期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 114, 期 13, 页码 3515-3520出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1615875114
关键词
malaria; artemisinin; drug resistance; immunity; serology
资金
- National Health and Medical Research Council of Australia [1060785, APP637406, 637396, APP1077636, 1104975]
- Australian Research Council [FT130101122, FT0992317]
- Ramaciotti Establishment Grant [3245/2011]
- Potter Foundation Grant
- Victorian State Government Operational Infrastructure Support grant
- UK Department for International Development
- Worldwide Antimalarial Resistance Network
- Intramural Research Program of the National Institute of Allergy and Infectious Diseases, NIH
- Wellcome Trust of Great Britain
- National Health and Medical Research Council of Australia [1060785] Funding Source: NHMRC
- Australian Research Council [FT0992317, FT130101122] Funding Source: Australian Research Council
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 independent of antimalarial drugs. We hypothesized 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 Plasmodium 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 (PCt(1/2)) after artesunate treatment and kelch13 mutations. Linear mixed-effects modeling of pooled individual patient data assessed the association between antibody responses and PCt(1/2). P. falciparum antibodies were lowest in areas where the prevalence of kelch13 mutations and slow PCt(1/2) were highest [Spearman. = -0.90 (95% confidence interval, -0.97, -0.65), and Spearman. = -0.94 (95% confidence interval, -0.98, -0.77), respectively]. P. falciparum antibodies were associated with faster PCt(1/2) (mean difference in PCt(1/2) according to seropositivity, -0.16 to -0.65 h, depending on antigen); antibodies have a greater effect on the clearance of kelch13 mutant compared with wild-type parasites (mean difference in PCt(1/2) according to seropositivity, -0.22 to -0.61 h faster in kelch13 mutants compared with wild-type parasites). Naturally acquired immunity accelerates the clearance of artemisininresistant 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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