaquone-proguanil (Malarone) for 3 days

P. vivax, P. ovale:

Chloroquine: 600mg base, then 300mg at 6–8h, 24h, 48h
Primaquine 15mg OD for 14 days: radical cure (eliminates hypnozoites) - check G6PD first (risk of haemolysis)

P. malariae/P. knowlesi:

Chloroquine (as above); ACT if P. knowlesi severe
No primaquine needed (no hypnozoites)

Chemoprophylaxis (prevention):

Atovaquone-proguanil (Malarone): start 1–2 days before, during, 7 days after travel
Doxycycline 100mg OD: start 1–2 days before, during, 4 weeks after
Mefloquine 250mg weekly: start 2–3 weeks before, during, 4 weeks after

Referral Criteria

All confirmed malaria: infectious diseases/tropical medicine
Severe malaria: ICU
Pregnancy with malaria: obstetric + infectious diseases

Prognosis

Uncomplicated P. falciparum: mortality <1% with prompt treatment
Severe P. falciparum: mortality 15–20% even with optimal treatment
Cerebral malaria: mortality 15–25%; neurological sequelae in 10–25% of survivors
UK case-fatality rate: ~0.5% (deaths primarily due to delayed diagnosis)
P. vivax/ovale: very low mortality but relapse risk if hypnozoites not treated
Mortality increases significantly with delayed treatment - each 6-hour delay in treatment of severe malaria increases mortality
Non-immune travellers at much higher risk than semi-immune individuals

Other Relevant Information

WHO Criteria for Severe Malaria (P. falciparum)

Feature	Threshold
Impaired consciousness	GCS <11
Prostration	Unable to sit/stand
Multiple convulsions	>2 in 24 hours
Acidosis	pH <7.25 or bicarb <15
Hypoglycaemia	Glucose <2.2 mmol/L
Severe anaemia	Hb <70 g/L
Renal impairment	Creatinine >265 µmol/L
Jaundice	Bilirubin >50 + parasitaemia >2%
Pulmonary oedema/ARDS	Radiological evidence
Significant bleeding	Spontaneous
Shock	SBP <80 mmHg
Parasitaemia	>10%

Malaria Chemoprophylaxis

Drug	Start	During Travel	After Return
Atovaquone-proguanil	1–2 days before	Daily	7 days
Doxycycline	1–2 days before	Daily	4 weeks
Mefloquine	2–3 weeks before	Weekly	4 weeks

NICE Guidelines / CKS

Dengue Fever

An arboviral infection caused by dengue virus (serotypes 1–4), transmitted by Aedes mosquitoes. Presents with high fever, severe headache, retro-orbital pain, myalgia, and rash. Severe dengue with plasma leakage, haemorrhage, or organ failure occurs in ~5% of cases.

MRCP Part 1 · MRCP Part 2 · PLAB 1 · UKMLA · MRCGP AKT · MSRA

Key Facts

Dengue virus: 4 serotypes (DENV-1 to 4); infection with one serotype confers lifelong immunity to that type but increases risk of severe dengue with subsequent heterologous infection
Aedes aegypti and Aedes albopictus mosquitoes: daytime biters - unlike Anopheles (malaria)
Classic triad: high fever + severe headache/retro-orbital pain + maculopapular rash
Severe dengue warning signs: abdominal pain, persistent vomiting, mucosal bleeding, lethargy, hepatomegaly, rising haematocrit with falling platelets
Diagnosis: NS1 antigen (positive days 1–5), dengue IgM/IgG (positive from day 5+), PCR
No specific antiviral treatment - supportive care with careful fluid management is the cornerstone
Thrombocytopenia is characteristic - avoid NSAIDs and aspirin (bleeding risk); use paracetamol for fever
UK imported cases: ~300–500/year; acquired in Southeast Asia, Caribbean, Latin America - notifiable disease

Overview

Key Facts

Dengue is the most common arboviral infection worldwide, with increasing incidence due to urbanisation and climate change. Most UK cases are imported from endemic areas. Management is supportive, with careful attention to the critical phase around day 3–7.

Epidemiology

Global: ~100–400 million infections/year; ~500,000 severe dengue cases; ~25,000 deaths (WHO)
Endemic in >100 countries (tropical/subtropical)
UK: ~300–500 imported cases/year; no autochthonous transmission (yet)
Peak incidence in travellers returning from Southeast Asia (Thailand, India) and Caribbean
Most common in adults aged 20–40

Aetiology

Dengue virus: family Flaviviridae, 4 serotypes
Transmitted by Aedes mosquitoes (bite during daytime)
Incubation period: 4–10 days
Risk of severe dengue: secondary infection with different serotype (antibody-dependent enhancement)

Pathophysiology

Dengue virus infects monocytes, macrophages, dendritic cells

Immune activation

cytokine storm

increased vascular permeability

Antibody-dependent enhancement (ADE)

pre-existing non-neutralising antibodies from prior infection with different serotype enhance viral uptake

higher viraemia

more severe disease

Plasma leakage: occurs around defervescence (days 3–7) → haemoconcentration, pleural effusions, ascites
Thrombocytopenia: peripheral destruction and bone marrow suppression
Severe dengue: dengue haemorrhagic fever (DHF) or dengue shock syndrome (DSS)

Clinical Presentation

Febrile Phase (Days 1–3)

Sudden high fever (40°C)
Severe headache, retro-orbital pain
Myalgia, arthralgia (breakbone fever)
Nausea, vomiting
Maculopapular rash (may appear later)
Facial flushing

Critical Phase (Days 3–7 - around defervescence)

Temperature drops but clinical deterioration
Plasma leakage: haemoconcentration (rising haematocrit), pleural effusion, ascites
Haemorrhage: petechiae, epistaxis, gingival bleeding, menorrhagia, GI bleeding
Dengue shock syndrome: tachycardia, narrow pulse pressure, hypotension, poor perfusion

Recovery Phase (Days 7–10)

Gradual improvement
Fluid reabsorption (risk of fluid overload if over-resuscitated)
Convalescent rash (islands of white in sea of red)
Pruritus

Red Flags (WHO warning signs for severe dengue)

Abdominal pain or tenderness
Persistent vomiting
Clinical fluid accumulation (pleural effusion, ascites)
Mucosal bleeding
Lethargy/restlessness
Hepatomegaly >2cm
Laboratory: increasing haematocrit with rapidly decreasing platelets

Differential Diagnosis

Diagnosis	Key Features	Investigation
Malaria	Evening mosquito bites, rigors, endemic area overlap	Blood films, RDT
Chikungunya	Similar travel, severe joint pain (more than dengue), less thrombocytopenia	Chikungunya PCR/IgM
Zika virus	Milder fever, conjunctivitis, pregnancy risk	Zika PCR, IgM
Typhoid	South Asian travel, relative bradycardia, rose spots	Blood cultures
Leptospirosis	Water exposure, conjunctival suffusion, jaundice, AKI	Leptospira serology, PCR
Measles	Unvaccinated, coryza, Koplik spots, rash	Measles IgM
Acute HIV	Rash, pharyngitis, lymphadenopathy, risk factors	HIV test

Diagnosis / Investigation

Bedside

Observations: temperature, BP (narrow pulse pressure in shock), HR
Tourniquet test: inflate BP cuff between systolic and diastolic for 5 min - ≥20 petechiae per square inch = positive
Blood glucose: hypoglycaemia in severe disease

Bloods

NS1 antigen: positive days 1–5 (highly sensitive early)
Dengue IgM/IgG: positive from day 5; IgG positive in secondary infection from day 1
Dengue PCR: if available, confirms and serotypes
FBC: leucopenia, thrombocytopenia (can be very severe <20 × 10⁹/L), haematocrit (rising = haemoconcentration)
LFTs: transaminitis (AST > ALT typically)
U&Es: AKI in severe cases
Coagulation: prolonged in severe dengue/DIC
CRP: usually low (helps distinguish from bacterial infection)

Imaging

CXR: pleural effusions
USS abdomen: ascites, gallbladder wall thickening (oedema), pleural effusions

Special Tests

Serial haematocrit: rising haematocrit = plasma leakage (critical phase)
Serial platelet count: guide bleeding risk
Blood group and cross-match: if bleeding risk

Management

Non-pharmacological

Supportive care is the mainstay - no specific antiviral exists
Oral fluid replacement: encourage oral rehydration in uncomplicated dengue
Bed rest: during febrile and critical phases
Close monitoring: daily FBC (haematocrit, platelets) during critical phase
Avoid NSAIDs and aspirin: increased bleeding risk - use paracetamol only

Pharmacological

Uncomplicated dengue:

Paracetamol 1g QDS for fever and pain (avoid NSAIDs)
Oral rehydration solution
Monitor for warning signs

Dengue with warning signs:

IV crystalloid: 0.9% NaCl or Hartmann's - 5–7 ml/kg/hr for 1–2 hours, then reduce based on response
Serial haematocrit and clinical assessment to guide fluid rate
Avoid excessive fluids (risk of pulmonary oedema in recovery phase)

Severe dengue/dengue shock:

Rapid IV crystalloid: 20 ml/kg bolus over 15–30 min
If no improvement: consider colloid (e.g. gelatin solutions) or blood products
Platelet transfusion: only if active bleeding with platelets <10 × 10⁹/L (prophylactic platelet transfusion not recommended)
Packed red cells: if significant haemorrhage
ICU admission: for shock, organ failure

Surgical/Interventional

Rarely needed
Pleural/peritoneal drainage: only if compromising respiration

Referral Criteria

Infectious diseases/tropical medicine: all confirmed cases
ICU: severe dengue, shock, organ failure
Haematology: severe thrombocytopenia with bleeding
Notify public health (notifiable disease in the UK)

Prognosis

Overall dengue case-fatality rate: <1% with access to care
Severe dengue without treatment: mortality up to 20%
Severe dengue with expert management: mortality <1–5%
Full recovery expected in uncomplicated dengue within 1–2 weeks
Post-dengue fatigue: may persist for weeks to months
Secondary infection with different serotype: higher risk of severe disease (ADE)
UK imported dengue: no deaths in most years; rare fatalities with delayed recognition

Other Relevant Information

WHO Dengue Classification (2009)

Category	Features
Dengue without warning signs	Fever + 2 of: nausea, rash, aches, leucopenia, positive tourniquet test
Dengue with warning signs	Above + abdominal pain, persistent vomiting, fluid accumulation, mucosal bleeding, lethargy, hepatomegaly, rising HCT + falling platelets
Severe dengue	Severe plasma leakage (shock, fluid accumulation with respiratory distress), severe bleeding, or organ impairment

Dengue Timeline

Phase	Days	Key Features
Febrile	1–3	High fever, myalgia, headache
Critical	3–7	Defervescence, plasma leakage, bleeding risk
Recovery	7–10	Fluid reabsorption, convalescent rash

NICE Guidelines / CKS

COVID-19

Respiratory illness caused by SARS-CoV-2, ranging from asymptomatic infection to severe pneumonia, ARDS, and multi-organ failure. Vaccines, antivirals (nirmatrelvir/ritonavir), and dexamethasone have transformed outcomes since the pandemic onset in 2020.

MRCP Part 1 · MRCP Part 2 · PLAB 1 · UKMLA · MRCGP AKT · MSRA

Key Facts

SARS-CoV-2: RNA coronavirus; spike protein binds ACE2 receptor - basis of vaccines and monoclonal antibody therapy
RECOVERY trial (Oxford): dexamethasone 6mg OD for 10 days reduces mortality by 1/3 in ventilated patients and 1/5 in those on oxygen - only beneficial if requiring respiratory support
Nirmatrelvir/ritonavir (Paxlovid): oral antiviral for high-risk patients within 5 days of symptom onset - reduces hospitalisation by ~89% (EPIC-HR trial)
Vaccination: mRNA (Pfizer BNT162b2, Moderna mRNA-1273) and viral vector (AstraZeneca) - booster programme ongoing for vulnerable groups
Long COVID: symptoms persisting >12 weeks in ~10% of infected individuals; fatigue, breathlessness, cognitive dysfunction (brain fog)
NICE NG191: rapid COVID-19 guidelines including oxygen targets, prone positioning, VTE prophylaxis
High-risk groups: age >70, immunosuppressed, chronic lung/heart/kidney disease, diabetes, obesity, unvaccinated
Complications: ARDS, PE/VTE (COVID-associated coagulopathy), myocarditis, MIS-C (children), secondary bacterial/fungal infection

Overview

Key Facts

COVID-19 emerged in late 2019 and became a global pandemic. Caused by SARS-CoV-2, it has resulted in over 200,000 deaths in the UK. Evidence-based treatments from the RECOVERY trial and vaccine rollout have dramatically reduced mortality.

Epidemiology

UK: >24 million confirmed cases, >200,000 deaths (as of 2024)
Global: >770 million cases, >6.9 million deaths (WHO)
IFR varies by age: <0.01% (age <20) to >10% (age >80, unvaccinated)
Now endemic with seasonal waves; predominantly Omicron sub-lineages
Vaccination has reduced hospitalisation and death by >90%

Aetiology

SARS-CoV-2: betacoronavirus, enveloped RNA virus
Transmission: respiratory droplets, aerosols, fomites; incubation 2–14 days (median 5)
Variants of concern: Alpha, Beta, Delta, Omicron (and sub-lineages)
Spike protein mutations drive immune evasion and transmissibility changes

Pathophysiology

Spike protein binds ACE2 receptor (lung, heart, kidney, endothelium, GI tract) → cell entry via TMPRSS2
Phase 1 (viral replication): upper/lower respiratory tract - pyrexia, cough, anosmia
Phase 2 (immune-mediated): cytokine storm (IL-6, TNF-α) → ARDS, multi-organ failure
COVID-associated coagulopathy: endothelial damage + complement activation → VTE, microthrombi
Post-acute sequelae (Long COVID): immune dysregulation, viral persistence, autoimmunity hypotheses

Clinical Presentation

Mild Disease (80%)

Fever, dry cough, fatigue
Anosmia/ageusia (more common with earlier variants)
Sore throat, headache, myalgia
GI symptoms: nausea, diarrhoea

Moderate Disease (15%)

Dyspnoea, SpO2 <94% on air
Pneumonia on CXR (bilateral, peripheral, ground-glass opacities)
Requiring supplemental oxygen

Severe/Critical Disease (5%)

ARDS: PaO2/FiO2 <300, bilateral opacities
Septic shock
Multi-organ failure
Requiring NIV, CPAP, or invasive ventilation

Complications

VTE: PE and DVT - incidence 20–30% in ICU patients
Myocarditis/pericarditis: troponin elevation, arrhythmias
AKI: ~20–40% of hospitalised patients
Secondary infections: bacterial pneumonia, invasive aspergillosis
MIS-C (children): Kawasaki-like syndrome 2–6 weeks post-infection

Long COVID (>12 weeks)

Fatigue (most common), breathlessness, brain fog, palpitations, joint pain, depression/anxiety
Affects ~10% of infected individuals; may persist for months to years

Red Flags

SpO2 <92% on air (or <94% if chronic lung disease)
Silent hypoxia (low SpO2 without dyspnoea)
RR >30, accessory muscle use
Worsening on days 7–10 (immune-mediated phase)
New confusion or drowsiness
Haemoptysis
Chest pain (PE or myocarditis)

Differential Diagnosis

Diagnosis	Key Features	Investigation
Influenza	Similar symptoms, seasonal, often more myalgia	Influenza PCR
Bacterial pneumonia	Productive cough, focal consolidation, high CRP	Sputum culture, CXR, procalcitonin
Pulmonary embolism	Pleuritic pain, leg swelling, risk factors	CTPA, D-dimer
Heart failure exacerbation	Orthopnoea, peripheral oedema, previous HF history	BNP, echo, CXR
PCP pneumonia	HIV/immunocompromised, bilateral infiltrates, dry cough	HIV test, BAL, LDH
Hypersensitivity pneumonitis	Occupational/environmental exposure	HRCT, precipitins

Diagnosis / Investigation

Bedside

SARS-CoV-2 PCR (RT-PCR on nasopharyngeal swab): gold standard
Lateral flow test (LFT): rapid antigen detection - less sensitive, useful for screening
SpO2: on air and on exertion (6-minute walk test desaturation)
NEWS2: calculate and escalate
ECG: myocarditis, PE

Bloods

FBC: lymphopenia (prognostic), neutrophilia (secondary infection)
CRP: significantly elevated in severe disease
D-dimer: markedly elevated in COVID coagulopathy/PE
Ferritin: very high in cytokine storm (often >1000)
LDH: elevated - correlates with disease severity
Troponin: myocardial injury
IL-6: where available - guides tocilizumab use
U&Es, LFTs: organ function
Procalcitonin: distinguish bacterial co-infection (low in viral)
Blood gas: respiratory failure assessment

Imaging

CXR: bilateral peripheral ground-glass opacities, consolidation (later)
CT chest: ground-glass opacities (GGO), crazy paving pattern, bilateral and peripheral predominance
CTPA: if PE suspected (low threshold given high VTE risk)
Echocardiography: RV strain (PE), myocarditis

Special Tests

Genomic sequencing: variant identification
Anti-spike antibody: post-vaccination response (research/monitoring)
CT pulmonary angiography: VTE assessment

Management

Non-pharmacological

Oxygen therapy: target SpO2 92–96% (88–92% if COPD)
Prone positioning: awake proning in non-intubated patients improves oxygenation
CPAP/NIV: if SpO2 <92% despite 15L O2 via non-rebreathe mask
Invasive ventilation: lung-protective strategy (Vt 6ml/kg IBW)
Isolation: respiratory precautions (FFP3 mask for AGPs)
VTE prophylaxis: all hospitalised COVID patients - LMWH at prophylactic dose (or therapeutic if ICU - REMAP-CAP, ATTACC trials)

Pharmacological

Hospitalised patients requiring oxygen:

Dexamethasone 6mg OD (oral or IV) for 10 days - RECOVERY trial: reduces 28-day mortality by ~1/3 (ventilated) and ~1/5 (oxygen only); NO benefit if not requiring oxygen
Tocilizumab 8mg/kg IV (single dose): for patients on oxygen with CRP ≥75 and within 48 hours of ICU admission - REMAP-CAP, RECOVERY trials
Baricitinib 4mg OD (oral, 14 days): alternative to tocilizumab (COV-BARRIER trial)
Remdesivir 200mg IV day 1, then 100mg OD for 5 days: modest benefit if early in disease course (ACTT-1 trial)

Non-hospitalised high-risk patients (within 5 days of symptoms):

Nirmatrelvir/ritonavir (Paxlovid): 300mg/100mg BD for 5 days - EPIC-HR trial (89% reduction in hospitalisation). Check drug interactions (ritonavir is CYP3A4 inhibitor)
Molnupiravir 800mg BD for 5 days: alternative if Paxlovid contraindicated

Anticoagulation:

Prophylactic LMWH: all hospitalised patients
Consider therapeutic LMWH: critically ill patients on ward (REMAP-CAP platform trial data)
Post-discharge VTE prophylaxis: 14 days if high VTE risk

Landmark trials:

RECOVERY: dexamethasone, tocilizumab, baricitinib, convalescent plasma (no benefit), hydroxychloroquine (no benefit), azithromycin (no benefit)
REMAP-CAP: tocilizumab, therapeutic anticoagulation
PANORAMIC: molnupiravir in community (modest benefit)

Referral Criteria

Hospital admission: SpO2 <92%, severe symptoms, high-risk patient deteriorating
ICU: requiring CPAP/NIV, intubation, vasopressors
Long COVID clinic: symptoms >12 weeks affecting function

Prognosis

Overall IFR: ~0.5–1% (pre-vaccine era); substantially lower now with vaccination
ICU mortality (ventilated, pre-dexamethasone): ~40–50%; with dexamethasone + tocilizumab: ~25–30%
Vaccinated hospitalised patients: mortality ~5–10%
Long COVID: affects ~10% of all infections; ~2% have symptoms >1 year
Post-COVID VTE risk: elevated for 6 months post-infection
MIS-C: mortality <2% with treatment
Post-COVID cognitive impairment: reported in ~10–20% of hospitalised patients
Full recovery from acute infection: >95% in uncomplicated cases

Other Relevant Information

RECOVERY Trial Key Results

Intervention	Outcome
Dexamethasone	Mortality reduced by 1/3 (ventilated) and 1/5 (oxygen)
Tocilizumab	Reduced mortality and time to discharge in severe disease
Baricitinib	Mortality benefit similar to tocilizumab
Convalescent plasma	No significant benefit
Hydroxychloroquine	No benefit, excess toxicity
Azithromycin	No benefit
Colchicine	No benefit

COVID-19 Severity Classification

Severity	SpO2	Oxygen Need	Management
Mild	≥94%	None	Community care
Moderate	90–94%	Supplemental O2	Hospital ward, dexamethasone
Severe	<90%	CPAP/NIV/ventilation	ICU, dexamethasone + tocilizumab

NICE Guidelines / CKS

Influenza

Acute respiratory infection caused by influenza A or B viruses, characterised by fever, myalgia, cough, and headache. Seasonal epidemics cause significant morbidity and mortality, particularly in the elderly and high-risk groups. Annual vaccination is the primary prevention strategy.

MRCP Part 1 · MRCP Part 2 · PLAB 1 · UKMLA · MRCGP AKT · MSRA

Key Facts

Influenza A and B cause seasonal epidemics; influenza A causes pandemics due to antigenic shift (reassortment of genome segments)
Annual UK vaccination programme: offered to all aged ≥65, pregnant women, chronic disease, healthcare workers, children aged 2–10 (nasal spray)
Oseltamivir (Tamiflu) 75mg BD for 5 days: neuraminidase inhibitor - effective if started within 48 hours of symptom onset (NICE TA168)
Complications: secondary bacterial pneumonia (S. aureus, S. pneumoniae), myocarditis, encephalitis, Guillain-Barré syndrome, Reye syndrome (aspirin in children)
UK burden: ~10,000–25,000 excess deaths/year in severe influenza seasons

Antigenic drift

minor mutations

seasonal epidemics; antigenic shift: major reassortment

pandemics (1918, 1957, 1968, 2009)

High-risk groups for complications: >65, <2 years, pregnancy, chronic respiratory/cardiac/renal/liver disease, immunocompromised, diabetes, BMI >40
Diagnosis: nasopharyngeal swab for influenza PCR (rapid point-of-care tests also available)

Overview

Key Facts

Influenza is a major cause of morbidity and mortality in the UK, particularly during winter months. Vaccination remains the most effective preventive strategy. Antiviral treatment should be initiated promptly in at-risk patients.

Epidemiology

UK: ~10,000–25,000 excess winter deaths attributable to influenza in severe seasons
Global: 3–5 million severe cases/year; 290,000–650,000 deaths/year (WHO)
Seasonal peaks: November–March in Northern Hemisphere
Attack rate: 5–10% of adults, 20–30% of children annually
Pandemics: H1N1 (2009), H3N2 (1968), H2N2 (1957), H1N1 (1918 - 50 million deaths)

Aetiology

Influenza A: subtypes defined by haemagglutinin (H1–18) and neuraminidase (N1–11); infects humans, birds, pigs
Influenza B: two lineages (Victoria, Yamagata); humans only; typically milder
Influenza C: mild, sporadic
Transmission: respiratory droplets, aerosols, fomites; incubation 1–4 days; infectious from 1 day before to 5–7 days after symptom onset

Pathophysiology

Virus binds sialic acid residues on respiratory epithelial cells via haemagglutinin

Neuraminidase cleaves sialic acid

release of progeny virions

spread

Epithelial cell death

mucosal inflammation

susceptibility to secondary bacterial infection

Systemic inflammatory response: cytokine release → fever, myalgia, malaise
Severe disease: viral pneumonitis → ARDS; secondary bacterial pneumonia (S. aureus, S. pneumoniae)
Antigenic drift: point mutations in HA/NA genes → seasonal epidemics (need annual vaccine update)

Antigenic shift

reassortment between human and animal influenza A strains

novel virus

pandemic

Clinical Presentation

Typical Presentation

Sudden onset high fever (>38.5°C), rigors
Severe myalgia and arthralgia
Headache
Dry cough
Sore throat
Prostration and malaise (often more severe than common cold)
Duration: 5–7 days (cough may persist 2 weeks)

Complications

Primary viral pneumonia: progressive dyspnoea, bilateral infiltrates → ARDS
Secondary bacterial pneumonia: classically S. aureus (rapid onset, cavitation) or S. pneumoniae (after initial improvement)
Myocarditis/pericarditis: chest pain, troponin elevation
Encephalitis/encephalopathy: rare, confusion, seizures
Rhabdomyolysis: myalgia, raised CK, AKI
Reye syndrome: hepatic encephalopathy in children given aspirin
Exacerbation of chronic disease: COPD, asthma, heart failure

Red Flags

Dyspnoea, tachypnoea, SpO2 <92%
Haemoptysis
Persistent fever >5 days (secondary infection)
Confusion or altered consciousness
Dehydration, unable to tolerate oral fluids
High-risk patient with typical influenza symptoms

Differential Diagnosis

Diagnosis	Key Features	Investigation
COVID-19	Similar presentation, anosmia, endemic	SARS-CoV-2 PCR
RSV	Bronchiolitis (children), elderly	RSV PCR
Common cold (rhinovirus)	Milder, coryzal symptoms predominate, no prostration	Clinical diagnosis
Bacterial pneumonia	Productive cough, focal consolidation, higher CRP	CXR, sputum culture
Mycoplasma pneumoniae	Younger adults, dry cough, gradual onset, erythema multiforme	Mycoplasma PCR/serology
Meningitis	Neck stiffness, photophobia, rash	LP, blood cultures

Diagnosis / Investigation

Bedside

Nasopharyngeal swab: influenza PCR (gold standard) - also tests for COVID-19 and RSV (multiplex PCR)
Point-of-care rapid influenza test: less sensitive (~60–70%) but fast (15 min)
SpO2: assess severity
NEWS2: escalation tool

Bloods

FBC: lymphopenia, relative leucopenia (high WCC suggests secondary bacterial infection)
CRP/procalcitonin: CRP moderately raised; procalcitonin low in viral, high if bacterial superinfection
U&Es, LFTs: assess organ function
CK: if rhabdomyolysis suspected
Blood cultures: if secondary bacterial infection suspected
Blood gas: if respiratory compromise

Imaging

CXR: if pneumonia suspected - bilateral interstitial infiltrates (viral) or lobar consolidation (bacterial)
CT chest: if complicated pneumonia, ARDS

Special Tests

Viral typing/subtyping: for surveillance (PHE/UKHSA)
Sputum culture: if secondary bacterial pneumonia suspected

Management

Non-pharmacological

Rest and hydration: adequate oral fluid intake
Isolation: respiratory droplet precautions; stay home for ≥5 days from symptom onset
Infection control in hospital: surgical mask, hand hygiene, single room if possible

Pharmacological

Antivirals (NICE TA168):

Oseltamivir (Tamiflu) 75mg BD for 5 days: indicated in at-risk patients within 48 hours of symptoms
Zanamivir (Relenza) 10mg BD inhaled for 5 days: alternative if oseltamivir contraindicated
Consider in hospitalised patients even if >48 hours from onset (may still reduce duration)
Post-exposure prophylaxis: oseltamivir 75mg OD for 10 days for close contacts of confirmed cases who are at risk

Symptomatic treatment:

Paracetamol/ibuprofen for fever and myalgia
Avoid aspirin in children <16 (Reye syndrome risk)

Secondary bacterial pneumonia:

Treat per NICE NG138 (community-acquired pneumonia guidelines)
Co-amoxiclav 625mg TDS or doxycycline 200mg loading then 100mg OD
If severe/S. aureus suspected: flucloxacillin 1g QDS IV ± gentamicin

Vaccination (annual):

Quadrivalent inactivated vaccine: ≥65 (adjuvanted - aQIV), pregnant women, at-risk adults
Live attenuated nasal spray (LAIV): children aged 2–10
Healthcare workers: annual vaccination recommended
Timing: September–November (before flu season peak)

Surgical/Interventional

Not applicable for uncomplicated influenza
Ventilatory support (NIV/invasive) for ARDS
ECMO: in refractory ARDS (specialist centres)

Referral Criteria

Hospital admission: severe symptoms, SpO2 <92%, dehydration, complications
ICU: ARDS, septic shock, multi-organ failure
Public health notification: not individually notifiable but outbreaks are reportable

Prognosis

Uncomplicated influenza: self-limiting in 5–7 days in most healthy adults
Hospitalisation rate: ~1% overall, much higher in elderly and high-risk groups
UK excess winter deaths attributable to influenza: 10,000–25,000 in severe seasons
Secondary bacterial pneumonia mortality: 10–30%
ARDS from influenza: ICU mortality ~30–40%
Vaccination reduces hospitalisation by 40–60% (higher in well-matched seasons)
Oseltamivir: reduces symptom duration by ~1 day and reduces complications in at-risk groups
Pandemic influenza (e.g. 1918 H1N1): case-fatality rate was ~2–3% (50 million deaths globally)
Children: generally good prognosis; rare fulminant cases with encephalopathy

Other Relevant Information

UK Influenza Vaccination Programme

Group	Vaccine Type
Age ≥65	Adjuvanted QIV (aQIV)
Age 50–64	QIV
Pregnant women	QIV (any trimester)
Chronic disease (heart, lung, kidney, liver, diabetes)	QIV
Immunosuppressed	QIV (avoid LAIV)
Healthcare workers	QIV
Children 2–10 years	LAIV (nasal spray)
Carers and household contacts of immunocompromised	QIV

Influenza vs Common Cold

Feature	Influenza	Common Cold
Onset	Sudden	Gradual
Fever	High (>38.5°C)	Low-grade/absent
Myalgia	Severe	Mild
Cough	Dry, prominent	Mild
Prostration	Marked	Rare
Duration	5–7 days	3–5 days

NICE Guidelines / CKS

Measles

Highly contagious viral infection caused by the measles morbillivirus, characterised by fever, cough, coryza, conjunctivitis, Koplik spots, and a maculopapular rash. Vaccine-preventable (MMR) but re-emerging due to declining vaccination rates. Notifiable disease in the UK.

MRCP Part 1 · MRCP Part 2 · PLAB 1 · UKMLA · MRCGP AKT · MSRA

Key Facts

Prodrome: fever, cough, coryza, conjunctivitis (the 3 Cs + fever) followed by Koplik spots (pathognomonic white spots on buccal mucosa)
Rash: maculopapular, starts behind ears/hairline, spreads cephalocaudally - appears day 3–5 of illness
Highly contagious: R0 = 12–18; airborne transmission; infectious from 4 days before to 4 days after rash onset
MMR vaccine: 2 doses (12–13 months and 3 years 4 months); 97% effective after 2 doses
Complications: otitis media (~7%), pneumonia (~6%), encephalitis (~0.1%), SSPE (subacute sclerosing panencephalitis - fatal, years later)
Notifiable disease: must notify local health protection team immediately on clinical suspicion
Vitamin A supplementation: recommended by WHO in severe measles (200,000 IU for 2 days in children >12 months)
UK resurgence: outbreaks in under-vaccinated communities; 2024 had significant outbreaks in Birmingham and London

Overview

Key Facts

Measles is one of the most contagious infectious diseases known. Despite effective vaccination, outbreaks continue to occur in under-vaccinated populations. It remains a leading cause of vaccine-preventable death in children globally.

Epidemiology

Global: ~9 million cases/year; ~128,000 deaths/year (WHO 2023)
UK: largely eliminated but periodic outbreaks in under-vaccinated communities
2023–2024: significant UK outbreak with >1,000 confirmed cases (primarily unvaccinated children)
UK MMR uptake: ~85% first dose (below 95% herd immunity threshold)
Most deaths in children <5 years and immunocompromised

Aetiology

Measles morbillivirus (family Paramyxoviridae, genus Morbillivirus)
Single-stranded RNA virus; only one serotype (vaccine highly effective)
Transmission: airborne (droplet nuclei) - can remain airborne for 2 hours in enclosed spaces
Incubation: 10–14 days (to rash onset)

Pathophysiology

Virus enters via respiratory epithelium

replicates in lymphoid tissue

viraemia

widespread dissemination

Infects dendritic cells, macrophages, T and B lymphocytes → transient but profound immunosuppression (immune amnesia lasting weeks to months)
Endothelial infection → Warthin-Finkeldey giant cells in lymphoid tissue
Rash: immune-mediated (T-cell response to infected endothelial cells) - immunocompromised patients may not develop rash
Complications arise from immunosuppression (secondary bacterial infection) or direct viral damage (encephalitis)

Clinical Presentation

Prodromal Phase (2–4 days)

High fever (often >40°C)
Cough (dry), coryza, conjunctivitis (the 3 Cs)
Koplik spots: bluish-white spots on erythematous buccal mucosa (opposite molars) - pathognomonic, appear 1–2 days before rash
Malaise, irritability

Exanthem Phase

Maculopapular rash

starts behind ears and hairline

face

trunk

extremities (cephalocaudal spread)

Rash becomes confluent, may desquamate
Fever peaks with rash onset then resolves
Lymphadenopathy

Complications

Otitis media: ~7% (most common complication)
Pneumonia: ~6% (leading cause of measles death)
Febrile seizures: ~1%
Encephalitis: ~0.1% (1 in 1,000 cases) - 15% mortality, 25% permanent brain damage
SSPE: ~1 in 25,000 - occurs 7–10 years post-infection; fatal progressive neurological deterioration

Red Flags

Respiratory distress (pneumonia)
Altered consciousness (encephalitis)
Immunocompromised patient (severe/prolonged disease, absence of rash)
Pregnancy (increased maternal mortality, preterm delivery)
Infants <12 months (too young for vaccination)

Differential Diagnosis

Diagnosis	Key Features	Investigation
Rubella	Milder, postauricular lymphadenopathy, pink rash, arthralgia	Rubella IgM
Scarlet fever	Sandpaper rash, strawberry tongue, preceding pharyngitis	Throat swab, ASO titre
Parvovirus B19	Slapped cheek, lacy reticular rash, arthropathy	Parvovirus IgM
Roseola (HHV-6)	High fever then rash on defervescence, infants	Clinical, HHV-6 PCR
Kawasaki disease	Persistent fever, conjunctivitis, strawberry tongue, desquamation	Clinical criteria, echo
Drug eruption	Temporal relationship with medication	Drug history
Infectious mononucleosis	Pharyngitis, lymphadenopathy, rash with amoxicillin	Monospot, EBV serology

Diagnosis / Investigation

Bedside

Clinical diagnosis: prodrome + Koplik spots + characteristic rash is usually sufficient
Observations: temperature, SpO2

Bloods

Measles IgM: positive from rash onset (send within 5 days of rash for UKHSA confirmation)
Oral fluid swab (salivary IgM): preferred sample for UKHSA confirmation in UK
Measles RNA PCR: throat swab, nasopharyngeal swab, or urine - for genotyping and confirmation
FBC: leucopenia, lymphopenia (characteristic)
LFTs: transaminitis in complicated cases

Imaging

CXR: if pneumonia suspected (interstitial infiltrates or secondary bacterial consolidation)
CT head: if encephalitis suspected

Special Tests

Lumbar puncture: if encephalitis - lymphocytic CSF, elevated protein, measles PCR/IgM in CSF
UKHSA notification: mandatory notification on clinical suspicion; send confirmation samples

Management

Non-pharmacological

Isolation: airborne precautions; infectious from 4 days before to 4 days after rash onset
Supportive care: rest, fluids, antipyretics (paracetamol)
Notification: immediately notify local health protection team on clinical suspicion
Contact tracing: identify susceptible contacts; offer MMR within 72 hours of exposure (post-exposure prophylaxis)

Pharmacological

Vitamin A: WHO recommends for all children with measles - 200,000 IU for age >12 months (50,000 IU for 6–11 months) for 2 consecutive days
Antibiotics: only for secondary bacterial complications (otitis media, pneumonia)
Human normal immunoglobulin (HNIG): post-exposure prophylaxis for immunocompromised, pregnant, or infants <6 months if exposed - within 6 days of exposure
Ribavirin: considered in severe/immunocompromised cases (evidence limited)

Post-exposure prophylaxis:

MMR vaccine within 72 hours of exposure: for unvaccinated contacts aged ≥6 months
HNIG: for immunocompromised, pregnant, infants <6 months who cannot receive MMR

Surgical/Interventional

Not applicable

Referral Criteria

Hospital admission: pneumonia, encephalitis, immunocompromised, severe dehydration, pregnancy
Public health: all cases (statutory notification)
Paediatrics: infants, complicated cases

Prognosis

Uncomplicated measles: full recovery in 7–10 days
Overall case-fatality rate: 0.1–0.3% in developed countries; up to 5–10% in developing countries
Pneumonia: leading cause of measles death (~60% of fatalities)
Encephalitis: 15% mortality, 25% permanent neurological sequelae
SSPE: universally fatal (onset 7–10 years post-infection)
Immunocompromised patients: mortality up to 30%
Measles in pregnancy: increased risk of spontaneous abortion, preterm birth, maternal pneumonia
Immune amnesia: measles infection resets immune memory - increased susceptibility to other infections for months

Other Relevant Information

UK MMR Vaccination Schedule

Dose	Age	Vaccine
1st	12–13 months	MMR
2nd	3 years 4 months	MMR
Catch-up	Any age (if missed)	2 doses, 1 month apart

Measles Complications by Frequency

Complication	Incidence
Otitis media	~7%
Pneumonia	~6%
Diarrhoea	~8%
Febrile seizures	~1%
Encephalitis	~0.1% (1 in 1,000)
Death	~0.1–0.3% (developed countries)
SSPE	~1 in 25,000 (years later)

NICE Guidelines / CKS

Mumps

Acute viral infection caused by mumps virus (Paramyxoviridae) characterised by fever and painful parotid gland swelling. Vaccine-preventable with MMR. Complications include orchitis (20–30% post-pubertal males), meningitis, and pancreatitis. Notifiable disease.

MRCP Part 1 · MRCP Part 2 · PLAB 1 · UKMLA · MRCGP AKT · MSRA

Key Facts

Parotitis: bilateral painful parotid swelling in ~70% of symptomatic cases - pathognomonic appearance
Orchitis: 20–30% of post-pubertal males; usually unilateral; subfertility rare (~1%)
Meningitis: ~10% of mumps cases; usually self-limiting aseptic meningitis
MMR vaccine: 2 doses; 88% effective after 2 doses against mumps (less effective than measles component)
Sensorineural deafness: ~1 in 20,000 - usually unilateral; was leading cause of acquired deafness in children pre-vaccine era
Notifiable disease: must be reported to local health protection team
Incubation period: 14–25 days (average 17 days)
Outbreaks continue in universities/young adults - often in those who received only 1 MMR dose

Overview

Key Facts

Mumps is a systemic viral infection with predilection for glandular and nervous tissue. Despite MMR vaccination, outbreaks still occur, particularly in young adults in close-contact settings.

Epidemiology

UK: ~1,000–5,000 confirmed cases/year; periodic outbreaks in universities
Most cases in 15–30-year-olds (born before complete 2-dose MMR programme or received only 1 dose)
Pre-vaccine era: ~1,200 cases/100,000/year
30% of infections are subclinical

Aetiology

Mumps virus: Paramyxoviridae family, genus Rubulavirus; single-stranded RNA
Transmission: respiratory droplets, direct contact with saliva
Incubation: 14–25 days
Infectious: 2 days before to 5 days after parotid swelling onset

Pathophysiology

Virus replicates in nasopharyngeal epithelium

viraemia

tropism for glandular tissue (salivary, pancreas, testes, ovaries) and CNS

Parotid inflammation: lymphocytic infiltration, oedema, ductal obstruction
Orchitis: interstitial oedema and lymphocytic infiltration → seminiferous tubule damage (rarely causes complete infertility due to usual unilateral involvement)
Meningitis: direct viral invasion of meninges

Clinical Presentation

Typical Presentation

Prodrome: fever, malaise, headache, myalgia (1–2 days)
Parotid swelling: painful, bilateral (70%) or unilateral; earache, difficulty chewing
Jaw angle obliterated; earlobe pushed upward and outward
Swelling peaks at day 3, resolves over 7–10 days

Complications

Orchitis: 20–30% post-pubertal males; painful testicular swelling 4–8 days after parotitis; usually unilateral
Oophoritis: 5% post-pubertal females; pelvic pain
Meningitis: ~10%; headache, neck stiffness, photophobia - usually self-limiting
Encephalitis: ~0.1%; more serious, seizures, altered consciousness
Pancreatitis: ~5%; epigastric pain, vomiting, raised amylase
Sensorineural deafness: ~1 in 20,000; usually unilateral

Red Flags

Severe headache and neck stiffness (meningitis/encephalitis)
Severe testicular pain and swelling
Severe abdominal pain (pancreatitis)
Altered consciousness

Differential Diagnosis

Diagnosis	Key Features	Investigation
Bacterial parotitis	Unilateral, purulent discharge from Stensen's duct, elderly/dehydrated	USS, pus swab for culture
Parotid calculus (sialolithiasis)	Intermittent swelling with eating, palpable stone	USS, sialography
Parotid tumour	Painless, progressive, firm mass, facial nerve involvement	USS, FNA, MRI
EBV (glandular fever)	Pharyngitis, generalised lymphadenopathy, splenomegaly	Monospot, EBV serology
HIV parotitis	Bilateral, painless, cystic parotid enlargement	HIV test
Sjögren syndrome	Dry eyes, dry mouth, bilateral parotid swelling, arthralgia	Anti-Ro/La, Schirmer test

Diagnosis / Investigation

Bedside

Clinical diagnosis: bilateral parotid swelling in appropriate context is usually sufficient
Temperature: fever monitoring

Bloods

Mumps IgM: positive from symptom onset (oral fluid sample preferred in UK for UKHSA confirmation)
Mumps PCR: buccal/throat swab or urine
Serum amylase: elevated (parotitis and/or pancreatitis)
FBC: leucopenia or normal; may see lymphocytosis
LFTs: mildly deranged in some cases

Imaging

USS parotid: if diagnosis uncertain or abscess suspected
USS testes: if orchitis - exclude testicular torsion

Special Tests

LP: if meningitis - lymphocytic CSF, elevated protein, normal glucose, mumps PCR in CSF
UKHSA confirmation: oral fluid sample for IgM (gold standard in UK surveillance)

Management

Non-pharmacological

Supportive care: rest, oral fluids, soft diet (chewing worsens pain)
Isolation: 5 days from parotid swelling onset (droplet precautions)
Notification: statutory notification to local health protection team
Warm/cold compresses to parotid area for comfort

Pharmacological

Paracetamol/ibuprofen: for fever and pain
Orchitis: bed rest, scrotal support, analgesia (NSAIDs), consider short course prednisolone (evidence limited)
No specific antiviral treatment
IV fluids: if unable to eat/drink due to pain or pancreatitis

Surgical/Interventional

Not applicable for uncomplicated mumps
Orchitis: rule out torsion with USS if diagnostic uncertainty

Referral Criteria

Hospital admission: meningitis, encephalitis, severe orchitis, pancreatitis, dehydration
Urology: orchitis with diagnostic uncertainty (exclude torsion)
ENT: if parotid abscess suspected
Public health: all cases (notification)

Prognosis

Uncomplicated parotitis: full recovery in 7–10 days
Orchitis: testicular atrophy in 30–50% of affected testes; infertility rare (~1%) due to usually unilateral involvement
Meningitis: self-limiting, full recovery in most; rarely permanent sensorineural deafness
Encephalitis: mortality <1% but neurological sequelae possible
Deafness: 1 in 20,000; usually unilateral, permanent
Pancreatitis: self-limiting; no evidence of increased diabetes risk
MMR provides ~88% protection (waning immunity may explain outbreaks in young adults)

Other Relevant Information

Mumps Complications Summary

Complication	Incidence	Notes
Parotitis	70% of symptomatic	Bilateral in 70%
Orchitis	20–30% (post-pubertal males)	Usually unilateral
Meningitis	~10%	Self-limiting
Pancreatitis	~5%	Raised amylase
Oophoritis	~5% (post-pubertal females)	Fertility usually preserved
Encephalitis	~0.1%	Serious, rare
Deafness	1 in 20,000	Unilateral, sensorineural

NICE Guidelines / CKS

Rubella

Mild viral exanthem caused by rubella virus (Togaviridae), characterised by low-grade fever, maculopapular rash, and postauricular lymphadenopathy. Primary importance is congenital rubella syndrome (CRS) when infection occurs in early pregnancy, causing cataracts, deafness, and cardiac defects.

MRCP Part 1 · MRCP Part 2 · PLAB 1 · UKMLA · MRCGP AKT · MSRA

Key Facts

Congenital rubella syndrome (CRS): cataracts, sensorineural deafness, congenital heart defects (PDA, pulmonary stenosis), microcephaly - risk highest if infection in first trimester (>80%)
Postauricular and suboccipital lymphadenopathy: characteristic and may precede the rash

Rash

pink, maculopapular, starts on face

trunk

extremities; lasts 3 days (German measles = 3-day measles)

MMR vaccine: eliminated endemic rubella in the UK; WHO-verified rubella elimination status since 2017
Arthralgia/arthritis: common in adult women (up to 70%); small joint polyarthritis
Notifiable disease: must report to local health protection team
Non-immune pregnant women: urgent rubella IgG and IgM if exposed; consider HNIG if non-immune and exposed before 20 weeks
Diagnosis: rubella IgM (acute infection) and rubella IgG (immunity); rubella PCR for confirmation

Overview

Key Facts

Rubella is a mild childhood exanthem in most cases but its significance lies in teratogenicity during early pregnancy. The MMR vaccination programme has effectively eliminated endemic rubella in the UK.

Epidemiology

UK: endemic rubella eliminated (WHO verified 2017); rare imported cases
Pre-vaccine era: epidemics every 6–9 years; up to 300 CRS cases/year in the UK
Current UK: <10 confirmed cases/year (mostly imported)
CRS: extremely rare in UK now (<1 case/year)

Aetiology

Rubella virus: Togaviridae family, genus Rubivirus; single-stranded RNA
Transmission: respiratory droplets; incubation 14–21 days
Infectious: 7 days before to 7 days after rash onset
Congenital rubella: viraemia during pregnancy → transplacental infection

Pathophysiology

Virus replicates in nasopharyngeal epithelium

viraemia

rash (immune-mediated)

In pregnancy: virus crosses placenta

fetal infection

cell damage during organogenesis

CRS pathogenesis: viral inhibition of cell division, apoptosis, vasculitis in developing organs
Risk of CRS by gestational age: <12 weeks ~80%; 12–16 weeks ~50%; 16–20 weeks ~25%; >20 weeks minimal risk

Clinical Presentation

Postnatal Rubella

Low-grade fever
Postauricular, suboccipital, and posterior cervical lymphadenopathy (precedes rash by 1–5 days)

Pink maculopapular rash: face

trunk

extremities; lasts ~3 days

Arthralgia/arthritis: especially adult women (small joints - fingers, wrists)
Generally mild; 25–50% subclinical

Congenital Rubella Syndrome

Classic triad: sensorineural deafness, congenital heart defects (PDA, pulmonary stenosis), cataracts/glaucoma
Additional: microcephaly, intellectual disability, hepatosplenomegaly, thrombocytopenia (blueberry muffin baby), radiolucent bone disease
Infant may excrete virus for months (contagious)

Red Flags

Rubella exposure in non-immune pregnant woman (especially <20 weeks)
Rash illness in early pregnancy
Neonate with cataracts + heart murmur + deafness

Differential Diagnosis

Diagnosis	Key Features	Investigation
Measles	Higher fever, 3 Cs, Koplik spots, more unwell	Measles IgM/PCR
Parvovirus B19	Slapped cheek, reticular rash, arthropathy	Parvovirus IgM
Scarlet fever	Sandpaper rash, strawberry tongue, pharyngitis	Throat swab, ASO titre
Drug eruption	Temporal drug relationship	Drug history
Enteroviral exanthem	Various rash patterns, hand-foot-mouth	Enterovirus PCR
EBV	Tonsillar exudate, splenomegaly, atypical lymphocytes	Monospot, EBV serology

Diagnosis / Investigation

Bloods

Rubella IgM: positive in acute infection (detectable from rash onset, peaks at 1–2 weeks)
Rubella IgG: seroconversion or 4-fold rise in paired sera confirms acute infection; positive IgG indicates immunity
Rubella PCR: throat swab or urine - for confirmation and genotyping
FBC: mild thrombocytopenia, leucopenia

In Pregnancy

Rubella IgG: check immune status (antenatal booking blood)
If exposed and non-immune: urgent rubella IgM and IgG; repeat at 2–3 weeks
Amniocentesis: rubella PCR on amniotic fluid if maternal infection confirmed (after 15 weeks)

Congenital Rubella

Rubella IgM in neonate: indicates congenital infection (does not cross placenta)
Rubella PCR: on infant blood, urine, throat swab
Ophthalmology: cataracts, glaucoma
Audiology: sensorineural deafness
Echocardiography: PDA, pulmonary stenosis
Cranial USS/MRI: microcephaly, calcification

Management

Non-pharmacological

Supportive care: rest, fluids, paracetamol for fever/arthralgia
Isolation: 7 days after rash onset; keep away from pregnant women
Notification: statutory notification
Contact tracing: identify susceptible pregnant contacts

Pharmacological

No specific antiviral treatment
HNIG (human normal immunoglobulin): may be offered to non-immune pregnant women exposed before 20 weeks - does NOT prevent infection but may reduce severity
Post-exposure MMR: not recommended in pregnancy (live vaccine contraindicated)
Arthralgia: NSAIDs (not in pregnancy)

Vaccination

MMR vaccine: 2 doses in childhood; catch-up for non-immune women of childbearing age
Post-partum vaccination: offer MMR to non-immune women after delivery (avoid pregnancy for 1 month after)
Live vaccine: contraindicated in pregnancy and immunocompromised

Referral Criteria

Fetal medicine: if rubella infection confirmed in pregnancy - discuss options including termination if first-trimester infection
Paediatrics: CRS management (multidisciplinary - cardiology, ophthalmology, audiology)
Public health: all cases

Prognosis

Postnatal rubella: excellent prognosis, self-limiting in 3–5 days
Arthritis: self-limiting in 2–4 weeks; chronic arthritis rare
CRS first trimester infection: >80% risk of fetal abnormalities
CRS second trimester: ~25% risk (mainly deafness)
CRS after 20 weeks: minimal risk
CRS infant: lifelong disabilities in most cases
Deafness in CRS: most common single defect (~60–75%)
CRS mortality in infancy: ~10–20% in severe cases

Other Relevant Information

Congenital Rubella Syndrome Features

System	Manifestations
Eye	Cataracts, microphthalmos, glaucoma, retinopathy
Ear	Sensorineural deafness (most common)
Heart	PDA (most common cardiac), pulmonary stenosis, VSD
CNS	Microcephaly, intellectual disability, meningoencephalitis
Haematological	Thrombocytopenia, anaemia (blueberry muffin baby)
Other	Hepatosplenomegaly, IUGR, radiolucent bone disease

Risk of CRS by Gestational Age

Gestational Age	Risk of Fetal Infection	Risk of Defects
<12 weeks	>80%	>80%
12–16 weeks	~50%	~50% (mainly deafness)
16–20 weeks	~25%	~25% (deafness)
>20 weeks	Minimal	Minimal

NICE Guidelines / CKS

Varicella Zoster

Primary infection with varicella-zoster virus (VZV) causes chickenpox (varicella), characterised by a pruritic vesicular rash. Reactivation from dorsal root ganglia causes shingles (herpes zoster). Complications include pneumonia, encephalitis, and secondary bacterial infection. Significant risk in pregnancy and immunocompromised patients.

MRCP Part 1 · MRCP Part 2 · PLAB 1 · UKMLA · MRCGP AKT · MSRA

Key Facts

Chickenpox rash

crops of lesions in different stages (macules

papules

vesicles

pustules

crusts) - centripetal distribution

Infectious period: 2 days before rash until all lesions crusted over (usually 5–7 days)
Shingles: dermatomal vesicular rash; post-herpetic neuralgia in ~20% of patients >50 years
Varicella in pregnancy: risk of varicella pneumonia (mortality up to 10%); fetal varicella syndrome if <20 weeks (limb hypoplasia, eye defects, skin scarring)
VZIG (varicella-zoster immunoglobulin): for non-immune pregnant women, neonates, and immunocompromised exposed to VZV - within 10 days of exposure
Aciclovir: 800mg 5× daily for 7 days (chickenpox in adults/high-risk); 800mg 5× daily for 7 days (shingles within 72 hours of rash onset)
Shingrix vaccine (recombinant): offered to adults aged 70–79 in UK; >90% effective against shingles and PHN
Notifiable disease: varicella deaths must be reported; individual cases not routinely notifiable but outbreaks should be reported

Overview

Key Facts

VZV is a highly contagious herpesvirus that establishes lifelong latency in dorsal root ganglia. Primary infection (chickenpox) is common in childhood; reactivation (shingles) increases with age and immunosuppression.

Epidemiology

Chickenpox: ~600,000 cases/year in UK; ~90% by age 15
Shingles: ~50,000 cases/year in UK; lifetime risk ~25–30%
Shingles incidence increases sharply >50 years
Varicella pneumonia: up to 10–20% of adult chickenpox cases
UK shingles vaccination programme: ages 70–79 (Shingrix from 2023)

Aetiology

VZV: human herpesvirus 3 (HHV-3); double-stranded DNA, enveloped
Transmission: airborne (highly infectious - R0 ~10) + direct contact with vesicle fluid
Incubation: 10–21 days (chickenpox)
After primary infection, virus lies dormant in dorsal root ganglia → reactivation = shingles

Pathophysiology

Primary infection: virus replicates in oropharynx

viraemia

skin (vesicle formation) + visceral dissemination

Latency: VZV DNA remains in sensory ganglia neurons

Reactivation: declining cell-mediated immunity

virus travels down sensory nerve

dermatomal vesicular rash

Post-herpetic neuralgia: nerve fibre damage, neuroinflammation, altered pain signalling

Clinical Presentation

Chickenpox (Primary VZV)

Prodrome: low-grade fever, malaise (1–2 days)

Pruritic rash

crops at different stages (macules

papules

vesicles

crusts)

Centripetal distribution: trunk > face > limbs; scalp involvement common
Vesicles on erythematous base: described as 'dewdrop on a rose petal'
New crops continue for 3–5 days

Shingles (Reactivated VZV)

Prodromal pain/burning in dermatomal distribution (2–3 days before rash)
Unilateral dermatomal vesicular rash - does NOT cross midline
Most common: thoracic dermatomes (T3–L2)
Herpes zoster ophthalmicus: V1 (ophthalmic division of trigeminal) - Hutchinson sign (vesicles on nose tip) indicates nasociliary nerve involvement → risk of keratitis
Ramsay Hunt syndrome: VZV reactivation in geniculate ganglion → facial nerve palsy + vesicles in ear/palate

Complications

Secondary bacterial infection: S. aureus, Group A Strep
Varicella pneumonia: adults, smokers, pregnancy - bilateral nodular infiltrates
Encephalitis/cerebellitis: ataxia, confusion
Post-herpetic neuralgia: pain persisting >90 days after rash; ~20% of >50s
Disseminated zoster: immunocompromised - multi-dermatomal, visceral involvement

Red Flags

Immunocompromised patient with VZV (dissemination risk)
Pregnancy (varicella pneumonia, fetal varicella syndrome)
Neonate exposed perinatally
Eye involvement (herpes zoster ophthalmicus)
Facial nerve involvement (Ramsay Hunt)
Respiratory symptoms (varicella pneumonia)

Differential Diagnosis

Diagnosis	Key Features	Investigation
HSV (herpes simplex)	Grouped vesicles, recurrent, localised	HSV PCR/swab
Impetigo	Honey-crusted lesions, superficial, localised	Wound swab
Contact dermatitis	Distribution follows contact pattern, pruritic	History, patch testing
Insect bites	Papular urticaria, exposed areas	Clinical
Disseminated HSV	Immunocompromised, widespread vesicles	HSV PCR
Dermatitis herpetiformis	Grouped vesicles, elbows/knees, associated coeliac	Anti-tTG, skin biopsy (IgA)

Diagnosis / Investigation

Bedside

Clinical diagnosis: usually sufficient for typical chickenpox and shingles
Vesicle swab for VZV PCR: gold standard confirmation

Bloods

VZV IgG: determines immune status (important for contacts and pregnancy)
VZV IgM: acute infection
FBC, LFTs, CRP: if complicated
CXR: if varicella pneumonia suspected

Imaging

CXR: bilateral nodular infiltrates in varicella pneumonia
MRI brain: if encephalitis suspected

Special Tests

VZV PCR on vesicle fluid: most sensitive and specific
Tzanck smear: multinucleated giant cells (non-specific for VZV vs HSV; rarely used)
LP: if meningitis/encephalitis - lymphocytic CSF, VZV PCR

Management

Non-pharmacological

Isolation: until all lesions crusted (usually 5–7 days from rash onset)
Avoid contact with high-risk individuals: pregnant women, neonates, immunocompromised
Calamine lotion, cool baths: for pruritus
Keep nails short: reduce secondary infection from scratching

Pharmacological

Chickenpox in adults/high-risk:

Aciclovir 800mg 5× daily for 7 days: start within 24 hours of rash if >14 years, immunocompromised, chronic skin/lung disease, or on steroids
Not routinely recommended for healthy children

Shingles:

Aciclovir 800mg 5× daily for 7 days or valaciclovir 1g TDS for 7 days: start within 72 hours of rash (or if new lesions still appearing)
Treat ALL immunocompromised patients regardless of timing

Severe/disseminated/immunocompromised:

IV aciclovir 10mg/kg TDS for 7–14 days

Varicella in pregnancy:

Aciclovir 800mg 5× daily for 7 days if >20 weeks (or any gestation if severe)
VZIG: for non-immune pregnant women exposed to VZV (within 10 days)

Post-herpetic neuralgia:

Amitriptyline 10–75mg ON, or gabapentin 300–3600mg/day, or pregabalin 75–600mg/day
5% lidocaine patches: topical option
Capsaicin cream 0.075%: alternative

Vaccination:

Shingrix (recombinant adjuvanted): 2 doses, 2 months apart; offered to 70–79-year-olds in UK; >90% efficacy
Varicella vaccine: not in routine UK childhood schedule but used for susceptible healthcare workers and close contacts of immunocompromised

Referral Criteria

Ophthalmology: herpes zoster ophthalmicus (same-day referral)
ENT: Ramsay Hunt syndrome
Hospital admission: varicella pneumonia, encephalitis, disseminated zoster, immunocompromised
Fetal medicine: varicella in pregnancy <20 weeks
Neonatology: neonatal varicella exposure

Prognosis

Childhood chickenpox: self-limiting, excellent prognosis; mortality <1 per 100,000
Adult chickenpox: higher complication rate; mortality ~1–2 per 100,000
Varicella pneumonia: mortality 10–30% untreated, ~5% with aciclovir
Shingles: most resolve in 2–4 weeks; PHN risk increases with age
PHN: can persist for months to years; ~20% of >50s, ~30% of >80s
Fetal varicella syndrome: ~2% risk if maternal infection <20 weeks; limb hypoplasia, eye defects, CNS abnormalities
Neonatal varicella (maternal rash 5 days before to 2 days after delivery): mortality up to 30% without treatment

Other Relevant Information

UK Shingles Vaccination Programme

Age	Vaccine	Schedule
70–79 years	Shingrix (recombinant)	2 doses, 2 months apart
Immunocompromised (50+)	Shingrix	2 doses
Zostavax (live)	Previously used	No longer recommended

Fetal Varicella Syndrome Features

Feature	Frequency
Skin scarring (cicatricial)	Common
Limb hypoplasia	~70%
Eye defects (chorioretinitis, cataracts)	~60%
CNS abnormalities	~50%
Low birth weight	~50%

NICE Guidelines / CKS

Herpes Simplex

Infection with herpes simplex virus type 1 (orolabial) or type 2 (genital), causing painful vesicular lesions. Establishes lifelong latency in sensory ganglia with periodic reactivation. HSV encephalitis is a medical emergency requiring urgent IV aciclovir.

MRCP Part 1 · MRCP Part 2 · PLAB 1 · UKMLA · MRCGP AKT · MSRA

Key Facts

HSV-1: predominantly orolabial (cold sores); HSV-2: predominantly genital herpes - but either can cause either
HSV encephalitis: most common sporadic viral encephalitis - temporal lobe predilection; mortality >70% untreated, ~20% with IV aciclovir
Neonatal herpes: devastating infection acquired during delivery - mortality up to 30% even with treatment
Treatment: oral aciclovir 400mg TDS for 5 days (genital primary); IV aciclovir 10mg/kg TDS for 14–21 days (encephalitis)
Suppressive therapy: aciclovir 400mg BD long-term for frequent recurrences (≥6/year)
Eczema herpeticum: widespread HSV in atopic eczema - medical emergency requiring IV aciclovir
Erythema multiforme: HSV is the most common trigger for recurrent erythema multiforme
Diagnosis: HSV PCR on vesicle swab (gold standard) or HSV PCR on CSF (encephalitis)

Overview

Key Facts

HSV infections are extremely common, affecting over two-thirds of the global population. Most infections are asymptomatic or mild, but severe manifestations including encephalitis and neonatal herpes can be life-threatening.

Epidemiology

HSV-1 seroprevalence: ~50–80% of UK adults
HSV-2 seroprevalence: ~10–15% of UK adults
Genital herpes: ~30,000 new diagnoses/year in UK sexual health clinics
HSV encephalitis: ~2–4 per million/year in UK
Neonatal herpes: ~1.65 per 100,000 live births in UK

Aetiology

HSV-1 and HSV-2: double-stranded DNA viruses (Herpesviridae, Alphaherpesvirinae)
Transmission: direct contact with infected secretions (saliva, genital secretions)
Asymptomatic shedding accounts for most transmission
Incubation: 2–12 days

Pathophysiology

Virus enters through mucosal surfaces or skin breaks

replicates in epithelial cells

vesicle formation

Retrograde axonal transport to sensory ganglia (trigeminal for HSV-1, sacral for HSV-2)
Establishes latency in neuronal cell bodies

Reactivation: stress, UV light, immunosuppression, menstruation

anterograde transport

recurrent lesions

HSV encephalitis: typically reactivation (HSV-1) → temporal lobe inflammation and necrosis

Clinical Presentation

Primary Orolabial Herpes (Gingivostomatitis)

Children/young adults; fever, malaise
Painful vesicles and ulcers on lips, gums, tongue, palate
Lymphadenopathy, dysphagia
Duration: 10–14 days

Recurrent Orolabial Herpes (Cold Sores)

Prodrome: tingling/burning at lip margin

Grouped vesicles on vermilion border

crust

heal in 7–10 days

Milder and shorter than primary

Primary Genital Herpes

Painful vulval/penile vesicles and ulcers; dysuria
Bilateral inguinal lymphadenopathy
Systemic symptoms: fever, malaise, headache
Duration: 2–3 weeks

Severe Manifestations

HSV encephalitis: fever, headache, confusion, seizures, temporal lobe signs (dysphasia, personality change)
Eczema herpeticum: widespread vesiculopustular rash in atopic eczema
Neonatal herpes: skin/eye/mouth disease, CNS disease, or disseminated disease
HSV keratitis: dendritic ulcer on fluorescein staining

Red Flags

New confusion/seizures with fever (encephalitis)
Widespread vesicles in eczema (eczema herpeticum)
Genital herpes in late pregnancy (neonatal risk)
Eye pain with HSV (keratitis)
Immunocompromised with HSV (dissemination risk)

Differential Diagnosis

Diagnosis	Key Features	Investigation
VZV (chickenpox/shingles)	Dermatomal (shingles) or widespread different stages (chickenpox)	VZV PCR
Aphthous ulcers	Recurrent, non-vesicular, no systemic symptoms	Clinical
Behçet disease	Oral + genital ulcers, uveitis, pathergy	Clinical criteria
Syphilitic chancre	Painless ulcer, inguinal lymphadenopathy	Dark-field microscopy, syphilis serology
Hand-foot-mouth disease	Vesicles on hands, feet, mouth; enterovirus	Enterovirus PCR
Impetigo	Honey-crusted, superficial, S. aureus/Strep	Wound swab

Diagnosis / Investigation

Bedside

HSV PCR on vesicle swab: gold standard for mucocutaneous HSV
Viral swab in transport medium: if PCR not available

Bloods

HSV type-specific serology: IgG for HSV-1 and HSV-2 (useful for determining primary vs recurrent)
FBC, CRP, LFTs: if systemic illness

Special Tests

CSF HSV PCR: gold standard for HSV encephalitis (sensitivity >95%)
MRI brain: temporal lobe oedema, haemorrhage (HSV encephalitis)
EEG: periodic lateralised epileptiform discharges (PLEDs) in HSV encephalitis
Slit-lamp examination: dendritic ulcer (HSV keratitis)
Tzanck smear: multinucleated giant cells (non-specific, rarely used)

Management

Non-pharmacological

Avoid sexual contact during active genital herpes
Saline bathing of genital lesions for comfort
Topical anaesthetic: lidocaine 2% gel for pain
Education: lifelong infection, recurrence, asymptomatic shedding

Pharmacological

Orolabial herpes:

Primary gingivostomatitis: aciclovir 200mg 5× daily for 5 days
Recurrent cold sores: topical aciclovir 5% cream (limited benefit); oral aciclovir if severe/frequent

Genital herpes (BASHH guidelines):

Primary: aciclovir 400mg TDS for 5 days (or valaciclovir 500mg BD for 5 days)
Recurrent: aciclovir 800mg TDS for 2 days (short course) or 400mg TDS for 5 days
Suppressive therapy (≥6 recurrences/year): aciclovir 400mg BD continuously; review at 12 months

HSV encephalitis (MEDICAL EMERGENCY):

IV aciclovir 10mg/kg TDS for 14–21 days - start EMPIRICALLY if suspected (do NOT wait for PCR result)
Adequate IV hydration to prevent aciclovir crystalluria

Eczema herpeticum:

IV aciclovir 5–10mg/kg TDS until improvement, then oral to complete 10–14 days

Neonatal herpes:

IV aciclovir 20mg/kg TDS for 14–21 days

Pregnancy:

Primary genital HSV in third trimester: aciclovir 400mg TDS from 36 weeks; consider caesarean section if active lesions at delivery
Recurrent genital HSV: suppressive aciclovir from 36 weeks; vaginal delivery usually safe

Referral Criteria

Ophthalmology: HSV keratitis (urgent)
Neurology/ID: HSV encephalitis
GUM/sexual health: genital herpes (counselling and management)
Neonatology: suspected neonatal herpes
Dermatology: eczema herpeticum

Prognosis

Orolabial herpes: self-limiting; recurrences decrease over time
Genital herpes: primary episode more severe; recurrences milder and less frequent; HSV-2 recurs more than HSV-1 genitally
HSV encephalitis: mortality >70% untreated; ~20% with IV aciclovir; ~50% have long-term neurological sequelae
Neonatal herpes: SEM disease ~2% mortality with treatment; CNS disease ~6% mortality; disseminated ~30% mortality
Eczema herpeticum: good prognosis with prompt IV aciclovir
Suppressive therapy: reduces recurrences by 70–80% and transmission by ~50%

Other Relevant Information

HSV-1 vs HSV-2 Comparison

Feature	HSV-1	HSV-2
Primary site	Orolabial	Genital
Latency site	Trigeminal ganglion	Sacral ganglia
Seroprevalence (UK)	50–80%	10–15%
Genital recurrence rate	~1/year	~4–5/year
Encephalitis	Most common cause	Rare (neonatal)

HSV Treatment Summary

Condition	Treatment	Duration
Primary genital	Aciclovir 400mg TDS	5 days
Recurrent genital	Aciclovir 800mg TDS	2 days
Suppressive	Aciclovir 400mg BD	Continuous
Encephalitis	IV aciclovir 10mg/kg TDS	14–21 days
Eczema herpeticum	IV aciclovir 5–10mg/kg TDS	10–14 days

NICE Guidelines / CKS

Infectious Mononucleosis

Acute infection caused by Epstein-Barr virus (EBV/HHV-4) characterised by fever, pharyngitis, and lymphadenopathy (the classic triad). Common in adolescents and young adults. Complications include splenic rupture, hepatitis, and airway obstruction. Associated with Burkitt lymphoma, nasopharyngeal carcinoma, and PTLD.

MRCP Part 1 · MRCP Part 2 · PLAB 1 · UKMLA · MRCGP AKT · MSRA

Key Facts

Classic triad: fever, pharyngitis (often with tonsillar exudate), and cervical lymphadenopathy (especially posterior triangle)
Amoxicillin/ampicillin rash: maculopapular rash in ~90% of glandular fever patients given amoxicillin - NOT a true allergy
Monospot test (heterophile antibody): positive in ~85% of adults by week 2; false-negative in children <4 years
Atypical lymphocytes on blood film: >10% of total WCC (activated T-cells reacting to EBV-infected B-cells)
Splenic rupture: rare (~0.1–0.5%) but potentially fatal - avoid contact sports for ≥4 weeks
EBV is associated with Burkitt lymphoma, Hodgkin lymphoma, nasopharyngeal carcinoma, PTLD, and oral hairy leukoplakia
Chronic fatigue: may persist for weeks to months after acute infection
95% of adults are EBV seropositive; primary infection in adolescence causes clinical mononucleosis in ~50%

Overview

Key Facts

Infectious mononucleosis (glandular fever) is the clinical syndrome caused by primary EBV infection, predominantly affecting adolescents and young adults. Most infections are self-limiting but complications can be serious.

Epidemiology

95% of adults worldwide are EBV seropositive
Primary infection in early childhood: usually subclinical
Adolescent/young adult primary infection: symptomatic mononucleosis in ~50%
Peak incidence: 15–24 years
Known as the 'kissing disease' - spread via saliva

Aetiology

EBV (HHV-4): double-stranded DNA virus, Herpesviridae family (Gammaherpesvirinae)
Transmission: saliva (kissing, shared utensils); rare: blood transfusion, transplant
Incubation: 4–6 weeks (adolescents/adults)
After primary infection, EBV establishes lifelong latency in B-lymphocytes

Pathophysiology

EBV infects oropharyngeal epithelial cells → B-lymphocyte infection via CD21 receptor

Infected B-cells proliferate

polyclonal B-cell activation

atypical lymphocytes (reactive CD8+ T-cells)

Heterophile antibodies: cross-reactive IgM antibodies (basis of Monospot test)
Splenomegaly: reactive lymphoid hyperplasia
Oncogenic potential: EBV latent genes (LMP1, EBNA) promote B-cell immortalisation → lymphoma risk in immunocompromised

Clinical Presentation

Typical Presentation

Prodrome: malaise, fatigue, headache (1–2 weeks)
Sore throat: severe pharyngitis with tonsillar enlargement and grey-white exudate (can mimic streptococcal pharyngitis)
Fever: high, lasting 1–2 weeks
Lymphadenopathy: cervical (especially posterior triangle), generalised in some
Splenomegaly: ~50% (usually mild)
Hepatomegaly: ~10%
Fatigue: prominent, may persist for weeks to months

Other Features

Periorbital oedema (Hoagland sign)
Petechiae at junction of hard and soft palate
Jaundice (hepatitis in ~5%)
Rash: spontaneous in ~5%; ~90% if given amoxicillin

Complications

Airway obstruction: massive tonsillar enlargement
Splenic rupture: rare, 0.1–0.5%; usually weeks 2–3; avoid contact sports ≥4 weeks
Haemolytic anaemia: cold agglutinins (anti-i)
Thrombocytopenia: immune-mediated
Hepatitis: raised transaminases in ~80% (usually mild)
Neurological: Guillain-Barré, cranial nerve palsies, meningoencephalitis (rare)

Red Flags

Stridor or drooling (airway compromise)
Left upper quadrant pain (splenic rupture)
Severe jaundice
Prolonged or worsening symptoms >4 weeks
Immunocompromised patient (risk of lymphoproliferative disease)

Differential Diagnosis

Diagnosis	Key Features	Investigation
Streptococcal pharyngitis	Acute onset, tender anterior lymph nodes, no hepatosplenomegaly	Throat swab, rapid strep test, ASO titre
CMV mononucleosis	Similar syndrome but pharyngitis less prominent	CMV IgM, PCR
Acute HIV seroconversion	Rash, oral ulcers, risk factors	HIV test (4th-gen)
Toxoplasmosis	Lymphadenopathy, milder pharyngitis	Toxoplasma IgM/IgG
Lymphoma	Persistent lymphadenopathy, B symptoms, weight loss	Biopsy, LDH, CT
Leukaemia	Lymphadenopathy, hepatosplenomegaly, cytopenias	FBC, blood film, bone marrow

Diagnosis / Investigation

Bedside

Throat examination: tonsillar enlargement, exudate, palatal petechiae
Abdominal palpation: splenomegaly (gentle - risk of rupture)

Bloods

FBC and blood film: lymphocytosis with >10% atypical lymphocytes (large, reactive T-cells)
Monospot test (Paul-Bunnell/heterophile antibody): positive in ~85% by week 2; may be negative early or in children <4 years
EBV serology: VCA IgM (acute infection), VCA IgG (past/current), EBNA IgG (past infection - negative in acute)
LFTs: elevated transaminases in ~80%; raised bilirubin in ~5%
CRP: mildly elevated
Throat swab: exclude concurrent Group A Strep (~5% co-infection rate)

Imaging

USS abdomen: if splenomegaly suspected or abdominal pain (assess splenic size)
CT neck: if airway compromise or parapharyngeal abscess suspected

Special Tests

EBV PCR: for immunocompromised patients or diagnostic uncertainty
Direct antiglobulin test (DAT/Coombs): if haemolysis suspected

Management

Non-pharmacological

Rest: avoid strenuous activity and contact sports for ≥4 weeks from symptom onset (splenic rupture risk)
Adequate hydration and nutrition
Avoid alcohol: during hepatitis phase
Return to sport: guided by symptoms; ultrasound to assess splenic size if uncertain

Pharmacological

Symptomatic: paracetamol and/or ibuprofen for fever and pain
Avoid amoxicillin/ampicillin: causes widespread maculopapular rash in EBV infection
Short course corticosteroids: only for specific complications:
- Airway obstruction (impending): dexamethasone 0.15mg/kg or prednisolone 1mg/kg for 3–5 days
- Severe thrombocytopenia
- Autoimmune haemolytic anaemia
Aciclovir: NOT routinely recommended (does not alter clinical course despite reducing viral shedding)
Antibiotics: only if confirmed secondary bacterial infection (NOT empirical)

Surgical/Interventional

Tonsillectomy: rarely needed for recurrent obstruction
Splenectomy: for splenic rupture (emergency)
Emergency airway management: if severe tonsillar swelling

Referral Criteria

ENT: airway compromise, peritonsillar abscess
Haematology: severe cytopenias, suspected lymphoproliferative disease
Emergency surgery: suspected splenic rupture
GP follow-up: most cases managed in primary care with safety-netting

Prognosis

Self-limiting in most cases; acute illness resolves in 2–4 weeks
Fatigue may persist for 3–6 months (occasionally longer)
Splenic rupture: ~0.1–0.5%; mortality <5% with prompt surgery
Full recovery expected in >95% of immunocompetent patients
EBV-associated malignancy: lifetime risk increased but absolute risk low in immunocompetent
PTLD: major risk in transplant recipients on immunosuppression
Chronic active EBV infection: extremely rare; poor prognosis

Other Relevant Information

EBV Serology Interpretation

Marker	Acute Infection	Past Infection	Reactivation
VCA IgM	Positive	Negative	Variable
VCA IgG	Positive (rising)	Positive (stable)	Positive
EBNA IgG	Negative	Positive	Positive
EA IgG	Positive	Negative	Positive

EBV-Associated Conditions

Condition	Association
Burkitt lymphoma	Endemic (Africa) - EBV in >95%; sporadic - ~20%
Hodgkin lymphoma	~40% EBV-positive
Nasopharyngeal carcinoma	>95% EBV-associated
PTLD	Post-transplant, EBV-driven
Oral hairy leukoplakia	HIV/immunocompromised

NICE Guidelines / CKS

Cytomegalovirus

Ubiquitous herpesvirus (HHV-5) causing asymptomatic infection in most immunocompetent individuals but severe disease in immunocompromised (transplant recipients, HIV with CD4 <100) and congenital infection. Manifestations include retinitis, colitis, pneumonitis, and encephalitis.

MRCP Part 1 · MRCP Part 2 · PLAB 1 · UKMLA · MRCGP AKT · MSRA

Key Facts

CMV seroprevalence: 50–90% of UK adults; primary infection usually asymptomatic or mononucleosis-like
Congenital CMV: most common congenital infection - ~1 in 200 births; 10% symptomatic at birth; leading non-genetic cause of sensorineural deafness
CMV retinitis: occurs at CD4 <50 in HIV - 'pizza-pie' fundoscopy appearance; treat with valganciclovir 900mg BD for 21 days
Post-transplant CMV: major cause of morbidity; D+/R– (donor positive/recipient negative) highest risk; monitor with CMV PCR
Treatment: ganciclovir 5mg/kg BD IV or valganciclovir 900mg BD oral for 21 days induction then maintenance
Main side effect of ganciclovir: bone marrow suppression (neutropenia) - monitor FBC
Foscarnet: second-line for ganciclovir-resistant CMV; nephrotoxic
Diagnosis: CMV PCR (quantitative viral load) on blood; tissue biopsy shows owl-eye inclusion bodies

Overview

Key Facts

CMV is a major pathogen in immunocompromised individuals and the leading cause of congenital viral infection. In transplant medicine, CMV reactivation is one of the most important complications.

Epidemiology

Seroprevalence: 50–60% in UK (higher in lower socioeconomic groups); >90% in some developing countries
Congenital CMV: ~1 in 200 live births (UK); ~10% symptomatic; ~12% of asymptomatic develop sequelae
Post-transplant: CMV disease in 20–60% of D+/R– solid organ transplant recipients without prophylaxis
HIV: CMV retinitis in ~30% of AIDS patients pre-ART era; now rare with effective ART

Aetiology

CMV (HHV-5): double-stranded DNA, Herpesviridae (Betaherpesvirinae)
Transmission: saliva, urine, sexual contact, blood transfusion, organ transplant, vertical (in utero, perinatal, breast milk)
Lifelong latency in myeloid progenitor cells; reactivation with immunosuppression

Pathophysiology

CMV infects epithelial cells, endothelial cells, monocytes/macrophages, fibroblasts
Latent in CD34+ haemopoietic stem cells and monocytes

Immunosuppression

viral reactivation

cytopathic effect on target organs

CMV immune evasion: downregulates MHC class I, produces viral IL-10 homologue, expresses Fc receptor
Congenital CMV: transplacental transmission during maternal viraemia → widespread fetal organ damage

Clinical Presentation

Immunocompetent

Usually asymptomatic (90%)
CMV mononucleosis: fever, malaise, lymphocytosis, mild hepatitis - pharyngitis less prominent than EBV; heterophile antibody negative

Immunocompromised (HIV CD4 <100, Transplant)

CMV retinitis: painless visual loss, floaters; 'pizza-pie' fundoscopy (haemorrhages + exudates)
CMV colitis: diarrhoea (often bloody), abdominal pain, fever
CMV oesophagitis: odynophagia, large shallow ulcers (vs HSV small deep ulcers)
CMV pneumonitis: interstitial pneumonia (especially post-BMT); high mortality
CMV encephalitis/ventriculitis: confusion, cranial nerve palsies

Congenital CMV

10% symptomatic at birth: petechiae, hepatosplenomegaly, jaundice, microcephaly, periventricular calcification, chorioretinitis
90% asymptomatic at birth: ~12% develop late sequelae (sensorineural deafness most common)

Red Flags

Visual symptoms in immunocompromised (retinitis emergency)
Persistent diarrhoea in transplant/HIV patient
Rising CMV viral load post-transplant
Microcephaly or intracranial calcification in neonate

Differential Diagnosis

Diagnosis	Key Features	Investigation
EBV mononucleosis	Pharyngitis more prominent, heterophile antibody positive	Monospot, EBV serology
HIV seroconversion	Rash, oral ulcers, risk factors	HIV test
Toxoplasmosis	Lymphadenopathy, ring-enhancing brain lesions (HIV)	Toxoplasma IgM/IgG, MRI
PCP pneumonia	Bilateral infiltrates, dry cough, HIV/immunocompromised	BAL, PCP PCR
Congenital toxoplasmosis	Hydrocephalus, intracranial calcification (diffuse vs periventricular in CMV)	Toxoplasma IgM, PCR

Diagnosis / Investigation

Bloods

CMV PCR (quantitative viral load): gold standard for diagnosis and monitoring
CMV IgM/IgG: useful for determining immune status; IgM for acute/recent infection
FBC: atypical lymphocytes (monocyte-predominant); leucopenia
LFTs: raised transaminases

Imaging

Fundoscopy: CMV retinitis - haemorrhages, exudates, 'pizza-pie' appearance
CT/MRI brain: periventricular calcification (congenital); ventriculitis/encephalitis (immunocompromised)
CXR: interstitial infiltrates (pneumonitis)

Special Tests

Tissue biopsy: owl-eye inclusion bodies (large intranuclear + smaller cytoplasmic inclusions) - diagnostic on colonic/oesophageal biopsy
BAL PCR: CMV pneumonitis (distinguish colonisation from disease)
Neonatal CMV: CMV PCR on urine or saliva (within 3 weeks of birth to confirm congenital vs perinatal)
Audiology: all congenital CMV cases - serial hearing assessments

Management

Non-pharmacological

Hygiene education: hand washing (especially around young children - main source of CMV for pregnant women)
CMV-negative blood products: for CMV-seronegative transplant recipients and pregnant women (leucodepleted products reduce risk)

Pharmacological

CMV disease in immunocompromised:

Induction: ganciclovir 5mg/kg BD IV for 14–21 days, OR valganciclovir 900mg BD oral for 21 days
Maintenance: valganciclovir 900mg OD until immune reconstitution (e.g. CD4 >100 on ART for 6 months)
CMV retinitis: valganciclovir 900mg BD for 21 days then 900mg OD maintenance; intravitreal ganciclovir for immediate sight-threatening disease
Second-line: foscarnet 90mg/kg BD IV (if ganciclovir-resistant or neutropenic) - nephrotoxic, electrolyte disturbance
Third-line: cidofovir (nephrotoxic - co-prescribe probenecid and IV saline)

Transplant prophylaxis:

Valganciclovir 900mg OD for 3–6 months post-transplant (D+/R– highest risk)
OR pre-emptive strategy: monitor CMV PCR weekly; treat if viraemia detected

Congenital CMV:

Symptomatic: valganciclovir 16mg/kg BD oral for 6 months - improves hearing and neurodevelopmental outcomes
Monitoring: FBC weekly (neutropenia risk), LFTs, serial audiology

Side effects of ganciclovir/valganciclovir:

Neutropenia (most common - up to 40%): monitor FBC weekly; may need G-CSF
Thrombocytopenia, anaemia
Teratogenic: effective contraception required

Referral Criteria

Ophthalmology: CMV retinitis (urgent)
Transplant team: CMV viraemia/disease post-transplant
Fetal medicine: maternal CMV seroconversion in pregnancy
Paediatrics: congenital CMV - multidisciplinary (audiology, ophthalmology, neurology)

Prognosis

Immunocompetent primary CMV: excellent prognosis; self-limiting in 2–6 weeks
CMV retinitis (with treatment): vision stabilised in ~80%; relapse common if immune reconstitution incomplete
CMV pneumonitis post-BMT: mortality 30–50% even with treatment
Congenital CMV (symptomatic): mortality ~5%; 50–60% develop long-term sequelae (deafness, intellectual disability)
Congenital CMV (asymptomatic): ~12% develop late sensorineural deafness
Valganciclovir for congenital CMV: significant improvement in hearing and neurodevelopment (Kimberlin et al.)
Post-transplant CMV disease: mortality 5–20% depending on organ and level of immunosuppression

Other Relevant Information

CMV Disease by Organ

Organ	Key Feature	Diagnosis
Eye (retinitis)	Pizza-pie fundus, painless visual loss	Fundoscopy
Colon (colitis)	Bloody diarrhoea, deep ulcers	Colonoscopy + biopsy (owl-eye cells)
Oesophagus	Odynophagia, large shallow ulcers	OGD + biopsy
Lung (pneumonitis)	Interstitial infiltrates, cough, dyspnoea	BAL PCR, CXR/CT
CNS	Encephalitis, ventriculitis	CSF CMV PCR, MRI

CMV Risk in Transplant (D/R Serostatus)

D/R Status	Risk	Strategy
D+/R–	Highest risk	Prophylaxis (valganciclovir 3–6 months)
D+/R+	Intermediate (reactivation)	Pre-emptive monitoring
D–/R+	Intermediate (reactivation)	Pre-emptive monitoring
D–/R–	Low risk	CMV-negative blood products

NICE Guidelines / CKS

Meningococcal Disease

Invasive infection with Neisseria meningitidis causing meningitis and/or meningococcaemia (septicaemia). A medical emergency with rapidly progressive course. Non-blanching purpuric rash is the hallmark of meningococcal septicaemia. Case-fatality rate ~5–10% even with optimal treatment.

MRCP Part 1 · MRCP Part 2 · PLAB 1 · UKMLA · MRCGP AKT · MSRA

Key Facts

Non-blanching petechial/purpuric rash in unwell febrile patient is meningococcal disease until proven otherwise - glass test
IM benzylpenicillin in the community BEFORE hospital transfer: 1.2g (adult), 600mg (child 1–9), 300mg (infant <1)
Serogroups: B and W now predominant in UK; MenACWY and MenB vaccines in routine UK immunisation schedule
Lumbar puncture: raised WCC (neutrophils), raised protein, low glucose, Gram-negative diplococci - BUT do NOT delay antibiotics for LP
IV ceftriaxone 2g BD (adult) or cefotaxime: empirical treatment - start immediately
Chemoprophylaxis for contacts: single-dose ciprofloxacin 500mg (adult) or rifampicin 600mg BD for 2 days
Notifiable disease: must notify local health protection team immediately - urgent contact tracing
Waterhouse-Friderichsen syndrome: bilateral adrenal haemorrhage in fulminant meningococcaemia - DIC, shock, adrenal crisis

Overview

Key Facts

Meningococcal disease is a medical emergency that can progress from initial symptoms to death within hours. Rapid recognition and immediate antibiotic treatment are essential. UK vaccination programmes have significantly reduced incidence.

Epidemiology

UK: ~500–1,000 cases/year (declining due to vaccination)
Peak incidence: children <5 years and adolescents 15–19
Case-fatality rate: ~5–10% (meningitis); ~20–30% (meningococcaemia/septicaemia)
Winter/spring seasonality
University freshers: increased risk (close living, social mixing)

Aetiology

Neisseria meningitidis: Gram-negative diplococcus; polysaccharide capsule determines serogroup
Serogroups: B (~50% of UK cases), W, Y, C (rare since MenC vaccine)
Transmission: respiratory droplets, close contact; carriage rate ~10% in adolescents
Risk factors: asplenia, complement deficiency, crowded living (dormitories, barracks), recent viral URTI

Pathophysiology

Nasopharyngeal colonisation

bloodstream invasion

bacteraemia

Endotoxin (LOS - lipooligosaccharide) triggers massive inflammatory response

Complement activation

DIC

purpura fulminans

Meningeal inflammation → raised ICP, cerebral oedema
Adrenal gland haemorrhage → Waterhouse-Friderichsen syndrome
Rapid progression: can deteriorate from well to critically ill within hours

Clinical Presentation

Meningitis Presentation

Headache, photophobia, neck stiffness
Fever, vomiting
Altered consciousness, irritability
Kernig sign (unable to extend knee with hip flexed), Brudzinski sign (neck flexion causes hip/knee flexion)
Bulging fontanelle in infants

Meningococcaemia (Septicaemia)

Non-blanching petechial/purpuric rash - may start as blanching maculopapular then progress to purpura
Fever, rigors, myalgia
Rapid deterioration: tachycardia, hypotension, cold extremities
Purpura fulminans: large ecchymoses, skin necrosis, DIC
Shock, multi-organ failure

Red Flags

Non-blanching rash + fever in child/young person
Rapidly progressive purpuric rash
Signs of shock (tachycardia, hypotension, prolonged cap refill)
Reduced consciousness (GCS <12)
Neck stiffness + fever + headache
Infants: bulging fontanelle, high-pitched cry, poor feeding, floppiness

Differential Diagnosis

Diagnosis	Key Features	Investigation
Viral meningitis	Milder course, lymphocytic CSF, enterovirus common	CSF PCR (enterovirus)
Pneumococcal meningitis	Older adults, post-splenectomy, otitis media, Gram-positive diplococci	Blood/CSF culture
Haemophilus meningitis	Now rare in UK (Hib vaccine); young children	CSF culture
ITP	Non-blanching rash BUT well child, no fever	FBC (isolated thrombocytopenia), blood film
HSP (IgA vasculitis)	Purpuric rash on buttocks/legs, arthralgia, abdominal pain	Clinical, urinalysis
Sepsis (other)	Same shock presentation, different source	Blood cultures, source investigation

Diagnosis / Investigation

Bedside

Glass test: non-blanching rash does not fade under pressure
Observations: HR, BP, RR, SpO2, GCS, capillary refill, temperature
Blood glucose: hypoglycaemia

Bloods

Blood cultures: BEFORE antibiotics (but do NOT delay treatment to obtain)
Meningococcal PCR: on EDTA blood - can be positive even after antibiotics
FBC: leucocytosis or leucopenia
CRP, lactate: severity markers
Coagulation screen: DIC (prolonged PT/APTT, low fibrinogen, raised D-dimer)
U&Es, LFTs: organ dysfunction
Blood gas: metabolic acidosis

Special Tests

Lumbar puncture (if safe - NO LP if signs of raised ICP, haemodynamic instability, coagulopathy, GCS ≤12):
- CSF: turbid, raised WCC (neutrophils), raised protein (>1 g/L), low glucose (<50% of blood glucose)
- Gram stain: Gram-negative diplococci
- CSF PCR: meningococcal DNA
- CSF culture

Imaging

CT head: before LP if signs of raised ICP (papilloedema, focal neurology, GCS ≤12)
CXR: if respiratory compromise

Management

Non-pharmacological

Do NOT delay antibiotics for any investigation
Resuscitation: ABC approach, high-flow oxygen, IV access × 2
IV fluids: 20 ml/kg 0.9% NaCl bolus, reassess, repeat up to 60 ml/kg
ICU referral: early if septic shock, DIC, or GCS ≤12

Pharmacological

Pre-hospital:

IM/IV benzylpenicillin: 1.2g adult, 600mg child 1–9, 300mg <1 year - give IMMEDIATELY on clinical suspicion before transfer

In-hospital:

IV ceftriaxone 2g BD (adult); 80mg/kg in children; continue for 7 days (5 days if confirmed meningococcal)
OR IV cefotaxime: alternative
Dexamethasone 0.15mg/kg QDS IV for 4 days: if suspected bacterial meningitis in adults - give with or before first antibiotic dose; NOT if meningococcal septicaemia without meningitis
DIC management: cryoprecipitate, FFP, platelets as needed
Vasopressors: noradrenaline if fluid-refractory shock

Close contacts:

Ciprofloxacin 500mg stat (adult) or rifampicin 600mg BD for 2 days
Children: rifampicin or ceftriaxone IM
Offer to household contacts and 'kissing contacts' within 7 days
MenACWY + MenB vaccine for contacts if outbreak serogroup matches

Referral Criteria

All cases: infectious diseases, ICU
Public health: immediate statutory notification; contact tracing
ENT/neurosurgery: if complications (abscess, hydrocephalus)
Rehabilitation: for survivors with sequelae

Prognosis

Overall case-fatality rate: 5–10%
Meningococcal septicaemia without meningitis: mortality 20–30%
Meningitis alone (without septicaemia): mortality ~5%
Purpura fulminans/Waterhouse-Friderichsen: mortality >50%
Survivors: 10–20% have long-term sequelae (deafness, limb amputation, cognitive impairment, skin scarring)
Sensorineural deafness: ~5% of survivors
Limb loss (from gangrene/DIC): ~7% of survivors
With prompt treatment and intensive care, majority survive

Other Relevant Information

UK Meningococcal Vaccination Schedule

Vaccine	Age	Protection
MenB (Bexsero)	8 weeks, 16 weeks, 12 months	Serogroup B
MenACWY	14 years (school Year 9) + university freshers	Serogroups A, C, W, Y
MenC (historical)	Replaced by MenACWY	Serogroup C

CSF Findings in Meningitis

Parameter	Bacterial	Viral	TB
Appearance	Turbid	Clear	Fibrinous
WCC	Neutrophils ↑↑	Lymphocytes ↑	Lymphocytes ↑
Protein	↑↑	Normal/↑	↑↑↑
Glucose	↓↓ (<50% blood)	Normal	↓↓
Gram stain	May show organism	Negative	ZN often negative

NICE Guidelines / CKS

Bacterial Meningitis

Life-threatening infection of the meninges caused predominantly by N. meningitidis, S. pneumoniae, and Group B Streptococcus (in neonates). Presents with fever, headache, neck stiffness, and altered consciousness. Requires immediate empirical antibiotics and dexamethasone per NICE CG102.

MRCP Part 1 · MRCP Part 2 · PLAB 1 · UKMLA · MRCGP AKT · MSRA

Key Facts

Commonest organisms by age: neonates - Group B Strep, E. coli, Listeria; children - N. meningitidis, S. pneumoniae; adults - S. pneumoniae (#1), N. meningitidis; elderly - S. pneumoniae, Listeria
NICE CG102: IV ceftriaxone 2g BD (adult) - start immediately; add amoxicillin 2g QDS IV if Listeria suspected (age >60, immunocompromised, pregnancy)
Dexamethasone 0.15mg/kg QDS for 4 days: give with or before first antibiotic dose - reduces mortality and hearing loss in pneumococcal meningitis
Classic triad: fever, neck stiffness, altered mental status - present in only ~44% of adults
LP findings: turbid CSF, neutrophilic pleocytosis, raised protein (>1 g/L), low glucose (<50% of blood glucose or <2.2 mmol/L)
Do NOT delay antibiotics for LP or CT - if LP delayed, give empirical antibiotics and dexamethasone immediately
Complications: hearing loss (~10%), hydrocephalus, cerebral abscess, seizures, cranial nerve palsies, cognitive impairment
Mortality: S. pneumoniae ~20–30%; N. meningitidis ~5–10%; Listeria ~20–30%

Overview

Key Facts

Bacterial meningitis is a medical emergency requiring immediate empirical antibiotic treatment. Delayed treatment dramatically increases mortality and morbidity. The causative organism varies by age, and adjunctive dexamethasone improves outcomes in pneumococcal meningitis.

Epidemiology

UK: ~1,000–2,000 cases/year of bacterial meningitis
S. pneumoniae: most common in adults; ~30% mortality
N. meningitidis: most common in children/adolescents; declining with vaccination
Listeria: elderly, immunocompromised, pregnancy; ~20–30% mortality
Neonatal GBS meningitis: ~0.3 per 1,000 live births

Aetiology

Neonates (<3 months): Group B Streptococcus, E. coli, Listeria monocytogenes
Children (3 months–5 years): N. meningitidis, S. pneumoniae, H. influenzae (rare post-Hib vaccine)
Adults: S. pneumoniae (most common), N. meningitidis
Elderly/immunocompromised: S. pneumoniae, Listeria, Gram-negatives
Post-neurosurgical: S. aureus, coagulase-negative staphylococci, Gram-negatives

Pathophysiology

Bacteraemia

crossing blood-brain barrier (BBB)

subarachnoid space infection

Bacterial components (LPS, peptidoglycan) trigger innate immune response in CSF

Cytokines (TNF-α, IL-1)

meningeal inflammation

BBB disruption

cerebral oedema

Raised intracranial pressure

reduced cerebral perfusion

neuronal injury

Vasculitis → cerebral infarction
Cochlear damage → sensorineural deafness (especially S. pneumoniae)

Clinical Presentation

Adults

Headache: severe, global
Fever: high-grade
Neck stiffness (meningism): pain on flexion
Altered mental status: confusion, drowsiness → GCS decline
Photophobia
Nausea and vomiting
Seizures: ~20% of cases
Kernig and Brudzinski signs: sensitivity ~5% (poor sensitivity, high specificity)

Infants/Children

Non-specific: irritability, poor feeding, lethargy
High-pitched cry
Bulging fontanelle (infants)
Neck stiffness may be absent in young infants
Seizures
Non-blanching rash (meningococcal)

Red Flags

Rapidly declining GCS
Signs of raised ICP: papilloedema, focal neurology, bradycardia + hypertension + abnormal breathing (Cushing triad)
Non-blanching purpuric rash
Seizures
Shock (septicaemia component)
Immunocompromised or extremes of age

Differential Diagnosis

Diagnosis	Key Features	Investigation
Viral meningitis	Milder course, lymphocytic CSF, enterovirus	CSF PCR
Subarachnoid haemorrhage	Thunderclap headache, xanthochromia	CT head, LP
Encephalitis (HSV, etc.)	Altered behaviour, seizures, temporal lobe signs	MRI, CSF HSV PCR
Brain abscess	Focal neurology, fever, raised ICP	CT/MRI with contrast
TB meningitis	Subacute, cranial nerve palsies, lymphocytic CSF, very low glucose	CSF AFB/PCR, MRI
Cerebral malaria	Travel history, P. falciparum, altered consciousness	Blood films

Diagnosis / Investigation

Bedside

GCS assessment: serial monitoring
Blood glucose: paired with CSF glucose
Blood gas: lactate, acidosis

Bloods (BEFORE LP)

Blood cultures: essential - positive in 50–70%
FBC, CRP, lactate: infection markers
U&Es: SIADH (hyponatraemia)
Coagulation: DIC screen
Meningococcal/pneumococcal PCR: on EDTA blood

LP (if no contraindications)

Contraindications to immediate LP: GCS ≤12, focal neurology, papilloedema, haemodynamic instability, coagulopathy, local skin infection, signs of raised ICP
CT head before LP: if any of the above
CSF analysis: appearance, WCC (differential), protein, glucose (+ paired blood glucose), Gram stain, culture, PCR (meningococcal, pneumococcal)
Opening pressure: typically elevated

Imaging

CT head: before LP if indicated (see above); excludes space-occupying lesion/hydrocephalus
MRI: if complications suspected (abscess, cerebral venous sinus thrombosis)

Management

Non-pharmacological

ABC approach: secure airway if GCS declining
Do NOT delay antibiotics for any investigation
Isolation: droplet precautions for meningococcal disease until 24 hours of effective treatment
Fluid management: avoid overhydration (risk of cerebral oedema); maintain euvolaemia
ICU referral: GCS ≤12, haemodynamic instability, seizures

Pharmacological

Empirical antibiotics (NICE CG102):

IV ceftriaxone 2g BD (adult) - start immediately
Add IV amoxicillin 2g QDS if Listeria suspected (age >60, immunocompromised, pregnant)
Neonates: cefotaxime + amoxicillin (ampicillin equivalent)
Post-neurosurgical: vancomycin + meropenem

Adjunctive dexamethasone:

Dexamethasone 0.15mg/kg (max 10mg) QDS IV for 4 days - give with or before first antibiotic dose
Evidence: reduces mortality and hearing loss in pneumococcal meningitis (European Dexamethasone study, de Gans et al.)
Discontinue if non-pneumococcal meningitis confirmed (benefit less clear for meningococcal)

Duration:

N. meningitidis: 5–7 days
S. pneumoniae: 10–14 days
Listeria: 21 days (ampicillin + gentamicin)
GBS (neonatal): 14–21 days

Close contacts (meningococcal):

Ciprofloxacin 500mg stat (adult) or rifampicin 600mg BD for 2 days

Referral Criteria

All cases: infectious diseases, ICU consideration
Neurosurgery: hydrocephalus, abscess
Audiology: all bacterial meningitis survivors (hearing assessment)
Public health: notification (meningococcal); contact tracing

Prognosis

S. pneumoniae meningitis: mortality 20–30%; neurological sequelae in 30–50% of survivors
N. meningitidis meningitis: mortality 5–10%
Listeria meningitis: mortality 20–30%
Neonatal GBS meningitis: mortality 10%; neurodevelopmental sequelae in 25–50%
Overall hearing loss: ~10% (higher with S. pneumoniae - up to 30%)
Cognitive impairment: 10–30% of survivors
Dexamethasone: reduces mortality from 34% to 14% in pneumococcal meningitis (de Gans trial)
Delay in antibiotics: each hour increases mortality by 3–10%

Other Relevant Information

CSF Interpretation

Parameter	Normal	Bacterial	Viral	TB
Appearance	Clear	Turbid/purulent	Clear	Fibrinous/viscous
WCC (/µL)	<5	100–10,000 (neutrophils)	10–500 (lymphocytes)	10–500 (lymphocytes)
Protein (g/L)	<0.45	>1.0	0.5–1.0	>1.0
Glucose (mmol/L)	>2.2 (>50% blood)	<2.2 (<50% blood)	Normal	Very low
Gram stain	Negative	Positive ~60%	Negative	ZN rarely positive

Empirical Antibiotics by Age

Age	Empirical Antibiotic
Neonate (<3 months)	Cefotaxime + amoxicillin
Child (3 months–5 years)	Ceftriaxone
Adult (16–60)	Ceftriaxone
Elderly (>60) / immunocompromised	Ceftriaxone + amoxicillin

NICE Guidelines / CKS

Cellulitis

Acute bacterial skin infection involving the dermis and subcutaneous tissue, most commonly caused by beta-haemolytic streptococci and S. aureus. Presents with erythema, warmth, swelling, and pain, usually affecting the lower limbs. Managed with oral or IV antibiotics per NICE NG141.

MRCP Part 1 · MRCP Part 2 · PLAB 1 · UKMLA · MRCGP AKT · MSRA

Key Facts

Commonest organisms: Group A Streptococcus (S. pyogenes) and S. aureus
NICE NG141: first-line oral antibiotic is flucloxacillin 500mg–1g QDS for 5–7 days
Eron classification: guides severity - Class I (no comorbidities, systemically well) to Class IV (sepsis/necrotising fasciitis)
Mark the margin: draw around advancing erythema border with pen and date/time to monitor progression
Risk factors: lymphoedema, leg ulcers, tinea pedis (portal of entry), obesity, diabetes, peripheral vascular disease
Not an abscess: cellulitis is non-purulent, diffuse; abscess is a localised collection requiring drainage
Bilateral cellulitis is rare - consider alternative diagnoses (venous eczema, DVT, lipodermatosclerosis)
IV antibiotics: flucloxacillin 1–2g QDS IV for Eron Class III–IV; add clindamycin if necrotising fasciitis suspected

Overview

Key Facts

Cellulitis is one of the most common presentations to primary and emergency care. Correct diagnosis, appropriate antibiotic selection, and identification of complications are essential. Recurrence is common (~30%) and preventive measures including treating tinea pedis and managing lymphoedema are important.

Epidemiology

~80,000–100,000 hospital admissions/year for cellulitis in England
Lower limb accounts for ~70–80% of cases
Recurrence rate: ~20–30% within 3 years
More common in older adults, obese patients, and those with lymphoedema

Aetiology

Group A Streptococcus (S. pyogenes): most common cause overall
S. aureus: more likely if purulent/abscess component
Portal of entry: tinea pedis (most common), leg ulcers, wounds, insect bites, eczema
Special situations: MRSA (IV drug users, healthcare-associated); water exposure (Aeromonas, Vibrio); cat/dog bite (Pasteurella); immunocompromised (Gram-negatives, fungi)

Pathophysiology

Bacteria enter through break in skin barrier → spread through dermis and subcutaneous tissue
Bacterial enzymes (hyaluronidase, streptokinase) facilitate tissue spread
Inflammatory response: vasodilation, oedema, neutrophil infiltration → clinical features of erythema, warmth, swelling, pain

Lymphatic damage from recurrent cellulitis

lymphoedema

further cellulitis (vicious cycle)

Clinical Presentation

Typical Presentation

Unilateral erythema with poorly defined margin
Warmth, swelling, tenderness
Usually lower limb
Fever, malaise in moderate-severe cases
Regional lymphadenopathy

Erysipelas (superficial cellulitis)

Well-defined, raised erythematous margin
Typically facial or lower limb
More sharply demarcated than deep cellulitis
Streptococcal aetiology (almost always)

Red Flags (suggesting necrotising fasciitis or severe sepsis)

Pain out of proportion to clinical signs
Rapidly spreading erythema despite antibiotics
Crepitus (gas gangrene)
Skin necrosis, bullae, ecchymosis
Systemic toxicity: high fever, tachycardia, hypotension
Altered consciousness

Differential Diagnosis

Diagnosis	Key Features	Investigation
DVT	Unilateral leg swelling, calf tenderness, risk factors	D-dimer, Doppler USS
Venous eczema (stasis dermatitis)	Bilateral, chronic, scaly, varicose veins, haemosiderin	Clinical, Doppler USS
Necrotising fasciitis	Pain out of proportion, crepitus, skin necrosis, toxic	Urgent surgical exploration, CT
Lipodermatosclerosis	Chronic, inverted champagne bottle leg, bilateral	Clinical
Contact dermatitis	Pruritic, well-demarcated, exposure history	Patch testing
Gout	Joint involvement, tophi, raised urate	Joint aspiration, urate level
Abscess	Fluctuant, localised, purulent	USS, aspiration

Diagnosis / Investigation

Bedside

Mark the erythema margin with pen (date and time)
Observations: temperature, HR, BP, NEWS2
Blood glucose: undiagnosed diabetes

Bloods

FBC: leucocytosis
CRP: elevated; useful for monitoring response
U&Es: if sepsis or IV antibiotics anticipated
Blood cultures: only if systemically unwell (Eron III–IV); positive in <5% of cellulitis
HbA1c: if diabetes suspected

Imaging

Not routinely required for uncomplicated cellulitis
Doppler USS: if DVT cannot be excluded clinically
USS: if abscess suspected (localised fluctuance)
CT/MRI: if necrotising fasciitis suspected - gas in tissues, fascial thickening

Special Tests

Wound swab: only if open wound or purulent discharge - not from intact skin
Skin surface swab: not recommended (low yield)
Interdigital examination: check for tinea pedis (portal of entry)

Management

Non-pharmacological

Elevation: affected limb above heart level to reduce oedema
Mark erythema margins: monitor progression/response
Rest: especially if lower limb
Treat portal of entry: tinea pedis (topical antifungal), leg ulcers, eczema
Emollients: for surrounding dry skin
Compression: may be needed after acute phase if lymphoedema

Pharmacological

Eron Class I (mild - no comorbidities, systemically well):

Flucloxacillin 500mg–1g QDS oral for 5–7 days (NICE NG141)
Penicillin allergy: clarithromycin 500mg BD or doxycycline 200mg then 100mg OD

Eron Class II (systemic illness OR comorbidities):

Oral flucloxacillin 1g QDS + consider adding phenoxymethylpenicillin 500mg QDS (Strep cover)
Close review at 24–48 hours

Eron Class III (significant systemic toxicity):

IV flucloxacillin 1–2g QDS ± IV benzylpenicillin 1.2g QDS
Switch to oral when improving (OPAT may facilitate earlier discharge)

Eron Class IV (sepsis or necrotising fasciitis):

IV flucloxacillin 2g QDS + IV clindamycin 600mg QDS (clindamycin inhibits toxin production)
Urgent surgical review for necrotising fasciitis

MRSA suspected:

Add doxycycline 200mg then 100mg OD or trimethoprim (guided by local sensitivities)
IV: vancomycin 15–20mg/kg BD

Recurrence prevention:

Treat tinea pedis, manage lymphoedema (compression)
Prophylactic antibiotics: phenoxymethylpenicillin 250mg BD long-term if ≥2 episodes/year (NICE NG141, PATCH trial)

Surgical/Interventional

Incision and drainage: if concurrent abscess
Surgical debridement: necrotising fasciitis (emergency)

Referral Criteria

Hospital admission: Eron III–IV, failed oral therapy, diagnostic uncertainty
Surgery: suspected necrotising fasciitis (urgent)
Vascular: recurrent cellulitis with chronic venous insufficiency
Dermatology: if diagnostic uncertainty persists

Prognosis

Uncomplicated cellulitis: excellent prognosis with appropriate antibiotics
Expected improvement within 48–72 hours (erythema may initially spread before improving - common in first 24 hours)
Recurrence: 20–30% within 3 years
Prophylactic penicillin (PATCH trial): reduces recurrence by ~45%
Necrotising fasciitis: mortality 20–40% even with treatment
Post-cellulitis lymphoedema: may develop or worsen (perpetuating cycle)
Hospital admission ~2–5 days average; OPAT reduces length of stay

Other Relevant Information

Eron Classification of Cellulitis Severity

Class	Features	Management
I	No comorbidities, systemically well	Oral flucloxacillin
II	Systemically unwell OR significant comorbidities	Oral/IV depending on response
III	Significant systemic toxicity	IV antibiotics
IV	Sepsis or necrotising fasciitis	IV antibiotics + urgent surgical review

PATCH Trial (Prophylactic Antibiotics for Cellulitis)

Finding	Detail
Drug	Penicillin V 250mg BD
Duration	12 months
Effect	45% reduction in cellulitis recurrence
Indication	≥2 episodes of cellulitis in past 12 months

NICE Guidelines / CKS

Necrotising Fasciitis

A rapidly progressive, life-threatening soft tissue infection involving necrosis of the fascia and subcutaneous tissue. Mortality is 20–40% even with treatment. Requires urgent surgical debridement and IV antibiotics. Key early sign is pain out of proportion to clinical findings.

MRCP Part 1 · MRCP Part 2 · PLAB 1 · UKMLA · MRCGP AKT · MSRA

Key Facts

Pain out of proportion to clinical signs is the hallmark early feature - high index of suspicion required
Type I (polymicrobial): mixed aerobes and anaerobes - often abdominal, perineal (Fournier gangrene); diabetes, elderly
Type II (monomicrobial): Group A Streptococcus ± S. aureus - limbs; younger, healthier patients
LRINEC score ≥6 suggests necrotising fasciitis: CRP, WCC, Hb, sodium, creatinine, glucose
Treatment: urgent surgical debridement + IV antibiotics - meropenem 1g TDS + clindamycin 600mg QDS + flucloxacillin 2g QDS
Clindamycin: added specifically to inhibit toxin production (Streptococcal/Staphylococcal exotoxins)
Mortality: 20–40% overall; >70% if surgery delayed >24 hours
Fournier gangrene: necrotising fasciitis of perineum/genitalia - high mortality; urological emergency

Overview

Key Facts

Necrotising fasciitis is a surgical emergency. Rapid diagnosis and early aggressive debridement are the most important determinants of survival. Antibiotic therapy alone is insufficient.

Epidemiology

UK incidence: ~500–1,000 cases/year
Mortality: 20–40% (higher with delayed surgery)
Mean age: 50–60 years; M:F ~2:1
Risk factors: diabetes (most common), immunosuppression, peripheral vascular disease, obesity, alcohol excess, IVDU, recent surgery/trauma

Aetiology

Type I (polymicrobial - 70–80%): mixed aerobes (E. coli, Enterococcus, Klebsiella) + anaerobes (Bacteroides, Clostridium) - abdominal wall, perineum
Type II (monomicrobial - 20–30%): Group A Streptococcus (most common), S. aureus - limbs; can occur in healthy individuals after minor trauma
Type III (gas gangrene): Clostridium perfringens - crepitus, rapid gas production
Portal of entry: often minor (insect bite, skin abrasion, injection site) or post-surgical

Pathophysiology

Bacteria enter subcutaneous tissue → rapid spread along fascial planes (fascial blood supply is relatively poor)

Bacterial enzymes and toxins

tissue necrosis, thrombosis of perforating vessels

skin ischaemia

Streptococcal superantigens → toxic shock syndrome (TSS)

Positive feedback loop: necrosis

anaerobic environment

further bacterial proliferation

more necrosis

Overlying skin may initially appear normal despite deep necrosis (iceberg phenomenon)

Clinical Presentation

Early Features

Pain out of proportion to visible skin changes (most important early sign)
Erythema, warmth, swelling - may resemble cellulitis initially
Fever, malaise, tachycardia
Tenderness extending beyond visible erythema

Progressive Features (hours to days)

Rapidly spreading erythema/dusky discolouration
Skin bullae (haemorrhagic or serous)
Skin necrosis (purple/black discolouration)
Crepitus (gas in tissues - Type I/III)
Anaesthesia of overlying skin (cutaneous nerve destruction)
Systemic toxicity: septic shock, multi-organ failure

Red Flags

Pain disproportionate to examination findings
Rapid progression despite antibiotic therapy
Crepitus on palpation
Skin necrosis or bullae
Sepsis with skin/soft tissue focus
Perineal involvement (Fournier gangrene)

Differential Diagnosis

Diagnosis	Key Features	Investigation
Cellulitis	Less severe pain, no necrosis, responds to antibiotics	Clinical; may need CT/MRI to distinguish
Gas gangrene (Clostridium)	Severe pain, rapid gas production, myonecrosis	CT (gas), surgical exploration
DVT	Unilateral swelling, no skin necrosis, non-tender	Doppler USS, D-dimer
Abscess	Localised fluctuance, less systemic toxicity	USS, aspiration
Pyoderma gangrenosum	Painful ulcer with violaceous undermined border; pathergy	Biopsy (diagnosis of exclusion)
Calciphylaxis	CKD patients, painful skin necrosis, calcification	Biopsy, calcium/phosphate

Diagnosis / Investigation

Bedside

Observations: NEWS2 - will be elevated (sepsis)
Blood glucose: often elevated (diabetes common)
Finger test: bedside incision under local - lack of bleeding, dishwater grey necrotic fascia, absence of tissue resistance = diagnostic

Bloods

LRINEC score: CRP >150 (4 points), WCC >25 (2), Hb <110 (2), Na <135 (2), Cr >141 (2), Glucose >10 (1) - score ≥6 suspicious, ≥8 strongly predictive
FBC: leucocytosis (may be leucopenic in severe sepsis)
CRP: markedly elevated (often >300)
U&Es: AKI
Lactate: elevated
CK: elevated if myonecrosis
Blood cultures: before antibiotics
Coagulation: DIC screen

Imaging

CT with contrast: gas in soft tissues (pathognomonic), fascial thickening, fluid tracking along fascial planes
MRI: more sensitive for fascial involvement but time-consuming - do NOT delay surgery for imaging
Plain X-ray: may show subcutaneous gas
USS: can show subcutaneous oedema and fluid along fascia

Special Tests

Surgical exploration: the definitive diagnostic test - non-bleeding, dishwater grey fascia, lack of tissue resistance
Tissue samples: intraoperative samples for culture and histology

Management

Non-pharmacological

URGENT surgical debridement is the definitive treatment - within 6–12 hours of diagnosis
Radical excision of all necrotic tissue; often requires multiple returns to theatre (planned second look at 24–48 hours)
ICU admission: almost always required
Nutritional support: high caloric and protein requirements

Pharmacological

Empirical antibiotics (start immediately - do NOT delay for surgery):

Meropenem 1g TDS IV (broad Gram-negative and anaerobe cover)
+ Clindamycin 600mg–1.2g QDS IV (inhibits toxin production - essential for streptococcal/staphylococcal superantigens)
+ Flucloxacillin 2g QDS IV (anti-staphylococcal)
OR: piperacillin-tazobactam + clindamycin ± vancomycin (if MRSA risk)

Supportive care:

Aggressive IV fluid resuscitation
Vasopressors for septic shock
Blood product support (DIC)
VTE prophylaxis

IV immunoglobulin (IVIG):

Consider for streptococcal toxic shock syndrome (neutralises superantigens) - evidence limited but used in practice

Surgical/Interventional

Radical debridement: all necrotic fascia and involved tissue
Second-look surgery: at 24–48 hours to assess for further necrosis
Negative-pressure wound therapy (VAC): for large wounds after debridement
Skin grafting/flap reconstruction: once wound clean and granulating
Amputation: may be necessary for extremity involvement
Fournier gangrene: may require diverting colostomy/suprapubic catheter

Referral Criteria

Immediate surgical referral: any suspicion of necrotising fasciitis
ICU: all cases
Plastic surgery: for wound reconstruction
Microbiology/infectious diseases: antibiotic guidance

Prognosis

Overall mortality: 20–40%
Mortality if surgery delayed >24 hours: >70%
Fournier gangrene: mortality 20–40%
Type II (GAS): can cause toxic shock syndrome - mortality up to 50%
Factors associated with worse prognosis: delay in diagnosis, diabetes, immunosuppression, older age, truncal involvement, organ failure at presentation
Survivors: often require prolonged hospital stay (weeks to months), multiple surgeries, skin grafting
Long-term: significant morbidity including disfigurement, limb loss, chronic pain, psychological trauma

Other Relevant Information

LRINEC Score (Laboratory Risk Indicator for Necrotising Fasciitis)

Variable	Criteria	Score
CRP (mg/L)	<150 / ≥150	0 / 4
WCC (×10⁹/L)	<15 / 15–25 / >25	0 / 1 / 2
Haemoglobin (g/dL)	>13.5 / 11–13.5 / <11	0 / 1 / 2
Sodium (mmol/L)	≥135 / <135	0 / 2
Creatinine (µmol/L)	≤141 / >141	0 / 2
Glucose (mmol/L)	≤10 / >10	0 / 1
Score ≥6	Suspicious
Score ≥8	Strongly predictive

Types of Necrotising Fasciitis

Type	Organisms	Location	Key Feature
I (polymicrobial)	Mixed aerobes + anaerobes	Abdomen, perineum	Diabetes, elderly
II (monomicrobial)	Group A Strep ± S. aureus	Limbs	Younger, healthy
III (gas gangrene)	Clostridium perfringens	Limbs, trunk	Crepitus, rapid gas

NICE Guidelines / CKS

Clostridium Difficile Infection

Toxin-producing anaerobic infection (now Clostridioides difficile) causing antibiotic-associated diarrhoea and pseudomembranous colitis. Most common healthcare-associated infection. Treated with oral vancomycin per NICE NG199. Severe cases may require colectomy.

MRCP Part 1 · MRCP Part 2 · PLAB 1 · UKMLA · MRCGP AKT · MSRA

Key Facts

Most common cause of healthcare-associated infectious diarrhoea in the UK
Risk factors: recent antibiotics (especially 4Cs - co-amoxiclav, cephalosporins, ciprofloxacin, clindamycin), age >65, hospitalisation, PPI use
NICE NG199: first-line is oral vancomycin 125mg QDS for 10 days (replaces metronidazole as first-line)
Fidaxomicin 200mg BD for 10 days: for recurrent CDI or high recurrence risk - lower recurrence rate vs vancomycin (MODIFY I/II trials)
Diagnosis: C. difficile toxin EIA on stool (+ GDH screening); do NOT test formed stools
Toxic megacolon: colonic dilation >6cm, systemic toxicity - surgical emergency (subtotal colectomy)
Faecal microbiota transplantation (FMT): NICE-approved for recurrent CDI (≥2 recurrences) - highly effective (~90%)
Stop precipitating antibiotics if possible; isolate patient; enhanced environmental cleaning (sporicidal agents - alcohol gel ineffective against spores)

Overview

Key Facts

C. difficile infection (CDI) remains a major cause of morbidity and mortality in hospitalised patients. UK mandatory surveillance has driven significant reduction in healthcare-associated CDI through antibiotic stewardship and infection prevention measures.

Epidemiology

UK: ~13,000 cases/year reported (declining due to improved stewardship)
Accounts for 15–25% of antibiotic-associated diarrhoea
Mortality: 1–5% overall; up to 25–30% in fulminant colitis
30-day mortality: ~15% in elderly hospitalised patients
Community-acquired CDI increasing (~25% of cases)

Aetiology

Clostridioides difficile: Gram-positive, anaerobic, spore-forming bacillus
Produces toxin A (enterotoxin) and toxin B (cytotoxin) - cause mucosal damage
Binary toxin (CDT): produced by hypervirulent ribotype 027

Antibiotic exposure disrupts normal colonic microbiota

C. difficile colonisation

toxin production

Spores: resistant to alcohol-based hand gels and standard cleaning - require sporicidal agents (bleach, hydrogen peroxide)

Pathophysiology

Normal colonic flora provides colonisation resistance against C. difficile

Antibiotics (especially broad-spectrum) disrupt this

spore germination

vegetative growth

toxin production

Toxin A and B

disruption of tight junctions, cytoskeletal damage

inflammation, fluid secretion, mucosal necrosis

Pseudomembrane formation: raised yellow-white plaques on colonic mucosa

Severe colitis

toxic megacolon

perforation

Clinical Presentation

Mild-Moderate CDI

Watery diarrhoea (≥3 loose stools in 24 hours) - NOT bloody
Lower abdominal cramping
Low-grade fever
Recent antibiotic history (onset typically 5–10 days after antibiotics but can be up to 8 weeks)

Severe CDI

Profuse diarrhoea (>10 stools/day)
Fever >38.5°C
Raised WCC (>15 × 10⁹/L)
Rising creatinine (>50% above baseline)
Dehydration, electrolyte disturbance

Fulminant/Life-Threatening CDI

Toxic megacolon: abdominal distension, absent bowel sounds, peritonism
Ileus: may paradoxically have REDUCED diarrhoea
Septic shock, multi-organ failure
Lactate >2.2 mmol/L

Red Flags

Abdominal distension with peritonism (toxic megacolon/perforation)
WCC >15 or <1.5 × 10⁹/L
Rising lactate or creatinine
Ileus (reduced stool output may indicate worsening, not improvement)
Temperature >38.5°C despite treatment
Failure to improve after 48–72 hours of treatment

Differential Diagnosis

Diagnosis	Key Features	Investigation
Antibiotic-associated diarrhoea (non-CDI)	Milder, no toxin positive, resolves on stopping antibiotics	C. difficile toxin negative
Norovirus	Vomiting predominant, contact history, winter seasonality	Stool norovirus PCR
IBD flare	Known IBD, bloody diarrhoea, systemic features	Calprotectin, colonoscopy
Ischaemic colitis	Elderly, vascular disease, bloody diarrhoea, LIF pain	CT angiography, colonoscopy
Overflow diarrhoea	Constipation history, faecal loading on AXR	AXR, rectal exam

Diagnosis / Investigation

Bedside

Stool sample: ONLY test loose/watery stools (Bristol type 5–7) - do NOT test formed stools
Observations: temperature, HR, BP, NEWS2

Bloods

FBC: leucocytosis (WCC >15 = marker of severity)
U&Es: AKI, dehydration
CRP: elevated
Lactate: raised in severe/fulminant
Albumin: low (poor prognostic marker)

Stool Tests

Two-stage testing: GDH (glutamate dehydrogenase) screen → if positive, toxin EIA (enzyme immunoassay) for toxin A/B
GDH+/Toxin+: confirmed CDI
GDH+/Toxin–: may be carrier; consider clinical context and PCR if available
NAAT/PCR: highly sensitive but may detect carriers (positive for toxin gene, not necessarily active toxin)

Imaging

AXR: if toxic megacolon suspected (colonic dilation >6cm)
CT abdomen: colonic wall thickening (accordion sign), pericolonic fat stranding, ascites; free air if perforation

Management

Non-pharmacological

Stop precipitating antibiotics if possible (or switch to lower-risk agents)
Isolation: single room with dedicated bathroom; contact precautions
Hand washing with soap and water: alcohol gel does NOT kill spores
Environmental cleaning: sporicidal agents (bleach-based)
Review PPI: stop if not essential (associated with CDI recurrence)
Avoid antidiarrhoeal agents (loperamide): risk of toxic megacolon

Pharmacological

First episode (NICE NG199):

Oral vancomycin 125mg QDS for 10 days (first-line)
OR fidaxomicin 200mg BD for 10 days (if high risk of recurrence: >65, severe, concurrent antibiotics)
Metronidazole 400mg TDS oral for 10 days: only if vancomycin/fidaxomicin unavailable

First recurrence:

Fidaxomicin 200mg BD for 10 days (preferred - lower recurrence rate)

OR vancomycin tapering/pulsed regimen: 125mg QDS 14 days

125mg BD 7 days

125mg OD 7 days

125mg every 2–3 days for 2–4 weeks

Second or subsequent recurrence:

Faecal microbiota transplantation (FMT): ~90% effective; recommended by NICE for ≥2 recurrences
Fidaxomicin or vancomycin taper as bridge to FMT

Severe/fulminant CDI:

Oral vancomycin 500mg QDS (higher dose)
± IV metronidazole 500mg TDS if ileus (oral vancomycin may not reach colon)
± Rectal vancomycin 500mg in 100ml NaCl QDS (via rectal tube) if complete ileus

MODIFY I/II trials:

Fidaxomicin non-inferior to vancomycin for initial cure; superior for recurrence prevention (~13% vs ~27%)

Surgical/Interventional

Subtotal colectomy: for toxic megacolon, perforation, or refractory fulminant CDI
Loop ileostomy with colonic vancomycin lavage: emerging alternative to colectomy

Referral Criteria

Gastroenterology: severe CDI, recurrent CDI for FMT
Surgery: toxic megacolon, perforation, failure to improve on maximum medical therapy
Infection prevention team: all cases (mandatory reporting)

Prognosis

Mild-moderate CDI: >90% cure rate with oral vancomycin
Recurrence rate: ~20–25% after first episode; ~40–60% after second episode
Fidaxomicin: reduces recurrence by ~50% compared to vancomycin
FMT: ~90% cure for recurrent CDI
Severe CDI: 15–20% mortality
Fulminant CDI/toxic megacolon: mortality 30–50%
30-day all-cause mortality in hospitalised CDI: ~15% (elderly)
Long-term: most patients recover fully; some develop post-infectious IBS
UK mandatory surveillance has contributed to >50% reduction in healthcare-associated CDI since 2007

Other Relevant Information

CDI Severity Classification

Severity	Features	Treatment
Mild	<3 stools/day, no raised WCC	Oral vancomycin 125mg QDS
Moderate	3–5 stools/day, raised WCC/CRP	Oral vancomycin 125mg QDS
Severe	WCC >15, Cr >50% rise, temp >38.5°C	Oral vancomycin 500mg QDS
Fulminant	Toxic megacolon, ileus, shock	Vanc 500mg QDS + IV metro + surgical review

High-Risk Antibiotics for CDI (4Cs)

Antibiotic	Risk Level
Co-amoxiclav	High
Cephalosporins	High
Ciprofloxacin (fluoroquinolones)	High
Clindamycin	High

NICE Guidelines / CKS

MRSA

Methicillin-resistant Staphylococcus aureus is a major healthcare-associated pathogen resistant to flucloxacillin and all beta-lactams via the mecA gene (PBP2a). Causes skin/soft tissue infections, bacteraemia, endocarditis, and surgical site infections. UK rates have declined >80% since mandatory screening and decolonisation programmes.

MRCP Part 1 · MRCP Part 2 · PLAB 1 · UKMLA · MRCGP AKT · MSRA

Key Facts

mecA gene encodes altered penicillin-binding protein (PBP2a) → resistance to ALL beta-lactams (penicillins, cephalosporins, carbapenems)
UK mandatory screening: all elective and emergency admissions screened with nasal swab ± other sites
Decolonisation: mupirocin 2% nasal ointment TDS for 5 days + chlorhexidine 4% body wash for 5 days
MRSA bacteraemia: treat with IV vancomycin 15–20mg/kg BD (target trough 15–20 mg/L) or IV daptomycin 6–10mg/kg OD
MRSA-related deaths in UK: declined >80% since 2007 mandatory surveillance and screening programmes
Community-acquired MRSA (CA-MRSA): Panton-Valentine leukocidin (PVL) producing strains - recurrent boils, skin abscesses, necrotising pneumonia in young healthy individuals
Linezolid 600mg BD: oral option for MRSA soft tissue infection; monitor FBC weekly (myelosuppression)
Hand hygiene and isolation are the most important infection prevention measures

Overview

Key Facts

MRSA is one of the most important healthcare-associated pathogens worldwide. UK programmes of mandatory screening, decolonisation, and antimicrobial stewardship have achieved dramatic reductions in MRSA bacteraemia.

Epidemiology

UK MRSA bacteraemia: ~780 cases/year (2022) - down from >7,000/year in 2007
MRSA accounts for ~5–10% of S. aureus bacteraemia in UK (historically >40%)
Healthcare-associated MRSA declining; community-acquired strains increasingly recognised
PVL-MRSA: particular concern in young, otherwise healthy individuals

Aetiology

S. aureus carrying SCCmec (staphylococcal cassette chromosome mec) with mecA gene
HA-MRSA: hospital-acquired, often multi-drug resistant
CA-MRSA: community strains, often PVL-positive, may be susceptible to more agents (e.g. doxycycline, trimethoprim)
Carriage: nasal carriage in ~2–5% of UK population; higher in healthcare workers, IVDU, prisoners

Pathophysiology

PBP2a: altered penicillin-binding protein with low affinity for beta-lactams → resistance
Same virulence factors as MSSA: protein A, coagulase, toxins

PVL (Panton-Valentine leukocidin): pore-forming toxin

leucocyte lysis

tissue necrosis; associated with CA-MRSA

Biofilm formation: important in prosthetic device infections

Clinical Presentation

HA-MRSA

Surgical site infection
Bacteraemia (often line-related)
Pneumonia (ventilator-associated)
Prosthetic joint/device infection
Wound infections

CA-MRSA (PVL-positive)

Recurrent skin boils/abscesses (buttocks, axillae, groin)
Necrotising pneumonia: young, previously healthy; post-influenza; haemoptysis, multi-lobar cavitating consolidation - high mortality
Necrotising fasciitis
Bone and joint infections

Red Flags

S. aureus bacteraemia not responding to flucloxacillin (suspect MRSA)
Recurrent skin abscesses (PVL-MRSA)
Young healthy patient with cavitating pneumonia post-flu illness
Prosthetic device with persistent infection

Differential Diagnosis

Diagnosis	Key Features	Investigation
MSSA infection	Same clinical features, susceptible to flucloxacillin	Culture and sensitivity
PVL-positive MSSA	Recurrent boils, necrotising pneumonia (same as PVL-MRSA)	Culture + PVL gene testing
Streptococcal infection	Cellulitis, impetigo, pharyngitis	Wound/blood culture
Fungal skin infection	Chronic, non-purulent, scaling	KOH prep, culture
Hidradenitis suppurativa	Recurrent abscesses in flexures, sinus tracts	Clinical, biopsy

Diagnosis / Investigation

Screening

Nasal swab (bilateral nares): standard MRSA screening
Additional sites: groin, axillae, wounds, catheter sites, throat
Enrichment culture or PCR: for rapid detection

Infection Diagnosis

Wound swab/pus: culture and sensitivity
Blood cultures: essential in suspected bacteraemia
Susceptibility testing: determines antibiogram (e.g. vancomycin MIC)
PVL gene testing: request if recurrent abscesses or necrotising infection

Bloods

FBC, CRP, lactate: infection markers
Vancomycin trough levels: target 15–20 mg/L for serious infections

Imaging

Echocardiography: all S. aureus bacteraemia (TEE preferred) - endocarditis occurs in ~10–25%
CT/MRI: metastatic infection (bone, joints, epidural abscess)
CXR/CT chest: pneumonia

Special Tests

Repeat blood cultures at 48–72 hours: all S. aureus bacteraemia to confirm clearance
Removable source identification: lines, prosthetics, abscesses

Management

Non-pharmacological

Contact precautions: isolation in single room, gown and gloves
Hand hygiene: soap and water (MRSA spores resistant to alcohol gel - though MRSA is not spore-forming; hand hygiene with alcohol gel is effective but soap and water preferred)
Environmental cleaning: enhanced cleaning of patient environment
Source removal: remove/replace infected lines, drain abscesses

Decolonisation (MRSA carriers)

Mupirocin 2% nasal ointment TDS for 5 days (both nares)
Chlorhexidine 4% body wash OD for 5 days
Chlorhexidine mouthwash: if throat carriage
Re-screen 48 hours after completion; repeat if still positive

Pharmacological

MRSA bacteraemia:

IV vancomycin 15–20mg/kg BD (target trough 15–20 mg/L) for minimum 14 days (28 days if endocarditis)
IV daptomycin 6–10mg/kg OD: alternative (NOT for pneumonia - inactivated by surfactant)
Duration: minimum 14 days for uncomplicated bacteraemia; 4–6 weeks for endocarditis, osteomyelitis

MRSA skin/soft tissue:

Oral: doxycycline 200mg then 100mg OD, trimethoprim 200mg BD, or linezolid 600mg BD (guided by sensitivities)
IV: vancomycin, daptomycin, or linezolid
Linezolid: monitor FBC weekly (thrombocytopenia, anaemia); max 28 days

MRSA pneumonia:

IV vancomycin or IV linezolid 600mg BD (linezolid achieves higher lung concentrations)

Incision and drainage:

Essential for abscesses - antibiotics alone insufficient

Referral Criteria

Infectious diseases/microbiology: all MRSA bacteraemia
Cardiology: echocardiography for S. aureus bacteraemia
Surgery: abscess drainage, prosthetic device removal
Infection prevention team: all MRSA-positive patients

Prognosis

MRSA bacteraemia: mortality 20–30% (similar to MSSA bacteraemia when appropriately treated)
PVL-necrotising pneumonia: mortality 30–75%
Endocarditis: mortality 20–40%
Skin/soft tissue MRSA: generally good prognosis with appropriate drainage and antibiotics
UK MRSA bacteraemia rates reduced >80% since mandatory surveillance (2007)
Decolonisation: effective in ~75% of carriers with single course
Recurrent MRSA carriage: common; may need repeated decolonisation or systemic antibiotics

Other Relevant Information

MRSA Treatment Summary

Infection	First-Line Treatment
Bacteraemia	IV vancomycin (trough 15–20) or daptomycin
Endocarditis	IV vancomycin ± gentamicin (or daptomycin)
Pneumonia	IV vancomycin or linezolid (NOT daptomycin)
Skin/soft tissue	Doxycycline, trimethoprim, or linezolid PO
Osteomyelitis	IV vancomycin then oral (rifampicin + another agent)
Decolonisation	Mupirocin nasal + chlorhexidine body wash

NICE Guidelines / CKS

Healthcare-Associated Infections

Infections acquired during or as a result of healthcare delivery, not present on admission. Include MRSA bacteraemia, C. difficile infection, catheter-associated UTI, ventilator-associated pneumonia, and surgical site infections. UK mandatory surveillance has driven significant reductions through infection prevention and antimicrobial stewardship.

MRCP Part 1 · MRCP Part 2 · PLAB 1 · UKMLA · MRCGP AKT · MSRA

Key Facts

Prevalence: ~6.4% of hospital inpatients have an HAI at any one time (PPS 2016); ~300,000 HAIs/year in England
Most common HAIs: UTI (~22%), surgical site infection (~16%), pneumonia (~15%), bloodstream infection (~12%)
NICE QS113: healthcare-associated infections quality standard - covers hand hygiene, antimicrobial stewardship, device management
High Impact Interventions (HIIs): care bundles for central lines, peripheral cannulae, urinary catheters, ventilators - reduce infection rates
Antimicrobial stewardship: essential to reduce CDI, MRSA, and antimicrobial resistance - review antibiotics at 48–72 hours, limit broad-spectrum use
Mandatory reporting: MRSA bacteraemia, MSSA bacteraemia, C. difficile, E. coli bacteraemia, Klebsiella, Pseudomonas
Hand hygiene: WHO 5 Moments - the single most important infection prevention measure
Cost: HAIs cost the NHS an estimated £1–2 billion/year

Overview

Key Facts

HAIs represent a major burden on the NHS in terms of patient harm, mortality, and cost. Many are preventable through evidence-based infection prevention measures and antimicrobial stewardship.

Epidemiology

~300,000 HAIs/year in England
HAI prevalence: 6.4% (PPS 2016)
Attributable mortality: ~5,000 deaths/year in England
MRSA bacteraemia: ~780/year (down from 7,000+ in 2007)
C. difficile: ~13,000/year (down from 55,000 in 2007)
E. coli bacteraemia: ~40,000/year (most common Gram-negative BSI - urinary source most common)

Aetiology

Common HAIs:

Catheter-associated UTI (CAUTI): E. coli, Klebsiella, Enterococcus, Candida
Central line-associated bloodstream infection (CLABSI): coag-neg staph, S. aureus, Enterococcus, Gram-negatives
Ventilator-associated pneumonia (VAP): Pseudomonas, S. aureus, Acinetobacter, Gram-negatives
Surgical site infection (SSI): S. aureus, coag-neg staph, Gram-negatives
C. difficile infection: antibiotic-associated

Pathophysiology

Healthcare devices (catheters, lines, ventilators) bypass natural defence barriers

bacterial colonisation

biofilm formation

infection

Hospital environment: reservoirs of resistant organisms (MRSA, VRE, CPE, C. difficile spores)
Host factors: immunosuppression, extremes of age, invasive procedures, prolonged hospitalisation
Antibiotic pressure: selects for resistant organisms; disrupts normal microbiome

Clinical Presentation

CAUTI

Fever, dysuria, suprapubic pain, cloudy/offensive urine
Catheterised patient - symptoms may be non-specific (confusion in elderly)

CLABSI

Fever, rigors, especially during/after line use
Erythema at exit site, purulent discharge
Positive blood cultures with organism typical of line infection

VAP

New/worsening fever, purulent secretions, new infiltrate on CXR
Developing ≥48 hours after intubation

SSI

Wound erythema, warmth, discharge, dehiscence
Within 30 days of surgery (or 1 year if implant)

Red Flags

Sepsis signs in any hospitalised patient with device
Positive blood cultures for typical healthcare-associated organism
New onset CDI diarrhoea during or after hospital admission
Multi-drug resistant organism identified

Differential Diagnosis

Diagnosis	Key Features	Investigation
Community-acquired infection	Present on admission or <48 hours	Timing, clinical context
Drug fever	Temporal drug relationship, diagnosis of exclusion	Drug history, eosinophil count
Non-infectious fever	VTE, malignancy, transfusion reaction, drug reaction	Imaging, D-dimer, tryptase
Colonisation vs infection	Positive culture without clinical signs	Clinical correlation essential

Diagnosis / Investigation

General Approach

Blood cultures: before antibiotics if HAI suspected
Specific site cultures: urine (MSU/CSU), wound swab, sputum/BAL, line tip
FBC, CRP, procalcitonin: infection markers
Imaging: CXR (pneumonia), USS/CT (abscess/collection)

Surveillance

Mandatory reporting to UKHSA: MRSA, MSSA, E. coli, Klebsiella, Pseudomonas bacteraemia; C. difficile
SSI surveillance: optional but recommended for orthopaedic, cardiac, and other high-risk surgery
Point prevalence surveys: periodic assessment of HAI rates

Special Tests

MRSA screening: nasal ± groin swab on admission
CPE screening: rectal swab for high-risk patients (travel, ICU transfer)
C. difficile toxin: loose stool only

Management

Non-pharmacological - Prevention

Hand hygiene (WHO 5 Moments):

Before patient contact
Before aseptic task
After body fluid exposure risk
After patient contact
After contact with patient surroundings

Device management:

Urinary catheters: insert only when indicated, review daily, remove as soon as possible; aseptic insertion technique
Central lines: aseptic insertion (Matching Michigan bundle), daily review of ongoing need, chlorhexidine dressings
Ventilators: head of bed elevation, daily sedation holds, oral chlorhexidine, subglottic aspiration

Antimicrobial stewardship:

Review antibiotics at 48–72 hours: stop if no infection, narrow spectrum based on cultures, switch IV to oral
Restrict high-risk antibiotics (4Cs) - co-amoxiclav, cephalosporins, ciprofloxacin, clindamycin
Guidelines adherence: local antibiotic guidelines based on resistance patterns

Environmental:

Enhanced cleaning of patient areas
Isolation of infected/colonised patients (side rooms)
Sporicidal cleaning for C. difficile

Pharmacological - Treatment

Treat specific HAI according to organism and site:
- CAUTI: per local guidelines (often nitrofurantoin, trimethoprim, or gentamicin based on culture)
- CLABSI: empirical vancomycin ± gentamicin; definitive based on culture
- VAP: piperacillin-tazobactam or meropenem ± vancomycin; de-escalate per culture
- SSI: flucloxacillin (MSSA) or vancomycin (MRSA); Gram-negative cover if abdominal
- CDI: oral vancomycin per NICE NG199

Referral Criteria

Infection prevention and control team: all HAIs
Microbiology: resistant organisms, complex infections
Antimicrobial stewardship team: review of antibiotic use
Surgery: SSI requiring wound management or debridement

Prognosis

HAIs increase hospital stay by an average of 5–10 days
Attributable mortality: varies by infection type - CLABSI ~12–25%, VAP ~13%, CDI ~5–15%
NHS cost: £1–2 billion/year
UK programmes have achieved >80% reduction in MRSA bacteraemia and >50% reduction in CDI since 2007
E. coli bacteraemia: remains a challenge - ambition to reduce by 50%
Prevention is far more effective than treatment - most HAIs are preventable

Other Relevant Information

Mandatory Reporting Organisms (UKHSA)

Organism	Reporting
MRSA bacteraemia	Mandatory
MSSA bacteraemia	Mandatory
C. difficile	Mandatory
E. coli bacteraemia	Mandatory
Klebsiella spp. bacteraemia	Mandatory
Pseudomonas aeruginosa bacteraemia	Mandatory

High Impact Interventions (Care Bundles)

Device	Key Bundle Elements
Central venous catheter	Hand hygiene, maximal barrier, chlorhexidine skin prep, optimal site, daily review
Peripheral cannula	Aseptic insertion, review every 72 hours, remove when no longer needed
Urinary catheter	Insert only when indicated, aseptic technique, closed drainage, daily review, early removal
Ventilator	Head elevation 30–45°, oral care, daily sedation hold, DVT/peptic ulcer prophylaxis

NICE Guidelines / CKS

Urinary Tract Infection

Bacterial infection of the urinary tract, classified as lower (cystitis) or upper (pyelonephritis). The most common bacterial infection in women. E. coli causes >80% of uncomplicated UTIs. Managed with nitrofurantoin or trimethoprim for uncomplicated cases per NICE NG109.

MRCP Part 1 · MRCP Part 2 · PLAB 1 · UKMLA · MRCGP AKT · MSRA

Key Facts

E. coli causes >80% of uncomplicated UTIs; other: Klebsiella, Proteus (staghorn calculi), Enterococcus, Staphylococcus saprophyticus (young women)
NICE NG109: first-line for uncomplicated lower UTI in women - nitrofurantoin 100mg MR BD for 3 days or trimethoprim 200mg BD for 3 days
Nitrofurantoin: contraindicated if eGFR <45 (ineffective - not concentrated in urine; also risk of peripheral neuropathy)
Dipstick: nitrites (most specific) + leucocytes; negative nitrites + negative leucocytes effectively excludes UTI
Complicated UTI: male, pregnant, catheterised, renal tract abnormality, immunocompromised, recurrent - requires longer treatment and investigation
Recurrent UTI (≥3/year or ≥2 in 6 months): consider prophylaxis - nitrofurantoin 50–100mg ON or trimethoprim 100mg ON
Asymptomatic bacteriuria: only treat in pregnancy (risk of pyelonephritis/preterm labour) and before urological procedures
Pyelonephritis: loin pain, fever, rigors, nausea/vomiting - treat with cefalexin 500mg BD–TDS for 7–10 days or IV co-amoxiclav if severe

Overview

Key Facts

UTI is one of the most common infections encountered in both primary and secondary care. Accurate diagnosis, appropriate antibiotic selection, and avoidance of overtreatment (especially of asymptomatic bacteriuria) are key principles.

Epidemiology

~50% of women experience at least one UTI in their lifetime
Incidence: ~150 million UTIs globally/year
Female:male ratio: ~8:1 in young adults; ratio narrows with age (BPH in men)
Recurrent UTI: affects ~25% of women within 6 months of first episode
CAUTI: accounts for ~40% of hospital-acquired infections

Aetiology

E. coli: >80% of uncomplicated UTIs (uropathogenic strains - UPEC)
Klebsiella pneumoniae: 5–10%
Proteus mirabilis: associated with alkaline urine and staghorn calculi (urease producer)
S. saprophyticus: young sexually active women (~5–15%)
Enterococcus: associated with catheterisation, hospital acquisition
Pseudomonas: catheter-associated, structural abnormalities

Pathophysiology

Ascending infection

perineal bacteria

urethra

bladder (cystitis)

ureters

kidneys (pyelonephritis)

UPEC express type 1 fimbriae (adhere to uroepithelium) and P fimbriae (ascend to kidneys)
Shorter female urethra → increased susceptibility
Risk factors: sexual intercourse, spermicides, post-menopausal atrophic changes, catheterisation, obstruction, vesicoureteric reflux, pregnancy, diabetes

Clinical Presentation

Lower UTI (Cystitis)

Dysuria (burning on urination)
Frequency, urgency
Suprapubic pain/discomfort
Haematuria
Cloudy, offensive-smelling urine
Absence of systemic features

Upper UTI (Pyelonephritis)

Loin/flank pain (often unilateral), renal angle tenderness
High fever, rigors
Nausea, vomiting
Malaise
May have preceding lower UTI symptoms

UTI in Elderly

Often atypical: new confusion/delirium, falls, functional decline
Do NOT treat asymptomatic bacteriuria in elderly - very common finding (up to 50% in care home residents)

Red Flags

Signs of sepsis (tachycardia, hypotension, fever, confusion)
Loin pain + fever (pyelonephritis)
Haematuria in >60 years (possible malignancy - 2-week wait referral)
UTI in pregnancy (pyelonephritis risk)
Urinary retention
Suspected obstruction (single kidney, known stones)

Differential Diagnosis

Diagnosis	Key Features	Investigation
Vaginal candidiasis	Discharge, pruritus, no dysuria between voids	HVS, KOH prep
STI (chlamydia, gonorrhoea)	Discharge, sexual history, young adult	NAAT (first-void urine)
Interstitial cystitis	Chronic pelvic pain, frequency without infection	Urine culture negative, cystoscopy
Overactive bladder	Urgency, frequency without dysuria or infection	Bladder diary, culture negative
Renal stones	Colicky loin pain, haematuria	CT KUB
Prostatitis	Male, perineal pain, tender prostate on DRE	PSA (may be elevated), urine culture

Diagnosis / Investigation

Bedside

Urine dipstick: nitrites (most specific - ~95% specific), leucocytes (sensitive but non-specific)
- Nitrite+ AND leucocyte+ → high probability of UTI
- Nitrite– AND leucocyte– → UTI unlikely (NPV >95%)
MSU for culture and sensitivity: send if complicated UTI, treatment failure, pregnancy, male, recurrent, catheterised
Urine pregnancy test: if reproductive age

Bloods

Not required for uncomplicated lower UTI
FBC, CRP, U&Es, blood cultures: if pyelonephritis or sepsis
Lactate: if sepsis suspected

Imaging

Not routinely required for uncomplicated UTI
Renal USS: if pyelonephritis not responding to treatment (exclude obstruction/abscess)
CT KUB: if stones suspected
USS/DMSA scan: recurrent UTIs in children (vesicoureteric reflux)

Special Tests

Post-void residual volume: if recurrent UTIs (incomplete emptying)
Cystoscopy: recurrent UTIs with haematuria (exclude malignancy)
Urodynamics: if lower urinary tract symptoms with recurrent UTIs

Management

Non-pharmacological

Adequate hydration: encourage oral fluids
Paracetamol/ibuprofen: for pain and fever
Cranberry products: limited evidence; not recommended by NICE for prevention
Vaginal oestrogen (post-menopausal): topical oestradiol cream reduces recurrent UTI
Behavioural: void after intercourse, front-to-back wiping

Pharmacological

Uncomplicated lower UTI in women (NICE NG109):

First-line: nitrofurantoin 100mg MR BD for 3 days
Second-line: trimethoprim 200mg BD for 3 days (if low local resistance)
Third-line: pivmecillinam 400mg stat then 200mg TDS for 3 days
Avoid fluoroquinolones for uncomplicated UTI (reserve for serious infections)

Lower UTI in men:

Trimethoprim 200mg BD for 7 days or nitrofurantoin 100mg MR BD for 7 days
Consider prostatitis if recurrent - longer course required

Pyelonephritis:

Mild (oral): cefalexin 500mg BD–TDS for 7–10 days, or co-amoxiclav 500/125mg TDS
Severe (IV): co-amoxiclav 1.2g TDS IV, or gentamicin 5mg/kg OD IV + amoxicillin 1g TDS IV
Switch to oral when improving; total 7–14 days

UTI in pregnancy:

Treat all: including asymptomatic bacteriuria
Nitrofurantoin (avoid at term - neonatal haemolysis), cefalexin, or amoxicillin (guided by sensitivities)
Avoid trimethoprim in first trimester (folate antagonist)
MSU culture at booking; treat positive results

Recurrent UTI (≥3/year):

Antibiotic prophylaxis: nitrofurantoin 50–100mg ON or trimethoprim 100mg ON for 6 months, then review
Post-coital prophylaxis: single-dose antibiotic after intercourse
Vaginal oestrogen: topical oestradiol for post-menopausal women
Self-start antibiotics: patient-initiated treatment with safety-netting

Referral Criteria

Urology: recurrent UTIs in men (exclude structural cause), recurrent UTIs with haematuria
Nephrology: recurrent pyelonephritis, renal scarring
Gynaecology: post-menopausal vaginal atrophy management
2-week wait: visible haematuria in >60 years (exclude bladder cancer)

Prognosis

Uncomplicated lower UTI: >90% cure with appropriate antibiotics
Pyelonephritis: >95% recovery with treatment; ~5% develop bacteraemia
Recurrent UTI: ~25% of women have recurrence within 6 months
Prophylactic antibiotics: reduce recurrence by ~80%
UTI in pregnancy: untreated bacteriuria → 20–30% develop pyelonephritis; treatment reduces this to <5%
CAUTI: major source of morbidity; duration of catheterisation is the strongest risk factor
Trimethoprim resistance in E. coli: ~30% in UK - use nitrofurantoin first-line

Other Relevant Information

UTI Antibiotic Summary (NICE NG109)

Condition	First-Line	Duration
Uncomplicated lower UTI (women)	Nitrofurantoin 100mg MR BD	3 days
Lower UTI (men)	Trimethoprim 200mg BD	7 days
Pyelonephritis (mild)	Cefalexin 500mg BD	7–10 days
Pyelonephritis (severe)	IV co-amoxiclav 1.2g TDS	7–14 days
UTI in pregnancy	Nitrofurantoin (avoid at term)	7 days
Recurrent UTI prophylaxis	Nitrofurantoin 50mg ON	6 months

Urine Dipstick Interpretation

Result	Likelihood of UTI
Nitrite+ Leucocyte+	High probability - treat
Nitrite+ Leucocyte–	Probable UTI - treat
Nitrite– Leucocyte+	Possible - send MSU, consider other causes
Nitrite– Leucocyte–	UTI unlikely (NPV >95%)

NICE Guidelines / CKS

Catheter-Associated UTI

Urinary tract infection occurring in a patient with an indwelling urethral catheter, usually due to biofilm-associated uropathogens. Diagnosis and management differ from uncomplicated cystitis; removal of the catheter where possible is central to treatment.

MRCP Part 1 · MRCP Part 2 · PLAB 1 · UKMLA · MRCGP AKT · MSRA

Key Facts

Key points
Definition: significant bacteriuria (often ≥10⁵ CFU/mL) plus symptoms/signs of UTI in a patient with a urethral catheter (or within 48 hours of removal).
Common organisms: Escherichia coli, Klebsiella spp., Enterococcus spp., Pseudomonas aeruginosa; consider multidrug resistance in healthcare-associated cases.
Do not treat asymptomatic bacteriuria except in pregnancy or before invasive urological procedures (per local policy).
First-line antibiotics (when treatment indicated): guided by culture; common choices include nitrofurantoin (only if eGFR ≥45 mL/min/1.73 m² and no catheter obstruction), trimethoprim, or a cephalosporin - adjust per sensitivity and severity.
Catheter management: remove if possible; if needed, change catheter at treatment onset; avoid silver-coated catheters for routine infection prevention.
Duration: typically 7 days if prompt response; longer courses if slow response or severe sepsis (follow local stewardship guidance).

Overview

Definition and epidemiology

Catheter-associated urinary tract infection (CAUTI) is one of the commonest healthcare-associated infections. Indwelling urethral catheters breach normal urinary defence mechanisms and allow biofilm formation on the catheter surface.

Pathophysiology

Biofilms harbour bacteria that are relatively protected from antibiotics and host immunity. Catheter blockage, inadequate closed-drainage systems, and breaches in aseptic technique increase risk.

Prevention (UK practice)

Use catheters only when clearly indicated; review need daily.
Maintain closed drainage; avoid unnecessary irrigation.
Hand hygiene and aseptic insertion by trained staff.
Consider alternatives (intermittent catheterisation, condom drainage) where appropriate.

Clinical Presentation

Symptoms and signs

New or worsening suprapubic pain, loin pain, rigors, fever, confusion (especially older adults), hypotension (sepsis).
Catheter-related symptoms may be subtle; hypothermia or delirium may be the only clue.

Examination

Fever, tachycardia, suprapubic tenderness; assess for acute kidney injury and septic shock.

Red flags

Sepsis (NEWS2 escalation), anuria, refractory hypotension, concern for obstructive uropathy (requires urgent urology input).

Differential Diagnosis

Diagnosis	Clues	Notes
Asymptomatic bacteriuria	No systemic/local symptoms	Do not treat except specific indications
Non-infective catheter irritation	Dysuria without fever	Review catheter need
Clostridioides difficile colitis	Diarrhoea, toxins	Concurrent antibiotic exposure
Acute pyelonephritis without catheter	Similar presentation	Catheter still increases complexity
Prostatitis/epididymo-orchitis	Local examination findings	Consider if catheter recently removed
Other sources of sepsis	Alternative focus	Parallel assessment (chest, line, abdomen)

Diagnosis / Investigation

Bedside

NEWS2, urine dipstick (limited specificity with catheters), urine microscopy if available.
Urine culture from a freshly placed catheter or after catheter change (avoid sampling from drainage bags).

Bloods

FBC, CRP, U&Es, LFTs, blood cultures if systemic features.

Imaging

Renal tract ultrasound if obstruction suspected (hydronephrosis).
CT KUB if calculus/abscess suspected.

Microbiology

Culture identifies organism and resistance; check prior isolates.

Management

Immediate care

Sepsis 6 if septic: oxygen, IV access, fluids, lactate, antibiotics, urine output monitoring.
Analgesia and antipyretics as needed.

Catheter strategy

Remove if no longer needed; if retention risk, replace at start of therapy.
Do not routinely irrigate unless obstruction.

Antibiotics (examples - follow local formulary and culture)

Oral (mild, outpatient where appropriate):

Nitrofurantoin 50–100 mg QDS for 7 days (avoid if eGFR <45; not for upper tract sepsis as sole agent if concern).
Trimethoprim 200 mg BD for 7 days if sensitive.
Pivmecillinam 400 mg TDS (where available) per sensitivity.

IV (inpatient/severe):

Co-amoxiclav 1.2 g TDS (if non-severe and susceptible).
Ceftriaxone 1–2 g OD (adjust renal/hepatic impairment).
Piperacillin/tazobactam 4.5 g TDS if Gram-negative resistance risk.
Meropenem 1 g TDS only when MDR risk and specialist advice.

Duration: commonly 7 days if improving; extend if bacteraemia/abscess.

Escalation

ICU if persistent shock; urology for obstruction/stone.

Prognosis

With prompt catheter management and appropriate antibiotics, most patients improve within 48–72 hours. Bacteraemia and obstructive uropathy worsen prognosis. Recurrence is common if catheters remain in situ unnecessarily.

Other Relevant Information

Stewardship pearls

Treat symptoms + culture, not colonisation.
Document indication and removal plan for every catheter.
Avoid prophylactic antibiotics solely to prolong catheter use.

NICE Guidelines / CKS

Infective Endocarditis

Infection of the endocardium, typically involving heart valves, causing fever, embolic phenomena, and heart failure. *Staphylococcus aureus* and oral streptococci are common; diagnosis integrates blood cultures and echocardiography; treatment is prolonged high-dose bactericidal antibiotics and sometimes surgery.

MRCP Part 1 · MRCP Part 2 · PLAB 1 · UKMLA · MRCGP AKT · MSRA

Key Facts

Key points
Modified Duke criteria integrate major/minor clinical, microbiological, and imaging features.
Three sets of blood cultures before antibiotics (different sites, 30 minutes apart) unless critically unwell.
Empirical IV therapy if unstable: often flucloxacillin 2 g IV 4-hourly (or vancomycin if MRSA risk) plus gentamicin only when synergy indicated (e.g. streptococcal native valve) - seek local protocol.
Native valve streptococcal IE: benzylpenicillin 2.4 g IV 4-hourly (or ceftriaxone) plus short-course gentamicin synergy in selected cases per guideline.
MRSA: vancomycin IV (monitor levels) or daptomycin in right-sided IE when appropriate.
Indications for surgery: heart failure, uncontrolled infection, embolic events, perivalvular abscess/fistula.

Overview

Epidemiology and risk

Incidence peaks in older adults and in people with prosthetic valves, prior endocarditis, injection drug use, or rheumatic valve disease.

Pathogenesis

Endothelial damage allows platelet–fibrin deposition; transient bacteraemia seeds vegetations. Biofilm on prosthetic material complicates eradication.

Organisms

Native valves: viridans streptococci, S. aureus, enterococci.
Prosthetic early: coagulase-negative staphylococci, S. aureus.
IVDU: S. aureus (often right-sided).

Clinical Presentation

Features

Fever, night sweats, malaise, new murmur (or change), splinter haemorrhages, Osler nodes, Janeway lesions, Roth spots (classic but not sensitive).

Embolic and systemic

Stroke, limb ischaemia, splenic/renal infarcts, mycotic aneurysm.

Prosthetic valve

Paravalvular leak, heart block (abscess), persistent fever.

Differential Diagnosis

Diagnosis	Clues
Non-infective marantic endocarditis	Malignancy, TTE/TOE vegetation morphology
Acute rheumatic fever	Migratory arthritis, chorea, recent strep
Atrial myxoma	Tumour plop, echo mass
Q fever/Coxiella IE	Culture-negative, serology, travel/animal exposure
Libman–Sacks (SLE)	Autoantibodies, clinical context

Diagnosis / Investigation

Microbiology

≥3 blood culture sets from peripheral sites.
If culture-negative: consider Coxiella, Bartonella, HACEK, fungi - specialist lab advice.

Cardiac imaging

TTE first; TOE if prosthetic valves, suspected complications, or negative TTE with high suspicion.

Other

ECG (heart block), CT if abscess/embolic stroke assessment, CRP/FBC, renal function before nephrotoxic agents.

Management

Empirical (before sensitivities - follow local guideline)

Example combinations (adjust renal function):

Flucloxacillin 2 g IV 4-hourly + gentamicin synergy only when indicated.
Vancomycin IV (loading per protocol) if MRSA risk or penicillin anaphylaxis (consult microbiology).

Streptococcal native valve (example)

Benzylpenicillin 2.4 g IV 4-hourly or ceftriaxone 2 g IV OD; duration commonly 4–6 weeks depending on organism and complications.

Staphylococcus aureus

Flucloxacillin 2 g IV 4-hourly (native); longer courses for prosthetic/right-sided disease per guideline.

Enterococcal

Amoxicillin or ampicillin based regimens ± gentamicin synergy - nephrotoxicity risk; alternative: ceftriaxone + ampicillin for certain E. faecalis.

Surgery

Heart failure, refractory infection, abscess, embolic stroke with large vegetation - MDT decision.

Antibiotic prophylaxis (UK)

Routine dental prophylaxis not recommended solely for IE in most patients; manage specific high-risk groups per NICE.

Prognosis

In-hospital mortality remains substantial, especially with S. aureus, heart failure, and neurological complications. Surgical treatment improves outcomes in selected cases. Long-term follow-up for valve dysfunction is essential.

Other Relevant Information

Gentamicin synergy

Use only with clear indication and monitor levels and renal function; many centres shorten aminoglycoside exposure due to toxicity.

Outpatient OPAT

Selected stable patients may complete IV therapy via OPAT services.

NICE Guidelines / CKS

Osteomyelitis

Bone infection arising from haematogenous seeding, contiguous spread, or direct inoculation. *Staphylococcus aureus* is the commonest organism in adults. MRI is the imaging modality of choice; treatment combines prolonged antibiotics and sometimes surgical debridement.

MRCP Part 1 · MRCP Part 2 · PLAB 1 · UKMLA · MRCGP AKT · MSRA

Key Facts

Key points
Acute haematogenous osteomyelitis: children (metaphysis) and adults (vertebral).
MRI is most sensitive for early bone oedema; plain radiographs lag by 10–14 days.
Blood cultures may be positive; bone biopsy for microbiology where safe/practical guides therapy.
Flucloxacillin 2 g IV 4-hourly for MSSA (typical 4–6 weeks total - IV then oral switch per clinical response).
Vancomycin IV if MRSA risk; clindamycin 600 mg IV QDS oral step-down alternative for penicillin allergy (confirm susceptibility).
Diabetic foot osteomyelitis: polymicrobial; often co-amoxiclav or piperacillin/tazobactam; surgical offloading and revascularisation are key.

Overview

Classification

Acute vs chronic (symptoms >6 weeks suggests chronic).
Haematogenous vs contiguous (adjacent soft-tissue/decubitus) vs post-operative/traumatic.

Risk factors

Diabetes mellitus, peripheral vascular disease, immunosuppression, IV drug use, prosthetic material.

Pathophysiology

Bacterial invasion causes inflammatory bone destruction; sequestrum formation in chronic disease impairs antibiotic penetration.

Clinical Presentation

Presentation

Local pain, swelling, reduced weight-bearing; fever may be absent, especially in diabetes.

Vertebral osteomyelitis

Back pain, focal tenderness; epidural abscess may cause neurological deficit - urgent MRI.

Red flags

Neurological signs, sepsis, spreading soft-tissue infection - emergency assessment.

Differential Diagnosis

Condition	Clues
Cellulitis/abscess without bone involvement	MRI negative for marrow oedema
Charcot neuro-osteoarthropathy	Warm swollen foot, neuropathy, different MRI pattern
Malignancy/bone metastasis	Systemic symptoms, imaging pattern
Fracture/stress injury	History of trauma, linear marrow oedema

Diagnosis / Investigation

Imaging

MRI first-line for suspected osteomyelitis.
Plain radiographs if chronic changes suspected or MRI unavailable.
WBC-labelled scan occasionally if MRI contraindicated.

Microbiology

Blood cultures before antibiotics.
Bone/deep tissue culture (avoid superficial swabs in diabetic foot).

Bloods

CRP, ESR, FBC, HbA1c if diabetes.

Management

Acute MSSA (example adult regimen - follow local protocol)

Flucloxacillin 2 g IV 6-hourly until stable, then oral flucloxacillin 500 mg–1 g QDS to complete 4–6 weeks typical total.
MRSA: vancomycin IV (target trough 15–20 mg/L for serious infections per local guidance) or daptomycin 6–10 mg/kg OD (not pneumonia).

Gram-negative / polymicrobial (diabetic foot)

Piperacillin/tazobactam 4.5 g TDS IV or co-amoxiclav if mild and susceptible.
Add metronidazole 500 mg TDS if anaerobic concern.

Chronic staphylococcal (oral combination - specialist)

Rifampicin 300–450 mg BD plus fusidic acid or flucloxacillin - never rifampicin monotherapy; check interactions.

Surgery

Drain abscess; remove necrotic bone/hardware; revascularisation when ischaemic.

Prognosis

Acute haematogenous osteomyelitis in children often resolves with antibiotics alone. Adult vertebral and diabetic foot infections have higher morbidity and recurrence; multidisciplinary foot care reduces amputation risk.

Other Relevant Information

OPAT

Early switch to oral therapy is standard when clinically appropriate and microbiology supports oral agents.

NICE Guidelines / CKS

Sexually Transmitted Infections

A group of infections transmitted by sexual contact, including chlamydia, gonorrhoea, syphilis, HIV, trichomoniasis, and viral hepatitis. UK care emphasises confidential testing, partner notification, and syndrome-based management when empirical therapy is required.

MRCP Part 1 · MRCP Part 2 · PLAB 1 · UKMLA · MRCGP AKT · MSRA

Key Facts

Key points
Asymptomatic infection is common - screen high-risk groups and contacts.
Dual testing for HIV and syphilis serology is routine in sexual health screens.
Gonorrhoea: treat with ceftriaxone 1 g IM/IV plus azithromycin 1 g PO** (UK BASHH - check current national guidance for resistance patterns).
Chlamydia: doxycycline 100 mg BD for 7 days first-line; azithromycin 1 g** alternative if pregnancy/doxycycline contraindicated (local policy).
Partner notification: index case should inform partners from the relevant look-back period; clinics can use accelerated partner therapy where appropriate.
PrEP (HIV pre-exposure prophylaxis) with tenofovir disoproxil/emtricitabine for eligible individuals - specialist initiation.

Overview

Epidemiology (UK context)

Highest rates are seen in young adults and MSM; inequality and stigma remain barriers to testing.

Syndromes

Urethritis, cervicitis, PID, epididymo-orchitis, proctitis, pharyngeal infection, genital ulceration.

Public health

Confidential GUM/sexual health services provide testing, treatment, and contact tracing.

Clinical Presentation

Presenting complaints

Urethral/vaginal discharge, dysuria, intermenstrual/post-coital bleeding, pelvic pain, testicular pain, anorectal symptoms, ulcers, rash.

Examination

Speculum examination where indicated; testicular examination; lymph nodes; rash (palmar/plantar in secondary syphilis).

Differential Diagnosis

Syndrome	Important differentials
Urethritis	Gonorrhoea, chlamydia, Mycoplasma genitalium, UTI
Genital ulcer	Syphilis, HSV, chancroid (rare UK), lymphogranuloma venereum
Pelvic pain	PID, ectopic pregnancy, appendicitis, endometriosis

Diagnosis / Investigation

Tests

NAAT swabs/urine for chlamydia/gonorrhoea; extragenital sites as indicated.
Syphilis serology (EIA + confirmatory algorithm).
HIV Ag/Ab test with consent and pre-test discussion.
Hepatitis B/C serology depending on risk.
Microscopy of urethral discharge if available (Gram-negative diplococci).

Management

Empirical syndromic therapy (example - follow BASHH)

Suspected gonorrhoea: ceftriaxone 1 g IM/IV stat + azithromycin 1 g PO stat.
Chlamydia: doxycycline 100 mg BD 7 days.

Pelvic inflammatory disease (inpatient severe)

Ceftriaxone 1 g IV OD + metronidazole 400 mg BD + doxycycline 100 mg BD (14-day course common) - per guideline.

Support

Condoms, vaccination (HPV, hepatitis A/B where indicated), PrEP referral.

Prognosis

Most bacterial STIs are curable; viral infections (HSV, HIV, hepatitis) require longer-term management. Early treatment reduces complications (infertility, chronic hepatitis).

Other Relevant Information

Confidentiality and safeguarding

Follow GMC and local policies; involve safeguarding leads where minors or vulnerable adults are at risk.

NICE Guidelines / CKS

Syphilis

Systemic infection caused by *Treponema pallidum*, presenting in stages (primary, secondary, latent, tertiary) and with neurosyphilis or ocular involvement. Penicillin remains definitive treatment; serological follow-up is essential.

MRCP Part 1 · MRCP Part 2 · PLAB 1 · UKMLA · MRCGP AKT · MSRA

Key Facts

Key points
Primary: painless chancre; secondary: rash (often palmar/plantar), mucous patches, condylomata lata.
Latent: positive serology without clinical signs; early latent (<2 years) vs late latent.
Neurosyphilis: meningitis, stroke, general paresis, tabes dorsalis - LP if suspected.
Treatment early syphilis: benzathine benzylpenicillin G 2.4 million units IM stat (split doses if needed per local policy).
Penicillin allergy: doxycycline 100 mg BD 14 days (early) - avoid in pregnancy; seek specialist advice.
Jarisch–Herxheimer reaction: fever within 24 h of therapy - counsel patients.

Overview

Epidemiology

Resurgence in UK MSM populations; HIV co-infection affects presentation and management.

Pathogenesis

Haematogenous dissemination follows primary inoculation; treponemes cross placenta (congenital syphilis) - antenatal screening is critical.

Clinical Presentation

Stages

Primary: single ulcer with rubbery lymphadenopathy.
Secondary: diffuse rash, alopecia, hepatitis, ocular involvement.
Tertiary: gummas, cardiovascular syphilis, neurosyphilis.

Congenital

Hepatosplenomegaly, rash, snuffles, bone changes - neonatal emergency.

Differential Diagnosis

Mimic	Notes
HSV ulcer	Painful grouped vesicles/ulcers
Chancroid	Painful ulcer, uncommon UK
Pityriasis rosea	Herald patch, collarette scale

Diagnosis / Investigation

Serology

EIA/CLIA screen; TPPA/TPHA confirmatory; RPR/VDRL titre for activity and follow-up.

CSF

If neurological/ocular signs: CSF VDRL, cell count, protein.

Management

Early syphilis (primary/secondary/early latent)

Benzathine benzylpenicillin 2.4 MU IM once (some centres give weekly doses for late latent - follow BASHH).

Late latent / unknown duration

Benzathine benzylpenicillin 2.4 MU IM weekly for 3 weeks (per guideline).

Neurosyphilis

Benzylpenicillin IV 1.8–2.4 g 4-hourly for 14 days (or ceftriaxone alternative in penicillin allergy - specialist).

Pregnancy

Penicillin is mandatory; desensitisation if allergy - do not use doxycycline.

Prognosis

Excellent if treated early; neurosyphilis and cardiovascular syphilis can cause permanent deficits if missed. Serological titres should decline after therapy.

Other Relevant Information

Follow-up

Repeat RPR/VDRL at 3, 6, 12 months; HIV co-testing at diagnosis.

NICE Guidelines / CKS

Gonorrhoea

Infection caused by *Neisseria gonorrhoeae*, commonly causing urethritis, cervicitis, and proctitis. Rising antimicrobial resistance makes guideline-concordant dual therapy and culture/sensitivity where available essential in the UK.

MRCP Part 1 · MRCP Part 2 · PLAB 1 · UKMLA · MRCGP AKT · MSRA

Key Facts

Key points
NAAT diagnosis from urine/swabs (include pharyngeal/rectal sites as indicated).
First-line (UK): ceftriaxone 1 g IM/IV plus azithromycin 1 g PO - verify current BASHH guidance.
Test of cure: recommended 2 weeks after treatment for pharyngeal infection; follow local policy for other sites.
Co-infection with chlamydia is common - treat both unless excluded.
Disseminated gonococcal infection: pustular rash, tenosynovitis, septic arthritis - blood cultures; longer IV ceftriaxone course.

Overview

Resistance

Reduced fluoroquinolone susceptibility led to ceftriaxone-centred regimens; azithromycin adjunct aims to cover chlamydia and reduce resistance selection pressure (policy evolving - check updates).

Complications

PID, epididymo-orchitis, infertility, neonatal ophthalmia (rare with screening).

Clinical Presentation

Symptoms

Purulent urethral discharge, dysuria, pelvic pain, rectal discomfort, sore throat.

Examination

Urethral meatus inflammation; cervical friability; epididymal tenderness.

Differential Diagnosis

Alternative	Notes
Chlamydia	Often milder discharge
NSU (M. genitalium)	May need specific testing
UTI	Nitrites, different risk profile

Diagnosis / Investigation

Tests

NAAT (urine/endocervical/rectal/pharyngeal).
Culture where available for sensitivity (especially treatment failure).

HIV/syphilis screen

Offer routinely.

Management

Uncomplicated anogenital/urogenital

Ceftriaxone 1 g IM/IV single dose + azithromycin 1 g PO single dose (per BASHH).

Severe PID / disseminated

Ceftriaxone 1 g IV OD (or higher dose per protocol) with hospital admission and longer courses.

Partner management

Treat current partners; abstain until therapy completed and symptoms resolved.

Prognosis

Excellent cure rates with effective therapy; reinfection common if partners untreated. Drug resistance threatens future treatment options.

Other Relevant Information

Public health

Mandatory reporting categories vary; maintain sexual health records confidentially.

NICE Guidelines / CKS

Chlamydia

Common bacterial STI caused by *Chlamydia trachomatis*, often asymptomatic but able to cause urethritis, cervicitis, PID, and infertility. First-line treatment in the UK is typically doxycycline for 7 days.

MRCP Part 1 · MRCP Part 2 · PLAB 1 · UKMLA · MRCGP AKT · MSRA

Key Facts

Key points
NAAT on first-void urine or vulvovaginal swabs (self-taken acceptable).
First-line: doxycycline 100 mg BD for 7 days.
Azithromycin 1 g single dose if doxycycline contraindicated (e.g. pregnancy - seek specialist advice; local protocols vary).
Test of cure 3–5 weeks after treatment if pregnant (NAAT can remain positive due to dead organisms - interpret carefully).
Lymphogranuloma venereum (LGV) serovars cause proctitis - doxycycline 100 mg BD for 21 days when LGV confirmed/suspected.

Overview

Epidemiology

Most common bacterial STI in young adults; frequently asymptomatic, driving screening programmes.

Pathophysiology

Intracellular organism; chronic inflammation leads to tubal scarring.

Clinical Presentation

Symptoms

Dysuria, mucoid discharge, post-coital bleeding, lower abdominal pain.

Complications

PID, perihepatitis (Fitz-Hugh–Curtis), reactive arthritis.

Differential Diagnosis

Condition	Notes
Gonorrhoea	Often more purulent; co-testing
M. genitalium	Persistent symptoms after treatment
UTI	Urine dipstick/culture

Diagnosis / Investigation

Testing

NAAT; consider M. genitalium if persistent symptoms.

Screen

HIV/syphilis serology as per sexual health protocol.

Management

Uncomplicated genital infection

Doxycycline 100 mg orally BD for 7 days.

Epididymo-orchitis (chlamydia suspected)

Doxycycline 100 mg BD 10–14 days ± ceftriaxone 500 mg–1 g IM if gonorrhoea not excluded.

Partner notification

Treat partners from prior 2 weeks (extend per guideline).

Prognosis

Excellent with correct antibiotics; delayed treatment increases infertility risk.

Other Relevant Information

Azithromycin resistance

Emerging resistance in M. genitalium - avoid inappropriate macrolide use.

NICE Guidelines / CKS

Hepatitis B

Blood-borne viral hepatitis caused by HBV; can present as acute icteric hepatitis or evolve into chronic infection with cirrhosis and hepatocellular carcinoma risk. UK management includes antiviral suppression for chronic disease and neonatal vaccination programmes.

MRCP Part 1 · MRCP Part 2 · PLAB 1 · UKMLA · MRCGP AKT · MSRA

Key Facts

Key points
Serology: HBsAg, anti-HBc (IgM in acute), anti-HBs after vaccination; HBeAg reflects replication in some cases.
Chronic HBV (HBsAg >6 months): assess HBV DNA, ALT, fibrosis (elastography/biomarkers).
First-line antivirals: tenofovir alafenamide 25 mg OD, tenofovir disoproxil 245 mg OD, or entecavir 500 mcg–1 mg OD (adjust renal impairment).
Pegylated interferon rarely used in selected cases - specialist.
Vaccination: Engerix B/HBVaxPRO schedules for infants, healthcare workers, risk groups.

Overview

Transmission

Parenteral, sexual, perinatal. Vaccination and antenatal HBsAg screening reduce vertical transmission.

Natural history

Acute infection may be anicteric; chronic infection risk is inversely related to age at acquisition.

Clinical Presentation

Acute

Malaise, jaundice, RUQ pain, arthralgia, urticaria (immune complex).

Chronic

Often asymptomatic until cirrhosis complications - screen at-risk migrants.

Differential Diagnosis

Condition	Serology pattern
Hepatitis A	Anti-HAV IgM positive
Hepatitis C	Anti-HCV, HCV RNA
Autoimmune hepatitis	Autoantibodies, IgG
Drug-induced liver injury	Drug history

Diagnosis / Investigation

Blood tests

LFTs, HBsAg, HBV DNA, HIV, HCV co-infection screen, AFP surveillance if cirrhosis.

Imaging

USS HCC surveillance if advanced fibrosis.

Management

Acute

Supportive care; tenofovir if severe acute HBV (specialist).

Chronic - treat if significant fibrosis or high DNA/ALT (criteria per EASL/NICE specialist pathways)

Entecavir 500 mcg OD (treatment-naïve) - check renal adjustment.
Tenofovir disoproxil 245 mg OD with renal monitoring.

Prevention

HBV vaccine for contacts; HBIG for needlestick exposure per protocol.

Prognosis

Suppression reduces fibrosis progression; HCC risk persists - surveillance continues.

Other Relevant Information

Pregnancy

Tenofovir may be used in third trimester if high viral load to reduce transmission - specialist.

NICE Guidelines / CKS

Hepatitis C

Blood-borne RNA virus causing acute and chronic hepatitis; most cases are asymptomatic until advanced liver disease. Direct-acting antiviral (DAA) regimens achieve >95% cure rates in the UK when adherence and regimen selection are correct.

MRCP Part 1 · MRCP Part 2 · PLAB 1 · UKMLA · MRCGP AKT · MSRA

Key Facts

Key points
Anti-HCV screening in risk cohorts; HCV RNA confirms viraemia.
Pangenotypic DAA regimens (examples): sofosbuvir/velpatasvir one tablet OD for 12 weeks in treatment-naïve without cirrhosis (duration varies by cirrhosis/retreatment - specialist).
Glecaprevir/pibrentasvir three tablets OD with food for 8–16 weeks depending on scenario.
Ribavirin sometimes added in decompensated disease - specialist.
Drug interactions via CYP/P-gp - check HCV DAA interaction checker before prescribing.

Overview

Epidemiology

People who inject drugs, recipients of blood products before 1991 in UK, HIV MSM cohorts.

Natural history

Chronic inflammation

cirrhosis

HCC; extrahepatic manifestations (cryoglobulinaemia).

Clinical Presentation

Acute

Often mild; may present as ALT flare.

Chronic

Fatigue; stigmata of chronic liver disease if cirrhosis.

Differential Diagnosis

Alternative	Clue
HBV	HBsAg positive
Alcohol-related liver disease	History, AST:ALT pattern
NAFLD	Metabolic risk, imaging

Diagnosis / Investigation

Virology

HCV RNA, genotype less critical with pangenotypic regimens but still used in some pathways.

Staging

Transient elastography (FibroScan), blood fibrosis scores.

HIV/HBV

Co-test before DAA.

Management

Treatment (examples - specialist-led)

Sofosbuvir/velpatasvir 400/100 mg OD for 12 weeks (common first line).
Decompensated cirrhosis: refer transplant centre; DAA regimens individualised.

Harm reduction

Needle exchange, opioid substitution, alcohol advice.

Prognosis

Sustained virological response (undetectable RNA 12 weeks post-therapy) equals cure in most; continue HCC surveillance if cirrhosis established.

Other Relevant Information

Reinfection

Risk persists with ongoing risk behaviours - counsel and test.

NICE Guidelines / CKS

Fungal Infections

A spectrum from superficial mucocutaneous candidiasis and dermatophyte infections to invasive mould disease in immunocompromised hosts. Management depends on immune status, site, and species identification with susceptibility testing where available.

MRCP Part 1 · MRCP Part 2 · PLAB 1 · UKMLA · MRCGP AKT · MSRA

Key Facts

Key points
Superficial dermatophytes (tinea): terbinafine 250 mg OD for 1–4 weeks** depending on site; topical terbinafine or clotrimazole for limited disease.
Oropharyngeal candidiasis: fluconazole 50–100 mg OD for 7 days** or nystatin suspension.
Invasive candidiasis: echinocandin first line in critically ill (anidulafungin loading 200 mg IV then 100 mg OD** - examples per BNF).
Invasive aspergillosis: voriconazole first line; liposomal amphotericin B alternatives.
Pneumocystis jirovecii pneumonia: co-trimoxazole high dose IV/oral - distinct from typical fungi but often grouped clinically.

Overview

Host factors

Neutropenia, transplant, TNF inhibitors, diabetes, ICU stay, broad-spectrum antibiotics predispose to invasive fungal disease.

Diagnostics

Culture, histopathology, (1→3)-β-D-glucan and galactomannan (aspergillosis) - interpret with context.

Clinical Presentation

Superficial

Itchy plaques, oral thrush, vaginal discharge.

Invasive

Persistent fever despite antibiotics, nodular lung infiltrates, skin lesions, fungaemia.

Differential Diagnosis

Setting	Consider
ICU sepsis	Bacterial sepsis, viral infection
Lung nodules	TB, malignancy, other moulds

Diagnosis / Investigation

Microbiology

Blood cultures (Candida), respiratory samples, biopsy when safe.

Imaging

CT thorax for suspected invasive pulmonary mould disease.

Management

Candidaemia (example)

Anidulafungin IV or caspofungin 70 mg loading then 50 mg OD IV - step-down to fluconazole 400–800 mg OD if susceptible and stable.

Tinea capitis/corporis

Terbinafine oral or itraconazole - duration varies.

Prognosis

Superficial infections resolve with therapy; invasive disease mortality remains high without immune recovery.

Other Relevant Information

Antifungal stewardship

Therapeutic drug monitoring for voriconazole, posaconazole, itraconazole where indicated.

NICE Guidelines / CKS

Invasive Aspergillosis

Angioinvasive pulmonary infection caused by *Aspergillus* spp., classically in prolonged neutropenia and transplant recipients. Voriconazole is first-line therapy; diagnosis integrates imaging, galactomannan, and culture.

MRCP Part 1 · MRCP Part 2 · PLAB 1 · UKMLA · MRCGP AKT · MSRA

Key Facts

Key points
Risk: prolonged neutropenia, allogeneic stem cell transplant, high-dose steroids, advanced HIV.
Imaging: CT chest may show halo sign early; cavitation later.
First-line: voriconazole 6 mg/kg IV 12-hourly for 2 doses, then 4 mg/kg 12-hourly (adjust oral dosing per weight); TDM recommended.
Alternatives: liposomal amphotericin B 3 mg/kg OD IV; isavuconazole loading then maintenance - specialist choice.
Surgical resection for single lesions/refractory haemoptysis in selected cases.
Galactomannan in BAL/serum supportive; not fully specific.

Overview

Species

A. fumigatus common; azole-resistant isolates increasingly reported - send cultures.

Forms

Invasive pulmonary, sinus, CNS, cutaneous (direct inoculation).

Clinical Presentation

Symptoms

Fever unresponsive to antibacterials, pleuritic pain, haemoptysis, sinus symptoms.

Examination

Focal lung signs; immunosuppression may blunt classic features.

Differential Diagnosis

Mimic	Notes
Mucormycosis	Ribbon necrosis on imaging; urgent ENT review
TB	Acid-fast bacilli, epidemiology
Bacterial pneumonia	Microbiology pattern

Diagnosis / Investigation

Labs

Galactomannan (serum/BAL), (1→3)-β-D-glucan (broad), Aspergillus PCR where available.

Imaging

High-resolution CT chest; consider brain MRI if neurological signs.

Management

Primary therapy

Voriconazole as above; maintain trough 1–5.5 mg/L (local lab ranges vary).

Salvage

Liposomal amphotericin or isavuconazole; consider caspofungin combination in refractory cases - ID MDT.

Immune recovery

Reduce immunosuppression where possible; G-CSF for neutropenia.

Prognosis

Mortality high in allogeneic transplant and prolonged neutropenia; early voriconazole improves outcomes.

Other Relevant Information

Drug interactions

Voriconazole is a CYP3A4 substrate/inhibitor - many contraindications (e.g. sirolimus).

NICE Guidelines / CKS

Candidiasis

Infections caused by *Candida* species ranging from mucosal disease to candidaemia and deep organ infection. *Candida albicans* remains common, but non-albicans species and azole resistance are increasingly relevant in hospitalised patients.

MRCP Part 1 · MRCP Part 2 · PLAB 1 · UKMLA · MRCGP AKT · MSRA

Key Facts

Key points
Oropharyngeal: fluconazole 50–100 mg OD 7–14 days**; nystatin topical alternative.
Vulvovaginal: fluconazole 150 mg** single oral dose; topical azoles.
Invasive/candidaemia: echinocandin first line (caspofungin 70 mg IV loading then 50 mg OD**).
Fluconazole step-down (400 mg OD) if susceptible isolate and stable.
Remove intravenous lines where possible; ophthalmology review for candidaemia (endophthalmitis screen).
Chronic mucocutaneous candidiasis suggests immune deficiency - investigate.

Overview

Risk factors for invasive disease

Central lines, TPN, broad-spectrum antibiotics, ICU, immunosuppression.

Clinical Presentation

Mucosal

White plaques, sore mouth; vulval itch/discharge.

Invasive

Fever with candidaemia; hepatosplenic lesions in chronic disseminated disease.

Differential Diagnosis

Condition	Notes
HSV oral ulcers	Vesicular, different distribution
Bacterial sepsis	Positive blood cultures

Diagnosis / Investigation

Microbiology

Blood cultures; species ID and susceptibility.

Imaging

Abdominal imaging if deep candidiasis suspected.

Management

Candidaemia

Anidulafungin/caspofungin/micafungin per BNF dosing.
Duration often ≥14 days after first negative culture and resolution of signs.

Oesophageal (HIV)

Fluconazole 200–400 mg OD until symptom resolution - maintain ART.

Prognosis

Mucocutaneous: excellent. Candidaemia: mortality significant; early echinocandin and line removal improve outcomes.

Other Relevant Information

C. auris

Outbreak risk in healthcare settings - infection control alert.

NICE Guidelines / CKS

Parasitic Infections

Protozoal and helminth infections acquired in endemic regions or through food/water/vector exposure. UK clinicians encounter imported malaria, intestinal helminths, schistosomiasis, and toxocariasis among travellers and migrants; diagnosis requires geography, eosinophil count, and targeted tests.

MRCP Part 1 · MRCP Part 2 · PLAB 1 · UKMLA · MRCGP AKT · MSRA

Key Facts

Key points
Malaria (falciparum): artesunate IV first line for severe (specialist); uncomplicated oral artemether/lumefantrine (Riamet) per weight-based dosing.
Threadworm: mebendazole 100 mg single dose; repeat in 2 weeks; treat household.
Hydatid disease: albendazole 400 mg BD** for months ± surgery - specialist.
Schistosomiasis: praziquantel 40 mg/kg** single dose or divided (acute/schistosomal policies vary).
Strongyloides: ivermectin 200 mcg/kg** for 2 days; albendazole alternative - treat before immunosuppression if possible.

Overview

Approach

Take a travel/food/water exposure history; eosinophilia suggests helminth or certain protozoa.

Protozoa vs helminths

Different diagnostics (stool O&P, serology, PCR) and treatments.

Clinical Presentation

Examples

Intermittent fever (malaria), GI symptoms, rash (acute schistosomiasis), Loeffler syndrome (migrating larvae).

Differential Diagnosis

Presentation	Consider
Eosinophilia	Helminths, allergy, adrenal
Fever returned traveller	Malaria, typhoid, dengue

Diagnosis / Investigation

Tests

Thick/thin films (malaria), stool PCR/O&P, serology (strongyloides, filariasis), eosinophil count.

Management

Principles

Treat specific parasite; address dehydration and anaemia.
G6PD screen before primaquine for malaria hypnozoites (vivax/ovale).

Prevention

Travellers' health advice, malaria chemoprophylaxis where indicated (e.g. atovaquone/proguanil).

Prognosis

Varies widely; delayed malaria treatment increases mortality; most intestinal helminths respond well.

Other Relevant Information

Neglected tropical diseases

Many require specialist tropical medicine input.

NICE Guidelines / CKS

Toxoplasmosis

Infection by *Toxoplasma gondii*; usually asymptomatic in immunocompetent hosts but causes retinochoroiditis, cerebral toxoplasmosis in advanced HIV, and congenital infection. Pyrimethamine-based regimens with folinic acid rescue are standard for cerebral disease; specialist care in pregnancy.

MRCP Part 1 · MRCP Part 2 · PLAB 1 · UKMLA · MRCGP AKT · MSRA

Key Facts

Key points
Serology: IgG indicates past exposure; IgM patterns need expert interpretation in pregnancy.
Cerebral toxoplasmosis (HIV): sulfadiazine 1–1.5 g QDS + pyrimethamine 200 mg loading then 50–75 mg OD + folinic acid 15–25 mg OD** (rescue) for ≥6 weeks induction - then maintenance until immune reconstitution.
Alternative: co-trimoxazole 960 mg BD** can be used for treatment/prophylaxis per guideline.
Pregnancy: spiramycin early infection (where available) vs pyrimethamine/sulfadiazine/folinic acid after 18 weeks - regional protocols - always specialist.
Primary prophylaxis in HIV when CD4 <200: co-trimoxazole 960 mg OD** (or thrice weekly per local policy).

Overview

Transmission

Oocysts in cat faeces/contaminated soil; tissue cysts in undercooked meat; transplacental.

Immunopathogenesis

Reactivation of latent cysts when cell-mediated immunity fails.

Clinical Presentation

Immunocompetent

Often subclinical; lymphadenopathy; chorioretinitis.

Immunosuppressed

Ring-enhancing brain lesions (MRI), confusion, focal neurology.

Congenital

Chorioretinitis, hydrocephalus, intracranial calcification.

Differential Diagnosis

Brain lesion HIV	Notes
Primary CNS lymphoma	Single lesion more typical; thallium PET
TB	Basal meningitis pattern
PML	White matter, JC virus

Diagnosis / Investigation

Imaging

MRI brain with contrast.

HIV

CD4 count; if not known HIV, test.

Ophthalmology

Urgent review if ocular symptoms.

Management

Cerebral toxoplasmosis

Start co-trimoxazole if pyrimethamine/sulfadiazine unavailable - per BASHH/HIV guidelines.

Steroids

Controversial around mass effect - specialist only.

ART

Start/restart when feasible; watch for IRIS.

Prognosis

Cerebral toxoplasmosis improves with therapy and immune recovery; congenital outcomes depend on gestational timing of acquisition.

Other Relevant Information

Pregnancy counselling

Avoid undercooked meat; hygiene around cats; serial ultrasound in seroconversion - specialist care.

NICE Guidelines / CKS

Antimicrobial Stewardship

A multidisciplinary framework to optimise antimicrobial use, improve outcomes, reduce adverse effects, and contain resistance. UK hospitals use stewardship teams, formulary restrictions, and audit with feedback aligned to NICE and UKHSA principles.

MRCP Part 1 · MRCP Part 2 · PLAB 1 · UKMLA · MRCGP AKT · MSRA

Key Facts

Key points
Start smart: right drug, dose, route, and narrowest effective spectrum as soon as cultures allow.
Document: indication, planned review/stop date (often 48–72 hours) on drug charts.
IV to oral switch when swallowing safe and clinically improving (e.g. co-amoxiclav 625 mg TDS**).
Peri-operative prophylaxis: typically single dose cefazolin 1–2 g IV** or co-amoxiclav 1.2 g IV** at induction for clean-contaminated surgery - repeat only if prolonged bleeding or short half-life drug - per local protocol.
C. difficile risk: minimise cephalosporins/quinolones/clindamycin when alternatives exist.
Antibiotic allergy: clarify true IgE-mediated allergy vs intolerance; delabelling programmes improve beta-lactam access.

Overview

Core interventions

Formulary, pre-authorisation for restricted agents, prospective audit, education, and IT decision support.

Metrics

Consumption (DDD/1000 OBD), C. difficile rates, resistance trends.

Clinical Presentation

Stewardship "presentation"

Not a disease - applies to every prescribing episode: sepsis, UTI, pneumonia, skin infection.

Differential Diagnosis

Misuse patterns to recognise

Treating asymptomatic bacteriuria.
Continuation beyond guideline duration without indication.
Broad-spectrum cover "just in case" without review.

Diagnosis / Investigation

Stewardship review checklist

Cultures, biomarkers (PCT where used), source control achieved?, drug levels (vancomycin, gentamicin).

Management

Practical steps (ward level)

De-escalate after sensitivities.
Stop duplicate cover unless clear reason.
Dose adjust for renal function (gentamicin extended interval; vancomycin AUC-guided where available).

Restricted antibiotics

Meropenem, linezolid, daptomycin - discuss with microbiology for appropriateness and duration.

Prognosis

Effective stewardship reduces resistant infections and hospital-acquired C. difficile over time.

Other Relevant Information

Primary care

Delayed/back-up prescriptions for minor RTIs; FeverPAIN/CENTOR criteria reduce unnecessary antibiotics.

NICE Guidelines / CKS

Antimicrobial Resistance

The ability of microorganisms to resist the effects of antimicrobial agents, rendering standard treatments ineffective. Declared a global health emergency by WHO, with an estimated 1.27 million deaths directly attributable to AMR worldwide in 2019. The UK 5-year AMR action plan targets a 50% reduction in inappropriate antibiotic prescribing.

MRCP Part 1 · MRCP Part 2 · PLAB 1 · UKMLA · MRCGP AKT · MSRA

Key Facts

1.27 million deaths directly attributable to AMR globally in 2019 (Lancet AMR study)
MRSA: methicillin-resistant S. aureus - mecA gene encoding altered PBP2a; treat with vancomycin or daptomycin
ESBL-producing Enterobacteriaceae: resistant to 3rd-gen cephalosporins; treat with carbapenems (meropenem)
CPE (carbapenemase-producing Enterobacteriaceae): resistant to carbapenems - last-resort antibiotics; treat with ceftazidime-avibactam, colistin
VRE: vancomycin-resistant Enterococcus - treat with linezolid 600mg BD or daptomycin
Start Smart - Then Focus: PHE toolkit for hospital prescribing - review at 48–72 hours
NICE NG15: antimicrobial stewardship - systems and processes for effective use
UK AMR 5-year action plan: reduce inappropriate prescribing, improve diagnostics, develop new antibiotics

Overview

Key Facts

AMR is one of the greatest threats to global health. Without action, AMR could cause 10 million deaths/year by 2050 (O'Neill Report). Antimicrobial stewardship programmes are central to the UK response.

Epidemiology

1.27 million deaths directly attributable to AMR globally (2019)
UK: ~5,000 deaths/year from drug-resistant infections
MRSA bacteraemia: reduced by >80% in UK since 2007 through IPC measures
C. difficile: reduced by >70% through antibiotic stewardship
CPE: increasing in UK - national surveillance programme

Aetiology

Intrinsic resistance: naturally occurring (e.g. Pseudomonas inherently resistant to many antibiotics)
Acquired resistance: horizontal gene transfer (plasmids, transposons, integrons), spontaneous mutation
Key mechanisms: enzyme production (beta-lactamases, ESBLs, carbapenemases), target modification (PBP alteration in MRSA), efflux pumps, reduced permeability

Pathophysiology

Selective pressure from antibiotic use drives resistance evolution
Inappropriate prescribing accelerates resistance development
Biofilm formation provides protected environment for resistant organisms
Healthcare settings act as reservoirs for MDR organisms

Clinical Presentation

Presentations of Resistant Infections

MRSA: wound infections, bacteraemia, pneumonia, osteomyelitis - often nosocomial
ESBL/CPE: UTIs, intra-abdominal infections, bacteraemia - often in patients with prior antibiotic exposure
VRE: UTIs, bacteraemia, intra-abdominal infections - immunocompromised/ICU patients
MDR TB: prolonged cough, weight loss, night sweats - failure of standard regimen
Resistant gonorrhoea: persistent urethral/cervical discharge despite treatment

Risk Factors for Resistant Infection

Recent antibiotic use
Recent hospitalisation/healthcare contact
ICU admission
Indwelling devices (catheters, central lines)
Immunosuppression
Travel to endemic areas

Red Flags

Treatment failure despite appropriate-seeming antibiotics
Sepsis not responding to empirical therapy
Known colonisation with MDR organism plus new infection

Differential Diagnosis

Diagnosis	Key Features	Investigation
Sensitive organism with inadequate dose/duration	Clinical improvement then relapse	Repeat culture, review dosing
Non-infectious cause of inflammation	Fever without microbiological evidence	Cultures negative, consider non-infective cause
Abscess/undrained collection	Persistent fever despite antibiotics	Imaging (CT/USS)
Wrong empirical antibiotic choice	Culture identifies organism not covered	Culture and sensitivity

Diagnosis / Investigation

Bedside

Clinical review: assess response to current antibiotics at 48–72 hours

Bloods

Blood cultures: before antibiotic changes - identify organism and sensitivities
FBC, CRP: trending to assess treatment response

Microbiology

Culture and sensitivity testing: essential for all suspected resistant infections
ESBL/CPE screening: rectal swab for at-risk patients (recent travel, hospitalisation)
MRSA screening: nasal swab (admission screening in many UK hospitals)
Rapid molecular diagnostics: PCR for mecA (MRSA), carbapenemase genes - results within hours

Special Tests

Antibiogram: local resistance patterns to guide empirical therapy
MIC (minimum inhibitory concentration): quantitative susceptibility for serious infections
Whole genome sequencing: outbreak investigation, resistance gene characterisation

Management

Prevention and Stewardship

Antimicrobial stewardship: Start Smart - Then Focus; review at 48–72 hours (stop, switch IV→oral, narrow, change, OPAT)
Infection prevention and control: hand hygiene, barrier precautions, isolation of colonised patients
MRSA decolonisation: mupirocin nasal ointment TDS 5 days + chlorhexidine body wash
Surveillance: mandatory reporting of MRSA/MSSA bacteraemia, C. difficile, CPE

Pharmacological - Treatment of Key Resistant Organisms

MRSA:

Bacteraemia: vancomycin 15–20mg/kg BD IV (trough target 15–20 mg/L) or daptomycin 6–10mg/kg OD IV
Skin/soft tissue: oral options - doxycycline 100mg BD, co-trimoxazole 960mg BD, linezolid 600mg BD

ESBL-producing organisms:

Serious infection: meropenem 1g TDS IV
UTI: based on sensitivities - nitrofurantoin, fosfomycin, or pivmecillinam may retain activity

CPE:

Ceftazidime-avibactam (KPC-producing); colistin-based regimens; meropenem-vaborbactam
Consult microbiology/infectious diseases

VRE:

Linezolid 600mg BD (oral or IV) or daptomycin

Referral Criteria

Microbiology/ID consultant: all serious resistant infections
PHE: mandatory reporting of CPE, outbreak situations
Infection prevention team: colonised/infected patients

Prognosis

MRSA bacteraemia: mortality ~20–30% (vs ~10–15% for MSSA)
CPE bacteraemia: mortality ~40–50%
ESBL bacteraemia: mortality ~30% if treated with inactive agent initially; reduced with carbapenems
Appropriate empirical therapy: key determinant of survival - delays increase mortality by 10–20%
UK MRSA bacteraemia rates have fallen dramatically with IPC interventions

Other Relevant Information

Key Resistance Mechanisms

Organism	Mechanism	Treatment
MRSA	mecA → altered PBP2a	Vancomycin, daptomycin
ESBL E. coli	CTX-M beta-lactamase	Carbapenems
CPE (KPC)	KPC carbapenemase	Ceftazidime-avibactam
VRE	vanA/vanB gene clusters	Linezolid, daptomycin
MDR Pseudomonas	Multiple mechanisms	Based on sensitivities

O'Neill Report (2016) Key Recommendations

Recommendation	Detail
Public awareness	Global campaign on AMR
Surveillance	Improve global data
Diagnostics	Rapid point-of-care tests
Stewardship	Reduce inappropriate use
New drugs	Incentivise development
Vaccines	Reduce antibiotic need

NICE Guidelines / CKS

Travel Medicine and Vaccination

Medical specialty encompassing pre-travel risk assessment, travel vaccinations, malaria chemoprophylaxis, and management of post-travel illness. Key considerations include destination-specific risks, mandatory versus recommended vaccines, and travellers' diarrhoea prevention. The Green Book and NaTHNaC provide UK guidance.

MRCP Part 1 · MRCP Part 2 · PLAB 1 · UKMLA · MRCGP AKT · MSRA

Key Facts

NaTHNaC (National Travel Health Network and Centre): provides UK travel health guidelines
Yellow fever vaccine: live attenuated; required for entry to some countries; International Certificate of Vaccination
Malaria chemoprophylaxis: atovaquone-proguanil (Malarone) or doxycycline 100mg OD; mefloquine weekly if contraindications
Hepatitis A: inactivated vaccine; recommended for most destinations outside Western Europe/N. America/Australasia
Typhoid: Vi polysaccharide (IM) or Ty21a (oral live); recommended for Indian subcontinent, parts of Africa/S. America
Japanese encephalitis, rabies, tick-borne encephalitis: risk-based pre-travel vaccines
Travellers' diarrhoea: most common travel illness (~30–50% of travellers); usually self-limiting; azithromycin if severe
Live vaccines contraindicated in pregnancy and immunosuppression (BCG, yellow fever, oral typhoid, MMR, varicella)

Overview

Key Facts

Travel medicine encompasses a wide range of preventive and therapeutic interventions. Pre-travel consultation should occur at least 4–6 weeks before departure to allow time for vaccine courses.

Epidemiology

~70 million UK residents travel abroad annually
~30–50% of travellers to developing countries experience health problems
Travellers' diarrhoea: most common (~30–50%)
~1,500 imported malaria cases/year in UK
~500 imported enteric fever cases/year in UK

Aetiology

Infectious: malaria, dengue, typhoid, hepatitis A, travellers' diarrhoea, respiratory infections
Environmental: heat-related illness, altitude sickness, envenomation
Non-infectious: DVT from long-haul flights, road traffic accidents (leading cause of death in young travellers)

Pathophysiology

Exposure to novel pathogens without pre-existing immunity
Change in climate, food/water sources, and hygiene standards
Insect vectors (Anopheles for malaria, Aedes for dengue/Zika)
Contaminated water/food (enteric infections)

Clinical Presentation

Pre-Travel Assessment

Destination, duration, type of travel (backpacking vs hotel)
Medical history, medications, immunosuppression, pregnancy
Previous vaccinations
Planned activities (safari, diving, altitude)

Common Travel-Related Illness

Travellers' diarrhoea: acute watery diarrhoea, usually 1st week of travel
Malaria: fever in returning traveller - must exclude (see Pyrexia in the Returning Traveller)
Dengue: fever, myalgia, rash, thrombocytopenia
Enteric fever (typhoid): insidious fever, relative bradycardia, rose spots
Respiratory: influenza, COVID-19, TB

Red Flags

Fever in returning traveller (malaria until proven otherwise)
Haemorrhagic symptoms (viral haemorrhagic fever - isolate immediately)
Meningism in returning traveller
Severe diarrhoea with dehydration

Differential Diagnosis

Diagnosis	Key Features	Investigation
Malaria	Fever, cyclical rigors, splenomegaly	Thick/thin blood films, rapid antigen test
Dengue	Fever, myalgia, rash, thrombocytopenia	Dengue NS1 antigen, IgM/IgG
Typhoid	Insidious fever, relative bradycardia	Blood culture, Widal test (unreliable)
Hepatitis A	Jaundice, raised ALT, recent travel	HAV IgM
Travellers' diarrhoea	Acute watery diarrhoea, self-limiting	Stool culture if severe/persistent

Diagnosis / Investigation

Pre-Travel

Review vaccination history
Baseline bloods if starting mefloquine (LFTs) or chloroquine (eye check)

Post-Travel Illness

Malaria films: thick and thin films ×3 over 24–48 hours if fever
FBC: eosinophilia (helminth), thrombocytopenia (dengue, malaria)
Blood cultures: enteric fever
Stool MC&S + ova/parasites: persistent diarrhoea
LFTs: hepatitis screen
HIV, hepatitis B/C serology: if risk exposure
CXR: if respiratory symptoms (TB)

Special Tests

Dengue NS1 + serology: febrile traveller from endemic area
Schistosoma serology + eosinophilia: freshwater exposure in endemic area
Strongyloides serology: if eosinophilia and tropical exposure

Management

Pre-Travel Vaccination

Routine (ensure up-to-date):

MMR, diphtheria-tetanus-polio, meningococcal

Travel-specific:

Hepatitis A: single dose; booster at 6–12 months for long-term protection
Typhoid: IM Vi polysaccharide (single dose, lasts 3 years) or oral Ty21a
Yellow fever: single dose live vaccine; lifelong (since 2016); International Certificate
Rabies: 3-dose pre-exposure course (days 0, 7, 21–28)
Japanese encephalitis: 2-dose course
Cholera: oral vaccine (Dukoral) - 2 doses

Malaria Prophylaxis

Atovaquone-proguanil (Malarone): 1 tablet OD; start 1–2 days before, continue 7 days after
Doxycycline 100mg OD: start 1–2 days before, continue 4 weeks after
Mefloquine 250mg weekly: start 2–3 weeks before, continue 4 weeks after
Plus: insect repellent (DEET 50%), bed nets, cover exposed skin at dusk/night

Travellers' Diarrhoea

Oral rehydration salts
Loperamide for symptom relief (avoid if dysentery)
Azithromycin 500mg OD for 3 days if severe

Referral Criteria

NaTHNaC or travel clinic: complex itineraries, immunosuppressed travellers
Infectious diseases: serious post-travel illness
Public health: notifiable diseases

Prognosis

Travellers' diarrhoea: self-limiting in 3–5 days in most cases
Malaria: excellent if diagnosed and treated promptly; fatal if delayed (P. falciparum)
Typhoid: <1% mortality with appropriate antibiotics
Prevention: pre-travel vaccination and prophylaxis are highly effective
Long-haul travel DVT risk: ~1 in 4,500 flights >4 hours

Other Relevant Information

Travel Vaccine Summary

Vaccine	Type	Schedule	Duration
Hepatitis A	Inactivated	1 dose (+booster 6–12m)	25+ years
Typhoid (IM)	Vi polysaccharide	1 dose	3 years
Yellow fever	Live	1 dose	Lifelong
Rabies	Inactivated	3 doses (0, 7, 21–28)	Long-term
Japanese encephalitis	Inactivated	2 doses (0, 28)	~5 years

Malaria Prophylaxis Comparison

Drug	Start	Continue After	Key Side Effects
Atovaquone-proguanil	1–2 days before	7 days after	GI upset
Doxycycline	1–2 days before	4 weeks after	Photosensitivity
Mefloquine	2–3 weeks before	4 weeks after	Neuropsychiatric

NICE Guidelines / CKS

Immunisation Schedule

The UK routine immunisation programme protects against multiple infectious diseases from birth through adulthood. Managed by UKHSA and guided by the Joint Committee on Vaccination and Immunisation (JCVI). Includes primary infant vaccinations (6-in-1, rotavirus, MenB, PCV13), childhood boosters, HPV, and adult programmes (flu, shingles, COVID-19).

MRCP Part 1 · MRCP Part 2 · PLAB 1 · UKMLA · MRCGP AKT · MSRA

Key Facts

6-in-1 vaccine (Infanrix hexa): diphtheria, tetanus, pertussis, polio, Hib, hepatitis B - given at 8, 12, 16 weeks
MenB (Bexsero): 8 weeks, 16 weeks, 12 months; give paracetamol prophylactically to reduce fever
Rotavirus (Rotarix): oral live vaccine at 8 and 12 weeks; must be given before 24 weeks of age
MMR: 12 months and 3 years 4 months (pre-school booster); live vaccine
HPV (Gardasil 9): all 12–13-year-olds (Year 8); single dose since 2023
MenACWY: 14 years (Year 9) - protects for university entry
Influenza: annual nasal spray (Fluenz) for 2–17-year-olds; injectable for ≥65s, at-risk groups, pregnant women
Shingles (Shingrix): recombinant vaccine; offered at 65 years and immunosuppressed from 50 years

Overview

Key Facts

The UK immunisation schedule is one of the most comprehensive globally. Uptake targets are 95% for herd immunity (WHO). The Green Book provides detailed guidance for all vaccines.

Epidemiology

UK childhood vaccination uptake: ~90–95% (declining in some areas)
MMR uptake fell after Wakefield fraud (1998); now recovering
HPV vaccination: expected to eliminate cervical cancer within decades
COVID-19 vaccination programme: largest in UK history

Key Principles

Live vaccines: MMR, BCG, rotavirus, nasal flu, oral typhoid, yellow fever, varicella - contraindicated in immunosuppression and pregnancy
Inactivated vaccines: safe in immunosuppression but may have reduced efficacy
Minimum intervals: must be observed between doses of same vaccine; no maximum interval
Multiple live vaccines: give simultaneously or ≥4 weeks apart
Green Book: definitive UK reference for all immunisation queries

Pathophysiology of Vaccination

Active immunisation: antigen exposure

B-cell and T-cell activation

memory cells

rapid response on re-exposure

Live vaccines: attenuated pathogen replicates → strong, durable immune response
Inactivated/subunit vaccines: non-replicating antigen → requires adjuvants and boosters for adequate response
Conjugate vaccines: polysaccharide linked to protein carrier → T-cell dependent response effective in infants (e.g. MenB, PCV, Hib)

Clinical Presentation

Vaccine-Preventable Disease Presentations

Measles: fever, cough, coryza, conjunctivitis, Koplik spots, maculopapular rash
Pertussis: paroxysmal cough, inspiratory whoop, post-tussive vomiting
Meningococcal disease: non-blanching purpuric rash, meningism, septic shock
Rotavirus: severe watery diarrhoea in infants, dehydration
HPV-related: cervical cancer, genital warts

Vaccine Adverse Effects

Common: injection site pain, fever, irritability (especially MenB)
Rare: febrile convulsion (~1 in 3,000 after MMR), anaphylaxis (~1 in 1,000,000)
Specific: intussusception after rotavirus (very rare; 1–2 per 100,000)

Red Flags

Anaphylaxis post-vaccination (adrenaline 1:1000 IM)
Fever >39°C in neonate post-vaccination
Encephalopathy within 7 days of pertussis-containing vaccine (extremely rare)

Differential Diagnosis

Diagnosis	Key Features	Investigation
Vaccine reaction	Temporal relationship, self-limiting	Clinical observation
Coincidental infection	Symptoms beyond expected vaccine reaction	Septic screen if unwell
Kawasaki disease	Persistent fever >5 days, conjunctivitis, rash, extremity changes	ESR, CRP, echo
Immune thrombocytopenia	Petechiae/bruising post-MMR (rare)	FBC, blood film

Diagnosis / Investigation

Pre-Vaccination

Check contraindications: immunosuppression, pregnancy, severe allergy to previous dose/component
Immunoglobulin levels: if suspected immunodeficiency

Post-Vaccination (if concerns)

Antibody titres: to confirm seroconversion in immunocompromised
Hepatitis B surface antibody: check response after HBV vaccination in healthcare workers (anti-HBs ≥10 mIU/mL)
Yellow Card reporting: report suspected adverse reactions to MHRA

Special Situations

HIV patients: check CD4 count - live vaccines if CD4 >200
Post-transplant: re-vaccination schedule needed
Asplenic patients: ensure MenACWY, PCV13/PPV23, Hib, influenza

Management

UK Routine Childhood Schedule (2024)

8 weeks: 6-in-1 (1st), rotavirus (1st), MenB (1st) 12 weeks: 6-in-1 (2nd), rotavirus (2nd), PCV13 (1st) 16 weeks: 6-in-1 (3rd), MenB (2nd) 12 months: Hib/MenC booster, MMR (1st), MenB (3rd), PCV13 (2nd) 3 years 4 months: dTaP/IPV (pre-school booster), MMR (2nd) 12–13 years: HPV (Gardasil 9 - single dose) 14 years: MenACWY, Td/IPV (school leaver booster)

Adult Programme

Influenza: annually for ≥65, at-risk, pregnant, healthcare workers
Pneumococcal (PPV23): ≥65 (single dose)
Shingles (Shingrix): 65 years; 2 doses at 0 and 2 months
COVID-19: per JCVI seasonal recommendations

Special Groups

Pregnancy: pertussis (from 16 weeks gestation), influenza, COVID-19
Asplenia: MenACWY, Hib, PCV13, PPV23, annual influenza
HIV/immunosuppressed: avoid live vaccines if severely immunosuppressed; inactivated vaccines safe
Healthcare workers: hepatitis B, influenza, MMR, varicella (if non-immune)

Catch-Up

Missed vaccines should be given as soon as identified - no need to restart courses

Prognosis

UK immunisation programme prevents an estimated 5,000 deaths/year
MMR: >99% effective after 2 doses
HPV vaccination: projected to eliminate cervical cancer in vaccinated cohorts
Hib disease reduced by >99% since vaccine introduction
MenB: ~75% effective against MenB disease
Vaccine hesitancy: WHO top 10 global health threats - declining uptake risks outbreaks

Other Relevant Information

UK Childhood Immunisation Schedule Summary

Age	Vaccines
8 weeks	6-in-1, Rotavirus, MenB
12 weeks	6-in-1, Rotavirus, PCV13
16 weeks	6-in-1, MenB
12 months	Hib/MenC, MMR, MenB, PCV13
3y 4m	dTaP/IPV, MMR
12–13y	HPV
14y	MenACWY, Td/IPV

Live vs Inactivated Vaccines

Live Vaccines	Inactivated/Subunit
MMR	6-in-1
BCG	MenB
Rotavirus	PCV13
Nasal flu (Fluenz)	Injectable flu
Yellow fever	Hepatitis A/B
Varicella	HPV
Oral typhoid (Ty21a)	Shingrix

NICE Guidelines / CKS

Fever of Unknown Origin

Defined as fever >38.3°C on several occasions, lasting >3 weeks, with no diagnosis despite 1 week of inpatient investigation (Petersdorf & Beeson criteria). The three main categories are infection (~30%), malignancy (~20%), and autoimmune/inflammatory conditions (~20%). Approximately 10–15% remain undiagnosed despite thorough investigation.

MRCP Part 1 · MRCP Part 2 · PLAB 1 · UKMLA · MRCGP AKT · MSRA

Key Facts

Classic definition: fever >38.3°C on several occasions, duration >3 weeks, no diagnosis after 1 week of investigation
Infections (~30%): TB, endocarditis, abscess, osteomyelitis, CMV, EBV, HIV
Malignancy (~20%): lymphoma (most common), renal cell carcinoma, hepatocellular carcinoma, leukaemia
Autoimmune/inflammatory (~20%): adult-onset Still's disease, SLE, GCA/PMR, vasculitis, sarcoidosis
Adult-onset Still's disease: quotidian (daily spiking) fever, salmon-pink evanescent rash, arthralgia, ferritin markedly elevated (>10,000 μg/L)
PET-CT: increasingly used to identify occult infection or malignancy - sensitivity ~85–90% for FUO
Undiagnosed FUO: ~10–15% remain without diagnosis; most have benign course and fever resolves
Drug fever: consider in all FUO cases - temporal correlation with drug initiation; resolves on withdrawal

Overview

Key Facts

FUO requires a systematic and thorough approach. The differential is vast but can be narrowed by careful history, examination, and staged investigations.

Epidemiology

Infections: declining proportion due to improved diagnostics; TB remains important
Malignancy: lymphoma is the single most common malignant cause
Autoimmune: increasingly recognised with better diagnostics
Drug fever: underdiagnosed cause in hospitalised patients

Aetiology

Infectious (~30%): TB, endocarditis, abscess (intra-abdominal, pelvic, dental), osteomyelitis, CMV, EBV, HIV, Q fever, brucellosis Malignant (~20%): lymphoma, leukaemia, renal cell carcinoma, HCC, atrial myxoma Autoimmune (~20%): adult-onset Still's, SLE, GCA/PMR, PAN, sarcoidosis, Crohn's Miscellaneous (~15%): drug fever, factitious fever, thyrotoxicosis, adrenal insufficiency, PE, familial Mediterranean fever

Pathophysiology

Fever: regulated by hypothalamic set-point elevation via prostaglandin E2 (PGE2)
Pyrogens: exogenous (microbial products) and endogenous (IL-1, IL-6, TNF-alpha)
Multiple pathological processes can sustain chronic febrile response

Clinical Presentation

Key History

Fever pattern: quotidian (daily spike - Still's), tertian/quartan (malaria), Pel-Ebstein (Hodgkin's lymphoma - rare)
Travel history, animal/occupational exposure
Medication list (drug fever)
Family history (familial Mediterranean fever)
Immunosuppression, HIV risk factors

Key Examination

Lymphadenopathy (lymphoma, TB, SLE)
Heart murmur (endocarditis)
Hepatosplenomegaly (haematological malignancy, infection)
Dental examination (dental abscess)
Temporal artery tenderness (GCA)
Skin rash (Still's, vasculitis, SLE)

Red Flags

Weight loss >10% (malignancy, TB)
Night sweats (lymphoma, TB, endocarditis)
New heart murmur (endocarditis)
Neurological symptoms (CNS lymphoma, TB meningitis)

Differential Diagnosis

Diagnosis	Key Features	Investigation
TB	Weight loss, night sweats, lymphadenopathy, immigration history	CXR, sputum AFB, IGRA
Endocarditis	New murmur, splinter haemorrhages, embolic phenomena	Blood cultures ×3, TOE
Lymphoma	Lymphadenopathy, B-symptoms, hepatosplenomegaly	CT TAP, lymph node biopsy
Adult-onset Still's	Quotidian fever, evanescent rash, arthralgia, ferritin >10,000	Ferritin, FBC, LFTs
GCA/PMR	Age >50, headache, jaw claudication, proximal myalgia	ESR/CRP, temporal artery biopsy
Drug fever	Temporal relationship with drug, eosinophilia	Drug history, withdrawal trial

Diagnosis / Investigation

First-Line

FBC with differential: leucocytosis, lymphopenia, eosinophilia, cytopenias
CRP/ESR: degree of inflammation
LFTs, U&Es, LDH: organ involvement
Blood cultures: minimum 3 sets from different sites
Urinalysis and urine culture
CXR: TB, lymphoma, sarcoidosis
HIV test: always include

Second-Line

CT thorax/abdomen/pelvis: abscess, lymphadenopathy, solid organ malignancy
Autoimmune screen: ANA, ANCA, RF, complement, ferritin
Serology: CMV, EBV, hepatitis, Q fever, Brucella, Bartonella
IGRA or Mantoux: TB
TTE/TOE: endocarditis
Peripheral blood film: haematological malignancy, haemophagocytosis

Third-Line

PET-CT: sensitivity ~85–90% for identifying source in FUO - increasingly first choice
Bone marrow biopsy: lymphoma, granulomatous disease, haemophagocytic lymphohistiocytosis
Temporal artery biopsy: if GCA suspected (age >50, raised ESR)
Liver biopsy: granulomatous hepatitis
Lymph node biopsy: if lymphadenopathy

Management

General Approach

Avoid empirical antibiotics unless clinically deteriorating - they obscure diagnosis
Systematic investigation: staged approach (first, second, third-line)
Review medication list: stop non-essential drugs to exclude drug fever
Repeat examination: daily - new signs may emerge

Specific Treatment

Treat underlying cause once identified
TB: standard quadruple therapy (RIPE)
Endocarditis: prolonged IV antibiotics
Lymphoma: oncology referral for chemotherapy
Adult-onset Still's: NSAIDs, corticosteroids (prednisolone 0.5–1mg/kg), IL-1 inhibitors (anakinra) if refractory
GCA: prednisolone 40–60mg OD (start immediately if visual symptoms)
Drug fever: withdraw causative drug - fever typically resolves within 48–72 hours

Naproxen Test

Naproxen 250mg BD for 3 days
Historically suggested: fever resolution suggests neoplastic cause (Naprosyn test) - limited evidence but still referenced

Referral Criteria

Infectious diseases: complex cases, unexplained FUO
Haematology: suspected lymphoma/leukaemia
Rheumatology: suspected autoimmune cause
Nuclear medicine: PET-CT for unexplained FUO

Prognosis

~85–90% of FUO cases eventually diagnosed with thorough investigation
10–15% remain undiagnosed - majority have benign course with spontaneous resolution
Prognosis depends entirely on underlying cause
Undiagnosed FUO: 5-year mortality ~3% (generally favourable)
Infection-related FUO: good prognosis with appropriate treatment
Malignancy-related FUO: variable depending on type and stage

Other Relevant Information

Categories of FUO

Category	Definition	Common Causes
Classic	Fever >3 weeks, no diagnosis after 1 week inpatient	TB, lymphoma, Still's, endocarditis
Nosocomial	Hospitalised ≥24h, fever develops after admission	Line infection, C. difficile, drug fever, PE
Neutropenic	Neutrophils <0.5 ×10⁹/L, fever >3 days	Opportunistic fungi, resistant bacteria
HIV-associated	HIV+, fever >4 weeks (outpatient) or >3 days (inpatient)	TB, MAC, CMV, lymphoma, PCP

FUO Investigation Yield

Investigation	Diagnostic Yield
Blood cultures	5–10%
CT TAP	15–20%
PET-CT	50–70%
Bone marrow biopsy	5–15%
Temporal artery biopsy	Variable (if indicated)

NICE Guidelines / CKS

Pyrexia in the Returning Traveller

Fever developing within weeks of returning from travel abroad requires urgent assessment. Malaria must be excluded in ALL febrile returning travellers from endemic areas - it is the most important diagnosis not to miss. Other causes include dengue, typhoid, viral hepatitis, and viral haemorrhagic fever.

MRCP Part 1 · MRCP Part 2 · PLAB 1 · UKMLA · MRCGP AKT · MSRA

Key Facts

Malaria must be excluded in ALL febrile travellers from endemic areas - thick and thin blood films ×3; rapid antigen test
P. falciparum malaria: most dangerous; can progress to cerebral malaria, ARDS, multi-organ failure within hours
Incubation periods: malaria 7–30 days (up to 1 year for P. vivax/ovale); dengue 4–10 days; typhoid 7–14 days
Dengue: fever + severe myalgia/arthralgia ('breakbone fever') + rash + thrombocytopenia; NO specific antiviral
Typhoid/enteric fever: insidious onset, high sustained fever, relative bradycardia, rose spots; treat with azithromycin or ceftriaxone
Viral haemorrhagic fever (VHF): if Ebola/Marburg/Lassa risk - IMMEDIATE ISOLATION and contact PHE; risk assessment based on travel to specific areas
Returned traveller screen: malaria films, FBC, U&Es, LFTs, blood cultures, stool MC&S, urinalysis, HIV test, hepatitis serology
PHE advisory service: 24/7 advice for imported infections - 0344 225 4524

Overview

Key Facts

Pyrexia in a returning traveller is a medical emergency until malaria is excluded. A systematic approach considering incubation period, geographic exposure, and clinical features is essential.

Epidemiology

UK: ~1,500 imported malaria cases/year; ~5–10 deaths (mostly P. falciparum)
Dengue: ~800 confirmed cases/year in England (imported)
Enteric fever: ~500 cases/year (mainly travel to Indian subcontinent)
Schistosomiasis: freshwater exposure in Africa

Aetiology by Incubation Period

Short (<10 days): dengue, chikungunya, Zika, rickettsial, enteric bacteria, VHF Medium (10–21 days): malaria, typhoid, hepatitis A, leptospirosis, acute HIV Long (>21 days): malaria (P. vivax/ovale), TB, hepatitis B, visceral leishmaniasis, amoebic liver abscess

Pathophysiology

Malaria: Plasmodium parasites invade erythrocytes

haemolysis, cytokine storm, endothelial activation

microvascular obstruction (cerebral malaria)

Dengue: antibody-dependent enhancement in secondary infection

vascular leak

dengue haemorrhagic fever

Typhoid: Salmonella typhi invades Peyer's patches

bacteraemia

systemic infection

Clinical Presentation

Key History

Destination: sub-Saharan Africa (malaria, VHF), South/Southeast Asia (dengue, typhoid), South America
Timing: date of return, onset of fever relative to travel
Activities: freshwater exposure (schistosomiasis), animal contact (rabies, Q fever), unprotected sex (HIV, hepatitis B)
Prophylaxis: malaria chemoprophylaxis compliance, vaccinations received
Insect bites: mosquitoes, ticks

Presentations by Diagnosis

Malaria: paroxysmal fever/rigors, headache, myalgia, splenomegaly, jaundice
Dengue: high fever, severe headache/retro-orbital pain, myalgia/arthralgia, rash, thrombocytopenia
Typhoid: insidious high fever, relative bradycardia, rose spots (2–4mm salmon-pink macules on trunk), constipation then diarrhoea
Hepatitis A: jaundice, nausea, RUQ pain, markedly raised ALT

Red Flags

Malaria parasitaemia >2% (severe malaria)
Haemorrhagic features (VHF, severe dengue)
Altered consciousness (cerebral malaria, meningitis)
Jaundice + fever (malaria, hepatitis, leptospirosis)

Differential Diagnosis

Diagnosis	Key Features	Investigation
Malaria	Cyclical fever, rigors, splenomegaly, jaundice	Thick/thin films ×3, RDT
Dengue	Fever, severe myalgia, rash, thrombocytopenia	NS1 antigen, IgM/IgG
Typhoid	Insidious fever, relative bradycardia, rose spots	Blood culture (gold standard)
Hepatitis A	Jaundice, raised ALT	HAV IgM
Rickettsial infection	Eschar, rash, fever after tick bite	Serology
Acute HIV seroconversion	Fever, rash, pharyngitis, lymphadenopathy	HIV p24 antigen, RNA

Diagnosis / Investigation

Immediate (All Febrile Returning Travellers)

Thick and thin blood films for malaria - ×3 over 24–48h; DO NOT wait for cyclical fever
Malaria rapid diagnostic test (RDT): adjunct but does not replace films
FBC: thrombocytopenia (dengue, malaria), eosinophilia (schistosomiasis, helminths)
U&Es, LFTs: organ involvement, hepatitis
CRP: degree of inflammation
Blood cultures: typhoid, bacteraemia
HIV test: always include

Directed Investigations

Dengue NS1 + serology: if travel to endemic area within 14 days
Hepatitis A/B/C serology: if jaundice or raised LFTs
Stool MC&S + ova/parasites: if diarrhoea
Schistosoma serology: if freshwater exposure + eosinophilia (test at ≥12 weeks post-exposure)
CXR: if respiratory symptoms (TB, PCP)
Urinalysis: schistosomiasis (haematuria)

VHF Risk Assessment

PHE algorithm

travel to VHF-endemic area + fever within 21 days

risk assessment

if high risk: IMMEDIATE ISOLATION, contact PHE

Management

Malaria (P. falciparum)

Uncomplicated (parasitaemia <2%, no severity criteria):

Artemisinin-based combination therapy (ACT): artemether-lumefantrine (Riamet) for 3 days
Or atovaquone-proguanil (Malarone) for 3 days

Severe malaria (parasitaemia ≥2%, organ dysfunction, cerebral):

IV artesunate 2.4mg/kg at 0, 12, 24 hours then daily until oral tolerated
HDU/ICU admission; exchange transfusion if parasitaemia >30%

P. vivax/ovale:

ACT or chloroquine for 3 days
PLUS primaquine 15mg OD for 14 days (radical cure - eliminates hypnozoites); check G6PD first

Dengue

Supportive: fluids, paracetamol (AVOID NSAIDs/aspirin - bleeding risk)
Monitor for dengue haemorrhagic fever/shock syndrome
No specific antiviral

Typhoid

Azithromycin 500mg OD for 7 days (uncomplicated)
IV ceftriaxone 2g OD if severe or quinolone-resistant
Stool cultures after treatment to confirm clearance

VHF

Strict isolation, full PPE, contact PHE
Supportive care; ribavirin for Lassa fever

Referral Criteria

All suspected malaria: immediate assessment (same-day malaria films)
Infectious diseases: complex/severe cases
PHE: VHF risk, notifiable diseases
ICU: severe malaria, dengue shock syndrome

Prognosis

Uncomplicated P. falciparum: excellent with prompt treatment (mortality <0.1%)
Severe P. falciparum: mortality 10–20% even with treatment
Dengue: mortality <1% with supportive care; dengue shock syndrome mortality up to 20% without treatment
Typhoid: <1% mortality with antibiotics; complications include intestinal perforation
Delay in diagnosis is the major risk factor for poor outcome in malaria

Other Relevant Information

Causes of Fever by Incubation Period

Incubation	Diagnoses
<10 days	Dengue, chikungunya, rickettsial, travellers' diarrhoea
10–21 days	Malaria, typhoid, hepatitis A, leptospirosis, acute HIV
>21 days	P. vivax/ovale malaria, TB, hepatitis B, visceral leishmaniasis

Severe Malaria Criteria (WHO)

Feature	Detail
Cerebral malaria	GCS <11
Severe anaemia	Hb <70 g/L
Parasitaemia	>10%
Renal failure	Creatinine >265 μmol/L
ARDS	Pulmonary oedema
Hypoglycaemia	Glucose <2.2 mmol/L
Acidosis	pH <7.25 or lactate >5