Age of exposure and immunity to malaria in infants

针对恶性疟原虫疟疾的自然获得性免疫（NAI）的发展知之甚少。先前对婴儿连续和间歇性化学预防的研究提供了证据，表明婴儿期首次接触恶性疟原虫的年龄可能对确定NAI的发展很重要，这可以通过生命第二年的临床疟疾发病率来衡量。这些研究表明，在5个月大之前暴露于恶性疟原虫不会导致NAI的发展，而在5个月大之后暴露于恶性疟原虫会导致NAI的发展。总体目标是评估在婴儿不同时期暴露于恶性疟原虫红细胞期抗原对NAI发展的影响。为了探讨年龄对NAI形成的影响，我们在莫桑比克南部的一个流行区设计了一项3臂随机双盲安慰剂对照试验，在该试验中，我们选择性地控制在婴儿期不同时期（2-5个月、5-10个月或无）接触恶性疟原虫，每月用磺胺嘧啶-乙胺嘧啶+青蒿琥酯进行化学预防。婴儿将在出生时从艾滋病毒阴性妇女中招募，并分配到三个队列中的一个，每个队列98名儿童。参与者将通过主动和被动病例检测和横断面调查进行随访，直至24个月大。将比较两个队列在出生后第二年内临床疟疾和贫血的风险，以及其与免疫应答类型和质量（几种恶性疟原虫抗原的抗体、细胞因子）、氧化应激标志物和宿主遗传因素的相关性。这些结果应阐明生命早期抗恶性疟原虫反应发展的决定因素和生命早期免疫接种的潜在限制。

The development of naturally acquired immunity (NAI) against Plasmodium falciparum (P.falciparum) malaria is poorly understood. Previous studies of continuous and intermittent chemoprophylaxis in infants have provided evidence that the age of first exposure to P.falciparum during infancy may be important in determining the development of NAI, as measured by incidence of clinical malaria during the second year of life. These studies suggest that exposure to P. falciparum prior to 5 months of age does not result in the development of NAI, while exposure to P. falciparum after 5 months of age leads to development of NAI. The overall objective is to evaluate the effect of exposure to P. falciparum erythrocytic stage antigens during different periods of infancy on the development of NAI. In order to explore the effect of age in the build-up of NAI we have designed a 3-arm randomized double-blind placebo-controlled trial in an endemic area of southern Mozambique in which we selectively control exposure to P. falciparum at different periods during infancy (2-5 months, 5-10 months or none) with monthly chemoprophylaxis with Sulphadoxine- Pyrimethamine + Artesunate. Infants will be enrolled at birth from HIV-negative women and allocated to one of three cohorts of 98 children each. Participants will be followed up by active and passive case detection and cross-sectional surveys until 24 months of age. The risk of clinical malaria and anaemia during the second year of life will be compared between cohorts, as well as its correlation with the type and quality of immune responses (antibodies to several P. falciparum antigens, cytokines), oxidative stress markers and host genetic factors. These results should shed light on the determinants of the development of anti-P. falciparum responses early in life and the potential constraints to early life immunisation.