London School of Hygiene & Tropical Medicine

Artemisinin combination therapy (ACT), the most widely used drug treatment for malaria, may not be as effective in clearing malaria parasites as previously thought, according to research published in the Journal of Infectious Diseases.

The study, led by researchers at the London School of Hygiene & Tropical Medicine and partners in the MALACTRES consortium, was carried out partly in response to observations from Cambodia and surrounding countries suggesting that resistance to ACT is developing there.

The new research showed for the first time that ACT treatment did not immediately clear all the malaria parasites in some children in Western Kenya.

Researchers devised a new method – a sensitive DNA based test - to check for malaria parasites, enabling them to take fewer blood samples than in previous studies which used microscopy, and still get an indicator of how quickly the parasites were clearing.

They tested 154 of the 300 children in the trial using the new method and found that around a third had residual sub-microscopic parasites remaining three days after starting ACT treatment, levels which would not have been detected using a microscope.

Further analysis  and follow-up of patients showed that children who had residual parasites three days after starting treatment  were significantly more likely to be infectious to mosquitoes at day seven, therefore contributing to further malaria transmission.

The authors concluded that there may also be consequences for individual patients, as children with residual parasites were also more likely to experience recurrent parasites, visible under the microscope, four to six weeks after treatment.

Dr Colin Sutherland, Head of the School’s Immunology and Infection Department and study co-author said: “We were surprised to find that a large proportion of children still had detectable parasites by this new DNA method three days after treatment, below the level of detection of the microscope.  It makes us ask if this has always been the case with apparently effective drugs, that actually do they often leave this small residual population of parasites.

“From the data we have so far we’re not really alarmed, because by all the usual criteria for judging the efficacy of drugs these ones have worked well, but it does remind us that we need to keep working on new treatments. It takes a long time to develop a new malaria drug and we must keep that effort going.”

The researchers are now investigating the genetic signals of the residual parasites that are present three days after treatment to see if the drugs have affected them, effectively selecting a particular type of parasite.

The study was funded by the European Community’s Seventh Framework Programme, the Bill and Melinda Gates Foundation, Public Health England and the EDCTP WANECAM Consortium.

Podcast

Colin Sutherland discusses the study and its implications.

Publication

• Beshir, KB; Sutherland, CJ; Sawa, P et al. Residual Plasmodium falciparum parasitemia in Kenyan children after artemisinin-combination therapy is associated with increased transmission to mosquitoes and parasite recurrence. The Journal of Infectious Diseases. DOI: 10.1093/infdis/jit431