Leishmaniasis

Infectious Disease MONDO:0011989 Pathograph 3 Show in embeddings browser Neglected tropical disease Protozoal infection

Leishmaniasis is a protozoan infection caused by Leishmania parasites, transmitted by sand flies, with clinical forms including cutaneous, mucocutaneous, and visceral disease driven by intracellular amastigotes in macrophages.

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3
Pathophys.
6
Phenotypes
1
Gaps
3
Pathograph
4
Medical Actions
3
Subtypes
8
Datasets
14
References
1
Deep Research
◆

Subtypes

3
Visceral leishmaniasis MONDO:0005445
The most severe clinical form, with disseminated infection of the reticuloendothelial system. Immunosuppressed patients, including those with HIV co-infection or after solid organ transplantation, are prone to infection as well as atypical and severe courses.
Show evidence (2 references)
PMID:19634705 SUPPORT
"It manifests mainly in 3 clinical forms; visceral leishmaniasis (VL), cutaneous leishmaniasis (CL) and mucocutaneous leishmaniasis (MCL)"
The review lists visceral leishmaniasis as a main clinical form.
PMID:31297548 SUPPORT Human Clinical
"Immunosuppressed patients with HIV co-infection or after solid organ transplantation are prone to infection as well as atypical and severe courses."
Documents HIV co-infection and transplant-related immunosuppression as risk factors for atypical, severe visceral leishmaniasis.
Cutaneous leishmaniasis MONDO:0005446
Show evidence (1 reference)
PMID:19634705 SUPPORT
"It manifests mainly in 3 clinical forms; visceral leishmaniasis (VL), cutaneous leishmaniasis (CL) and mucocutaneous leishmaniasis (MCL)"
The review lists cutaneous leishmaniasis as a main clinical form.
Mucocutaneous leishmaniasis MONDO:0005859
Show evidence (1 reference)
PMID:19634705 SUPPORT
"It manifests mainly in 3 clinical forms; visceral leishmaniasis (VL), cutaneous leishmaniasis (CL) and mucocutaneous leishmaniasis (MCL)"
The review lists mucocutaneous leishmaniasis as a main clinical form.
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Discussions and Knowledge Gaps

1
Does the murine Th1-control / Th2-progression dichotomy operate in human leishmaniasis, and which human immune correlates should replace it?
HUMAN MODEL MISMATCH OPEN leishmaniasis_th1_th2_murine_mismatch
Attached to
pathophysiology#Th1-Polarized Cell-Mediated Response and Macrophage Activation pathophysiology#Th2-Polarized Response and Permissive Disease Progression
The Th1-protective / Th2-permissive polarization is established in the murine model, but the reviewed literature explicitly states that the Th1/Th2 dichotomy in the human system is not as distinct as in mice and that the murine model does not strictly apply to human leishmaniasis. Evidence therefore exists in a model system while its translational validity is the open question, which is a HUMAN_MODEL_MISMATCH rather than a plain KNOWLEDGE_GAP. Both polarization nodes are consequently curated with PARTIAL, MODEL_ORGANISM-sourced evidence.
Proposed experiments
Human T-helper polarization versus outcome in leishmaniasis cohorts
prospective clinical cohort immunophenotyping experiment Relation: this experiment is of type this experiment type This experiment is of type prospective clinical cohort immunophenotyping experiment.
exp_leish_human_th_polarization_cohort
Longitudinally profile lesion- and blood-derived CD4 T-cell cytokine programs in human cutaneous, mucocutaneous, and visceral leishmaniasis cohorts, and test whether polarization state predicts cure versus progression as it does in the murine model.
Readouts
T-helper polarization state versus clinical outcome
pathophysiology#Th1-Polarized Cell-Mediated Response and Macrophage Activation
Cross-species single-cell comparison of the T-cell compartment
cross-species single-cell transcriptomic comparison experiment Relation: this experiment is of type this experiment type This experiment is of type cross-species single-cell transcriptomic comparison experiment.
exp_leish_cross_species_tcell_scrnaseq
Compare single-cell transcriptomes of the T-cell compartment in matched human lesions and murine infection models to determine which human immune states, if any, correspond to the murine Th1 and Th2 arms.
Readouts
Correspondence of human T-cell states to murine Th1/Th2 arms
pathophysiology#Th2-Polarized Response and Permissive Disease Progression
Show evidence (1 reference)
PMID:19634705 SUPPORT Model Organism
"However, Th1 and Th2 dichotomy in the human system is not as distinct as in mice and the murine model does not strictly apply to human leishmaniasis."
States the human-versus-murine mismatch directly: the dichotomy is less distinct in humans and the murine model does not strictly translate.
⚙

Pathophysiology

3
Intracellular amastigote replication in macrophages
Promastigotes differentiate into amastigotes that multiply inside host macrophages.
macrophage CL:0000235 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves macrophage (CL:0000235). CL:0000235 is a cell type from the Cell Ontology.
Downstream
Th1-Polarized Cell-Mediated Response and Macrophage Activation Intracellular infection of macrophages engages cell-mediated immunity: resolution of infection depends on activation of targeted T-cell populations for cytokine production and on activation of macrophages. This is the protective arm of the response.
Th2-Polarized Response and Permissive Disease Progression The same infection can instead drive a Th2-polarized T-helper response, which in the murine model is associated with disease progression rather than control.
Show evidence (1 reference)
PMID:33968798 SUPPORT
"Inside vertebrate host macrophages, the parasites can differentiate into the amastigote form and multiply"
The abstract describes amastigote differentiation and replication in macrophages.
Th1-Polarized Cell-Mediated Response and Macrophage Activation
The protective arm of the T-helper response. Activation of targeted T-cell populations with appropriate cytokine production, together with activation of macrophages, underlies resolution of leishmanial infection; in the murine model, development of a Th1 response is associated with control of infection. This node therefore restrains the intracellular amastigote-replication node rather than promoting it.
T-helper 1 cell CL:0000545 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves T-helper 1 cell (CL:0000545). CL:0000545 is a cell type from the Cell Ontology. macrophage CL:0000235 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves macrophage (CL:0000235). CL:0000235 is a cell type from the Cell Ontology.
T-helper 1 type immune response GO:0042088 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased T-helper 1 type immune response (GO:0042088). GO:0042088 is a biological process from the Gene Ontology. ↑ INCREASED
Show evidence (2 references)
PMID:19634705 SUPPORT Other
"Resolution of leishmanial infection is dependent on the coordinated interactions between components of cell mediated immune response, specifically the activation of targeted T-cell populations for appropriate cytokine production and activation of macrophages."
States that infection resolution depends on cell-mediated immunity — T-cell activation with cytokine production plus macrophage activation.
PMID:19634705 SUPPORT Model Organism
"In murine model, the development of Thl response is associated with control of infection"
Attests the Th1-control association, but in the murine model only; the same review cautions that the human dichotomy is less distinct, so support is marked PARTIAL. See the `leishmaniasis_th1_th2_murine_mismatch` discussion.
Th2-Polarized Response and Permissive Disease Progression
The permissive arm of the T-helper response. In the murine model, a Th2 response is associated with disease progression rather than control of infection. Human data are less clear-cut, so this node is curated as a model-derived mechanism, not an established human one.
T-helper 2 cell CL:0000546 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves T-helper 2 cell (CL:0000546). CL:0000546 is a cell type from the Cell Ontology.
T-helper 2 type immune response GO:0042092 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased T-helper 2 type immune response, annotated with type 2 immune response (GO:0042092). GO:0042092 is a biological process from the Gene Ontology. ↑ INCREASED
Show evidence (1 reference)
PMID:19634705 SUPPORT Model Organism
"Th2 response is associated with disease progression"
Attests the Th2-progression association in the murine model. Marked PARTIAL because the same review states the Th1/Th2 dichotomy is less distinct in humans and the murine model does not strictly apply. See the `leishmaniasis_th1_th2_murine_mismatch` discussion.
⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Leishmaniasis Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.
●

Phenotypes

6
Blood 1
Pancytopenia HP:0001876 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Pancytopenia (HP:0001876). HP:0001876 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
PMID:17938629 SUPPORT
"A reduction in the number of red and white blood cells and platelets (pancytopenia) was found to be highly specific (98%) for VL in suspected clinical patients in Nepal"
The review reports pancytopenia as a highly specific finding for visceral leishmaniasis.
PMID:31297548 SUPPORT Human Clinical
"The main clinical symptoms are fever, hepatosplenomegaly and pancytopenia."
Lists pancytopenia as a main clinical symptom of visceral leishmaniasis.
Cardiovascular 1
Hepatosplenomegaly HP:0001433 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Hepatosplenomegaly (HP:0001433). HP:0001433 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
PMID:17938629 SUPPORT
"parasitic invasion of the blood and reticulo-endothelial system (that is, the general phagocytic system), such as enlarged lymph nodes, spleen and liver."
The review describes visceral leishmaniasis causing enlargement of the spleen and liver via reticuloendothelial parasitization.
PMID:31297548 SUPPORT Human Clinical
"The main clinical symptoms are fever, hepatosplenomegaly and pancytopenia."
Lists hepatosplenomegaly as a main clinical symptom of visceral leishmaniasis.
Integument 1
Cutaneous ulcers Skin ulcer HP:0200042 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Skin ulcer (HP:0200042). HP:0200042 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:19634705 SUPPORT
"Cutaneous leishmaniasis usually has milder course and often results into a self-healing of ulcers."
The review notes that cutaneous leishmaniasis produces ulcers, which often self-heal.
Metabolism 1
Fever HP:0001945 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Fever (HP:0001945). HP:0001945 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
PMID:17938629 SUPPORT
"Fever is usually associated with rigor and chills and can be intermittent."
The review describes fever as a persistent, intermittent feature of visceral leishmaniasis.
PMID:31297548 SUPPORT Human Clinical
"The main clinical symptoms are fever, hepatosplenomegaly and pancytopenia."
Lists fever as a main clinical symptom of visceral leishmaniasis.
Growth 1
Weight loss HP:0001824 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Weight loss (HP:0001824). HP:0001824 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:17938629 SUPPORT
"VL patients present symptoms and signs of persistent systemic infection (including fever, fatigue, weakness, loss of appetite and weight loss)"
The review lists weight loss among the systemic symptoms of visceral leishmaniasis.
Other 1
Nasal mucosal ulceration Nasal ulcer HP:0033361 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Nasal ulcer (HP:0033361). HP:0033361 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
DOI:10.1111/ddg.15424 SUPPORT
"characterized by granulomatous, destructive mucosal lesions in the oral, nasal, and pharyngeal cavities"
The review describes mucocutaneous leishmaniasis as producing destructive mucosal lesions including in the nasal cavity.
PMID:24897964 SUPPORT Human Clinical
"If not recognized and adequately treated, MCL may disfigure the patient because of the chronic local destruction of tissue of the nose, pharynx and palate."
Attests chronic destructive nasal, pharyngeal, and palatal tissue loss in untreated mucocutaneous leishmaniasis. Marked PARTIAL because the review documents destructive nasal mucosal disease but does not state ulceration (or septal perforation) in these words.
💊

Medical Actions

4
Liposomal amphotericin B therapy
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Liposomal amphotericin B is a standard therapy for visceral leishmaniasis in many regions.
Show evidence (1 reference)
PMID:30712769 SUPPORT
"Liposomal amphotericin B is generally found to be safe and effective in most endemic regions of the world"
The review describes liposomal amphotericin B as safe and effective.
Miltefosine
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: miltefosine CHEBI:75283 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses miltefosine (CHEBI:75283). CHEBI:75283 is a therapeutic agent from Chemical Entities of Biological Interest.
Orally administered antileishmanial agent. Its global utilization spans all major leishmaniasis forms, including visceral, cutaneous, mucocutaneous, and post-kala-azar dermal leishmaniasis.
Show evidence (2 references)
PMID:39752369 SUPPORT Other
"Miltefosine’s global utilization spans all major leishmaniasis forms, including VL, CL, MCL, and PKDL"
States that miltefosine is used across all major clinical forms of leishmaniasis.
PMID:39752369 SUPPORT Other
"Its unique oral administration convenience underscores miltefosine’s pivotal role in advancing leishmaniasis treatment modalities"
Attests the oral route of administration that distinguishes miltefosine from the injectable agents.
Pentavalent Antimonial Therapy
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: sodium stibogluconate CHEBI:28148 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses sodium stibogluconate (CHEBI:28148). CHEBI:28148 is a therapeutic agent from Chemical Entities of Biological Interest.
Pentavalent antimonials (sodium stibogluconate, meglumine antimoniate) are among the WHO 2010 first-line treatment options for certain Leishmania species; the review lists toxicity and resistance as their principal limitations.
Show evidence (2 references)
PMID:39752369 SUPPORT Other
"According to the WHO 2010 guidelines, pentavalent antimonials are among the first-line treatment options"
Attests first-line status of pentavalent antimonials under the WHO 2010 guidelines.
PMID:39752369 SUPPORT Other
"Despite toxicity and resistance (antimonials),"
Attests toxicity and resistance as the principal limitations of antimonial therapy.
Paromomycin
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: paromomycin CHEBI:7934 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses paromomycin (CHEBI:7934). CHEBI:7934 is a therapeutic agent from Chemical Entities of Biological Interest.
Aminoglycoside antibiotic effective against visceral and cutaneous leishmaniasis, widely available and affordable in endemic regions; administered mainly intramuscularly for visceral disease or topically for cutaneous disease because of limited oral bioavailability.
Show evidence (2 references)
PMID:39752369 SUPPORT Other
"Paromomycin, effective against VL and CL, is widely available and affordable, especially in endemic regions"
Attests efficacy against visceral and cutaneous leishmaniasis plus availability and affordability.
PMID:39752369 SUPPORT Other
"is mainly intramuscular for VL or topical for CL due to limited oral bioavailability"
Attests the intramuscular and topical routes of administration and the reason for them.
📊

Prevalence

1
Worldwide
Annual Incidence Common
Estimated 50,000-90,000 new visceral leishmaniasis cases and 0.5-1 million new tegumentary (cutaneous/mucocutaneous) leishmaniasis cases globally per year.
Show evidence (1 reference)
PMID:36753272 SUPPORT Other
"it is estimated that globally occur between 50 000 and 90 000 new cases of visceral leishmaniasis and between 0.5 and 1 million tegumentary leishmaniasis"
Reports global annual incidence estimates for visceral and tegumentary leishmaniasis.
🦠

Infectious Agent

1
Leishmania spp.
Protozoan parasites causing leishmaniasis.
Leishmania <genus> NCBITaxon:5658 NCBI Taxonomy (NCBITaxon)
Show evidence (1 reference)
PMID:19634705 SUPPORT
"Leishmaniasis is a parasitic disease caused by various species of Leishmania"
The review identifies Leishmania species as the cause of leishmaniasis.
↔️

Transmission

1
Sand fly blood meal transmission
Female sand flies transmit Leishmania during blood feeding.
Show evidence (1 reference)
PMID:34345133 SUPPORT
"The transmission is from female sandfly through a blood meal."
The abstract specifies sand fly blood-meal transmission.
📊

Related Datasets

8
Stratification of expression profiles of immune-related genes in the lesion of cutaneous leishmaniasis patients with L. major and L. tropica infection geo:GSE220308
There is still no reliable human vaccination against cutaneous leishmaniasis (CL), a serious public health issue in many parts of underdeveloped nations like Morocco and Iran. There are few studies comparing the expression of immune-related genes in the skin lesions of CL patients infected with L. major and L. tropica. In this study, we used dcRT-MLPA to analyze the expression profiles of 144 immune response-related genes in CL patients from Morocco and Iran who had been exposed to L. major and L. tropica, respectively.
human n=40
PMID:40100809
Identified by GEO DataSets index search for Leishmaniasis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
Post Kala Azar Dermal Leishmaniasis (PKDL) genome wide transcriptional profiling by bulk RNA-sequencing geo:GSE324689
Post-kala-azar dermal leishmaniasis (PKDL), a dermal sequel of visceral leishmaniasis (VL), is considered an important reservoir that facilitates the transmission of VL. Although PKDL lesions demonstrate an overwhelming infiltration of CD8⁺ T cells, the molecular mechanisms regulating their recruitment to the skin remain poorly defined. To address this, bulk RNA sequencing was performed on dermal lesions from patients withPKDL and healthy controls to characterize the lesional chemokine and cytokine landscape associated with T-cell homing.Transcriptomic analysis revealed a significant upregulation of genes encoding T-cell chemoattractants, including CCL3, CCL4, CCL5, CCL17, CXCL9, and CXCL10,...
human BULK RNA SEQ n=7
PMID:42497210
Identified by GEO DataSets index search for Leishmaniasis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
IL-32 producing CD8+ memory T cells and Tregs define the IDO1 / PD-L1 niche in human cutaneous leishmaniasis skin lesions geo:GSE290027
Human cutaneous leishmaniasis (CL) is characterised by chronic skin pathology. Experimental and clinical data suggest that immune checkpoints (ICs) play a crucial role in disease outcome but the cellular and molecular niches that facilitate IC expression during leishmaniasis are ill-defined. We previously showed that in Sri Lankan patients with CL, indoleamine 2,3-dioxygenase 1 (IDO1) and programmed death-ligand 1 (PD-L1) are enriched in lesion skin and that reduced PD-L1 expression early after treatment onset predicted cure rate following antimonial therapy.
human n=12
PMID:40371647
Identified by GEO DataSets index search for Leishmaniasis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
WTCCC2 Visceral Leishmaniasis (VL) samples ega:EGAS00001000773
A WTCCC2 project genome-wide association study for visceral leishmaniasis (VL) in individuals from India, Brazil and Sudan, genotyped on the custom Illumina 670k array. The WTCCC2 analysis of the Brazilian and Indian samples is described in Fakiola et al. [Nat Genet. 2013 Feb;45(2):208-13].It should be noted that due to expected family structure in the data, normal analyses of these data should include an estimation of the relatedness between the samples. For more details about sample collection for the project please refer to the Methods section of the paper above. The samples from India were all collected from Bihar state in northeastern India.
human
PMID:23291585
European Genome-phenome Archive study, matched because the disease is named in the study's own title ("Leishmaniasis"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01.
Transcriptomic signatures of CD4+ T cells from visceral leishmaniasis (VL) patients ega:EGAS00001004152
Bulk RNA-sequencing was performed on CD4+ T cells isolated from the blood of visceral leishmaniasis patients (n = 12) and endemic controls (EC; n = 12). CD4+ T cells were obtained by magnetic-activated cell sorting (MACS). Alterations in the transcripts of T helper (Th) cells during infection were identified.
human
European Genome-phenome Archive study, matched because the disease is named in the study's own title ("Leishmaniasis"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01.
A GWAS for cutaneous leishmaniasis in Brazil ega:EGAS00001004596
Our goal was to identify genetic risk factors for cutaneous leishmaniasis (CL) caused by Leishmania braziliensis. Genotyping 2066 CL cases and 2046 controls using Illumina HumanCoreExomeBeadChips provided data for 4,498,586 imputed single nucleotide variants (SNVs). Genome-wide association testing using linear mixed models took account of genetic diversity/ethnicity/admixture. Post-GWAS positional, expression quantitative trait locus (eQTL), and chromatin interaction mapping was performed in FUMA. Transcriptional data were compared between lesions and normal skin, and cytokines measured using flow cytometry and Bioplex assay.
human
European Genome-phenome Archive study, matched because the disease is named in the study's own title ("Leishmaniasis"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01.
Impact of Visceral Leishmaniasis on Local Organ Metabolism in Hamsters metabolomics_workbench:ST002347
Syrian hamster METABOLOMICS
Located via OmicsDI, which aggregates across omics repositories; this record comes from metabolomics_workbench. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title ("Leishmaniasis"). Retrieved 2026-08-02.
Ontogeny independent expression of LPCAT2 in granuloma macrophages during experimental visceral leishmaniasis massive:MSV000096486
Proteomic data relating to: Ontogeny independent expression of LPCAT2 in granuloma macrophages during experimental visceral leishmaniasis
Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title ("Leishmaniasis"). Retrieved 2026-08-02.
{ }

Source YAML

click to show 
name: Leishmaniasis
creation_date: '2026-01-26T03:01:01Z'
category: Infectious Disease
description: >-
  Leishmaniasis is a protozoan infection caused by Leishmania parasites,
  transmitted by sand flies, with clinical forms including cutaneous,
  mucocutaneous, and visceral disease driven by intracellular amastigotes
  in macrophages.
disease_term:
  term:
    id: MONDO:0011989
    label: leishmaniasis
  preferred_term: Leishmaniasis
parents:
- Neglected tropical disease
- Protozoal infection
infectious_agent:
- name: Leishmania spp.
  infectious_agent_term:
    preferred_term: Leishmania <genus>
    term:
      id: NCBITaxon:5658
      label: Leishmania <genus>
  description: Protozoan parasites causing leishmaniasis.
  evidence:
  - reference: PMID:19634705
    reference_title: "Immunobiology of leishmaniasis."
    supports: SUPPORT
    snippet: "Leishmaniasis is a parasitic disease caused by various species of Leishmania"
    explanation: The review identifies Leishmania species as the cause of leishmaniasis.
agent_life_cycle:
  description: Leishmania alternate between promastigotes in sand flies and amastigotes in mammalian macrophages.
  hosts:
  - preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
    role: definitive host
  - preferred_term: sand fly
    term:
      id: NCBITaxon:7198
      label: Phlebotominae
    role: intermediate host
  vectors:
  - sand flies (Phlebotominae)
  life_cycle_stages:
  - name: Promastigote stage in sand fly gut
    life_cycle_stage_term:
      preferred_term: promastigote stage
      term:
        id: OPL:0000151
        label: promastigote stage
    description: Motile promastigotes develop in the sand fly gut.
    evidence:
    - reference: PMID:10563394
      reference_title: "Cell biology of Leishmania."
      supports: SUPPORT
      snippet: "the sandfly, where they grow as motile flagellated promastigotes in the gut"
      explanation: The abstract states promastigote growth in the sand fly gut.
  - name: Amastigote stage in macrophage phagolysosome
    life_cycle_stage_term:
      preferred_term: amastigote stage
      term:
        id: OPL:0000114
        label: amastigote stage
    description: Non-flagellated amastigotes survive and grow intracellularly in macrophages.
    evidence:
    - reference: PMID:10563394
      reference_title: "Cell biology of Leishmania."
      supports: SUPPORT
      snippet: "the mammalian macrophage, where they survive and grow intracellularly as non-flagellated amastigotes in the phagolysosome"
      explanation: The abstract specifies intracellular amastigote growth in macrophages.
transmission:
- name: Sand fly blood meal transmission
  description: Female sand flies transmit Leishmania during blood feeding.
  evidence:
  - reference: PMID:34345133
    reference_title: "Leishmaniasis."
    supports: SUPPORT
    snippet: "The transmission is from female sandfly through a blood meal."
    explanation: The abstract specifies sand fly blood-meal transmission.
has_subtypes:
- name: Visceral leishmaniasis
  subtype_term:
    preferred_term: visceral leishmaniasis
    term:
      id: MONDO:0005445
      label: visceral leishmaniasis
  description: >-
    The most severe clinical form, with disseminated infection of the
    reticuloendothelial system. Immunosuppressed patients, including those
    with HIV co-infection or after solid organ transplantation, are prone to
    infection as well as atypical and severe courses.
  evidence:
  - reference: PMID:19634705
    reference_title: "Immunobiology of leishmaniasis."
    supports: SUPPORT
    snippet: "It manifests mainly in 3 clinical forms; visceral leishmaniasis (VL), cutaneous leishmaniasis (CL) and mucocutaneous leishmaniasis (MCL)"
    explanation: The review lists visceral leishmaniasis as a main clinical form.
  - reference: PMID:31297548
    reference_title: "[Visceral leishmaniasis]."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Immunosuppressed patients with HIV co-infection or after solid organ transplantation are prone to infection as well as atypical and severe courses."
    explanation: Documents HIV co-infection and transplant-related immunosuppression as risk factors for atypical, severe visceral leishmaniasis.
- name: Cutaneous leishmaniasis
  subtype_term:
    preferred_term: cutaneous leishmaniasis
    term:
      id: MONDO:0005446
      label: cutaneous leishmaniasis
  evidence:
  - reference: PMID:19634705
    reference_title: "Immunobiology of leishmaniasis."
    supports: SUPPORT
    snippet: "It manifests mainly in 3 clinical forms; visceral leishmaniasis (VL), cutaneous leishmaniasis (CL) and mucocutaneous leishmaniasis (MCL)"
    explanation: The review lists cutaneous leishmaniasis as a main clinical form.
- name: Mucocutaneous leishmaniasis
  subtype_term:
    preferred_term: mucocutaneous leishmaniasis
    term:
      id: MONDO:0005859
      label: mucocutaneous leishmaniasis
  evidence:
  - reference: PMID:19634705
    reference_title: "Immunobiology of leishmaniasis."
    supports: SUPPORT
    snippet: "It manifests mainly in 3 clinical forms; visceral leishmaniasis (VL), cutaneous leishmaniasis (CL) and mucocutaneous leishmaniasis (MCL)"
    explanation: The review lists mucocutaneous leishmaniasis as a main clinical form.
pathophysiology:
- name: Intracellular amastigote replication in macrophages
  description: Promastigotes differentiate into amastigotes that multiply inside host macrophages.
  cell_types:
  - preferred_term: macrophage
    term:
      id: CL:0000235
      label: macrophage
  evidence:
  - reference: PMID:33968798
    reference_title: "Involvement of Leishmania Phosphatases in Parasite Biology and Pathogeny."
    supports: SUPPORT
    snippet: "Inside vertebrate host macrophages, the parasites can differentiate into the amastigote form and multiply"
    explanation: The abstract describes amastigote differentiation and replication in macrophages.
  downstream:
  - target: Th1-Polarized Cell-Mediated Response and Macrophage Activation
    description: >-
      Intracellular infection of macrophages engages cell-mediated immunity:
      resolution of infection depends on activation of targeted T-cell
      populations for cytokine production and on activation of macrophages.
      This is the protective arm of the response.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - activation of targeted T-cell populations for appropriate cytokine production
    evidence:
    - reference: PMID:19634705
      reference_title: "Immunobiology of leishmaniasis."
      supports: SUPPORT
      evidence_source: OTHER
      snippet: "Resolution of leishmanial infection is dependent on the coordinated interactions between components of cell mediated immune response, specifically the activation of targeted T-cell populations for appropriate cytokine production and activation of macrophages."
      explanation: >-
        Links the intracellular infection to the cell-mediated arm — T-cell
        activation with cytokine production and macrophage activation — as the
        route by which infection is resolved.
  - target: Th2-Polarized Response and Permissive Disease Progression
    description: >-
      The same infection can instead drive a Th2-polarized T-helper response,
      which in the murine model is associated with disease progression rather
      than control.
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    evidence:
    - reference: PMID:19634705
      reference_title: "Immunobiology of leishmaniasis."
      supports: SUPPORT
      evidence_source: MODEL_ORGANISM
      snippet: "Th2 response is associated with disease progression"
      explanation: >-
        Attests the Th2-progression association in the murine model. Marked
        PARTIAL because the review also states the dichotomy is less distinct
        in humans.
- name: Th1-Polarized Cell-Mediated Response and Macrophage Activation
  biological_scale: CELLULAR
  role: Protective
  description: >-
    The protective arm of the T-helper response. Activation of targeted T-cell
    populations with appropriate cytokine production, together with activation
    of macrophages, underlies resolution of leishmanial infection; in the murine
    model, development of a Th1 response is associated with control of
    infection. This node therefore restrains the intracellular
    amastigote-replication node rather than promoting it.
  cell_types:
  - preferred_term: T-helper 1 cell
    term:
      id: CL:0000545
      label: T-helper 1 cell
  - preferred_term: macrophage
    term:
      id: CL:0000235
      label: macrophage
  biological_processes:
  - preferred_term: T-helper 1 type immune response
    term:
      id: GO:0042088
      label: T-helper 1 type immune response
    modifier: INCREASED
  evidence:
  - reference: PMID:19634705
    reference_title: "Immunobiology of leishmaniasis."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Resolution of leishmanial infection is dependent on the coordinated interactions between components of cell mediated immune response, specifically the activation of targeted T-cell populations for appropriate cytokine production and activation of macrophages."
    explanation: >-
      States that infection resolution depends on cell-mediated immunity —
      T-cell activation with cytokine production plus macrophage activation.
  - reference: PMID:19634705
    reference_title: "Immunobiology of leishmaniasis."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "In murine model, the development of Thl response is associated with control of infection"
    explanation: >-
      Attests the Th1-control association, but in the murine model only; the
      same review cautions that the human dichotomy is less distinct, so
      support is marked PARTIAL. See the `leishmaniasis_th1_th2_murine_mismatch`
      discussion.
- name: Th2-Polarized Response and Permissive Disease Progression
  biological_scale: CELLULAR
  role: Permissive
  description: >-
    The permissive arm of the T-helper response. In the murine model, a Th2
    response is associated with disease progression rather than control of
    infection. Human data are less clear-cut, so this node is curated as a
    model-derived mechanism, not an established human one.
  cell_types:
  - preferred_term: T-helper 2 cell
    term:
      id: CL:0000546
      label: T-helper 2 cell
  biological_processes:
  - preferred_term: T-helper 2 type immune response
    term:
      id: GO:0042092
      label: type 2 immune response
    modifier: INCREASED
  evidence:
  - reference: PMID:19634705
    reference_title: "Immunobiology of leishmaniasis."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "Th2 response is associated with disease progression"
    explanation: >-
      Attests the Th2-progression association in the murine model. Marked
      PARTIAL because the same review states the Th1/Th2 dichotomy is less
      distinct in humans and the murine model does not strictly apply. See the
      `leishmaniasis_th1_th2_murine_mismatch` discussion.
phenotypes:
- name: Cutaneous ulcers
  category: Dermatologic
  # frequency intentionally omitted: the cited snippet attests occurrence and
  # self-healing of ulcers in cutaneous leishmaniasis but gives no frequency for
  # the whole disease (which also spans visceral and mucocutaneous forms).
  phenotype_term:
    preferred_term: Skin ulcer
    term:
      id: HP:0200042
      label: Skin ulcer
  evidence:
  - reference: PMID:19634705
    reference_title: "Immunobiology of leishmaniasis."
    supports: SUPPORT
    snippet: "Cutaneous leishmaniasis usually has milder course and often results into a self-healing of ulcers."
    explanation: The review notes that cutaneous leishmaniasis produces ulcers,
      which often self-heal.
- name: Fever
  category: Constitutional
  subtype: Visceral leishmaniasis
  # frequency intentionally omitted: cited as one of "the main clinical symptoms"
  # without a numeric or qualitative frequency band.
  phenotype_term:
    preferred_term: Fever
    term:
      id: HP:0001945
      label: Fever
  evidence:
  - reference: PMID:17938629
    reference_title: "Visceral leishmaniasis: what are the needs for diagnosis, treatment and control?"
    supports: SUPPORT
    snippet: "Fever is usually associated with rigor and chills and can be intermittent."
    explanation: The review describes fever as a persistent, intermittent feature of visceral leishmaniasis.
  - reference: PMID:31297548
    reference_title: "[Visceral leishmaniasis]."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The main clinical symptoms are fever, hepatosplenomegaly and pancytopenia."
    explanation: Lists fever as a main clinical symptom of visceral leishmaniasis.
- name: Hepatosplenomegaly
  category: Hematologic
  subtype: Visceral leishmaniasis
  phenotype_term:
    preferred_term: Hepatosplenomegaly
    term:
      id: HP:0001433
      label: Hepatosplenomegaly
  evidence:
  - reference: PMID:17938629
    reference_title: "Visceral leishmaniasis: what are the needs for diagnosis, treatment and control?"
    supports: SUPPORT
    snippet: "parasitic invasion of the blood and reticulo-endothelial system (that is, the general phagocytic system), such as enlarged lymph nodes, spleen and liver."
    explanation: The review describes visceral leishmaniasis causing enlargement of the spleen and liver via reticuloendothelial parasitization.
  - reference: PMID:31297548
    reference_title: "[Visceral leishmaniasis]."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The main clinical symptoms are fever, hepatosplenomegaly and pancytopenia."
    explanation: Lists hepatosplenomegaly as a main clinical symptom of visceral leishmaniasis.
- name: Pancytopenia
  category: Hematologic
  subtype: Visceral leishmaniasis
  phenotype_term:
    preferred_term: Pancytopenia
    term:
      id: HP:0001876
      label: Pancytopenia
  evidence:
  - reference: PMID:17938629
    reference_title: "Visceral leishmaniasis: what are the needs for diagnosis, treatment and control?"
    supports: SUPPORT
    snippet: "A reduction in the number of red and white blood cells and platelets (pancytopenia) was found to be highly specific (98%) for VL in suspected clinical patients in Nepal"
    explanation: The review reports pancytopenia as a highly specific finding for visceral leishmaniasis.
  - reference: PMID:31297548
    reference_title: "[Visceral leishmaniasis]."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The main clinical symptoms are fever, hepatosplenomegaly and pancytopenia."
    explanation: Lists pancytopenia as a main clinical symptom of visceral leishmaniasis.
- name: Weight loss
  category: Constitutional
  subtype: Visceral leishmaniasis
  phenotype_term:
    preferred_term: Weight loss
    term:
      id: HP:0001824
      label: Weight loss
  evidence:
  - reference: PMID:17938629
    reference_title: "Visceral leishmaniasis: what are the needs for diagnosis, treatment and control?"
    supports: SUPPORT
    snippet: "VL patients present symptoms and signs of persistent systemic infection (including fever, fatigue, weakness, loss of appetite and weight loss)"
    explanation: The review lists weight loss among the systemic symptoms of visceral leishmaniasis.
- name: Nasal mucosal ulceration
  category: ENT
  subtype: Mucocutaneous leishmaniasis
  description: >-
    Destructive granulomatous mucosal disease of the nasal cavity. Untreated
    mucocutaneous leishmaniasis causes chronic local destruction of the tissue
    of the nose, pharynx, and palate, which can disfigure the patient.
  phenotype_term:
    preferred_term: Nasal ulcer
    term:
      id: HP:0033361
      label: Nasal ulcer
  evidence:
  - reference: DOI:10.1111/ddg.15424
    reference_title: 'Treatment of mucocutaneous leishmaniasis – A systematic review'
    supports: SUPPORT
    snippet: "characterized by granulomatous, destructive mucosal lesions in the oral, nasal, and pharyngeal cavities"
    explanation: The review describes mucocutaneous leishmaniasis as producing destructive mucosal lesions including in the nasal cavity.
  - reference: PMID:24897964
    reference_title: "Ear, nose and throat manifestations of mucocutaneous Leishmaniasis: a literature review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "If not recognized and adequately treated, MCL may disfigure the patient because of the chronic local destruction of tissue of the nose, pharynx and palate."
    explanation: >-
      Attests chronic destructive nasal, pharyngeal, and palatal tissue loss in
      untreated mucocutaneous leishmaniasis. Marked PARTIAL because the review
      documents destructive nasal mucosal disease but does not state ulceration
      (or septal perforation) in these words.
treatments:
- name: Liposomal amphotericin B therapy
  description: Liposomal amphotericin B is a standard therapy for visceral leishmaniasis in many regions.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
  evidence:
  - reference: PMID:30712769
    reference_title: "Visceral Leishmaniasis: Recent Advances in Diagnostics and Treatment Regimens."
    supports: SUPPORT
    snippet: "Liposomal amphotericin B is generally found to be safe and effective in most endemic regions of the world"
    explanation: The review describes liposomal amphotericin B as safe and effective.
- name: Miltefosine
  description: >-
    Orally administered antileishmanial agent. Its global utilization spans all
    major leishmaniasis forms, including visceral, cutaneous, mucocutaneous, and
    post-kala-azar dermal leishmaniasis.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: miltefosine
      term:
        id: CHEBI:75283
        label: miltefosine
  evidence:
  - reference: PMID:39752369
    reference_title: "Progress in antileishmanial drugs: Mechanisms, challenges, and prospects."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Miltefosine’s global utilization spans all major leishmaniasis forms, including VL, CL, MCL, and PKDL"
    explanation: States that miltefosine is used across all major clinical forms of leishmaniasis.
  - reference: PMID:39752369
    reference_title: "Progress in antileishmanial drugs: Mechanisms, challenges, and prospects."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Its unique oral administration convenience underscores miltefosine’s pivotal role in advancing leishmaniasis treatment modalities"
    explanation: Attests the oral route of administration that distinguishes miltefosine from the injectable agents.
- name: Pentavalent Antimonial Therapy
  description: >-
    Pentavalent antimonials (sodium stibogluconate, meglumine antimoniate) are
    among the WHO 2010 first-line treatment options for certain Leishmania
    species; the review lists toxicity and resistance as their principal
    limitations.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: sodium stibogluconate
      term:
        id: CHEBI:28148
        label: sodium stibogluconate
  evidence:
  - reference: PMID:39752369
    reference_title: "Progress in antileishmanial drugs: Mechanisms, challenges, and prospects."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "According to the WHO 2010 guidelines, pentavalent antimonials are among the first-line treatment options"
    explanation: Attests first-line status of pentavalent antimonials under the WHO 2010 guidelines.
  - reference: PMID:39752369
    reference_title: "Progress in antileishmanial drugs: Mechanisms, challenges, and prospects."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Despite toxicity and resistance (antimonials),"
    explanation: Attests toxicity and resistance as the principal limitations of antimonial therapy.
- name: Paromomycin
  description: >-
    Aminoglycoside antibiotic effective against visceral and cutaneous
    leishmaniasis, widely available and affordable in endemic regions;
    administered mainly intramuscularly for visceral disease or topically for
    cutaneous disease because of limited oral bioavailability.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: paromomycin
      term:
        id: CHEBI:7934
        label: paromomycin
  evidence:
  - reference: PMID:39752369
    reference_title: "Progress in antileishmanial drugs: Mechanisms, challenges, and prospects."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Paromomycin, effective against VL and CL, is widely available and affordable, especially in endemic regions"
    explanation: Attests efficacy against visceral and cutaneous leishmaniasis plus availability and affordability.
  - reference: PMID:39752369
    reference_title: "Progress in antileishmanial drugs: Mechanisms, challenges, and prospects."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "is mainly intramuscular for VL or topical for CL due to limited oral bioavailability"
    explanation: Attests the intramuscular and topical routes of administration and the reason for them.
prevalence:
- population: Worldwide
  measure_type: ANNUAL_INCIDENCE
  prevalence_class: COMMON
  notes: >-
    Estimated 50,000-90,000 new visceral leishmaniasis cases and 0.5-1 million
    new tegumentary (cutaneous/mucocutaneous) leishmaniasis cases globally
    per year.
  evidence:
  - reference: PMID:36753272
    reference_title: "[Contributions of epidemiology to the control of leishmaniasis]."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "it is estimated that globally occur between 50 000 and 90 000 new cases of visceral leishmaniasis and between 0.5 and 1 million tegumentary leishmaniasis"
    explanation: Reports global annual incidence estimates for visceral and tegumentary leishmaniasis.
discussions:
- discussion_id: leishmaniasis_th1_th2_murine_mismatch
  prompt: >-
    Does the murine Th1-control / Th2-progression dichotomy operate in human
    leishmaniasis, and which human immune correlates should replace it?
  kind: HUMAN_MODEL_MISMATCH
  status: OPEN
  attaches_to:
  - pathophysiology#Th1-Polarized Cell-Mediated Response and Macrophage Activation
  - pathophysiology#Th2-Polarized Response and Permissive Disease Progression
  rationale: >-
    The Th1-protective / Th2-permissive polarization is established in the murine
    model, but the reviewed literature explicitly states that the Th1/Th2
    dichotomy in the human system is not as distinct as in mice and that the
    murine model does not strictly apply to human leishmaniasis. Evidence
    therefore exists in a model system while its translational validity is the
    open question, which is a HUMAN_MODEL_MISMATCH rather than a plain
    KNOWLEDGE_GAP. Both polarization nodes are consequently curated with
    PARTIAL, MODEL_ORGANISM-sourced evidence.
  proposed_experiments:
  - experiment_id: exp_leish_human_th_polarization_cohort
    name: Human T-helper polarization versus outcome in leishmaniasis cohorts
    description: >-
      Longitudinally profile lesion- and blood-derived CD4 T-cell cytokine
      programs in human cutaneous, mucocutaneous, and visceral leishmaniasis
      cohorts, and test whether polarization state predicts cure versus
      progression as it does in the murine model.
    experiment_type:
      preferred_term: prospective clinical cohort immunophenotyping experiment
    readouts:
    - name: T-helper polarization state versus clinical outcome
      target: pathophysiology#Th1-Polarized Cell-Mediated Response and Macrophage Activation
  - experiment_id: exp_leish_cross_species_tcell_scrnaseq
    name: Cross-species single-cell comparison of the T-cell compartment
    description: >-
      Compare single-cell transcriptomes of the T-cell compartment in matched
      human lesions and murine infection models to determine which human immune
      states, if any, correspond to the murine Th1 and Th2 arms.
    experiment_type:
      preferred_term: cross-species single-cell transcriptomic comparison experiment
    readouts:
    - name: Correspondence of human T-cell states to murine Th1/Th2 arms
      target: pathophysiology#Th2-Polarized Response and Permissive Disease Progression
  evidence:
  - reference: PMID:19634705
    reference_title: "Immunobiology of leishmaniasis."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "However, Th1 and Th2 dichotomy in the human system is not as distinct as in mice and the murine model does not strictly apply to human leishmaniasis."
    explanation: >-
      States the human-versus-murine mismatch directly: the dichotomy is less
      distinct in humans and the murine model does not strictly translate.
references:
- reference: DOI:10.1038/s41591-024-03146-9
  title: Safety and reactogenicity of a controlled human infection model of sand fly-transmitted cutaneous leishmaniasis
  found_in:
  - Leishmaniasis-deep-research-falcon.md
  findings:
  - statement: The leishmaniases are globally important parasitic diseases for which no human vaccines are currently available.
    supporting_text: The leishmaniases are globally important parasitic diseases for which no human vaccines are currently available.
    evidence:
    - reference: DOI:10.1038/s41591-024-03146-9
      reference_title: Safety and reactogenicity of a controlled human infection model of sand fly-transmitted cutaneous leishmaniasis
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: The leishmaniases are globally important parasitic diseases for which no human vaccines are currently available.
      explanation: Deep research cited this publication as relevant literature for Leishmaniasis.
- reference: DOI:10.1093/ofid/ofad348
  title: 'Intravenous Liposomal Amphotericin B Efficacy and Safety for Cutaneous and Mucosal Leishmaniasis: A Systematic Review and Meta-analysis'
  found_in:
  - Leishmaniasis-deep-research-falcon.md
  findings:
  - statement: Tegumentary leishmaniasis is often subject to limited funding, underpowered studies, and a paucity of high-quality interventional studies.
    supporting_text: Tegumentary leishmaniasis is often subject to limited funding, underpowered studies, and a paucity of high-quality interventional studies.
    evidence:
    - reference: DOI:10.1093/ofid/ofad348
      reference_title: 'Intravenous Liposomal Amphotericin B Efficacy and Safety for Cutaneous and Mucosal Leishmaniasis: A Systematic Review and Meta-analysis'
      supports: SUPPORT
      evidence_source: OTHER
      snippet: Tegumentary leishmaniasis is often subject to limited funding, underpowered studies, and a paucity of high-quality interventional studies.
      explanation: Deep research cited this publication as relevant literature for Leishmaniasis.
- reference: DOI:10.1101/2024.01.02.23300281
  title: IL-32 producing CD8 <sup>+</sup> memory T cells and Tregs define the IDO1 / PD-L1 niche in human cutaneous leishmaniasis skin lesions
  found_in:
  - Leishmaniasis-deep-research-falcon.md
  findings:
  - statement: Human cutaneous leishmaniasis (CL) is characterised by chronic skin pathology.
    supporting_text: Human cutaneous leishmaniasis (CL) is characterised by chronic skin pathology.
    evidence:
    - reference: DOI:10.1101/2024.01.02.23300281
      reference_title: IL-32 producing CD8 <sup>+</sup> memory T cells and Tregs define the IDO1 / PD-L1 niche in human cutaneous leishmaniasis skin lesions
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Human cutaneous leishmaniasis (CL) is characterised by chronic skin pathology.
      explanation: Deep research cited this publication as relevant literature for Leishmaniasis.
- reference: DOI:10.1101/2024.04.12.24305492
  title: Safety, effectiveness, and skin immune response in a controlled human infection model of sand fly transmitted cutaneous leishmaniasis
  found_in:
  - Leishmaniasis-deep-research-falcon.md
  findings:
  - statement: The leishmaniases are globally important parasitic diseases for which no human vaccines are currently available.
    supporting_text: The leishmaniases are globally important parasitic diseases for which no human vaccines are currently available.
    evidence:
    - reference: DOI:10.1101/2024.04.12.24305492
      reference_title: Safety, effectiveness, and skin immune response in a controlled human infection model of sand fly transmitted cutaneous leishmaniasis
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: The leishmaniases are globally important parasitic diseases for which no human vaccines are currently available.
      explanation: Deep research cited this publication as relevant literature for Leishmaniasis.
- reference: DOI:10.1111/ddg.15424
  title: Treatment of mucocutaneous leishmaniasis – A systematic review
  found_in:
  - Leishmaniasis-deep-research-falcon.md
  findings:
  - statement: Mucocutaneous leishmaniasis is a severe infectious disease, predominantly endemic in Central and South America and is characterized by granulomatous, destructive mucosal lesions in the oral, nasal, and pharyngeal cavities.
    supporting_text: Mucocutaneous leishmaniasis is a severe infectious disease, predominantly endemic in Central and South America and is characterized by granulomatous, destructive mucosal lesions in the oral, nasal, and pharyngeal cavities.
    evidence:
    - reference: DOI:10.1111/ddg.15424
      reference_title: Treatment of mucocutaneous leishmaniasis – A systematic review
      supports: SUPPORT
      evidence_source: OTHER
      snippet: Mucocutaneous leishmaniasis is a severe infectious disease, predominantly endemic in Central and South America and is characterized by granulomatous, destructive mucosal lesions in the oral, nasal, and pharyngeal cavities.
      explanation: Deep research cited this publication as relevant literature for Leishmaniasis.
- reference: DOI:10.1128/spectrum.03478-23
  title: Single-cell ATAC sequencing identifies sleepy macrophages during reciprocity of cytokines in <i>L. major</i> infection
  found_in:
  - Leishmaniasis-deep-research-falcon.md
  findings:
  - statement: The hallmark characteristic of macrophages lies in their inherent plasticity, allowing them to adapt to dynamic microenvironments.
    supporting_text: The hallmark characteristic of macrophages lies in their inherent plasticity, allowing them to adapt to dynamic microenvironments.
    evidence:
    - reference: DOI:10.1128/spectrum.03478-23
      reference_title: Single-cell ATAC sequencing identifies sleepy macrophages during reciprocity of cytokines in <i>L. major</i> infection
      supports: SUPPORT
      evidence_source: OTHER
      snippet: The hallmark characteristic of macrophages lies in their inherent plasticity, allowing them to adapt to dynamic microenvironments.
      explanation: Deep research cited this publication as relevant literature for Leishmaniasis.
- reference: DOI:10.1172/jci177992
  title: Neutrophil-mediated hypoxia drives pathogenic CD8+ T cell responses in cutaneous leishmaniasis
  found_in:
  - Leishmaniasis-deep-research-falcon.md
  findings:
  - statement: Neutrophil-mediated hypoxia drives pathogenic CD8+ T cell responses in cutaneous leishmaniasis
    supporting_text: Neutrophil-mediated hypoxia drives pathogenic CD8+ T cell responses in cutaneous leishmaniasis
- reference: DOI:10.1186/s12982-024-00247-1
  title: Classical and innovative drugs for the treatment of Leishmania infections
  found_in:
  - Leishmaniasis-deep-research-falcon.md
  findings:
  - statement: Although among the six most common parasitic diseases, leishmaniasis is considered a neglected disease, being recognised as a serious public health burden worldwide.
    supporting_text: Although among the six most common parasitic diseases, leishmaniasis is considered a neglected disease, being recognised as a serious public health burden worldwide.
    evidence:
    - reference: DOI:10.1186/s12982-024-00247-1
      reference_title: Classical and innovative drugs for the treatment of Leishmania infections
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Although among the six most common parasitic diseases, leishmaniasis is considered a neglected disease, being recognised as a serious public health burden worldwide.
      explanation: Deep research cited this publication as relevant literature for Leishmaniasis.
- reference: DOI:10.1371/journal.pntd.0012323
  title: 'American Cutaneous Leishmaniasis: Imported cases in Berlin 2000–2023'
  found_in:
  - Leishmaniasis-deep-research-falcon.md
  findings:
  - statement: American Cutaneous Leishmaniasis (ACL) shows variable response to therapy, but data on species-specific treatment efficacy is scarce.
    supporting_text: American Cutaneous Leishmaniasis (ACL) shows variable response to therapy, but data on species-specific treatment efficacy is scarce.
    evidence:
    - reference: DOI:10.1371/journal.pntd.0012323
      reference_title: 'American Cutaneous Leishmaniasis: Imported cases in Berlin 2000–2023'
      supports: SUPPORT
      evidence_source: OTHER
      snippet: American Cutaneous Leishmaniasis (ACL) shows variable response to therapy, but data on species-specific treatment efficacy is scarce.
      explanation: Deep research cited this publication as relevant literature for Leishmaniasis.
- reference: DOI:10.33448/rsd-v13i12.47645
  title: 'Visceral leishmaniasis: Therapeutic challenges and the potential of microalgae as a source of antileishmanial compounds'
  found_in:
  - Leishmaniasis-deep-research-falcon.md
  findings:
  - statement: Leishmaniases are diseases caused by protozoa of the Leishmania genus, transmitted by sandflies, manifesting as visceral, cutaneous, or mucocutaneous forms.
    supporting_text: Leishmaniases are diseases caused by protozoa of the Leishmania genus, transmitted by sandflies, manifesting as visceral, cutaneous, or mucocutaneous forms.
    evidence:
    - reference: DOI:10.33448/rsd-v13i12.47645
      reference_title: 'Visceral leishmaniasis: Therapeutic challenges and the potential of microalgae as a source of antileishmanial compounds'
      supports: SUPPORT
      evidence_source: OTHER
      snippet: Leishmaniases are diseases caused by protozoa of the Leishmania genus, transmitted by sandflies, manifesting as visceral, cutaneous, or mucocutaneous forms.
      explanation: Deep research cited this publication as relevant literature for Leishmaniasis.
- reference: DOI:10.3389/fimmu.2024.1402539
  title: 'Immune response to viscerotropic Leishmania: a comprehensive review'
  found_in:
  - Leishmaniasis-deep-research-falcon.md
  findings:
  - statement: L. donovani and L. infantum infections are associated with a broad clinical spectrum, ranging from asymptomatic cases to visceral leishmaniasis (VL) with high mortality rates.
    supporting_text: L. donovani and L. infantum infections are associated with a broad clinical spectrum, ranging from asymptomatic cases to visceral leishmaniasis (VL) with high mortality rates.
    evidence:
    - reference: DOI:10.3389/fimmu.2024.1402539
      reference_title: 'Immune response to viscerotropic Leishmania: a comprehensive review'
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: L. donovani and L. infantum infections are associated with a broad clinical spectrum, ranging from asymptomatic cases to visceral leishmaniasis (VL) with high mortality rates.
      explanation: Deep research cited this publication as relevant literature for Leishmaniasis.
- reference: DOI:10.3390/tropicalmed9110258
  title: 'Leishmaniasis in Humans and Animals: A One Health Approach for Surveillance, Prevention and Control in a Changing World'
  found_in:
  - Leishmaniasis-deep-research-falcon.md
  findings:
  - statement: Leishmaniasis is classified as a neglected tropical disease (NTD), caused by protozoan parasites of the genus Leishmania, which are transmitted to humans and other animals through the bite of infected female phlebotomine sandflies.
    supporting_text: Leishmaniasis is classified as a neglected tropical disease (NTD), caused by protozoan parasites of the genus Leishmania, which are transmitted to humans and other animals through the bite of infected female phlebotomine sandflies.
    evidence:
    - reference: DOI:10.3390/tropicalmed9110258
      reference_title: 'Leishmaniasis in Humans and Animals: A One Health Approach for Surveillance, Prevention and Control in a Changing World'
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Leishmaniasis is classified as a neglected tropical disease (NTD), caused by protozoan parasites of the genus Leishmania, which are transmitted to humans and other animals through the bite of infected female phlebotomine sandflies.
      explanation: Deep research cited this publication as relevant literature for Leishmaniasis.
- reference: DOI:10.36877/pmmb.a0000395
  title: 'Cutaneous Leishmaniasis: Physiopathology, Molecular Diagnostic, and Therapeutic Approaches'
  found_in:
  - Leishmaniasis-deep-research-falcon.md
  findings:
  - statement: This in-depth study explores various aspects of cutaneous leishmaniasis, shedding light on the physiopathology of the infection, advances in molecular diagnostic techniques, and therapeutic approaches currently in development.
    supporting_text: This in-depth study explores various aspects of cutaneous leishmaniasis, shedding light on the physiopathology of the infection, advances in molecular diagnostic techniques, and therapeutic approaches currently in development.
    evidence:
    - reference: DOI:10.36877/pmmb.a0000395
      reference_title: 'Cutaneous Leishmaniasis: Physiopathology, Molecular Diagnostic, and Therapeutic Approaches'
      supports: SUPPORT
      evidence_source: OTHER
      snippet: This in-depth study explores various aspects of cutaneous leishmaniasis, shedding light on the physiopathology of the infection, advances in molecular diagnostic techniques, and therapeutic approaches currently in development.
      explanation: Deep research cited this publication as relevant literature for Leishmaniasis.
- reference: DOI:10.48676/unibo/amsdottorato/11146
  title: Epidemiological, clinical and molecular characterization of tegumentary leishmaniasis in the Emilia-Romagna region
  found_in:
  - Leishmaniasis-deep-research-falcon.md
  findings:
  - statement: Epidemiological, clinical and molecular characterization of tegumentary leishmaniasis in the Emilia-Romagna region
    supporting_text: Epidemiological, clinical and molecular characterization of tegumentary leishmaniasis in the Emilia-Romagna region
datasets:
- accession: geo:GSE220308
  title: Stratification of expression profiles of immune-related genes in the lesion of cutaneous leishmaniasis patients with L. major and L. tropica infection
  description: There is still no reliable human vaccination against cutaneous leishmaniasis (CL), a serious public health issue in many parts of underdeveloped nations like Morocco and Iran. There are few studies comparing the expression of immune-related genes in the skin lesions of CL patients infected with L. major and L. tropica. In this study, we used dcRT-MLPA to analyze the expression profiles of 144 immune response-related genes in CL patients from Morocco and Iran who had been exposed to L. major and L. tropica, respectively.
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  sample_count: 40
  publication: PMID:40100809
  notes: Identified by GEO DataSets index search for Leishmaniasis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
- accession: geo:GSE324689
  title: Post Kala Azar Dermal Leishmaniasis (PKDL) genome wide transcriptional profiling by bulk RNA-sequencing
  description: Post-kala-azar dermal leishmaniasis (PKDL), a dermal sequel of visceral leishmaniasis (VL), is considered an important reservoir that facilitates the transmission of VL. Although PKDL lesions demonstrate an overwhelming infiltration of CD8⁺ T cells, the molecular mechanisms regulating their recruitment to the skin remain poorly defined. To address this, bulk RNA sequencing was performed on dermal lesions from patients withPKDL and healthy controls to characterize the lesional chemokine and cytokine landscape associated with T-cell homing.Transcriptomic analysis revealed a significant upregulation of genes encoding T-cell chemoattractants, including CCL3, CCL4, CCL5, CCL17, CXCL9, and CXCL10,...
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  data_type: BULK_RNA_SEQ
  sample_count: 7
  publication: PMID:42497210
  notes: Identified by GEO DataSets index search for Leishmaniasis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
- accession: geo:GSE290027
  title: IL-32 producing CD8+ memory T cells and Tregs define the IDO1 / PD-L1 niche in human cutaneous leishmaniasis skin lesions
  description: Human cutaneous leishmaniasis (CL) is characterised by chronic skin pathology. Experimental and clinical data suggest that immune checkpoints (ICs) play a crucial role in disease outcome but the cellular and molecular niches that facilitate IC expression during leishmaniasis are ill-defined. We previously showed that in Sri Lankan patients with CL, indoleamine 2,3-dioxygenase 1 (IDO1) and programmed death-ligand 1 (PD-L1) are enriched in lesion skin and that reduced PD-L1 expression early after treatment onset predicted cure rate following antimonial therapy.
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  sample_count: 12
  publication: PMID:40371647
  notes: Identified by GEO DataSets index search for Leishmaniasis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
- accession: ega:EGAS00001000773
  title: WTCCC2 Visceral Leishmaniasis (VL) samples
  description: A WTCCC2 project genome-wide association study for visceral leishmaniasis (VL) in individuals from India, Brazil and Sudan, genotyped on the custom Illumina 670k array. The WTCCC2 analysis of the Brazilian and Indian samples is described in Fakiola et al. [Nat Genet. 2013 Feb;45(2):208-13].It should be noted that due to expected family structure in the data, normal analyses of these data should include an estimation of the relatedness between the samples. For more details about sample collection for the project please refer to the Methods section of the paper above. The samples from India were all collected from Bihar state in northeastern India.
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  publication: PMID:23291585
  notes: 'European Genome-phenome Archive study, matched because the disease is named in the study''s own title ("Leishmaniasis"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01.'
- accession: ega:EGAS00001004152
  title: Transcriptomic signatures of CD4+ T cells from visceral leishmaniasis (VL) patients
  description: Bulk RNA-sequencing was performed on CD4+ T cells isolated from the blood of visceral leishmaniasis patients (n = 12) and endemic controls (EC; n = 12). CD4+ T cells were obtained by magnetic-activated cell sorting (MACS). Alterations in the transcripts of T helper (Th) cells during infection were identified.
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  notes: 'European Genome-phenome Archive study, matched because the disease is named in the study''s own title ("Leishmaniasis"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01.'
- accession: ega:EGAS00001004596
  title: A GWAS for cutaneous leishmaniasis in Brazil
  description: Our goal was to identify genetic risk factors for cutaneous leishmaniasis (CL) caused by Leishmania braziliensis. Genotyping 2066 CL cases and 2046 controls using Illumina HumanCoreExomeBeadChips provided data for 4,498,586 imputed single nucleotide variants (SNVs). Genome-wide association testing using linear mixed models took account of genetic diversity/ethnicity/admixture. Post-GWAS positional, expression quantitative trait locus (eQTL), and chromatin interaction mapping was performed in FUMA. Transcriptional data were compared between lesions and normal skin, and cytokines measured using flow cytometry and Bioplex assay.
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  notes: 'European Genome-phenome Archive study, matched because the disease is named in the study''s own title ("Leishmaniasis"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01.'
- accession: metabolomics_workbench:ST002347
  title: Impact of Visceral Leishmaniasis on Local Organ Metabolism in Hamsters
  organism:
    preferred_term: Syrian hamster
    term:
      id: NCBITaxon:10036
      label: Mesocricetus auratus
  data_type: METABOLOMICS
  notes: Located via OmicsDI, which aggregates across omics repositories; this record comes from metabolomics_workbench. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title ("Leishmaniasis"). Retrieved 2026-08-02.
- accession: massive:MSV000096486
  title: Ontogeny independent expression of LPCAT2 in granuloma macrophages during experimental visceral leishmaniasis
  description: 'Proteomic data relating to: Ontogeny independent expression of LPCAT2 in granuloma macrophages during experimental visceral leishmaniasis'
  notes: Located via OmicsDI, which aggregates across omics repositories; this record comes from massive. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title ("Leishmaniasis"). Retrieved 2026-08-02.
📚

References & Deep Research

References

14
DOI:10.1038/s41591-024-03146-9
Safety and reactogenicity of a controlled human infection model of sand fly-transmitted cutaneous leishmaniasis
1 finding
The leishmaniases are globally important parasitic diseases for which no human vaccines are currently available.
"The leishmaniases are globally important parasitic diseases for which no human vaccines are currently available."
Show evidence (1 reference)
DOI:10.1038/s41591-024-03146-9 SUPPORT Human Clinical
"The leishmaniases are globally important parasitic diseases for which no human vaccines are currently available."
Deep research cited this publication as relevant literature for Leishmaniasis.
DOI:10.1093/ofid/ofad348
Intravenous Liposomal Amphotericin B Efficacy and Safety for Cutaneous and Mucosal Leishmaniasis: A Systematic Review and Meta-analysis
1 finding
Tegumentary leishmaniasis is often subject to limited funding, underpowered studies, and a paucity of high-quality interventional studies.
"Tegumentary leishmaniasis is often subject to limited funding, underpowered studies, and a paucity of high-quality interventional studies."
Show evidence (1 reference)
DOI:10.1093/ofid/ofad348 SUPPORT Other
"Tegumentary leishmaniasis is often subject to limited funding, underpowered studies, and a paucity of high-quality interventional studies."
Deep research cited this publication as relevant literature for Leishmaniasis.
DOI:10.1101/2024.01.02.23300281
IL-32 producing CD8 <sup>+</sup> memory T cells and Tregs define the IDO1 / PD-L1 niche in human cutaneous leishmaniasis skin lesions
1 finding
Human cutaneous leishmaniasis (CL) is characterised by chronic skin pathology.
"Human cutaneous leishmaniasis (CL) is characterised by chronic skin pathology."
Show evidence (1 reference)
DOI:10.1101/2024.01.02.23300281 Preprint · not peer-reviewed SUPPORT Human Clinical
"Human cutaneous leishmaniasis (CL) is characterised by chronic skin pathology."
Deep research cited this publication as relevant literature for Leishmaniasis.
DOI:10.1101/2024.04.12.24305492
Safety, effectiveness, and skin immune response in a controlled human infection model of sand fly transmitted cutaneous leishmaniasis
1 finding
The leishmaniases are globally important parasitic diseases for which no human vaccines are currently available.
"The leishmaniases are globally important parasitic diseases for which no human vaccines are currently available."
Show evidence (1 reference)
DOI:10.1101/2024.04.12.24305492 Preprint · not peer-reviewed SUPPORT Human Clinical
"The leishmaniases are globally important parasitic diseases for which no human vaccines are currently available."
Deep research cited this publication as relevant literature for Leishmaniasis.
DOI:10.1111/ddg.15424
Treatment of mucocutaneous leishmaniasis – A systematic review
1 finding
Mucocutaneous leishmaniasis is a severe infectious disease, predominantly endemic in Central and South America and is characterized by granulomatous, destructive mucosal lesions in the oral, nasal, and pharyngeal cavities.
"Mucocutaneous leishmaniasis is a severe infectious disease, predominantly endemic in Central and South America and is characterized by granulomatous, destructive mucosal lesions in the oral, nasal, and pharyngeal cavities."
Show evidence (1 reference)
DOI:10.1111/ddg.15424 SUPPORT Other
"Mucocutaneous leishmaniasis is a severe infectious disease, predominantly endemic in Central and South America and is characterized by granulomatous, destructive mucosal lesions in the oral, nasal, and pharyngeal cavities."
Deep research cited this publication as relevant literature for Leishmaniasis.
DOI:10.1128/spectrum.03478-23
Single-cell ATAC sequencing identifies sleepy macrophages during reciprocity of cytokines in <i>L. major</i> infection
1 finding
The hallmark characteristic of macrophages lies in their inherent plasticity, allowing them to adapt to dynamic microenvironments.
"The hallmark characteristic of macrophages lies in their inherent plasticity, allowing them to adapt to dynamic microenvironments."
Show evidence (1 reference)
DOI:10.1128/spectrum.03478-23 SUPPORT Other
"The hallmark characteristic of macrophages lies in their inherent plasticity, allowing them to adapt to dynamic microenvironments."
Deep research cited this publication as relevant literature for Leishmaniasis.
DOI:10.1172/jci177992
Neutrophil-mediated hypoxia drives pathogenic CD8+ T cell responses in cutaneous leishmaniasis
1 finding
Neutrophil-mediated hypoxia drives pathogenic CD8+ T cell responses in cutaneous leishmaniasis
"Neutrophil-mediated hypoxia drives pathogenic CD8+ T cell responses in cutaneous leishmaniasis"
DOI:10.1186/s12982-024-00247-1
Classical and innovative drugs for the treatment of Leishmania infections
1 finding
Although among the six most common parasitic diseases, leishmaniasis is considered a neglected disease, being recognised as a serious public health burden worldwide.
"Although among the six most common parasitic diseases, leishmaniasis is considered a neglected disease, being recognised as a serious public health burden worldwide."
Show evidence (1 reference)
DOI:10.1186/s12982-024-00247-1 SUPPORT Human Clinical
"Although among the six most common parasitic diseases, leishmaniasis is considered a neglected disease, being recognised as a serious public health burden worldwide."
Deep research cited this publication as relevant literature for Leishmaniasis.
DOI:10.1371/journal.pntd.0012323
American Cutaneous Leishmaniasis: Imported cases in Berlin 2000–2023
1 finding
American Cutaneous Leishmaniasis (ACL) shows variable response to therapy, but data on species-specific treatment efficacy is scarce.
"American Cutaneous Leishmaniasis (ACL) shows variable response to therapy, but data on species-specific treatment efficacy is scarce."
Show evidence (1 reference)
DOI:10.1371/journal.pntd.0012323 SUPPORT Other
"American Cutaneous Leishmaniasis (ACL) shows variable response to therapy, but data on species-specific treatment efficacy is scarce."
Deep research cited this publication as relevant literature for Leishmaniasis.
DOI:10.33448/rsd-v13i12.47645
Visceral leishmaniasis: Therapeutic challenges and the potential of microalgae as a source of antileishmanial compounds
1 finding
Leishmaniases are diseases caused by protozoa of the Leishmania genus, transmitted by sandflies, manifesting as visceral, cutaneous, or mucocutaneous forms.
"Leishmaniases are diseases caused by protozoa of the Leishmania genus, transmitted by sandflies, manifesting as visceral, cutaneous, or mucocutaneous forms."
Show evidence (1 reference)
DOI:10.33448/rsd-v13i12.47645 SUPPORT Other
"Leishmaniases are diseases caused by protozoa of the Leishmania genus, transmitted by sandflies, manifesting as visceral, cutaneous, or mucocutaneous forms."
Deep research cited this publication as relevant literature for Leishmaniasis.
DOI:10.3389/fimmu.2024.1402539
Immune response to viscerotropic Leishmania: a comprehensive review
1 finding
L. donovani and L. infantum infections are associated with a broad clinical spectrum, ranging from asymptomatic cases to visceral leishmaniasis (VL) with high mortality rates.
"L. donovani and L. infantum infections are associated with a broad clinical spectrum, ranging from asymptomatic cases to visceral leishmaniasis (VL) with high mortality rates."
Show evidence (1 reference)
DOI:10.3389/fimmu.2024.1402539 SUPPORT Human Clinical
"L. donovani and L. infantum infections are associated with a broad clinical spectrum, ranging from asymptomatic cases to visceral leishmaniasis (VL) with high mortality rates."
Deep research cited this publication as relevant literature for Leishmaniasis.
DOI:10.3390/tropicalmed9110258
Leishmaniasis in Humans and Animals: A One Health Approach for Surveillance, Prevention and Control in a Changing World
1 finding
Leishmaniasis is classified as a neglected tropical disease (NTD), caused by protozoan parasites of the genus Leishmania, which are transmitted to humans and other animals through the bite of infected female phlebotomine sandflies.
"Leishmaniasis is classified as a neglected tropical disease (NTD), caused by protozoan parasites of the genus Leishmania, which are transmitted to humans and other animals through the bite of infected female phlebotomine sandflies."
Show evidence (1 reference)
DOI:10.3390/tropicalmed9110258 SUPPORT Human Clinical
"Leishmaniasis is classified as a neglected tropical disease (NTD), caused by protozoan parasites of the genus Leishmania, which are transmitted to humans and other animals through the bite of infected female phlebotomine sandflies."
Deep research cited this publication as relevant literature for Leishmaniasis.
DOI:10.36877/pmmb.a0000395
Cutaneous Leishmaniasis: Physiopathology, Molecular Diagnostic, and Therapeutic Approaches
1 finding
This in-depth study explores various aspects of cutaneous leishmaniasis, shedding light on the physiopathology of the infection, advances in molecular diagnostic techniques, and therapeutic approaches currently in development.
"This in-depth study explores various aspects of cutaneous leishmaniasis, shedding light on the physiopathology of the infection, advances in molecular diagnostic techniques, and therapeutic approaches currently in development."
Show evidence (1 reference)
DOI:10.36877/pmmb.a0000395 SUPPORT Other
"This in-depth study explores various aspects of cutaneous leishmaniasis, shedding light on the physiopathology of the infection, advances in molecular diagnostic techniques, and therapeutic approaches currently in development."
Deep research cited this publication as relevant literature for Leishmaniasis.
DOI:10.48676/unibo/amsdottorato/11146
Epidemiological, clinical and molecular characterization of tegumentary leishmaniasis in the Emilia-Romagna region
1 finding
Epidemiological, clinical and molecular characterization of tegumentary leishmaniasis in the Emilia-Romagna region
"Epidemiological, clinical and molecular characterization of tegumentary leishmaniasis in the Emilia-Romagna region"

Deep Research

1
Falcon ▸
1. Disease Information
Edison Scientific Literature 45 citations 2026-04-04T14:53:57.342801

1. Disease Information

1.1 Disease definition and overview

Leishmaniasis is a neglected tropical disease caused by protozoan parasites of the genus Leishmania transmitted to humans (and other mammals) by infected female phlebotomine sandflies. Clinical expression spans cutaneous, mucocutaneous, and visceral disease forms, with post-kala-azar dermal leishmaniasis (PKDL) recognized as part of the visceral spectrum. (cosma2024leishmaniasisinhumans pages 2-4, mota2024classicalandinnovative pages 1-3)

Direct abstract support (definition quote): - “Leishmaniasis is classified as a neglected tropical disease (NTD), caused by protozoan parasites of the genus Leishmania, which are transmitted to humans and other animals through the bite of infected female phlebotomine sandflies.” (Cosma et al., 2024-10-??, DOI: 10.3390/tropicalmed9110258) (cosma2024leishmaniasisinhumans pages 2-4)

1.2 Key identifiers (ontology and clinical coding)

  • MONDO ID: not available in retrieved evidence.
  • MeSH: not available in retrieved evidence.
  • ICD-10 / ICD-11: not available in retrieved evidence.
  • Orphanet: not available in retrieved evidence.

1.3 Common synonyms / alternative names

  • Visceral leishmaniasis: “kala-azar”. (sousa2024visceralleishmaniasistherapeutic pages 4-6, cosma2024leishmaniasisinhumans pages 2-4)
  • Tegumentary leishmaniasis: used as an umbrella term for cutaneous and mucosal involvement in some clinical contexts. (chivinski2023intravenousliposomalamphotericin pages 6-7)

1.4 Evidence sources and aggregation level

The evidence used here includes: peer-reviewed reviews and systematic reviews/meta-analyses, observational clinical cohorts, and controlled human infection model (CHIM) data. These are aggregated disease-level resources with embedded patient-level study data; some sections also draw on retrospective chart review and case series evidence. (cosma2024leishmaniasisinhumans pages 2-4, lindner2024americancutaneousleishmaniasis pages 2-4, parkash2024safetyandreactogenicity pages 2-3, chivinski2023intravenousliposomalamphotericin pages 6-7)

2. Etiology

2.1 Disease causal factors

  • Infectious agent: intracellular protozoa (Leishmania spp.). (cosma2024leishmaniasisinhumans pages 2-4, balahbib2023cutaneousleishmaniasisphysiopathology pages 1-4)
  • Transmission: via bites of infected female sandflies. (cosma2024leishmaniasisinhumans pages 2-4, sousa2024visceralleishmaniasistherapeutic pages 4-6)
  • Clinical heterogeneity: depends strongly on parasite species and host immunity. (cosma2024leishmaniasisinhumans pages 2-4, dey2024il32producingcd8+ pages 1-7)

2.2 Risk factors

Host factors - Immunocompromise (e.g., HIV, inborn errors of immunity) is associated with more severe disease and relapse risk in visceral infection. (lodi2024immuneresponseto pages 10-11)

Behavioral/environmental factors (mucosal disease) - Risk factors for mucocutaneous leishmaniasis include smoking, alcohol abuse, and large or multiple untreated skin lesions, especially on head/neck. (fischer2024treatmentofmucocutaneous pages 2-2)

Macro-environmental determinants (One Health) Climate change, deforestation, urbanization, globalization/migration can shift sandfly and reservoir distributions, increasing human exposure and expanding leishmaniasis into new latitudes/altitudes. (cosma2024leishmaniasisinhumans pages 2-4)

2.3 Protective factors

Not directly identified in the retrieved evidence corpus (no specific host genetic protective alleles or environmental protective exposures were evidenced).

2.4 Gene–environment interactions

Explicit gene–environment interaction evidence was not present in the retrieved corpus. The best-supported interaction framework here is “parasite species × host immune state × environment/vector ecology” determining clinical form and outcomes. (cosma2024leishmaniasisinhumans pages 2-4, fischer2024treatmentofmucocutaneous pages 2-2)

3. Phenotypes

3.1 Core clinical phenotypes by form (with suggested HPO terms)

Cutaneous leishmaniasis (CL) - Skin ulcer(s) / papules/plaques; lesions may persist months–years; atrophic scarring common. (balahbib2023cutaneousleishmaniasisphysiopathology pages 4-6, balahbib2023cutaneousleishmaniasisphysiopathology pages 1-4) - Suggested HPO: Skin ulcer (HP:0031432); Scar (HP:0100716); Skin papule (HP:0200037). - Typical incubation reported as 1–4 months and spontaneous healing over 2–10 months in some cases. (balahbib2023cutaneousleishmaniasisphysiopathology pages 1-4)

Mucocutaneous leishmaniasis (MCL/ML) - Destructive granulomatous lesions of oral/nasal/pharyngeal mucosa; complications include impaired swallowing/speech, aspiration pneumonia, bacterial superinfection/sepsis, and need for reconstructive surgery. (fischer2024treatmentofmucocutaneous pages 2-2) - Suggested HPO: Nasal septum perforation (HP:0011833); Dysphagia (HP:0002015); Dysarthria (HP:0001260).

Visceral leishmaniasis (VL; kala-azar) - Systemic syndrome including fever, weight loss, hepatosplenomegaly, and cytopenias (pancytopenia/anemia). (balahbib2023cutaneousleishmaniasisphysiopathology pages 4-6, cosma2024leishmaniasisinhumans pages 2-4) - Suggested HPO: Fever (HP:0001945); Weight loss (HP:0001824); Splenomegaly (HP:0001744); Hepatomegaly (HP:0002240); Anemia (HP:0001903); Pancytopenia (HP:0001876).

Post-kala-azar dermal leishmaniasis (PKDL) - Recognized as post-VL dermal manifestation; detailed phenotype frequencies not evidenced in the retrieved set. (cosma2024leishmaniasisinhumans pages 2-4)

3.2 Quality of life impact

CL and MCL can cause scarring/disfigurement with substantial psychosocial morbidity. (cosma2024leishmaniasisinhumans pages 2-4, balahbib2023cutaneousleishmaniasisphysiopathology pages 4-6)

4. Genetic / Molecular Information

4.1 Human causal genes / Mendelian causes

Leishmaniasis is not a monogenic inherited disease; causal pathogen is Leishmania spp. Host genetics can modulate susceptibility and course, but specific loci were not evidenced in the retrieved corpus.

4.2 Molecular mechanisms (host–pathogen) and ontology suggestions

4.2.1 Cellular tropism and immune evasion (VL and CL)

  • Parasite survival involves immune evasion mechanisms that favor anti-inflammatory environments, including immune checkpoint activity and cytokine skewing. (lodi2024immuneresponseto pages 10-11, dey2024il32producingcd8+ pages 1-7)

Phagosome manipulation (VL) - L. donovani lipophosphoglycan (LPG) can exclude vesicular proton-ATPase (V-ATPase) from phagosomes by impairing Synaptotagmin V recruitment, limiting acidification. (lodi2024immuneresponseto pages 10-11)

TLR pathway suppression - Parasites can exploit host deubiquitinating enzyme A20, a negative regulator of TLR signaling, to subvert innate responses. (lodi2024immuneresponseto pages 10-11)

Suggested ontologies: - GO biological process: response to protozoan (GO:0009617); phagosome maturation (GO:0090382); regulation of Toll-like receptor signaling pathway (GO:0034121). - CL cell types: macrophage (CL:0000235); neutrophil (CL:0000775); dendritic cell (CL:0000451); CD8-positive, alpha-beta T cell (CL:0000625); regulatory T cell (CL:0000815).

4.2.2 Immune checkpoints and localized immunosuppressive niches (human CL; 2024)

Spatial and single-cell profiling of human CL lesions identified myeloid-centered niches co-expressing PD-L1 (CD274) and IDO1, with neighboring IL-32–producing CD8+ memory T cells and Tregs. Mechanistically, IDO1-mediated tryptophan catabolism can suppress T-cell proliferation and promote regulatory phenotypes, and PD-L1 can suppress T-cell activation via PD-1 engagement. (dey2024il32producingcd8+ pages 7-11, dey2024il32producingcd8+ pages 11-15)

Quantitative prognostic finding (treatment response): Higher IL-32+ CD8+ T cell abundance was associated with slower cure; IL-32-low patients cured earlier with hazard ratios reported in the preprint. (dey2024il32producingcd8+ pages 11-15)

Suggested ontologies: - GO: tryptophan catabolic process (GO:0006569); negative regulation of T cell activation (GO:0050868).

4.2.3 Hypoxia–neutrophil–CD8 cytotoxic pathology in CL (2024)

A 2024 mechanistic study supports a causal chain in CL lesions: neutrophil recruitment increases oxygen consumption and reactive oxygen species (ROS) generation, amplifying local hypoxia; hypoxia drives Blimp-1/PRDM1 and induces cytolytic differentiation and granzyme B expression in lesion CD8+ T cells. Downstream, cytolysis activates NLRP3 inflammasome/IL-1β and perpetuates neutrophilic inflammation and tissue damage. Human CL lesions exhibit hypoxia transcriptional signatures correlated with neutrophils. (fowler2024neutrophilmediatedhypoxiadrives pages 1-2)

Suggested ontologies: - GO: response to hypoxia (GO:0001666); neutrophil degranulation (GO:0043312); T cell mediated cytotoxicity (GO:0001913); NLRP3 inflammasome complex assembly (GO:0072557).

4.2.4 Epigenetic regulation and IL-10/IL-12 reciprocity (macrophage; 2024)

Single-cell ATAC-seq analysis in a macrophage infection model identified a transient “sleepy macrophage” state and a reciprocal IL-10/IL-12 axis; the work emphasizes transcription-factor-driven chromatin remodeling and epigenetic control of inflammatory cytokine programs in infected macrophages. (khandibharad2024singlecellatacsequencing pages 1-2)

Suggested ontologies: - GO: chromatin remodeling (GO:0006338); regulation of interleukin-10 production (GO:0032666); regulation of interleukin-12 production (GO:0032655).

4.2.5 Single-cell atlas of parasite development in the vector (2024)

Single-cell analysis of Leishmania development in sandflies identified heterogeneity in transmitted parasite forms beyond classical nondividing metacyclic promastigotes, including “replicating early metacyclics” and haptomonad stages, with in vivo mouse infection indicating pathology is not restricted to a single transmitted stage. (parkash2024safetyandreactogenicity pages 2-3)

5. Environmental Information

5.1 Environmental and ecological drivers (One Health)

Environmental disruptions (climate change, deforestation, urbanization) and human/animal movement can expand sandfly range and human-vector contact, contributing to emergence in previously non-endemic areas. (cosma2024leishmaniasisinhumans pages 2-4)

5.2 Reservoirs and zoonotic ecology

Domestic dogs are highlighted as primary reservoirs for zoonotic visceral leishmaniasis in some settings, with additional roles for wild reservoirs. (sousa2024visceralleishmaniasistherapeutic pages 4-6)

6. Anatomical Structures Affected

6.1 Primary organs/tissues

  • Skin (cutaneous lesions; scarring). (balahbib2023cutaneousleishmaniasisphysiopathology pages 4-6)
  • Suggested UBERON: skin of body (UBERON:0002097)
  • Mucosa of upper aerodigestive tract (nasal/oral/pharyngeal). (fischer2024treatmentofmucocutaneous pages 2-2)
  • Suggested UBERON: nasal mucosa (UBERON:0001707); oral mucosa (UBERON:0000344)
  • Spleen, liver, bone marrow (visceral leishmaniasis systemic involvement and diagnostic sampling sites). (cosma2024leishmaniasisinhumans pages 2-4, gritti2024epidemiologicalclinicaland pages 30-35)
  • Suggested UBERON: spleen (UBERON:0002106); liver (UBERON:0002107); bone marrow (UBERON:0002371)

6.2 Subcellular compartments

Not explicitly evidenced in the retrieved corpus; infection is intracellular (amastigotes in host cells). (mota2024classicalandinnovative pages 1-3)

7. Temporal Development

  • CL incubation: reported 1–4 months in a 2023 review; typical spontaneous healing 2–10 months (variable). (balahbib2023cutaneousleishmaniasisphysiopathology pages 1-4)
  • MCL evolution: may occur after untreated/inadequately treated CL, potentially years later. (balahbib2023cutaneousleishmaniasisphysiopathology pages 4-6, fischer2024treatmentofmucocutaneous pages 2-2)
  • VL progression: can be fatal if untreated; Sousa 2024 reports untreated mortality exceeding 95%. (sousa2024visceralleishmaniasistherapeutic pages 4-6)

8. Inheritance and Population

8.1 Epidemiology (recent statistics)

  • Global annual incidence often cited as 700,000–1,000,000 new cases/year. (cosma2024leishmaniasisinhumans pages 2-4)
  • For CL, WHO reported 253,435 new cases in 2018; a review cites 500,000–1,000,000 new cases annually. (balahbib2023cutaneousleishmaniasisphysiopathology pages 4-6)
  • For VL, a 2024 review estimates 50,000–90,000 new cases/year, with only 25–45% officially reported, and untreated mortality >95%. (sousa2024visceralleishmaniasistherapeutic pages 4-6)
  • VL is concentrated in India, Sudan, Brazil, and Kenya (reported as 68% of cases). (sousa2024visceralleishmaniasistherapeutic pages 4-6)

8.2 Geographic distribution and expansion

Leishmaniasis is endemic across Africa, Asia, Southern Europe, the Middle East, and Central/South America, with recent reports of autochthonous transmission in previously non-endemic Western Europe and North America attributed to climate and migration drivers. (cosma2024leishmaniasisinhumans pages 2-4)

9. Diagnostics

9.1 Parasitological diagnosis (microscopy, histology, culture)

  • VL: microscopy sensitivity differs by sampling site: splenic aspirate/biopsy microscopy reported >90% sensitivity, bone marrow aspirate 50–80%, with a quoted 0.1% fatality risk for splenic sampling. (gritti2024epidemiologicalclinicaland pages 30-35)
  • CL: microscopy of skin biopsy for amastigotes is used; one cited study reports direct exam sensitivity ~89.3%, decreasing with older lesions. (balahbib2023cutaneousleishmaniasisphysiopathology pages 9-12, balahbib2023cutaneousleishmaniasisphysiopathology pages 12-15)
  • Culture: reported as uncommon in some settings due to long growth time; sensitivity cited as 60–85%. (gritti2024epidemiologicalclinicaland pages 35-39)

9.2 Serology

  • rK39 antigen is cited as useful for VL; performance may vary by geography (high performance in Indian subcontinent, lower sensitivity in Eastern Africa and southern Europe). (balahbib2023cutaneousleishmaniasisphysiopathology pages 12-15, gritti2024epidemiologicalclinicaland pages 35-39)

9.3 Molecular diagnostics and species typing

  • PCR can detect as few as 10 parasites/mL, with sensitivity 86–95% in acute lesions but lower in chronic disease (~45.5% in one report). (balahbib2023cutaneousleishmaniasisphysiopathology pages 12-15)
  • For imported ACL cases in Germany, diagnosis was clinical + PCR confirmation, with typing via ITS1/SSU rRNA PCR-RFLP and later HSP70 PCR-RFLP. (lindner2024americancutaneousleishmaniasis pages 2-4)
  • Molecular typing: MLEE is described as historical gold standard but laborious and requires culture; high-copy targets used for molecular typing include kDNA minicircles, miniexon, and hsp70 (widely validated for species typing). (gritti2024epidemiologicalclinicaland pages 39-44, gritti2024epidemiologicalclinicaland pages 35-39)

9.4 Diagnostics used in recent spatial-omics CL studies

Studies of human CL lesions used slit-skin smears (Giemsa), PCR/qPCR confirmation, and RNA-FISH probes (e.g., amastin) for parasite detection in tissue sections. (dey2024il32producingcd8+ pages 19-22)

10. Outcome / Prognosis

  • VL is described as potentially fatal if untreated; one 2024 review states untreated mortality exceeds 95%. (sousa2024visceralleishmaniasistherapeutic pages 4-6)
  • In Brazil, a 2024 narrative review reports 50,478 cases and 3,945 deaths through Aug 2024 with mortality 7.02% (as reported in that secondary source). (sousa2024visceralleishmaniasistherapeutic pages 4-6)
  • CL and MCL often lead to chronic morbidity via scarring/disfigurement and mucosal destruction. (fischer2024treatmentofmucocutaneous pages 2-2, cosma2024leishmaniasisinhumans pages 2-4)

11. Treatment

11.1 Standard pharmacotherapy and real-world use

Common antileishmanial agents across syndromes include pentavalent antimonials, amphotericin B (including liposomal), miltefosine, paromomycin, and pentamidine; choice often depends on setting/availability and host factors. (sousa2024visceralleishmaniasistherapeutic pages 4-6, fischer2024treatmentofmucocutaneous pages 2-2)

11.2 Quantitative treatment outcomes from recent evidence

Liposomal amphotericin B for cutaneous/mucosal disease (systematic review/meta-analysis; 2023)

  • Pooled cure rate (case series): 87.0% (95% CI 79–92%) across 38 case series. (Chivinski et al., 2023-07, DOI: 10.1093/ofid/ofad348) (chivinski2023intravenousliposomalamphotericin pages 1-2)
  • Case reports cure: 65/92 (82.3%). (chivinski2023intravenousliposomalamphotericin pages 1-2)
  • Adverse reactions: in pooled data, adverse reactions reported in 40.7% of cases; most commonly renal toxicity and infusion reactions. (chivinski2023intravenousliposomalamphotericin pages 7-9)

Mucocutaneous leishmaniasis therapies (systematic review; 2024)

  • Species-stratified outcomes show high reported success for L-AmB in multiple small series (e.g., L. braziliensis 57/64 (89%)). (fischer2024treatmentofmucocutaneous pages 4-4)
  • Combination therapy NMA + pentoxifylline had 9/10 cured in one report and an overall cure rate reported as 95% for the combination. (fischer2024treatmentofmucocutaneous pages 6-7)

Post-kala-azar dermal leishmaniasis (PKDL) randomized trial (2021)

  • Per-protocol final cure: 74.5% (liposomal amphotericin B) vs 86.9% (miltefosine). (pandey2021arandomizedopenlabel pages 3-4)
  • Adverse events: 82% vs 56% (mostly grade I–II). (pandey2021arandomizedopenlabel pages 3-4)

11.3 Treatment guidelines (evidence limitation)

Formal WHO/IDSA guideline text was not retrieved in this corpus; treatment regimen details referenced in the meta-analysis include mention of guideline cumulative dosing (e.g., IDSA cumulative 18–21 mg/kg for L-AmB) but without full guideline retrieval. (chivinski2023intravenousliposomalamphotericin pages 7-9)

11.4 MAXO term suggestions (treatments)

  • Liposomal amphotericin B therapy: MAXO:0000743 (antifungal/antiparasitic drug therapy) (placeholder—MAXO IDs not evidenced in corpus).
  • Cryotherapy for localized CL lesions (used in CHIM recurrences): MAXO:0000549 (cryotherapy) (placeholder—MAXO IDs not evidenced in corpus). (parkash2024safetyandreactogenicity pages 1-2)

12. Prevention

12.1 Vector/reservoir control and One Health prevention

Integrated surveillance and prevention strategies targeting vectors, animal reservoirs (notably dogs), and human exposure are emphasized in the One Health literature; drivers such as climate change and land-use change motivate adaptive surveillance. (cosma2024leishmaniasisinhumans pages 2-4, sousa2024visceralleishmaniasistherapeutic pages 4-6)

12.2 Vaccines and CHIM as a vaccine-enabling technology (2024)

A major 2024 development is the establishment of a controlled human infection model (CHIM) for sand fly–transmitted L. major CL to accelerate vaccine development. (parkash2024safetyandreactogenicity pages 2-3, parkash2024safetyandreactogenicity pages 1-2)

Direct abstract support (CHIM quote): - “The leishmaniases are globally important parasitic diseases for which no human vaccines are currently available.” (Parkash et al., Nature Medicine, 2024-08, DOI: 10.1038/s41591-024-03146-9) (parkash2024safetyandreactogenicity pages 1-2)

13. Other Species / Natural Disease (One Health)

  • Dogs are highlighted as primary domestic reservoirs for visceral leishmaniasis in the Americas, with implications for zoonotic transmission and control. (sousa2024visceralleishmaniasistherapeutic pages 4-6)
  • Leishmaniasis is framed as a human–animal–environment system, influenced by pet trade, breeding, and migration affecting reservoir movement. (cosma2024leishmaniasisinhumans pages 2-4)

14. Model Organisms and Experimental Systems

14.1 Human CHIM (real-world implementation for translational research)

  • Model: sand fly–transmitted CL CHIM (L. major via Phlebotomus duboscqi). (parkash2024safetyandreactogenicity pages 2-3)
  • Take rate: 64% overall (9/14), 82% among confirmed bites (9/11). (parkash2024safetyandreactogenicity pages 2-3)
  • Trial registration: NCT04512742. (parkash2024safetyandreactogenicity pages 1-2)
  • Safety: no severe/serious adverse events; recurrences treated successfully with cryotherapy; scarring observed. (parkash2024safetyandreactogenicity pages 1-2)

14.2 Mouse models

Mechanistic work in mice supports roles for neutrophils/hypoxia and CD8 cytotoxicity in CL pathology. (fowler2024neutrophilmediatedhypoxiadrives pages 1-2)

14.3 Macaque model (visceral persistence; single-cell)

A rhesus macaque VL model with post-treatment tissue reservoirs and single-cell transcriptomic profiling is described (preprint), highlighting parasite persistence in spleen, bone marrow, and lymph nodes after miltefosine. (parkash2024safetyandreactogenicity pages 2-3)

15. Clinical Trials and Development Pipeline (selected)

ClinicalTrials.gov trials retrieved include: - NCT04512742: sand fly-transmitted CL CHIM (vaccine-enabling model). (parkash2024safetyandreactogenicity pages 1-2) - VL combination therapy trials (completed): NCT01122771, NCT00696969, NCT00523965, NCT00371995. (clinical-trials tool output; not chunk-cited in current evidence set) - Cutaneous/mucosal treatment trials: NCT01377974 (miltefosine for mucosal leishmaniasis), NCT03829917 (oral miltefosine + topical paromomycin in ACL). (clinical-trials tool output; not chunk-cited in current evidence set)

Expert interpretation and analysis (2023–2024 emphasis)

  1. Diagnostics are moving toward molecular confirmation and species typing, driven by heterogeneous treatment response across Leishmania species and the need to guide therapy; PCR-RFLP and HSP70 typing are used in real-world clinical practice for imported cases. (lindner2024americancutaneousleishmaniasis pages 2-4, gritti2024epidemiologicalclinicaland pages 39-44)
  2. Pathophysiology is increasingly understood as spatially compartmentalized immunopathology, where distinct immune niches and checkpoints exist within lesions; spatial transcriptomics and single-cell methods identify actionable pathways (PD-L1/IDO1; hypoxia-driven cytotoxicity). (dey2024il32producingcd8+ pages 7-11, fowler2024neutrophilmediatedhypoxiadrives pages 1-2)
  3. A major translational development is the CL CHIM that directly supports vaccine development by enabling controlled assessment of protective immunity and lesion biology in humans, including spatial immune mapping. (parkash2024safetyandreactogenicity pages 1-2, parkash2024safetyeffectivenessand pages 13-17)
  4. One Health framing is essential: climate change and land-use shifts are not only upstream risk drivers but also determinants of future geographic spread, requiring surveillance strategies integrating humans, vectors, and reservoir animals (notably dogs). (cosma2024leishmaniasisinhumans pages 2-4, sousa2024visceralleishmaniasistherapeutic pages 4-6)

Key URLs (publication pages)

  • Cosma et al. 2024 (One Health perspective): https://doi.org/10.3390/tropicalmed9110258 (published 2024-10) (cosma2024leishmaniasisinhumans pages 2-4)
  • Parkash et al. 2024 (Nature Medicine CHIM): https://doi.org/10.1038/s41591-024-03146-9 (published 2024-08) (parkash2024safetyandreactogenicity pages 1-2)
  • Chivinski et al. 2023 (L-AmB meta-analysis): https://doi.org/10.1093/ofid/ofad348 (published 2023-07) (chivinski2023intravenousliposomalamphotericin pages 1-2)
  • Fischer et al. 2024 (MCL treatment systematic review): https://doi.org/10.1111/ddg.15424 (published 2024-05) (fischer2024treatmentofmucocutaneous pages 2-2)
  • Fowler et al. 2024 (hypoxia/CD8 pathology): https://doi.org/10.1172/jci177992 (published 2024-06) (fowler2024neutrophilmediatedhypoxiadrives pages 1-2)
  • Khandibharad & Singh 2024 (scATAC “sleepy macrophages”): https://doi.org/10.1128/spectrum.03478-23 (published 2024-03) (khandibharad2024singlecellatacsequencing pages 1-2)

Not-yet-fulfilled template elements (data not present in retrieved evidence)

  • Curated IDs (MONDO, MeSH, ICD-10/11, Orphanet) and validated ontology mappings (MAXO IDs, specific UBERON/HPO/GO IDs) were not available in the evidence corpus and therefore remain incomplete.
  • Specific host genetic susceptibility loci/variants and protective factors were not retrieved.

References

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