The Intransigence of Malaria in Malawi: Understanding Hidden Reservoirs, Successful Vectors and Prevention Failures

马拉维疟疾的顽固性：了解隐藏的宿主、成功的媒介和预防失败

• 批准号: 9902313
• 负责人: Don P Mathanga
• 金额: $ 164.69万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9902313
• 关键词: 5 year old; Address; Africa; Anopheles Genus; Anti-Inflammatory Agents; Cerebral Malaria; Characteristics; Child; Clinical; Clonality; Communities; Country; DNA analysis; Data; Diagnostic tests; Disease; Disease Progression; Distributional Activity; Effectiveness; Entomology; Environment; Epidemiology; Evaluation; Failure; Frequencies; Goals; Growth; Heterogeneity; Hospitals; Hot Spot; Human; Immune response; Incidence; Individual; Infection; Insect Vectors; Insecticide Resistance; Insecticides; Intervention; Investigation; Knowledge; Laboratories; Life; Link; Longitudinal Studies; Malaria; Malaria prevention; Malawi; Medicine; Methods; Parasitemia; Parasites; Parasitic infection; Pathogenesis; Pattern; Pediatric Research; Peripheral Blood Mononuclear Cell; Plasma; Plasmodium; Population; Positioning Attribute; Prevalence; Prevention; Probability; Procedures; Process; RNA; Radial; Recommendation; Research; Research Design; Rural; Sampling; School-Age Population; Scourge; Severity of illness; Source; Southern Africa; Suggestion; Surface Antigens; Surveys; Symptoms; Teaching Hospitals; Training; Treatment Efficacy; Universities; Variant; age group; base; cohort; college; electronic data; epidemiology study; evidence based guidelines; experience; improved; malaria infection; malaria transmission; member; molecular vector; mortality; pathogen; prevent; programs; success; transmission process; vector; ward

At the population level, malaria remains an intractable problem in Malawi, a small but ecologically diverse country in southeastern Africa. The reasons for malaria's intransigence are enigmatic, but new findings emerging from our current ICEMR investigations have provided some clues:  Plasmodium parasite infection prevalence is greater in school-age children than in under-five year olds  School-age children are also most likely to carry gametocytes, the stage infectious to Anopheles vectors  Molecular (q-PCR) diagnostic tests revealed low-level infection in people who were asymptomatic, hence not being treated ("hidden reservoirs"), hence a likely source of undetected transmission  Anopheles vector abundance varied across a 20-km radius around a major urban center, with "hot spots" being linked to micro-environmental heterogeneity, and not to a simple urban-rural designation  Prevention failures may result from insecticide resistance and patterns of insecticide treated net use. At the individual level, only a small proportion of people infected with Plasmodium parasites ever experience symptoms of malaria illness; most co-exist asymptomatically with the parasite. An even smaller proportion evolves into severe and complicated malaria, but the mortality rates are high. The mechanisms underlying progression along the infection-to-disease spectrum are not known, in part because reliably identifying individuals at the infection extremes (persistently asymptomatic and life-threatening cerebral malaria) has only recently become feasible. The Malawi ICEMR team has the capacity to sustain long-term observations of human cohorts in different transmission settings and to collect extensive ecological, entomological and parasitological data to evaluate:  patterns of pathogen transmission and human host responses,  effectiveness of multiple interventions against transmission and infection in different environments,  relationships between infection frequency/duration and disease severity,  impacts of insecticide resistance and insecticide treated net (ITN) quality and use on disease patterns,  contributions of parasite growth rate, clonality, pro- and anti-inflammatory host responses  importance of “holes” in the immune response to variant surface antigens to disease progression. Over the course of seven years of research, which will span Malawi's next large national ITN distribution program, the Malawi ICEMR will identify why malaria control efforts in Malawi have been ineffective thus far, and will provide data-driven suggestions regarding approaches that are more likely to be effective. Studies will be undertaken in three ecologically and epidemiologically different districts that span a range of transmission intensities. Analyses of changing transmission and disease will compare patterns before, during and after the nation-wide ITN distribution program.

在人口层面，疟疾仍然是马拉维的一个棘手问题，马拉维是一个面积虽小但生态多样化的国家。 疟疾顽固不化的原因是个谜，但有新的发现。 我们目前的 ICEMR 调查提供了一些线索：  学龄儿童的疟原虫感染患病率高于五岁以下儿童 学龄儿童也最有可能携带配子体，这是按蚊媒介的传染阶段  分子 (q-PCR) 诊断测试显示无症状人群中存在低水平感染，因此 没有得到治疗（“隐藏的储存库”），因此可能是未被发现的传播源  按蚊媒介丰度在主要城市中心周围 20 公里半径范围内变化，存在“热点” 与微观环境异质性有关，而不是与简单的城乡名称有关  预防失败可能是由于杀虫剂抗药性和杀虫剂处理过的蚊帐使用模式造成的。 在个人层面上，只有一小部分感染疟原虫的人曾经经历过 疟疾疾病的症状；大多数与寄生虫无症状共存，比例甚至更小。 演变为严重且复杂的疟疾，但死亡率很高。 其背后的机制。 沿着感染到疾病谱的进展尚不清楚，部分原因是可靠地识别 处于感染极端（持续无症状且危及生命的脑型疟疾）的个体仅 最近变得可行。 马拉维 ICEMR 团队有能力对不同地区的人类群体进行长期观察 传播环境并收集广泛的生态、昆虫学和寄生虫学数据以评估： 病原体传播和人类宿主反应的模式，  在不同环境中针对传播和感染采取多种干预措施的有效性，  感染频率/持续时间与疾病严重程度之间的关系，  杀虫剂抗性和杀虫剂处理网 (ITN) 质量和使用对疾病模式的影响， 寄生虫生长率、克隆性、促炎和抗炎宿主反应的贡献  对变异表面抗原的免疫反应中的“漏洞”对疾病进展的重要性。 经过七年的研究，这将涵盖马拉维下一个大型全国驱虫蚊帐分布 计划中，马拉维 ICEMR 将查明马拉维的疟疾控制工作迄今为止为何无效的原因， 并将提供有关更可能有效的方法的数据驱动建议。 在三个生态和流行病学不同的地区进行，这些地区跨越了不同的传播范围 对传播和疾病变化的分析将比较传播之前、期间和之后的模式。 全国 ITN 分发计划。