The Severe Malaria in African Children network (SMAC) through hospitals located in Gabon and Malawi recruited 171 children aged between six months and 10 years old as part of this phase II clinical trial. All children with severe malaria that fulfilled the study recruitment criteria were enrolled and randomised into two groups with different treatment regimens of intravenously administered artesunate. One group was given the current WHO recommended regimen of five doses over 72 hours , and the other group given a slightly higher dose but only in three doses over 48 hours. All the children received the same overall quantity of artesunate. In all patients, parasite clearance occurred rapidly and only two deaths were registered in the 3-dose regimen. The results showed that the 3-dose regimen were similar to 5-dose regimen at clearing parasites.

In the press release by the St. George’s Hospital (University of London), Prof. Kremsner is quoted as saying: “The 5-dose regimen has been in place for a number of years, but the WHO’s recommendations are based on large studies mainly looking at improvements in survival. We suggested there was a better, simpler way to administer this highly effective drug, so we looked at how the parasites actually respond to the treatment. Now we know the shorter treatment works as effectively, this could lead to very significant improvements in how we use artesunate.” He added that the next step in further improving treatment regimens is to explore the benefits of delivering artesunate intramuscularly instead of intravenously.

Background
The study was funded under an EDCTP call (2004) to address a serious gap in the antimalarial strategies of major global funding agencies, which concentrated on the treatment of uncomplicated malaria.

In some Southeast Asian countries artemisinins are already used in preference to quinine for treating severe malaria. Previous large studies in Asia and Africa comparing quinine with artemether for treating severe malaria showed a mortality of 14% with artemether and 17% with quinine (P = 0.08). However, this result has not changed clinical practice.

Artesunate is a water-soluble artemisinin-derivative that can be given intravenously, making it one of the most rapidly acting antiparasitic agents. Therefore, artesunate could be an alternative to intravenous quinine as the chemotherapy of choice for severe malaria in children.

Partnership
SMAC consists of five centres: the Royal Victoria Hospital/Medical Research Council (MRC) Laboratories in Banjul in The Gambia, the School of Medical Sciences at the University of Science and Technology in Kumasi in Ghana, the Albert Schweitzer Hospital in Lambaréné in Gabon, the Centre for Geographic Medicine (Coast) Kenya Medical Research Institute in Kilifi in Kenya and the Queen Elizabeth Central Hospital in Blantyre in Malawi.The study was led by Prof. Kremsner at the Albert Schweitzer Research Centre in Lambaréné and Libreville, Gabon. The study coordination and management was done by Dr. Dr. Carsten Köhler at the University of Tübingen.

The trial was cofunded by Federal ministry of Education and Research (BMBF; Germany); Medicines for Malaria Venture (Switzerland); St.George’s University of London (United Kingdom); Vienna School of Clinical Research (Austria); Bernhard Nocht Institute for Tropical Medicine (Germany), Institute for Tropical Medicine; GlaxoSmithKline Foundation (United States); Department for International Development (DFID, United Kingdom).

The artesunate for injection was kindly donated by the Walter Reed Army Institute of Research (United States).

More information
See the publication on the website of the Journal of Infectious Diseases
See also press release of St. George’s Hospital (London University, United Kingdom)
See also press release by University of Tübingen (in German)
See also website of Medical Research Unit Albert Schweitzer Hospital, Lambaréné, Gabon
The clinical trial is registered at the NIH ClinicalTrials.gov registry under number: NCT00522132