Exposure to Diverse Plasmodium falciparum Genotypes Shapes the Risk of Symptomatic Malaria in Incident and Persistent Infections: A Longitudinal Molecular Epidemiologic Study in Kenya

Kelsey M Sumner; Elizabeth Freedman; Judith N Mangeni; Andrew A Obala; Lucy Abel; Jessie K Edwards; Michael Emch; Steven R Meshnick; Brian W Pence; Wendy Prudhomme-O'Meara; Steve M Taylor

doi:10.1093/cid/ciab357

Exposure to Diverse Plasmodium falciparum Genotypes Shapes the Risk of Symptomatic Malaria in Incident and Persistent Infections: A Longitudinal Molecular Epidemiologic Study in Kenya

Clin Infect Dis. 2021 Oct 5;73(7):1176-1184. doi: 10.1093/cid/ciab357.

Authors

Kelsey M Sumner^{1

2}, Elizabeth Freedman², Judith N Mangeni³, Andrew A Obala⁴, Lucy Abel⁵, Jessie K Edwards¹, Michael Emch^{1

6}, Steven R Meshnick¹, Brian W Pence¹, Wendy Prudhomme-O'Meara^{2

3

7}, Steve M Taylor^{1

2

7}

Affiliations

¹ Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA.
² Division of Infectious Diseases, School of Medicine, Duke University, Durham, NC, USA.
³ School of Public Health, College of Health Sciences, Moi University, Eldoret, Kenya.
⁴ School of Medicine, College of Health Sciences, Moi University, Eldoret, Kenya.
⁵ Academic Model Providing Access to Healthcare, Moi Teaching and Referral Hospital, Eldoret, Kenya.
⁶ Department of Geography, University of North Carolina, Chapel Hill, NC, USA.
⁷ Duke Global Health Institute, Duke University, Durham, NC, USA.

Abstract

Background: Repeated exposure to malaria infections could protect against symptomatic progression as people develop adaptive immunity to infections acquired over time.

Methods: We investigated how new, recurrent, and persistent Plasmodium falciparum infections were associated with the odds of developing symptomatic compared with asymptomatic malaria. Using a 14-month longitudinal cohort in Western Kenya, we used amplicon deep sequencing of 2 polymorphic genes (pfama1 and pfcsp) to assess overlap of parasite genotypes (represented by haplotypes) acquired within an individual's successive infections. We hypothesized infections with novel haplotypes would increase the odds of symptomatic malaria.

Results: After excluding initial infections, we observed 534 asymptomatic and 88 symptomatic infections across 186 people. We detected 109 pfcsp haplotypes, and each infection was classified as harboring novel, recurrent, or persistent haplotypes. Incident infections with only new haplotypes had higher odds of symptomatic malaria when compared with infections with only recurrent haplotypes [odds ratio (OR): 3.24; 95% confidence interval (CI), 1.20-8.78], but infections with both new and recurrent haplotypes (OR: 0.64; 95% CI: 0.15-2.65) did not. Assessing persistent infections, those with mixed (persistent with new or recurrent) haplotypes (OR: 0.77; 95% CI: 0.21-2.75) had no association with symptomatic malaria compared with infections with only persistent haplotypes. Results were similar for pfama1.

Conclusions: These results confirm that incident infections with only novel haplotypes were associated with increased odds of symptomatic malaria compared with infections with only recurrent haplotypes but this relationship was not seen when haplotypes persisted over time in consecutive infections.

Keywords: adaptive immunity; asymptomatic; falciparum malaria.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Asymptomatic Infections
Genotype
Humans
Kenya / epidemiology
Longitudinal Studies
Malaria, Falciparum* / epidemiology
Plasmodium falciparum* / genetics

Abstract

Publication types

MeSH terms

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