Researchers in Cameroon, for example, are presenting new preliminary evidence confirming the declining effectiveness of commonly used malaria drugs, particularly sulfadoxine-pyrimethamine (SP) but also amodiaquine (AQ), and the two in combination, AQ+SP. (Tuesday, 3:20 p.m., Bubinga Hall, Parallel Session 9, Presentation 57)
Wilfred Mbacham of the University of Yaoundé, a lead investigator on the study, which was funded by the Gates Malaria Partnership, said, "Scientists have known the drugs were losing their effectiveness to varying degrees but we lacked comprehensive data showing precisely how people in Cameroon responded to the medications. Such analysis is critical to providing solid support for changing treatment policies to those that advocate replacing older drugs with newer so-called artemisinin-based combination therapies or ACT's."
Scientists have found that malaria today responds quickly and is less likely to develop resistance to a course of treatment that combines artemisinin, a particularly potent antimalarial derived from the wormwood plant, with another antimalarial. The challenge now for many governments is to procure sufficient supplies of ACT's both at a price that is affordable and in a form that simplifies treatment.
In addition, Mbacham said another challenge is to systematically monitor patients and the malaria parasite for any signs of resistance emerging to ACT's. For example, he said scientists are studying parasites in malaria endemic areas for evidence of any genetic mutation that may be linked with an ability to overcome ACT's.
But as his recent study of drug resistance in Cameroon--which involved more than 750 patients at three different sites--revealed, resistance can be difficult to detect as responses to malaria medications can vary among different populations.
"We were surprised to find that between populations in the north and the south of Cameroon, there are different levels of resistance to certain malaria drugs, between the north and the south," said Mbacham. "We know that there are genetic differences between the parasite populations in the north compared to the south, but we do not know whether that increases responsiveness to the drugs or not. We also know that you can compare different West African populations living side by side and find different levels of malaria-specific antibodies which may also affect treatment outcome."
Robert Guiguemde of the Muraz Center in Burkina-Faso, who is chairing the MIM session on drug resistance, said the critical issue now is preventing the emergence of resistance to ACT's in Africa, and that will require educating patients about the need to adhere to a specific treatment regimen.
"We often see people stopping their treatment as soon as they feel better," he said. "But even if they believe they have recovered, there are still parasites in their system that have not all been killed and those that remain are likely to be the parasites least sensitive to the drug. They will then multiply and spread and the drugs will start losing their effectiveness."
"A key to keeping track of resistance is to maintain the research capacity in Africa required to routinely monitor both people and parasites," said Andreas Heddini, the MIM Secretariat coordinator. "You need the scientists on the ground collecting blood samples in different populations and different geographic areas, and you need the laboratory instrumentation and expertise required to quickly probe these samples for some of the known genetic markers of resistance. We also need to study patient behavior since resistance can be linked to a variety of behavior issues, such as whether people take a full course of treatment."
The MIM conference will feature several presentations offering evidence of parasite resistance to familiar malaria drugs and the challenges of replacing these treatments with ACT's. For example:
- Michael Alifrangis of the Center for Medical Parasitology in Copenhagen will discuss a study that found evidence in blood samples taken in two villages in northern Tanzania of a genetic variation in the malaria parasite that may be associated with an ability to resist amodiaquine (AQ), which is sometimes used in combination with artemisinin. The study notes that while amodiaquine resistance has been noted at several sites in Africa, the genetic variation linked to resistance had not yet been observed on the continent. Researchers conclude that "its occurrence on the African continent is of great concern to the future use of AQ, including in artemisinin-based combination." (Thursday, 12:25 p.m., Ebony Hall, Parallel Session 22, Presentation 145)
- New data from a study of children in Western Kenya challenges the position that ACT's can substantially reduce transmission of malaria by clearing children of the malaria parasite at the stage in its lifecycle in which it is passed from humans back to mosquitoes. Researchers from the Radboud University Medical Center in the Netherlands, along with colleagues from Kenya's International Center for Insect Physiology and Ecology (ICIPE) and the Kenyan Medical Research Institute (KEMRI), found that the majority of ACT-treated children they studied were capable of infecting mosquitoes. "The presented findings are sobering for future interventions aimed at reducing malaria transmission by the use of antimalaria drugs," the study concludes. (Wednesday, 1:00 p.m., Poster Session 8, Poster 143B)
- While ACT's are now the preferred treatment for malaria, Tom Sukwa of the World Health Organization's Regional Office for Africa will present a report that notes, among other things, that ACT's cost ten times more than once commonly used--but increasingly ineffective--drugs. His presentation will also address the fact that there is only one "pre-qualified fixed formulation of ACT registered with WHO and that, in 2005, demand exceeded supply." The report also considers the need for more data on the safety of ACT's and the lack of oversight systems in African countries for monitoring adverse reactions. (Thursday, 2:50 p.m., Bubinga Hall, Parallel Session 25, Presentation 161)
To provide coordinated international approach to fighting malaria, the Roll Back Malaria Partnership (RBM) (www.rollbackmalaria.org) was launched in 1998 by the World Health Organization, the United Nations Children's Fund (UNICEF), the United Nations Development Programme (UNDP) and the World Bank. The Partnership now brings together governments of countries affected by malaria, their bilateral and multilateral development partners, the private sector, non-governmental and community-based organizations, foundations, and research and academic institutions around the common goal of halving the global burden of malaria by 2010. World Malaria Report 2005 http://rbm.
The Multilateral Initiative on Malaria (MIM) (www.mim.su.se), launched in Dakar, Senegal in 1997, is an international alliance of organizations and individuals seeking to maximize the impact of scientific research against malaria in Africa to ensure that research findings yield practical health benefits. The MIM Secretariat was previously hosted for 3-years terms by the Wellcome Trust (UK) and the Fogarty International Center at the National Institutes of Health (US). In 2003, the Secretariat moved to Stockholm, Sweden, where it is hosted by the Karolinska Institute and Stockholm University.
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