Fact-checked by Grok 2 weeks ago

Yaws

Yaws is a chronic, disfiguring, and debilitating infectious disease that primarily affects the skin, bones, and joints of children in tropical and subtropical regions.^[1] Caused by the spirochete bacterium Treponema pallidum subsp. pertenue, a close relative of the syphilis-causing pathogen, yaws is one of the four endemic treponematoses and is classified as a neglected tropical disease.^[2] It manifests in three stages—primary, secondary, and tertiary—with early lesions resembling raspberry-like papillomas that can ulcerate and spread, potentially leading to severe bone destruction and disfigurement if untreated.^[3] Transmission occurs through direct skin-to-skin contact with open sores from infected individuals, typically via minor skin injuries in humid environments that facilitate bacterial entry.^[1] The disease is highly contagious among children aged 5 to 15, with 75–80% of cases occurring in those under 15 years old, and it thrives in rural, impoverished communities with limited access to healthcare.^[2] Endemic in 16 countries—primarily in West and Central Africa, parts of Southeast Asia, and the Pacific islands such as Papua New Guinea and the Solomon Islands—yaws reported 152,164 suspected cases in 2024 from 10 countries, the majority in the Western Pacific Region.^[4]^[5] The primary stage begins 9–90 days after exposure (average 21 days) with a single, painless "mother yaw" lesion at the site of inoculation, which heals spontaneously in 3–6 months but remains infectious.^[2] Secondary yaws, developing weeks to months later, involves multiple disseminated skin lesions, generalized rash, fever, and bone pain due to osteoperiostitis, affecting long bones like the tibia and radius.^[1] Tertiary yaws, now rare due to interventions, emerges 5–10 years post-infection and causes destructive gummatous lesions, hyperkeratotic "saber shins," and facial deformities such as gangosa, leading to chronic disability in about 10% of untreated cases.^[2]^[6] Diagnosis relies on clinical presentation in endemic areas, supported by serological tests like the Venereal Disease Research Laboratory (VDRL) or Rapid Plasma Reagin (RPR) for non-treponemal antibodies, and confirmatory treponemal tests such as the Treponema pallidum particle agglutination (TPPA) assay.^[2] Darkfield microscopy can identify the spirochetes directly from lesions, though it requires specialized equipment often unavailable in remote settings.^[3] Treatment is highly effective with a single intramuscular dose of benzathine penicillin G (600,000 units for children under 10 years or 1.2 million units for older children and adults) or a single oral dose of azithromycin (30 mg/kg, up to 2 g), achieving cure rates of over 95% in early stages.^[1] Global efforts, led by the World Health Organization, aim for yaws eradication by 2030 through the Morges Strategy, which emphasizes total community treatment with mass drug administration of azithromycin, active case surveillance, and contact tracing.^[1] Since 2015, over 20 million people have received treatment in endemic areas, reducing prevalence by up to 90% in some regions after multiple rounds of mass administration.^[2] No vaccine exists, but improved diagnostics, such as loop-mediated isothermal amplification (LAMP) for rapid detection, and ongoing research into azithromycin resistance are supporting these initiatives.^[1]

Overview and Etiology

Definition and Classification

Yaws is a chronic, non-venereal bacterial infection that primarily affects the skin, bones, and joints, particularly in children living in tropical regions, and can lead to disfiguring lesions if left untreated.^[1] Caused by the spirochete Treponema pallidum subsp. pertenue, it is transmitted through non-sexual skin-to-skin contact with infectious lesions.^[7] Yaws is classified as one of the endemic treponematoses, a group of chronic infections that also includes bejel (endemic syphilis, caused by T. p. endemicum) and pinta (caused by the related species Treponema carateum), all distinct from the venereal syphilis pathogen (T. pallidum subsp. pallidum) and excluding congenital syphilis.^[8] These non-venereal diseases share similar microbiological features but differ in geographic distribution and clinical presentation, with yaws being predominantly tropical.^[1] Historically known as framboesia tropica, the term emphasizes its occurrence in tropical areas and raspberry-like appearance of early lesions, underscoring its non-sexually transmitted nature.^[9] The name "yaws" originates from the Carib word yaya, meaning "sore" or "lesion," reflecting the disease's visible skin manifestations as described by early observers in the 17th century.^[10]

Causative Agent

Yaws is caused by the bacterium Treponema pallidum subsp. pertenue, a motile, spiral-shaped, Gram-negative spirochete that measures approximately 6–20 μm in length and 0.1–0.2 μm in width, with 8–12 evenly spaced coils.^[2] This subspecies belongs to the Treponema pallidum complex, which includes pathogens responsible for syphilis (T. p. pallidum), bejel (T. p. endemicum), and pinta (T. carateum), but T. p. pertenue is distinguished by its exclusive tropism for skin and bone tissues rather than systemic or genital involvement seen in syphilis.^[11] Like other treponemes, T. p. pertenue cannot be cultured in vitro using standard artificial media due to its obligate parasitic nature and fastidious growth requirements, relying instead on experimental animal models for propagation and study.^[6] Genetically, T. p. pertenue shares approximately 99.8% genomic identity with T. p. pallidum, encompassing a linear chromosome of about 1.14 million base pairs with limited genetic variation concentrated in a few regions, such as the tpr gene family encoding outer membrane proteins.^[12] Recent genomic analyses (as of 2025) of multiple T. p. pertenue strains from humans and nonhuman primates continue to affirm the ~99.8% similarity with T. p. pallidum, with variations primarily in regions influencing tissue tropism.^[13] This high sequence similarity results in antigenic cross-reactivity, where serological tests for syphilis (e.g., VDRL or TPHA) detect T. p. pertenue antibodies due to shared epitopes on surface lipoproteins, though subspecies-specific polymorphisms in genes like tprC and tprD contribute to differences in tissue tropism and disease manifestation.^[2] Despite these close relations, T. p. pertenue exhibits distinct pathogenic adaptations, including reduced invasiveness into vascular and neural tissues compared to the syphilis agent.^[14] The bacterium is highly fragile and unable to survive outside a mammalian host, succumbing rapidly to desiccation, temperatures above 42°C, or common disinfectants, which necessitates direct skin-to-skin contact for transmission and explains its restriction to humid tropical environments.^[1] Although long considered to have no animal reservoir and maintained primarily in human populations (anthroponotic transmission), recent studies as of 2025 have identified nonhuman primates in sub-Saharan Africa as reservoirs for T. p. pertenue, with evidence of circulation and potential inter-species transmission.^[15]^[16] Historical efforts to isolate and characterize T. p. pertenue have relied on rabbit models, with initial experimental transmissions from human lesions to rabbits reported in the early 20th century; modern studies, including whole-genome sequencing of strains propagated in rabbits in 2012, have confirmed its morphological and genetic treponemal traits, such as motility via axial filaments and the absence of significant genomic rearrangements from ancestral strains.^[17]

Transmission and Pathogenesis

Modes of Transmission

Yaws is primarily transmitted through direct skin-to-skin contact with open infectious lesions, particularly among children aged 2 to 15 years during activities such as playing or scratching that facilitate close physical interaction.^[1]^[2] This mode of spread is enabled by minor skin breaks that serve as entry points for the bacteria, with the causative agent Treponema pallidum subsp. pertenue requiring such immediate contact due to its inability to survive drying or prolonged exposure outside the host.^[8]^[18] Indirect transmission has not been established as a significant route for yaws, with no evidence supporting spread via fomites or objects; insect vectors such as flies have been proposed but remain unproven.^[1]^[8] Unlike syphilis, caused by a related subspecies, yaws is strictly non-sexual in nature, with no documented cases of congenital or vertical transmission from mother to child.^[1]^[2] Humans are the primary reservoir, though recent research as of 2025 has identified inter-species transmission among nonhuman primates in Tanzania, suggesting they may act as additional reservoirs, albeit without confirmed zoonotic transmission to humans.^[19] Several environmental and behavioral risk factors enhance transmission in affected communities, including overcrowding in rural households, poor personal hygiene, and barefoot walking that predisposes individuals to minor trauma and abrasions serving as portals of entry.^[2]^[20] These conditions are exacerbated in impoverished, humid tropical regions where close communal living and limited sanitation promote sustained person-to-person spread.^[8]

Pathogenic Mechanisms

Upon entry through minor skin abrasions, Treponema pallidum subsp. pertenue (TPE), the causative agent of yaws, adheres to host tissues using its motility conferred by periplasmic flagella, initiating local multiplication in the dermal layer. This invasion triggers an acute inflammatory response involving cytokine release and immune cell recruitment, leading to tissue damage at the primary site.^[21] Following primary localization, TPE disseminates systemically via hematogenous and lymphatic routes, with even minimal inocula sufficient for widespread colonization of skin, bones, and joints due to its extracellular persistence and rapid replication in vivo, as demonstrated in experimental animal models. To evade clearance, TPE employs antigenic variation, notably in the TprK outer membrane protein, which undergoes hypervariable region mutations to alter surface epitopes and subvert adaptive immunity, mirroring mechanisms in syphilis.^[21] The host immune response is predominantly T-cell mediated, with CD4+ T cells producing IFN-γ to activate macrophages for phagocytosis, while CD8+ and Th17 cells contribute IL-17 and other proinflammatory cytokines that amplify inflammation but fail to fully eliminate the spirochete owing to its low immunogenicity and immune suppression via regulatory T cells. This partial control results in lesion formation driven by granulocyte and lymphocyte infiltration, yet permits latency where viable treponemes persist asymptomatically in tissues.^[22] In protracted untreated infections, tertiary pathogenesis involves delayed-type hypersensitivity reactions and granulomatous inflammation, where persistent TPE antigens provoke exaggerated T-cell responses leading to periosteal bone involvement and cartilage degradation through matrix metalloproteinase activation and fibrotic remodeling.

Clinical Manifestations

Primary Stage

The primary stage of yaws begins after an incubation period averaging 21 days (range 9 to 90 days) following exposure to the causative spirochete through skin abrasions.^[1]^[2] It is characterized by the development of a single, painless papule, known as the "mother yaw," at the site of inoculation. This lesion typically evolves over several days into an exudative, raspberry-like papilloma or ulcer measuring 2 to 5 cm in diameter, with a yellowish base of granulation tissue and elevated borders.^[2]^[8] The mother yaw most commonly appears on the lower extremities, such as the legs or feet, though it can occur on any exposed skin surface. Accompanying features may include regional lymphadenopathy, with enlargement of nearby lymph nodes (e.g., inguinal), and occasionally mild fever or malaise, though these systemic signs are often absent or minimal. The lesion is highly infectious, as the exudate contains abundant viable Treponema pallidum subsp. pertenue spirochetes, facilitating transmission via direct skin-to-skin contact in humid tropical environments.^[1]^[8]^[2] Without treatment, the primary lesion is self-limiting, persisting for 3 to 6 months before healing spontaneously, often leaving a hyperpigmented or scarred area. Yaws in this stage predominantly affects children under 15 years in endemic regions, with cases being rare in adults.^[1]^[2]^[8]

Secondary Stage

The secondary stage of yaws typically develops 4 to 8 weeks after the initial primary lesion, resulting from hematogenous dissemination of Treponema pallidum subsp. pertenue from the primary site.^[1]^[2] This phase is characterized by multiple disseminated skin lesions, including yellowish papillomas and hyperkeratotic plaques that appear on the face, trunk, and extremities.^[1]^[23] These lesions often present as raised, scaly papules or macular rashes that can ulcerate, and in severe cases, hyperkeratotic involvement of the palms and soles may lead to painful fissuring known as "crab yaws," causing a characteristic gait.^[2]^[23] Bone involvement manifests as osteoperiostitis, affecting long bones such as the tibia, fibula, radius, and ulna, or digits (dactylitis), often resulting in nocturnal pain and swelling, though no permanent skeletal deformities occur at this stage.^[2]^[23] Mucosal lesions are uncommon but may include painless ulcers on the oral mucosa or genitals, transmitted non-sexually through close contact.^[2]^[23] The secondary lesions are highly infectious, teeming with spirochetes and capable of transmitting the disease via skin-to-skin contact, particularly among children.^[1]^[23] Without treatment, individual lesions often undergo spontaneous remission within 3 to 6 months, but infectious relapses can occur over 1 to 5 years, prolonging the contagious period.^[1]^[23]

Tertiary Stage

The tertiary stage of yaws develops in 10-20% of untreated cases, typically 5-15 years after initial infection, following a period of latency during which the infection remains dormant before reactivation.^[2]^[8] This stage is marked by severe, destructive bone and joint involvement, including hyperkeratotic papillomas on the palms and soles, chronic periostitis that leads to saber shins (anterior bowing of the tibia), and hypertrophic osteitis resulting in goundou, a nasal deformity characterized by bilateral exostoses of the paranasal maxilla and nasal bridge.^[2]^[8] Characteristic syndromes include gangosa, also known as rhinopharyngitis mutilans, which involves progressive destruction of the nasal septum, palate, and pharynx, leading to severe facial disfigurement; juxta-articular nodules, which are painful, subcutaneous swellings near joints that may ulcerate and cause necrosis; and gumma-like lesions, which are soft, destructive subcutaneous nodules affecting bones and soft tissues.^[2]^[8] These complications result in significant disability, including chronic pain from bone deformities, profound disfigurement such as saddle nose or palatal destruction, and increased risk of secondary bacterial infections due to ulcerated lesions, though the stage is associated with low infectivity owing to the scarcity of viable spirochetes in the destructive tissues.^[2]^[8]

Diagnosis

Clinical Diagnosis

Clinical diagnosis of yaws relies on a combination of patient history and characteristic physical findings, particularly in endemic regions where laboratory resources may be limited. Suspicion arises in individuals under 15 years of age with a history of residence or exposure in affected tropical areas, such as rural communities in Africa, Asia, or the Pacific Islands, often presenting with skin lesions following close contact in humid, overcrowded environments.^[2]^[1] Key physical examination hallmarks include the primary "mother yaw," a solitary raspberry-like papillomatous lesion or ulcerative nodule, typically 2-5 cm in diameter, appearing on the extremities such as legs or arms, often with raised borders and minimal pain unless secondarily infected. In the secondary stage, multiple disseminated lesions may appear, including papillomata, satellite ulcers, hyperkeratotic plaques on palms and soles (crab yaws), and signs of bone involvement like periostitis causing tenderness or dactylitis (painful swelling of fingers or toes). These features, evolving over weeks to months without treatment, guide initial recognition, with differentials including traumatic ulcers, pyoderma, or infections from other pathogens.^[2]^[1]^[24] The World Health Organization employs a syndromic approach for case surveillance, defining a suspected case as a person residing in an endemic area who presents with clinical signs consistent with active yaws, such as chronic skin ulcers, multiple papillomata, squamous macules, bone or joint lesions, or plantar hyperkeratosis. This definition facilitates rapid identification in field settings, prioritizing early intervention in children aged 5-10 years, the typical demographic affected.^[25] Challenges in clinical diagnosis persist in resource-poor endemic settings, where lesions overlap with other skin neglected tropical diseases like cutaneous leishmaniasis, fungal infections, or ulcers caused by Haemophilus ducreyi, leading to potential misdiagnosis in up to 40% of cases without further evaluation. The nonspecific nature of ulcerative presentations and limited access to experienced clinicians further complicate accurate syndromic assessment, underscoring the need for contextual awareness of local epidemiology.^[1]^[24]^[26]

Laboratory Diagnosis

Laboratory diagnosis of yaws is essential for confirming infection in clinically suspected cases, particularly in endemic areas where serological and molecular methods play key roles. Non-treponemal serological tests, such as the rapid plasma reagin (RPR) and Venereal Disease Research Laboratory (VDRL) assays, are commonly used for initial screening due to their ability to detect reagin antibodies produced in response to treponemal infection.^[2] These tests exhibit high sensitivity for active disease, with RPR showing approximately 80-98% sensitivity depending on titer levels, but they are nonspecific and can yield false positives from other conditions.^[27] For confirmation, treponemal serological tests like the Treponema pallidum hemagglutination assay (TPHA), Treponema pallidum particle agglutination (TPPA), and fluorescent treponemal antibody absorption (FTA-ABS) are employed, as they target specific antibodies against Treponema antigens and remain positive for life after infection.^[2] These assays have high specificity (over 95% in combined use) but cannot differentiate yaws from syphilis due to antigenic similarity between Treponema pallidum subsp. pertenue and T. pallidum subsp. pallidum.^[1]^[27] In yaws-endemic settings, a positive treponemal test combined with a nonreactive or low-titer non-treponemal test may indicate past infection rather than active disease, necessitating clinical correlation.^[28] Molecular diagnostics, particularly polymerase chain reaction (PCR) targeting T. pallidum subsp. pertenue DNA from lesion swabs, provide definitive confirmation by detecting the pathogen directly, offering advantages in early detection and species differentiation when sequenced.^[28] PCR assays demonstrate variable performance depending on the target and method, with reported sensitivities of 68-95% and specificities of 92-100%; for example, the common tpp47-targeted PCR has 68% sensitivity and 91.9% specificity across multiple studies, while CDC real-time PCR may achieve higher rates but can miss variants due to mutations.^[29]^[30] These tests are particularly valuable in resource-limited settings for distinguishing yaws from other ulcerative conditions like Haemophilus ducreyi infections.^[1] Advanced molecular methods, such as loop-mediated isothermal amplification (LAMP), offer rapid, field-applicable detection of T. p. pertenue DNA with sensitivity comparable to PCR and no need for specialized equipment, supporting surveillance in eradication programs as of 2020.^[31] Additionally, dual treponemal and nontreponemal rapid diagnostic tests (RDTs) have been introduced to differentiate active from past infections in point-of-care settings.^[28] Dark-field microscopy of fresh lesion exudate can visualize motile spirochetes, confirming the presence of T. p. pertenue during primary or secondary stages with high specificity (94-100%).^[2] However, its sensitivity is variable and often low (around 50-80% in treponemal lesions, lower in early stages), and it requires specialized equipment and trained personnel, limiting its practicality in remote endemic areas.^[29] Key limitations of yaws laboratory diagnosis include the lack of species-specific serological tests, leading to cross-reactivity with syphilis and challenges in interpreting results among adults with potential co-infections.^[1] Post-treatment monitoring relies on a fourfold decline in non-treponemal titers (e.g., RPR) within 6-12 months to indicate successful therapy, while treponemal tests do not revert and thus cannot assess cure.^[2]

Treatment and Management

Antibiotic Treatment

The primary antibiotic treatment for yaws targets the spirochete Treponema pallidum subsp. pertenue and is effective across all disease stages. The World Health Organization (WHO) recommends a single oral dose of azithromycin at 30 mg/kg (maximum 2 g) as the first-line regimen, which is suitable for individual cases and mass administration campaigns due to its ease of delivery and high patient compliance.^[1]^[28] This azithromycin regimen yields clinical cure rates of 95–100% in early yaws, with over 95% of patients showing complete lesion healing within four weeks of treatment.^[1]^[32] Serological cure in latent cases reaches approximately 94% at 24 months, though early-stage efficacy remains the benchmark for initial response.^[33] Relapse is rare, occurring in less than 5% of compliant cases, primarily linked to reinfection rather than treatment failure.^[32]^[1] However, recent studies have reported the emergence of azithromycin resistance in certain communities after multiple rounds of mass treatment, underscoring the importance of resistance surveillance and the use of alternative antibiotics like benzathine penicillin when needed.^[34]^[35] An alternative to azithromycin is a single intramuscular injection of benzathine penicillin G, dosed at 1.2 million units for adults and children over 10 years or 0.6 million units for children under 10 years; this is particularly used in outbreaks, for azithromycin resistance, or when oral administration is impractical.^[1]^[28] Benzathine penicillin achieves comparable clinical cure rates of around 97% in early yaws.^[32] Special considerations include preferring benzathine penicillin for pregnant individuals, as azithromycin's safety in pregnancy is less established for this indication.^[36]^[1] Treatment efficacy is assessed via clinical response, with patients reexamined at four weeks; persistent lesions prompt resistance testing and switch to penicillin if macrolide resistance is confirmed.^[1]^[37]

Supportive and Follow-up Care

Supportive care for yaws focuses on symptom relief, prevention of secondary complications, and ensuring proper healing following initiation of antibiotic therapy. Lesions, particularly ulcers in the primary and secondary stages, require regular cleaning with soap and water to reduce the risk of secondary bacterial infections, which are common due to open wounds in humid environments. Dressings may be applied to protect lesions from further trauma and contamination, promoting faster resolution.^[38] Bone and joint pain, often prominent in the secondary stage due to periostitis, can be managed with analgesics such as paracetamol or non-steroidal anti-inflammatory drugs to alleviate discomfort and improve mobility during recovery.^[2] Follow-up care is critical to assess treatment efficacy and detect any treatment failure or reinfection. Clinical reassessment typically occurs at 1, 3, and 6 months post-treatment to monitor lesion healing, with complete resolution observed in over 95% of cases by 4 weeks in uncomplicated early yaws.^[1] Serological monitoring using non-treponemal tests (e.g., VDRL or RPR) is recommended, with a four-fold decrease in titers indicating cure; persistent high titers may necessitate re-treatment or resistance testing.^[37]^[2] In tertiary yaws, where destructive bone and cartilage changes have occurred, rehabilitation addresses long-term deformities and disability. Surgical correction, such as osteotomy for saber shin tibia or rhinoplasty for goundou (hypertrophic nasal periostitis), may be required to restore function and aesthetics in severe cases.^[39] Physical therapy is essential to maintain joint mobility, reduce contractures, and support overall rehabilitation, particularly for hyperkeratotic plaques causing gait alterations.^[2] Monitoring for adverse effects post-antibiotic treatment includes vigilance for the Jarisch-Herxheimer reaction, which occurs in 10-20% of cases and manifests as transient fever, chills, headache, and rash intensification within 24 hours due to spirochete lysis. Management is supportive, involving antipyretics, hydration, and close observation of vital signs, as symptoms typically resolve within 24 hours without specific intervention.^[40]^[41]

Epidemiology

Global Distribution

Yaws remains endemic in 16 countries worldwide, primarily in rural, impoverished communities within tropical regions of West and Central Africa, Southeast Asia, and the Pacific Islands.^[4] In Africa, key endemic areas include Benin, Cameroon, Central African Republic, Republic of Congo, Côte d'Ivoire, Democratic Republic of the Congo, Ghana, Liberia, and Togo, where the disease persists in forested, remote villages. Southeast Asia reports cases in countries such as Indonesia, Malaysia, the Philippines, and Timor-Leste, while the Pacific region sees the highest concentration, with Papua New Guinea, Solomon Islands, and Vanuatu accounting for a significant proportion of confirmed infections.^[1] These areas are characterized by limited access to healthcare and close-knit populations that facilitate person-to-person transmission through skin contact in humid settings.^[1] The geographic prevalence of yaws is strongly influenced by environmental conditions, thriving in hot, humid tropical climates at altitudes below 1,000 meters, where high rainfall and moisture support the survival of the causative bacterium, Treponema pallidum subsp. pertenue.^[7] The pathogen's viability is enhanced in such environments, promoting skin lesions that serve as entry points for infection during direct contact. Urban migration from these rural hotspots tends to lower local incidence rates, as improved sanitation and reduced overcrowding in cities disrupt the close-contact transmission cycle typical of endemic foci.^[7] In non-endemic regions, yaws cases are exceedingly rare and usually involve imported infections among travelers or migrants from endemic zones, often misdiagnosed initially as other treponemal diseases like syphilis.^[42] The disease has been eliminated as a public health problem in the Americas, with transmission interrupted in Ecuador following control measures in the 1990s, as confirmed by serological surveys.^[43] Mapping efforts to delineate yaws distribution rely on WHO-supported serological surveys and active case detection in suspected hotspots, classifying countries into endemic (Group A), previously endemic with unknown status (Group B), or non-endemic (Group C) categories to guide targeted interventions.^[1] These initiatives, including community-based screening, have identified persistent foci in remote areas and occasional resurgence in previously affected territories through surveillance of clinical and laboratory-confirmed cases.^[1]

Disease Burden and Risk Factors

Yaws imposes a substantial health burden, with over 80,000 new cases occurring annually, though the true incidence is likely higher due to underreporting from inadequate surveillance in remote endemic areas.^[44] In 2024, the World Health Organization received reports of 152,164 suspected cases from 10 countries, but laboratory confirmation was achieved for only 996 cases across 7 countries, highlighting diagnostic and reporting challenges.^[4] Within affected communities, prevalence remains low at under 1%, with recent studies documenting rates of approximately 0.63% in surveyed hotspots.^[45] The disease disproportionately impacts children, accounting for 75–80% of cases in individuals under 15 years of age, with peak incidence observed in those aged 6–10 years.^[1] Males experience a higher incidence than females, potentially linked to greater exposure through outdoor play and minor skin injuries.^[7] Chronic disfigurement from untreated yaws contributes to disability. Key risk factors for yaws transmission include poverty, overcrowding, poor personal hygiene, and inadequate sanitation, which promote close skin-to-skin contact in humid environments.^[1] Limited access to healthcare in rural settings further exacerbates vulnerability, as early lesions often go untreated.^[20] Socioeconomically, yaws fosters stigma due to visible skin lesions and deformities, leading to school absenteeism among affected children and broader social exclusion.^[38] In agrarian communities, chronic disabilities from advanced disease result in reduced productivity and economic losses, perpetuating cycles of poverty.^[46]

History

Early History

Yaws, a chronic infectious disease primarily affecting children in tropical regions, has been recognized for centuries prior to modern medical understanding. Early European accounts of the disease emerged during the Age of Exploration in the Americas. In 1526, Spanish historian and naturalist Gonzalo Fernández de Oviedo y Valdés documented an outbreak of yaws on the island of Hispaniola, describing its characteristic skin lesions among indigenous populations shortly after Christopher Columbus's arrival in 1492. This marked one of the first recorded European encounters with the disease, which was initially referred to by local terms and observed to spread non-sexually, distinguishing it from syphilis despite superficial similarities in presentation.^[47] The term "yaws" derives from the Carib indigenous language word "yaya," meaning "sore" or "lesion," reflecting its berry-like raspberry (frambesia) eruptions, and entered common European usage by the mid-17th century. The first unambiguous clinical description came from Dutch physician Willem Piso in 1648, in his treatise De medicina Brasiliense, where he detailed the disease's progression in South American populations. By 1679, English physician Thomas Sydenham described yaws among African slaves in the Caribbean, initially conflating it with venereal syphilis due to shared causative spirochetes, but noting its transmission through direct skin-to-skin contact rather than sexual means.^[21] In the 19th century, missionaries and colonial physicians in the Pacific Islands and Africa provided further reports that solidified yaws' recognition as a distinct, contagious tropical ailment endemic to humid, rural areas. Observations from British and French missionaries highlighted its prevalence among children, spread via abrasions during play or communal activities, often in overcrowded settlements. Prior to antibiotics, the disease was managed with folk remedies, including mercury applications—administered orally or topically—which were borrowed from syphilis treatments but proved ineffective and highly toxic, sometimes exacerbating symptoms or causing fatalities. Arsenical compounds like arsphenamine (Salvarsan), introduced in the early 20th century, offered limited relief but were not curative until penicillin's advent.

Modern History and Campaigns

In the early 20th century, significant advances in understanding yaws' etiology occurred when the causative spirochete was identified in skin lesions from affected patients. Aldo Castellani first observed the treponemal organism in 1905 during examinations in Ceylon (now Sri Lanka), marking a pivotal moment in recognizing yaws as a treponemal infection similar to syphilis.^[48] Shortly thereafter, in 1906, French parasitologist Raphaël Blanchard proposed the name Treponema pertenue for the pathogen, distinguishing it preliminarily from the syphilis-causing Treponema pallidum.^[2] By the 1920s, researchers developed animal models, particularly using monkeys, to propagate the organism and confirm its distinct pathogenicity from syphilis treponemes through experimental inoculations, which helped solidify the subspecies classification as T. pallidum subsp. pertenue. The mid-20th century saw the launch of ambitious global control efforts against yaws. From 1952 to 1964, the World Health Organization (WHO) and the United Nations Children's Fund (UNICEF) coordinated mass treatment campaigns across 46 endemic countries, screening approximately 300 million people and administering penicillin injections to over 50 million individuals with active or latent infections.^[49] These initiatives dramatically reduced the global prevalence of yaws by about 95%, from an estimated 50 million cases to around 2.5 million, demonstrating the efficacy of single-dose benzathine penicillin as a curative treatment.^[50] Following these successes, control programs faltered in the post-1970s era, leading to a resurgence of the disease. The collapse of dedicated vertical programs, often due to their premature integration into broader health systems without sustained funding or surveillance, combined with factors like civil conflicts disrupting healthcare access and urbanization facilitating transmission in crowded settings, allowed cases to rebound. By the 1990s, WHO estimates indicated approximately 460,000 infectious cases by 1995, highlighting the need for renewed focus.^[51] Key scientific milestones in the late 20th century further advanced yaws research. In the 1980s, serological studies utilizing monoclonal antibodies against T. pallidum subsp. pallidum successfully differentiated yaws-specific immune responses, confirming the treponemal etiology and aiding in diagnostic refinement.^[52]

Eradication Efforts

WHO Strategies

The World Health Organization (WHO) developed the Morges Strategy in 2012 as the primary framework for yaws eradication, emphasizing a two-pronged approach of total community treatment (TCT) followed by targeted treatment to interrupt transmission in endemic areas.^[53] Under this strategy, TCT involves administering a single oral dose of azithromycin (30 mg/kg, up to a maximum of 2 g) to all residents and close contacts in affected communities, aiming for at least 90% coverage to eliminate the pathogen Treponema pallidum subsp. pertenue rapidly and comprehensively.^[1] This is followed by targeted treatment, which focuses on treating confirmed cases and their contacts identified through surveillance, using the same azithromycin regimen as the preferred antibiotic due to its efficacy and ease of administration in field settings.^[54] Integration of yaws control into broader neglected tropical disease (NTD) programs is a core component, particularly with skin-related NTDs such as leprosy and leishmaniasis, to optimize resources and enhance surveillance efficiency.^[55] This includes combining mass drug administration (MDA) efforts and active case detection activities, where yaws screening is incorporated into routine skin NTD patrols and serological surveys for mapping endemic foci.^[1] Serological surveys, often conducted in children aged 1–5 years, utilize non-treponemal tests like the rapid plasma reagin (RPR) test alongside treponemal tests such as the Treponema pallidum particle agglutination (TPPA) assay to detect active infection and monitor transmission.^[56] Operational tools central to the strategy include active case detection through community-based searches for ulcerative skin lesions, followed by immediate contact tracing and empirical treatment of household and play contacts to prevent resurgence.^[53] Single-dose MDA rounds, typically three every six months in high-prevalence areas, form the backbone of TCT implementation, supported by donated azithromycin to ensure accessibility.^[1] For monitoring, RPR/TPPA dual testing confirms serological responses post-treatment, with persistent high titers indicating potential treatment failure or reinfection.^[54] The overarching goals are to interrupt yaws transmission at the community level and validate elimination at district or national scales according to WHO criteria, which require no confirmed cases detected through surveillance for 24 months following the last MDA round.^[53] Validation involves comprehensive serological and clinical assessments to confirm absence of transmission, paving the way for certification of elimination as yaws-free.^[56]

Progress and Challenges

Significant progress has been made in yaws eradication efforts since the adoption of the World Health Organization's (WHO) Morges strategy in 2012, which emphasizes total community treatment (TCT) with azithromycin. Global prevalence has declined substantially, with studies showing reductions of up to 90% in active yaws cases in treated communities through mass drug administration (MDA).^[25]^[57] As of 2024, only 996 confirmed cases were reported to WHO from seven countries, a marked decrease from estimates of 65,000–82,000 annual cases in 2015, reflecting improved surveillance and treatment coverage. In 2023, 222,652 suspected cases were reported from 13 countries, with 1,477 confirmed in 9 countries; in 2024, 152,164 suspected cases were reported from 10 countries.^[4]^[58] India remains the only country officially certified by WHO as free of yaws transmission in 2016, following verification of interrupted transmission. Several other nations, including Ecuador and select Pacific islands such as Vanuatu, have reported local interruption of transmission, though formal certification is pending for most. The number of endemic countries has stabilized at around 15–16, with active cases concentrated in West Africa and Papua New Guinea.^[59]^[60]^[35] In 2024, WHO reported 152,164 suspected yaws cases from 10 countries, with only 996 confirmed cases in 7 countries, highlighting significant underreporting due to diagnostic limitations, with the 2030 eradication target at risk but achievable through sustained funding and MDA expansion.^[4]^[61] Emergence of azithromycin resistance, though rare at under 1% of cases, poses a growing concern, with genomic studies identifying resistant strains in re-emerging foci post-MDA. Logistical barriers in remote, forested, or nomadic communities hinder access for surveillance and treatment, while environmental factors like climate change may expand vector habitats for transmission via flies.^[35] Looking ahead, integrated neglected tropical disease (NTD) platforms could enhance efficiency by combining yaws efforts with other interventions, while genomic surveillance is essential for early resistance detection. Robust post-elimination verification, including serological surveys, will be critical to confirm and sustain interruption of transmission toward the 2030 goal.^[61]^[62]

References

[1]
Yaws - World Health Organization (WHO)
Jan 12, 2023 · Yaws is a chronic disfiguring and debilitating childhood infectious disease. The disease affects skin, bone and cartilage.
[2]
Yaws - StatPearls - NCBI Bookshelf - NIH
Yaws is a non-venereal tropical infectious disease caused by the organism Treponema pertenue.[1] This organism is closely related to the syphilitic ...
[3]
Yaws: MedlinePlus Medical Encyclopedia
Dec 31, 2023 · Yaws is a long-term (chronic) bacterial infection that mainly affects the skin, bones, and joints.
[4]
Epidemiology of yaws: an update - PMC - PubMed Central
Apr 2, 2014 · Yaws is a neglected tropical disease caused by Treponema pallidum subspecies pertenue. This bacterium causes a chronic relapsing nonvenereal ...
[5]
The Endemic Treponematoses - PMC - PubMed Central - NIH
The human treponematoses comprise venereal syphilis and the endemic treponematoses called yaws, bejel, and pinta.
[6]
Yaws: A Second (and Maybe Last?) Chance for Eradication - PMC
Aug 27, 2008 · Yaws (the name is believed to originate from “yaya,” which in the indigenous Caribbean language means sore), or framboesia tropica (also known ...Missing: etymology | Show results with:etymology
[7]
Etymologia - PMC - NIH
From either the Carib yaya, for sore or lesion, or yaw, an African word for berry. The term yaws was in common use by the 17th Century.
[8]
Treponema - Medical Microbiology - NCBI Bookshelf - NIH
Treponema pallidum subsp pallidum, the most invasive of the pathogenic treponemes, produces highly destructive lesions in almost any tissue of the body, ...Missing: tropism | Show results with:tropism
[9]
Bejel, Pinta, and Yaws - Infectious Diseases - Merck Manuals
The Treponema species causing bejel and yaws are morphologically and serologically indistinguishable from the agent of syphilis, T. pallidum subspecies pallidum ...
[10]
A Loop-Mediated Isothermal Amplification Assay for the Detection of ...
... Treponema pallidum subsp. pertenue (TPE). It is currently known to be ... First, the genomic structure of TPE which causes yaws has nearly 99.8% similarity with T ...
[11]
Most of the Genetic Differences Are Localized in Six Regions
Most of the genetic differences between T. p. pallidum and T. p. pertenue strains were accumulated in six genomic regions.Missing: tropism | Show results with:tropism
[12]
https://pmc.ncbi.nlm.nih.gov/articles/PMC7356415/
[13]
Syphilis and Treponematosis: Background, Etiology, Pathophysiology
Oct 27, 2025 · Bejel is transmitted skin to skin but can also be transmitted mouth to mouth and on fomites (eg, via shared eating utensils or cups).
[14]
Factors associated with cutaneous ulcers among children in two ...
Mar 12, 2020 · Poor personal hygiene, overcrowding and lack of access to improved sanitary facilities are the factors that facilitate the transmission of yaws.Missing: barefoot | Show results with:barefoot
[15]
https://wwwnc.cdc.gov/eid/article/31/4/24-1562_article
[16]
The Significance of the Cell-Mediated Host Immune Response in ...
T. pallidum can evade the immune response, allowing it to persist and spread within the host. This is due to the spirochete's adaptive abilities, including ...
[17]
Yaws - PMC - PubMed Central - NIH
Dec 18, 2014 · Yaws is an infectious disease caused by Treponema pallidum ssp. pertenue and is one of the four treponemal diseases affecting humans.Clinical Features · Secondary Yaws · Attenuated Disease
[18]
Challenges in Recognition and Diagnosis of Yaws in Children in ...
It has been reported that the disease may show a milder form or an atypical form, with less florid skin lesions. Moreover, laboratory diagnosis of yaws is based ...
[19]
https://pmc.ncbi.nlm.nih.gov/articles/PMC11864524/
[20]
Yaws in Africa: Past, Present and Future - MDPI
Yaws is an infectious neglected tropical disease (NTD) caused by a corkscrew-shaped Gram-negative bacterium Treponema pallidum subspecies pertenue (TPE), a ...Yaws In Africa: Past... · 2. Materials And Methods · 3. Results
[21]
Metaanalysis of the Performance of a Combined Treponemal ... - NIH
A combined treponemal and nontreponemal rapid diagnostic test was found to have good sensitivity and specificity for both syphilis and yaws.
[22]
Diagnosis and treatment - Control of Neglected Tropical Diseases
Polymerase chain reaction (PCR) can be used to definitively confirm yaws by detecting the organisms in the skin lesions. It can also be used to monitor ...
[23]
Diagnostics for Yaws Eradication - PubMed Central - NIH
Yaws is an important cause of skin disease in tropical countries. Using next-generation sequencing, we tested yaws-like ulcers, which were negative using ...<|control11|><|separator|>
[24]
Advantages and limitations of current diagnostic laboratory ...
For secondary syphilis, DFM sensitivity ranges from 58% to 71% and specificity is up to 100% [12,22]. The sensitivity of DFM decreases as syphilis infection ...
[25]
A Single Dose Oral Azithromycin versus Intramuscular Benzathine Penicillin for the Treatment of Yaws-A Randomized Non Inferiority Trial in Ghana
### Summary of Cure Rates, Dosages, and Relapse Info for Yaws Treatment
[26]
Mass Treatment with Single-Dose Azithromycin for Yaws
Feb 19, 2015 · The prevalence of active infectious yaws was reduced from 2.4% before mass treatment to 0.3% at 12 months (difference, 2.1 percentage points; P ...
[27]
Advances in the Treatment of Yaws - PMC - PubMed Central - NIH
Aug 29, 2018 · Closely-related treponemal infections have been identified in primate populations, but zoonotic transmission to humans has not been established ...
[28]
Yaws - InfoNTD
WASH and Wound management[1]. Water, sanitation and hygiene (WASH) are critical in the prevention and care for yaws and NTDs in general. Provision of safe ...Yaws · Clinical Features · Diagnosis
[29]
Reconstructive Surgery for the Neglected Tropical Diseases
May 17, 2023 · In this article, we provide an overview of the major disfiguring NTDs and discuss the processes and barriers that impede access to reconstructive surgical ...Missing: correction rehabilitation
[30]
Bejel, Pinta, and Yaws - Infectious Diseases - MSD Manuals
The Treponema species causing bejel and yaws are morphologically and serologically indistinguishable from the agent of syphilis, T. pallidum subspecies pallidum ...<|control11|><|separator|>
[31]
Jarisch-Herxheimer Reaction - StatPearls - NCBI Bookshelf
Jul 7, 2025 · Management is primarily supportive, with antipyretics and close monitoring of vital signs recommended during the acute phase. Potential ...Missing: rehabilitation CDC
[32]
Yaws (Endemic treponematoses) - World Health Organization (WHO)
In 2024, 16 countries are considered as currently endemic for yaws, while 82 countries, areas and territories are considered previously endemic, with current ...
[33]
A Suspected Case of Imported Yaws in New York
Jul 17, 2023 · Yaws is an endemic non-venereal treponematoses, which is caused by ... However, due to migration, cases can be seen outside of its endemic region.
[34]
Yaws elimination in Ecuador: Findings of a serological survey of ...
May 25, 2022 · Yaws has been targeted for eradication as part of the WHO roadmap for control of neglected tropical diseases, requiring certification of ...
[35]
Yaws (Endemic treponematoses) - World Health Organization (WHO)
Overview. Yaws is a chronic skin infection characterized by papillomas (noncancerous lumps) and ulcers. · Symptoms. There are two stages of yaws infection.
[36]
Seroprevalence and geospatial epidemiology of yaws
This study found an overall yaws prevalence of 0.63% but with significantly clustered hotspots in some parts of the districts. The findings from this study ...
[37]
Years of life that could be lived without late-stage yaws, 2015–2050....
1 In the absence of an eradication campaign, yaws would be estimated to cause 1.6 million disability-adjusted life-years lost between 2015-2050. 2 The finding ...
[38]
Yaws: Neglected tropical disease is re-emerging - Debug
Oct 8, 2020 · ... yaws (endemic treponematoses) was added to bacterial infections. A ... co-infections between NTDs and HIV/AIDS, malaria, and tuberculosis.<|separator|>
[39]
Stigma, psychosocial and economic effects of yaws in the Philippines
Jul 6, 2022 · A tertiary stage with destructive bone disease can develop when yaws remains untreated. In between stages, yaws enters a latent stage with ...
[40]
[PDF] Yaws in the Americas, 1950—1975
Yaws was introduced into the Americas by African slaves beginning in the 16th cen tury and may have already been present before the arrivalof Columbus. In ...
[41]
Etymologia: Yaws - Volume 17, Number 6—June 2011 - CDC (.gov)
From either the Carib yaya, for sore or lesion, or yaw, an African word for berry. The term yaws was in common use by the 17th Century, when Dutch physician ...
[42]
Yaws: 110 Years After Castellani's Discovery of Treponema ... - NIH
Yaws is a neglected infectious disease that affects mostly children and adolescents living in poor, rural communities in humid, tropical areas of Africa, ...<|control11|><|separator|>
[43]
Yaws eradication - World Health Organization (WHO)
Feb 28, 2018 · An estimated 300 million people were screened and over 50 million treated, reducing the disease burden by 95%. ©WHO/C.J. Hackett, 1952 ...
[44]
Eradication of Yaws: Historical Efforts and Achieving WHO's 2020 ...
Sep 25, 2014 · Single-dose treatment with azithromycin (oral) given in one or two rounds of large-scale treatment, depending on the initial coverage, may be ...Missing: folk remedies
[45]
Prioritizing surveillance activities for certification of yaws eradication ...
Dec 4, 2018 · The World Health Organization (WHO) has targeted yaws for global eradication. Eradication requires certification that all countries are yaws- ...
[46]
A new attempt to distinguish serologically the subspecies of ...
In an effort to serologically differentiate syphilis from yaws, 69 monoclonal antibody species raised against Treponema pallidum subsp. pallidum were tested ...Missing: confirming | Show results with:confirming
[47]
Yaws | British Medical Bulletin | Oxford Academic
Dec 18, 2014 · Serological detection of yaws requires detection of two distinct antibodies: one against a treponemal antigen and one against a non-treponemal ...
[48]
Summary report of a consultation on the eradication of yaws
Mar 7, 2012 · In March 2012, WHO organized a first consultation in Morges, Switzerland, to prepare a strategy for the eradication of yaws. The agenda, the ...
[49]
Eradication of yaws – the Morges Strategy
May 18, 2012 · The roadmap targets the eradication of yaws by 2020. This is the second attempt to achieve the eradication goal since the uncompleted mass campaign led by WHO.
[50]
Ending the neglect to attain the sustainable development goals: a strategic framework for integrated control and management of skin-related neglected tropical diseases
### Summary of Yaws in Skin NTDs
[51]
guidance for serological surveys to assess interruption of transmision
Sep 6, 2025 · This document summarizes guidance developed for national programmes on conducting serosurveys to assess whether interruption of yaws ...Missing: care | Show results with:care
[52]
Trial of Three Rounds of Mass Azithromycin Administration for Yaws ...
Jan 5, 2022 · The reduction in the community prevalence of yaws was greater with three rounds of mass administration of azithromycin at 6-month intervals.
[53]
Global epidemiology of yaws: a systematic review - PMC
May 19, 2015 · Prevalence of active disease ranged from 0·31% to 14·54% in yaws-endemic areas, and prevalence of latent yaws ranged from 2·45% to 31·05%.
[54]
Certifying countries for interruption of yaws transmission
India is the only country to be certified by WHO in 2016 but there are a number of countries that were never endemic and will be certified in due course.
[55]
Prioritizing surveillance activities for certification of yaws eradication ...
In this study, we reviewed the literature for reports of active yaws cases and developed a descriptive model to identify countries in which passive ...
[56]
Yaws could soon be eradicated — 70 years behind schedule - Nature
including antibiotic ...
[57]
Guidance for conducting and evaluating serological surveys to ...
Apr 23, 2025 · According to World Health Organization (WHO) data, yaws is endemic in at least 16 countries, with most cases reported from WHO's Western Pacific ...
[58]
Eradication of yaws – procedures for verification and certification of ...
Jan 16, 2018 · This document sets out the criteria and procedures to be followed by countries in verifying the interruption of yaws transmission.