Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA.
Division of Infectious Diseases, School of Medicine, Duke University, Durham, NC, USA.
Clin Infect Dis. 2021 Oct 5;73(7):1176-1184. doi: 10.1093/cid/ciab357.
Repeated exposure to malaria infections could protect against symptomatic progression as people develop adaptive immunity to infections acquired over time.
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.
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.
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.
人们对感染获得的适应性免疫会随着时间的推移而增强，因此反复接触疟疾感染可能会防止症状进展。
我们研究了新的、反复的和持续的恶性疟原虫感染如何与出现症状的疟疾相比与无症状疟疾的发病几率相关。我们使用肯尼亚西部的一个为期 14 个月的纵向队列，使用两种多态性基因（pfama1 和 pfcsp）的扩增子深度测序来评估个体连续感染中获得的寄生虫基因型（由单倍型表示）的重叠。我们假设新的单倍型感染会增加出现症状性疟疾的几率。
排除初始感染后，我们在 186 人中共观察到 534 例无症状感染和 88 例有症状感染。我们检测到 109 个 pfcsp 单倍型，每个感染都被归类为含有新的、反复的或持续的单倍型。与仅反复出现的单倍型感染相比，仅出现新单倍型的偶发性感染发生有症状疟疾的几率更高[比值比（OR）：3.24；95%置信区间（CI）：1.20-8.78]，但同时出现新的和反复的单倍型（OR：0.64；95% CI：0.15-2.65）则不然。评估持续感染，与仅有持续单倍型的感染相比，具有混合（持续存在新的或反复的单倍型）单倍型的感染（OR：0.77；95% CI：0.21-2.75）与有症状疟疾无关。pfama1 的结果相似。
这些结果证实，与仅反复出现的单倍型感染相比，仅有新单倍型的偶发性感染与出现症状性疟疾的几率增加相关，但当单倍型在连续感染中持续存在时，这种关系并不明显。
