Yaws Disease

Yaws Disease

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Yaws Disease

Yaws is a disfiguring non-venereal disease caused by infection with the spirochaete Treponema pallidum subspecies pertenue which is closely related to the causative agent of syphilis and those of the other endemic treponematoses, bejel and pinta. The disease is endemic in certain areas of the World Health Organization (WHO) African, South-East Asia and Western Pacific region.

About 50 million people were treated with a single dose of long-acting penicillin during the mass treatment campaigns conducted by WHO and the United Nations Children’s Fund between 1952 and 1964, and the prevalence of yaws disease was reduced by more than 95% from 50 million to 2.5 million.

The lack of sustained political commitment and resources slowed the campaign’s progress to eradicate the disease. As a result, by the late 1970s the disease had begun to resurge, prompting the Thirty-first World Health Assembly in 1978 to adopt resolution WHA31.58 to renew efforts towards controlling endemic treponematoses in West Africa, but implementation of the resolution was not sustained. Subsequently, in 1995, WHO estimated 2.5 million cases of the endemic treponematoses (mostly yaws), with an incidence of 460 000 new cases per year

A single intramuscular dose of long-acting penicillin has long been used in mass treatment campaigns in areas where yaws is endemic. In 2012, the efficacy of a single oral dose of azithromycin (30 mg/kg body weight) in curing the disease was published. The same year, WHO held a consultation of yaws experts in Morges, Switzerland and recommended mass treatment using single-dose oral azithromycin to eradicate the disease by 2020. This new treatment strategy has been referred to as the Morges Strategy.

Yaws Disease

Causative organism

Yaws is caused by infection with Treponema pallidum subspecies pertenue, a spiral bacterium (spirochete) closely related to the causative organism of syphilis. Related spirochetes are the cause of the other nonvenereal treponematoses bejel (T. pallidum subspecies endemicum) and pinta (T. carateum).

Transmission

Yaws is transmitted from person to person by direct skin contact with fluid from untreated early, infectious lesions (skin papillomas and ulcerations). Although the lesions may heal spontaneously, some lesions may recur. Without treatment, the disease may resolve spontaneously or become latent and re-emerge as late yaws. Late yaws lesions of 2 years or more (palmar and plantar hyperkeratotic lesions, bone lesions) are generally not infectious.

Cases of yaws are often seen in temporal clusters within neighbouring communities, as transmission occurs primarily among children at home, at school or at play. Poor hygienic conditions (limited access to water) and overcrowding are some of the factors that are believed to promote transmission of the disease. About 75% of new yaws cases are seen among children aged less than 15 years. The incubation period is between 9 and 90 days, with an average period of 21 days.

Clinical features

Primary stage: A papule (a raised lesion) forms at the organisms’ site of entry (such as a micro abrasion) after an incubation period of 9–90 days. The papule may then develop into a small yellowish cauliflower-like lesion (papilloma), which grows gradually and develops a punched-out centre covered with a yellow crust (ulcer and ulceropapilloma). In 65–85% of cases, the primary lesions of yaws are seen on the legs and ankles. However, they may be found on the face, neck, armpits, arms, hands and buttocks.

The initial lesions, which are highly infectious, may take 3–6 months to heal, leaving a pitted scar with dark margins.

Secondary stage: The secondary stage of yaws is characterized by more generalized lesions, which may appear on the face, neck, armpits, arms, legs and buttocks. These lesions may also occur on the soles of the feet, forcing the patient to walk in an odd position; this condition has been termed “crab-yaws” (hyperkeratosis).

Secondary lesions occur following spread of the causative organism to the blood and lymph, and multiple lesions most commonly within the first 2 years following the appearance of the primary yaws lesion. Joint pain (arthralgia) and malaise are probably the commonest, nonspecific symptoms of secondary yaws.

Latent yaws: If left untreated, the infectious lesions of primary and secondary yaws will heal spontaneously and the disease may enter a period of latency with no physical signs. Latent yaws can only be detected as a result of serological testing.

Tertiary stage: Although spontaneous healing may occur in many cases, a minority may progress from latency to the tertiary stage. This destructive, non-infectious stage of the disease is characterized by gumma formation and may appear after a variable period of latency. This stage affects the bones, joints and soft tissues, and frequently leads to deformities of the skin, cartilage and bone. Such cases may develop severe disfigurement of the face and legs, resulting in disabilities that prevent children from attending school and adults from working. Thus, the socioeconomic and humanitarian impact of yaws justifies intensification of yaws eradication activities.

Diagnosis and differential diagnosis

All individuals with suspected yaws lesions should be examined by trained health workers. A clinical diagnosis should be established based on the patient’s history, endemicity of yaws in the area and characteristics of the lesions. Health workers should refer to the WHO yaws recognition booklet.

Clinical diagnosis

A clinical diagnosis is based on the following features:

• History of living in or having lived in a yaws endemic area;

• Age of an individual (more common among children aged < 15 years);

• Clinical appearance of skin/bone lesions suspicious of yaws (papilloma, ulceropapilloma, ulcer, papule, macule);

• Typical distribution being most common sites: lower limbs (70%); upper limbs (11%); trunk (6.2%); head and neck (8.2%); and multiple sites (4.0%)

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Serological confirmation of clinically diagnosed yaws cases

Testing for treponemal and non-treponemal antibodies should be done to confirm a diagnosis of yaws so that reporting of cases by countries will shift from clinically suspected cases to laboratory-confirmed cases. Traditional laboratory methods such as rapid plasma reagin (RPR) and Treponema pallidum haemagglutination assay (TPHA) or Treponema pallidum particle agglutination assay (TPPA) testing can be used, but the delay in obtaining test results may negatively impact early treatment. Treponemal point-of-care (POC) tests can be used in the field for rapid screening and to exclude non-yaws cases, but subsequent confirmation of positive cases is necessary using a non-treponemal test. Treponemal and non-treponemal antibodies can also be simultaneously detected using a dual POC test such as the dual path platform (DPP) syphilis screen and confirm assay. Both tests can be performed by trained health workers in the field using a finger-prick blood sample and the results read within 20 minutes, thus facilitating immediate treatment.

The dual DPP test has been found to be sensitive and specific for confirmation of both syphilis and yaws and is easy to apply under field conditions.

A specimen containing treponemal and non-treponemal antibodies exhibits three lines (treponemal, non-treponemal and control) in a developed test, indicating a confirmed reactive sample, while a specimen containing neither treponemal nor non-treponemal antibody will exhibit only a control line.

Note: Reactive results do not necessarily mean that the lesion is active yaws, as it could be caused by other agents.

By detecting both treponemal and non-treponemal antibodies, the use of this test should greatly reduce the rates of overtreatment inherent in current (treponemal only) rapid testing and permit a single point-of-care device to be used for yaws sero-surveillance. Where available, RDT and DPP tests may be used in combination

Differential diagnosis of yaws

A variety of skin diseases may be common among population groups living in areas where yaws is endemic. These may be mistaken for the lesions of primary and secondary stage yaws. The most common differential diagnoses are tropical ulcers and lesions caused by Haemophilus ducreyi

Treatment

Yaws is amenable to treatment with either one of these two medicines: azithromycin or benzathine benzylpenicillin. Historically, mass treatment campaigns have relied on long-acting penicillin, which remains an effective treatment. Recently, however, oral azithromycin has been shown to be effective and is recommended by WHO for the eradication of yaws due to its ease of administration, the absence of a risk of anaphylaxis as is seen with penicillin and the fact that a cold chain is not required for storage.

Azithromycin

A single oral dose of azithromycin has been recommended for use in treatment of early yaws (primary and secondary) based on the results of clinical trials conducted in Papua New Guinea and Ghana. In these studies, a single dose of azithromycin (30 mg/kg body weight; to a maximum dose of 2 g) has been found to be both effective and well tolerated with minimal adverse side-effects. The cure rate (> 98%) was found to be equivalent to that of a single intramuscular injection of long-acting penicillin, which was previously considered the treatment of choice for the disease. In 2017, the WHO Essential Medicines List has included azithromycin as an indication for the treatment of yaws

Intramuscular benzathine benzylpenicillin

Intramuscular long-acting penicillin remains effective in the treatment of yaws (dosage for adults, 1.2 million units; children aged less than 10 years, 600 000 units). In some countries, the doses are doubled. Given the advantages of oral azithromycin, intramuscular benzathine benzylpenicillin should be considered as an alternative therapy only when cases or their contacts develop severe adverse events to azithromycin or for those who cannot tolerate or take azithromycin. Intramuscular benzathine benzylpenicillin is known to rarely cause severe hypersensitivity reactions, which can be fatal. Pain at the injection site and vasovagal reactions are the most common adverse events recorded.

Reference

1. Accelerating work to overcome the global impact of neglected tropical diseases: a roadmap for implementation [Roadmap approved by the Strategic and Technical Advisory Group for Neglected Tropical Diseases in 2011]. Geneva: World Health Organization; 2012 (WHO/HTM/NTD/2012.1; http://www.who.int/neglected_diseases/NTD_RoadMap_2012_Fullversion.pdf).

2. Resolution WHA2.36: Bejel and other treponematoses. In: Second World Health Assembly, Rome, 13 June to 6 July 1949. Decisions and resolutions, Plenary meetings, Committees, Annexes. Geneva: World Health Organization; 1949:27 (http://www.who.int/neglected_diseases/mediacentre/WHA_2.36_Eng.pdf).

3. Summary report of a consultation on the eradication of yaws. Morges, 5–7 March 2012. Geneva: World Health Organization; 2012 (http://apps.who.int/iris/bitstream/10665/75528/1/WHO_HTM_NTD_IDM_2012.2_eng.pdf).

4. Report of an informal consultation on endemic treponematoses. Geneva, Switzerland, 6–7 July 1995. Geneva: World Health Organization; 1995.

5. Mitjà O, Hays R, Ipai A, Penias M, Paru R, Fagaho D et al. Single-dose azithromycin versus benzathine benzylpenicillin for treatment of yaws in children in Papua New Guinea: an open-label, non-inferiority, randomised trial. Lancet. 2012;379:342–7. doi:10.1016/S0140-6736(11)61624-3.

6. Kwakye-Maclean C, Agana N, Gyapong J, Nortey P, Adu-Sarkodie Y, Aryee E et al. A single dose oral azithromycin versus intramuscular benzathine penicillin for the treatment of yaws: a randomized non inferiority trial in Ghana. PLoS Negl Trop Dis. 2017;11(1):e0005154. doi:10.1371/journal.pntd.0005154.

7. Epidemiological situation. In: Yaws eradication [website]. Geneva: World Health Organization; 2017 (http://www.who.int/yaws/epidemiology/en/).

8. Status of endemicity for yaws: data by country. In: Global Health Observatory data repository [website]. Geneva: World Health Organization; 2014 (http://apps.who.int/gho/data/node.main.NTDYAWSEND?lang).

9. Friedrich MJ. WHO declares India free of yaws and maternal and neonatal tetanus. JAMA. 2016;316:1141. doi:10.1001/jama,2016.12649.

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