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

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)

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

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

• 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

WHO Criteria for Severe Malaria (P. falciparum)

Malaria Chemoprophylaxis