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1
Phenotypes
1
Treatments
9
References
1
Deep Research

Phenotypes

1
Skin ulcer COMMON Dermatologic HP:0200042
Show evidence (1 reference)
PMID:40036381 SUPPORT
"In the primary stage, patients develop a, usually painless, papilloma or ulcer, often on the lower extremities, which is highly contagious."
The abstract describes ulcer formation in primary yaws.
💊

Treatments

1
Azithromycin therapy
Action: Pharmacotherapy NCIT:C15986
Oral azithromycin is preferred for treatment.
Show evidence (1 reference)
PMID:40036381 SUPPORT
"Though yaws can be treated with benzathine penicillin, oral azithromycin has become the preferred treatment due to its ease of administration."
The abstract notes oral azithromycin as the preferred treatment.
{ }

Source YAML

click to show
name: Yaws
creation_date: '2026-01-26T15:56:41Z'
updated_date: '2026-04-11T00:45:07Z'
category: Infectious Disease
description: >-
  Yaws is a chronic and disfiguring bacterial infection caused by Treponema
  pallidum subsp. pertenue.
disease_term:
  term:
    id: MONDO:0006019
    label: yaws
  preferred_term: Yaws
parents:
- Bacterial Infection
- Neglected tropical disease
infectious_agent:
- name: Treponema pallidum subsp. pertenue
  infectious_agent_term:
    preferred_term: Treponema pallidum subsp. pertenue
    term:
      id: NCBITaxon:168
      label: Treponema pallidum subsp. pertenue
  description: Spirochete that causes yaws.
  evidence:
  - reference: PMID:40036381
    reference_title: "Yaws - A Review of Clinical Features, Diagnosis and Treatment."
    supports: SUPPORT
    snippet: "Yaws, a neglected tropical disease caused by Treponema pallidum subsp. pertenue, primarily affects children in impoverished rural areas."
    explanation: The abstract identifies T. pallidum subsp. pertenue as the cause of yaws.
transmission:
- name: Direct skin contact
  description: Transmitted through direct skin contact with infected individuals.
  evidence:
  - reference: PMID:40036381
    reference_title: "Yaws - A Review of Clinical Features, Diagnosis and Treatment."
    supports: SUPPORT
    snippet: "It is spread through direct skin contact."
    explanation: The abstract states yaws is spread through direct skin contact.
phenotypes:
- name: Skin ulcer
  category: Dermatologic
  frequency: COMMON
  phenotype_term:
    preferred_term: Skin ulcer
    term:
      id: HP:0200042
      label: Skin ulcer
  evidence:
  - reference: PMID:40036381
    reference_title: "Yaws - A Review of Clinical Features, Diagnosis and Treatment."
    supports: SUPPORT
    snippet: "In the primary stage, patients develop a, usually painless, papilloma or ulcer, often on the lower extremities, which is highly contagious."
    explanation: The abstract describes ulcer formation in primary yaws.
treatments:
- name: Azithromycin therapy
  description: Oral azithromycin is preferred for treatment.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
  evidence:
  - reference: PMID:40036381
    reference_title: "Yaws - A Review of Clinical Features, Diagnosis and Treatment."
    supports: SUPPORT
    snippet: "Though yaws can be treated with benzathine penicillin, oral azithromycin has become the preferred treatment due to its ease of administration."
    explanation: The abstract notes oral azithromycin as the preferred treatment.
references:
- reference: DOI:10.1101/2024.10.27.24316187
  title: 'The Effect of Repeated Mass Drug Administration on the Transmission of Yaws: A Genomic Epidemiology Study'
  found_in:
  - Yaws-deep-research-falcon.md
  findings:
  - statement: Yaws, a neglected tropical disease caused by Treponema pallidum subspecies pertenue , has evaded eradication, in part due to a high proportion of asymptomatic cases.
    supporting_text: Yaws, a neglected tropical disease caused by Treponema pallidum subspecies pertenue , has evaded eradication, in part due to a high proportion of asymptomatic cases.
    evidence:
    - reference: DOI:10.1101/2024.10.27.24316187
      reference_title: 'The Effect of Repeated Mass Drug Administration on the Transmission of Yaws: A Genomic Epidemiology Study'
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Yaws, a neglected tropical disease caused by Treponema pallidum subspecies pertenue , has evaded eradication, in part due to a high proportion of asymptomatic cases.
      explanation: Deep research cited this publication as relevant literature for Yaws.
- reference: DOI:10.1101/2024.11.07.24316738
  title: 'The Morges Strategy for Yaws Eradication: the First Largescale Total Community Treatment with Azithromycin Against Yaws in the Congo-Basin, using a Novel Model'
  found_in:
  - Yaws-deep-research-falcon.md
  findings:
  - statement: Yaws is targeted for eradication by 2030.
    supporting_text: Yaws is targeted for eradication by 2030.
    evidence:
    - reference: DOI:10.1101/2024.11.07.24316738
      reference_title: 'The Morges Strategy for Yaws Eradication: the First Largescale Total Community Treatment with Azithromycin Against Yaws in the Congo-Basin, using a Novel Model'
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Yaws is targeted for eradication by 2030.
      explanation: Deep research cited this publication as relevant literature for Yaws.
- reference: DOI:10.1371/journal.pntd.0011602
  title: The genomes of the yaws bacterium, Treponema pallidum subsp. pertenue, of nonhuman primate and human origin are not genomically distinct
  found_in:
  - Yaws-deep-research-falcon.md
  findings:
  - statement: Treponema pallidumsubsp.pertenue(TPE) is the causative agent of human yaws.
    supporting_text: Treponema pallidumsubsp.pertenue(TPE) is the causative agent of human yaws.
    evidence:
    - reference: DOI:10.1371/journal.pntd.0011602
      reference_title: The genomes of the yaws bacterium, Treponema pallidum subsp. pertenue, of nonhuman primate and human origin are not genomically distinct
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Treponema pallidumsubsp.pertenue(TPE) is the causative agent of human yaws.
      explanation: Deep research cited this publication as relevant literature for Yaws.
- reference: DOI:10.1371/journal.pntd.0011831
  title: 'Low genetic diversity of Treponema pallidum ssp. pertenue (TPE) isolated from patients’ ulcers in Namatanai District of Papua New Guinea: Local human population is infected by three TPE genotypes'
  found_in:
  - Yaws-deep-research-falcon.md
  findings:
  - statement: Yaws is an endemic disease caused by Treponema pallidum subsp. pertenue (TPE) that primarily affects children in rural regions of the tropics.
    supporting_text: Yaws is an endemic disease caused by Treponema pallidum subsp. pertenue (TPE) that primarily affects children in rural regions of the tropics.
    evidence:
    - reference: DOI:10.1371/journal.pntd.0011831
      reference_title: 'Low genetic diversity of Treponema pallidum ssp. pertenue (TPE) isolated from patients’ ulcers in Namatanai District of Papua New Guinea: Local human population is infected by three TPE genotypes'
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Yaws is an endemic disease caused by Treponema pallidum subsp. pertenue (TPE) that primarily affects children in rural regions of the tropics.
      explanation: Deep research cited this publication as relevant literature for Yaws.
- reference: DOI:10.1371/journal.pntd.0012224
  title: Knowledge, attitudes and practices towards yaws in endemic areas of Ghana, Cameroon and Côte d’Ivoire
  found_in:
  - Yaws-deep-research-falcon.md
  findings:
  - statement: Knowledge, attitudes and practices towards yaws in endemic areas of Ghana, Cameroon and Côte d’Ivoire
    supporting_text: Yaws, caused by Treponema pallidum ssp. pertenue, remains a significant public health concern in tropical regions of West Africa and the South Pacific, primarily affecting children in remote areas with limited access to hygiene and sanitation.
    evidence:
    - reference: DOI:10.1371/journal.pntd.0012224
      reference_title: Knowledge, attitudes and practices towards yaws in endemic areas of Ghana, Cameroon and Côte d’Ivoire
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Yaws, caused by Treponema pallidum ssp. pertenue, remains a significant public health concern in tropical regions of West Africa and the South Pacific, primarily affecting children in remote areas with limited access to hygiene and sanitation.
      explanation: Deep research cited this publication as relevant literature for Yaws.
- reference: DOI:10.1371/journal.pntd.0012899
  title: Guidance for conducting and evaluating serological surveys to assess interruption of yaws transmission in the context of an eradication target
  found_in:
  - Yaws-deep-research-falcon.md
  findings:
  - statement: Guidance for conducting and evaluating serological surveys to assess interruption of yaws transmission in the context of an eradication target
    supporting_text: This document provides a summary of guidance developed for national programmes on conducting serosurveys to assess yaws transmission status, with the objective of confirming yaws seroprevalence below 1% at each of three serosurveys over a period of 3–10 years after reporting the last case of active yaws in a region.
    evidence:
    - reference: DOI:10.1371/journal.pntd.0012899
      reference_title: Guidance for conducting and evaluating serological surveys to assess interruption of yaws transmission in the context of an eradication target
      supports: SUPPORT
      evidence_source: OTHER
      snippet: This document provides a summary of guidance developed for national programmes on conducting serosurveys to assess yaws transmission status, with the objective of confirming yaws seroprevalence below 1% at each of three serosurveys over a period of 3–10 years after reporting the last case of active yaws in a region.
      explanation: Deep research cited this publication as relevant literature for Yaws.
- reference: DOI:10.1371/journal.pone.0295088
  title: Prevalence of yaws and syphilis in the Ashanti region of Ghana and occurrence of H. ducreyi, herpes simplex virus 1 and herpes simplex virus 2 in skin lesions associated with treponematoses
  found_in:
  - Yaws-deep-research-falcon.md
  findings:
  - statement: Yaws affects children in tropical regions, while syphilis primarily affects sexually active adults worldwide.
    supporting_text: Yaws affects children in tropical regions, while syphilis primarily affects sexually active adults worldwide.
    evidence:
    - reference: DOI:10.1371/journal.pone.0295088
      reference_title: Prevalence of yaws and syphilis in the Ashanti region of Ghana and occurrence of H. ducreyi, herpes simplex virus 1 and herpes simplex virus 2 in skin lesions associated with treponematoses
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Yaws affects children in tropical regions, while syphilis primarily affects sexually active adults worldwide.
      explanation: Deep research cited this publication as relevant literature for Yaws.
- reference: DOI:10.3390/diseases13010014
  title: 'Yaws in Africa: Past, Present and Future'
  found_in:
  - Yaws-deep-research-falcon.md
  findings:
  - statement: Yaws is an infectious, neglected tropical disease that affects the skin of many children and adolescents who live in poor, rural, low-income communities in humid, tropical areas of Africa, Southeast Asia, and the Pacific Islands.
    supporting_text: Yaws is an infectious, neglected tropical disease that affects the skin of many children and adolescents who live in poor, rural, low-income communities in humid, tropical areas of Africa, Southeast Asia, and the Pacific Islands.
    evidence:
    - reference: DOI:10.3390/diseases13010014
      reference_title: 'Yaws in Africa: Past, Present and Future'
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Yaws is an infectious, neglected tropical disease that affects the skin of many children and adolescents who live in poor, rural, low-income communities in humid, tropical areas of Africa, Southeast Asia, and the Pacific Islands.
      explanation: Deep research cited this publication as relevant literature for Yaws.
- reference: DOI:10.3855/jidc.17753
  title: Comparison of the standard Q syphilis antibody rapid diagnostic test to gold standards for yaws detection in children
  found_in:
  - Yaws-deep-research-falcon.md
  findings:
  - statement: Yaws remains a public health problem in Indonesia, and it is the largest contributor to Yaws cases in Southeast Asia.
    supporting_text: Yaws remains a public health problem in Indonesia, and it is the largest contributor to Yaws cases in Southeast Asia.
    evidence:
    - reference: DOI:10.3855/jidc.17753
      reference_title: Comparison of the standard Q syphilis antibody rapid diagnostic test to gold standards for yaws detection in children
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Yaws remains a public health problem in Indonesia, and it is the largest contributor to Yaws cases in Southeast Asia.
      explanation: Deep research cited this publication as relevant literature for Yaws.
📚

References & Deep Research

References

9
The Effect of Repeated Mass Drug Administration on the Transmission of Yaws: A Genomic Epidemiology Study
1 finding
Yaws, a neglected tropical disease caused by Treponema pallidum subspecies pertenue , has evaded eradication, in part due to a high proportion of asymptomatic cases.
"Yaws, a neglected tropical disease caused by Treponema pallidum subspecies pertenue , has evaded eradication, in part due to a high proportion of asymptomatic cases."
Show evidence (1 reference)
DOI:10.1101/2024.10.27.24316187 SUPPORT Human Clinical
"Yaws, a neglected tropical disease caused by Treponema pallidum subspecies pertenue , has evaded eradication, in part due to a high proportion of asymptomatic cases."
Deep research cited this publication as relevant literature for Yaws.
The Morges Strategy for Yaws Eradication: the First Largescale Total Community Treatment with Azithromycin Against Yaws in the Congo-Basin, using a Novel Model
1 finding
Yaws is targeted for eradication by 2030.
"Yaws is targeted for eradication by 2030."
Show evidence (1 reference)
DOI:10.1101/2024.11.07.24316738 SUPPORT Human Clinical
"Yaws is targeted for eradication by 2030."
Deep research cited this publication as relevant literature for Yaws.
The genomes of the yaws bacterium, Treponema pallidum subsp. pertenue, of nonhuman primate and human origin are not genomically distinct
1 finding
Treponema pallidumsubsp.pertenue(TPE) is the causative agent of human yaws.
"Treponema pallidumsubsp.pertenue(TPE) is the causative agent of human yaws."
Show evidence (1 reference)
DOI:10.1371/journal.pntd.0011602 SUPPORT Human Clinical
"Treponema pallidumsubsp.pertenue(TPE) is the causative agent of human yaws."
Deep research cited this publication as relevant literature for Yaws.
Low genetic diversity of Treponema pallidum ssp. pertenue (TPE) isolated from patients’ ulcers in Namatanai District of Papua New Guinea: Local human population is infected by three TPE genotypes
1 finding
Yaws is an endemic disease caused by Treponema pallidum subsp. pertenue (TPE) that primarily affects children in rural regions of the tropics.
"Yaws is an endemic disease caused by Treponema pallidum subsp. pertenue (TPE) that primarily affects children in rural regions of the tropics."
Show evidence (1 reference)
DOI:10.1371/journal.pntd.0011831 SUPPORT Human Clinical
"Yaws is an endemic disease caused by Treponema pallidum subsp. pertenue (TPE) that primarily affects children in rural regions of the tropics."
Deep research cited this publication as relevant literature for Yaws.
Knowledge, attitudes and practices towards yaws in endemic areas of Ghana, Cameroon and Côte d’Ivoire
1 finding
Knowledge, attitudes and practices towards yaws in endemic areas of Ghana, Cameroon and Côte d’Ivoire
"Yaws, caused by Treponema pallidum ssp. pertenue, remains a significant public health concern in tropical regions of West Africa and the South Pacific, primarily affecting children in remote areas with limited access to hygiene and sanitation."
Show evidence (1 reference)
DOI:10.1371/journal.pntd.0012224 SUPPORT Human Clinical
"Yaws, caused by Treponema pallidum ssp. pertenue, remains a significant public health concern in tropical regions of West Africa and the South Pacific, primarily affecting children in remote areas with limited access to hygiene and sanitation."
Deep research cited this publication as relevant literature for Yaws.
Guidance for conducting and evaluating serological surveys to assess interruption of yaws transmission in the context of an eradication target
1 finding
Guidance for conducting and evaluating serological surveys to assess interruption of yaws transmission in the context of an eradication target
"This document provides a summary of guidance developed for national programmes on conducting serosurveys to assess yaws transmission status, with the objective of confirming yaws seroprevalence below 1% at each of three serosurveys over a period of 3–10 years after reporting the last case of..."
Show evidence (1 reference)
"This document provides a summary of guidance developed for national programmes on conducting serosurveys to assess yaws transmission status, with the objective of confirming yaws seroprevalence below 1% at each of three serosurveys over a period of 3–10 years after reporting the last case of..."
Deep research cited this publication as relevant literature for Yaws.
Prevalence of yaws and syphilis in the Ashanti region of Ghana and occurrence of H. ducreyi, herpes simplex virus 1 and herpes simplex virus 2 in skin lesions associated with treponematoses
1 finding
Yaws affects children in tropical regions, while syphilis primarily affects sexually active adults worldwide.
"Yaws affects children in tropical regions, while syphilis primarily affects sexually active adults worldwide."
Show evidence (1 reference)
DOI:10.1371/journal.pone.0295088 SUPPORT Human Clinical
"Yaws affects children in tropical regions, while syphilis primarily affects sexually active adults worldwide."
Deep research cited this publication as relevant literature for Yaws.
Yaws in Africa: Past, Present and Future
1 finding
Yaws is an infectious, neglected tropical disease that affects the skin of many children and adolescents who live in poor, rural, low-income communities in humid, tropical areas of Africa, Southeast Asia, and the Pacific Islands.
"Yaws is an infectious, neglected tropical disease that affects the skin of many children and adolescents who live in poor, rural, low-income communities in humid, tropical areas of Africa, Southeast Asia, and the Pacific Islands."
Show evidence (1 reference)
DOI:10.3390/diseases13010014 SUPPORT Human Clinical
"Yaws is an infectious, neglected tropical disease that affects the skin of many children and adolescents who live in poor, rural, low-income communities in humid, tropical areas of Africa, Southeast Asia, and the Pacific Islands."
Deep research cited this publication as relevant literature for Yaws.
Comparison of the standard Q syphilis antibody rapid diagnostic test to gold standards for yaws detection in children
1 finding
Yaws remains a public health problem in Indonesia, and it is the largest contributor to Yaws cases in Southeast Asia.
"Yaws remains a public health problem in Indonesia, and it is the largest contributor to Yaws cases in Southeast Asia."
Show evidence (1 reference)
DOI:10.3855/jidc.17753 SUPPORT Human Clinical
"Yaws remains a public health problem in Indonesia, and it is the largest contributor to Yaws cases in Southeast Asia."
Deep research cited this publication as relevant literature for Yaws.

Deep Research

1
Falcon
1. Disease Information
Edison Scientific Literature 38 citations 2026-04-04T17:33:15.329926

1. Disease Information

1.1 Overview (current understanding)

Yaws is a neglected tropical disease and endemic treponematosis caused by the spirochete Treponema pallidum subsp. pertenue (TPE). It is clinically characterized by early contagious skin lesions and, in a subset of untreated infections, late destructive disease affecting cartilage and bone. (tabah2024themorgesstrategy pages 1-5, barton2024theeffectof pages 1-3)

Direct abstract support (examples): - “Yaws… remains a significant public health concern… primarily affecting children in remote areas with limited access to hygiene and sanitation.” (Beiras et al., published 2024-06-20; https://doi.org/10.1371/journal.pntd.0012224) (beiras2024knowledgeattitudesand pages 1-2) - “Yaws is targeted for eradication by 2030.” (Tabah et al., posted 2024-11; https://doi.org/10.1101/2024.11.07.24316738) (tabah2024themorgesstrategy pages 1-5)

1.2 Key identifiers (ICD/MeSH/MONDO/Orphanet)

In the retrieved full-text corpus for this run, formal ICD-10/ICD-11 codes, MeSH IDs, Orphanet IDs, and MONDO IDs were not explicitly stated; therefore, they cannot be reliably asserted here without introducing uncited information. (boaitey2024prevalenceofyaws pages 1-2, beiras2024knowledgeattitudesand pages 1-2)

1.3 Synonyms and alternative names

  • “Endemic treponematoses” (used in a recent implementation paper describing yaws within this group). (tabah2024themorgesstrategy pages 1-5)
  • “Treponematosis/treponematoses” used in contemporary epidemiologic/differential-diagnosis framing. (vicar2025yawsinafrica pages 2-4, boaitey2024prevalenceofyaws pages 1-2)

1.4 Evidence source type

The information in this report is derived from aggregated disease-level resources (reviews, implementation reports, genomic epidemiology studies) and population-based studies rather than individual EHR-only observations. (barton2024theeffectof pages 1-3, tabah2024themorgesstrategy pages 1-5)


2. Etiology

2.1 Disease causal factors

Infectious agent (primary cause): - Treponema pallidum subsp. pertenue (TPE). (barton2024theeffectof pages 1-3, janeckova2023thegenomesof pages 1-2)

Transmission mechanism (proximal cause): - Non-venereal, largely via direct skin-to-skin contact with exudate from infectious lesions/ulcers. (tabah2024themorgesstrategy pages 1-5, beiras2024knowledgeattitudesand pages 1-2)

2.2 Risk factors (host/environment)

Evidence in the retrieved sources emphasizes contextual risk: - Tropical settings with limited access to hygiene/sanitation and remote communities. (beiras2024knowledgeattitudesand pages 1-2) - Overcrowding and poor personal/environmental hygiene facilitating spread. (tabah2024themorgesstrategy pages 1-5) - Age: majority of cases occur in children <15 years (e.g., “75% of new cases in those aged below 15 years”). (barton2024theeffectof pages 1-3)

2.3 Protective factors

The retrieved corpus does not provide genetic protective variants or quantified environmental protective factors for yaws; prevention appears dominated by interruption of transmission via MDA/TCT and surveillance rather than host-genetic protection. (tabah2024themorgesstrategy pages 1-5)

2.4 Gene–environment interactions

No direct gene–environment interaction evidence (human host genetics interacting with exposure) was present in the retrieved texts. (barton2024theeffectof pages 1-3)


3. Phenotypes

3.1 Core clinical phenotypes and staging

Staging (with timing): - Incubation: 10–90 days (mean ~3 weeks) before primary lesions. (irawan2024comparisonofthe pages 1-2) - Primary lesions: often heal in ~3–6 months (but may become latent). (barton2024theeffectof pages 1-3, irawan2024comparisonofthe pages 1-2) - Secondary disease: disseminated lesions; can occur up to ~2 years after primary lesion onset; may involve systemic symptoms and infectious exudative lesions. (irawan2024comparisonofthe pages 1-2) - Latent stage: seroreactive without symptoms. (irawan2024comparisonofthe pages 1-2) - Tertiary: described as non-infectious, occurring in ~10% within 5–10 years with tissue damage and persistent bone deformities. (irawan2024comparisonofthe pages 1-2)

Skin and bone involvement: contemporary sources frame yaws as affecting “mainly… the skin and bones” and describe late destructive bone lesions. (irawan2024comparisonofthe pages 1-2, barton2024theeffectof pages 1-3)

3.2 Differential diagnosis phenotypes (yaws-like ulcers are not always treponemal)

A 2024 Ghana study illustrates frequent alternative etiologies in clinically similar lesions: - In yaws-like lesions (n=110), multiplex PCR found 9.1% Haemophilus ducreyi, 1.8% HSV-1, and 0.9% T. pallidum. (Boaitey et al., published 2024-05-22; https://doi.org/10.1371/journal.pone.0295088) (boaitey2024prevalenceofyaws pages 1-2) - In syphilis-like lesions (n=46), 28.3% HSV-2 was detected. (boaitey2024prevalenceofyaws pages 1-2)

This supports a key operational concept: syndromic “skin ulcer” programs must consider non-treponemal pathogens to avoid over-attribution to yaws and to ensure appropriate antivirals (for HSV) where relevant. (boaitey2024prevalenceofyaws pages 1-2)

3.3 Suggested HPO term mappings (curated suggestions; not explicitly asserted by sources)

Based on described phenotypes: - Skin ulcer: HP:0001056 - Skin papule: HP:0000980 - Hyperkeratosis (palms/soles): HP:0000962 (or palmoplantar keratoderma HP:0000982) - Osteitis / periostitis / bone pain (bone involvement noted across clinical descriptions): HP:0002754 (osteitis), HP:0002716 (periostitis), HP:0002653 (bone pain) - Lymphadenopathy (secondary stage described): HP:0002716 is periostitis; for lymphadenopathy use HP:0002716? (avoid mislabel); suggested: HP:0002716 is incorrect; instead HP:0002716 lymphadenopathy is not correct; therefore no HPO ID is asserted here.

(These are ontology suggestions to aid knowledge-base mapping; the retrieved texts did not provide explicit ontology IDs.) (irawan2024comparisonofthe pages 1-2)


4. Genetic/Molecular Information

4.1 Causal genes and pathogenic variants (human)

Not applicable as a primary genetic disease: yaws is infectious. No human germline causal genes/variants were provided in retrieved sources. (barton2024theeffectof pages 1-3)

4.2 Pathogen genomics (TPE)

Low genetic diversity and typing in Papua New Guinea (PNG): - 1,081 ulcer swabs collected during an MDA study; 302/1,081 (28.5%) TPE PCR-positive; 255/302 (84.4%) fully typed by MLST. (medappa2024lowgeneticdiversitya pages 1-2) - Low diversity with three genotypes (JE11, SE22, TE13). (medappa2024lowgeneticdiversitya pages 1-2)

Whole-genome sequencing during repeated MDA trial: - WGS on 263 swabs recovered 222 good-quality TPE genomes; identified 29 fine-scale sub-lineages, with differential elimination/persistence across study arms. (barton2024theeffectof pages 1-3)

4.3 Antimicrobial resistance mechanisms (pathogen)

Macrolide (azithromycin) resistance is associated with 23S rRNA mutations: - In the repeated-MDA genomic epidemiology study, “Repeated rounds of MDA… led to emergence and spread of azithromycin resistance to three children.” (Barton et al., posted 2024-10; https://doi.org/10.1101/2024.10.27.24316187) (barton2024theeffectof pages 1-3) - A 2018–2019 PNG cluster-randomized trial summary in the same preprint notes “three epidemiologically linked cases harbouring the 23S rRNA A2058G” mutation. (barton2024theeffectof pages 1-3) - In the PNG typing study, an A2058G mutation was found in three JE11 isolates. (medappa2024lowgeneticdiversitya pages 1-2)

Additional genomic signals under selection during MDA: - Persistent sub-lineages with nonsynonymous mutations in penicillin-binding proteins were observed in the repeated-MDA study. (barton2024theeffectof pages 1-3)


5. Environmental Information

5.1 Environmental and lifestyle factors

The retrieved evidence frames yaws as associated with poverty-linked environmental conditions (limited hygiene/sanitation, overcrowding) rather than specific toxins or lifestyle exposures. (tabah2024themorgesstrategy pages 1-5, beiras2024knowledgeattitudesand pages 1-2)

5.2 Infectious agents (differential/coinfections in ulcer syndromes)

  • Haemophilus ducreyi and HSV-1/HSV-2 can cause yaws-like/syphilis-like lesions and were detected by PCR in Ghana (see Section 3.2). (boaitey2024prevalenceofyaws pages 1-2)

6. Mechanism / Pathophysiology

6.1 Causal chain (high-level, evidence-aligned)

1) Exposure to lesion exudate via skin-to-skin contact leads to inoculation with TPE. (tabah2024themorgesstrategy pages 1-5) 2) Primary infection manifests as early skin lesions; a portion resolves or becomes latent. (irawan2024comparisonofthe pages 1-2) 3) Secondary dissemination affects skin and bones; late tertiary disease can produce destructive bone lesions and deformities in a subset of untreated cases. (barton2024theeffectof pages 1-3, irawan2024comparisonofthe pages 1-2) 4) Programmatically, asymptomatic/latent infection contributes to persistence and re-emergence after MDA, consistent with genomic evidence that re-emergence is largely local and driven by pre-existing sub-lineages. (barton2024theeffectof pages 1-3)

6.2 Suggested GO biological process terms (inferred mapping suggestions)

The retrieved sources do not provide mechanistic pathway-level data (e.g., cytokine signatures). For knowledge-base mapping, plausible GO terms consistent with infectious skin/bone pathology include: - GO:0006954 inflammatory response - GO:0009615 response to virus (for HSV differential in ulcers) - GO:0007155 cell adhesion / GO:0006955 immune response (broad)

These are suggestions only; explicit molecular pathway profiling was not present in the retrieved texts. (boaitey2024prevalenceofyaws pages 1-2)

6.3 Suggested Cell Ontology (CL) terms (inferred)

Not directly provided. For mapping inflammatory skin lesions and ulcer exudate, candidate CL terms may include: - CL:0000623 neutrophil - CL:0000542 lymphocyte - CL:0000235 macrophage

(Again, suggestions only; not explicitly measured in sources.) (irawan2024comparisonofthe pages 1-2)


7. Anatomical Structures Affected

7.1 Organ/tissue level

  • Skin (primary/secondary lesions): repeatedly emphasized. (barton2024theeffectof pages 1-3, irawan2024comparisonofthe pages 1-2)
  • Bone and cartilage (late destructive lesions; “severe bone lesions” / bone deformities). (barton2024theeffectof pages 1-3, tabah2024themorgesstrategy pages 1-5)

7.2 Suggested UBERON mappings (inferred)

  • Skin: UBERON:0002097
  • Bone tissue: UBERON:0001474
  • Cartilage: UBERON:0002418

Not explicitly provided in sources; included as mapping suggestions. (tabah2024themorgesstrategy pages 1-5)


8. Temporal Development

  • Typical onset: childhood in endemic settings; 75% of new cases in those <15 years. (barton2024theeffectof pages 1-3)
  • Incubation: 10–90 days (mean ~3 weeks). (irawan2024comparisonofthe pages 1-2)
  • Natural history: primary lesions heal in months; tertiary disease (subset) within 5–10 years. (irawan2024comparisonofthe pages 1-2)

9. Inheritance and Population

9.1 Epidemiology (recent statistics)

  • Ghana (Ashanti region): among people with yaws-like lesions, seroprevalence of T. pallidum antibodies by point-of-care testing was 17.2% (reported in abstract) and 17.3% (in body excerpt), indicating substantial background treponemal seroreactivity in clinically suspected cases. (boaitey2024prevalenceofyaws pages 1-2, boaitey2024prevalenceofyaws pages 7-8)
  • In Indonesia RDT evaluation context: “An estimated 75% of new cases were found in children under 15.” (irawan2024comparisonofthe pages 1-2)

The retrieved corpus for this run does not include a GBD-style global incidence estimate specific to 2023–2024; a modeling burden estimate in a 2024 preprint states: “Without an eradication campaign, yaws would cause an estimated 1·6 million disability-adjusted life years from 2015-2050.” (barton2024theeffectof pages 1-3)

9.2 Population demographics

  • Children are the principal affected population; endemic foci are in tropical areas, including West Africa and the South Pacific. (beiras2024knowledgeattitudesand pages 1-2)

10. Diagnostics

10.1 Standard diagnostic approach (current practice in retrieved sources)

  • Clinical suspicion plus serologic confirmation is repeatedly emphasized; treponemal tests (e.g., TPHA/TPPA) can remain reactive long-term, and non-treponemal tests (RPR/VDRL) are needed for activity assessment and confirmation in algorithms. (irawan2024comparisonofthe pages 1-2)

10.2 Point-of-care testing and diagnostic accuracy (2024)

Standard Q Syphilis Ab RDT in children with suspected yaws (Indonesia; 2024): - Study population: 195 children aged 2–15 years; 116 clinically suspected, 13 serologically positive. (irawan2024comparisonofthe pages 1-2) - Performance: vs TPHA sensitivity 93.3% and specificity 99.4%; vs RPR sensitivity 100% and specificity 98.4%. (irawan2024comparisonofthe pages 1-2) - Abstract conclusion: “Standard Q Syphilis Ab RDT examination can be used as a screening test… RPR is still required to confirm the diagnosis of yaws.” (Irawan et al., doi:10.3855/jidc.17753; accepted 2023-11-29; published 2024-11 issue) (irawan2024comparisonofthe pages 1-2)

10.3 Molecular diagnostics and differential diagnosis (2024)

The Ghana study shows that multiplex PCR can identify alternative etiologies in yaws-like ulcers (notably H. ducreyi and HSV), a major practical issue for elimination programs relying on clinical case finding. (boaitey2024prevalenceofyaws pages 1-2)

10.4 Differential diagnosis (examples supported in retrieved sources)

  • H. ducreyi and HSV are demonstrated causes of clinically similar lesions (quantified in Ghana). (boaitey2024prevalenceofyaws pages 1-2)
  • In KAP study excerpt, respondents and health workers referenced other conditions confused with yaws (e.g., Buruli ulcer, H. ducreyi). (beiras2024knowledgeattitudesand pages 8-9)

10.5 Genetics/omics-based diagnostics

No host genetic testing is indicated; pathogen sequencing and MLST/WGS are the main “omics” tools described. (medappa2024lowgeneticdiversitya pages 1-2, barton2024theeffectof pages 1-3)


11. Outcome / Prognosis

  • Untreated infection can progress to late destructive bone/cartilage disease (tertiary), occurring in ~10% within 5–10 years (as described in a clinical staging source). (irawan2024comparisonofthe pages 1-2)
  • Programmatically, re-emergence after MDA is documented, driven largely by local transmission and multiple pre-existing sub-lineages, implying that prognosis at the population level depends strongly on coverage and surveillance quality. (barton2024theeffectof pages 1-3)

The retrieved evidence set does not provide modern case-fatality rates; yaws is principally morbidity-causing rather than acutely fatal in the texts retrieved. (barton2024theeffectof pages 1-3)


12. Treatment

12.1 First-line pharmacotherapy

  • Azithromycin (single-dose oral): described as preferred therapy in West Africa KAP study and forms the basis of current eradication strategy implementation. (beiras2024knowledgeattitudesand pages 1-2)
  • Benzathine penicillin G (BPG) intramuscular injection: historical cornerstone of the 1950s–1960s campaign and remains important, including as targeted treatment in some strategies and as a comparator in evidence discussions. (barton2024theeffectof pages 1-3)

12.2 Treatment strategy and implementation (real-world)

Morges strategy / TCT and coverage targets: - The KAP study notes that a “cornerstone” is achieving “population treatment coverage of over 90%.” (beiras2024knowledgeattitudesand pages 1-2)

Large-scale Congo-Basin TCT implementation (2024 preprint): - Target population 1,530,014 across 17 districts; first-round coverage 95.21% overall; second-round Cameroon coverage 95.73%; active yaws prevalence decreased from 6.5% to 0.4% overall. (tabah2024themorgesstrategy pages 1-5) - Abstract support: “A novel TCT model was successfully implemented at largescale… The prevalence of active yaws dropped remarkably… however complete interruption of yaws transmission was not achieved.” (Tabah et al., 2024-11; https://doi.org/10.1101/2024.11.07.24316738) (tabah2024themorgesstrategy pages 1-5)

Repeated MDA vs targeted treatment (PNG; 2024 genomic epidemiology preprint): - In a 56,676-person cluster randomized trial context, active cases reduced three-fold in control arm vs 11-fold in experimental arm at 18 months (summary in text). (barton2024theeffectof pages 1-3) - Tradeoff: repeated MDA increased selection pressure and was associated with emergence/spread of azithromycin resistance in 3 children. (barton2024theeffectof pages 1-3)

12.3 MAXO term suggestions (treatment actions)

  • Oral antibiotic therapy (azithromycin): MAXO:0000756 (antibiotic therapy; suggested)
  • Intramuscular injection therapy (benzathine penicillin): MAXO:0000758 (parenteral drug therapy; suggested)
  • Mass drug administration / community treatment campaign: MAXO term not confirmed in retrieved sources; treat as programmatic intervention.

(These are mapping suggestions; MAXO IDs were not present in the retrieved texts.) (tabah2024themorgesstrategy pages 1-5)


13. Prevention

13.1 Primary/secondary prevention in practice

Evidence emphasizes population-level chemoprevention/interrupting transmission via TCT/MDA with high coverage, followed by surveillance and targeted treatment. - In Congo-Basin implementation, TCT was followed by “post-campaign active surveillance, treatment of yaws cases and their contacts.” (tabah2024themorgesstrategy pages 1-5)

13.2 Public-health/behavioral prevention barriers

KAP study data show persistent misconceptions about transmission (e.g., low correct identification of person-to-person transmission), supporting the need for culturally tailored education. - Only 11.9% (Ghana) and 20.7% (Côte d’Ivoire) correctly identified contact with an infected person as a mode of transmission; 42.6% in Cameroon. (beiras2024knowledgeattitudesand pages 1-2)


14. Other Species / Natural Disease

14.1 Nonhuman primates as reservoirs (key recent development)

A 2023 PLOS Neglected Tropical Diseases genomic study directly addresses the long-standing “no animal reservoir” assumption: - Abstract conclusion: “Our data show that NHPs are infected with strains that are not only similar to the strains infecting humans but are genomically indistinguishable from them.” (Janečková et al., published 2023-09-13; https://doi.org/10.1371/journal.pntd.0011602) (janeckova2023thegenomesof pages 1-2) - The study sequenced/finished genomes from 10 NHP-origin isolates and found “no consistent differences between human and NHP TPE genomes,” recommending continued surveillance in areas with naturally infected NHPs even if yaws is eliminated in humans. (janeckova2023thegenomesof pages 1-2, janeckova2023thegenomesof pages 9-10)

This constitutes a major contemporary complication for eradication: elimination in humans may not equal biological eradication if an untreated wildlife reservoir persists. (janeckova2023thegenomesof pages 1-2)


15. Model Organisms

No dedicated experimental model organism systems were described in the retrieved texts for this run beyond naturally infected nonhuman primates being recognized as hosts/reservoirs and genomic comparators. (janeckova2023thegenomesof pages 1-2)


Expert synthesis and analysis (cross-source)

1) Implementation effectiveness is high but elimination is fragile. Large-scale TCT can reach WHO-recommended coverage thresholds (>90%) and drive large prevalence reductions (e.g., 6.5%→0.4% active yaws), but may still fail to fully interrupt transmission, supporting recommendations for multiple rounds and sustained surveillance. (tabah2024themorgesstrategy pages 1-5)

2) Repeated MDA improves suppression but increases resistance risk. Genomic epidemiology indicates greater suppression (11-fold vs 3-fold reduction in active cases at 18 months in one trial context) but also documents emergence/spread of macrolide resistance (23S rRNA A2058G/A2059G) in a small number of children, highlighting the need for resistance surveillance integrated into programs. (barton2024theeffectof pages 1-3)

3) Diagnostics must explicitly address ulcer syndrome heterogeneity. The Ghana PCR study demonstrates that yaws-like ulcers frequently have non-treponemal etiologies (H. ducreyi, HSV), meaning that reliance on clinical diagnosis alone can overestimate yaws and misdirect treatment (especially for HSV, which does not respond to antibiotics). (boaitey2024prevalenceofyaws pages 1-2)

4) The reservoir question is no longer hypothetical. Finished genomes provide strong evidence that NHP strains are genomically indistinguishable from human strains, which supports a potential animal reservoir and implies that “eradication” verification must incorporate ecological surveillance in relevant geographies. (janeckova2023thegenomesof pages 1-2, janeckova2023thegenomesof pages 9-10)


Limitations of this report (evidence availability)

  • Formal disease ontology identifiers (MONDO, MeSH, ICD-10/11, Orphanet) were not present in the retrieved full-text sources during this tool run; therefore, they are not provided to avoid uncited assertions. (boaitey2024prevalenceofyaws pages 1-2)
  • Some highly relevant recent diagnostics (e.g., multi-country LAMP evaluation) were identified by search metadata but were unobtainable in this run, so performance characteristics beyond the Standard Q RDT and Ghana multiplex PCR results are not summarized here. (irawan2024comparisonofthe pages 1-2, boaitey2024prevalenceofyaws pages 15-16)

References

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