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

季节性疟疾化学预防对马里儿童疟疾发病率、抗体反应和寄生虫储存库的特定年龄影响

• 批准号: 10596555
• 负责人: DRISSA COULIBALY
• 金额: $ 13.5万
• 依托单位: UNIV OF SCIENCES, TECH & TECH OF BAMAKO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-23 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10596555
• 关键词: Affect; Africa South of the Sahara; African; Age; Age Months; Alleles; Amodiaquine; Antibody Response; Antigens; Antimalarials; Area; Artemisinins; Beds; Biological Assay; Blood; Cause of Death; Cessation of life; Chemoprevention; Child; Childhood; Cohort Studies; Combined Modality Therapy; Communities; Culicidae; Custom; Disease; Dryness; Epidemiology; Future; Geographic Information Systems; Goals; Home; Human; Immune response; Impairment; Incidence; Insecticides; Intervention; Knowledge; Location; Malaria; Mali; Maps; Measures; Medicine; Molecular; Parasitemia; Parasites; Pharmaceutical Preparations; Plasmodium; Plasmodium falciparum; Population; Predisposition; Pregnancy; Pregnant Women; Preventive treatment; Prospective, cohort study; Protein Array; Protein Microchips; Pyrimethamine; Recommendation; Recording of previous events; Research; Risk; Rural; Seasons; Shapes; Site; Spatial Distribution; Sulfadoxine; Testing; Therapeutic; Time; Variant; Vulnerable Populations; World Health Organization; age group; aged; detection assay; disorder risk; human old age (65+); infancy; interest; malaria infection; malaria transmission; novel strategies; prevent; transmission process; vaccine evaluation

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.

项目摘要 根据世界卫生组织（WHO）的数据，2018年，估计有40.00万人死亡 疟疾。 5岁以下的儿童是受疟疾影响的最脆弱的群体，占67％ （272 000）全球所有疟疾死亡。非洲地区是最多的家园 疟疾死亡，2018年所有疟疾死亡的94％。在季节性疟疾传播高度的地区， 几项研究表明，通过间歇性预防性使用疟疾感染急剧下降 治疗三到五十九个月的孕妇和幼儿。季节性 这些幼儿中的疟疾化学预防（SMC）包括磺胺毒素 - 在疟疾季节以每月间隔给予乙胺胺加氨基喹喹以维持治疗 在最大的疟疾风险中，血液中的抗疟疾药物浓度。尽管有 SMC提供的重大好处，一个问题是SMC会损害获得保护 免疫反应，从而增加了后来的疾病风险。研究表明年龄变化 对疟疾的峰值敏感性，实施后，年龄较大的孩子更容易受到疾病的影响 控制策略。 2016年，SMC在马里全国实施。该项目将衡量年龄 - 班迪亚加拉（Bandiagara）的儿童疟疾的具体发病率是马里中部的一个乡村小镇 研究站点已有二十年。这将包括三个年龄组：0-4岁（代表目标组 SMC），5-10岁（一组“混合”的儿童，他们收到了SMC和未没有的年龄较大的孩子）和11-18 年（没有SMC的历史）。我们将比较渐近和症状疟疾的事件 在社区中实施季节性疟疾化学预防之前，以类似的地层进行测量。 使用自定义蛋白质微阵列，我们将按年龄组对疟疾抗原的抗体反应进行比较 使用SMC实施。我们将识别和绘制寄生虫储层的空间分布 （包括症状和不对称寄生虫载体）使用超敏感的分子测试和 定义无症状的寄生虫载体热点，尤其是在旱季（1月至5月）。干季是 特别值得一提的是，在此期间，寄生虫载体（有症状或不对称载体）和 传播（配子载体载体）非常低，寄生虫的人类储层显着降低。 因此，干旱季节是消除疟疾的关键临时机会窗口。这项研究的结果 将定义SMC在马里小儿种群中的后果，并识别寄生虫的水库，有助于 为未来的疟疾控制策略塑造新方法，包括治疗人口高 在定义的热点中，无症状的载体和靶向蚊子种群。