The age-specific impact of seasonal malaria chemoprevention on malaria incidence, antibody responses, and parasite reservoirs in Malian children

项目摘要 根据世界卫生组织（WHO）的数据，2018年，估计有40.5万人死于 疟疾5岁以下儿童是受疟疾影响的最脆弱群体，占67% (272 000）的疟疾死亡人数。世卫组织非洲区域是世界上 2018年疟疾死亡人数占所有疟疾死亡人数的94%。在疟疾季节性传播严重的地区， 几项研究表明，通过使用间歇性预防措施， 治疗孕妇和3至59个月的幼儿。季节性 这些幼儿的疟疾化学预防（SMC）包括磺胺嘧啶治疗疗程， 在疟疾流行季节每月给予乙胺嘧啶加阿莫地喹， 在疟疾风险最高的整个时期，抗疟疾药物在血液中的浓度。尽管 虽然SMC提供了大量好处，但一个问题是SMC会损害保护性的获得， 免疫反应，从而增加了晚年患病的风险。研究表明随着年龄的增长 疟疾易感性达到高峰，年龄较大的儿童在实施后更容易患病 的控制策略。2016年，SMC在马里全国范围内实施。这个项目将测量年龄- 马里中部农村城镇班迪亚加拉的儿童疟疾具体发病率，该城镇一直是疟疾流行区 20年的研究基地。这将包括三个年龄组：0-4岁（代表 5-10岁（接受SMC的儿童和未接受SMC的较大儿童的“混合”群体）和11-18岁（接受SMC的儿童和未接受SMC的较大儿童的“混合”群体）。 年（无SMC病史）。我们将比较无症状疟疾和有症状疟疾的发病率， 在社区实施季节性疟疾化学预防之前，在类似阶层中进行测量。 使用定制的蛋白质微阵列，我们将按年龄组比较疟疾抗原的抗体反应 实施SMC之前和之后。我们将确定并绘制寄生虫宿主的空间分布图 （包括有症状和无症状的寄生虫携带）， 定义无症状寄生虫携带者热点，特别是在旱季（一月至五月）。旱季是 特别令人感兴趣的是，在此期间，寄生虫携带（有症状或无症状携带）和 传播（配子体携带）的可能性非常低，人体寄生虫宿主显著减少。 因此，旱季是消灭疟疾的一个关键的时间窗口。本研究结果 将确定SMC在马里儿科人群中的后果，并确定寄生虫宿主， 为未来的疟疾控制战略制定新的方法，包括治疗高疟疾发病率人群， 无症状携带和以确定热点的蚊子种群为目标。

PROJECT SUMMARY According to the World Health Organization (WHO), in 2018, there were an estimated 405 000 deaths from malaria. Children aged under 5 years are the most vulnerable group affected by malaria and accounted for 67% (272 000) of all malaria deaths worldwide. The WHO African Region was home to the highest number of malaria deaths in with 94% of all malaria deaths in 2018. In regions with highly seasonal malaria transmission, several studies have shown a sharp decline in malaria infections through the use of intermittent preventive treatment pregnant women and young children between the ages of three and fifty-nine months. Seasonal malaria chemoprevention (SMC) in these young children consists of treatment courses of sulfadoxine– pyrimethamine plus amodiaquine given at monthly intervals during the malaria season to maintain therapeutic anti-malarial drug concentrations in the blood throughout the period of greatest malaria risk. Despite the substantial benefits provided by SMC, one concern is that SMC will impair the acquisition of protective immune responses, thereby increasing the risk of disease in later years. Studies have shown changes in the ages of peak susceptibility to malaria, with older children more vulnerable to disease following the implementation of control strategies. In 2016, SMC was implemented nationwide in Mali. This project will measure the age- specific incidence of malaria in children in Bandiagara, a rural town in central Mali that has been a malaria field research site for two decades. This will include three age groups: 0-4 years (representing the targeted group for SMC), 5-10 years (a “mixed” group of children who received SMC and older ones who did not) and 11-18 years (no history of SMC). We will compare the incidence of asymptomatic and symptomatic malaria to that measured in similar strata before the implementation of seasonal malaria chemoprevention in the community. Using custom protein microarrays, we will compare the antibody responses to malaria antigens by age group before and with SMC implementation. We will identify and map the spatial distribution of parasite reservoirs (including both symptomatic and asymptomatic parasite carriage) using ultra-sensitive molecular testing and define asymptomatic parasite carrier hotspots, particularly in the dry season (January to May). The dry season is of particular interest because during this period, parasite carriage (symptomatic or asymptomatic carriage) and transmission (gametocyte carriage) are very low, and the human reservoir of parasites is significantly reduced. The dry season is thus a critical temporal window of opportunity to eliminate malaria. The results of this study will define the consequences of SMC in pediatric populations in Mali and identify parasite reservoirs, helping to shape new approaches for future malaria control strategies, including treating populations with high asymptomatic carriage and targeting mosquito populations in defined hotspots.