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Correlation Between Malaria-Specific Antibody Profiles and Responses to Artemisinin Combination Therapy for Treatment of Uncomplicated Malaria in Western Kenya.

Odhiambo, Geoffrey; Bergmann-Leitner, Elke; Maraka, Moureen; Wanjala, Christine N L; Duncan, Elizabeth; Waitumbi, John; Andagalu, Ben; Jura, Walter G Z O; Dutta, Sheetij; Angov, Evelina; Ogutu, Bernhards R; Kamau, Edwin; Ochiel, Daniel.
J Infect Dis; 219(12): 1969-1979, 2019 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-30649381


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.


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 (t½) was determined.


There was no significant difference in t½, 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 t½ (AL, P = .03; ASMQ, P = .09), but negatively with clearance rate in both study arms (AL, P = .16; ASMQ, P = .02). The t½ correlated negatively with age in ASMQ group. When stratified based on t½, 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).


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. CLINICAL TRIALS REGISTRATION NCT01976780.
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