Granuloma Inguinale

Infectious Disease MONDO:0005777 Pathograph 11 Show in embeddings browser Bacterial Infection Sexually transmitted infection

Granuloma inguinale, also called donovanosis, is a sexually transmitted bacterial genital-ulcer disease caused by Klebsiella granulomatis, formerly Calymmatobacterium granulomatis. K. granulomatis persists within macrophage-lineage cells as Donovan bodies, driving chronic plasma-cell-rich granulomatous inflammation with progressively enlarging genital ulcers. Diagnosis is usually confirmed by cytologic detection of Donovan bodies, and treatment uses prolonged ribosome-targeting antibiotics, with azithromycin recommended weekly until all lesions have healed.

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6
Pathophys.
3
Phenotypes
11
Pathograph
2
Medical Actions
1
Subtypes
1
Deep Research
🏷

Classifications

Harrison's Part
INFECTIOUS DISEASES
◆

Subtypes

1
Extragenital donovanosis
Rare primary or secondary donovanosis at extragenital sites such as the foot, cervix, or pelvis, in addition to the typical genital presentation.
Show evidence (1 reference)
PMID:9924476 SUPPORT Human Clinical
"An extremely rare case of primary extragenital donovanosis affecting the dorsa of right foot is reported."
Documents extragenital (foot) donovanosis as a rare presentation.
⚙

Pathophysiology

6
K. granulomatis Intramacrophage Persistence
K. granulomatis persists in genital tissue biopsy specimens predominantly inside variably sized cytoplasmic vacuoles of macrophages, corresponding to the intracytoplasmic Donovan bodies used for diagnosis.
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
Plasma-Cell-Rich Granulomatous Inflammation Intracellular bacterial persistence drives a chronic macrophage- and plasma-cell-rich inflammatory reaction.
Show evidence (1 reference)
PMID:9856642 SUPPORT Human Clinical
"In tissue specimens the bacteria were located predominantly within vacuoles of varying sizes in the cytoplasm of the macrophages and, occasionally, extracellularly within the intercellular spaces of the stroma."
Ultrastructural examination of biopsy specimens places K. granulomatis in macrophage cytoplasmic vacuoles, the intracellular step represented by this node.
Plasma-Cell-Rich Granulomatous Inflammation
Donovanosis lesions are dominated by chronic granulomatous inflammation with macrophage-lineage histiocytes, neutrophils, and plasma cells. This persistent infiltrate supports granulation tissue and pseudoepitheliomatous epithelial reaction at the ulcer edge.
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. plasma cell CL:0000786 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves plasma cell (CL:0000786). CL:0000786 is a cell type from the Cell Ontology. neutrophil CL:0000775 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves neutrophil (CL:0000775). CL:0000775 is a cell type from the Cell Ontology.
inflammatory response GO:0006954 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased inflammatory response (GO:0006954). GO:0006954 is a biological process from the Gene Ontology. ↑ INCREASED
Downstream
Chronic Friable Genital Ulceration Persistent granulomatous inflammation and granulation tissue produce the enlarging genital ulcers that define the disease.
Lymphatic Obstruction Chronic scarring inflammation can obstruct lymphatic drainage of the genital region.
Show evidence (2 references)
PMID:18317211 SUPPORT Human Clinical
"granulation tissue containing a dense plasma cell infiltrate, aggregates of neutrophils, and vacuolated enlarged histiocytes containing Donovan bodies were noted."
Biopsy histology shows the dense plasma-cell, neutrophil, and histiocyte infiltrate this node asserts.
PMID:2777345 SUPPORT Human Clinical
"Other cells seen included plasma cells, polymorphonuclear cells and sparse lymphocytes."
Cytology confirms plasma cells and polymorphonuclear cells in the lesional infiltrate.
Chronic Friable Genital Ulceration
Genital papules enlarge into chronic ulcerogranulomatous, hypertrophic, necrotic, or sclerotic lesions; the ulcerogranulomatous phenotype predominates and produces the beefy, friable genital ulcer typical of donovanosis.
Downstream
Genital ulcers Granuloma inguinale presents with chronic genital ulcers.
Squamous cell carcinoma Long-standing donovanosis lesions can undergo malignant transformation to squamous cell carcinoma.
Enhanced HIV Transmission and Acquisition The chronic bleeding genital ulcer acts as a cofactor for HIV transmission and acquisition.
Show evidence (2 references)
PMID:26882914 SUPPORT Human Clinical
"The incubation period is approximately 50 days with genital papules developing into ulcers that increase in size."
Supports progression from papules to enlarging genital ulcers.
PMID:8509089 SUPPORT Human Clinical
"Lesions were ulcero-granulomatous in 162, hypertrophic in eight and necrotic in one."
Supports the dominance of ulcerogranulomatous lesions among 171 cytology-confirmed Durban donovanosis cases.
Lymphatic Obstruction
Chronic scarring donovanosis can obstruct genital lymphatic drainage, producing genital lymphedema (elephantiasis), one of the recognized late complications of bacterial genital-ulcer STIs.
Downstream
Lymphedema Lymphatic obstruction produces genital lymphedema/elephantiasis.
Show evidence (1 reference)
PMID:16510000 SUPPORT REVIEW SYNTHESIS Human Clinical
"a small but significant proportion of patients develop genital elephantiasis due to bacterial sexually transmitted infections (STIs), mainly lymphogranuloma venereum (LGV) and donovanosis."
Donovanosis is a bacterial STI cause of genital elephantiasis from lymphatic obstruction.
Enhanced HIV Transmission and Acquisition
Donovanosis genital ulcers bleed readily and are a recognized risk factor for HIV transmission and acquisition, and treatment failure can occur in advanced HIV disease.
Show evidence (1 reference)
PMID:7750949 SUPPORT REVIEW SYNTHESIS Human Clinical
"Donovanosis is an uncommon GUD with low infectivity characterised by large ulcers that bleed readily and has been identified as a risk factor for HIV in men in Durban, South Africa."
Donovanosis genital ulcers are identified as a risk factor for HIV.
Bacterial mRNA Translation by the Ribosome (Macrolide and Tetracycline Target)
K. granulomatis depends on bacterial 70S-ribosome translation. The principal donovanosis antibiotics, including azithromycin, erythromycin, and doxycycline, act through bacterial ribosomal targets and must be continued long enough to clear the chronic intracellular infection.
translation GO:0006412 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves translation (GO:0006412). GO:0006412 is a biological process from the Gene Ontology.
⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Granuloma Inguinale 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

3
Genitourinary 1
Genital ulcers VERY_FREQUENT HP:0003249 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Genital ulcers (HP:0003249). HP:0003249 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:26882914 SUPPORT Human Clinical
"Four types of lesions are described - ulcerogranulomatous, hypertrophic, necrotic and sclerotic."
Supports the recognized morphologic spectrum of ulcerative donovanosis lesions.
Integument 1
Squamous cell carcinoma HP:0002860 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Squamous cell carcinoma (HP:0002860). HP:0002860 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:19061590 SUPPORT Human Clinical
"In our case the patient did not respond to treatment for donovanosis and on biopsy we realized that the patient had coexistent SCC, which is hitherto unreported with granuloma inguinale."
Documents squamous cell carcinoma arising in a donovanosis lesion.
Metabolism 1
Lymphedema HP:0001004 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Genital elephantiasis (lymphedema), annotated with Lymphedema (HP:0001004). HP:0001004 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:16510000 SUPPORT REVIEW SYNTHESIS Human Clinical
"a small but significant proportion of patients develop genital elephantiasis due to bacterial sexually transmitted infections (STIs), mainly lymphogranuloma venereum (LGV) and donovanosis."
Genital elephantiasis is a recognized donovanosis complication.
💊

Medical Actions

2
Azithromycin 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: azithromycin CHEBI:2955 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses azithromycin (CHEBI:2955). CHEBI:2955 is a therapeutic agent from Chemical Entities of Biological Interest.
Platform: Small molecule
Azithromycin is the recommended oral macrolide therapy for donovanosis and is continued once weekly until lesions have completely healed.
Mechanism Target:
INHIBITS Bacterial mRNA Translation by the Ribosome (Macrolide and Tetracycline Target) — Azithromycin acts as a ribosome-targeting macrolide antibacterial agent against K. granulomatis.
Show evidence (2 references)
PMID:21097731 SUPPORT Human Clinical
"The recommended treatment is azithromycin 1 g weekly until complete healing is achieved."
Directly supports the guideline-recommended weekly azithromycin regimen for donovanosis.
PMID:12473810 SUPPORT REVIEW SYNTHESIS Human Clinical
"Azithromycin has emerged as the drug of choice and should be used if the diagnosis is confirmed or suspected."
The review names azithromycin as the drug of choice for donovanosis.
Doxycycline 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: doxycycline CHEBI:50845 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses doxycycline (CHEBI:50845). CHEBI:50845 is a therapeutic agent from Chemical Entities of Biological Interest.
Platform: Small molecule
Doxycycline is an oral tetracycline alternative for donovanosis, used as a prolonged ribosome-targeting antibacterial regimen until lesions heal.
Mechanism Target:
INHIBITS Bacterial mRNA Translation by the Ribosome (Macrolide and Tetracycline Target) — Doxycycline inhibits bacterial translation at the ribosome.
Show evidence (1 reference)
PMID:22335265 SUPPORT Human Clinical
"Lymphogranuloma venereum and donovanosis are treated with 21 days of oral doxycycline."
Supports a 21-day doxycycline regimen as an oral treatment option for donovanosis in genital-ulcer disease management.
🔬

Diagnosis

2
Cytologic detection of Donovan bodies
Donovanosis is usually confirmed by microscopic identification of characteristic intracytoplasmic Donovan bodies on stained tissue smears or crush preparations.
microscopy for Donovan bodies on tissue smears NCIT:C16853 NCI Thesaurus (NCIT)
Show evidence (1 reference)
PMID:26882914 SUPPORT REVIEW SYNTHESIS Human Clinical
"The diagnosis is usually confirmed by microscopic identification of characteristic Donovan bodies on stained tissue smears."
The guideline states Donovan-body microscopy is the usual diagnostic confirmation.
Polymerase chain reaction
PCR methods have been developed for detecting K. granulomatis in genital ulcer specimens.
polymerase chain reaction for K. granulomatis NCIT:C17003 NCI Thesaurus (NCIT)
Show evidence (1 reference)
PMID:21097731 SUPPORT REVIEW SYNTHESIS Human Clinical
"More recently, polymerase chain reaction (PCR) methods have been developed."
The guideline records PCR as a more recent diagnostic method for donovanosis.
📊

Prevalence

1
Worldwide
Unknown Rare
A rare sexually transmitted infection now seen mainly as sporadic cases in a few endemic regions.
Show evidence (1 reference)
PMID:26882914 SUPPORT REVIEW SYNTHESIS Human Clinical
"Donovanosis is a rare sexually transmitted infection now mainly seen in sporadic cases in Papua New Guinea, South Africa, India, Brazil and Australia."
The guideline characterizes donovanosis as rare and sporadic.
🦠

Infectious Agent

1
Klebsiella granulomatis
The Gram-negative bacterium that causes donovanosis and is visible as intracytoplasmic Donovan bodies in lesional macrophages.
Klebsiella granulomatis NCBITaxon:39824 NCBI Taxonomy (NCBITaxon)
Show evidence (2 references)
PMID:26882914 SUPPORT Human Clinical
"The causative organism is Calymmatobacterium granulomatis, though a proposal has been put forward that the organism be reclassified as Klebsiella granulomatis comb nov"
The guideline names the donovanosis bacterium and records the Klebsiella-granulomatis reclassification used by the NCBI Taxonomy term.
PMID:10555350 SUPPORT Other
"It is proposed that C. granulomatis should be reclassified as Klebsiella granulomatis comb. nov."
The 16S rRNA/phoE phylogenetic study provides the direct molecular basis for the current Klebsiella granulomatis name.
↔️

Transmission

1
Sexual transmission
K. granulomatis is acquired as a rare sexually transmitted infection in areas where donovanosis remains endemic or sporadic.
Show evidence (1 reference)
PMID:26882914 SUPPORT Human Clinical
"Donovanosis is a rare sexually transmitted infection now mainly seen in sporadic cases in Papua New Guinea, South Africa, India, Brazil and Australia."
Supports sexual transmission and the contemporary sporadic/endemic geography of granuloma inguinale.
{ }

Source YAML

click to show 
name: Granuloma Inguinale
creation_date: '2026-09-25T00:00:00Z'
category: Infectious Disease
description: >-
  Granuloma inguinale, also called donovanosis, is a sexually transmitted
  bacterial genital-ulcer disease caused by Klebsiella granulomatis, formerly
  Calymmatobacterium granulomatis. K. granulomatis persists within
  macrophage-lineage cells as Donovan bodies, driving chronic plasma-cell-rich
  granulomatous inflammation with progressively enlarging genital ulcers.
  Diagnosis is usually confirmed by cytologic detection of Donovan bodies, and
  treatment uses prolonged ribosome-targeting antibiotics, with azithromycin
  recommended weekly until all lesions have healed.
disease_term:
  preferred_term: granuloma inguinale
  term:
    id: MONDO:0005777
    label: granuloma inguinale
parents:
- Bacterial Infection
- Sexually transmitted infection
classifications:
  harrisons_chapter:
  - classification_value: INFECTIOUS_DISEASES
has_subtypes:
- name: Extragenital
  display_name: Extragenital donovanosis
  description: >-
    Rare primary or secondary donovanosis at extragenital sites such as the
    foot, cervix, or pelvis, in addition to the typical genital presentation.
  evidence:
  - reference: PMID:9924476
    reference_title: "Extragenital donovanosis of the foot."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      An extremely rare case of primary extragenital donovanosis affecting the
      dorsa of right foot is reported.
    explanation: Documents extragenital (foot) donovanosis as a rare presentation.
infectious_agent:
- name: Klebsiella granulomatis
  description: >-
    The Gram-negative bacterium that causes donovanosis and is visible as
    intracytoplasmic Donovan bodies in lesional macrophages.
  infectious_agent_term:
    preferred_term: Klebsiella granulomatis
    term:
      id: NCBITaxon:39824
      label: Klebsiella granulomatis
  evidence:
  - reference: PMID:26882914
    reference_title: 2016 European guideline on donovanosis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The causative organism is Calymmatobacterium granulomatis, though a
      proposal has been put forward that the organism be reclassified as
      Klebsiella granulomatis comb nov
    explanation: >-
      The guideline names the donovanosis bacterium and records the
      Klebsiella-granulomatis reclassification used by the NCBI Taxonomy term.
  - reference: PMID:10555350
    reference_title: >-
      Phylogenetic evidence for reclassification of Calymmatobacterium
      granulomatis as Klebsiella granulomatis comb. nov.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      It is proposed that C. granulomatis should be reclassified as Klebsiella
      granulomatis comb. nov.
    explanation: >-
      The 16S rRNA/phoE phylogenetic study provides the direct molecular basis
      for the current Klebsiella granulomatis name.
transmission:
- name: Sexual transmission
  description: >-
    K. granulomatis is acquired as a rare sexually transmitted infection in
    areas where donovanosis remains endemic or sporadic.
  evidence:
  - reference: PMID:26882914
    reference_title: 2016 European guideline on donovanosis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Donovanosis is a rare sexually transmitted infection now mainly seen in
      sporadic cases in Papua New Guinea, South Africa, India, Brazil and
      Australia.
    explanation: >-
      Supports sexual transmission and the contemporary sporadic/endemic
      geography of granuloma inguinale.
pathophysiology:
- name: K. granulomatis Intramacrophage Persistence
  description: >-
    K. granulomatis persists in genital tissue biopsy specimens predominantly
    inside variably sized cytoplasmic vacuoles of macrophages, corresponding to
    the intracytoplasmic Donovan bodies used for diagnosis.
  role: trigger
  cell_types:
  - preferred_term: macrophage
    term:
      id: CL:0000235
      label: macrophage
  downstream:
  - target: Plasma-Cell-Rich Granulomatous Inflammation
    description: >-
      Intracellular bacterial persistence drives a chronic macrophage- and
      plasma-cell-rich inflammatory reaction.
  evidence:
  - reference: PMID:9856642
    reference_title: >-
      Ultrastructure of Calymmatobacterium granulomatis: comparison of culture
      with tissue biopsy specimens.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      In tissue specimens the bacteria were located predominantly within
      vacuoles of varying sizes in the cytoplasm of the macrophages and,
      occasionally, extracellularly within the intercellular spaces of the
      stroma.
    explanation: >-
      Ultrastructural examination of biopsy specimens places K. granulomatis in
      macrophage cytoplasmic vacuoles, the intracellular step represented by
      this node.
- name: Plasma-Cell-Rich Granulomatous Inflammation
  description: >-
    Donovanosis lesions are dominated by chronic granulomatous inflammation with
    macrophage-lineage histiocytes, neutrophils, and plasma cells. This
    persistent infiltrate supports granulation tissue and pseudoepitheliomatous
    epithelial reaction at the ulcer edge.
  role: central_effector
  cell_types:
  - preferred_term: macrophage
    term:
      id: CL:0000235
      label: macrophage
  - preferred_term: plasma cell
    term:
      id: CL:0000786
      label: plasma cell
  - preferred_term: neutrophil
    term:
      id: CL:0000775
      label: neutrophil
  biological_processes:
  - preferred_term: inflammatory response
    modifier: INCREASED
    term:
      id: GO:0006954
      label: inflammatory response
  evidence:
  - reference: PMID:18317211
    reference_title: "Concomitant malacoplakia and granuloma inguinale of the cervix in acquired immune deficiency syndrome."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      granulation tissue containing a dense plasma cell infiltrate, aggregates
      of neutrophils, and vacuolated enlarged histiocytes containing Donovan
      bodies were noted.
    explanation: Biopsy histology shows the dense plasma-cell, neutrophil, and histiocyte infiltrate this node asserts.
  - reference: PMID:2777345
    reference_title: "An ultrastructural study of donovanosis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Other cells seen included plasma cells, polymorphonuclear cells and sparse
      lymphocytes.
    explanation: Cytology confirms plasma cells and polymorphonuclear cells in the lesional infiltrate.
  downstream:
  - target: Chronic Friable Genital Ulceration
    description: >-
      Persistent granulomatous inflammation and granulation tissue produce the
      enlarging genital ulcers that define the disease.
  - target: Lymphatic Obstruction
    description: >-
      Chronic scarring inflammation can obstruct lymphatic drainage of the
      genital region.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
- name: Chronic Friable Genital Ulceration
  description: >-
    Genital papules enlarge into chronic ulcerogranulomatous, hypertrophic,
    necrotic, or sclerotic lesions; the ulcerogranulomatous phenotype
    predominates and produces the beefy, friable genital ulcer typical of
    donovanosis.
  role: consequence
  downstream:
  - target: Genital ulcers
    description: Granuloma inguinale presents with chronic genital ulcers.
  - target: Squamous cell carcinoma
    description: >-
      Long-standing donovanosis lesions can undergo malignant transformation to
      squamous cell carcinoma.
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
  - target: Enhanced HIV Transmission and Acquisition
    description: >-
      The chronic bleeding genital ulcer acts as a cofactor for HIV
      transmission and acquisition.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
  evidence:
  - reference: PMID:26882914
    reference_title: 2016 European guideline on donovanosis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The incubation period is approximately 50 days with genital papules
      developing into ulcers that increase in size.
    explanation: >-
      Supports progression from papules to enlarging genital ulcers.
  - reference: PMID:8509089
    reference_title: "Clinico-epidemiological study of donovanosis in Durban, South Africa."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Lesions were ulcero-granulomatous in 162, hypertrophic in eight and
      necrotic in one.
    explanation: >-
      Supports the dominance of ulcerogranulomatous lesions among 171
      cytology-confirmed Durban donovanosis cases.
- name: Lymphatic Obstruction
  description: >-
    Chronic scarring donovanosis can obstruct genital lymphatic drainage,
    producing genital lymphedema (elephantiasis), one of the recognized
    late complications of bacterial genital-ulcer STIs.
  role: consequence
  downstream:
  - target: Lymphedema
    description: Lymphatic obstruction produces genital lymphedema/elephantiasis.
  evidence:
  - reference: PMID:16510000
    reference_title: "Genital elephantiasis and sexually transmitted infections - revisited."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      a small but significant proportion of patients develop genital
      elephantiasis due to bacterial sexually transmitted infections (STIs),
      mainly lymphogranuloma venereum (LGV) and donovanosis.
    explanation: Donovanosis is a bacterial STI cause of genital elephantiasis from lymphatic obstruction.
- name: Enhanced HIV Transmission and Acquisition
  description: >-
    Donovanosis genital ulcers bleed readily and are a recognized risk factor
    for HIV transmission and acquisition, and treatment failure can occur in
    advanced HIV disease.
  role: consequence
  evidence:
  - reference: PMID:7750949
    reference_title: "Global eradication of donovanosis: an opportunity for limiting the spread of HIV-1 infection."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Donovanosis is an uncommon GUD with low infectivity characterised by large
      ulcers that bleed readily and has been identified as a risk factor for HIV
      in men in Durban, South Africa.
    explanation: Donovanosis genital ulcers are identified as a risk factor for HIV.
- name: Bacterial mRNA Translation by the Ribosome (Macrolide and Tetracycline Target)
  description: >-
    K. granulomatis depends on bacterial 70S-ribosome translation. The principal
    donovanosis antibiotics, including azithromycin, erythromycin, and
    doxycycline, act through bacterial ribosomal targets and must be continued
    long enough to clear the chronic intracellular infection.
  role: therapeutic_vulnerability
  conforms_to: "bacterial_protein_synthesis_inhibition#Bacterial mRNA Translation by the Ribosome"
  biological_processes:
  - preferred_term: translation
    term:
      id: GO:0006412
      label: translation
phenotypes:
- name: Genital ulcers
  description: >-
    Granuloma inguinale causes genital papules that become progressively
    enlarging chronic ulcers, most often of the ulcerogranulomatous type.
  frequency: VERY_FREQUENT
  phenotype_term:
    preferred_term: Genital ulcers
    term:
      id: HP:0003249
      label: Genital ulcers
  evidence:
  - reference: PMID:26882914
    reference_title: 2016 European guideline on donovanosis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Four types of lesions are described - ulcerogranulomatous, hypertrophic,
      necrotic and sclerotic.
    explanation: >-
      Supports the recognized morphologic spectrum of ulcerative donovanosis
      lesions.
- name: Lymphedema
  description: >-
    Chronic lymphatic obstruction from long-standing donovanosis produces
    genital lymphedema (elephantiasis).
  phenotype_term:
    preferred_term: Genital elephantiasis (lymphedema)
    term:
      id: HP:0001004
      label: Lymphedema
  evidence:
  - reference: PMID:16510000
    reference_title: "Genital elephantiasis and sexually transmitted infections - revisited."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      a small but significant proportion of patients develop genital
      elephantiasis due to bacterial sexually transmitted infections (STIs),
      mainly lymphogranuloma venereum (LGV) and donovanosis.
    explanation: Genital elephantiasis is a recognized donovanosis complication.
- name: Squamous cell carcinoma
  description: >-
    Long-standing donovanosis lesions can undergo malignant transformation to
    squamous cell carcinoma.
  phenotype_term:
    preferred_term: Squamous cell carcinoma
    term:
      id: HP:0002860
      label: Squamous cell carcinoma
  evidence:
  - reference: PMID:19061590
    reference_title: "Malignant transformation of donovanosis (granuloma inguinale) in a HIV-positive patient."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      In our case the patient did not respond to treatment for donovanosis and
      on biopsy we realized that the patient had coexistent SCC, which is
      hitherto unreported with granuloma inguinale.
    explanation: Documents squamous cell carcinoma arising in a donovanosis lesion.
diagnosis:
- name: Cytologic detection of Donovan bodies
  description: >-
    Donovanosis is usually confirmed by microscopic identification of
    characteristic intracytoplasmic Donovan bodies on stained tissue smears or
    crush preparations.
  diagnosis_term:
    preferred_term: microscopy for Donovan bodies on tissue smears
    term:
      id: NCIT:C16853
      label: Microscopy
  evidence:
  - reference: PMID:26882914
    reference_title: 2016 European guideline on donovanosis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      The diagnosis is usually confirmed by microscopic identification of
      characteristic Donovan bodies on stained tissue smears.
    explanation: The guideline states Donovan-body microscopy is the usual diagnostic confirmation.
- name: Polymerase chain reaction
  description: >-
    PCR methods have been developed for detecting K. granulomatis in genital
    ulcer specimens.
  diagnosis_term:
    preferred_term: polymerase chain reaction for K. granulomatis
    term:
      id: NCIT:C17003
      label: Polymerase Chain Reaction
  evidence:
  - reference: PMID:21097731
    reference_title: "European guideline for the management of donovanosis, 2010."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: "More recently, polymerase chain reaction (PCR) methods have been developed."
    explanation: The guideline records PCR as a more recent diagnostic method for donovanosis.
prevalence:
- population: Worldwide
  measure_type: UNKNOWN
  prevalence_class: RARE
  notes: >-
    A rare sexually transmitted infection now seen mainly as sporadic cases in a
    few endemic regions.
  evidence:
  - reference: PMID:26882914
    reference_title: 2016 European guideline on donovanosis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Donovanosis is a rare sexually transmitted infection now mainly seen in
      sporadic cases in Papua New Guinea, South Africa, India, Brazil and
      Australia.
    explanation: The guideline characterizes donovanosis as rare and sporadic.
treatments:
- name: Azithromycin Therapy
  description: >-
    Azithromycin is the recommended oral macrolide therapy for donovanosis and
    is continued once weekly until lesions have completely healed.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: azithromycin
      term:
        id: CHEBI:2955
        label: azithromycin
  therapeutic_modality: SMALL_MOLECULE
  target_mechanisms:
  - target: Bacterial mRNA Translation by the Ribosome (Macrolide and Tetracycline Target)
    treatment_effect: INHIBITS
    description: >-
      Azithromycin acts as a ribosome-targeting macrolide antibacterial agent
      against K. granulomatis.
  evidence:
  - reference: PMID:21097731
    reference_title: "European guideline for the management of donovanosis, 2010."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The recommended treatment is azithromycin 1 g weekly until complete
      healing is achieved.
    explanation: >-
      Directly supports the guideline-recommended weekly azithromycin regimen
      for donovanosis.
  - reference: PMID:12473810
    reference_title: "Donovanosis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Azithromycin has emerged as the drug of choice and should be used if the
      diagnosis is confirmed or suspected.
    explanation: The review names azithromycin as the drug of choice for donovanosis.
- name: Doxycycline Therapy
  description: >-
    Doxycycline is an oral tetracycline alternative for donovanosis, used as a
    prolonged ribosome-targeting antibacterial regimen until lesions heal.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: doxycycline
      term:
        id: CHEBI:50845
        label: doxycycline
  therapeutic_modality: SMALL_MOLECULE
  target_mechanisms:
  - target: Bacterial mRNA Translation by the Ribosome (Macrolide and Tetracycline Target)
    treatment_effect: INHIBITS
    description: Doxycycline inhibits bacterial translation at the ribosome.
  evidence:
  - reference: PMID:22335265
    reference_title: Diagnosis and management of genital ulcers.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Lymphogranuloma venereum and donovanosis are treated with 21 days of oral
      doxycycline.
    explanation: >-
      Supports a 21-day doxycycline regimen as an oral treatment option for
      donovanosis in genital-ulcer disease management.
📚

References & Deep Research

Deep Research

1

Deep research results are used as seeds for research; they do not undergo the same validation as the main records and may contain errors. How we use deep research.

Evaluations and curation notes (1)

Create Granuloma Inguinale infectious disease entry · 2026-09-25T05:55:44Z · View source

Created a new Granuloma Inguinale entry from OpenScientist deep research with Klebsiella granulomatis infectious-agent curation, sexual transmission, an intramacrophage Donovan-body and granulomatous-ulcer pathophysiology chain, genital-ulcer phenotype curation, and ribosome-targeting azithromycin and doxycycline treatments.

OpenScientist ▸
1. Disease Information
openscientist-autonomous 2026-09-24T22:51:45.172633

1. Disease Information

  • Overview: A chronic ulcerative bacterial STI of the genital and inguinal region. Genital papules appear after a ~50-day incubation and evolve into progressively enlarging, painless, friable ulcers with a beefy-red granulation base that bleed on contact. Course is indolent and progressive without treatment; healing occurs with antibiotics.
  • Key identifiers:
  • MONDO: MONDO:0005777
  • ICD-10: A58 (Granuloma inguinale); ICD-11: 1A76 (Granuloma inguinale)
  • MeSH: D006099 "Granuloma Inguinale"
  • SNOMED CT: 5006005 (Granuloma inguinale)
  • OMIM / Orphanet: Not applicable as a Mendelian disorder (infectious disease; no OMIM phenotype entry). Orphanet does not list it as a rare genetic disease.
  • Causative organism NCBI Taxonomy: Klebsiella granulomatis (txid280) / Calymmatobacterium granulomatis.
  • Synonyms / alternative names: Donovanosis; granuloma venereum; granuloma inguinale tropicum; "serpiginous ulcer" (historical); ulcerating granuloma of the pudenda. (Note: distinct from granuloma inguinale tropicum/LGV historically confused terminology.)
  • Information source: Aggregated disease-level literature (guidelines, reviews, clinical case series), not individual-patient EHR.

Evidence: PMID 41016613 — "Donovanosis usually causes genital ulcers with a distinct clinical appearance… The causative organism is a gram-negative bacillus, Calymmatobacterium granulomatis." PMID 42486240 (historical review).

2. Etiology

  • Causal factor — infectious: Klebsiella granulomatis (formerly Calymmatobacterium granulomatis), an encapsulated, intracellular Gram-negative bacillus of family Enterobacteriaceae. Transmission is predominantly sexual (genital, and via ano-receptive/oro-genital contact); low infectivity, with autoinoculation contributing to spread. There is no genetic/heritable cause.
  • Risk factors (environmental/behavioral): residence in or travel to endemic areas; multiple sexual partners; low socioeconomic status/poor access to care; male sex and young adult age (peak in sexually active adults, ~15–40 y); poor genital hygiene; possibly fecal contamination/anal exposure. No genetic susceptibility loci have been identified.
  • Protective factors: condom use, partner notification/treatment, sexual abstinence during treatment, early antibiotic therapy, and general STI-control/health-education programs. No genetic protective variants (Not Applicable).
  • Gene–environment interactions: Not applicable to host genetics. The clinically relevant interaction is comorbidity with HIV, where immunodeficiency prolongs/worsens disease and requires extended therapy.

Evidence: PMID 10555350; PMID 10482295; PMID 22239475 — reclassification and phylogeny; PMID 41016613 — Gram-negative bacillus, nomenclature debate.

3. Phenotypes

Primary phenotype — chronic genital ulcer (HP:0000163 region; HP:0200035 "Genital ulcers"): - Type: clinical sign / physical manifestation (mucocutaneous ulceration). - Characteristics: adult-onset; typically painless or minimally painful; beefy-red, granulomatous, friable base that bleeds readily on contact; slowly progressive/enlarging; chronic (weeks–months). In a Durban series, ulcers persisted >28 days in ~55% of men and ~46% of women. - Four recognized morphologic subtypes: ulcerogranulomatous (most common), hypertrophic/verrucous, necrotic (deep, foul-smelling, destructive), and sclerotic/cicatricial (fibrotic).

Associated signs/complications: - Pseudobuboes — subcutaneous inguinal granulomas mimicking lymphadenopathy (HP:0002716 lymphadenopathy — note: true lymphadenitis is usually absent). - Genital/vulval swelling → elephantiasis (HP:0100820) from lymphatic obstruction (chronic cases). - Tissue destruction/mutilation, scarring, stricture; genital lymphedema. - Secondary squamous cell carcinoma (HP:0002860) in long-standing lesions (rare).

Frequency: Ulcerogranulomatous form predominates (>90% of lesions in series). Quality-of-life impact: substantial physical disability, disfigurement, sexual/urinary dysfunction, and psychological distress/stigma, particularly with elephantiasis or mutilating disease; formal EQ-5D/SF-36 data are not available for this rare disease. Stigma is amplified by sensationalist media: reports of a "flesh-eating infection donovanosis" are false and "only leading to hyperbole and increased stigma among those infected" (PMID 41016613).

Pregnancy & special populations: In a Durban series of 123 women, 42% were pregnant; in ~85% donovanosis had no effect on pregnancy outcome and there was no evidence of congenital disease in neonates (PMID 8735293), though extensive vulval lesions can complicate delivery. Erythromycin is the preferred agent in pregnancy. Disease behaves similarly in HIV-positive and HIV-negative women, though healing may be slower with advanced immunodeficiency.

Evidence: PMID 26882914 / 21097731 — incubation and lesion types; PMID 8509089 — lesion-type frequencies and chronicity; PMID 16510000 — elephantiasis.

4. Genetic / Molecular Information

Not applicable (host). Donovanosis is an infectious disease with no causal human gene, no pathogenic germline/somatic variant, no modifier genes, no disease-defining epigenetic changes, and no chromosomal abnormalities. There is no inheritance, penetrance, expressivity, or carrier frequency.

Pathogen molecular biology (limited): K. granulomatis shows ~95% 16S rRNA identity to Klebsiella and ~94% to Enterobacter; sequencing of 16S rRNA + phoE (2089 bp) supported reclassification as Klebsiella granulomatis comb. nov. Because the organism is fastidious and hard to culture, its genome and virulence factors remain poorly characterized; a defined virulence repertoire is not established.

Evidence: PMID 10555350; PMID 10482295; PMID 22239475 — "Because of the difficulty in growing this bacterium… its characteristics have not been sufficiently defined."

5. Environmental Information

  • Environmental/occupational toxins: none implicated.
  • Lifestyle factors: high-risk sexual behavior; multiple partners; migration between urban/rural endemic areas (identified as a driver of transmission and HIV co-risk in South African studies). Minimal condom use in affected populations.
  • Infectious agent: Klebsiella (Calymmatobacterium) granulomatis — Gram-negative bacillus; NCBI Taxonomy Klebsiella granulomatis; gamma-Proteobacteria; Enterobacteriaceae. Humans are the only known host/reservoir; no environmental or animal reservoir is established.

Evidence: PMID 1398660 — sexual-behavior/migration patterns; PMID 10482295 — taxonomy.

6. Mechanism / Pathophysiology

Ordered causal chain (initiating infection → clinical manifestation)

  1. Sexual/auto-inoculation exposure deposits K. granulomatis onto genital/inguinal epithelium (often at microabrasions) → leads to local colonization. (demonstrated: sexual transmission; exact portal inferred)
  2. Bacteria are phagocytosed by tissue macrophages/histiocytes and survive/replicate within cytoplasmic vacuoles (phagosomes) → results in an intracellular reservoir (Donovan bodies). (demonstrated by ultrastructure)
  3. Persisting intracellular bacteria drive chronic granulomatous inflammation — recruitment of plasma cells, neutrophils, and activated macrophages with few lymphocytes → leads to granulation-tissue formation. (demonstrated histologically)
  4. Ongoing inflammation and proteolysis erode the epithelium and induce pseudoepitheliomatous hyperplasia at ulcer margins → results in the characteristic beefy-red, friable, bleeding ulcer that enlarges peripherally. (demonstrated)
  5. Branch A (chronic fibrosis): persistent inflammation traps and constricts lymphatics → leads to lymphatic obstruction → genital elephantiasis / lymphedema and cicatricial/sclerotic scarring, strictures. (demonstrated mechanism, PMID 16510000)
  6. Branch B (neoplasia): decades-long chronic ulceration and epithelial hyperplasia predispose to malignant transformation → squamous cell carcinoma. (inferred from case reports)
  7. Branch C (HIV facilitation): the friable, readily bleeding ulcer disrupts the mucosal barrier → facilitates HIV-1 entry/transmission (portal of entry + blood contact). (epidemiologically demonstrated)
  8. Branch D (spread): direct extension/autoinoculation and (rarely) hematogenous/lymphatic dissemination → extragenital, pelvic, or disseminated lesions. (demonstrated in case reports)

Detail by category

  • Cellular processes: chronic inflammation (GO:0006954), phagocytosis (GO:0006909), granuloma formation; macrophage activation (increased lysosomes, rough ER, filopodia on ultrastructure).
  • Immune involvement: predominantly innate/macrophage-centered with prominent plasma-cell (humoral) infiltrate; sparse lymphocytes; the organism resists intracellular killing, enabling persistence. Immunodeficiency (HIV) worsens/prolongs disease.
  • Tissue damage mechanisms: inflammatory tissue destruction, ulceration, fibrosis/sclerosis, lymphatic obstruction; not toxin- or ischemia-driven.
  • Molecular pathways / metabolic / epigenetic / omics: Not characterized — no transcriptomic, proteomic, metabolomic, or defined signaling-pathway data exist for donovanosis (knowledge gap due to culture difficulty).
  • Cell types (CL): macrophage (CL:0000235), plasma cell (CL:0000786), neutrophil (CL:0000775). GO cellular component: phagocytic vesicle/phagosome (GO:0045335).

Evidence: PMID 9856642 (intramacrophage localization); PMID 2777345 (ultrastructure of inflammatory response); PMID 18317211 (plasma-cell/histiocyte histology, Donovan bodies); PMID 16510000 (lymphatic constriction → elephantiasis); PMID 2063236 (HIV facilitation).

7. Anatomical Structures Affected

  • Organ/system level: reproductive/genitourinary system and integumentary system (skin) are primary. Secondary: inguinal soft tissue, lymphatics (obstruction), and rarely pelvis/bone (dissemination).
  • Primary sites (~90%): external genitalia and inguinal/perineal region — penis, prepuce, coronal sulcus, glans; vulva, labia, fourchette; also uterine cervix (UBERON:0000002) and vagina (UBERON:0000996). Perianal/anal lesions with ano-receptive intercourse.
  • Extragenital (rare): lip/oral cavity, and skin sites such as the foot; disseminated pelvic/visceral disease historically reported.
  • Tissue/cell level: epithelial tissue (pseudoepitheliomatous hyperplasia) and dermal connective/granulation tissue; key cells = macrophages/histiocytes (CL:0000235), plasma cells (CL:0000786), neutrophils (CL:0000775).
  • Subcellular: bacteria within macrophage cytoplasmic vacuoles/phagosomes (GO:0045335).
  • Localization/lateralization: lesions localize to sites of sexual contact; inguinal involvement may be unilateral or bilateral; "kissing lesions" from autoinoculation on apposed skin.
  • UBERON suggestions: external genitalia; UBERON:0000996 (vagina); UBERON:0000002 (cervix); UBERON:0002097 (skin of body); inguinal region.

Evidence: PMID 8735293 (rectal/pelvic + genital); PMID 9924476 (extragenital foot); PMID 18317211 (cervix).

8. Temporal Development

  • Onset: adult-onset, in sexually active individuals; insidious/chronic onset after an incubation period of ~50 days (reported range ~1–12 weeks, up to months). Not congenital; neonatal/perinatal transmission is rare.
  • Progression: untreated disease is slowly progressive with peripheral enlargement and local tissue destruction over months–years; stages run from papule → early ulcer → extensive ulcerogranulomatous/hypertrophic disease → sclerotic/cicatricial end-stage with scarring, lymphedema/elephantiasis, and rare malignant transformation.
  • Course pattern: chronic progressive; not self-limiting. Relapse can occur 6–18 months after apparently adequate therapy, warranting follow-up.
  • Remission: treatment-induced (antibiotics) — healing from ulcer margins; spontaneous remission is uncommon.
  • Critical intervention window: early antibiotic treatment prevents tissue destruction, scarring, elephantiasis, and reduces HIV-cofactor risk.

Evidence: PMID 26882914 (incubation ~50 days; treat until healed); PMID 8509089 (chronicity).

9. Inheritance and Population

  • Epidemiology: rare and geographically restricted; endemic "hot spots" — Papua New Guinea, South Africa (KwaZulu-Natal/Durban epidemic 1988–97), India, Brazil, and formerly Aboriginal communities in Australia. Marked global decline; described in 2026 as "well on the way to being eradicated." Precise global incidence/prevalence figures are not maintained in standard registries (SEER/GBD do not track it separately); it is now seen mostly as sporadic imported cases in non-endemic countries.
  • Infectivity: low/mildly infectious — only 1/21 regular partners were infected in one Durban series, supporting feasibility of elimination programs.
  • Inheritance/penetrance/carrier frequency/founder effects/consanguinity: Not Applicable (infectious, non-genetic).
  • Demographics: affects sexually active adults, roughly 15–40 years (series mean age ~22 in women). Sex ratio varies by setting; classic literature reports a male predominance (e.g., 130 men vs 41 women in one Durban series), though other series (antenatal/gynecology clinics) are female-predominant, reflecting ascertainment. Higher burden in lower-income, rural, and marginalized populations in endemic regions.
  • Geographic variant distribution: Not characterized (limited pathogen genomics).

Evidence: PMID 41016613 ("significant global decline… well on the way to being eradicated"); PMID 26882914 (endemic countries); PMID 7750949 (unique geography); PMID 8509089 (sex distribution, low partner infectivity).

10. Diagnostics

  • Cornerstone — cytology/histopathology: microscopic identification of Donovan bodies (intracytoplasmic, bipolar "safety-pin" bacteria within macrophages/histiocytes) on crush/tissue smears stained with Giemsa/Wright/RapiDiff or on biopsy. Histology: granulation tissue with dense plasma-cell infiltrate, neutrophil microabscesses, enlarged vacuolated histiocytes containing Donovan bodies, and pseudoepitheliomatous hyperplasia.
  • Molecular: PCR (including colorimetric-detection assays) developed for genital-ulcer specimens; increases sensitivity/specificity where available. LOINC/SNOMED codes exist for genital-ulcer pathogen testing.
  • Culture: difficult/not routine (fastidious; grown historically in human peripheral-blood monocyte co-culture and Hep-2 cells).
  • Biomarkers/imaging/electrophysiology/omics: no specific serum biomarker; imaging only for complications (deep/pelvic/bone extension); no omics-based diagnostics.
  • Genetic testing: Not Applicable (no host genetic component; WGS/WES/panels/karyotype/CMA/FISH not indicated).
  • Clinical criteria & differential diagnosis: diagnosis is clinical + cytologic/PCR confirmation. Differential: primary syphilis (chancre), chancroid (H. ducreyi), lymphogranuloma venereum (C. trachomatis L1–L3), genital herpes, secondary bacterial/fungal infection; and non-infectious mimics — squamous cell carcinoma, Behçet disease, aphthosis, psoriasis, fixed drug eruption, sexual trauma. Distinguishing features of donovanosis: chronic, painless, beefy-red, friable, bleeding ulcer usually without true regional lymphadenitis. No pathogen is identified in up to 25% of genital-ulcer patients.
  • Screening: no asymptomatic/newborn/carrier screening; case-finding via STI services and partner notification.

Evidence: PMID 26882914 (Donovan bodies + PCR); PMID 22335265 (genital-ulcer differential; up to 25% undiagnosed); PMID 39566736 (non-infectious mimics); PMID 18317211 (histology).

11. Outcome / Prognosis

  • Prognosis with treatment: excellent — highly curable with antibiotics; ulcers re-epithelialize over weeks. Early treatment prevents disfigurement and complications.
  • Mortality: very low; donovanosis is rarely directly fatal. No standardized survival statistics (non-lethal, rare disease). Disease-specific mortality is negligible except via complications (secondary infection, or SCC).
  • Morbidity/disability: without treatment — extensive genital ulceration, tissue destruction/mutilation, scarring, urethral/vaginal/anal strictures, genital elephantiasis/lymphedema, and psychosexual morbidity. Long-standing lesions carry a small risk of squamous cell carcinoma.
  • Recovery: high recovery potential with therapy; established fibrosis/elephantiasis and tissue loss may be irreversible and require surgery.
  • Prognostic factors: duration/extent of lesions at presentation, HIV coinfection (prolonged healing, treatment failure risk), and treatment adherence. No molecular prognostic biomarkers.

Evidence: PMID 26882914 (treat until healed); PMID 7750949 (treatment failure in advanced HIV); PMID 19061590 / 24554002 / 26396449 (SCC complication); PMID 16510000 (elephantiasis).

12. Treatment

  • First-line pharmacotherapy: Azithromycin (macrolide; inhibits 50S ribosome) 1 g weekly (or 500 mg daily) continued until all lesions have fully healed (minimum ~3 weeks). NCIT:C734; CHEBI:2955; ATC J01FA10.
  • Alternative regimens (≥3 weeks / until healed):
  • Doxycycline 100 mg twice daily (tetracycline) — genital-ulcer guidance specifies 21 days. NCIT:C744; CHEBI:50845.
  • Trimethoprim–sulfamethoxazole (co-trimoxazole) 160/800 mg twice daily. NCIT:C265.
  • Erythromycin 500 mg four times daily (preferred in pregnancy). NCIT:C61780.
  • Ceftriaxone and ciprofloxacin reported as further alternatives.
  • Adjuncts: add a parenteral aminoglycoside (e.g., gentamicin) if lesions do not respond, especially in HIV-positive patients; prolonged therapy in advanced HIV.
  • Surgery/interventional: reserved for complications — excision of fibrotic/mutilating tissue, correction of strictures/elephantiasis, or resection of secondary SCC.
  • Supportive care: wound care, analgesia, treatment of secondary infection; partner evaluation/treatment.
  • Advanced/experimental therapeutics (gene/cell/RNA/targeted/immuno-therapy) and pharmacogenomics: Not Applicable — no gene-guided therapy; standard antibiotics suffice. No active registered clinical trials specific to donovanosis.
  • Treatment outcome: high response/cure rates; monitor for relapse at 6–18 months. Adverse events are drug-class–typical (GI upset with macrolides/tetracyclines; photosensitivity with doxycycline; sulfa hypersensitivity).

Evidence: PMID 26882914 / 21097731 (azithromycin first-line); PMID 22335265 (doxycycline 21 days).

13. Prevention

  • Primary prevention: safer-sex practices (condoms), reduction in number of partners, health education, and prompt treatment of index cases and sexual partners to interrupt transmission. No vaccine exists (immunization Not Applicable).
  • Secondary prevention: early detection/treatment in STI clinics; syndromic management of genital ulcer disease in endemic settings (adapted locally); partner notification/treatment; abstinence until lesions heal.
  • Tertiary prevention: complete antibiotic courses to prevent tissue destruction, strictures, elephantiasis, and malignant transformation; surveillance for relapse and SCC; management of HIV coinfection.
  • Public-health interventions: community-based elimination programs are feasible given low infectivity and restricted geography — the Australian Aboriginal donovanosis elimination program is a documented success and proposed model; donovanosis eradication is framed as an opportunity to also curb HIV-1 spread.
  • Genetic counseling/carrier screening: Not Applicable.

Evidence: PMID 12473810 (successful Australian elimination program; syndromic management); PMID 7750949 (global eradication opportunity linked to HIV control).

14. Other Species / Natural Disease

  • Host range: Humans are the only known natural host; no established zoonotic reservoir or naturally occurring animal disease is documented for K. granulomatis.
  • Taxonomy of pathogen: Klebsiella granulomatis (NCBI Taxonomy). Closely related human pathogens in the genus: K. pneumoniae, K. rhinoscleromatis (causes rhinoscleroma), K. oxytoca.
  • Comparative biology: mechanistic parallels with rhinoscleroma (K. rhinoscleromatis) — another chronic granulomatous Klebsiella infection with intramacrophage bacteria (Mikulicz cells analogous to Donovan-body–laden histiocytes).
  • Breeds/orthologous genes/zoonosis/cross-species susceptibility: Not Applicable / Not documented.

Evidence: PMID 10555350 (relatedness to K. pneumoniae, K. rhinoscleromatis).

15. Model Organisms

  • No established animal or genetic disease model exists. The organism's fastidious growth requirements (only re-cultured after >30 years in human peripheral-blood monocyte co-culture and Hep-2 cell systems) have precluded standard mouse/rat/zebrafish/invertebrate models, and there are no knockout/transgenic/humanized models (host genetics is irrelevant).
  • In vitro systems used: human monocyte co-cultures and Hep-2 cells for isolation and ultrastructural study.
  • Limitations / research gap: absence of tractable models and a complete genome is the principal barrier to studying virulence factors, immune evasion, and pathway-level mechanisms.

Evidence: PMID 9856642 (monocyte co-culture / tissue ultrastructure); PMID 22239475 (culture difficulty; "more studies needed to understand bacterial genetics").

Supported vs Refuted Hypotheses

Supported (evidence-backed): 1. Donovanosis is caused by intracellular Gram-negative Klebsiella (Calymmatobacterium) granulomatis (16S/phoE phylogeny). 2. Pathology is macrophage-based granulomatous inflammation with Donovan bodies (ultrastructure/histology). 3. Azithromycin is first-line, curative therapy (guidelines). 4. Disease is rare, geographically restricted, and declining toward eradication (reviews). 5. Donovanosis is a cofactor for HIV-1 acquisition/transmission (P=0.02 in men; risk rises with lesion duration). 6. Chronic disease causes elephantiasis (lymphatic obstruction) and rarely SCC (mechanism + case reports).

Refuted / Not Applicable: - No host causal gene, inheritance, penetrance, or carrier frequency (infectious disease). - No established animal model or knockout/transgenic system. - No omics/pathway-level molecular profiling; no vaccine; no gene/cell/RNA therapy.

Mechanistic Model (Synthesis)

 Sexual / auto-inoculation of K. granulomatis (~50-day incubation)
 │
 ▼
 Phagocytosis by dermal MACROPHAGES (CL:0000235)
 │
 ▼
 Intracellular survival in cytoplasmic vacuoles (GO:0045335)
→ DONOVAN BODIES  (pathognomonic)
 │
 ▼
 Chronic GRANULOMATOUS inflammation
 (plasma cells CL:0000786 + neutrophils CL:0000775)
 + pseudoepitheliomatous hyperplasia
 │
 ▼
 Beefy-red, FRIABLE, bleeding ULCER  (HP:0200035)
│              │                 │
▼              ▼                 ▼
  Lymphatic       Long-standing      Bleeding portal
  constriction    lesion →           → HIV-1 acquisition
  → ELEPHANTIASIS  SCC (rare)         & transmission (cofactor)
  (PMID 16510000)  (PMID 19061590)    (PMID 2063236)

The unifying theme is that donovanosis is a macrophage-parasitizing intracellular infection whose clinical severity flows from the chronicity of the granulomatous response rather than acute toxicity. This explains the slow tempo, the friable vascular ulcers, the late fibrotic/lymphatic and neoplastic complications, the HIV-cofactor role, and why a single mechanistic intervention — sustained intracellular-active antibiotic therapy (azithromycin) — is curative and why elimination programs succeed (breaking the sole human transmission chain).

Evidence Base — Key Papers and How They Support the Findings

PMID Paper (abbrev.) Type Supports
10555350 Reclassification as K. granulomatis comb. nov. Phylogenetic Etiology/taxonomy; relatedness to K. pneumoniae/K. rhinoscleromatis
10482295 16S rRNA phylogeny of C. granulomatis Phylogenetic ~95% Klebsiella, ~94% Enterobacter; distinct gamma-proteobacterium
22239475 Evolution of STI bacteria Computational/review Culture difficulty; sparse pathogen genetics (knowledge gap)
41016613 Donovanosis review (2026) Review Gram-negative bacillus; near-eradication; stigma/misinformation
26882914 2016 European guideline Guideline ~50-day incubation; 4 lesion types; Donovan bodies/PCR; azithromycin
21097731 2010 European guideline Guideline Diagnosis and first-line azithromycin
8509089 Durban clinico-epidemiological study Clinical series Lesion-type frequencies; chronicity; sex distribution
2063236 HIV-1 in Durban STD clinic Cross-sectional (human) Donovanosis–HIV-1 association (P=0.02, men); risk ↑ with lesion duration
7750949 Global eradication of donovanosis Review Unique geography; HIV risk factor; eradication opportunity
9856642 Ultrastructure: culture vs biopsy In vitro/ultrastructural Intramacrophage localization; absent surface structures
2777345 Ultrastructural study of donovanosis Ultrastructural Macrophage activation; inflammatory cell repertoire
18317211 Malacoplakia & GI of cervix in AIDS Case report Histology (Donovan bodies); cervical involvement
16510000 Genital elephantiasis & STIs Review Lymphatic constriction → elephantiasis mechanism
19061590 Malignant transformation (HIV+) Case report SCC complication of chronic donovanosis
8735293 GI in pregnancy & HIV Clinical series Benign pregnancy outcome; no congenital transmission
9924476 Extragenital donovanosis of foot Case report Rare extragenital localization
22335265 Diagnosis/management of genital ulcers Review Doxycycline 21 d; differential diagnosis; ≤25% undiagnosed
39566736 AEDV ulcerative-STI management Guideline Non-infectious mimics in differential
12473810 Donovanosis review Review Australian elimination program; declining incidence
11394976 Donovanosis: an update Review Re-culture after >30 y; prolonged therapy in HIV; cost of azithromycin

Consistency of evidence: Findings are internally consistent across independent guidelines (European 2010/2016), large clinical series (Durban), and mechanistic ultrastructural studies. Taxonomic reclassification is supported by two independent sequencing studies; the HIV-cofactor role by a large cross-sectional study with statistically significant associations. The main evidentiary weakness is reliance on case reports/series for complication rates (SCC, elephantiasis) and the near-total absence of pathogen omics data.

Limitations & Future Directions

  • The pathogen's culture difficulty leaves its genome, virulence factors, and molecular immunology poorly defined; whole-genome sequencing and in vitro/organoid infection models are key future needs.
  • Epidemiologic surveillance is sparse (no dedicated global registry); true incidence/prevalence and sex/age distributions are uncertain and setting-dependent.
  • Modern PCR-based diagnostics and controlled treatment trials are limited by the disease's rarity.
  • Evidence is dominated by case reports/series and expert-guideline consensus rather than RCTs.
  • Several template sections (host genetics, model organisms, omics, pharmacogenomics) are inherently Not Applicable to a non-genetic infectious disease.

Proposed Follow-up Actions

  1. Whole-genome sequencing of K. granulomatis from clinical isolates (via monocyte/Hep-2 co-culture) to define virulence factors, capsule/LPS loci, and confirm genome-scale Klebsiella placement.
  2. Develop a tractable infection model (humanized macrophage system, skin organoid, or small-animal model) to study intracellular persistence, Donovan-body formation, and antibiotic penetration.
  3. Standardized PCR surveillance in remaining endemic foci (PNG, India, Brazil) to quantify true incidence and monitor progress toward eradication.
  4. Prospective cohort follow-up to estimate the risk and triggers of squamous-cell-carcinoma transformation, currently known only anecdotally.
  5. Integrate donovanosis elimination with HIV-prevention programs, leveraging the demonstrated HIV-cofactor relationship (PMID 2063236).
  6. Cost-effectiveness analysis of azithromycin to support universal first-line adoption (historical cost barrier; PMID 11394976).
  7. Public-health communication to counter "flesh-eating infection" misinformation and reduce stigma (PMID 41016613).

Key Citations (PMID)

41016613 · 42486240 · 10555350 · 10482295 · 22239475 · 12635932 · 26882914 · 21097731 · 12473810 · 11394976 · 8509089 · 2063236 · 7750949 · 1398660 · 8735293 · 16510000 · 18317211 · 9856642 · 2777345 · 11100808 · 19061590 · 24554002 · 26396449 · 9924476 · 22335265 · 39566736

Artifacts

Reference Validation

Checked with linkml-reference-validator 0.3.0rc1.

Outcome Count
References checked 22
Resolved 22
Unresolved (possible confabulation) 0
Unverifiable 0
Quoted claims checked 1
Quoted claims found in source 1
Quoted claims not found in source 0
References weighed for topical relevance 22
On topic 19
Off topic 0

All extracted references resolved successfully.

Term Validation

Checked with linkml-term-validator 0.4.5, through the ols: adapter.

Outcome Count
Terms checked 21
Resolved 21
Unresolved (possible confabulation) 0
Obsolete 0
Unverifiable 0
Terms whose name was checked 7
Terms named correctly 2
Terms named as a different term 3
Terms whose name is worth a second look 2

Terms the report names something else

These identifiers resolve, so nothing about them looks wrong, and the ontology calls them something unrelated to what the report calls them. That usually means the identifier is not the one the sentence needs:

  • HP:0100820 (1 mention) - the report calls it "Genital/vulval swelling → elephantiasis"; HP calls it Glomerulopathy
  • GO:0006954 (1 mention) - the report calls it "Cellular processes: chronic inflammation"; GO calls it inflammatory response**
  • GO:0045335 (3 mentions) - the report calls it "cytoplasmic vacuoles/phagosomes", "Subcellular: bacteria within macrophage cytoplasmic vacuoles/phagosomes"; GO calls it phagocytic vesicle

Terms whose name is worth a second look

The report's name for these is recognisably related to the term's own name without being one of them. A loose paraphrase reads the same way as a citation of the wrong sibling term - and so does a related synonym, which the ontology records precisely because it names something adjacent rather than the same thing - so these are listed rather than judged:

  • HP:0002860 (1 mention) - the report calls it "Secondary squamous cell carcinoma"; HP calls it Squamous cell carcinoma
  • UBERON:0000002 (2 mentions) - the report calls it "uterine cervix", "cervix"; UBERON calls it uterine cervix, and lists "cervix" among its other names

Terms named inconsistently

The report gives these identifiers more than one name of its own:

  • GO:0045335 - called "cytoplasmic vacuoles/phagosomes", "Subcellular: bacteria within macrophage cytoplasmic vacuoles/phagosomes"
  • UBERON:0000002 - called "uterine cervix", "cervix"