Host immunity to Plasmodium falciparum and the assessment of emerging artemisinin resistance in a multinational cohort
JournalProceedings of the National Academy of Sciences of the United States of America
PublisherNational Academy of Sciences
MetadataShow full item record
AbstractArtemisinin-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 (PCt1/2) after artesunate treatment and kelch13 mutations. Linear mixed-effects modeling of pooled individual patient data assessed the association between antibody responses and PCt1/2. P. falciparum antibodies were lowest in areas where the prevalence of kelch13 mutations and slow PCt1/2 were highest [Spearman ρ = −0.90 (95% confidence interval, −0.97, −0.65), and Spearman ρ = −0.94 (95% confidence interval, −0.98, −0.77), respectively]. P. falciparum antibodies were associated with faster PCt1/2 (mean difference in PCt1/2 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 PCt1/2 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 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.
SponsorsAntibody work and analysis was supported by the National Health and Medical Research Council of Australia, the Australian Research Council, Ramaciotti Establishment Grant 3245/2011 and Ian Potter Foundation Grant, and a Victorian State Government Operational Infrastructure Support grant. The clinical trials were funded by the UK Department for International Development, with additional support from the Worldwide Antimalarial Resistance Network and the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, NIH.
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85016431294&doi=10.1073%2fpnas.1615875114&partnerID=40&md5=2c78bfb454deab871df8b0421cab04d0; http://hdl.handle.net/10713/10029