L. major infection: Natural history and determinants of resistance

L. 重大感染：自然史和耐药性的决定因素

• 批准号: 7284542
• 负责人: AFIF BEN SALAH
• 金额: $ 14.55万
• 依托单位: INSTITUT PASTEUR DE TUNIS
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-10-01 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7284542
• 关键词: Address; Age; Age Distribution; Antibodies; Antigens; Area; Atrophic; Bite; Burn injury; Characteristics; Cicatrix; Clinical; Cohort Studies; Color; Communities; Condition; Cosmetics; Cutaneous; Cutaneous Leishmaniasis; Development; Disease; Economic Factors; Educational Background; Environmental Risk Factor; Evaluation; Exposure to; Failure; Family; Future; Gender; Goals; Head; Height; Heterogeneity; Household; Hyperpigmentation; Hypersensitivity skin testing; Hypertrophy; Hypopigmentation; Immune; Immune response; Immunologic Factors; Incidence; Income; Individual; Infection; Intervention; Jird; Knowledge; Leishmania; Leishmaniasis; Lesion; Life; Location; Measures; Natural History; Natural Resistance; Older Population; Outcome; Parasites; Patients; Pharmaceutical Preparations; Plastic Surgeon; Policy Maker; Population; Predictive Value; Predisposition; Prevalence; Prevention; Prevention strategy; Preventive; Primary Prevention; Property; Prospective Studies; Psammomys; Public Health; Rate; Reaction; Recording of previous events; Recurrence; Relative (related person); Research Design; Research Personnel; Resistance; Risk; Risk Factors; Saliva; Sampling; Sand Flies; Score; Severities; Severity of illness; Skin; System; Testing; Time; Ulcer; Vaccine Clinical Trial; Vaccines; Weight; age group; base; cohort; concept; cytotoxic; disease transmission; drug efficacy; follow-up; improved; leishmanin; outcome forecast; pressure; programs; prospective; size; tool; transmission process; vaccine evaluation; vector

Determinants of susceptibility/resistance and natural history of L. major infection in endemic foci include environmental and host related risk factors. Our long term goal is to elucidate the natural history of L. major infection and to weight the relative importance of host related risk factors of cutaneous leishmaniasis (CL) emergence and severity considering the confounding effect of environmental factors influencing exposure. The specific hypothesis is that the natural history of L. major infection and the clinical expression of cutaneous leishmaniasis varies according to past history of transmission and to the type of biotope in the study area. Host related immunological surrogates of protection other than leishmanin skin test (LSI)prior to transmission might explain resistance to the disesase and might be used as efficacy criteria in the context of vaccines' evaluation in the field. Based on these observations the focus of project 1 is to refine bya prospective cohort population based study the estimation of the epidemetric parameters and clinical description of disease and transmission dynamics to improve the understanding of natural history of Leishmania (L.)major infection and its determinants. The specific aims are to: 1. Elucidate epidemetric parameters of L. major infection. We will use leishmanin skin test (LST) and clinical observations, the incidence of CL versus asymptomatic infection (LST+/lesions-) in a two years prospective study in order to determine: i) the prevalence of LST positivity, ii) the rate of conversion and reversion of LST, iii)the incidence of symptomatic/ asymptomatic infection, iv) the score severity of disease, v) the rate of recurrence, vi) the predictive value and the protection fraction of LST positivity. 2. To evaluate the relative importance of immune host related factors and environmental on the natural history and clinical expression of the disease. These include LST, cytotoxic immune response and antibodies against sand flies' saliva antigens, distance to colonized area by reservoirs, characteristics of dwelling and its compound, socio-economic factors and pathogenic properties of L. major isolates. 3. To develop and validate scales for severity of cutaneous lesions and quality of resulting scars. The scale items include size of the ulcer, color (hypopigmentation, hyperpigmentation, normal skin) and height.

感病/抗性和自然史的决定因素。地方性疫源地的主要感染包括 环境和宿主相关风险因素。我们的长期目标是阐明L.主要 感染并权衡皮肤利什曼病（CL）宿主相关危险因素的相对重要性 考虑到影响暴露的环境因素的混杂效应， 具体的假设是，L.主要感染和临床表现 皮肤利什曼病根据过去的传播史和 研究区宿主相关的免疫保护替代物，而不是利什曼宁皮肤试验（LSI）， 传播可以解释对疾病的抵抗，并可用作治疗的有效性标准。 疫苗的实地评估。基于这些观察，项目1的重点是改进 基于前瞻性队列人群的研究， 描述疾病和传播动力学，以提高对自然历史的理解， 利什曼原虫（L.）主要感染及其决定因素。具体目标是： 1.阐明了L.严重感染我们将使用 利什曼菌素皮肤试验（LST）和临床观察，CL与无症状感染的发生率 (LST+/病变-），以确定：i）LST阳性的患病率，ii） LST的转换和逆转率，iii）有症状/无症状感染的发生率，iv） 疾病严重程度评分，v）复发率，vi）预测值和保护分数， LST阳性。 2.评价免疫宿主相关因素和环境因素对自然免疫的相对重要性， 病史和临床表现。这些包括LST，细胞毒性免疫反应和抗体 对白蛉唾液抗原的敏感性、距水库定殖区的距离、栖息地的特征、 其组成、社会经济因素和致病特性。主要分离株。 3.开发和验证皮肤病变严重程度和瘢痕质量的量表。规模 项目包括溃疡的大小、颜色（色素沉着不足、色素沉着过度、正常皮肤）和身高。