Spatial Analysis of Host-parasite Interactions in Cutaneous Leishmaniasis in Ethiopia (SpatialCL)

Institute of Tropical Medicine, Belgium

Status: Completed

Conditions: Cutaneous Leishmaniases

Treatments: Diagnostic Test: skin biopsy; Genetic: venous blood sample (HLA); Genetic: skin slit; Diagnostic Test: venous blood sample (plasma, PBMC, WB)

Study type: Observational

Funder types: Other

Identifiers

NCT05332093

1451/20

Details and patient eligibility

About

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.

Full 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.

Enrollment: 92 patients

Sex: All

Ages: 12 to 50 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Willing and able to provide informed consent
• Clinically confirmed CL diagnosis
• Between 12 and 50 years of age

Exclusion criteria

• 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

Trial design

92 participants in 5 patient groups

Local cutaneous leishmaniasis patients group (LCL)

Description:

local cutaneous leishmaniasis patients

Treatment:

Diagnostic Test: venous blood sample (plasma, PBMC, WB)

Genetic: skin slit

Genetic: venous blood sample (HLA)

Diagnostic Test: skin biopsy

Mucocutaneous leishmaniasis patients group (MCL)

Description:

mucocutaneous leishmaniasis patients

Treatment:

Diagnostic Test: venous blood sample (plasma, PBMC, WB)

Genetic: skin slit

Genetic: venous blood sample (HLA)

Diagnostic Test: skin biopsy

Diffuse cutaneous leishmaniasis patients group (DCL)

Description:

diffuse cutaneous leishmaniasis patients

Treatment:

Diagnostic Test: venous blood sample (plasma, PBMC, WB)

Genetic: skin slit

Genetic: venous blood sample (HLA)

Diagnostic Test: skin biopsy

Healthy control patients group Ethiopia (HC - Ethiopia)

Description:

healthy control patients undergoing elective surgery in Northern Ethiopia

Treatment:

Diagnostic Test: skin biopsy

Healthy control patients group Belgium (HC - Belgium)

Description:

healthy control patients undergoing plastic surgery in Belgium

Treatment:

Diagnostic Test: skin biopsy