Rectal artesunate study wins BMJ research paper of year award
A WHO/TDR study that showed rectal artesunate prevents death and disability in severe malaria has been chosen as the British Medical Journal’s research paper of the year. The award, announced March 10, recognizes original clinical research that contributes significantly to improving health and health care.
''This goes beyond just winning an award'' said TDR scientist Melba Gomes, the trial director. ''It's about using scientific endeavour to transform simple ideas into practical solutions. It's also about demonstrating that simple ideas can have an important impact on public health.''
The outcome of Study 13 was published in The Lancet in February 2009. The study focused on the value of applying rectal artesunate to arrest malaria’s progress in people at risk of death or permanent brain damage for long enough to enable them to reach proper treatment.
The BMJ judges said that Gomes and her team had produced an outstanding study. "Time is of the essence in treating severe malaria, yet many sufferers live days away from definitive treatment. This trial provided a rigorous test of a treatment strategy adapted to such circumstances. The researchers demonstrated that those children who received the study treatment early were less likely to die or be left with a disability," the judges said.
In many parts of Africa and Asia, travel is difficult if not dangerous or impossible for the very ill, as transport is rarely available in the evening. A few hours’ delay can mean the difference between life and death for those with severe malaria. For patients that survive, this can still mean living with permanent neurological damage.
Previous studies demonstrated that an artesunate suppository was effective in killing parasites in patients brought to hospital, and that it was superior to quinine. This study addressed the question of whether trained community members in remote rural areas could give a suppository to patients unable to take oral medication and then send them to clinics for further diagnosis and treatment. Malaria currently claims the life of one African child nearly every 30 seconds.
The study showed that for patients who came too late for treatment and for those able to get to a clinic quickly, rectal artesunate could not help much. But for patients who could not get to a clinic within six hours after treatment (half of whom could not get to a clinic within 15 hours), pre-referral rectal artesunate halved the risk of death or permanent disability.
Rectal artesunate is under development as an inexpensive generic product for which marketing approval is being sought. Should it gain regulatory approval, it could help reduce malaria mortality as an affordable and accessible complement to the artemisinin combination therapies (ACTs), which TDR also studied and provided evidence for effectiveness and use in rural areas. All efforts will be made to keep the price of each suppository under 10 U.S. cents.
TDR Director Robert Ridley said this study is a good example of TDR's focus – how to get treatments that work to people in poor, remote areas. "By working with local investigators and community members, simple, workable solutions were identified and proven. This is a critical approach that will help develop a better overall health system."
The preparatory work and the clinical trial itself took nearly ten years and involved more than 17 800 malaria patients, mainly children, in remote areas of Bangladesh, Ghana and the United Republic of Tanzania. Gomes said the “brilliant” investigators and dedicated field researchers deserve credit for the study’s successful outcome.
Abul M Faiz led the trial in Bangladesh, first supported by a capacity-building grant and subsequently by R&D funding for the clinical trial on rectal artesunate. During his career, he has been professor of medicine, principal and acting dean of Dhaka Medical College, director of the new Bangladesh Institute for Tropical Diseases and director-general of the nation's Health Services.
John Gyapong, director of the Health Research Unit of Ghana’s Health Service, was principal investigator in that country, supported by Fred Binka, now dean of the School of Public Health, College of Health Sciences, University of Ghana. Marian Warsame, formerly with the United Republic of Tanzania’s National Institute of Medical Research (NIMR) and now with the Case Management Unit of WHO's Global Malaria Programme, led the trial in the United Republic of Tanzania, with support from Andrew Kitua, former NIMR director-general.
“Huge credit must also go to the thinking that led to this work – from Peter Folb, Nicholas White and Richard Peto – who supported the concept and contributed to the strategy, design and analyses,” Gomes said.
Gomes joined TDR in 1991 to build capacity in field research/epidemiology, and led a task force to improve use of antimalarials and a task force on severe disease later in that decade. While working in South East Asia, the observation that locally produced artemisinin suppositories had helped reduced malaria mortality led her to persuade TDR’s director and its steering committee on malaria chemotherapy, among whose members were Folb and White to test this approach using artesunate. Thus began the drug development path, and eventually the field trials.
''The simple idea is near to becoming a reality in remote locations where it is impossible to reach the hospital at night,'' said Gomes. ''An affordable drug available for severe malaria is within sight; the next step is to ensure that available tools - bednets, ACTs and rectal artesunate - are affordable and used to prevent mortality.''