Department of Medicine, Stanford University, Stanford, California, USA.
Infectious Diseases Research Collaboration, Kampala, Uganda.
Clin Infect Dis. 2021 Nov 16;73(10):1887-1895. doi: 10.1093/cid/ciab245.
Infants are protected against Plasmodium falciparum malaria. Mechanisms that drive this protection remain unclear due to a poor understanding of malaria clinical phenotypes during infancy.
We enrolled a birth cohort of 678 infants in Busia, Uganda, an area of high malaria transmission. We followed infants through 12 months of age and quantified protection against parasitemia and clinical disease.
Symptomatic malaria incidence increased from 1.2 to 2.6 episodes per person-year between 0 and <6 months and between 6 and 12 months of age, while the monthly probability of asymptomatic parasitemia given infection decreased from 32% to 21%. Sickle cell trait (HbAS) was protective against symptomatic malaria (incidence rate ratio = 0.57 comparing HbAS vs hemoglobin AA (HbAA); 95% confidence interval, 0.44-0.74; P < .001), but age modified this relationship (Pint = <0.001), with nonlinear protection that waned between 0 and 9 months of age before increasing. Increasing age was associated with higher parasite densities at the time of infection and, in infants with HbAS, a reduced ability to tolerate high parasite densities without fever.
Age-dependent changes in HbAS protective efficacy in infancy were accompanied by differential loss of antiparasite and antidisease protection among HbAS and HbAA infants. This provides a framework for investigating the mechanisms that underlie infant protection against malaria.
NCT02793622.
婴儿对恶性疟原虫疟疾具有免疫力。由于对婴儿期疟疾临床表型缺乏了解，导致驱动这种保护的机制仍不清楚。
我们在乌干达布西亚的一个高疟疾传播地区招募了 678 名婴儿的出生队列。我们对婴儿进行了 12 个月的随访，并量化了对寄生虫血症和临床疾病的保护作用。
有症状疟疾的发病率从 0 至<6 个月和 6 至 12 个月时的 1.2 例/人年增加到 2.6 例/人年，而感染后无症状寄生虫血症的每月概率从 32%下降到 21%。镰状细胞特征（HbAS）对有症状疟疾具有保护作用（HbAS 与血红蛋白 AA（HbAA）相比，发病率比为 0.57；95%置信区间，0.44-0.74；P<0.001），但年龄改变了这种关系（Pint<0.001），0 至 9 个月时保护作用呈非线性减弱，然后增加。年龄增长与感染时寄生虫密度增加有关，并且在 HbAS 婴儿中，在不发热的情况下耐受高寄生虫密度的能力降低。
婴儿期 HbAS 保护效果随年龄变化而变化，同时 HbAS 和 HbAA 婴儿的抗寄生虫和抗疾病保护作用也发生差异丧失。这为研究婴儿对疟疾的保护机制提供了框架。
NCT02793622。
