Malaria prevention, diagnosis and treatment

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Human malaria follows inoculation of Plasmodium sporozoites, hepatic replication and cyclical invasion of red cells. P. falciparum can sequester infected erythrocytes in small vessels and cause cerebral, respiratory, renal and metabolic failure. P. knowlesi can also become severe rapidly. P. vivax, P. ovale and P. malariae usually progress less abruptly, but all species can cause important morbidity.

A complete risk history records every country and region, rural or urban location, dates, season, accommodation, night exposure, prophylaxis choice, adherence, vomiting and return date. Previous residence in an endemic country does not provide dependable protection after living in the UK; travellers visiting friends and relatives are a major risk group.

Pre-travel advice is individual rather than a universal drug hierarchy. UKHSA country recommendations define whether chemoprophylaxis is advised, while age, weight, pregnancy, renal function, comorbidity, interactions, previous intolerance and itinerary determine which suitable option is chosen.

Key points

Malaria is transmitted by female Anopheles mosquitoes; P. falciparum causes most fatal imported disease, while P. vivax and P. ovale can relapse from dormant liver hypnozoites.
Fever after malaria-risk travel, often with headache, myalgia, rigors or gastrointestinal symptoms, is the key trigger; a regular cycle is not required.
First-line diagnosis is urgent expert thick and thin blood-film microscopy with parasite density; add a rapid diagnostic test, but never use it as the sole rule-out test.
If initial films are negative but suspicion remains, repeat films 12 to 24 hours apart until three appropriately examined sets are negative, while reassessing for sepsis and other imported infections.
Severe malaria requires intravenous artesunate 2.4 mg/kg at 0, 12 and 24 hours, then every 24 hours until oral treatment is possible, followed by a complete effective oral course under specialist direction.
Uncomplicated falciparum malaria can be treated with artemether-lumefantrine: four 20/120 mg tablets at 0, 8, 24, 36, 48 and 60 hours with food containing fat, if the patient can absorb oral medicine.
Prevention combines awareness, bite avoidance and itinerary-specific chemoprophylaxis; no tablet is completely protective, so post-travel fever still needs immediate testing.
Malaria is notifiable in England; notify suspected or confirmed disease according to current jurisdictional rules and urgently alert health protection if UK acquisition is possible.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Mosquito inoculation

An infected female Anopheles mosquito injects sporozoites during feeding; transfusion, transplantation, shared needles and congenital transmission are uncommon alternatives.

Falciparum predominance

P. falciparum accounts for most fatal imported malaria because infected erythrocytes sequester and all red-cell ages can be invaded.

Relapsing parasites

P. vivax and P. ovale leave dormant hepatic hypnozoites that can reactivate months after the infective journey despite clearance of circulating parasites.

Zoonotic knowlesi

P. knowlesi is acquired from macaque-associated mosquito cycles in parts of South-East Asia and has a short replication cycle capable of rapid deterioration.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Hepatic amplification
Sporozoites invade hepatocytes and multiply before releasing merozoites into blood; this clinically silent phase precedes erythrocyte infection.
2
Erythrocyte rupture
Repeated red-cell invasion and rupture release parasites and inflammatory mediators, producing fever, haemolysis, thrombocytopenia and splenic clearance.
3
Microvascular sequestration
Falciparum-infected cells adhere to endothelium and obstruct tissue microcirculation, driving cerebral dysfunction, acidosis, renal injury and placental disease.
4
Metabolic failure
Parasite glucose consumption, impaired hepatic production, poor intake and severe systemic stress combine to cause hypoglycaemia and lactic acidosis.
5
Dormant liver reservoir
Vivax and ovale hypnozoites remain outside the reach of blood-stage therapy, explaining relapse unless safe radical cure is completed.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Fever after exposureRed flag

Fever, sweats or rigors after time in a malaria-risk area is the cardinal trigger for urgent testing, regardless of prophylaxis use or elapsed months.

Cerebral involvementRed flag

Confusion, agitation, drowsiness, seizure, abnormal posturing or coma in parasitaemia indicates cerebral malaria once alternative causes are addressed.

Respiratory deteriorationRed flag

Tachypnoea can reflect fever or acidosis, while hypoxaemia, crackles and increasing oxygen requirement may mark pulmonary oedema or acute respiratory distress syndrome.

Relapsing species

Vivax or ovale infection can present months after exposure because dormant hepatic stages reactivate; prior treated episodes may recur without radical cure.

Pregnancy phenotypeRed flag

Maternal illness may be severe with hypoglycaemia, anaemia and placental sequestration; miscarriage, growth restriction and preterm birth can occur.

Red flags requiring action

Any fever or systemic illness after travel to a malaria-risk area requires same-day malaria testing, even when prophylaxis was taken or another diagnosis appears plausible.
Confusion, seizure, prostration, shock, respiratory distress, pulmonary oedema, significant bleeding, haemoglobinuria, hypoglycaemia or acidosis indicates potentially severe malaria.
Acute kidney injury, severe anaemia, marked thrombocytopenia or jaundice accompanied by another organ abnormality requires urgent senior and specialist review.
Pregnancy, infancy, older age, asplenia and immune compromise lower the threshold for admission because complications can evolve before a large peripheral parasite count is visible.
A first negative blood film does not exclude malaria when exposure and illness fit; repeat expert microscopy while pursuing alternative diagnoses.
A patient unable to swallow or retain oral therapy needs parenteral treatment and monitored care rather than repeated oral doses.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
First-line thick and thin blood filmsFirst stepFirst line
Why
Detect parasites, identify species, quantify parasitaemia and provide a baseline for response.
Interpretation and limitations
Thick film is sensitive for detection and thin film supports species and percentage parasitaemia; request urgent expert examination and state travel history, pregnancy and clinical severity.
02
Repeat parasite testing
Why
Address fluctuating or initially low parasitaemia when clinical suspicion remains.
Interpretation and limitations
Repeat thick and thin films 12 to 24 hours apart to a total of three negative sets; do not wait for the series before treating physiologically severe suspected malaria.
03
Immediate severity panel
Why
Identify organ failure and treatment hazards at presentation.
Interpretation and limitations
Check bedside glucose repeatedly, FBC, coagulation, urea, creatinine, electrolytes, bilirubin, ALT, venous or arterial gas, lactate and group-and-save; abnormalities influence admission and critical-care decisions.
04
G6PD quantitative assay
Why
Prevent oxidant haemolysis before radical treatment of vivax or ovale hypnozoites.
Interpretation and limitations
Obtain a quantitative result before primaquine or tafenoquine; acute haemolysis or transfusion can give misleading activity, so specialist interpretation and sometimes repeat testing are needed.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Enteric fever

Sustained fever, abdominal symptoms and cytopenias after food or water exposure overlap substantially; obtain cultures without postponing malaria microscopy.

Dengue and arbovirus

Fever, headache, myalgia, rash and thrombocytopenia may suggest dengue, but capillary-leak warning signs and targeted virology distinguish it.

Bacterial sepsis

Pneumonia, pyelonephritis, meningitis and bloodstream infection can mimic or coexist with malaria, especially when shock or focal findings develop.

Viral haemorrhagic fever

Compatible geography, timing and exposure may require immediate isolation risk assessment before routine sampling, although malaria testing remains essential.

Acute viral infection

Influenza, COVID-19, EBV, CMV and acute hepatitis can cause fever and cytopenias but lack demonstrable blood-stage parasites.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01TEST NOWAssess fever after malaria exposureFirst stepA patient is febrile or reports recent fever after travel to any malaria-risk area.

1Record precise countries, regions and dates, then send urgent thick and thin films plus a rapid diagnostic test through a laboratory able to report immediately.
2Perform ABCDE and check bedside glucose while obtaining FBC, renal and liver profiles, coagulation, gas and lactate; assess pregnancy and oral absorption.
3If initial testing is negative but suspicion persists, arrange repeat microscopy 12 to 24 hours apart until three sets are negative and actively investigate concurrent sepsis.
4Notify malaria under current national rules; if local acquisition, transfusion, transplant or needlestick transmission is plausible, contact health protection promptly.

02SEVERETreat organ-threatening malariaParasitaemia or a compatible exposure is accompanied by cerebral, respiratory, circulatory, renal, metabolic, haematological or other severe features.

1DefinitiveInvolve infection or tropical medicine, pharmacy and critical care immediately; start intravenous artesunate without waiting for definitive species or transfer.
2Give artesunate 2.4 mg/kg intravenously at 0, 12 and 24 hours, then every 24 hours until oral therapy is tolerated, using a locally governed preparation pathway.
3Manage hypoglycaemia, seizures, shock, acidosis, renal failure and respiratory failure with careful fluids and organ support; avoid reflex fluid loading because pulmonary oedema is a risk.
4DefinitiveWhen oral absorption is reliable, complete a full effective oral antimalarial course selected with the specialist team rather than counting parenteral doses as definitive cure.
5Arrange post-artesunate haemolysis surveillance after discharge, explaining that delayed anaemia can develop after apparent parasite clearance.

03ORALManage uncomplicated falciparum malariaFalciparum malaria is confirmed without severe criteria and the patient can reliably swallow and absorb treatment.

1Admit or manage in a monitored specialist pathway, because early deterioration, vomiting and changing parasite density can alter the route of treatment.
2Use a recommended oral regimen such as artemether-lumefantrine or atovaquone-proguanil after checking previous prophylaxis, interactions, pregnancy, weight and organ function.
3Give artemether-lumefantrine with food or a milky drink and directly address nausea; vomiting soon after a dose requires urgent advice on replacement and possible parenteral therapy.
4Repeat clinical observations, glucose, blood counts, renal function and parasite density until a safe falling trajectory and reliable oral completion are established.

04NON-FALCIPARUMClear blood and liver stagesVivax, ovale, malariae or knowlesi infection is identified or strongly suspected.

1Treat the acute blood-stage infection with a species-, geography- and severity-appropriate regimen; manage severe knowlesi or any severe phenotype as severe malaria.
2For vivax or ovale, request quantitative G6PD testing and involve tropical medicine before prescribing primaquine because haemolysis risk and regional relapse patterns affect dosing.
3Do not give primaquine or tafenoquine during pregnancy; arrange specialist plans for suppressive management and postpartum radical cure where appropriate.
4Reassess recurrent fever with fresh films rather than assuming relapse, because reinfection, recrudescence, mixed species and a new non-malarial illness require different action.

05PREVENTBuild an individual prevention planA traveller will enter a destination for which malaria risk assessment is required.

1Check the current UKHSA country and subnational recommendation using exact itinerary, season, trip duration, accommodation, activities and access to care.
2Explain awareness and bite avoidance, including repellent, clothing and insecticide-treated nets, then choose a suitable recommended prophylactic option through shared decision making.
3Check pregnancy possibility, age, weight, kidney and liver function, psychiatric and seizure history, medicines, allergies and prior adverse effects before prescribing.
4Provide the complete start, daily or weekly schedule and post-exposure tail in writing; discuss food instructions, missed doses, vomiting and when to seek urgent help.
5Emphasise that prophylaxis reduces but does not abolish risk and that any fever during travel or within a year of return needs immediate medical assessment with the itinerary declared.

Key medicines and prescribing safety7 treatments · regimens, roles and cautions

First-line treatment for severe malaria of any species and for patients unable to absorb oral therapy.

Intravenous artesunate

Give 2.4 mg/kg intravenously at 0, 12 and 24 hours, then 2.4 mg/kg every 24 hours until reliable oral treatment is possible, followed by a complete effective oral course.

Do not delay for parasitology in a critically ill exposed patient; use specialist pharmacy preparation, monitor glucose and parasite density, and arrange delayed haemolysis surveillance for about four weeks.

Recommended oral treatment for uncomplicated falciparum malaria when absorption is reliable; current UK prevention guidance accepts use throughout pregnancy.

Artemether-lumefantrine

For an adult weighing at least 35 kg, give four tablets containing 20 mg/120 mg each at 0, 8, 24, 36, 48 and 60 hours with food containing fat.

Review QT-prolonging medicines and cardiac disease, repeat or escalate after vomiting according to specialist advice, and never use as sole therapy for severe malaria.

Alternative oral regimen for uncomplicated falciparum malaria when susceptibility, prior prophylaxis and host factors make it suitable.

Atovaquone-proguanil treatment

Give four adult tablets, each containing atovaquone 250 mg with proguanil 100 mg, orally once daily with food or a milky drink for three consecutive days.

Avoid as treatment after failed atovaquone-proguanil prophylaxis, obtain specialist advice in pregnancy, and do not use with severe renal impairment or unreliable gastrointestinal absorption.

Itinerary-dependent chemoprophylaxis option with a short post-exposure course and rapid start.

Atovaquone-proguanil prophylaxis

Take one 250 mg/100 mg adult tablet orally once daily with food from one to two days before entering risk until seven days after leaving the malaria area.

Not recommended when estimated glomerular filtration rate is below 30 mL/min/1.73 m² or during dialysis; pregnancy, low body weight, vomiting and interacting medicines require individual review.

Itinerary-dependent prophylaxis option that also reduces some rickettsial risks and is useful when a rapid start is needed.

Doxycycline prophylaxis

Take doxycycline 100 mg orally once daily from one to two days before entering risk, throughout exposure and for four weeks after leaving the malaria area.

Avoid routinely in pregnancy and children under 12 years; counsel on photosensitivity, oesophagitis, upright administration with water, separation from polyvalent cations and completing the four-week tail.

Weekly itinerary-dependent prophylaxis option, sometimes useful for prolonged travel and during pregnancy after expert risk assessment.

Mefloquine prophylaxis

For an adult weighing at least 45 kg, take 250 mg orally once weekly, normally starting two to three weeks before exposure and continuing weekly until four weeks after leaving.

Do not use with active or previous significant psychiatric disorder, epilepsy or relevant cardiac conduction risk; begin early enough to assess tolerability and act promptly on neuropsychiatric symptoms.

Eradicates dormant hepatic hypnozoites of vivax and ovale malaria to prevent later relapses.

Primaquine radical cure

Use a specialist-selected oral dose and duration based on Plasmodium species, likely geographic relapse pattern, body weight and a reliable quantitative G6PD result after blood-stage treatment.

Contraindicated in pregnancy and unsafe in significant G6PD deficiency; breastfeeding requires confirmation of infant G6PD status, and haemoglobin monitoring may be needed during treatment.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Cerebral malaria

Sequestered parasites, endothelial activation and metabolic disturbance produce seizures, impaired consciousness, coma and possible persistent neurological injury.

Multiorgan failure

Shock, acute kidney injury, acidosis, pulmonary oedema, respiratory distress, hepatic dysfunction and coagulopathy can develop together within hours.

Severe haemolysis

Parasite rupture and splenic removal cause anaemia, jaundice and haemoglobinuria; artesunate-associated delayed haemolysis can appear after initial recovery.

Pregnancy loss

Placental sequestration and maternal anaemia increase miscarriage, stillbirth, fetal growth restriction, low birth weight and preterm delivery.

Relapse or recrudescence

Hypnozoite activation causes vivax or ovale relapse, whereas incomplete blood-stage clearance or resistance produces recrudescence and renewed parasitaemia.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Repeat observations, mental state, urine output and bedside glucose frequently in severe disease; hypoglycaemia may recur and can resemble cerebral deterioration.
Track haemoglobin, platelets, renal function, bilirubin, lactate and parasite density; clinical organ recovery matters more than one isolated percentage parasitaemia.
After intravenous artesunate, arrange haemoglobin and haemolysis-marker review weekly or through the specialist schedule for approximately four weeks to detect post-artesunate delayed haemolysis.
For vivax or ovale, document the G6PD result, radical-cure plan and contraception or pregnancy considerations; recurrent fever requires repeat films.
Report malaria under current jurisdictional arrangements and preserve an accurate travel and prophylaxis history for surveillance and any investigation of possible local transmission.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Prophylaxis does not rule out malaria

Breakthrough disease follows missed doses, vomiting, resistance, incorrect itinerary advice or imperfect protection, so symptoms always outrank reported adherence.

Density is species dependent

A modest peripheral count can accompany severe falciparum sequestration, while knowlesi parasitaemia can rise quickly; physiology and species both shape risk.

One film is insufficient

Parasitaemia fluctuates and early density may be below detection; serial properly examined films protect against a false negative first sample.

Artesunate needs aftercare

Rapid parasite clearance does not end risk because delayed immune removal of once-infected erythrocytes can produce clinically important haemolysis weeks later.

Scope boundary

Malaria-specific testing, treatment and prevention are developed here; isolation decisions and the complete imported-fever differential remain part of the broader returning-traveller assessment.

11Common pitfallsFrequent interpretation and management errors.

01
Do not reassure a febrile traveller because prophylaxis was prescribed, because no mosquito bite was remembered or because fever lacks a regular cycle.
02
Do not rely on a rapid diagnostic test alone; it neither quantifies parasites nor safely excludes every species or low-density infection.
03
Do not delay intravenous artesunate in severe suspected malaria while awaiting reference PCR, a second film, transfer or a precise species label.
04
Do not use aggressive fluid boluses without repeated perfusion and respiratory reassessment; severe malaria can combine intravascular depletion with pulmonary oedema risk.
05
Do not prescribe primaquine from a qualitative recollection of G6PD status, during pregnancy or without defining species, geography and follow-up.
06
Do not forget post-artesunate haemolysis surveillance after the patient feels well and parasitaemia has cleared.