TY - JOUR
T1 - Rational deployment of antimalarial drugs in Africa
T2 - Ahould first-line combination drugs be reserved for paediatric malaria cases?
AU - Sutherland, Colin J.
AU - Babiker, Hamza
AU - MacKinnon, Margaret J.
AU - Ranford-Cartwright, Lisa
AU - Sayed, Badria Babiker E.L.
PY - 2011/10
Y1 - 2011/10
N2 - Artemisinin-based combination therapy is exerting novel selective pressure upon populations of Plasmodium falciparum across Africa. Levels of resistance to non-artemisinin partner drugs differ among parasite populations, and so the artemisinins are not uniformly protected from developing resistance, already present in South East Asia. Here, we consider strategies for prolonging the period of high level efficacy of combination therapy for two particular endemicities common in Africa. Under high intensity transmission, two alternating first-line combinations, ideally with antagonistic selective effects on the parasite genome, are advocated for paediatric malaria cases. This leaves second-line and other therapies for adult cases, and for intermittent preventive therapy. The drug portfolio would be selected to protect the "premier" combination regimen from selection for resistance, while maximising impact on severe disease and mortality in children. In endemic areas subject to low, seasonal transmission of Plasmodium falciparum, such a strategy may deliver little benefit, as children represent a minority of cases. Nevertheless, the deployment of other drug-based interventions in low transmission and highly seasonal areas, such as mass drug administration aimed to interrupt malaria transmission, or intermittent preventive therapy, does provide an opportunity to diversify drug pressure. We thus propose an integrated approach to drug deployment, which minimises direct selective pressure on parasite populations from any one drug component. This approach is suitable for qualitatively and quantitatively different burdens of malaria, and should be supported by a programme of routine surveillance for emerging resistance.
AB - Artemisinin-based combination therapy is exerting novel selective pressure upon populations of Plasmodium falciparum across Africa. Levels of resistance to non-artemisinin partner drugs differ among parasite populations, and so the artemisinins are not uniformly protected from developing resistance, already present in South East Asia. Here, we consider strategies for prolonging the period of high level efficacy of combination therapy for two particular endemicities common in Africa. Under high intensity transmission, two alternating first-line combinations, ideally with antagonistic selective effects on the parasite genome, are advocated for paediatric malaria cases. This leaves second-line and other therapies for adult cases, and for intermittent preventive therapy. The drug portfolio would be selected to protect the "premier" combination regimen from selection for resistance, while maximising impact on severe disease and mortality in children. In endemic areas subject to low, seasonal transmission of Plasmodium falciparum, such a strategy may deliver little benefit, as children represent a minority of cases. Nevertheless, the deployment of other drug-based interventions in low transmission and highly seasonal areas, such as mass drug administration aimed to interrupt malaria transmission, or intermittent preventive therapy, does provide an opportunity to diversify drug pressure. We thus propose an integrated approach to drug deployment, which minimises direct selective pressure on parasite populations from any one drug component. This approach is suitable for qualitatively and quantitatively different burdens of malaria, and should be supported by a programme of routine surveillance for emerging resistance.
KW - Malaria
KW - drug resistance
KW - rational therapeutics
UR - http://www.scopus.com/inward/record.url?scp=84855698085&partnerID=8YFLogxK
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U2 - 10.1017/S0031182011001144
DO - 10.1017/S0031182011001144
M3 - Article
C2 - 21810298
AN - SCOPUS:84855698085
SN - 0031-1820
VL - 138
SP - 1459
EP - 1468
JO - Parasitology
JF - Parasitology
IS - 12
ER -