Elsevier

The Lancet

Volume 381, Issue 9868, 2–8 March 2013, Pages 763-773
The Lancet

Seminar
Yaws

https://doi.org/10.1016/S0140-6736(12)62130-8Get rights and content

Summary

Yaws is an infectious disease caused by Treponema pallidum pertenue—a bacterium that closely resembles the causative agent of syphilis—and is spread by skin-to-skin contact in humid tropical regions. Yaws causes disfiguring, and sometimes painful lesions of the skin and bones. As with syphilis, clinical manifestations can be divided into three stages; however, unlike syphilis, mother-to-child transmission does not occur. A major campaign to eradicate yaws in the 1950s and 1960s, by mass treatment of affected communities with longacting, injectable penicillin, reduced the number of cases by 95% worldwide, but yaws has reappeared in recent years in Africa, Asia, and the western Pacific. In 2012, one oral dose of azithromycin was shown to be as effective as intramuscular penicillin in the treatment of the disease, and WHO launched a new initiative to eradicate yaws by 2020.

Introduction

Yaws is an infectious disease caused by Treponema pallidum pertenue. Unlike syphilis, which is caused by the almost identical Treponema pallidum pallidum, yaws is not sexually transmitted, but is spread by skin-to-skin contact in warm humid environments, mainly among children. The disease is one of the endemic, non-venereal treponematoses. The other treponematoses are bejel (ie, endemic syphilis), which used to be prevalent in parts of northern Africa, eastern Europe, and the Middle East, and pinta, which is confined to South America. All these diseases affect poor, rural populations.

The term yaws—from either the Carib word for sore or lesion yaya, or the African word for berry yaw—was in common use by the 17th century, when the Dutch physician Willem Piso provided one of the earliest recorded clinical descriptions of the disease in South America.1 In his 1679 epistle on venereal disease,2 Thomas Sydenham clearly described yaws—believed to be common among African slaves—and thought that it was the same disease as syphilis. In 1905, Castellani discovered spirochaetes in the ulcers of patients with yaws in Ceylon.3 Because the lesions of yaws resemble raspberries, the disease was also known as framboesia tropica, from the French word for raspberry (framboise).

Bone changes typical of yaws have been found in skeletons of Homo erectus in Kenya dating from 1·6 million years ago.4, 5 Phylogenetic analyses identify the yaws subspecies as the oldest of the treponemal diseases, and suggest that the bejel and syphilis subspecies evolved subsequently.6, 7 This finding supports the so-called unitarian hypothesis put forward by Hudson, who believed that venereal syphilis in Europe arose from yaws, which was introduced into Europe in the 15th century as a result of the slave trade.8 Strains of T pallidum pertenue that are almost indistinguishable from human isolates with molecular analysis have been isolated from wild non-human primates in central Africa, suggesting a possible animal origin of yaws.9, 10, 11 However, the genetic data used to build the phylogenetic tree are scarce because of the few available strains, and some evidence suggests a fairly parallel evolution of the three subspecies.12 Therefore, conclusions about how old yaws is and where it came from should be made with caution.13

Section snippets

Causative agent

T pallidum pertenue belongs to a family of Gram-negative, spiral-shaped bacteria, the Spirochaetaceae, and is closely related to other pathogenic subspecies of T pallidum, from which it is morphologically and, up to now, serologically identical.13 T pallidum pallidum, T pallidum endemicum (bejel), and Treponema carateum (pinta) can be differentiated from T pallidum pertenue by the clinical manifestations of their respective diseases and, more recently, by identification of minor genetic

Genomics: yaws versus syphilis

The T pallidum pertenue genome was sequenced in 2010,15 and was compared with T pallidum pallidum strains. The genome size—roughly 1139 kilobases—was much the same, and the gene structure of T pallidum pertenue was identical to that of T pallidum pallidum. The overall sequence identity between the two genomes was 99·8%, which suggests that the two pathogens are very closely related.30 Most of the differences between subspecies are localised to six genomic regions, which probably contribute to

Pathogenesis

T pallidum pertenue presumably enters the human host through small breaks in the skin.38 Treponemes move through epithelial cells via tight junctions and invasively attach to fibronectin-coated surfaces on the extracellular matrix of host cells.39 In the hamster model, rate of appearance and resolution of cutaneous lesions varies with the size of the inoculum, and the minimum infective dose is about 103–104 bacteria.40, 41 The organisms appear in lymph nodes within minutes and disseminate

Epidemiology

Yaws is transmitted by direct skin-to-skin, non-sexual contact with infectious lesions. Because T pallidum pertenue is temperature and humidity dependent, yaws is found in warm, moist climates, mainly in forested tropical regions. The incidence of yaws skin lesions is higher in the wet season than in the dry season;52 high humidity promotes exuberant growth of papillomata and survival of treponemes in serous exudates, which increases infectiousness and transmission. Yaws predominantly affects

Clinical features

As for syphilis, the clinical manifestations of yaws arise in three distinct stages (figure 3). The initial or primary lesion—so-called mother yaw—appears at the site of inoculation on an exposed part of the body.54, 77 The scarce experimental data suggest that the incubation period of yaws could be between 10 and 90 days (mean 21 days).54 Similar results on the incubation period were reported in a cohort of uninfected individuals with a wound or breach of the skin surface who were continually

Diagnosis

Clinical diagnosis of yaws is generally straightforward in known endemic communities, although the diagnosis of attenuated yaws can be more challenging. Yaws can be confused with several diseases that are common in the tropics—eg, tropical ulcer or cutaneous leishmaniasis in a patient with cutaneous ulcers, scabies or fungal infections in a patient with squamous maculae, and tuberculosis or sickle cell disease in a patient with dactylitis. Health-care workers who are not familiar with the

Management

Longacting penicillin, given as one intramuscular dose, was shown to be effective in 1948,110 and has been the mainstay of yaws treatment and eradication efforts for the past 60 years.111 A single intramuscular dose of 1·2 MU and 0·6 MU of benzathine benzylpenicillin for patients older than 10 years, and younger than 10 years, respectively, is the recommended regimen.86 Larger doses are recommended in syphilis because venereal treponemes invade tissues that are difficult for penicillin to

Prognosis and follow-up

Yaws lesions become non-infectious within 24 h of treatment; joint pains usually disappear in 24–48 h, and complete healing of the primary and secondary lesions usually happens within 2–4 weeks after treatment.113, 129 Although treatment in early stages results in cure in almost 100% of patients, it will not reverse destructive changes in the late tertiary stage. An early-stage lesion that has not healed in 4 weeks must be regarded as a treatment failure. In such cases, a serological test to

Eradication strategy: lessons learnt from the past

The history of disease eradication is closely related to that of yaws. After the founding of WHO in 1948, yaws was the first disease to be targeted for global eradication, on the basis of a previous attempt at elimination in Haiti.129 Although mass treatment campaigns greatly reduced the number of cases of the disease worldwide, the subsequent complacency led to gradual dismantling of the vertical control programmes, and premature integration of yaws control activities into primary health-care

Unanswered questions

To eradicate yaws, some unanswered questions will need to be addressed (panel 2). First, the true geographical extent of the disease needs to be established with careful mapping of populations in whom yaws is known or suspected to be endemic. Remarkably few recent data for the prevalence of pinta and bejel exist, although sporadic cases are still reported.142, 143 Communities in which these infections are endemic are also candidates for eradication campaigns. Second, the effect of mass

Search strategy and selection criteria

We searched Medline, Cochrane Library, and WHO databases from Jan 1, 1905, to Sept 1, 2012, in all languages. Many articles were identified through searches of the files of the authors and reference lists from relevant review articles. Search terms were “yaws”, “pian”, “endemic treponematoses”, “Treponema pallidum pertenue”, and “eradication”. Data from original articles, reviews, and book chapters published in English, French, Spanish, and Portuguese are summarised in this Seminar.

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