Yaws

Infectious Disease MONDO:0006019 Pathograph 26 Show in embeddings browser Bacterial Infection Neglected tropical disease

Yaws is a chronic and disfiguring bacterial infection caused by Treponema pallidum subsp. pertenue.

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7
Pathophys.
16
Phenotypes
26
Pathograph
3
Medical Actions
3
Differentials
9
References
1
Deep Research
⚙

Pathophysiology

7
Cutaneous Treponemal Inoculation
Direct skin contact with an infectious lesion introduces Treponema pallidum subsp. pertenue into skin, where primary yaws presents as a highly contagious papilloma or ulcer.
symbiont entry into host GO:0044409 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves symbiont entry into host (GO:0044409). GO:0044409 is a biological process from the Gene Ontology.
skin UBERON:0002097 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in skin, annotated with skin of body (UBERON:0002097). UBERON:0002097 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Disseminated Secondary Yaws Untreated primary disease may progress to disseminated secondary yaws.
Skin ulcer Primary cutaneous infection produces a usually painless papilloma or ulcer.
Primary yaws papilloma Primary cutaneous infection produces a contagious papillomatous lesion.
Show evidence (2 references)
PMID:40036381 SUPPORT Other
"It is spread through direct skin contact."
Supports direct skin contact as the inoculation route.
PMID:40036381 SUPPORT Other
"In the primary stage, patients develop a, usually painless, papilloma or ulcer, often on the lower extremities, which is highly contagious."
Supports the primary cutaneous lesion at the inoculation site.
Disseminated Secondary Yaws
Untreated primary infection can disseminate through the skin, producing widespread lesions and palmoplantar hyperkeratosis; osteoarticular involvement can produce bone pain, periostitis, and dactylitis.
skin UBERON:0002097 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in skin, annotated with skin of body (UBERON:0002097). UBERON:0002097 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Tertiary Destructive Disease A minority of untreated infections progress to disfiguring tertiary disease.
Disseminated skin eruption Secondary dissemination produces widespread skin lesions and scaly papules.
Painful palmoplantar hyperkeratosis Secondary dissemination produces painful palmoplantar hyperkeratotic plaques.
Bone pain Secondary-stage osteoarticular involvement can cause pain localized to bone.
Periostitis Early yaws can produce multifocal osteoperiostitis.
Finger dactylitis Phalangeal osteoarticular involvement can present as dactylitis.
Fever Secondary dissemination can be accompanied by fever.
Malaise Secondary dissemination can be accompanied by malaise.
Generalized lymphadenopathy Secondary dissemination can produce generalized lymphadenopathy.
Show evidence (1 reference)
PMID:40036381 SUPPORT Other
"If untreated, this lesion heals spontaneously but may progress to secondary yaws, characterised by disseminated skin lesions, scaly papules and painful hyperkeratotic plaques on the palms and soles."
Directly supports the manifestations modeled in this secondary-stage node.
Tertiary Destructive Disease
Untreated yaws can rarely progress to a tertiary stage with severe, disfiguring tissue damage, including chronic destructive lesions of bone. Cartilage may also be involved in later stages, but the cited evidence does not characterize that involvement as destructive. This stage is now uncommon where treatment is available.
Downstream
Severe disfigurement Tertiary disease can cause severe disfigurement.
Late bone destruction Untreated late disease can cause chronic destructive bone lesions.
Later-stage cartilage involvement Cartilage may be involved in later-stage yaws; destructive change is not asserted.
Tertiary gumma Late tissue destruction can produce suppurative gummatous lesions.
Gangosa Late destructive disease can cause gangosa (rhinopharyngitis mutilans).
Saber tibia Persistent late bone deformity can include saber-shaped tibial bowing.
Show evidence (1 reference)
PMID:40036381 SUPPORT Other
"Tertiary cases occur in 10% of untreated individuals and can cause severe disfigurement, but with the wider availability of treatment this is rare today."
Directly supports both the untreated-case proportion and severe disfigurement claim.
Treponemal Ribosomal Translation (Azithromycin Target)
Treponema pallidum subsp. pertenue depends on bacterial ribosomal translation. Azithromycin inhibits bacterial protein synthesis by binding the 50S component of the 70S ribosome, creating a therapeutically exploitable vulnerability.
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.
Downstream
23S rRNA A2058G/A2059G-Mediated Azithromycin Resistance Mutation of 23S rRNA modifies the ribosomal macrolide target and permits therapeutic escape.
Show evidence (1 reference)
PMID:1319048 SUPPORT Other
"Structurally related to the macrolide antibiotic erythromycin, its mechanism of activity (similar to erythromycin) is interference with bacterial protein synthesis by binding to the 50S component of the 70S ribosomal subunit."
Directly supports azithromycin's inhibition of bacterial protein synthesis through the 50S ribosomal component.
23S rRNA A2058G/A2059G-Mediated Azithromycin Resistance
A2058G and A2059G substitutions in TPE 23S rRNA are associated with azithromycin resistance. A2058G was reported in three isolates from one PNG study, while a separate longitudinal cohort identified A2059G in five treatment-failure cases linked within one village. These localized findings establish resistance emergence, not its population prevalence.
Response to Antibiotic GO:0046677 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves Response to Antibiotic (GO:0046677). GO:0046677 is a biological process from the Gene Ontology.
Downstream
Azithromycin Clinical Failure in a Localized Resistant Cluster 23S rRNA resistance mutations were detected in five active-yaws cases with azithromycin clinical failure in one village.
Show evidence (2 references)
PMID:38166151 SUPPORT Human Clinical
"Moreover, the A2058G mutation in the 23S rRNA genes of three JE11 isolates was found, resulting in azithromycin resistance."
Directly identifies A2058G in three human ulcer isolates; this evidence is retained as a localized observation and not generalized to prevalence.
PMID:29428183 SUPPORT Human Clinical
"Of 208 PCR-confirmed active yaws cases in the post-MDA period, the 23S rRNA gene could be amplified by PCR in 186 (89·4%), of which 181 (97·3%) had wild-type strains, but two cases at 36 months and three cases at 42 months revealed A2059G mutations associated with macrolide-resistance."
Directly identifies A2059G in the five localized post-MDA resistant cases.
Azithromycin Clinical Failure in a Localized Resistant Cluster
Five active-yaws cases from one village showed clinical failure after azithromycin, with PCR-detected 23S rRNA resistance mutations. The cited evidence does not assign these cases to primary or secondary clinical stage and is not generalized to community-wide re-emergence.
Show evidence (1 reference)
PMID:29428183 SUPPORT Human Clinical
"At months 36 and 42, five cases of active yaws, all from the same village, showed clinical failure following azithromycin treatment, with PCR-detected mutations in the 23S ribosomal RNA genes conferring resistance to azithromycin."
Directly supports localized azithromycin clinical failure without assigning a clinical stage.
Benzathine Benzylpenicillin Treatment Vulnerability
Benzathine benzylpenicillin is clinically effective against yaws. General beta-lactam pharmacology supports inhibition of peptidoglycan transpeptidation, but the cited evidence does not establish a TPE-specific penicillin-binding-protein mechanism.
Show evidence (2 references)
PMID:22203377 SUPPORT Other
"although glycan chain polymerization occurs in the absence of transpeptidation (for example, in the presence of penicillin), efficient transpeptidation requires ongoing GTase reactions"
Supports the generic penicillin-transpeptidation mechanism, but not a TPE-specific molecular target; the yaws-specific claim is limited to clinical treatment susceptibility below.
PMID:40036381 SUPPORT Other
"Though yaws can be treated with benzathine penicillin, oral azithromycin has become the preferred treatment due to its ease of administration."
Directly supports benzathine penicillin as the yaws treatment exploiting this vulnerability.
⬡

Pathograph

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

16
Cardiovascular 1
Generalized lymphadenopathy HP:0008940 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Generalized lymphadenopathy (HP:0008940). HP:0008940 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:39693168 SUPPORT Human Clinical
"This stage is generally accompanied by systemic symptoms such as fever, malaise, and generalized lymphadenopathy."
Directly supports generalized lymphadenopathy during secondary yaws.
Immune 1
Disseminated skin eruption Skin rash HP:0000988 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Disseminated skin eruption, annotated with Skin rash (HP:0000988). HP:0000988 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:40036381 SUPPORT Other
"If untreated, this lesion heals spontaneously but may progress to secondary yaws, characterised by disseminated skin lesions, scaly papules and painful hyperkeratotic plaques on the palms and soles."
Directly supports the disseminated and scaly secondary eruption.
Integument 3
Primary yaws papilloma Verrucous papule HP:0012500 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Verrucous papule (HP:0012500). HP:0012500 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:40036381 SUPPORT Other
"In the primary stage, patients develop a, usually painless, papilloma or ulcer, often on the lower extremities, which is highly contagious."
Directly supports a papillomatous primary-stage lesion.
Skin ulcer HP:0200042 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Skin ulcer (HP:0200042). HP:0200042 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:40036381 SUPPORT Other
"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.
Painful palmoplantar hyperkeratosis Palmoplantar keratoderma HP:0000982 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Painful palmoplantar hyperkeratosis, annotated with Palmoplantar keratoderma (HP:0000982). HP:0000982 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:40036381 SUPPORT Other
"If untreated, this lesion heals spontaneously but may progress to secondary yaws, characterised by disseminated skin lesions, scaly papules and painful hyperkeratotic plaques on the palms and soles."
Directly supports painful palmoplantar hyperkeratotic plaques.
Limbs 1
Saber tibia Tibial bowing HP:0002982 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Tibial bowing (HP:0002982). HP:0002982 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:39693168 SUPPORT Human Clinical
"Advanced lesions may include gummas, ulcers, gangosa, and tibial sabers"
Directly supports the saber-tibia manifestation, represented by the broader HPO tibial-bowing concept.
Metabolism 1
Fever HP:0001945 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Fever (HP:0001945). HP:0001945 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:39693168 SUPPORT Human Clinical
"This stage is generally accompanied by systemic symptoms such as fever, malaise, and generalized lymphadenopathy."
Directly supports fever during secondary yaws.
Musculoskeletal 1
Late bone destruction Osteolysis HP:0002797 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Osteolysis (HP:0002797). HP:0002797 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:25193248 SUPPORT Other
"It causes lesions of the skin, mucous membranes and bones which, without treatment, can become chronic and destructive."
Directly supports chronic destructive bone lesions in untreated yaws.
Constitutional 2
Bone pain HP:0002653 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Bone pain (HP:0002653). HP:0002653 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
url:https://pmc.ncbi.nlm.nih.gov/articles/PMC3122353/ SUPPORT Human Clinical
"Marked pain in the long bones of extremities with or without visible bone or soft-tissue swelling or deformity on examination was present in 10 (15.9%) of secondary stage cases."
Directly documents long-bone pain in secondary-stage cases.
Malaise HP:0033834 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Malaise (HP:0033834). HP:0033834 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:39693168 SUPPORT Human Clinical
"This stage is generally accompanied by systemic symptoms such as fever, malaise, and generalized lymphadenopathy."
Directly supports malaise during secondary yaws.
Other 6
Periostitis HP:0040165 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Periostitis (HP:0040165). HP:0040165 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:28193743 SUPPORT Human Clinical
"Bone lesions in the form of osteoperiostitis are common and occur in numerous bones simultaneously in early stages."
Directly supports early multifocal osteoperiostitis.
Finger dactylitis HP:0031090 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Finger dactylitis (HP:0031090). HP:0031090 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
url:https://pmc.ncbi.nlm.nih.gov/articles/PMC3122353/ SUPPORT Human Clinical
"Includes seven cases of radiologically confirmed yaws osteoperiostitis among three patients who had dactylilitis."
Directly documents dactylitis in patients with radiologically confirmed yaws osteoperiostitis.
Later-stage cartilage involvement
Show evidence (1 reference)
PMID:38166151 SUPPORT Human Clinical
"Clinical manifestations in the primary stage include chronic skin ulcers and other skin lesions, potentially affecting bones and cartilage in the later stages"
Directly supports later-stage cartilage involvement without characterizing it as destructive.
Tertiary gumma
Show evidence (1 reference)
PMID:39693168 SUPPORT Human Clinical
"Advanced lesions may include gummas, ulcers, gangosa, and tibial sabers"
Directly identifies gummas among advanced yaws lesions.
Gangosa
Show evidence (1 reference)
PMID:39693168 SUPPORT Human Clinical
"Advanced lesions may include gummas, ulcers, gangosa, and tibial sabers"
Directly identifies gangosa among advanced yaws lesions; no sufficiently specific HPO term is assigned.
Severe disfigurement
Show evidence (1 reference)
PMID:40036381 SUPPORT Other
"Tertiary cases occur in 10% of untreated individuals and can cause severe disfigurement, but with the wider availability of treatment this is rare today."
Directly supports severe disfigurement as a tertiary manifestation.
💊

Medical Actions

3
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.
Preferred regimen for individual or mass treatment: one oral dose of 30 mg/kg, capped at 2 g.
Mechanism Target:
INHIBITS Treponemal Ribosomal Translation (Azithromycin Target) — Azithromycin binds the bacterial 50S ribosomal component and inhibits protein synthesis.
Show evidence (1 reference)
PMID:1319048 SUPPORT Other
"Structurally related to the macrolide antibiotic erythromycin, its mechanism of activity (similar to erythromycin) is interference with bacterial protein synthesis by binding to the 50S component of the 70S ribosomal subunit."
Directly supports the modeled treatment-to-target mechanism.
Show evidence (3 references)
PMID:28072863 SUPPORT Human Clinical
"Participants who met the inclusion criteria were randomized to receive treatment with either a single dose oral azithromycin administered at a dose of 30mg/kg (maximum of 2g) or a single dose of benzathine penicillin administered as an intramuscular injection of 1.2 million units for subjects..."
Directly supports the exact single-dose azithromycin regimen and maximum dose.
PMID:40036381 SUPPORT Other
"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.
PMID:24396138 SUPPORT Other
"This challenging but potentially feasible endeavor is favored by the adoption of oral azithromycin for mass treatment"
Directly supports oral azithromycin as the mass-treatment agent in yaws eradication.
Benzathine penicillin 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: benzathine benzylpenicillin CHEBI:51352 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses benzathine benzylpenicillin, annotated with benzylpenicillin benzathine (CHEBI:51352). CHEBI:51352 is a therapeutic agent from Chemical Entities of Biological Interest.
Alternative or azithromycin-failure rescue treatment. In the cited Ghana trial, the single intramuscular BPG dose was 0.6 million units for participants under 10 years and 1.2 million units for participants aged 10–15 years; this trial does not establish the 1.2-million-unit dose outside that age range.
Mechanism Target:
INHIBITS Benzathine Benzylpenicillin Treatment Vulnerability — Clinical efficacy establishes TPE susceptibility to benzathine benzylpenicillin; inhibition of peptidoglycan transpeptidation is retained only as generic beta-lactam class context, not a demonstrated TPE-specific mechanism.
Show evidence (1 reference)
PMID:22203377 SUPPORT Other
"although glycan chain polymerization occurs in the absence of transpeptidation (for example, in the presence of penicillin), efficient transpeptidation requires ongoing GTase reactions"
Supports generic penicillin inhibition of transpeptidation, but not a TPE-specific penicillin-binding-protein mechanism.
Show evidence (3 references)
PMID:28072863 SUPPORT Human Clinical
"Participants who met the inclusion criteria were randomized to receive treatment with either a single dose oral azithromycin administered at a dose of 30mg/kg (maximum of 2g) or a single dose of benzathine penicillin administered as an intramuscular injection of 1.2 million units for subjects..."
Directly supports the exact age-stratified single-dose BPG regimen.
PMID:29428183 SUPPORT Human Clinical
"All presented with worsening skin lesions 2-weeks after azithromycin treatment and were subsequently treated with benzathine benzylpenicillin."
Directly supports BPG rescue after azithromycin-resistant clinical failure.
PMID:40036381 SUPPORT Other
"Though yaws can be treated with benzathine penicillin, oral azithromycin has become the preferred treatment due to its ease of administration."
Directly supports benzathine penicillin as an effective yaws treatment.
Morges eradication strategy
Begin with total community treatment (TCT) using single-dose azithromycin in the entire endemic community, then use repeat TCT or active case-finding and total targeted treatment of active cases and their household, school, and play contacts. Continue active post-campaign surveillance; contact-only targeting can miss geographically dispersed latent infections.
Show evidence (7 references)
PMID:29140407 SUPPORT Computational
"The World Health Organization strategy mandates an initial round of total community treatment (TCT) with single-dose azithromycin followed either by further TCT or active case-finding and treatment of cases and their contacts (the Morges strategy)."
Directly defines the TCT and case/contact components of the Morges strategy.
PMID:29140407 SUPPORT Computational
"This analysis indicated that targeted treatment of cases and their household contacts would miss a large fraction of asymptomatic infections (65%-100%)."
Supports the limitation of contact-only targeting for latent infection.
DOI:10.1101/2024.11.07.24316738 Preprint · not peer-reviewed SUPPORT Human Clinical
"TCT was followed by post-campaign active surveillance, treatment of yaws cases and their contacts."
Directly supports post-campaign surveillance and case/contact treatment in implementation.
+ 4 more references
🌍

Environmental Factors

2
Limited access to hygiene and sanitation
Show evidence (1 reference)
PMID:38900827 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."
Directly describes the affected remote-community context and limited access to hygiene and sanitation.
Mechanism Target:
PREDISPOSES Cutaneous Treponemal Inoculation — Remote-community conditions with limited hygiene and sanitation access are associated with yaws burden and can increase opportunities for skin-to-skin transmission, but the cited study does not isolate a direct causal effect.
Show evidence (1 reference)
PMID:38900827 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."
Supports the observed remote-community and limited-access association; causal intermediates are not directly tested.
Natural TPE infection in nonhuman primates (potential reservoir)
Naturally infected nonhuman primates harbor TPE strains genomically indistinguishable from human strains, supporting potential reservoir status. Current spillover evidence is missing, so this record does not assert ongoing zoonotic transmission.
Show evidence (2 references)
PMID:37703251 SUPPORT Model Organism
"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."
Natural infection directly supports TPE infection of nonhuman primates and their potential reservoir role; it does not establish human spillover.
PMID:37703251 SUPPORT Model Organism
"Although interspecies transmission in NHPs is a rare event and evidence for current spillover events is missing, the existence of the yaws bacterium in NHPs is demonstrated."
Preserves the key caveat that a reservoir does not establish current spillover to humans.
🔬

Diagnosis

4
Clinical examination with serological confirmation
Clinical suspicion requires combined serology, but serology does not identify T. pallidum subsp. pertenue. Treponemal reactivity cannot distinguish yaws from syphilis or another treponematosis and generally cannot distinguish past or treated infection from current infection. RPR is a nonspecific nontreponemal activity/treatment-response marker, not a test of TPE identity.
Results: Interpret a treponemal result as evidence of treponemal exposure and an RPR titre as evidence bearing on activity; use lesion molecular testing when organism and subspecies identity matter.
Show evidence (4 references)
PMID:39693168 SUPPORT Human Clinical
"The diagnosis of yaws is based on clinical findings with serological confirmation."
Directly supports the combined clinical and serologic diagnostic approach.
PMID:23016260 SUPPORT Other
"Serological tests cannot distinguish between yaws and syphilis or other non-venereal treponematoses."
Directly supports the organism-identity limitation of serology.
PMID:38319847 SUPPORT Other
"T reponemal antibodies generally persist after treatment and cannot be used to distinguish between a current infection or a previously treated infection."
Supports the past-versus-current limitation of treponemal antibody tests.
+ 1 more reference
Standard Q Syphilis Antibody rapid diagnostic test
Point-of-care screening test evaluated against TPHA and RPR in children with yaws.
Results: High sensitivity and specificity; RPR remains necessary for confirmation when findings are unusual.
Show evidence (2 references)
PMID:39693168 SUPPORT Human Clinical
"The sensitivity and specificity of RDT compared to TPHA were 93.3% and 99.4%, respectively. The sensitivity and specificity of RDT compared to RPR were 100% and 98.4%, respectively."
Directly reports the screening test's accuracy against both comparators.
PMID:39693168 SUPPORT Human Clinical
"However, unusual clinical findings, like scars in RDT reactive patients, indicated that RPR is still required to confirm the diagnosis of yaws."
Directly supports retaining RPR confirmation for unusual presentations.
Lesion PCR and multiplex differential diagnosis of yaws-like ulcers
PCR on material from an active skin lesion directly detects T. pallidum DNA; subspecies-specific targets or sequencing are needed to establish TPE. Multiplex testing should also assess Haemophilus ducreyi and HSV-1/HSV-2 in clinically similar ulcers.
Results: TPE-positive lesion PCR supports active yaws; detection of H. ducreyi or HSV identifies a non-yaws ulcer cause, while serology alone may reflect latent or past treponemal infection.
Show evidence (2 references)
PMID:29428183 SUPPORT Human Clinical
"Active yaws confirmed by PCR specific for Treponema pallidum was the primary outcome indicator."
Directly supports lesion molecular confirmation of active yaws.
PMID:38776332 SUPPORT Human Clinical
"Multiplex PCR results showed that 9.1%, 1.8% and 0.9% of yaws-like lesions were positive for Haemophilus ducreyi, herpes simplex virus-1 (HSV-1) and T. pallidum respectively."
Directly demonstrates pathogen heterogeneity among clinically yaws-like lesions.
Four-week post-treatment response and resistance assessment
Re-examine treated lesions at four weeks. Persistent lesions require renewed etiologic evaluation, lesion PCR confirmation, and testing of 23S rRNA for macrolide-resistance mutations; presumed azithromycin failure is managed with intramuscular benzathine penicillin G rescue.
Results: Complete healing supports treatment response. A persistent PCR-confirmed TPE lesion with A2058G or A2059G supports macrolide-resistant treatment failure.
Show evidence (3 references)
PMID:41911295 SUPPORT Human Clinical
"Treatment was with a single dose of oral azithromycin and outcomes were evaluated 4 weeks post-treatment, assessing clinical resolution and time to healing, with results stratified by the identified aetiological agents."
Directly supports the four-week clinical response assessment.
PMID:29428183 SUPPORT Human Clinical
"At months 36 and 42, five cases of active yaws, all from the same village, showed clinical failure following azithromycin treatment, with PCR-detected mutations in the 23S ribosomal RNA genes conferring resistance to azithromycin."
Directly supports PCR-based investigation of azithromycin treatment failure.
PMID:29428183 SUPPORT Human Clinical
"Of 208 PCR-confirmed active yaws cases in the post-MDA period, the 23S rRNA gene could be amplified by PCR in 186 (89·4%), of which 181 (97·3%) had wild-type strains, but two cases at 36 months and three cases at 42 months revealed A2059G mutations associated with macrolide-resistance."
Directly supports A2059G testing in the localized treatment-failure cluster.
🪜

Stages

4
Primary yaws
After an incubation period of 10–90 days (mean about three weeks), primary yaws presents as a usually painless, highly contagious papilloma or ulcer, often on a lower extremity.
Show evidence (2 references)
PMID:40036381 SUPPORT Other
"In the primary stage, patients develop a, usually painless, papilloma or ulcer, often on the lower extremities, which is highly contagious."
Directly defines the primary-stage lesion.
PMID:39693168 SUPPORT Human Clinical
"In the primary stage, skin lesions appear after an incubation period of 10-90 days (with a mean of three weeks)."
Directly supports the primary-stage incubation range and mean.
Secondary yaws
Disseminated skin lesions, scaly papules, and painful palmoplantar hyperkeratotic plaques, with osteoarticular manifestations including bone pain, periostitis, and dactylitis; fever, malaise, and generalized lymphadenopathy can accompany this stage.
Show evidence (4 references)
PMID:40036381 SUPPORT Other
"If untreated, this lesion heals spontaneously but may progress to secondary yaws, characterised by disseminated skin lesions, scaly papules and painful hyperkeratotic plaques on the palms and soles."
Directly defines secondary-stage progression and manifestations.
PMID:21734134 SUPPORT Human Clinical
"A high proportion of cases (46%) were in the secondary stage; 92% of them had osteoarticular involvement, and only 24% had a Venereal Disease Research Laboratory titer greater than 1:32."
Directly places osteoarticular involvement in secondary yaws.
PMID:28193743 SUPPORT Human Clinical
"Bone lesions in the form of osteoperiostitis are common and occur in numerous bones simultaneously in early stages."
Directly supports early multifocal periostitis.
+ 1 more reference
Latent or asymptomatic yaws
Seroreactive infection without active skin lesions or other symptoms can persist for years and later reactivate. Latent infections form a clinically silent reservoir that can be missed by lesion-based case finding.
Show evidence (3 references)
PMID:23016260 SUPPORT Other
"The infection remains asymptomatic for several years."
This review directly supports a prolonged asymptomatic stage.
PMID:29428183 SUPPORT Human Clinical
"A sustained decrease in the prevalence of high-titre latent yaws from 13·7% to <1·5% in asymptomatic children aged 1-5 years old and of genetic diversity of yaws strains from 0·139 to less than 0·046 between months 24 and 42 indicated a reduction in transmission of infection."
Longitudinal human surveillance directly measured high-titre latent yaws among asymptomatic children in this age-defined study cohort; the rate is not presented as global prevalence.
PMID:34986286 SUPPORT Human Clinical
"The prevalence of latent yaws at 18 months was 6.54% (95% CI, 5.00 to 8.08) among 994 children in the control group and 3.28% (95% CI, 2.14 to 4.42) among 945 children in the experimental group (relative risk adjusted for clustering and age, 2.03; 95% CI, 1.12 to 3.70)."
Directly measures latent infection in asymptomatic children enrolled in the trial; these selected-cohort rates are not generalized globally.
Tertiary yaws
Rare late stage, historically occurring within 5–10 years after inoculation in about 10% of untreated cases, with severe disfigurement, gummas, gangosa, saber tibia, destructive bone lesions, and reported later-stage cartilage involvement.
Show evidence (4 references)
PMID:40036381 SUPPORT Other
"Tertiary cases occur in 10% of untreated individuals and can cause severe disfigurement, but with the wider availability of treatment this is rare today."
Directly defines tertiary-stage frequency in untreated individuals and current rarity.
PMID:38166151 SUPPORT Human Clinical
"Clinical manifestations in the primary stage include chronic skin ulcers and other skin lesions, potentially affecting bones and cartilage in the later stages"
Directly supports later-stage involvement of bone and cartilage without characterizing the cartilage involvement as destructive.
PMID:39693168 SUPPORT Human Clinical
"The tertiary stage is a non-infectious stage that occurs in 10% of cases within 5-10 years after bacterial inoculation."
Directly supports the reported tertiary-stage interval and untreated-era proportion.
+ 1 more reference
📊

Prevalence

1
Countries where yaws remains endemic
Unknown Unknown
Yaws is reported as endemic in at least 15 countries, but inadequate surveillance prevents a defensible global prevalence estimate. The 0.50%-43.0% range reported by the same review comes from selected studies in 11 African countries and is not represented as worldwide prevalence.
Show evidence (1 reference)
PMID:39851478 SUPPORT Other
"Yaws is currently endemic in at least 15 countries, but adequate surveillance data are lacking."
Supports endemic-country distribution and the decision not to derive a global numerical prevalence from selected study cohorts.
🌍

Epidemiology

1
Endemic childhood disease of rural humid tropical communities
Yaws is concentrated among children and adolescents living in poor, rural, low-income communities in humid tropical areas of Africa, Southeast Asia, and the Pacific Islands.
childhood and adolescence rural residence poverty and low income humid tropical climate
Show evidence (1 reference)
PMID:39851478 SUPPORT Other
"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."
This review directly supports the age, socioeconomic, rural, climatic, and geographic epidemiology summarized here.
🦠

Infectious Agent

1
Treponema pallidum subsp. pertenue
Spirochete that causes yaws.
Treponema pallidum subsp. pertenue NCBITaxon:168 NCBI Taxonomy (NCBITaxon)
Show evidence (1 reference)
PMID:40036381 SUPPORT Other
"Yaws, a neglected tropical disease caused by Treponema pallidum subsp. pertenue, primarily affects children in impoverished rural areas."
The abstract identifies T. pallidum subsp. pertenue as the cause of yaws.
↔️

Transmission

1
Direct skin contact
Transmitted through direct skin contact with infected individuals.
Show evidence (1 reference)
PMID:40036381 SUPPORT Other
"It is spread through direct skin contact."
The abstract states yaws is spread through direct skin contact.
🔀

Differential Diagnoses

3

Conditions with similar clinical presentations that must be differentiated from Yaws:

Syphilis
Overlapping Features Venereal syphilis and yaws both produce reactive treponemal serology and can have overlapping cutaneous manifestations.
Distinguishing Features
  • Sexual and congenital transmission context favors syphilis; childhood skin-to-skin transmission in an endemic rural tropical community favors yaws.
  • Serology alone cannot assign the infecting T. pallidum subspecies; lesion molecular testing is needed when identity is consequential.
Show evidence (1 reference)
PMID:25193248 SUPPORT Other
"Infection with yaws or syphilis results in reactive treponemal serology and there is no widely available test to distinguish between these infections."
Directly supports syphilis as a serologically overlapping differential.
Haemophilus ducreyi-associated cutaneous ulcer
Overlapping Features H. ducreyi can cause a clinically yaws-like skin ulcer.
Distinguishing Features
  • Multiplex lesion PCR detects H. ducreyi rather than T. pallidum DNA.
Show evidence (1 reference)
PMID:38776332 SUPPORT Human Clinical
"Multiplex PCR results showed that 9.1%, 1.8% and 0.9% of yaws-like lesions were positive for Haemophilus ducreyi, herpes simplex virus-1 (HSV-1) and T. pallidum respectively."
Directly identifies H. ducreyi in clinically yaws-like lesions.
Herpes simplex virus-associated ulcer
Overlapping Features HSV-1 or HSV-2 can produce an ulcer in the treponematosis differential.
Distinguishing Features
  • Multiplex lesion PCR detects HSV-1 or HSV-2 rather than T. pallidum DNA.
Show evidence (1 reference)
PMID:38776332 SUPPORT Human Clinical
"Multiplex PCR results showed that 9.1%, 1.8% and 0.9% of yaws-like lesions were positive for Haemophilus ducreyi, herpes simplex virus-1 (HSV-1) and T. pallidum respectively."
Directly identifies HSV-1 in clinically yaws-like lesions.
{ }

Source YAML

click to show 
name: Yaws
creation_date: '2026-01-26T15:56:41Z'
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
    evidence_source: OTHER
    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
    evidence_source: OTHER
    snippet: "It is spread through direct skin contact."
    explanation: The abstract states yaws is spread through direct skin contact.
epidemiology:
- name: Endemic childhood disease of rural humid tropical communities
  description: >-
    Yaws is concentrated among children and adolescents living in poor, rural,
    low-income communities in humid tropical areas of Africa, Southeast Asia,
    and the Pacific Islands.
  factors:
  - childhood and adolescence
  - rural residence
  - poverty and low income
  - humid tropical climate
  evidence:
  - reference: PMID:39851478
    reference_title: "Yaws in Africa: Past, Present and Future."
    supports: SUPPORT
    evidence_source: OTHER
    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: >-
      This review directly supports the age, socioeconomic, rural, climatic,
      and geographic epidemiology summarized here.
prevalence:
- population: Countries where yaws remains endemic
  measure_type: UNKNOWN
  prevalence_class: UNKNOWN
  notes: >-
    Yaws is reported as endemic in at least 15 countries, but inadequate
    surveillance prevents a defensible global prevalence estimate. The
    0.50%-43.0% range reported by the same review comes from selected studies
    in 11 African countries and is not represented as worldwide prevalence.
  evidence:
  - reference: PMID:39851478
    reference_title: "Yaws in Africa: Past, Present and Future."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Yaws is currently endemic in at least 15 countries, but adequate
      surveillance data are lacking.
    explanation: >-
      Supports endemic-country distribution and the decision not to derive a
      global numerical prevalence from selected study cohorts.
pathophysiology:
- name: Cutaneous Treponemal Inoculation
  biological_scale: TISSUE
  description: >-
    Direct skin contact with an infectious lesion introduces Treponema pallidum
    subsp. pertenue into skin, where primary yaws presents as a highly contagious
    papilloma or ulcer.
  biological_processes:
  - preferred_term: symbiont entry into host
    term:
      id: GO:0044409
      label: symbiont entry into host
  locations:
  - preferred_term: skin
    term:
      id: UBERON:0002097
      label: skin of body
  downstream:
  - target: Disseminated Secondary Yaws
    description: Untreated primary disease may progress to disseminated secondary yaws.
    evidence:
    - reference: PMID:40036381
      reference_title: "Yaws - A Review of Clinical Features, Diagnosis and Treatment."
      supports: SUPPORT
      evidence_source: OTHER
      snippet: >-
        If untreated, this lesion heals spontaneously but may progress to secondary
        yaws, characterised by disseminated skin lesions, scaly papules and painful
        hyperkeratotic plaques on the palms and soles.
      explanation: Directly supports progression from an untreated primary lesion to secondary yaws.
  - target: Skin ulcer
    description: Primary cutaneous infection produces a usually painless papilloma or ulcer.
    evidence:
    - reference: PMID:40036381
      reference_title: "Yaws - A Review of Clinical Features, Diagnosis and Treatment."
      supports: SUPPORT
      evidence_source: OTHER
      snippet: >-
        In the primary stage, patients develop a, usually painless, papilloma or
        ulcer, often on the lower extremities, which is highly contagious.
      explanation: Directly links the primary-stage mechanism to its cutaneous phenotype.
  - target: Primary yaws papilloma
    description: Primary cutaneous infection produces a contagious papillomatous lesion.
    evidence:
    - reference: PMID:40036381
      reference_title: "Yaws - A Review of Clinical Features, Diagnosis and Treatment."
      supports: SUPPORT
      evidence_source: OTHER
      snippet: >-
        In the primary stage, patients develop a, usually painless, papilloma or
        ulcer, often on the lower extremities, which is highly contagious.
      explanation: Directly links primary yaws to the papillomatous lesion.
  evidence:
  - reference: PMID:40036381
    reference_title: "Yaws - A Review of Clinical Features, Diagnosis and Treatment."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "It is spread through direct skin contact."
    explanation: Supports direct skin contact as the inoculation route.
  - reference: PMID:40036381
    reference_title: "Yaws - A Review of Clinical Features, Diagnosis and Treatment."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      In the primary stage, patients develop a, usually painless, papilloma or
      ulcer, often on the lower extremities, which is highly contagious.
    explanation: Supports the primary cutaneous lesion at the inoculation site.
- name: Disseminated Secondary Yaws
  biological_scale: TISSUE
  description: >-
    Untreated primary infection can disseminate through the skin, producing
    widespread lesions and palmoplantar hyperkeratosis; osteoarticular
    involvement can produce bone pain, periostitis, and dactylitis.
  locations:
  - preferred_term: skin
    term:
      id: UBERON:0002097
      label: skin of body
  downstream:
  - target: Tertiary Destructive Disease
    description: A minority of untreated infections progress to disfiguring tertiary disease.
    evidence:
    - reference: PMID:40036381
      reference_title: "Yaws - A Review of Clinical Features, Diagnosis and Treatment."
      supports: SUPPORT
      evidence_source: OTHER
      snippet: >-
        Tertiary cases occur in 10% of untreated individuals and can cause severe
        disfigurement, but with the wider availability of treatment this is rare today.
      explanation: Directly quantifies tertiary progression among untreated individuals.
  - target: Disseminated skin eruption
    description: Secondary dissemination produces widespread skin lesions and scaly papules.
    evidence:
    - reference: PMID:40036381
      reference_title: "Yaws - A Review of Clinical Features, Diagnosis and Treatment."
      supports: SUPPORT
      evidence_source: OTHER
      snippet: >-
        If untreated, this lesion heals spontaneously but may progress to secondary
        yaws, characterised by disseminated skin lesions, scaly papules and painful
        hyperkeratotic plaques on the palms and soles.
      explanation: Directly links secondary yaws to the disseminated eruption.
  - target: Painful palmoplantar hyperkeratosis
    description: Secondary dissemination produces painful palmoplantar hyperkeratotic plaques.
    evidence:
    - reference: PMID:40036381
      reference_title: "Yaws - A Review of Clinical Features, Diagnosis and Treatment."
      supports: SUPPORT
      evidence_source: OTHER
      snippet: >-
        If untreated, this lesion heals spontaneously but may progress to secondary
        yaws, characterised by disseminated skin lesions, scaly papules and painful
        hyperkeratotic plaques on the palms and soles.
      explanation: Directly links secondary yaws to the painful palmoplantar phenotype.
  - target: Bone pain
    description: Secondary-stage osteoarticular involvement can cause pain localized to bone.
    evidence:
    - reference: url:https://pmc.ncbi.nlm.nih.gov/articles/PMC3122353/
      reference_title: Challenges in Recognition and Diagnosis of Yaws in Children in Papua New Guinea - PMC
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Marked pain in the long bones of extremities with or without visible
        bone or soft-tissue swelling or deformity on examination was present in
        10 (15.9%) of secondary stage cases.
      explanation: Directly documents long-bone pain in secondary-stage cases.
  - target: Periostitis
    description: Early yaws can produce multifocal osteoperiostitis.
    evidence:
    - reference: PMID:28193743
      reference_title: "Yaws Osteoperiostitis Treated with Single-Dose Azithromycin."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Bone lesions in the form of osteoperiostitis are common and occur in
        numerous bones simultaneously in early stages.
      explanation: Directly supports early multifocal osteoperiostitis in yaws.
  - target: Finger dactylitis
    description: Phalangeal osteoarticular involvement can present as dactylitis.
    evidence:
    - reference: url:https://pmc.ncbi.nlm.nih.gov/articles/PMC3122353/
      reference_title: Challenges in Recognition and Diagnosis of Yaws in Children in Papua New Guinea - PMC
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Includes seven cases of radiologically confirmed yaws osteoperiostitis among three patients who had dactylilitis.
      explanation: Directly documents dactylitis in patients with radiologically confirmed yaws osteoperiostitis.
  - target: Fever
    description: Secondary dissemination can be accompanied by fever.
    evidence:
    - reference: PMID:39693168
      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: >-
        This stage is generally accompanied by systemic symptoms such as fever,
        malaise, and generalized lymphadenopathy.
      explanation: Directly identifies fever as a systemic manifestation of secondary yaws.
  - target: Malaise
    description: Secondary dissemination can be accompanied by malaise.
    evidence:
    - reference: PMID:39693168
      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: >-
        This stage is generally accompanied by systemic symptoms such as fever,
        malaise, and generalized lymphadenopathy.
      explanation: Directly identifies malaise as a systemic manifestation of secondary yaws.
  - target: Generalized lymphadenopathy
    description: Secondary dissemination can produce generalized lymphadenopathy.
    evidence:
    - reference: PMID:39693168
      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: >-
        This stage is generally accompanied by systemic symptoms such as fever,
        malaise, and generalized lymphadenopathy.
      explanation: Directly identifies generalized lymphadenopathy in secondary yaws.
  evidence:
  - reference: PMID:40036381
    reference_title: "Yaws - A Review of Clinical Features, Diagnosis and Treatment."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      If untreated, this lesion heals spontaneously but may progress to secondary
      yaws, characterised by disseminated skin lesions, scaly papules and painful
      hyperkeratotic plaques on the palms and soles.
    explanation: Directly supports the manifestations modeled in this secondary-stage node.
- name: Tertiary Destructive Disease
  biological_scale: TISSUE
  description: >-
    Untreated yaws can rarely progress to a tertiary stage with severe,
    disfiguring tissue damage, including chronic destructive lesions of bone.
    Cartilage may also be involved in later stages, but the cited evidence does
    not characterize that involvement as destructive. This stage is now uncommon
    where treatment is available.
  downstream:
  - target: Severe disfigurement
    description: Tertiary disease can cause severe disfigurement.
    evidence:
    - reference: PMID:40036381
      reference_title: "Yaws - A Review of Clinical Features, Diagnosis and Treatment."
      supports: SUPPORT
      evidence_source: OTHER
      snippet: >-
        Tertiary cases occur in 10% of untreated individuals and can cause severe
        disfigurement, but with the wider availability of treatment this is rare today.
      explanation: Directly links tertiary yaws to severe disfigurement.
  - target: Late bone destruction
    description: Untreated late disease can cause chronic destructive bone lesions.
    evidence:
    - reference: PMID:25193248
      reference_title: "Yaws."
      supports: SUPPORT
      evidence_source: OTHER
      snippet: >-
        It causes lesions of the skin, mucous membranes and bones which, without
        treatment, can become chronic and destructive.
      explanation: Directly supports chronic destructive bone lesions in untreated yaws.
  - target: Later-stage cartilage involvement
    description: Cartilage may be involved in later-stage yaws; destructive change is not asserted.
    evidence:
    - reference: PMID:38166151
      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: >-
        Clinical manifestations in the primary stage include chronic skin ulcers
        and other skin lesions, potentially affecting bones and cartilage in the
        later stages
      explanation: Directly supports later-stage cartilage involvement without characterizing it as destructive.
  - target: Tertiary gumma
    description: Late tissue destruction can produce suppurative gummatous lesions.
    evidence:
    - reference: PMID:39693168
      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: Advanced lesions may include gummas, ulcers, gangosa, and tibial sabers
      explanation: Directly identifies gummas among advanced yaws lesions.
  - target: Gangosa
    description: Late destructive disease can cause gangosa (rhinopharyngitis mutilans).
    evidence:
    - reference: PMID:39693168
      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: Advanced lesions may include gummas, ulcers, gangosa, and tibial sabers
      explanation: Directly identifies gangosa among advanced yaws lesions.
  - target: Saber tibia
    description: Persistent late bone deformity can include saber-shaped tibial bowing.
    evidence:
    - reference: PMID:39693168
      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: Advanced lesions may include gummas, ulcers, gangosa, and tibial sabers
      explanation: Directly identifies tibial saber deformity among advanced yaws lesions.
  evidence:
  - reference: PMID:40036381
    reference_title: "Yaws - A Review of Clinical Features, Diagnosis and Treatment."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Tertiary cases occur in 10% of untreated individuals and can cause severe
      disfigurement, but with the wider availability of treatment this is rare today.
    explanation: Directly supports both the untreated-case proportion and severe disfigurement claim.
- name: Treponemal Ribosomal Translation (Azithromycin Target)
  biological_scale: MOLECULAR
  description: >-
    Treponema pallidum subsp. pertenue depends on bacterial ribosomal translation.
    Azithromycin inhibits bacterial protein synthesis by binding the 50S component
    of the 70S ribosome, creating a therapeutically exploitable vulnerability.
  role: therapeutic_vulnerability
  conforms_to: "bacterial_protein_synthesis_inhibition#Bacterial mRNA Translation by the Ribosome"
  downstream:
  - target: 23S rRNA A2058G/A2059G-Mediated Azithromycin Resistance
    description: Mutation of 23S rRNA modifies the ribosomal macrolide target and permits therapeutic escape.
    evidence:
    - reference: PMID:29428183
      reference_title: "Re-emergence of yaws after single mass azithromycin treatment followed by targeted treatment: a longitudinal study."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Of 208 PCR-confirmed active yaws cases in the post-MDA period, the 23S rRNA
        gene could be amplified by PCR in 186 (89·4%), of which 181 (97·3%) had
        wild-type strains, but two cases at 36 months and three cases at 42 months
        revealed A2059G mutations associated with macrolide-resistance.
      explanation: Directly links 23S rRNA target mutation to macrolide resistance in TPE.
  biological_processes:
  - preferred_term: Translation
    term:
      id: GO:0006412
      label: translation
  evidence:
  - reference: PMID:1319048
    reference_title: "Azithromycin--spectrum of activity, pharmacokinetics, and clinical applications."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Structurally related to the macrolide antibiotic erythromycin, its mechanism
      of activity (similar to erythromycin) is interference with bacterial protein
      synthesis by binding to the 50S component of the 70S ribosomal subunit.
    explanation: >-
      Directly supports azithromycin's inhibition of bacterial protein synthesis
      through the 50S ribosomal component.
- name: 23S rRNA A2058G/A2059G-Mediated Azithromycin Resistance
  biological_scale: MOLECULAR
  conforms_to: "bacterial_protein_synthesis_inhibition#Ribosomal Target Resistance"
  role: adaptive_escape
  description: >-
    A2058G and A2059G substitutions in TPE 23S rRNA are associated with
    azithromycin resistance. A2058G was reported in three isolates from one PNG
    study, while a separate longitudinal cohort identified A2059G in five
    treatment-failure cases linked within one village. These localized findings
    establish resistance emergence, not its population prevalence.
  downstream:
  - target: Azithromycin Clinical Failure in a Localized Resistant Cluster
    description: 23S rRNA resistance mutations were detected in five active-yaws cases with azithromycin clinical failure in one village.
    evidence:
    - reference: PMID:29428183
      reference_title: "Re-emergence of yaws after single mass azithromycin treatment followed by targeted treatment: a longitudinal study."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        At months 36 and 42, five cases of active yaws, all from the same village,
        showed clinical failure following azithromycin treatment, with PCR-detected
        mutations in the 23S ribosomal RNA genes conferring resistance to azithromycin.
      explanation: Directly links 23S rRNA resistance mutations to clinical failure in a localized cluster.
  biological_processes:
  - preferred_term: Response to Antibiotic
    term:
      id: GO:0046677
      label: response to antibiotic
  evidence:
  - reference: PMID:38166151
    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: >-
      Moreover, the A2058G mutation in the 23S rRNA genes of three JE11 isolates
      was found, resulting in azithromycin resistance.
    explanation: >-
      Directly identifies A2058G in three human ulcer isolates; this evidence is
      retained as a localized observation and not generalized to prevalence.
  - reference: PMID:29428183
    reference_title: "Re-emergence of yaws after single mass azithromycin treatment followed by targeted treatment: a longitudinal study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Of 208 PCR-confirmed active yaws cases in the post-MDA period, the 23S rRNA
      gene could be amplified by PCR in 186 (89·4%), of which 181 (97·3%) had
      wild-type strains, but two cases at 36 months and three cases at 42 months
      revealed A2059G mutations associated with macrolide-resistance.
    explanation: Directly identifies A2059G in the five localized post-MDA resistant cases.
- name: Azithromycin Clinical Failure in a Localized Resistant Cluster
  biological_scale: ORGANISM
  description: >-
    Five active-yaws cases from one village showed clinical failure after
    azithromycin, with PCR-detected 23S rRNA resistance mutations. The cited
    evidence does not assign these cases to primary or secondary clinical stage
    and is not generalized to community-wide re-emergence.
  evidence:
  - reference: PMID:29428183
    reference_title: "Re-emergence of yaws after single mass azithromycin treatment followed by targeted treatment: a longitudinal study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      At months 36 and 42, five cases of active yaws, all from the same village,
      showed clinical failure following azithromycin treatment, with PCR-detected
      mutations in the 23S ribosomal RNA genes conferring resistance to azithromycin.
    explanation: Directly supports localized azithromycin clinical failure without assigning a clinical stage.
- name: Benzathine Benzylpenicillin Treatment Vulnerability
  biological_scale: CELLULAR
  description: >-
    Benzathine benzylpenicillin is clinically effective against yaws. General
    beta-lactam pharmacology supports inhibition of peptidoglycan
    transpeptidation, but the cited evidence does not establish a
    TPE-specific penicillin-binding-protein mechanism.
  role: therapeutic_vulnerability
  evidence:
  - reference: PMID:22203377
    reference_title: From the regulation of peptidoglycan synthesis to bacterial growth and morphology.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      although glycan chain polymerization occurs in the absence of
      transpeptidation (for example, in the presence of penicillin), efficient
      transpeptidation requires ongoing GTase reactions
    explanation: >-
      Supports the generic penicillin-transpeptidation mechanism, but not a
      TPE-specific molecular target; the yaws-specific claim is limited to
      clinical treatment susceptibility below.
  - reference: PMID:40036381
    reference_title: "Yaws - A Review of Clinical Features, Diagnosis and Treatment."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Though yaws can be treated with benzathine penicillin, oral azithromycin has
      become the preferred treatment due to its ease of administration.
    explanation: Directly supports benzathine penicillin as the yaws treatment exploiting this vulnerability.
phenotypes:
- name: Primary yaws papilloma
  category: Dermatologic
  description: Primary yaws commonly produces a usually painless, highly contagious papillomatous papule.
  phenotype_term:
    preferred_term: Verrucous papule
    term:
      id: HP:0012500
      label: Verrucous papule
  evidence:
  - reference: PMID:40036381
    reference_title: "Yaws - A Review of Clinical Features, Diagnosis and Treatment."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      In the primary stage, patients develop a, usually painless, papilloma or
      ulcer, often on the lower extremities, which is highly contagious.
    explanation: Directly supports a papillomatous primary-stage lesion.
- name: Skin ulcer
  category: Dermatologic
  description: >-
    Primary yaws commonly presents as a usually painless, highly contagious
    papilloma or ulcer, often on a lower extremity.
  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
    evidence_source: OTHER
    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.
- name: Disseminated skin eruption
  category: Dermatologic
  description: Secondary yaws produces disseminated skin lesions and scaly papules.
  phenotype_term:
    preferred_term: Disseminated skin eruption
    term:
      id: HP:0000988
      label: Skin rash
  evidence:
  - reference: PMID:40036381
    reference_title: "Yaws - A Review of Clinical Features, Diagnosis and Treatment."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      If untreated, this lesion heals spontaneously but may progress to secondary
      yaws, characterised by disseminated skin lesions, scaly papules and painful
      hyperkeratotic plaques on the palms and soles.
    explanation: Directly supports the disseminated and scaly secondary eruption.
- name: Painful palmoplantar hyperkeratosis
  category: Dermatologic
  description: Secondary yaws can cause painful thickened plaques on the palms and soles.
  phenotype_term:
    preferred_term: Painful palmoplantar hyperkeratosis
    term:
      id: HP:0000982
      label: Palmoplantar keratoderma
  evidence:
  - reference: PMID:40036381
    reference_title: "Yaws - A Review of Clinical Features, Diagnosis and Treatment."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      If untreated, this lesion heals spontaneously but may progress to secondary
      yaws, characterised by disseminated skin lesions, scaly papules and painful
      hyperkeratotic plaques on the palms and soles.
    explanation: Directly supports painful palmoplantar hyperkeratotic plaques.
- name: Bone pain
  category: Musculoskeletal
  description: Secondary-stage osteoarticular yaws can cause pain localized to affected bones.
  phenotype_term:
    preferred_term: Bone pain
    term:
      id: HP:0002653
      label: Bone pain
  evidence:
  - reference: url:https://pmc.ncbi.nlm.nih.gov/articles/PMC3122353/
    reference_title: Challenges in Recognition and Diagnosis of Yaws in Children in Papua New Guinea - PMC
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Marked pain in the long bones of extremities with or without visible bone
      or soft-tissue swelling or deformity on examination was present in 10
      (15.9%) of secondary stage cases.
    explanation: Directly documents long-bone pain in secondary-stage cases.
- name: Periostitis
  category: Musculoskeletal
  description: Early yaws can produce multifocal osteoperiostitis.
  phenotype_term:
    preferred_term: Periostitis
    term:
      id: HP:0040165
      label: Periostitis
  evidence:
  - reference: PMID:28193743
    reference_title: "Yaws Osteoperiostitis Treated with Single-Dose Azithromycin."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Bone lesions in the form of osteoperiostitis are common and occur in
      numerous bones simultaneously in early stages.
    explanation: Directly supports early multifocal osteoperiostitis.
- name: Finger dactylitis
  category: Musculoskeletal
  description: Secondary osteoarticular yaws can involve the phalanges and present as dactylitis.
  phenotype_term:
    preferred_term: Finger dactylitis
    term:
      id: HP:0031090
      label: Finger dactylitis
  evidence:
  - reference: url:https://pmc.ncbi.nlm.nih.gov/articles/PMC3122353/
    reference_title: Challenges in Recognition and Diagnosis of Yaws in Children in Papua New Guinea - PMC
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Includes seven cases of radiologically confirmed yaws osteoperiostitis among three patients who had dactylilitis.
    explanation: Directly documents dactylitis in patients with radiologically confirmed yaws osteoperiostitis.
- name: Fever
  category: Systemic
  description: Secondary yaws can be accompanied by fever.
  phenotype_term:
    preferred_term: Fever
    term:
      id: HP:0001945
      label: Fever
  evidence:
  - reference: PMID:39693168
    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: >-
      This stage is generally accompanied by systemic symptoms such as fever,
      malaise, and generalized lymphadenopathy.
    explanation: Directly supports fever during secondary yaws.
- name: Malaise
  category: Systemic
  description: Secondary yaws can be accompanied by malaise.
  phenotype_term:
    preferred_term: Malaise
    term:
      id: HP:0033834
      label: Malaise
  evidence:
  - reference: PMID:39693168
    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: >-
      This stage is generally accompanied by systemic symptoms such as fever,
      malaise, and generalized lymphadenopathy.
    explanation: Directly supports malaise during secondary yaws.
- name: Generalized lymphadenopathy
  category: Lymphatic
  description: Secondary yaws can be accompanied by generalized lymphadenopathy.
  phenotype_term:
    preferred_term: Generalized lymphadenopathy
    term:
      id: HP:0008940
      label: Generalized lymphadenopathy
  evidence:
  - reference: PMID:39693168
    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: >-
      This stage is generally accompanied by systemic symptoms such as fever,
      malaise, and generalized lymphadenopathy.
    explanation: Directly supports generalized lymphadenopathy during secondary yaws.
- name: Late bone destruction
  category: Musculoskeletal
  severity: SEVERE
  description: Untreated late yaws can cause chronic destructive bone lesions.
  phenotype_term:
    preferred_term: Osteolysis
    term:
      id: HP:0002797
      label: Osteolysis
  evidence:
  - reference: PMID:25193248
    reference_title: "Yaws."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      It causes lesions of the skin, mucous membranes and bones which, without
      treatment, can become chronic and destructive.
    explanation: Directly supports chronic destructive bone lesions in untreated yaws.
- name: Later-stage cartilage involvement
  category: Musculoskeletal
  description: Cartilage may be involved in later stages of yaws.
  phenotype_term:
    preferred_term: Later-stage cartilage involvement
  evidence:
  - reference: PMID:38166151
    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: >-
      Clinical manifestations in the primary stage include chronic skin ulcers
      and other skin lesions, potentially affecting bones and cartilage in the
      later stages
    explanation: Directly supports later-stage cartilage involvement without characterizing it as destructive.
- name: Tertiary gumma
  category: Dermatologic
  severity: SEVERE
  description: Late yaws can produce suppurative gummatous lesions of skin and subcutaneous tissue.
  evidence:
  - reference: PMID:39693168
    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: Advanced lesions may include gummas, ulcers, gangosa, and tibial sabers
    explanation: Directly identifies gummas among advanced yaws lesions.
- name: Gangosa
  category: ENT
  severity: SEVERE
  description: Gangosa is destructive late rhinopharyngeal disease (rhinopharyngitis mutilans).
  evidence:
  - reference: PMID:39693168
    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: Advanced lesions may include gummas, ulcers, gangosa, and tibial sabers
    explanation: Directly identifies gangosa among advanced yaws lesions; no sufficiently specific HPO term is assigned.
- name: Saber tibia
  category: Musculoskeletal
  severity: SEVERE
  description: Late yaws can cause saber-shaped tibial bowing.
  phenotype_term:
    preferred_term: Tibial bowing
    term:
      id: HP:0002982
      label: Tibial bowing
  evidence:
  - reference: PMID:39693168
    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: Advanced lesions may include gummas, ulcers, gangosa, and tibial sabers
    explanation: Directly supports the saber-tibia manifestation, represented by the broader HPO tibial-bowing concept.
- name: Severe disfigurement
  category: Clinical
  severity: SEVERE
  description: Tertiary yaws can cause severe disfigurement in untreated individuals.
  evidence:
  - reference: PMID:40036381
    reference_title: "Yaws - A Review of Clinical Features, Diagnosis and Treatment."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Tertiary cases occur in 10% of untreated individuals and can cause severe
      disfigurement, but with the wider availability of treatment this is rare today.
    explanation: Directly supports severe disfigurement as a tertiary manifestation.
stages:
- name: Primary yaws
  description: >-
    After an incubation period of 10–90 days (mean about three weeks), primary
    yaws presents as a usually painless, highly contagious papilloma or ulcer,
    often on a lower extremity.
  evidence:
  - reference: PMID:40036381
    reference_title: "Yaws - A Review of Clinical Features, Diagnosis and Treatment."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      In the primary stage, patients develop a, usually painless, papilloma or
      ulcer, often on the lower extremities, which is highly contagious.
    explanation: Directly defines the primary-stage lesion.
  - reference: PMID:39693168
    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: >-
      In the primary stage, skin lesions appear after an incubation period of
      10-90 days (with a mean of three weeks).
    explanation: Directly supports the primary-stage incubation range and mean.
- name: Secondary yaws
  description: >-
    Disseminated skin lesions, scaly papules, and painful palmoplantar
    hyperkeratotic plaques, with osteoarticular manifestations including bone
    pain, periostitis, and dactylitis; fever, malaise, and generalized
    lymphadenopathy can accompany this stage.
  evidence:
  - reference: PMID:40036381
    reference_title: "Yaws - A Review of Clinical Features, Diagnosis and Treatment."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      If untreated, this lesion heals spontaneously but may progress to secondary
      yaws, characterised by disseminated skin lesions, scaly papules and painful
      hyperkeratotic plaques on the palms and soles.
    explanation: Directly defines secondary-stage progression and manifestations.
  - reference: PMID:21734134
    reference_title: "Challenges in recognition and diagnosis of yaws in children in Papua New Guinea."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      A high proportion of cases (46%) were in the secondary stage; 92% of
      them had osteoarticular involvement, and only 24% had a Venereal Disease
      Research Laboratory titer greater than 1:32.
    explanation: Directly places osteoarticular involvement in secondary yaws.
  - reference: PMID:28193743
    reference_title: "Yaws Osteoperiostitis Treated with Single-Dose Azithromycin."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Bone lesions in the form of osteoperiostitis are common and occur in
      numerous bones simultaneously in early stages.
    explanation: Directly supports early multifocal periostitis.
  - reference: PMID:39693168
    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: >-
      This stage is generally accompanied by systemic symptoms such as fever,
      malaise, and generalized lymphadenopathy.
    explanation: Directly supports the systemic manifestations accompanying secondary yaws.
- name: Latent or asymptomatic yaws
  description: >-
    Seroreactive infection without active skin lesions or other symptoms can
    persist for years and later reactivate. Latent infections form a clinically
    silent reservoir that can be missed by lesion-based case finding.
  evidence:
  - reference: PMID:23016260
    reference_title: "Yaws, a non-venereal treponemal infection. Still endemic in some parts of the world."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "The infection remains asymptomatic for several years."
    explanation: This review directly supports a prolonged asymptomatic stage.
  - reference: PMID:29428183
    reference_title: "Re-emergence of yaws after single mass azithromycin treatment followed by targeted treatment: a longitudinal study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      A sustained decrease in the prevalence of high-titre latent yaws from
      13·7% to <1·5% in asymptomatic children aged 1-5 years old and of genetic
      diversity of yaws strains from 0·139 to less than 0·046 between months 24
      and 42 indicated a reduction in transmission of infection.
    explanation: >-
      Longitudinal human surveillance directly measured high-titre latent yaws
      among asymptomatic children in this age-defined study cohort; the rate is
      not presented as global prevalence.
  - reference: PMID:34986286
    reference_title: "Trial of Three Rounds of Mass Azithromycin Administration for Yaws Eradication."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The prevalence of latent yaws at 18 months was 6.54% (95% CI, 5.00 to
      8.08) among 994 children in the control group and 3.28% (95% CI, 2.14 to
      4.42) among 945 children in the experimental group (relative risk adjusted
      for clustering and age, 2.03; 95% CI, 1.12 to 3.70).
    explanation: >-
      Directly measures latent infection in asymptomatic children enrolled in
      the trial; these selected-cohort rates are not generalized globally.
- name: Tertiary yaws
  description: >-
    Rare late stage, historically occurring within 5–10 years after inoculation
    in about 10% of untreated cases, with severe disfigurement, gummas, gangosa,
    saber tibia, destructive bone lesions, and reported later-stage cartilage
    involvement.
  evidence:
  - reference: PMID:40036381
    reference_title: "Yaws - A Review of Clinical Features, Diagnosis and Treatment."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Tertiary cases occur in 10% of untreated individuals and can cause severe
      disfigurement, but with the wider availability of treatment this is rare today.
    explanation: Directly defines tertiary-stage frequency in untreated individuals and current rarity.
  - reference: PMID:38166151
    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: >-
      Clinical manifestations in the primary stage include chronic skin ulcers
      and other skin lesions, potentially affecting bones and cartilage in the
      later stages
    explanation: Directly supports later-stage involvement of bone and cartilage without characterizing the cartilage involvement as destructive.
  - reference: PMID:39693168
    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: >-
      The tertiary stage is a non-infectious stage that occurs in 10% of cases
      within 5-10 years after bacterial inoculation.
    explanation: Directly supports the reported tertiary-stage interval and untreated-era proportion.
  - reference: PMID:39693168
    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: Advanced lesions may include gummas, ulcers, gangosa, and tibial sabers
    explanation: Directly supports classic advanced manifestations of tertiary yaws.
diagnosis:
- name: Clinical examination with serological confirmation
  description: >-
    Clinical suspicion requires combined serology, but serology does not identify
    T. pallidum subsp. pertenue. Treponemal reactivity cannot distinguish yaws
    from syphilis or another treponematosis and generally cannot distinguish past
    or treated infection from current infection. RPR is a nonspecific
    nontreponemal activity/treatment-response marker, not a test of TPE identity.
  results: >-
    Interpret a treponemal result as evidence of treponemal exposure and an RPR
    titre as evidence bearing on activity; use lesion molecular testing when
    organism and subspecies identity matter.
  evidence:
  - reference: PMID:39693168
    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: "The diagnosis of yaws is based on clinical findings with serological confirmation."
    explanation: Directly supports the combined clinical and serologic diagnostic approach.
  - reference: PMID:23016260
    reference_title: "Yaws, a non-venereal treponemal infection. Still endemic in some parts of the world."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Serological tests cannot distinguish between yaws and syphilis or other
      non-venereal treponematoses.
    explanation: Directly supports the organism-identity limitation of serology.
  - reference: PMID:38319847
    reference_title: "CDC Laboratory Recommendations for Syphilis Testing, United States, 2024."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      T reponemal antibodies generally persist after treatment and cannot be used
      to distinguish between a current infection or a previously treated infection.
    explanation: >-
      Supports the past-versus-current limitation of treponemal antibody tests.
  - reference: PMID:38319847
    reference_title: "CDC Laboratory Recommendations for Syphilis Testing, United States, 2024."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      None of the nontreponemal (lipoidal antigen) or treponemal tests can
      distinguish infections caused by other T. pallidum subspecies.
    explanation: >-
      Supports that neither RPR nor treponemal serology establishes TPE identity.
- name: Standard Q Syphilis Antibody rapid diagnostic test
  description: Point-of-care screening test evaluated against TPHA and RPR in children with yaws.
  results: High sensitivity and specificity; RPR remains necessary for confirmation when findings are unusual.
  evidence:
  - reference: PMID:39693168
    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: >-
      The sensitivity and specificity of RDT compared to TPHA were 93.3% and
      99.4%, respectively. The sensitivity and specificity of RDT compared to RPR
      were 100% and 98.4%, respectively.
    explanation: Directly reports the screening test's accuracy against both comparators.
  - reference: PMID:39693168
    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: >-
      However, unusual clinical findings, like scars in RDT reactive patients,
      indicated that RPR is still required to confirm the diagnosis of yaws.
    explanation: Directly supports retaining RPR confirmation for unusual presentations.
- name: Lesion PCR and multiplex differential diagnosis of yaws-like ulcers
  description: >-
    PCR on material from an active skin lesion directly detects T. pallidum DNA;
    subspecies-specific targets or sequencing are needed to establish TPE.
    Multiplex testing should also assess Haemophilus ducreyi and HSV-1/HSV-2 in
    clinically similar ulcers.
  results: >-
    TPE-positive lesion PCR supports active yaws; detection of H. ducreyi or HSV
    identifies a non-yaws ulcer cause, while serology alone may reflect latent or
    past treponemal infection.
  evidence:
  - reference: PMID:29428183
    reference_title: "Re-emergence of yaws after single mass azithromycin treatment followed by targeted treatment: a longitudinal study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Active yaws confirmed by PCR specific for Treponema pallidum was the primary outcome indicator."
    explanation: Directly supports lesion molecular confirmation of active yaws.
  - reference: PMID:38776332
    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: >-
      Multiplex PCR results showed that 9.1%, 1.8% and 0.9% of yaws-like lesions
      were positive for Haemophilus ducreyi, herpes simplex virus-1 (HSV-1) and
      T. pallidum respectively.
    explanation: Directly demonstrates pathogen heterogeneity among clinically yaws-like lesions.
- name: Four-week post-treatment response and resistance assessment
  description: >-
    Re-examine treated lesions at four weeks. Persistent lesions require renewed
    etiologic evaluation, lesion PCR confirmation, and testing of 23S rRNA for
    macrolide-resistance mutations; presumed azithromycin failure is managed with
    intramuscular benzathine penicillin G rescue.
  results: >-
    Complete healing supports treatment response. A persistent PCR-confirmed TPE
    lesion with A2058G or A2059G supports macrolide-resistant treatment failure.
  evidence:
  - reference: PMID:41911295
    reference_title: "Assessment of the role of Haemophilus ducreyi coinfection on outcomes of Yaws treatment in the southwestern part of Ghana."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Treatment was with a single dose of oral azithromycin and outcomes were
      evaluated 4 weeks post-treatment, assessing clinical resolution and time
      to healing, with results stratified by the identified aetiological agents.
    explanation: Directly supports the four-week clinical response assessment.
  - reference: PMID:29428183
    reference_title: "Re-emergence of yaws after single mass azithromycin treatment followed by targeted treatment: a longitudinal study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      At months 36 and 42, five cases of active yaws, all from the same village,
      showed clinical failure following azithromycin treatment, with PCR-detected
      mutations in the 23S ribosomal RNA genes conferring resistance to azithromycin.
    explanation: Directly supports PCR-based investigation of azithromycin treatment failure.
  - reference: PMID:29428183
    reference_title: "Re-emergence of yaws after single mass azithromycin treatment followed by targeted treatment: a longitudinal study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Of 208 PCR-confirmed active yaws cases in the post-MDA period, the 23S rRNA
      gene could be amplified by PCR in 186 (89·4%), of which 181 (97·3%) had
      wild-type strains, but two cases at 36 months and three cases at 42 months
      revealed A2059G mutations associated with macrolide-resistance.
    explanation: Directly supports A2059G testing in the localized treatment-failure cluster.
differential_diagnoses:
- name: Syphilis
  description: >-
    Venereal syphilis and yaws both produce reactive treponemal serology and can
    have overlapping cutaneous manifestations.
  distinguishing_features:
  - Sexual and congenital transmission context favors syphilis; childhood skin-to-skin transmission in an endemic rural tropical community favors yaws.
  - Serology alone cannot assign the infecting T. pallidum subspecies; lesion molecular testing is needed when identity is consequential.
  evidence:
  - reference: PMID:25193248
    reference_title: "Yaws."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Infection with yaws or syphilis results in reactive treponemal serology
      and there is no widely available test to distinguish between these infections.
    explanation: Directly supports syphilis as a serologically overlapping differential.
- name: Haemophilus ducreyi-associated cutaneous ulcer
  description: H. ducreyi can cause a clinically yaws-like skin ulcer.
  distinguishing_features:
  - Multiplex lesion PCR detects H. ducreyi rather than T. pallidum DNA.
  evidence:
  - reference: PMID:38776332
    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: >-
      Multiplex PCR results showed that 9.1%, 1.8% and 0.9% of yaws-like lesions
      were positive for Haemophilus ducreyi, herpes simplex virus-1 (HSV-1) and
      T. pallidum respectively.
    explanation: Directly identifies H. ducreyi in clinically yaws-like lesions.
- name: Herpes simplex virus-associated ulcer
  description: HSV-1 or HSV-2 can produce an ulcer in the treponematosis differential.
  distinguishing_features:
  - Multiplex lesion PCR detects HSV-1 or HSV-2 rather than T. pallidum DNA.
  evidence:
  - reference: PMID:38776332
    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: >-
      Multiplex PCR results showed that 9.1%, 1.8% and 0.9% of yaws-like lesions
      were positive for Haemophilus ducreyi, herpes simplex virus-1 (HSV-1) and
      T. pallidum respectively.
    explanation: Directly identifies HSV-1 in clinically yaws-like lesions.
environmental:
- name: Limited access to hygiene and sanitation
  influences_mechanisms:
  - target: Cutaneous Treponemal Inoculation
    environmental_effect: PREDISPOSES
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    description: >-
      Remote-community conditions with limited hygiene and sanitation access
      are associated with yaws burden and can increase opportunities for
      skin-to-skin transmission, but the cited study does not isolate a direct
      causal effect.
    evidence:
    - reference: PMID:38900827
      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: >-
        Supports the observed remote-community and limited-access association;
        causal intermediates are not directly tested.
  effect: Associated risk context
  evidence:
  - reference: PMID:38900827
    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: Directly describes the affected remote-community context and limited access to hygiene and sanitation.
- name: Natural TPE infection in nonhuman primates (potential reservoir)
  notes: >-
    Naturally infected nonhuman primates harbor TPE strains genomically
    indistinguishable from human strains, supporting potential reservoir status.
    Current spillover evidence is missing, so this record does not assert ongoing
    zoonotic transmission.
  evidence:
  - reference: PMID:37703251
    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: MODEL_ORGANISM
    snippet: >-
      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.
    explanation: >-
      Natural infection directly supports TPE infection of nonhuman primates
      and their potential reservoir role; it does not establish human spillover.
  - reference: PMID:37703251
    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: MODEL_ORGANISM
    snippet: >-
      Although interspecies transmission in NHPs is a rare event and evidence for
      current spillover events is missing, the existence of the yaws bacterium in
      NHPs is demonstrated.
    explanation: Preserves the key caveat that a reservoir does not establish current spillover to humans.
treatments:
- name: Azithromycin therapy
  description: >-
    Preferred regimen for individual or mass treatment: one oral dose of
    30 mg/kg, capped at 2 g.
  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: Treponemal Ribosomal Translation (Azithromycin Target)
    treatment_effect: INHIBITS
    description: >-
      Azithromycin binds the bacterial 50S ribosomal component and inhibits protein synthesis.
    evidence:
    - reference: PMID:1319048
      reference_title: "Azithromycin--spectrum of activity, pharmacokinetics, and clinical applications."
      supports: SUPPORT
      evidence_source: OTHER
      snippet: >-
        Structurally related to the macrolide antibiotic erythromycin, its mechanism
        of activity (similar to erythromycin) is interference with bacterial protein
        synthesis by binding to the 50S component of the 70S ribosomal subunit.
      explanation: Directly supports the modeled treatment-to-target mechanism.
  evidence:
  - reference: PMID:28072863
    reference_title: "A Single Dose Oral Azithromycin versus Intramuscular Benzathine Penicillin for the Treatment of Yaws-A Randomized Non Inferiority Trial in Ghana."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Participants who met the inclusion criteria were randomized to receive
      treatment with either a single dose oral azithromycin administered at a
      dose of 30mg/kg (maximum of 2g) or a single dose of benzathine penicillin
      administered as an intramuscular injection of 1.2 million units for
      subjects 10-15years, and 0.6 million units for those below 10 years of age.
    explanation: Directly supports the exact single-dose azithromycin regimen and maximum dose.
  - reference: PMID:40036381
    reference_title: "Yaws - A Review of Clinical Features, Diagnosis and Treatment."
    supports: SUPPORT
    evidence_source: OTHER
    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.
  - reference: PMID:24396138
    reference_title: The endemic treponematoses.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      This challenging but potentially feasible endeavor is favored by the adoption
      of oral azithromycin for mass treatment
    explanation: Directly supports oral azithromycin as the mass-treatment agent in yaws eradication.
- name: Benzathine penicillin therapy
  description: >-
    Alternative or azithromycin-failure rescue treatment. In the cited Ghana
    trial, the single intramuscular BPG dose was 0.6 million units for participants
    under 10 years and 1.2 million units for participants aged 10–15 years; this
    trial does not establish the 1.2-million-unit dose outside that age range.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: benzathine benzylpenicillin
      term:
        id: CHEBI:51352
        label: benzylpenicillin benzathine
  therapeutic_modality: SMALL_MOLECULE
  target_mechanisms:
  - target: Benzathine Benzylpenicillin Treatment Vulnerability
    treatment_effect: INHIBITS
    description: >-
      Clinical efficacy establishes TPE susceptibility to benzathine
      benzylpenicillin; inhibition of peptidoglycan transpeptidation is retained
      only as generic beta-lactam class context, not a demonstrated TPE-specific mechanism.
    evidence:
    - reference: PMID:22203377
      reference_title: From the regulation of peptidoglycan synthesis to bacterial growth and morphology.
      supports: SUPPORT
      evidence_source: OTHER
      snippet: >-
        although glycan chain polymerization occurs in the absence of
        transpeptidation (for example, in the presence of penicillin), efficient
        transpeptidation requires ongoing GTase reactions
      explanation: >-
        Supports generic penicillin inhibition of transpeptidation, but not a
        TPE-specific penicillin-binding-protein mechanism.
  evidence:
  - reference: PMID:28072863
    reference_title: "A Single Dose Oral Azithromycin versus Intramuscular Benzathine Penicillin for the Treatment of Yaws-A Randomized Non Inferiority Trial in Ghana."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Participants who met the inclusion criteria were randomized to receive
      treatment with either a single dose oral azithromycin administered at a
      dose of 30mg/kg (maximum of 2g) or a single dose of benzathine penicillin
      administered as an intramuscular injection of 1.2 million units for
      subjects 10-15years, and 0.6 million units for those below 10 years of age.
    explanation: Directly supports the exact age-stratified single-dose BPG regimen.
  - reference: PMID:29428183
    reference_title: "Re-emergence of yaws after single mass azithromycin treatment followed by targeted treatment: a longitudinal study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      All presented with worsening skin lesions 2-weeks after azithromycin
      treatment and were subsequently treated with benzathine benzylpenicillin.
    explanation: Directly supports BPG rescue after azithromycin-resistant clinical failure.
  - reference: PMID:40036381
    reference_title: "Yaws - A Review of Clinical Features, Diagnosis and Treatment."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Though yaws can be treated with benzathine penicillin, oral azithromycin has
      become the preferred treatment due to its ease of administration.
    explanation: Directly supports benzathine penicillin as an effective yaws treatment.
- name: Morges eradication strategy
  description: >-
    Begin with total community treatment (TCT) using single-dose azithromycin in
    the entire endemic community, then use repeat TCT or active case-finding and
    total targeted treatment of active cases and their household, school, and
    play contacts. Continue active post-campaign surveillance; contact-only
    targeting can miss geographically dispersed latent infections.
  evidence:
  - reference: PMID:29140407
    reference_title: "Targeted Treatment of Yaws With Household Contact Tracing: How Much Do We Miss?"
    supports: SUPPORT
    evidence_source: COMPUTATIONAL
    snippet: >-
      The World Health Organization strategy mandates an initial round of total
      community treatment (TCT) with single-dose azithromycin followed either by
      further TCT or active case-finding and treatment of cases and their contacts
      (the Morges strategy).
    explanation: Directly defines the TCT and case/contact components of the Morges strategy.
  - reference: PMID:29140407
    reference_title: "Targeted Treatment of Yaws With Household Contact Tracing: How Much Do We Miss?"
    supports: SUPPORT
    evidence_source: COMPUTATIONAL
    snippet: >-
      This analysis indicated that targeted treatment of cases and their
      household contacts would miss a large fraction of asymptomatic infections
      (65%-100%).
    explanation: Supports the limitation of contact-only targeting for latent infection.
  - 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: >-
      TCT was followed by post-campaign active surveillance, treatment of yaws
      cases and their contacts.
    explanation: Directly supports post-campaign surveillance and case/contact treatment in implementation.
  - reference: PMID:29428183
    reference_title: "Re-emergence of yaws after single mass azithromycin treatment followed by targeted treatment: a longitudinal study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Second, there may be substantial benefit in distributing a second or
      third round of azithromycin at 6–12 months intervals.
    explanation: Supports repeated MDA after re-emergence following a single mass-treatment round.
  - reference: PMID:29428183
    reference_title: "Re-emergence of yaws after single mass azithromycin treatment followed by targeted treatment: a longitudinal study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Finally, there is the need for clinical and biological surveillance to
      immediately detect drug resistance through the strengthening of capacities
      of laboratory networks in endemic countries.
    explanation: Directly supports active surveillance for emergent drug resistance.
  - reference: PMID:34986286
    reference_title: "Trial of Three Rounds of Mass Azithromycin Administration for Yaws Eradication."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The reduction in the community prevalence of yaws was greater with three
      rounds of mass administration of azithromycin at 6-month intervals than
      with one round of mass administration of azithromycin followed by two
      rounds of targeted treatment.
    explanation: Directly supports three repeated MDA rounds in this randomized trial.
  - reference: PMID:34986286
    reference_title: "Trial of Three Rounds of Mass Azithromycin Administration for Yaws Eradication."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Monitoring for the emergence and spread of antimicrobial resistance is needed.
    explanation: Directly supports resistance surveillance during repeated mass 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: PMID:37703251
  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: Naturally infected nonhuman primates carry TPE strains that are genomically indistinguishable from human strains, making them potential reservoirs while current spillover remains unproven.
    supporting_text: 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.
    evidence:
    - reference: PMID:37703251
      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: MODEL_ORGANISM
      snippet: 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.
      explanation: Supports natural NHP infection and potential reservoir status, without establishing spillover to humans.
- reference: PMID:38166151
  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: This Papua New Guinea study detected the A2058G 23S rRNA resistance mutation in three JE11 isolates, a localized finding rather than a population prevalence estimate.
    supporting_text: Moreover, the A2058G mutation in the 23S rRNA genes of three JE11 isolates was found, resulting in azithromycin resistance.
    evidence:
    - reference: PMID:38166151
      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: Moreover, the A2058G mutation in the 23S rRNA genes of three JE11 isolates was found, resulting in azithromycin resistance.
      explanation: Supports a localized A2058G resistance observation in three isolates without generalizing its frequency.
- reference: PMID:38900827
  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: Yaws primarily affects children in remote tropical communities with limited access to hygiene and sanitation.
    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: PMID:38900827
      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: Directly supports the affected population and access context.
- reference: PMID:40267048
  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: Post-elimination verification guidance calls for three serosurveys showing yaws seroprevalence below 1% over 3–10 years after the last reported active case.
    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: PMID:40267048
      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: Directly states the serosurvey threshold and verification interval.
- reference: PMID:38776332
  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: PMID:38776332
      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: PMID:39851478
  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: PMID:39851478
      reference_title: 'Yaws in Africa: Past, Present and Future'
      supports: SUPPORT
      evidence_source: OTHER
      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: PMID:39693168
  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: PMID:39693168
      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
DOI:10.1101/2024.10.27.24316187
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 Preprint · not peer-reviewed 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.
DOI:10.1101/2024.11.07.24316738
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 Preprint · not peer-reviewed SUPPORT Human Clinical
"Yaws is targeted for eradication by 2030."
Deep research cited this publication as relevant literature for Yaws.
PMID:37703251
The genomes of the yaws bacterium, Treponema pallidum subsp. pertenue, of nonhuman primate and human origin are not genomically distinct
1 finding
Naturally infected nonhuman primates carry TPE strains that are genomically indistinguishable from human strains, making them potential reservoirs while current spillover remains unproven.
"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."
Show evidence (1 reference)
PMID:37703251 SUPPORT Model Organism
"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."
Supports natural NHP infection and potential reservoir status, without establishing spillover to humans.
PMID:38166151
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
This Papua New Guinea study detected the A2058G 23S rRNA resistance mutation in three JE11 isolates, a localized finding rather than a population prevalence estimate.
"Moreover, the A2058G mutation in the 23S rRNA genes of three JE11 isolates was found, resulting in azithromycin resistance."
Show evidence (1 reference)
PMID:38166151 SUPPORT Human Clinical
"Moreover, the A2058G mutation in the 23S rRNA genes of three JE11 isolates was found, resulting in azithromycin resistance."
Supports a localized A2058G resistance observation in three isolates without generalizing its frequency.
PMID:38900827
Knowledge, attitudes and practices towards yaws in endemic areas of Ghana, Cameroon and Côte d’Ivoire
1 finding
Yaws primarily affects children in remote tropical communities with limited access to hygiene and sanitation.
"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)
PMID:38900827 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."
Directly supports the affected population and access context.
PMID:40267048
Guidance for conducting and evaluating serological surveys to assess interruption of yaws transmission in the context of an eradication target
1 finding
Post-elimination verification guidance calls for three serosurveys showing yaws seroprevalence below 1% over 3–10 years after the last reported active case.
"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)
PMID:40267048 SUPPORT Other
"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..."
Directly states the serosurvey threshold and verification interval.
PMID:38776332
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)
PMID:38776332 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.
PMID:39851478
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)
PMID:39851478 SUPPORT Other
"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.
PMID:39693168
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)
PMID:39693168 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)

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