Pinta and yaws

Evidence Levels: A Double-blind study B Clinical trial ≥ 20 subjects C Clinical trial < 20 subjects D Series ≥ 5 subjects E Anecdotal case reports

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Pinta and yaws belong to the group of neglected endemic and non-venereal treponematoses. These distinct and chronic diseases predominantly affect economically disadvantaged, isolated, rural areas of tropical and subtropical countries.

Yaws is currently thought to be endemic in 14 countries, mostly in West Africa, Southeast Asia, and the Pacific, while pinta is restricted to Latin America, in particular Mexico and Colombia. Pinta is caused by Treponema carateum and yaws by T. pallidum ssp. pertenue . Both are Gram-negative spirochetes, morphologically and antigenically identical to each other and to the etiologic agent of syphilis; therefore, specification has to be based on clinical and epidemiological aspects. Recent genome sequencing showed that intrastrain heterogeneity within individual treponemal strains exists, differentiating T. pallidum ssp. pallidum from T. pallidum ssp. pertenue , as well as differences in genomes from treponemes that belong to the same subspecies, but are originated from various geographic locations. This phenomenon likely represents both the selection of adaptive changes during host infection as well as an ongoing diversifying evolutionary process. The only known reservoir is humans.

Both treponematoses are transmitted by direct skin contact. Spirochetes cannot enter intact skin; it must be facilitated by breaks in the skin from small cuts, scratches, or other skin damage. Most patients acquire the infection during childhood. Both diseases comprise multiple stages.

Pinta is considered the most benign among them, with skin-limited manifestations. It is classified into two different clinical stages. The primary stage is divided into two phases: an early phase (initial period) and a secondary phase (period of cutaneous dissemination). The primary lesions appear 7–10 days after inoculation, characterized by erythematous papules on the face and upper and lower extremities. These lesions tend to grow in extension, producing erythematosquamous or hyperpigmented asymptomatic plaques. Within 6 months to 2–3 years of the first lesions’ appearance, erythematohypochromic patches take place, initiating the period of cutaneous dissemination. They are polymorphic and referred to as pintides , affecting larger areas of the body with normal skin in the center.

The hallmark of the late stage, 2–5 years after the first lesion, is the appearance of achromic patches, especially over body prominences. Plantar hyperkeratosis is frequent. There is no evidence of involvement of other organs, even after many years of evolution.

The initial lesion of yaws is called ‘ mother yaws ’, arising at the site of entry of the organism most commonly on the lower limbs, 21 days after inoculation. Mother yaw is an erythematous infiltrated papule or a group of papules on an erythematous base. Those lesions may form a vegetative, raspberry-like round to oval ulcer. They are painless and considered highly infectious. Mother yaws frequently heals spontaneously, leaving an atrophic and hypopigmented scar. Systemic symptoms such as fever and joint pain are sometimes present, as well as regional lymphadenopathy.

Disseminated cutaneous lesions appear in untreated cases after the healing of the initial lesion, characterizing the secondary stage: a bilateral and symmetrical eruption that may be present in two main clinical features: a large one that resembles the mother yaws and is called ‘ daughter yaws ’ and a micropapular type, called ‘ miniature yaws ’. The mostly affected locations are the face and intertriginous moist surfaces. Usually the soles present hyperkeratotic plaques with fissures and pain, forcing the patients to walk with a peculiar gait known as ‘ crab yaws ’. Cutaneous lesions usually heal, leaving a hypochromic area. Painful osteoperiostitis and polydactylitis may occur, as well as systemic symptoms (fever, headache, generalized adenopathy, and nocturnal bone pain).

Late tertiary yaws appears in 10% of cases after several years, involving subcutaneous tissues, mucous membranes, bones, and joints. The presence of neurological, cardiovascular, and ophthalmological lesions is very controversial. The lesions of late yaws are characterized by nodular and tubercular pianides, gummatous lesions, palmar and plantar keratoderma, osteoarticular lesions, palate and nasal septum destruction ( gangosa ), exostoses of the nasal bridge ( goundou ), and juxtaarticular nodes.

Serological tests, such as rapid plasma reagin, venereal disease research laboratory (VDRL), FTA-ABS, and treponema pallidum particle agglutination and hemagglutination (TPHA) assays remain the cornerstone of the diagnosis, although they cannot distinguish syphilis from any of the non-venereal treponematoses. Dark-field microscopic examination and radiological and histopathological studies have also been used. Pathogenic treponemes cannot be cultured in vitro. Rapid point-of-care (PoC) treponemal tests have become available in the form of immunochromatographic strips; however, it is not able to differentiate between active and treated infection. Available T. pallidum polymerase chain reaction (PCR) assays can be applied to the diagnosis of endemic treponematoses as a direct method with high sensitivity.

There is no proof of a spontaneous cure for the disease and because cell-mediated immunity is not completely effective, the infection persists indefinitely. Patients may harbor subclinical disease and be contagious for a long time.

Intramuscular benzathine penicillin remains the mainstay of treatment for the endemic treponemal diseases for over 50 years. A single dose is effective, which ranges from 1.2 million units for patients over 10 years old, with half the dose necessary for patients aged under 10 and contacts.

World Health Organization (WHO) programs in the 1950s–60s successfully reduced the number of cases of yaws by administering single-dose penicillin, but failure to adequately identify and treat contacts and latent cases led to non-eradication of the disease.

A study was conducted in infected children with a 30 mg/kg single oral dose of azithromycin and it was proven to be non-inferior to penicillin, with the benefit of avoiding the need for injection equipment and medically trained personnel. Changing to the simpler azithromycin treatment regimen could enable yaws elimination through mass drug administration programs, renewing WHO’s efforts to eradicate the disease by 2020 – the Morges Strategy. Follow-up at 6 months includes clinical and serological surveys to detect and treat remaining cases and their contacts. Awareness to the possibility of azithromycin resistance is important, as it has occurred in syphilis.

At present date, WHO has not yet developed a specific strategy for the control or eradication of pinta.