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J Infect Dis. 2017 Sep 15;216(6):723-731. doi: 10.1093/infdis/jix371.

Declining Transmission and Immunity to Malaria and Emerging Artemisinin Resistance in Thailand: A Longitudinal Study.

Author information

1
Disease Elimination Program, Burnet Institute.
2
Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot,Thailand.
3
Texas Biomedical Research Institute, San Antonio.
4
Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne.
5
Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand.
6
Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine Research, University of Oxford, United Kingdom.
7
Department of Epidemiology and Preventive Medicine, Department of Infectious Diseases, Monash University, Melbourne, Australia.

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.

KEYWORDS:

Plasmodium falciparum; antibodies; artemisinin; drug resistance; immunity; malaria

PMID:
28934435
PMCID:
PMC5853569
DOI:
10.1093/infdis/jix371
[Indexed for MEDLINE]
Free PMC Article

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