- Yaws is a chronic infectious disease caused by Treponema pallidum subspecies pertenue.
- It affects the skin, bone and cartilage; if left untreated, it can lead to deformities of the nose and bones of the leg.
- It has long been considered that yaws can be eradicated because humans are the only reservoir.
- The discovery in 2012 that a single, oral dose of the antibiotic azithromycin can completely cure yaws has reopened the prospects of yaws eradication.
- 2 countries, Ecuador and India, which were once endemic, reported interruption of transmission in 2003.
- 13 currently endemic countries need support to implement WHO’s new eradication strategy.
- 73 previously endemic countries need to confirm the absence or presence of the disease.
Yaws forms part of a group of chronic bacterial infections caused by treponemes which include endemic syphilis (bejel) and pinta, and are commonly known as endemic treponematoses. Yaws is the most common of these infections.
The causative organism – Treponema pallidum subspecies pertenue – is genetically closely related to the less common nonvenereal endemic treponematoses, bejel and pinta, and T. pallidum subspecies pallidum, the causative agent of syphilis.
The disease is found primarily in poor communities in warm, humid and tropical forest areas of Africa, Asia, Latin America and the Pacific.
Yaws is transmitted through direct (person-to-person), non-sexual contact with the fluid from the lesion of an infected person to an uninfected persons through minor injuries. Most lesions occur on the limbs. The initial lesion of yaws is teemed with the bacteria. The incubation period is 9–90 days (average 21 days).
About 75% of people affected are children under 15 years old (peak incidence occurs in children aged 6–10 years). Males and females are equally affected.
Overcrowding, poor hygiene and socioeconomic conditions facilitate the spread of the yaws. Without treatment, infection can lead to chronic disfigurement and disability.
Scope of the problem
The eradication campaigns of 1952–1964 targeted 46 countries. Since 1990, formal reporting of yaws to WHO stopped due to the discontinuation of yaws eradication programmes in many countries. Only a few countries kept yaws as part of their public health agenda.
A review of historical documents from the 1950s1 shows that at least 88 countries and territories within the tropical belt of 20 degrees north and south of the Equator were endemic for yaws. However, only 13 are known to be currently endemic for yaws, while 2 countries, Ecuador and India, which claim to have interrupted transmission in 2003, need to be verified. Furthermore, WHO also plans to assess the status of yaws in 73 previously endemic countries.
There are two basic stages of yaws: early (infectious) and late (non-infectious).
- In early yaws, an initial papilloma (a circular, solid swelling on the skin, with no visible fluid) develops at the site of entry of the bacterium. This papilloma is full of organisms and may persist for 3–6 months followed by natural healing. Bone pain and bone lesions may also occur in the early stage.
- Late yaws appears after 5 years of the initial infection and is characterized by disfigurement of the nose and bones, and thickening and cracking of the palms of the hand and soles of the feet. These complications on the soles of the feet make it difficult for patients to walk.
In the field, diagnosis is primarily based on clinical and epidemiological findings. However, recent discovery that leg ulcers caused by Haemophilus ducreyi can clinically mimic yaws calls for the need for using rapid diagnostic tests to confirm suspected yaws cases in the field.
WHO has published a clinical pictorial guide to help health and community health workers identify the disease.
Standard laboratory-based tests
Serological tests are widely used to diagnose treponemal infections (e.g. syphilis and yaws). Serological tests cannot distinguish yaws from syphilis and its interpretation on adults in yaws endemic areas need careful clinical assessment as well. Laboratory tests (TPPA and RPR) using venous blood are labour intensive.
Rapid point-of-care tests
Rapid tests allow the point-of-care2 diagnosis and treatment of patients. There are 2 types of rapid tests:
- Rapid treponemal tests are widely used in the diagnosis of syphilis; however, these tests cannot distinguish between present active yaws and past infections. Therefore, its use alone could lead to overtreatment of patients and over-reporting of cases.
- New rapid dual (non-treponemal and treponemal) point-of-care syphilis test allows simultaneous yet separate detection of both antibodies. This test has been evaluated for yaws in a number of countries (Ghana, Papua New Guinea, Solomon Islands and Vanuatu). It is now being used in yaws eradication efforts.
Genomic analysis using polymerase chain reaction (PCR) 3 can be used to definitely confirm yaws, and this test will be very useful in the last phase of the eradication programme. The PCR technique can also be used to determine azithromycin resistance from swabs taken from yaws lesions.
Two antibiotics may be used to treat yaws:
- Azithromycin (single oral dose) at 30 mg/kg (maximum 2 gm).
- Benzathine penicillin (single intramuscular dose) at 1.2 million units (adults) and 600 000 units (children).
Without treatment, about 10% of affected people develop disfiguring and disabling complications – deformities of the legs and nose – after 5 years. The disease and its complications lead to school absenteeism and prevent adults from farming activities.
There is no vaccine for yaws. Prevention is based on the interruption of transmission through early diagnosis and treatment of individual cases and mass or targeted treatment of affected populations or communities. Health education and improvement in personal hygiene are essential components of prevention.
Past eradication efforts
Between 1952 and 1964, WHO and UNICEF provided assistance to 46 countries with the aim of eradicating endemic treponematoses. Mass campaigns in these countries examined over 300 million people and treated 50 million. By 1964, the prevalence of these diseases had decreased by 95% (2.5 million).
This achievement is considered to be one of the success stories in public health but this achievement was not sustained until the end goal: eradication. The premature integration of yaws-control activities into the weak primary health care systems and lack of continued surveillance were partly responsible for the world’s inability to eradicate yaws. Resurgence in the 1970s prompted the World Health Assembly Resolution WHA31.58.
Criteria for eradication
In 1960, the WHO Expert Committee on Venereal Infections and Treponematoses4 set 2 criteria for the eradication of yaws from a public health perspective:
- Epidemiological eradication: considered as the intermediate stage to complete eradication, defined as the absence of an indigenous infectious case in the population for 3 consecutive years
- Complete eradication: considered as the final stage of achievement of eradication (interruption of transmission), defined as the absence of an indigenous infectious case in the population for 3 consecutive years plus no seroreactor in the age group of under-5 years.
With today’s technology, in the final stages of the eradication efforts PCR can be used to complement the serological confirmation of the last cases.
Eradication of yaws in India
As per a paper published in the WHO Weekly Epidemiological Report on 17 April,5 India appears to have eliminated yaws. The last case was reported in 2003 and, following the criteria set in 1960, serological testing involving over 57 000 samples from children aged 1–5 years randomly selected from former endemic and non-endemic villages yielded no positive results (i.e. no seroreactor). These results confirm that there is no ongoing transmission of the disease. The details of the process followed are presented in the report and can guide other countries aiming to achieve the same outcome.
Renewed eradication efforts: progress so far
The “WHO Roadmap for NTDs” and WHA resolution 66.12 have set the year 2020 as the target for the eradication of yaws from the remaining endemic countries. In 2012, WHO and experts in yaws developed the new eradication strategy (referred to as the “Morges Strategy”) based on the use of oral azithromycin, a shift from 60 years of use of injection benzathine penicillin.
The Morges Strategy has been piloted successfully in Congo, Ghana, Papua New Guinea and Vanuatu. The results from Papua New Guinea was published in the New England Journal of Medicine in February 20156 showing the dramatic reduction of cases and transmission after one round of mass treatment of the population at risk. Similar findings have been recorded in Ghana and Vanuatu (unpublished results). These findings provide the empirical evidence that if azithromycin donation and funds for implementation can be secured, the eradication of yaws this time round is likely to be successful.7
A number of operational research topics have been already been identified by yaws experts (manuscript in press), which will be carried out during the full-scale implementation of the eradication strategy. Lessons learned will help continuously refine the strategy and its implementation as efforts proceed.
Of immediate interest is the study in Ghana and Papua New Guinea planned for 2015 to determine the efficacy of a lower dose of 20mg/kg (recommended dose used in trachoma) compared with the standard treatment of yaws given at 30mg/kg. If successful, the results could help harmonize treatment policies of both the diseases in countries where they overlap.
The following institutions are currently involved in yaws eradication efforts:
- Barcelona Institute for Global Health, Barcelona, Spain.
- Centers for Disease Control and Prevention, Atlanta, USA.
- London School of Hygiene and Tropical Medicine, London, United Kingdom.
- Noguchi Memorial Institute for Medical Research, Accra, Ghana.
- Papua New Guinea Institute of Medical Research, Goroka, Papua New Guinea.
- University of Washington, Seattle, USA.
Yaws is eradicable as humans are the only reservoir. Largescale treatment of at-risk populations with Benzathine penicillin (as in the past) and now with oral azithromycin will interrupt transmission and help eliminate the disease in a given area within a relatively short time.
The interest and momentum to achieve this is gathering pace, and WHO, together with partners, is spearheading renewed efforts to eradicate yaws.
The donation of azithromycin remains the critical bottleneck. Funding for implementation would be easier if access to the drugs can be found. The eradication of yaws is feasible and within reach.
The availability of a rapid diagnostic tests and adequate funding are critical to ensure the smooth implementation of activities to reach the 2020 target.
1Status of yaws endemicity by country (2013): http://apps.who.int/gho/data/node.main.NTDYAWSEND?lang=en
2Ayove T et al. Sensitivity and specificity of a rapid point-of-care test for active yaws: a comparative study. Lancet Global Health, 2014 (http://dx.doi.org/10.1016/S2214109X(14)70231-1).
3 Chi KH, Danavall D, Taleo F, Pillay A, Ye T, Nachamkin E, Kool JL, Fegan D, Asiedu K, Vestergaard LS, Ballard RC, Chen CY. Molecular differentiation of Treponema pallidum subspecies in skin ulceration clinically suspected as yaws in Vanuatu using real-time multiplex PCR and serological methods.Am J Trop Med Hyg. 2015 Jan;92(1):134-8. doi: 10.4269/ajtmh.14-0459. Epub 2014 Nov 17.
4WHO (1960) Technical Report Series no. 190: Expert Committee on venereal infections and treponematoses (fifth report). Geneva: World Health Organization. Available: http://whqlibdoc.who.int/trs/WHO_TRS_190.pdf
5Eradication of yaws in India: http://www.who.int/entity/wer/2015/wer9016.pdf?ua=1
6Mass Treatment with Single-Dose Azithromycin for Yaws: http://www.nejm.org/doi/pdf/10.1056/NEJMoa1408586
7James W. Kazura. Yaws Eradication — A Goal Finally within Reach. N Engl J Med 2015; 372:693-695