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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name: Leishmaniasis
creation_date: '2026-01-26T03:01:01Z'
updated_date: '2026-04-11T01:06:52Z'
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
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.
- 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.
phenotypes:
- name: Cutaneous ulcers
category: Dermatologic
frequency: FREQUENT
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 self-healing ulcers in cutaneous leishmaniasis.
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.
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
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)
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)
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)
Not directly identified in the retrieved evidence corpus (no specific host genetic protective alleles or environmental protective exposures were evidenced).
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)
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)
CL and MCL can cause scarring/disfigurement with substantial psychosocial morbidity. (cosma2024leishmaniasisinhumans pages 2-4, balahbib2023cutaneousleishmaniasisphysiopathology pages 4-6)
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.
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).
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).
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).
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).
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)
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)
Domestic dogs are highlighted as primary reservoirs for zoonotic visceral leishmaniasis in some settings, with additional roles for wild reservoirs. (sousa2024visceralleishmaniasistherapeutic pages 4-6)
Not explicitly evidenced in the retrieved corpus; infection is intracellular (amastigotes in host cells). (mota2024classicalandinnovative pages 1-3)
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)
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)
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)
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)
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)
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)
Mechanistic work in mice supports roles for neutrophils/hypoxia and CD8 cytotoxicity in CL pathology. (fowler2024neutrophilmediatedhypoxiadrives pages 1-2)
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)
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)
References
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