Malaria

Malaria is a life threatening parasitic infection caused by Plasmodium species, transmitted through the bite of an infected female Anopheles mosquito. It remains one of the leading causes of infectious mortality worldwide.

The infecting species fundamentally determines clinical severity, complication profile and management approach. The critical distinction is between Plasmodium falciparum, responsible for the overwhelming majority of severe and fatal disease, and the other, generally less severe species.

Species and pathophysiology

• Plasmodium falciparum causes the most severe disease. It can infect red blood cells of any age (unlike other species with more restricted age preference) and produce very high parasitaemia.
• Cytoadherence of infected red cells to vascular endothelium causes sequestration and microvascular obstruction. This is the pathophysiological basis for severe organ specific complications including cerebral malaria.
• Plasmodium vivax and Plasmodium ovale form dormant hepatic hypnozoites capable of causing relapse months to years after the initial infection if not specifically eradicated. This is an important consideration for radical cure treatment.
• Plasmodium malariae causes generally milder but more chronic disease, with a recognised, though uncommon, association with nephrotic syndrome from immune complex deposition.
• Plasmodium knowlesi is a zoonotic species acquired from macaque monkeys in specific regions of Southeast Asia. It has a twenty four hour asexual life cycle and can produce severe disease with rapidly rising parasitaemia, given this short replicative cycle.

• Fever, often with rigors, together with headache, myalgia, malaise and gastrointestinal symptoms (nausea, vomiting, diarrhoea), characterises the typical presentation.
• It develops after an incubation period generally of one to four weeks depending on species. This can be substantially longer for Plasmodium vivax and Plasmodium ovale, given the possibility of prolonged hepatic latency before symptomatic relapse.
• Classical periodic fever patterns are described: tertian fever every forty eight hours for Plasmodium vivax, ovale and falciparum, and quartan fever every seventy two hours for Plasmodium malariae.
• These patterns are frequently absent or irregular, particularly early in the illness, and should never be relied upon to exclude the diagnosis.
• Severe falciparum malaria is defined by specific clinical and laboratory criteria, including any one of the following:
• Impaired consciousness or seizures (cerebral malaria)
• Respiratory distress or acute respiratory distress syndrome
• Circulatory collapse or shock
• Acute kidney injury
• Significant bleeding or disseminated intravascular coagulation
• Jaundice with other severity criteria
• Severe anaemia (haemoglobin below 70 g per litre)
• Hypoglycaemia (blood glucose below 2.2 mmol per litre)
• Acidosis (bicarbonate below 15 mmol per litre, or lactate above 5 mmol per litre)
• Parasitaemia above 10 percent of red cells
• Blackwater fever, a severe complication with massive intravascular haemolysis and haemoglobinuria, and hyperparasitaemia, both carry substantial associated mortality risk requiring intensive management.
• Any traveller returning from a malaria endemic region presenting with fever should be regarded as having malaria until proven otherwise, given the potential for rapid deterioration in falciparum infection.
• Never exclude the diagnosis solely on the basis of appropriate prior chemoprophylaxis, which reduces but does not eliminate risk.

• Thick and thin blood films remain the diagnostic reference standard. The thick film gives greater sensitivity for detecting parasitaemia. The thin film allows accurate species identification and parasitaemia quantification, essential for guiding both severity assessment and treatment decisions.
• A single negative blood film does not exclude malaria, particularly early in illness or with low level parasitaemia.
• Repeat films at twelve to twenty four hour intervals over a total of three sets are recommended before the diagnosis can be confidently excluded in a patient with a compatible clinical picture and relevant travel history.
• Rapid diagnostic antigen tests detect specific Plasmodium antigens (histidine rich protein 2 for falciparum, and pan species lactate dehydrogenase or aldolase). They are a rapid, accessible adjunct to microscopy.
• Use them alongside, rather than as a complete substitute for, blood film examination, given differing sensitivity profiles between species and the ongoing need for accurate speciation and parasitaemia quantification.
• Full blood count typically shows thrombocytopenia, a common and useful supportive finding, together with variable anaemia.
• Renal function, liver function, glucose, lactate and coagulation studies are essential in every confirmed case to assess for features of severe disease.

• Uncomplicated falciparum malaria is treated with artemisinin based combination therapy. Artemether with lumefantrine is a widely used first line regimen.
• The standard adult dose is four tablets, each containing 20 mg artemether and 120 mg lumefantrine, given twice daily for three days. Take with fatty food to optimise lumefantrine absorption.
• Severe falciparum malaria is a medical emergency requiring intravenous artesunate 2.4 mg per kg given at zero, twelve and twenty four hours, then once daily.
• Give a minimum of twenty four hours of intravenous therapy before any switch to oral completion therapy, once the patient tolerates oral intake and parasitaemia is falling appropriately.
• Intravenous artesunate is superior to intravenous quinine for severe malaria.
• Quinine is reserved as an alternative where artesunate is unavailable. Give a loading dose of 20 mg per kg over four hours, then 10 mg per kg every eight hours, with cardiac monitoring given quinidine like arrhythmia risk.
• Non falciparum malaria (vivax, ovale, malariae, knowlesi) is generally treated with chloroquine where susceptibility is confirmed. Artemisinin combination therapy is increasingly used given rising chloroquine resistance in several regions, particularly for Plasmodium vivax.
• Radical cure for Plasmodium vivax and ovale requires addition of primaquine (0.25 to 0.5 mg per kg once daily for fourteen days) to eradicate dormant hepatic hypnozoites and prevent relapse.
• Glucose 6 phosphate dehydrogenase testing is mandatory before primaquine administration, given the risk of severe haemolysis in deficient individuals.
• Supportive management of severe malaria complications is delivered within an appropriate high dependency or intensive care setting.
• It includes careful fluid management (avoiding over resuscitation given risk of pulmonary oedema), correction of hypoglycaemia, management of seizures, renal replacement therapy for significant acute kidney injury, and transfusion for severe anaemia.
• Exchange transfusion may be considered for extreme hyperparasitaemia in some protocols. Its use has declined given improved outcomes with prompt artesunate therapy alone.
• Preventive counselling for travellers is essential. It covers chemoprophylaxis (agent selection guided by destination resistance patterns) and mosquito bite avoidance (repellent, protective clothing, bed nets).
• Advise travellers to seek prompt medical attention for any fever occurring during or after travel to an endemic region.