2nd August 2023

Malaria

Malaria is a protozoal infection caused by Plasmodium species. It is the most common parasitic infection worldwide, with the main burden of disease largely in Africa. It is transmitted through the bite of the female Anopheles mosquito and has four different types that cause infection in humans: P. falciparum, P. vivax, P. ovale and P. malariae. Certain haemoglobinopathies (sickle cell disease, G6PD deficiency and thalassaemias) are protective against malaria as the parasites are less able to infect erythrocytes, or the red blood cells are more likely to die from oxidative stress. It is believed that regions endemic to malaria have higher rates of these haemoglobinopathies as it confers a natural selection advantage.

The gold standard diagnosis is with microscopy of Giemsa-stained blood films. Three samples should be sent on three successive days and are often complemented with rapid diagnostic tests (RDTs) for early management and referral. RDTs are restricted by speciation and do not help with the quantification of parasitaemia (percentage of infected cells in the blood).

Prevention for travellers is aimed at mosquito avoidance measures (e.g. mosquito nets) in conjunction with prophylaxis therapy in high-risk areas. Atovaquone-proguanil, mefloquine, doxycycline and tafenoquine are all effective agents, with the first two having the best side effect profiles. In pregnancy, travel to malaria endemic areas should be avoided, but if necessary, mefloquine is the drug of choice for prophylaxis.

Falciparum malaria

P. falciparum is the most common and severest form of malaria. The incubation period is usually 12 to 14 days. After the initial bite, sporozoites infect hepatocytes, undergo mitosis and become merozoites. Merozoites enter the bloodstream and infect erythrocytes, where they replicate further and differentiate. The erythrocyte ruptures, releasing more merozoites into the bloodstream.

Features in uncomplicated, mild disease are usually non-specific: fever, malaise, fatigue, tachycardia, nausea, abdominal pain and arthralgias. Cyclical fevers, a late disease manifestation, are rarely seen now due to early recognition and treatment.

Severe malaria is defined as parasitaemia with one or more of the following complications:

• Metabolic acidosis
• Respiratory distress or ARDS
• Renal failure and haemoglobinuria (blackwater fever)
• Circulatory collapse
• DIC or severe anaemia or haemolysis
• Hypoglycaemia
• Cerebral malaria (altered consciousness, delirium, seizures)

Treatment in uncomplicated falciparum malaria is with artemisinin-based combination therapies (ACT) in both chloroquine resistant and sensitive areas unless ACT is not readily available. In severe malaria, IV artesunate is the treatment of choice. Exchange transfusion is considered when parasitaemia > 10% and there is evidence of end-organ damage. However, the benefits are indeterminate.

Non-falciparum malaria

The most common form of non-falciparum malaria is P. vivax, followed by P. ovale and P. malariae. Vivax is endemic to central America and the Indian subcontinent, whereas ovale and malariae are more commonly seen in Africa. As part of their replication cycle, vivax and ovale produce liver hypnozoites that remain dormant and predispose to relapse anywhere between weeks to years after the initial infection.

Features are generally non-specific, including high-grade pyrexia, diaphoresis, abdominal pain, nausea and vomiting, myalgia and arthralgia. Physical examination often reveals hepatosplenomegaly and jaundice. Features of severe malaria are consistent with all species.

Treatment is similar to uncomplicated falciparum malaria, with WHO advising the use of artemisinin-based combination therapies (ACT) in both chloroquine resistant and sensitive areas unless ACT is not readily available. In the case of ovale and vivax, primaquine should be added to eradicate any liver hypnozoites.