Yaws: Tropical Syphilis, Causes and Treatment

Yaws, also known as tropical syphilis or yaws, is a chronic, non-venereal infection of the skin, bones, and joints caused by the spirochete Treponema pallidum subspecies pertenue. The disease primarily affects children in tropical and humid regions and is transmitted by close skin-to-skin contact, most often within families and children's groups. Unlike venereal syphilis, transmission is through household contact via microtrauma to the skin, rather than sexual intercourse. Clinically, the disease begins with a "parent" papule or plaque, followed by wave-like relapses and late bone lesions. [1]

Today, yaws is considered a neglected tropical disease, but the World Health Organization supports its eradication program. The current approach emphasizes early detection, treatment with a single dose of azithromycin, and mass courses in outbreak areas, which dramatically reduces the prevalence of the disease. Challenges remain: incomplete treatment coverage, population migration, and limited laboratory capacity in rural areas. [2]

The serological tests we use for syphilis also react to yaws, but they do not differentiate between the two infections. Therefore, diagnosis is based on the clinical picture and epidemiological context, and, when possible, is confirmed by molecular tests. In the field, "dual" rapid tests are increasingly used, which simultaneously detect both treponemal and non-treponemal components. [3]

The first-line treatment is azithromycin at a single dose of 30 mg/kg (maximum 2 g), which is convenient for mass campaigns. Benzathine penicillin, administered intramuscularly as a single dose, remains an option, especially if macrolide failure is suspected or azithromycin is contraindicated. These regimens are recommended by the World Health Organization and supported by clinical trials. [4]

Code according to ICD-10 and ICD-11

In the International Classification of Diseases, Tenth Revision, yaws is coded under block A66 "Yaws," which includes primary, secondary, tertiary, and osteoarticular forms, as well as unspecified yaws. Example: A66.0 "Primary lesions," A66.6 "Osteoarticular lesions," A66.9 "Yaws, unspecified." This is convenient for statistics and clinical reporting. [5]

The International Classification of Diseases, Eleventh Revision, uses the code 1C1D "Yaws" with sublevels: primary (1C1D.0), secondary (1C1D.1), tertiary (1C1D.2), latent (1C1D.3) forms, and "unspecified" (1C1D.Z). This level of detail facilitates data comparison and planning of public health measures. [6]

Table 1. ICD codes for yaws

Classification	Code	Name	Note
ICD-10	A66	Yaws	Block "Other spirochetoses"
ICD-10	A66.0	Initial lesions of yaws	"Mother" plaque
ICD-10	A66.6	Osteoarticular lesions of the yaws	Late complications
ICD-10	A66.9	Yaws, unspecified	Diagnosis without staging
ICD-11	1C1D	Yaws	Code group
ICD-11	1C1D.0-1C1D.3	Primary-latent forms	Sublevels
ICD-11	1C1D.Z	Yaws, unspecified	Sublevel

Epidemiology

Yaws is endemic in tropical and humid regions of Africa, Asia, and Oceania, particularly in rural, poor communities. The World Health Organization estimates that the disease is endemic in at least 15 countries, although data is incomplete due to poor surveillance. The vast majority of cases occur in children under 15 years of age. [7]

Historic campaigns in the 1950s and 1960s reduced the disease burden by 95%, but after the programs were discontinued, yaws returned in isolated pockets. In 2012, the World Health Organization adopted the "Walrus Strategy" to eradicate yaws, emphasizing mass treatment with azithromycin. However, the 2020 target was not met, and efforts are ongoing. [8]

Mass treatment with a single dose of azithromycin in outbreak areas leads to a sharp decline in the proportion of active and latent infections over a 12-month period, as confirmed by field clusters in the Pacific Islands and Africa. Mathematical models show that a sustainable effect requires an optimal combination of full coverage in the first wave and several "catch-up" rounds. [9]

Population mobility between villages, "hidden" asymptomatic carriers, and the quality of active case detection impact these indicators. This requires integrating surveillance in communities, schools, and seasonal work settings, as well as the use of rapid serological tests in the field. [10]

Table 2. Where and in whom yaws is most common

Factor	Characteristic	Explanation
Geography	Tropics of Africa, Asia, Oceania	Humid climate, rural communities
Age	Children 5-15 years old	Skin-to-skin contacts, games
Social conditions	Poverty, overcrowding	Microtraumas, general everyday life
Migration	Travel between villages	Re-introduction of foci

Reasons

The causative agent is Treponema pallidum subspecies pertenue, a close relative of the causative agent of venereal syphilis, but with a different transmission route. The spirochodist enters the skin through micro-damage caused by direct contact with the patient's weeping papules or plaques. The pathogen is unstable in the environment, so indirect transmission is unlikely. [11]

The infection begins with localized proliferation of treponemas in the skin and regional lymph nodes. Intense inflammation explains the characteristic "raspberry" (yaws, from the French framboise, meaning "raspberry") papules and plaques. Without treatment, hematogenous spread and recurrence of the rash are possible. [12]

At the molecular level, T. pallidum pertenue lacks classical toxicity factors, and tissue damage is caused by the host immune response and the persistence of spirochetes in tissues. This is similar to syphilis, but the targets and tissues involved in yaws are primarily the skin and bones in children. [13]

Macrolides (azithromycin) exhibit high activity against treponemes and can be administered as a single dose, which is critical for rural outbreaks with limited access to injections. However, mutations in 23S ribosomal RNA (A2058G and A2059G) associated with resistance in T. pallidum have been described, so the eradication program includes monitoring for treatment failures. [14]

Risk factors

The main factor is close skin-to-skin contact with an infected child or family member with open lesions. Playing on the ground, lack of shoes, minor injuries, and scratches increase the likelihood of pathogen penetration. The greater the crowding and the poorer the hygiene, the higher the risk. [15]

Ages 5–15 years are the period of greatest vulnerability due to active play and thin skin. Older children often care for younger children, coming into contact with lesions, which maintains circulation within households. School contacts and seasonal work by adolescents also contribute. [16]

Social determinants—poverty, limited access to clean water, overcrowded housing, and distance from health facilities—increase the spread and complicate timely treatment. The risk of resurgence persists with inter-village migration. [17]

The risk of macrolide resistance increases with incomplete coverage of mass rounds and repeated use of azithromycin outside of protocols. Therefore, the World Health Organization recommends using benzathine penicillin when treatment failure is suspected and conducting surveillance. [18]

Pathogenesis

After penetrating through a microfissure in the skin, treponemas multiply in the dermis, causing papules with serous discharge rich in the pathogen. Nearby lymph nodes enlarge and become painful. This stage is known as the "mother" plaque and serves as a source of further dissemination throughout the home and village. [19]

The secondary phase is associated with dissemination and an immune response, resulting in multiple papules and plaques across the body, sometimes ulcerating. The lesions may become weeping, increasing contagiousness. Without treatment, relapses occur in waves over months and years. [20]

Late stages are characterized by granulomatous lesions and bone involvement, particularly of the long bones of the tibia, with pain, deformities, and limited joint mobility. In children, physical activity may be delayed and stigmatization may occur due to visible skin defects. [21]

Immunopathology plays a key role: T. pallidum pertenue exhibits virtually no direct cytotoxicity; tissue damage is the result of chronic inflammation and the persistence of spirochetes in the lesions. This explains the good efficacy of antibiotics in the early stages and the slower recovery in late bone lesions. [22]

Symptoms

The incubation period is usually 9-90 days. The first to appear is a single papule or plaque on exposed areas—the legs, arms, and face—with a moist, crusty surface and a "raspberry-colored" appearance. Nearby lymph nodes often become enlarged. The lesion is painful when injured or rubbed by clothing. [23]

Secondary rashes appear weeks or months later: multiple papules and plaques spread over the body, sometimes with a warty surface, oozing, and an unpleasant odor. The child may complain of itching and pain, making walking and sleeping difficult. General well-being is moderately affected. [24]

Late manifestations include deep ulcers, scars, and osteoarticular lesions: periostitis, osteomyelitis, thickening and curvature of the tibia, and contractures. Without treatment, these defects can persist for life, impairing function and appearance. [25]

In some children, the disease is latent: there are no active skin lesions, but serological tests are positive. It is this "hidden" group that maintains circulation in outbreaks and requires active searches during visits to villages and schools. [26]

Classification, forms and stages

Classically, primary, secondary, tertiary, and latent forms are distinguished, similar to syphilis, but with predominantly cutaneous and osseous symptoms in children. The primary form is characterized by a single "mother" plaque, the secondary form by multiple lesions, the tertiary form by granulomas and bone lesions, and the latent form by serological signs only. This staging is useful for treatment planning and monitoring. [27]

It's also practical to classify lesions by location: limited cutaneous, widespread cutaneous, and cutaneous-osseous. This helps assess the need for pain relief, dressings, and bone examination. A visual severity scale is used for field screening to prioritize treatment. [28]

Epidemiologists also use the categories of "active" and "latent" infection during mass screenings, as it is active infections that provide the bulk of community transmission. Immediate treatment of active cases and contacts is key to breaking the chain. [29]

Table 3. Clinical forms of yaws and landmarks

Form	Key Features	Broadcast	Tactics
Primary	A single weeping "raspberry" plaque, lymphadenitis	Maximum	Immediate single-dose therapy
Secondary	Multiple papules and plaques, ulcers	High	Single-dose therapy, skin care
Latent	There is no rash, serology is positive.	Low	Treatment based on contacts and MDA algorithms
Tertiary	Granulomas, bones, deformities	No (usually)	Antibiotics + rehabilitation, observation

Complications and consequences

Without treatment, deep ulcers, dense scars, and disfiguring defects are possible, especially on the face and shins. Bone and joint damage leads to chronic pain, limited mobility, deformities, and even disability. In schoolchildren, this reduces attendance and academic performance. [30]

Social consequences include stigma and psychological stress for the family. Children may avoid play and activities, which impairs development. Timely treatment can prevent most late complications and return the child to normal activity. [31]

At the community level, prolonged circulation is maintained by latent infection and untreated active cases. Therefore, the negative "cost" of missing treatment for one child often becomes a persistent outbreak in the village. Mass campaigns have proven that short-term investments quickly pay off in reduced burden. [32]

Rarely, but crucially, monitoring for potential macrolide resistance is crucial, as it can lead to treatment failure and prolong the epidemic. In such situations, reverting to benzathine penicillin and strict surveillance is beneficial. [33]

When to see a doctor

A child should seek medical attention if they develop a persistent, oozing, crusted papule or plaque, especially on the legs and arms, while living in or traveling to a tropical area. Any "raspberry" sore in a schoolchild from an endemic area warrants examination and treatment. The sooner treatment is started, the faster the infection subsides. [34]

Signs of a secondary skin infection, such as increasing pain, pus, and high fever, warrant an urgent visit. If bone pain, lameness, or deformities of the shins are present, the musculoskeletal system should be assessed and rehabilitation should be initiated in conjunction with antibiotics. [35]

If a confirmed case is identified in a family or class, all close contacts should be examined, even if no rash is present. This is a public health standard to prevent chain infections and recurrences. [36]

If rash or pain persists 2-4 weeks after single-dose therapy, a follow-up visit is important: the doctor will check adherence, exclude repeated contact, and assess whether benzathine penicillin is required. [37]

Diagnostics

The first step is a clinical assessment and epidemiological history: residence or stay in an endemic area, the presence of a "raspberry" plaque, multiple papules, lymphadenitis, and bone pain in the child. In typical cases, the diagnosis is clinical, with immediate initiation of treatment according to the program. [38]

The second step is serology using syphilis algorithms: one treponemal and one non-treponemal test. The DPP Syphilis Screen & Confirm kit and its analogs are convenient in the field because they simultaneously display both components and help differentiate the active stage of the disease. However, serology does not differentiate between venereal syphilis and yaws—the context is important. [39]

The third step is molecular confirmation, if available: polymerase chain reaction from a scraping of the lesion with genotyping of Treponema pallidum pertenue. Research and reference laboratories also search for the A2058G and A2059G mutations of the 23S ribosomal RNA gene, associated with macrolide resistance. [40]

The fourth step is an assessment of bones and joints for pain and deformities: a clinical examination and, if possible, radiographic signs of periostitis and osteomyelitis of the long bones. Instrumental methods are used in children according to indications and availability, after the start of antibacterial therapy. [41]

Table 4. Diagnostic tools for yaws

Method	What does it give?	Restrictions	Where is it used?
Clinical examination	Quick diagnosis, treatment decision	Requires experience, "mask"	Field and rural points
Serology (treponemal + non-treponemal)	Confirmation of infection and activity	Doesn't distinguish syphilis from yaws	Field tests, areas
Polymerase chain reaction	Etiological confirmation, resistance monitoring	Limited availability	Reference laboratories
X-ray of bones	Confirmation of bone lesions	Availability, radiation	According to the readings

Differential diagnosis

Yaws is most often confused with pyoderma and impetigo, especially in children with weeping, crusted lesions. Bacterial skin infections are typically accompanied by severe pus, pain, and a rapid response to topical antiseptics and antibiotics, whereas yaws has a "raspberry-colored" warty surface and regional lymphadenitis. Epidemiological history helps clarify the distinction. [42]

In endemic areas, it is necessary to differentiate yaws from other skin ulcers, including tropical ulcers, mycoses, cutaneous leishmaniasis, and traumatic injuries. When in doubt, a "therapeutic test" with a single dose of azithromycin is warranted, with an assessment of the dynamics after 2-4 weeks and subsequent clarification. [43]

Venereal syphilis in children is extremely rare and requires a separate evaluation for possible abuse. Since serology cannot differentiate between syphilis and YAWS, clinical characteristics, age, location, and family background are crucial. If there is any doubt, child protection specialists are consulted. [44]

Table 5. How yaws differs from “similar” conditions

State	What is similar	What makes it different	What helps in diagnosis
Impetigo	Weeping, crusting	Acute purulent component, rapid response to topical antibiotics	Sowing, clinical examination
Cutaneous leishmaniasis	Chronic ulcers	Geography, parasites in smear	Parasitological tests
Venereal syphilis	Papules, serology "plus"	Route of transmission, age, localization	History, context
Fungal infections	Plaques	Clear edges, scales	Microscopy, culture

Treatment

The preferred regimen is a single oral dose of azithromycin, 30 mg/kg, with a maximum of 2 g. A single-dose regimen is critical in rural areas where returning to appointments is difficult and injection facilities are limited. Clinical improvement is usually noticeable within 7-14 days, with ulcers and plaques shrinking and pain decreasing. A lack of significant improvement after 2-4 weeks is a reason to reconsider the diagnosis and treatment plan. [45]

An alternative remains benzathine penicillin in a single intramuscular dose: 0.6 million units for children under 10 years of age and 1.2 million units for individuals 10 years of age and older. This option is indicated in cases of suspected macrolide failure, in cases of azithromycin intolerance, and in resistance monitoring programs. Injection provides a reliable depot but requires trained personnel and safety precautions. [46]

Skin care is the second pillar of therapy: gentle cleansing, dry dressings on oozing areas, and protection from injury and friction. In the case of secondary bacterial infection, topical antiseptics and systemic antibiotics are used as indicated. This accelerates healing and reduces pain, reducing the risk of scarring. [47]

Household contacts and classmates in the outbreak area are given preventive treatment using mass approach algorithms, even in the absence of rashes, as some children may be latent carriers. This "covert" approach reduces the likelihood of hidden circulation and recurrence of outbreaks in the village. [48]

Mass treatment is based on two approaches: "total community treatment" (TCT)—a single dose administered to all residents of an outbreak, regardless of status—and "totally targeted treatment" (TTT)—repeat visits with treatment of identified cases and contacts. A combination of TCT with multiple rounds of TTT has shown the best results in models and field studies. [49]

Clinical response monitoring includes follow-up after 2-4 weeks and then at the timeframes established by the program. If the response is incomplete, azithromycin is followed by a switch to benzathine penicillin, and samples are sent for molecular resistance testing, if available. Documentation of treatment failures is an important part of global surveillance. [50]

Pain relief and rehabilitation are important for osteoarticular forms: simple analgesics, gentle mobilization, and exercises. For significant deformities, children are referred for orthopedic evaluation. Even after microbiological cure, functional recovery takes time. [51]

Family education: how to care for lesions, not sharing towels and clothing, keeping nails short, and covering oozing lesions with bandages. These measures reduce autoinoculation and household transmission, accelerating the lesion's resolution. Simple explanations increase adherence. [52]

Integration with neglected tropical disease programs enhances the impact: joint visits with trachomatis, helminth, and cutaneous NTD teams increase coverage and conserve resources. The use of portable "dual" tests simplifies on-site triage and reduces patient loss. [53]

Table 6. Treatment regimens and accompanying measures

Situation	Mode	Dose	Comments
First-line treatment	Azithromycin orally	30 mg/kg single dose, maximum 2 g	Convenience, high coverage
Alternative/Failure	Benzathine penicillin intramuscularly	<10 years: 0.6 million IU; ≥10 years: 1.2 million IU	If there are contraindications to azithromycin or if resistance is suspected
Skin care	Bandages, hygiene	Daily	Less pain and household contacts
Relapse/no response	Change of regimen + examination	According to protocol	Report to the supervisory authority, if possible - test for 23S rRNA mutations

Table 7. Mass approaches to eradication (Walrus Strategy)

Approach	To whom	Target	When
TCT - Total Community Treatment	To all residents of the hearth	Quickly interrupt the transmission	First round
TTT - Totally Targeted Therapy	Cases + contacts	Catch up and eliminate the "tails"	Repeat rounds after 6-12 months
Monitoring	The whole village	Identify hidden cases	Regular visits and "school days"
Laboratory control	Suspicious failures	Monitor sustainability	According to the program protocol

Prevention

Prevention relies on early detection and simultaneous treatment of all cases and contacts. Families and schools should follow these rules: cover wet spots with bandages, avoid sharing towels and clothing, wash hands regularly, and trim nails. These simple steps dramatically reduce the likelihood of household transmission. [54]

At the community level, the key is high coverage with the first round of TCT and disciplined "catch-up" TTT visits. Linking with other neglected tropical disease programs increases efficiency and allows for more frequent "seeing" of children who missed the first round. [55]

Macrolide resistance monitoring involves clinical monitoring of unresponsive cases and, where possible, molecular verification of the A2058G/A2059G mutations. If resistance is suspected, the program switches the outbreak to benzathine penicillin. This reduces the risk of resistant clusters forming. [56]

Table 8. Prevention memo for families and schools

Advice	For what
Treat active lesions immediately.	Interrupts transmission
Cover the weeping areas	Less contact with discharge
Individual towels and clothing	Reducing household transfer
Short nails and hand hygiene	Less autoinoculation
Report cases to school/healthcare provider	Quick contact check

Forecast

With single-dose therapy, the prognosis is favorable: most skin lesions diminish within 1-2 weeks and then heal. The earlier treatment is started, the lower the risk of scarring and deformity. Late bone lesions require long-term observation and rehabilitation. [57]

At the population level, mass treatment rounds can quickly "break" transmission, but for sustainable results, monitoring and follow-up visits are necessary to catch latent and new cases. Otherwise, outbreaks re-emerge with population migration. [58]

The program's prognosis depends on the quality of surveillance, treatment coverage, and resistance management. With a well-designed combination of TCT and TTT, coupled with family education, yaws elimination remains an achievable goal, albeit later than originally stated. [59]

FAQ

1. Is yaws "syphilis"?
It is a close relative of syphilis, caused by a different subspecies of the same bacterium, but is not transmitted sexually, but through skin-to-skin contact in children. Serological tests are equally "positive," so clinical and contextual information are important. [60]

2. Is yaws treated with a single tablet?
Yes, a single dose of azithromycin 30 mg/kg orally (maximum 2 g) is recommended. In case of intolerance or suspected failure, a single dose of benzathine penicillin intramuscularly is used. [61]

3. Why does the disease sometimes return to villages?
The reasons include low coverage in the first round, missed latent cases, migration, and reintroductions. Therefore, repeat "catch-up" visits and screenings are conducted in schools. [62]

4. How do you know if the treatment has failed?
If there is no improvement after 2-4 weeks, the doctor considers an alternative to benzathine penicillin and, if possible, sends the sample for a macrolide resistance test (23S rRNA mutations A2058G/A2059G). [63]

5. What codes should be used in documents?
ICD-10: block A66 with subcategories (e.g. A66.0, A66.6, A66.9). ICD-11: 1C1D with sublevels for stages (1C1D.0-1C1D.3, 1C1D.Z). [64]