Spatial Analysis of Host-parasite Interactions in Cutaneous Leishmaniasis in Ethiopia

NCT05332093 | Completed DMC

• 1 other identifier: 1451/20
• Study Type: observational
• Target: 92
• Locations: 1 country
• Sites: 1

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.

Conditions

Cutaneous Leishmaniases

Keywords

leishmania; leishmaniasis; cutaneous leishmaniasis; neglected tropical disease; immunoparasitology

Outcome Measures

Primary Outcomes (5)

• Spatially resolved immunological characterization of the CL lesion using single cell RNA sequencing and digital spatial profiling

  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.

  Day 0

• Genomic characterization of L. aethiopica using whole genome sequencing

  Whole genome sequencing will allow us to study the genomic diversity of L. aethiopica and identify features associated with the different clinical presentations.

  Day 0

• Defining microenvironment and parasite niches in CL lesions using digital spatial profiling

  The digital spatial profiling will indicate the different microenvironmental conditions and parasite survival niches.

  Day 0

• Spatially resolved determination of the metabolic profile of the CL lesion using spatial OMx

  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.

  Day 0

• The association between host/parasite factors and patients after treatment using clinical parameters

  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.

  Month 6

Study Arms (5)

Local cutaneous leishmaniasis patients group (LCL)

local cutaneous leishmaniasis patients

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

Mucocutaneous leishmaniasis patients group (MCL)

mucocutaneous leishmaniasis patients

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

Diffuse cutaneous leishmaniasis patients group (DCL)

diffuse cutaneous leishmaniasis patients

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

Healthy control patients group Ethiopia (HC - Ethiopia)

healthy control patients undergoing elective surgery in Northern Ethiopia

Diagnostic Test: skin biopsy

Healthy control patients group Belgium (HC - Belgium)

healthy control patients undergoing plastic surgery in Belgium

Diagnostic Test: skin biopsy

Interventions

skin biopsy DIAGNOSTIC_TEST

4mm skin biopsy

Diffuse cutaneous leishmaniasis patients group (DCL); Healthy control patients group Belgium (HC - Belgium); Healthy control patients group Ethiopia (HC - Ethiopia); Local cutaneous leishmaniasis patients group (LCL); Mucocutaneous leishmaniasis patients group (MCL)

venous blood sample (plasma, PBMC, WB) DIAGNOSTIC_TEST

venous blood sample to acquire plasma, PBMCs and whole blood

Diffuse cutaneous leishmaniasis patients group (DCL); Local cutaneous leishmaniasis patients group (LCL); Mucocutaneous leishmaniasis patients group (MCL)

venous blood sample (HLA) GENETIC

venous blood sample used for HLA typing

Diffuse cutaneous leishmaniasis patients group (DCL); Local cutaneous leishmaniasis patients group (LCL); Mucocutaneous leishmaniasis patients group (MCL)

skin slit GENETIC

genome sequencing of parasite DNA that is extracted from the skin slit

Diffuse cutaneous leishmaniasis patients group (DCL); Local cutaneous leishmaniasis patients group (LCL); Mucocutaneous leishmaniasis patients group (MCL)

Eligibility Criteria

• Age: 12 Years - 50 Years
• Sex: all
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Probability Sample

Study Population

Patients presenting at the LRTC and Boru Meda Hospital with clinically suspected CL during the study period will be screened for eligibility. Suspicion for CL is assessed by physicians as per routine care. In general, children are included in the study population since they are commonly affected, and also make up the majority of DCL patients.

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Institute of Tropical Medicine, Belgium: lead
• University of Gondar: collaborator
• University of York: collaborator
• Maastricht University: collaborator
• University Hospital, Antwerp: collaborator

Study Sites (1)

University of Gondar

Gonder, Amhara, 6200, Ethiopia

Location

Biospecimen

Retention: SAMPLES WITH DNA

Blood, stool and skin samples will be isolated from CL patients and solely skin samples from healthy controls.

MeSH Terms

Conditions

Leishmaniasis, Cutaneous; Leishmaniasis; Neglected Diseases

Condition Hierarchy (Ancestors)

Euglenozoa Infections; Protozoan Infections; Parasitic Diseases; Infections; Skin Diseases, Parasitic; Vector Borne Diseases; Skin Diseases, Infectious; Skin Diseases; Skin and Connective Tissue Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Wim Adriaensen, PhD

  Institute of Tropical Medicine Antwerp

  PRINCIPAL INVESTIGATOR

• Mikias Woldetensay, MD

  University of Gondar

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Target Duration: 6 Months
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 8, 2022
• First Posted: April 18, 2022
• Study Start: March 21, 2022
• Primary Completion: March 30, 2024
• Study Completion: December 31, 2024
• Last Updated: January 9, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: After completion of the primary publication
• Access Criteria: Applicants will need to fill out a data access request form

Locations

ET (1)