Abstract

BACKGROUND: Reductions in malaria transmission decrease naturally acquired immunity, which may influence the emergence of Plasmodium falciparum artemisinin-resistant phenotypes and genotypes over time.

METHODS: Antibodies specific for P. falciparum antigens were determined in uncomplicated hyperparasitemic malaria patients over a 10-year period of declining malaria transmission and emerging artemisinin resistance in northwestern Thailand. We investigated the association between antibody levels and both parasite clearance time (PCt½) and artemisinin resistance-associated kelch13 genotypes over time.

RESULTS: Immunity to P. falciparum declined prior to 2004, preceding the emergence of artemisinin resistance-associated genotypes and phenotypes (maximum mean change in antibody level per year: anti-MSP142 = -0.17; 95% confidence interval [CI] = -.31 to -.04; P = .01). In this period of declining immunity, and in the absence of kelch13 mutations, PCt½ increased. Between 2007 and 2011, levels of antibodies fluctuated, and higher antibody levels were associated with faster PCt½ (maximum yearly change in PCt½, in hours: EBA140rII = -0.39; 95% CI = -.61 to -.17; P < .001).

CONCLUSIONS: Understanding the impact of changing transmission and immunity on the emergence of artemisinin resistance is important particularly as increased malaria control and elimination activities may enhance immunological conditions for the expansion of artemisinin-resistant P. falciparum.

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This work was supported by the National Health and Medical Research Council of Australia (NHMRC; training fellowship no. GNT1060785 to F. J. I. F.; senior research fellowship no. 1104975 to J. A. S. and no. 1077636 to J. G. B.; project grant no. 1046575 to F. J. I. F., J. A. S., and F. N.), Australian Research Council (Future Fellowship number FT130101122 to F.  J. I.  F.), Ramaciotti Establishment grant (to F.  J. I.  F.). Funding from the Victorian State Government Operational Infrastructure Support scheme and the NHMRC Independent Research Institutes Infrastructure Support Scheme supported the Burnet Institute. The clinical study was done as part of the Wellcome Trust–Mahidol University–Oxford Tropical Medicine Research Program (grant B9RTOZ2) supported by the Wellcome Trust of Great Britain. Work in San Antonio was funded by the National Institutes for Health (R37 AI048071 to T. A.) and the Bill and Melinda Gates Foundation (grant no. OPP1040463) and was conducted in facilities constructed with support from a Research Facilities Improvement Program grant (grant no. C06 RR013556) from the National Center for Research Resources.