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

• Published in: The Journal of infectious diseases 2019-05, Vol.219 (12), p.1969-1979
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Adolescent; Antibodies, Protozoan - blood; Antigens; Antimalarials - therapeutic use; Artemether; Artemether, Lumefantrine Drug Combination - therapeutic use; Artemisinin; Artesunate; Child; Child, Preschool; Circumsporozoite protein; Clinical trials; Combination therapy; Female; Humans; Immunoglobulin G; Infant; Kenya; Lag phase; Malaria; Malaria - drug therapy; Malaria - epidemiology; Malaria - immunology; Male; Mefloquine; Mefloquine - therapeutic use; Merozoite surface protein 1; Parasite Load; Proteins
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jiz027

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. NCT01976780.