Journal
JOURNAL OF INFECTIOUS DISEASES
Volume 219, Issue 12, Pages 1969-1979Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiz027
Keywords
malaria infections; malaria antigens; malaria immunity; artemisinin combination therapy; Western Kenya; malaria-holoendemic areas; drug treatment
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Funding
- Armed Forces Health Surveillance Center-Department of Defense Global Emerging Infections System
- Consortium for National Health Research [RCDG-2012-032/alternative-2014]
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Background. The impact of preexisting immunity on the efficacy of artemisinin combination therapy must be examined to monitor resistance, and for implementation of new treatment strategies. Methods. Serum samples obtained from a clinical trial in Western Kenya randomized to receive artemether-lumefantrine (AL) or artesunate-mefloquine (ASMQ) were screened for total immunoglobulin G against preerythrocytic and erythrocytic antigens. The association and correlation between different variables, and impact of preexisting immunity on parasite slope half-life (t(1/2)) was determined. Results. There was no significant difference in t(1/2), but the number of individuals with lag phase was significantly higher in the AL than in the ASMQ arm (29 vs 13, respectively; P <.01). Circumsporozoite protein-specific antibodies correlate positively with t(1/2) (AL, P =.03; ASMQ, P =.09), but negatively with clearance rate in both study arms (AL, P =.16; ASMQ, P =.02). The t(1/2) correlated negatively with age in ASMQ group. When stratified based on t(1/2), the antibody titers against circumsporozoite protein and merozoite surface protein 1 were significantly higher in participants who cleared parasites rapidly in the AL group (P =.01 and P =.02, respectively). Conclusion. Data presented here define immunoprofiles associated with distinct responses to 2 different antimalarial drugs, revealing impact of preexisting immunity on the efficacy of artemisinin combination therapy regimens in a malaria-holoendemic area.
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