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.

项目概要 据世界卫生组织 (WHO) 称，2018 年估计有 405 000 人死于流感 疟疾。5岁以下儿童是受疟疾影响最脆弱的群体，占67%。 世卫组织非洲区域的疟疾死亡人数最多，达到 272 000 人。 2018 年，疟疾死亡占所有疟疾死亡的 94%。在疟疾高度季节性传播的地区， 一些研究表明，通过使用间歇性预防措施，疟疾感染率急剧下降 治疗孕妇和三至五十九个月大的幼儿 季节性。 这些幼儿的疟疾化学预防（SMC）包括磺胺多辛治疗疗程—— 在疟疾季节期间，每月间隔一次给予乙胺嘧啶加阿莫地喹，以维持治疗效果 尽管在疟疾风险最大的时期，血液中抗疟药物的浓度。 SMC 提供了实质性的好处，但人们担心 SMC 会损害保护性的获得 研究表明，随着年龄的增长，免疫反应会增加，从而增加患病的风险。 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 2016 年，SMC 在马里全国实施。该项目将测量年龄。 马里中部乡村小镇班贾加拉 (Bandiagara) 儿童疟疾的具体发病率一直是疟疾疫区 研究地点二十年。这将包括三个年龄组：0-4 岁（代表目标群体）。 SMC）、5-10 岁（接受 SMC 的儿童和未接受 SMC 的年长儿童的“混合”组）和 11-18 岁 年（无 SMC 病史），我们将比较无症状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，在类似的阶层中进行了测量。 使用定制蛋白质微阵列，我们将按年龄组比较抗体对疟疾抗原的反应 在 SMC 实施之前和实施过程中，我们将识别并绘制寄生虫储存库的空间分布图。 （包括有症状和无症状的寄生虫携带）使用超灵敏的分子测试和 定义无症状寄生虫携带者热点，特别是在旱季（一月至五月）。 特别令人感兴趣，因为在此期间，寄生虫携带（有症状或无症状携带）和 传播（配子体携带）非常低，人体寄生虫储存库显着减少。 因此，旱季是消除疟疾的关键时间窗口。 将确定 SMC 对马里儿科人群的影响并确定寄生虫储存库，有助于 制定未来疟疾控制战略的新方法，包括治疗疟疾高发人群 无症状携带和针对特定热点地区的蚊子种群。