Integrating geographical and genetic mapping of salmonella disease in an endemic

整合地方性沙门氏菌病的地理和遗传图谱

• 批准号: 8472626
• 负责人: SAMUEL M KARIUKI
• 金额: $ 13.87万
• 依托单位: KENYA MEDICAL RESEARCH INSTITUTE (KEMRI)
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-02-15 至 2018-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8472626
• 关键词: 16 year old; Africa South of the Sahara; Age; Anemia; Antibiotic Resistance; Antibiotic susceptibility; Area; Bacterial Infections; Blood; Case-Control Studies; Child; Chromosome Mapping; Cities; Climate; Clinical; Code; Data; Diarrhea; Disease; Disease Management; Disease Outbreaks; Drug Formulations; Enrollment; Enteral; Environmental Risk Factor; Epidemiology; Epitopes; Feces; Fever; Frequencies; Future; Genes; Genetic; Genome; Genomics; Genotype; Geographic Distribution; HIV; Haplotypes; Health; Health care facility; Household; Immunity; Incidence; Infection; Institutes; Integration Host Factors; Intervention; Investigation; Kenya; Lead; Malaria; Malnutrition; Maps; Measures; Medical; Modeling; Molecular Epidemiology; Nepal; Nutritional status; Occupations; Online Systems; Outcome Study; Pathogenesis; Patients; Pattern; Persons; Phenotype; Phylogenetic Analysis; Population; Prevalence; Prevention; Prevention strategy; Preventive Intervention; Public Health; Research Infrastructure; Resistance; Resistance profile; Resources; Risk; Risk Factors; Salmonella; Salmonella infections; Sanitation; Sickle Cell Trait; Site; Slum; Spatial Distribution; Symptoms; Testing; Time; Typhoid Fever; Vaccination; Vaccines; Variant; Water Supply; Work; data mining; disorder prevention; modifiable risk; pathogen; population based; public health relevance; residence; rural area; sex; spatiotemporal; therapy design; transmission process; young adult

DESCRIPTION (provided by applicant): Little is known about the molecular epidemiology of Salmonella disease in persons residing in urban Sub-Saharan Africa. We hypothesize that there are unique genotypes of Salmonella in hotspots that cause invasive and diarrheal illnesses in children, perpetuated by specific host and environmental factors. We propose a 5-year study of population-based surveillance for invasive non-typhoidal Salmonella disease (NTS IBD) typhoid fever (TF), and NTS diarrhea (NTS D), in persons under 16 years of age in Mukuru, an urban Nairobi slum with 150,000 people. Surveillance will be undertaken at the two health care facilities serving the population. Blood and stool cultures will be obtained from age-eligible patients presenting with fever and diarrhea, respectively. Each Salmonella spp clinical isolate will undergo complete genetic sequencing and antibiotic susceptibility testing, and will be geographically mapped according to the residence of the patient. Cases of invasive and diarrheal illness will be enrolled into three case-control studies (one each for TF, invasive NTS and NTS diarrhea) to evaluate personal (including HIV and malaria co- infection, presence of sickle cell trait/disease, and nutritional status), household, and environmental risk factors. For each case age and sex-matched controls who present to the same medical facility for reasons other than fever, diarrhoea, or other enteric symptoms will be selected (1 for each TF case; 4 for NTS IBD; 4 for NTS D). We expect to enroll 93 cases of NTS IBD, 422 cases of TF, 109 cases of NTS D. With these data and activities we will 1) evaluate the incidence of invasive NTS, NTS diarrhea, and TF, as well as spatial and spatio-temporal clustering of these infections and their constituent genotypes; 2) define the transmission of NTS and TF in this setting by assessment of spatial and spatio-temporal clustering and of personal, household, and environmental risk factors for these infections and their genotypes; 3) assess the incidence and prevalence of antibiotic resistance among NTS and ST, spatial and spatio-temporal clustering of antibiotic-resistant isolates, and the association of antibiotic resistance with specific genotypes and personal, household, and environmental risk factors; 4) explore candidate genomic regions in NTS to better understand invasive NTS pathogenesis and to identify antigenic targets for future vaccines; and 5) prepare the site for future use of vaccines and non-vaccine preventive interventions by determining disease incidence, identifying potentially modifiable risk factors tha could lead to the design of interventions, and delineating risk factors and spatial-temporal clustering that facilitate targeting of interventions.

描述（由申请人提供）：关于撒哈拉以南非洲城市居民中沙门氏菌病的分子流行病学知之甚少。我们假设，在热点地区存在独特的沙门氏菌基因型，这些基因型会导致儿童的侵袭性和非传染性疾病，并由特定的宿主和环境因素延续。我们提出了一项为期5年的研究，以人群为基础的监测侵入性非伤寒沙门氏菌病（NTS IBD）伤寒（TF），和NTS腹泻（NTS D），在16岁以下的人在穆库鲁，城市内罗毕贫民窟与15万人。将在为居民服务的两个卫生保健设施进行监测。将分别从符合年龄条件的发热和腹泻患者中获得血液和粪便培养物。每种沙门氏菌临床分离株都将接受完整的基因测序和抗生素敏感性测试，并将根据患者的居住地进行地理定位。侵袭性和非侵袭性疾病病例将入组三项病例对照研究（TF、侵袭性NTS和NTS腹泻各一项），以评价个人（包括HIV和疟疾合并感染、镰状细胞性状/疾病的存在和营养状况）、家庭和环境风险因素。对于每例病例，将选择因发热、腹泻或其他肠道症状以外的原因到同一医疗机构就诊的年龄和性别匹配的对照组（每例TF病例1例; NTS IBD 4例; NTS D 4例）。我们预计将入组93例NTS IBD，422例TF，109例NTS D。通过这些数据和活动，我们将1）评估侵袭性NTS、NTS腹泻和TF的发病率，以及这些感染及其组成基因型的空间和时空聚集性; 2）通过评估空间和时空聚集性以及这些感染及其基因型的个人、家庭和环境风险因素，定义NTS和TF在这种情况下的传播; 3）评估NTS和ST中抗生素耐药性的发生率和流行率，抗生素耐药分离株的空间和时空聚集，以及抗生素耐药性与特定基因型和个人、家庭和环境风险因素的关联; 4）探索NTS中的候选基因组区域，以更好地理解侵袭性NTS发病机制并鉴定未来疫苗的抗原靶点;以及5）通过确定疾病发病率、确定可能导致干预措施设计的潜在可改变的风险因素、以及描述风险因素和便于干预措施目标确定的时空聚类，为未来使用疫苗和非疫苗预防干预措施做好准备。