Evaluating drugs and devising strategies for reducing malaria transmission

According to World Health Organization estimates, drug and mosquito control measures have brought about a 30% drop in malaria incidence since 2000.

However there were still 200 million reported cases of malaria worldwide in 2013, resulting in 600,000 deaths, mostly among African children under 5 years of age. Consequently, elimination of the disease has now been set as a global health priority, and research at the School has played a major role in developing a new strategy to help achieve this.

One of the key elements of this research has been to ensure that individuals who have been treated for malaria are no longer infectious to mosquitoes, thus breaking the chain of transmission between humans and mosquitoes.

Working in The Gambia and Kenya from 1998 to 2009, the School’s researchers found that, compared with other drug regimes, the addition of artemisinins to drug combinations induced a marked reduction in post-treatment prevalence, density and infectivity of gametocytes – the parasite stage responsible for transmission from human to insect.

Researchers teamed up with collaborators from more than 20 institutions to develop a method for measuring transmission from blood to mosquitoes. Using this membrane feeding assay, they found that artemisinin-based combination therapies (ACTs) minimised but did not completely stop transmission. They then looked at combining the drug primaquine (PQ) – which has long been known to lower transmission rates from human to insect – with ACT. They found that a single dose of PQ was effective and, importantly, did not have the side effects the drug is known to cause when given in higher doses.

Chris Drakeley, director of the School’s Malaria Centre, and Teun Bousema, senior lecturer, then tested who was responsible for human-to-insect transmission and how and where best to use PQ-ACT drug combinations, as they found there are often transmission hotspots. Drakeley presented these findings to a WHO scientific forum, which led to the organization recommending the addition of a single dose of PQ to the ACT regime.

This recommendation marked an important change in WHO’s malaria strategy – essentially, elimination requires a shift in focus from just treating individuals showing malaria symptoms to also treating asymptomatic carriers of the disease.

The Medicines for Malaria Venture – a leading product development public-private partnership in the field of antimalarial drug research and development – has now changed its definition of the target candidate profile for a malaria treatment to include killing gametocytes, to prevent transmission to the mosquito.

The School’s research on transmission hotspots has helped countries to map cases and target interventions to areas with a high caseload. In Mexico, this led to an 83% decrease in reported malaria cases between 2000 and 2010. Similarly, the targeting of interventions has had a startling impact in Swaziland, which saw the number of confirmed cases drop by 42% between January 2011 and June 2012. It aims to be the first country in mainland sub-Saharan Africa to eliminate malaria, with the School’s methods to identify transmission hotspots being an integral part of the strategy to be used towards this historic goal.