Host immunity and the assessment of emerging artemisinin resistance in a multinational cohort
38 Artemisinin-resistant falciparum malaria, defined by a slow-clearance phenotype and the presence of kelch13 mutants, has emerged in the Greater Mekong Subregion. Naturally-acquired immunity to malaria clears parasites independently of antimalarial drugs. We hypothesise that between- and within-po...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
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National Academy of Sciences
2017
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| Summary: | 38 Artemisinin-resistant falciparum malaria, defined by a slow-clearance phenotype and the presence of kelch13 mutants, has emerged in the Greater Mekong Subregion. Naturally-acquired immunity to malaria clears parasites independently of antimalarial drugs. We hypothesise that between- and within-population variations in host immunity influence parasite clearance after artemisinin treatment and the interpretation of emerging artemisinin resistance. Antibodies specific to 12 P. falciparum sporozoite and blood-stage antigens were determined in 959 patients (from 11 sites in Southeast Asia) participating in a multinational cohort study assessing parasite clearance half-life (PCt½) after artesunate treatment and kelch13 mutations. Linear mixed-effects modelling of pooled individual patient data assessed the association between antibody responses and PCt½. P. falciparum antibodies were lowest in areas where the prevalence of kelch13 mutations and slow PCt½ were highest (Spearman ρ = -0·90 (95% CI: -0·97, -0·65) and -0·94 (-0·98, -0·77) respectively). P. falciparum antibodies were associated with faster PCt½ (mean difference in PCt½ according to seropositivity -0·16 to -0·65 hours depending on antigen); antibodies have a greater impact on the clearance of kelch13 mutant compared to wild-type parasites (mean difference in PCt½ according to seropositivity -0·22 to -0·61 hours faster in kelch13 mutants compared to wild-type parasites). Naturally-acquired immunity accelerates the clearance of artemisinin-resistant parasites in patients with falciparum malaria, and may confound the current working definition of artemisinin resistance. Immunity may also play an important role in the emergence and transmission potential of artemisinin-resistant parasites. |
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