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. Using high-resolution genotyping of over 800 P falciparum infections collected in a 14-month Kenyan cohort, we observed that exposure to new genotypes increased the risk of symptomatic malaria, and this risk was attenuated by recurrent and persistent genotypes.
【저자키워드】 Adaptive immunity, Asymptomatic, falciparum malaria,