The World Health Organization reports that the status of yaws is currently known in only 15 countries, with Liberia and the Philippines as the most recent additions to the list of endemic countries.
The status of 76 previously endemic countries and territories remains unknown. Colombia, Ecuador, and Haiti have recently reported suspected yaws cases [ 15 ]. These countries with unknown yaws status may very well be in a similar situation as the Philippines where yaws is not recognized by health care providers anymore and is therefore unreported. This case series provides valuable information and a guide on the clinical appearance of active yaws among Filipino children and the serological tests needed to confirm the diagnosis in a country where yaws has been a virtually forgotten disease.
Health practitioners who used to recognize yaws are not present anymore. The documentation of adult latent yaws cases also raises awareness among health care providers that patients with reactive treponemal antibodies and non-treponemal antibodies may not have syphilis but may actually have latent yaws infections acquired during childhood in yaws-endemic communities.
The small number of study sites limited our search for yaws and led to underreporting of yaws cases. The WHO recommended diagnostic approach and criteria for confirmation of active yaws cases were used in this study: clinical skin signs compatible with yaws combined with serological confirmation of Treponema pallidum antibodies and non- Treponema pallidum antibodies.
Ideally, polymerase chain reaction PCR to confirm Treponema pallidum pertenue would have to be performed in order to confirm the etiologic agent of yaws-like skin ulcers among children since these may also be caused by Haemophilus ducreyi [ 16 ].
The study did not include PCR confirmation of the etiologic agent of the skin lesions found among the four children with papillomas. None of the detected cases had skin ulcers. PCR was not performed during this study also due to the lack of PCR facilities within the Philippines and the limited budget for the conduct of the yaws study. The investigators are currently planning a collaboration with an international laboratory for future confirmation studies of yaws cases in the Philippines.
The clinical, serological, and histopathological confirmation of four yaws cases among children prove that this disease is endemic in at least two out of nine municipalities of the Liguasan Marsh, Mindanao.
The Philippines is now the 14th country endemic for yaws. With the renewed knowledge about yaws and its public health importance, the national and local health authorities have been continuing the search for more hidden yaws cases and have detected additional active and latent yaws. An ongoing surveillance of yaws cases is being conducted in the rest of the country. Yaws should be taught to health personnel and communities at risk.
The current WHO yaws eradication strategy entails mapping, surveillance, strengthening primary health care services, Targeted or Total Community Treatment with one oral dose of azithromycin and encourages integration with other neglected tropical diseases programs [ 4 ].
Endemic nonvenereal treponematosis. Volume 1, 9th edn. Edited by Kang Sea. Nagreh DS. CAS Google Scholar. Summary report of a consultation on the eradication of yaws. Geneva: World Health Organization; Google Scholar. Google: Map of Liguasan Marsh, Mindanao. In: Google Maps. Accessed 11 Nov Map of the Philippines. Google: Map of the Philippines; Cruz AH. Integration of yaws control into the permanent health structure of the Philippines. Bull World Health Organ. J Philipp Med Assoc.
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World Health Stat Q. Haemophilus ducreyi as a cause of skin ulcers in children from a yaws-endemic area of Papua New Guinea: a prospective cohort study. Lancet Glob Health. Article Google Scholar. Download references.
The funders contributed the research question and general study design. Philippine Leprosy Mission, Inc. You can also search for this author in PubMed Google Scholar. BD developed the study protocol, supervised data collection, analyzed and interpreted data, and was a major contributor in the writing of the manuscript. SK and CT contributed to the study protocol, supervised data collection, analyzed and interpreted the serological tests. JR contributed to the interpretation of the data and writing of the manuscript.
All authors read and approved the final manuscript. Correspondence to Belen Lardizabal Dofitas. Ethical approval was granted by the St. Written informed consent to participate in the study were secured from the parents or guardians of minors and from adult participants.
Written informed consent for publication of study results and photographs were secured from the parents or guardians of minors and from adult participants. Reprints and Permissions. Dofitas, B. During all stages of the newly embraced yaws eradication programmes, regular surveillance and laboratory support is essential to assess the progress and identify lacunae and gaps.
During the mass-treatment phase, active case-finding and treatment campaigns will be organized and diagnosis will be mainly on clinical findings with serological confirmation [62] , [65].
During the verification phase after no new active cases have been reported, a combination of treponemal and nontreponemal serological tests will be required for confirmation of all new clinically suspected cases.
Interruption of transmission of yaws disease is measured by zero reporting of cases consistently for three consecutive years and verified by no sero-reactors among a randomly selected sample of children one to five years old [10] , [98]. If the new rapid dual test accuracy is determined, this could be easier to perform in the field during the verification phase instead of the traditional tests.
The nonvenereal treponematoses continue to be transmitted among rural communities in developing countries and a risk remains for importation of the disease into areas where it is not endemic, and subsequently for local transmission of the etiologic agent. Clinical identification of yaws, bejel, and pinta has important implications regarding diagnostic approach, case management and prevention strategies during implementation of eradication campaigns.
Therefore, the clinical assessment skills among health workers and community agents in endemic areas need to be developed through training courses. In addition, the diagnosis of ETs is difficult and usually requires serological confirmation; a combination of a treponemal and a nontreponemal test is advisable to exclude past-treated infection, but this is challenging in limited-resource settings.
Well-designed studies of diagnostic accuracy are needed for the new rapid and PoC combination assay that add potential value to the standard nontreponemal test because it can be easily performed in the field.
In recent years, much effort has been devoted to the development of molecular techniques that enable health care workers to distinguish between the T. However, at present the use of clinically useful molecular biological techniques that affect turnaround time, diagnosis accuracy, and patient outcome, and reduce overall costs, is not in sight. Further support is needed to facilitate and expedite the practical application of these scientific discoveries to clinical medicine. We thank A.
Abdolrasouli for his kind permission to use clinical photographs in Figure 2. Abstract Improved understanding of the differential diagnosis of endemic treponematoses is needed to inform clinical practice and to ensure the best outcome for a new global initiative for the eradication of yaws, bejel, and pinta.
Funding: The authors have indicated that no funding was received for this work. Introduction Treponematoses are infections caused by the spirochetal organisms of the Treponema species. Epidemiological and Geographical Differences For differentiation of treponematoses, a point that might give some assistance would be residence in an area where one of these treponematoses was preponderant or present to the exclusion of the others.
Download: PPT. Figure 1. Countries with reported data on yaws, bejel, and pinta from to [10] — [29] , [32]. Distinct Clinical Features The clinical symptoms and signs of ETs have been widely described and illustrated Table 1 [1] , [2] , [7].
Table 2. Differential diagnosis for the mucocutaneous manifestations of endemic treponematoses. Direct Diagnostic Methods Direct diagnostic methods are limited by the fact that the T. Serological Tests The serological tests used to diagnose ETs are the same as those used to diagnose syphilis [61]. Whole Genome Sequencing: New Diagnostic Targets Historically, syphilis and yaws treponemes were considered to be separate species based on differences in clinical manifestations of the corresponding diseases , but since they have been classified as subspecies [73] , based on DNA hybridization experiments [74].
Table 3. Genomic features and historic overview of selected genetic differences found in nonvenereal treponemes. Polymerase Chain Reaction Analyses of Clinical Samples During the past 20 years, there has been an increasing effort to apply polymerase chain reaction PCR techniques for direct diagnosis of treponematoses.
Figure 3. Identified genetic loci showing sequence differences in T. Laboratory Support and Approach to Evaluation of the Programme to Eradicate Yaws New WHO yaws eradication strategy and treatment policies for yaws with azithromycin were issued in Discussion The nonvenereal treponematoses continue to be transmitted among rural communities in developing countries and a risk remains for importation of the disease into areas where it is not endemic, and subsequently for local transmission of the etiologic agent.
Learning Points The clinical diagnosis for endemic treponematoses may be difficult because these infections produce lesions which can resemble several other diseases in the tropics; thus, support of laboratory techniques and epidemiologic characteristics is necessary. The serological tests are the same as those used to diagnose syphilis.
The nontreponemal tests are a better indication of active infection and ongoing transmission in an area. Available T. Bull World Health Organ 8: — Am J Trop Med Hyg — J Clin Microbiol — Acknowledgments We thank A. References 1. John RK, Causse G, et al.. Geneva: World Health Organization.
Microbes Infect 4: 83— View Article Google Scholar 3. World Health Organization Accelerating work to overcome the global impact of neglected tropical diseases: a roadmap for implementation — executive summary. View Article Google Scholar 5.
Hackett CJ Extent and nature of the yaws problem in Africa. View Article Google Scholar 8. Hudson H Bejel: syphilis as a contagious disease of children.
View Article Google Scholar 9. Genitourin Med 4—7. View Article Google Scholar Wkly Epidemiol Rec — Wirski WR Surveillance and control of resurgent yaws in the African region. Rev Infect Dis 7: s— P N G Med J — J Trop Med Health education and improvement of social conditions can contribute to halting the spread of the treponematoses. Supportive measures for the eradication of yaws include strengthening access to primary health care, training clinicians to detect and treat patients, general health education, improvement in the standard of living and in personal hygiene, and providing soap, water, and clothing to children.
Monitoring for treatment failure and resistance to azithromycin is important because there is biological evidence that antibiotic pressure can select for resistant strains in T. Macrolide resistance in T. A real-time PCR assay for detection of the above mentioned mutations has been developed that would enable molecular surveillance for rapid identification of macrolide-resistance in T.
Other challenges for eradication will be represented by: 1 incomplete information of the geographic scope of the disease due to inadequate surveillance, 2 the necessity to screen and treat populations difficult to reach, 3 and the possibility that animal reservoirs for human treponemal pathogens may exist.
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Re-emergence of yaws after single mass azithromycin treatment followed by targeted treatment: a longitudinal study.
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