Spatial Analysis of Host-parasite Interactions in Cutaneous Leishmaniasis in Ethiopia
- Conditions
- Cutaneous Leishmaniases
- Interventions
- Diagnostic Test: skin biopsyDiagnostic Test: venous blood sample (plasma, PBMC, WB)Genetic: venous blood sample (HLA)Genetic: skin slit
- Registration Number
- NCT05332093
- Lead Sponsor
- Institute of Tropical Medicine, Belgium
- Brief Summary
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.
- Detailed Description
Specific objectives:
1. 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).
2. To study the genomic diversity of L. aethiopica and identify features associated with the different clinical presentations (whole genome sequencing).
3. To understand how parasites respond to the microenvironmental conditions and define parasite survival niches (digital spatial profiling).
4. 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).
5. To investigate the association between patient outcomes and the above host/parasite factors at baseline.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 92
- Willing and able to provide informed consent
- Clinically confirmed CL diagnosis
- Between 12 and 50 years of age
- 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
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Mucocutaneous leishmaniasis patients group (MCL) skin slit mucocutaneous leishmaniasis patients Healthy control patients group Belgium (HC - Belgium) skin biopsy healthy control patients undergoing plastic surgery in Belgium Local cutaneous leishmaniasis patients group (LCL) venous blood sample (plasma, PBMC, WB) local cutaneous leishmaniasis patients Local cutaneous leishmaniasis patients group (LCL) venous blood sample (HLA) local cutaneous leishmaniasis patients Mucocutaneous leishmaniasis patients group (MCL) venous blood sample (HLA) mucocutaneous leishmaniasis patients Diffuse cutaneous leishmaniasis patients group (DCL) venous blood sample (plasma, PBMC, WB) diffuse cutaneous leishmaniasis patients Healthy control patients group Ethiopia (HC - Ethiopia) skin biopsy healthy control patients undergoing elective surgery in Northern Ethiopia Local cutaneous leishmaniasis patients group (LCL) skin biopsy local cutaneous leishmaniasis patients Mucocutaneous leishmaniasis patients group (MCL) venous blood sample (plasma, PBMC, WB) mucocutaneous leishmaniasis patients Diffuse cutaneous leishmaniasis patients group (DCL) skin biopsy diffuse cutaneous leishmaniasis patients Local cutaneous leishmaniasis patients group (LCL) skin slit local cutaneous leishmaniasis patients Mucocutaneous leishmaniasis patients group (MCL) skin biopsy mucocutaneous leishmaniasis patients Diffuse cutaneous leishmaniasis patients group (DCL) venous blood sample (HLA) diffuse cutaneous leishmaniasis patients Diffuse cutaneous leishmaniasis patients group (DCL) skin slit diffuse cutaneous leishmaniasis patients
- Primary Outcome Measures
Name Time Method Spatially resolved determination of the metabolic profile of the CL lesion using spatial OMx 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 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 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 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 Day 0 The digital spatial profiling will indicate the different microenvironmental conditions and parasite survival niches.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
University of Gondar
🇪🇹Gondar, Amhara, Ethiopia