Cutaneous Leishmaniases
Conditions
Keywords
leishmania, leishmaniasis, cutaneous leishmaniasis, neglected tropical disease, immunoparasitology
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.
Interventions
DIAGNOSTIC_TESTskin biopsy
4mm skin biopsy
DIAGNOSTIC_TESTvenous blood sample (plasma, PBMC, WB)
venous blood sample to acquire plasma, PBMCs and whole blood
GENETICvenous blood sample (HLA)
venous blood sample used for HLA typing
GENETICskin slit
genome sequencing of parasite DNA that is extracted from the skin slit
Sponsors
University of Gondar
University of York
Maastricht University
University Hospital, Antwerp
Institute of Tropical Medicine, Belgium
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
12 Years to 50 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
Countries
Ethiopia
Outcome results
None listed