Malaria’s silent spreaders account for a fifth of transmission
Malaria poses a threat to 3.4 billion people across the globe, and is responsible for almost half a million deaths annually, particularly among young children in Africa. Breaking the chain of infection between mosquito and human offers an opportunity to reduce the spread of the disease. The EU-funded COSMIC project sought to elucidate more clearly when patients infected with malaria become contagious to others. “In measles, 10-15 new infections are caused by each single infection,” says project lead Teun Bousema. “For malaria the figure is 105. It’s a phenomenally efficient spreader.”
Breaking the cycle
In the body, the malaria parasite matures in the liver before releasing spores which infect blood cells, causing clinical symptoms of the disease. These merozoites may then reproduce to form new merozoites, continuing the infection. Alternatively, they may differentiate into gametocytes, which can infect mosquitoes and carry the parasite to a new host. “It’s quite a complicated process to become infectious to mosquitoes,” adds Bousema. “It takes 12 to 14 days to become a transmitter.” To understand the conditions that produce gametocytes, volunteers at Radboud University Medical Centre in Nijmegen, the Netherlands, were infected with malaria. Highly sensitive blood tests which could detect genetic traces of early gametocytes, the infectious form of malaria parasite, were able to predict who would later go on to infect mosquitoes.
Hidden infections
Another study was carried out in Burkina Faso, following two cohorts of children infected with malaria. “Often these patients are without symptoms, or have very mild ones, so infection may not result in health-seeking behaviour,” notes Bousema. “This is an important reason why transmission numbers are so high.” All patients were treated for infection once clinical signs became apparent. The group found that patients were still infectious at very low parasite concentrations, where medics would consider a patient cured. Bousema concludes that a large number of infections occur through people who are contagious but have too few parasites in their blood for traditional tests to detect. These ‘stealth infections’ are estimated to account for 20 % of disease transmission. The work produced several papers, published in ‘Nature Communications’ and ‘The Lancet Infectious Diseases’. “The practical application of our work is that if you can target non-symptomatic infections, that often occur in school children, you can have a large community effect. Those individuals are the most important for spreading the disease,” says Bousema.
Malaria strategies
Through the work, Bousema and his group were also able to develop a tool that can predict how many infectious gametocytes are produced at different stages of the disease. “Using that we found the production of transmission types is quite low in early stages of infection, then picks up in chronic illness,” he explains. “This means if you catch infections early, you can prevent a lot of the transmission.” The project was supported by the European Research Council. “What’s great about ERC funding is it trusts you to use the money well without getting all caught up with small milestones, or practical implications,” says Bousema. “That for me was crucial.” The research is now being used to develop strategies to reduce malaria transmission, with support from the Bill and Melinda Gates Foundation.
Keywords
COSMIC, malaria, mosquito, gametocyte, infection, transmission, blood, parasite, Radboud
