Spatial Analysis of Host-parasite Interactions in the Skin Across the Clinical Spectrum of Cutaneous Leishmaniasis in Ethiopia
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 92
- 试验地点
- 1
- 主要终点
- Spatially resolved determination of the metabolic profile of the CL lesion using spatial OMx
研究概览
简要总结
Cutaneous leishmaniasis manifestations range from self-healing localized skin ulcers/nodules to diffusely spread chronic lesions. Knowledge on the host-parasite interactions underpinning the different clinical presentations is scarce, in particular for L. aethiopica infections where disease can be extremely severe. Our aim is to define differences in skin immune responses and parasite virulence in CL patients at single cell/parasite level and how it underpins the different clinical presentations (localised, mucocutaneous and diffuse), by producing the first spatially-resolved 'ecological' map of the lesions.
详细描述
Specific objectives:
- To profile the full heterogeneity in skin and lesion immunity (single cell RNAseq), and the cellular microenvironment surrounding infected and non-infected macrophages (digital spatial profiling).
- To study the genomic diversity of L. aethiopica and identify features associated with the different clinical presentations (whole genome sequencing).
- To understand how parasites respond to the microenvironmental conditions and define parasite survival niches (digital spatial profiling).
- Study metabolic determinants of skin immunity (e.g. lipid metabolism, bioenergetics, short-chain fatty acids) in the context of key structural features of the skin landscape known to influence local metabolism and immune response (e.g. adipose tissue, follicles, microvasculature) (SpatialOMx).
- To investigate the association between patient outcomes and the above host/parasite factors at baseline.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 12 Years 至 50 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Willing and able to provide informed consent
- •Clinically confirmed CL diagnosis
- •Between 12 and 50 years of age
排除标准
- •Difficult or too painful sampling zone (see skin biopsy procedure below)
- •(Primary) lesion size < 1 cm
- •Already receiving CL treatment or received CL treatment in the last 3 months (excluding traditional medicine)
- •Known major comorbidity at time of diagnosis (e.g. VL, HIV, TB, malaria, severe intestinal helminth infection)
- •Medical history of VL
- •Severely underweight (BMI<16)
- •Known pregnancy
- •Use of immunosuppressive medication in the last month
- •Known excessive alcohol use (between >10 intakes/day and >10 intakes/week)
- •History of hypersensitivity to local anaesthetics
- •Presence of keloids/hypertrophic scars
结局指标
主要结局
Spatially resolved determination of the metabolic profile of the CL lesion using spatial OMx
时间窗: Day 0
The metabolic determinants of skin immunity (e.g. lipid metabolism, bioenergetics, short-chain fatty acids) in the context of key structural features of the skin landscape known to influence local metabolism and immune response (e.g. adipose tissue, follicles, microvasculature) will be studied by SpatialOMx.
The association between host/parasite factors and patients after treatment using clinical parameters
时间窗: Month 6
Patients are clinically assessed at day 0 (baseline visit), day 28 and month 6. These clinical assessments include a medical questionnaire and lesion assessment, and are compared with the single cell RNA sequencing and spatial resolution data to define potential causal relations between patient outcomes and immunometabolic factors.
Spatially resolved immunological characterization of the CL lesion using single cell RNA sequencing and digital spatial profiling
时间窗: Day 0
Using single cell RNA sequencing and digital spatial profiling methods, we will profile the full heterogeneity in healthy skin/lesion immunity and the cellular microenvironment surrounding infected and non-infected macrophages, respectively.
Genomic characterization of L. aethiopica using whole genome sequencing
时间窗: Day 0
Whole genome sequencing will allow us to study the genomic diversity of L. aethiopica and identify features associated with the different clinical presentations.
Defining microenvironment and parasite niches in CL lesions using digital spatial profiling
时间窗: Day 0
The digital spatial profiling will indicate the different microenvironmental conditions and parasite survival niches.
次要结局
未报告次要终点