Clinical trial NCT05332093: Spatial Analysis of Host-parasite Interactions in Cutaneous Leishmaniasis in Ethiopia
Official title: Spatial Analysis of Host-parasite Interactions in the Skin Across the Clinical Spectrum of Cutaneous Leishmaniasis in Ethiopia
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Cutaneous Leishmaniases
Keywords: leishmania
leishmaniasis
cutaneous leishmaniasis
neglected tropical disease
immunoparasitology
Lead sponsor: Institute of Tropical Medicine, Belgium
Sponsor class: OTHER
Collaborators: name: University of Gondar
name: University of York
name: Maastricht University
name: University Hospital, Antwerp
First posted: 2022-04-18
Enrollment: 92
Sex: ALL
Minimum age (years): 12
Maximum age (years): 50
Standard ages: CHILD
ADULT
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Spatially resolved immunological characterization of the CL lesion using single cell RNA sequencing and digital spatial profiling
timeFrame: Day 0
measure: Genomic characterization of L. aethiopica using whole genome sequencing
timeFrame: Day 0
measure: Defining microenvironment and parasite niches in CL lesions using digital spatial profiling
timeFrame: Day 0
measure: Spatially resolved determination of the metabolic profile of the CL lesion using spatial OMx
timeFrame: Day 0
measure: The association between host/parasite factors and patients after treatment using clinical parameters
timeFrame: Month 6
Secondary outcomes:
Other outcomes:
Locations:
city: Gondar
country: Ethiopia
facility: University of Gondar
state: Amhara
Study officials:
affiliation: Institute of Tropical Medicine Antwerp
name: Wim Adriaensen, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Gondar
name: Mikias Woldetensay, MD
role: PRINCIPAL_INVESTIGATOR
References: