Epidemiology and molecular mechanisms of anthelminthic treatment failure in Kinta

近打驱虫药治疗失败的流行病学和分子机制

• 批准号: 9067288
• 负责人: Michael D Wilson
• 金额: $ 10.38万
• 依托单位: NOGUCHI MEMORIAL INSTITUTE / MEDICAL RES
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-06-13 至 2017-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9067288
• 关键词: Adult; Affect; Africa South of the Sahara; Albendazole; Ancylostoma (genus); Anemia; Area; Benzimidazoles; Child; Chronic; Collaborations; Communities; Country; Data; Dietary intake; Disease; Dose; Effectiveness; Epidemiology; Genes; Genetic Polymorphism; Ghana; Goals; Growth; HIV; Health; Health Personnel; Healthcare Systems; Helminths; High Prevalence; Hookworm Infections; Hookworms; Human; Immune response; Impairment; In Vitro; Infection; Institutes; Integration Host Factors; Intestines; Laboratories; Malaria; Malnutrition; Mediating; Methods; Molecular Epidemiology; Monitor; Morbidity - disease rate; Municipalities; Mutation; Necator americanus; Nematoda; Nutritional; Nutritional status; Parasite resistance; Pharmaceutical Preparations; Pilot Projects; Policies; Population; Populations at Risk; Predisposition; Pregnant Women; Prevalence; Prevention; Preventive; Recommendation; Report (document); Research; Research Personnel; Resistance; Resources; School-Age Population; Sentinel; Site; Soil; Time; Toxic effect; Training; Treatment Failure; Tropical Disease; Tuberculosis; Tubulin; Universities; Vulnerable Populations; Work; World Health Organization; base; benzimidazole; chemotherapy; co-infection; cognitive ability; cognitive development; diagnostic biomarker; disorder control; effective therapy; follow-up; neglected tropical diseases; next generation; prevent; programs; response; study population

DESCRIPTION (provided by applicant): Approximately one billion people are infected with hookworms (Necator americanus and Ancylostoma duodenal) which are a major global cause of anemia and malnutrition. Sub-Saharan Africa has the highest prevalence (29%) of global hookworm infection. Infections are responsible for sublime morbidity including impairment of both cognitive ability and growth observed in affected children. Vulnerable groups also include pregnant women. Evidence also suggests that chronic low intensity hookworm infection may impair the ability to control other tropical diseases, including HIV, tuberculosis, and malaria. Current global programs to control soil-transmitted nematodes rely primarily on mass drug administration (MDA) with anthelminthic drugs to either reduce or prevent morbidity - preventive chemotherapy - in endemic populations. We conducted pilot studies of the epidemiology of hookworm infection in communities in Kintampo North Municipality (KNM), Ghana in 2007 and found a high prevalence of hookworm infection (45%) that correlated with poor nutritional status in adults, as well as a high rate of treatment failure (39%) following administration of single dos albendazole (400mg). A follow-up study in 2010 confirmed the high prevalence of hookworm (39%) in school age children, and 56% albendazole treatment failure. These studies confirm the limited effectiveness of albendazole in the study population, the mechanisms of which remain to be elucidated. In another preliminary study we interrogated the ß-tubulin gene as a potential benzimidazole resistance marker in human hookworms isolated from the same sites and have identified mutations that are potential markers of resistance. The specific aims of this proposed research will further define the epidemiology of hookworm infection and the specific host factors associated with albendazole treatment failure in KNM and also establish methods to detect in vitro benzimidazole resistance and corresponding gene polymorphisms for use in sentinel sites throughout Ghana. We predict that host factors, including overall nutritional status and specific dietary intake influence response to albendazole therapy and susceptibility to re-infection with hookworm and that genetically mediated resistance of hookworms to anthelminthics will emerge in communities characterized by high coincident rates of treatment failure and malnutrition.

描述（由申请人提供）：大约十亿人感染钩虫（美洲钩虫和十二指肠钩虫），这是全球贫血和营养不良的主要原因。撒哈拉以南非洲地区的钩虫感染率最高（29%）。感染导致严重的发病率，包括受影响儿童的认知能力和生长发育受损。弱势群体还包括孕妇。证据还表明，慢性低强度钩虫感染可能会损害控制其他热带疾病的能力，包括艾滋病毒、结核病和疟疾。目前控制土源性线虫的全球计划主要依靠使用驱虫药进行大规模药物管理（MDA），以减少或预防流行人群的发病率（预防性化疗）。我们于 2007 年对加纳金坦波北市 (KNM) 社区的钩虫感染流行病学进行了初步研究，发现钩虫感染患病率很高 (45%)，这与成人营养状况不佳有关，并且单剂量阿苯达唑 (400 毫克) 治疗失败率很高 (39%)。 2010年的一项后续研究证实，学龄儿童钩虫患病率很高（39%），56%的阿苯达唑治疗失败。这些研究证实阿苯达唑在研究人群中的有效性有限，其机制仍有待阐明。在另一项初步研究中，我们对从相同位点分离的人类钩虫中作为潜在苯并咪唑抗性标记的 β-微管蛋白基因进行了研究，并鉴定了作为潜在抗性标记的突变。这项研究的具体目标是进一步明确钩虫感染的流行病学以及与 KNM 中阿苯达唑治疗失败相关的特定宿主因素，并建立检测体外苯并咪唑耐药性和相应基因多态性的方法，用于加纳各地的哨点。我们预测，宿主因素，包括总体营养状况和特定饮食摄入量，会影响对阿苯达唑治疗的反应和对钩虫再次感染的易感性，并且在治疗失败和营养不良同时发生率高的社区中，将出现钩虫对驱虫药的遗传介导的耐药性。

项目成果

Application of a Poisson distribution quality control measure to the analysis of two human hookworm drug treatment studies in Ghana.

应用泊松分布质量控制措施分析加纳的两项人类钩虫药物治疗研究。

• DOI: 10.1016/j.ijpddr.2014.01.001
• 发表时间: 2014
• 期刊: International journal for parasitology. Drugs and drug resistance
• 作者: Kotze,AndrewC;Dobson,RobertJ;Humphries,Debbie;Wilson,Michael;Cappello,Michael
• 通讯作者: Cappello,Michael

Carriage of sub-microscopic sexual and asexual Plasmodium falciparum stages in the dry season at Navrongo, Ghana.

• DOI: 10.4314/gmj.v50i4.4
• 发表时间: 2016-12-01
• 期刊: Ghana medical journal
• 作者: Atelu, Geoffrey R;Duah, Nancy O;Wilson, Michael D
• 通讯作者: Wilson, Michael D