Boosting natural immunity to tackle malaria

The World Health Organization (WHO) estimated that in 2010 malaria was the cause of 655,000 deaths. While this number has greatly decreased in the last decade it is still one of the world’s most important infectious diseases. Mortality is highest in African children; the WHO estimates that one child dies every minute from malaria. The disease is caused by protozoan Plasmodium parasites which are transmitted through bites from infected female mosquitoes.

Every year millions of travellers visit regions where malaria is endemic and take medicines to prevent them getting the infection. These drugs are also used in endemic regions for at-risk groups. However, studies have shown that this strategy is ineffective for whole populations in endemic areas because ensuring compliance is difficult and the risk of emerging drug resistance is substantial.

An effective vaccine for malaria would be an ideal solution but none are currently available. The significant diversity of the malarial parasite makes development of a subunit vaccine problematic and many targets have given a poor immune response. Approaches using whole-parasite vaccines have shown promise but none have been successfully produced.

The authors of this review discuss the possibility of giving anti-malarial drugs for set periods of time to people in endemic regions who will become naturally infected by malaria. There is experimental evidence using a ‘controlled human malaria infection’ approach to suggest that this strategy enhances natural immunity to the malaria parasite, preventing individuals from developing illness.

In one study, uninfected adult volunteers received 12-15 bites by Plasmodium falciparum-infected mosquitos monthly, for three months, while being given the common malaria-preventing drug, chloroquine. Three months after the anti-malarial therapy stopped, the volunteers did not develop malaria symptoms following further challenge with infected-mosquito bites. Impressively, two years later, many of the volunteers still displayed immunity.

This data is proof-of-concept, but the authors note that further studies could be carried out in areas where there is a transmission season with similar inoculation rates to those used in the study. This would validate the findings in true endemic areas. Also, different anti-malarial drugs would have to be investigated as resistance to chloroquine is widespread. One alternative is combination therapy with more than one antimicrobial with different modes of action, for example chloroquine and azithromycin. This approach would allow this novel therapy to be used even in areas where drug resistance is present.

Deirdre Hollingsworth from Imperial College London discusses how modelling malaria transmission patterns can inform intervention strategies in SGM's Microbe Talk podcast.