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: 10397138
• 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/10397138
• 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; 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-Sulfadoxine; Recording of previous events; Research; Risk; Rural; Seasons; Shapes; Site; Spatial Distribution; Testing; Therapeutic; Time; Variant; Vulnerable Populations; World Health Organization; age group; aged; base; disorder risk; 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.

项目总结 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岁以下儿童是最易受疟疾影响的群体，占67%。 占全世界疟疾死亡人数的272 000人。世卫组织非洲地区是感染人数最多的地区 2018年疟疾死亡人数占所有疟疾死亡人数的94%。在疟疾季节性传播较强的地区， 几项研究表明，通过使用间歇性预防措施，疟疾感染人数急剧下降 治疗3至59个月大的孕妇和幼儿。季节性 这些幼儿的疟疾化学预防(SMC)包括磺胺多辛疗程- 乙胺嘧啶加阿莫地喹在疟疾季节每月给药，以维持治疗效果 在整个疟疾风险最大的时期，抗疟疾药物在血液中的浓度。尽管 SMC提供的大量好处，一个令人担忧的问题是，SMC将损害获得保护性 免疫反应，从而增加了晚年患病的风险。研究表明，年龄的变化 疟疾易感性的高峰期，实施后年龄较大的儿童更容易感染疾病 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- 马里中部农村小镇班达卡拉的儿童疟疾发病率 二十年来的研究网站。这将包括三个年龄组：0-4岁(代表#年的目标群体 SMC)、5-10岁(接受SMC的“混合”儿童和没有接受SMC的大龄儿童)和11-18岁 年(没有SMC的历史)。我们会将无症状疟疾和有症状疟疾的发病率与 在社区实施季节性疟疾化学预防之前，在类似的地层中进行测量。 利用定制的蛋白质芯片，我们将按年龄组比较疟疾抗原的抗体反应。 在实施SMC之前和实施时。我们将识别和绘制寄生虫水库的空间分布图。 (包括有症状和无症状的寄生虫携带)使用超敏感的分子测试和 确定无症状寄生虫携带者热点，特别是在旱季(1月至5月)。旱季是 特别值得注意的是，在此期间，寄生虫携带(有症状或无症状携带)和 传播率(配子体携带)非常低，人体内寄生虫的储备量显著减少。 因此，旱季是消灭疟疾的关键时间窗口。这项研究的结果 将确定SMC在马里儿科人群中的后果，并确定寄生虫宿主，帮助 为未来的疟疾控制战略制定新的方法，包括治疗高发人群 在确定的热点地区无症状携带蚊子并以蚊子种群为目标。