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Oriol Mitjà - One of the best experts on this subject based on the ideXlab platform.
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Yaws in Southeast Asia: Towards Elimination
Neglected Tropical Diseases - East Asia, 2019Co-Authors: Michael Marks, Oriol MitjàAbstract:Yaws is a chronic infectious disease caused by Treponema pallidum subsp. pertenue, which causes disease of the skin, bones, and joints. Most cases are seen in young children living in remote communities in warm humid environments. Yaws is endemic in several countries in Asia, including the Philippines, Indonesia, and Timor-Lester. Azithromycin is now the first line treatment for Yaws and community mass treatment with azithromycin is the central component of the World Health Organization Yaws eradication strategy.
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programmatic goals and spatial epidemiology influence the merit of targeted versus of population wide interventions for Yaws eradication
bioRxiv, 2019Co-Authors: Eric Q Mooring, Oriol Mitjà, Michael Marks, Marcia C Castro, Marc Lipsitch, Megan MurrayAbstract:Abstract Infectious disease eradication programs often pursue spatially targeted interventions, but how well they perform might depend on the underlying spatial epidemiology and the specific goal of the program. We use a stochastic compartmental metapopulation model of Yaws transmission to investigate how total targeted treatment (TTT) performs compared to mass drug administration (MDA) in different settings. While TTT can efficiently control the prevalence of active Yaws disease, we consistently found that multiple rounds of TTT are required to match the impact of 1 round of MDA on the prevalence of latent Yaws infection. When complete eradication of Yaws is the goal, MDA can achieve the same result as TTT more quickly and probably at lower cost. We found that the performance of TTT is improved when there is little mixing between subpopulations and when there is spatial heterogeneity in transmissibility, but even in these settings, our model suggests that MDA will still outperform TTT. Significance Statement Yaws is a neglected tropical disease that causes skin lesions. Eradicating Yaws is challenging because people can be infected but not show any signs or symptoms for years. Using simulations, we found that targeting antibiotics to people with active Yaws and to their neighbors is a good way to combat active Yaws, but treating entire populations is a better way to get rid of all infections, including the hidden ones. Also, targeted treatment works better in populations in which people do not move around much and in which how easily the disease is transmitted varies from place to place. Overall, a targeted treatment strategy uses fewer antibiotics but takes longer than mass treatment to achieve results.
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re emergence of Yaws after single mass azithromycin treatment followed by targeted treatment a longitudinal study
The Lancet, 2018Co-Authors: Oriol Mitjà, Charmie Godornes, Wendy Houinei, Haina Abel, August Kapa, Raymond Paru, Camila Gonzalezbeiras, Sibauk BiebAbstract:Summary Background Yaws is a substantial cause of chronic disfiguring ulcers in children in at least 14 countries in the tropics. WHO's newly adopted strategy for Yaws eradication uses a single round of mass azithromycin treatment followed by targeted treatment programmes, and data from pilot studies have shown a short-term significant reduction of Yaws. We assessed the long-term efficacy of the WHO strategy for Yaws eradication. Methods Between April 15, 2013, and Oct 24, 2016, we did a longitudinal study on a Papua New Guinea island (Lihir; 16 092 population) in which Yaws was endemic. In the initial study, the participants were followed for 12 months; in this extended follow-up study, clinical, serological, and PCR surveys were continued every 6 months for 42 months. We used genotyping and travel history to identify importation events. Active Yaws confirmed by PCR specific for Treponema pallidum was the primary outcome indicator. The study is registered with ClinicalTrials.gov, number NCT01955252. Findings Mass azithromycin treatment (coverage rate of 84%) followed by targeted treatment programmes reduced the prevalence of active Yaws from 1·8% to a minimum of 0·1% at 18 months (difference from baseline −1·7%, 95% CI, −1·9 to −1·4; p Interpretation The implementation of the WHO strategy did not, in the long-term, achieve elimination in a high-endemic community mainly due to the individuals who were absent at the time of mass treatment in whom Yaws reactivated; repeated mass treatment might be necessary to eliminate Yaws. To our knowledge, this is the first report of the emergence of azithromycin-resistant T p pertenue and spread within one village. Communities' surveillance should be strengthened to detect any possible treatment failure and biological markers of resistance. Funding ISDIN laboratories, Newcrest Mining Limited, and US Public Health Service National Institutes of Health.
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development of a multilocus sequence typing mlst scheme for treponema pallidum subsp pertenue application to Yaws in lihir island papua new guinea
PLOS Neglected Tropical Diseases, 2017Co-Authors: Charmie Godornes, Oriol Mitjà, Lorenzo Giacani, Alyssa E Arry, Sheila A LukehaAbstract:Background Yaws is a neglected tropical disease, caused by Treponema pallidum subsp. pertenue. The disease causes chronic lesions, primarily in young children living in remote villages in tropical climates. As part of a global Yaws eradication campaign initiated by the World Health Organization, we sought to develop and evaluate a molecular typing method to distinguish different strains of T. pallidum subsp. pertenue for disease control and epidemiological purposes. Methods and principal findings Published genome sequences of strains of T. pallidum subsp. pertenue and pallidum were compared to identify polymorphic genetic loci among the strains. DNA from a number of existing historical Treponema isolates, as well as a subset of samples from Yaws patients collected in Lihir Island, Papua New Guinea, were analyzed using these targets. From these data, three genes (tp0548, tp0136 and tp0326) were ultimately selected to give a high discriminating capability among the T. pallidum subsp. pertenue samples tested. Intragenic regions of these three target genes were then selected to enhance the discriminating capability of the typing scheme using short readily amplifiable loci. This 3-gene multilocus sequence typing (MLST) method was applied to existing historical human Yaws strains, the Fribourg-Blanc simian isolate, and DNA from 194 lesion swabs from Yaws patients on Lihir Island, Papua New Guinea. Among all samples tested, fourteen molecular types were identified, seven of which were found in patient samples and seven among historical isolates or DNA. Three types (JG8, TD6, and SE7) were predominant on Lihir Island. Conclusions This MLST approach allows molecular typing and differentiation of Yaws strains. This method could be a useful tool to complement epidemiological studies in regions where T. pallidum subsp. pertenue is prevalent with the overall goals of improving our understanding of Yaws transmission dynamics and helping the Yaws eradication campaign to succeed.
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Effectiveness of single-dose azithromycin to treat latent Yaws: a longitudinal comparative cohort study
The Lancet. Global health, 2017Co-Authors: Oriol Mitjà, Camila González-beiras, Charmie Godornes, Reman Kolmau, Wendy Houinei, Haina Abel, August Kapa, Raymond Paru, Sibauk Bieb, James WangiAbstract:Summary Background Treatment of latent Yaws is a crucial component of the WHO Yaws eradication strategy to prevent relapse and the resulting transmission to uninfected children. We assessed the effectiveness of single-dose azithromycin to treat patients with latent Yaws. Methods This population-based cohort study included children (age Treponema pallidum subsp pertenue on PCR, and active Yaws was defined as ulcers positive for T pertenue on PCR. All children received one oral dose of 30 mg/kg azithromycin. The primary endpoint was serological cure, defined as a two-dilution decrease in rapid plasma reagin titre by 24 months after treatment. Treatment of latent Yaws was taken to be non-inferior to that of active Yaws if the lower limit of the two-sided 95% CI for the difference in rates was higher than or equal to −10%. This study is registered with ClinicalTrials.gov, number NCT01955252. Findings Of 311 participants enrolled, 273 (88%; 165 with latent Yaws and 108 with active Yaws) completed follow-up. The primary endpoint was achieved in 151 (92%) participants with latent Yaws and 101 (94%) with active Yaws (risk difference −2·0%, 95% CI −8·3 to 4·3), meeting the prespecified criteria for non-inferiority. Interpretation On the basis of decline in serological titre, oral single-dose azithromycin was effective in participants with latent Yaws. This finding supports the WHO strategy for the eradication of Yaws based on mass administration of the entire endemic community irrespective of clinical status. Funding Newcrest Mining Limited and ISDIN laboratories.
Michael Marks - One of the best experts on this subject based on the ideXlab platform.
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Yaws in Southeast Asia: Towards Elimination
Neglected Tropical Diseases - East Asia, 2019Co-Authors: Michael Marks, Oriol MitjàAbstract:Yaws is a chronic infectious disease caused by Treponema pallidum subsp. pertenue, which causes disease of the skin, bones, and joints. Most cases are seen in young children living in remote communities in warm humid environments. Yaws is endemic in several countries in Asia, including the Philippines, Indonesia, and Timor-Lester. Azithromycin is now the first line treatment for Yaws and community mass treatment with azithromycin is the central component of the World Health Organization Yaws eradication strategy.
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programmatic goals and spatial epidemiology influence the merit of targeted versus of population wide interventions for Yaws eradication
bioRxiv, 2019Co-Authors: Eric Q Mooring, Oriol Mitjà, Michael Marks, Marcia C Castro, Marc Lipsitch, Megan MurrayAbstract:Abstract Infectious disease eradication programs often pursue spatially targeted interventions, but how well they perform might depend on the underlying spatial epidemiology and the specific goal of the program. We use a stochastic compartmental metapopulation model of Yaws transmission to investigate how total targeted treatment (TTT) performs compared to mass drug administration (MDA) in different settings. While TTT can efficiently control the prevalence of active Yaws disease, we consistently found that multiple rounds of TTT are required to match the impact of 1 round of MDA on the prevalence of latent Yaws infection. When complete eradication of Yaws is the goal, MDA can achieve the same result as TTT more quickly and probably at lower cost. We found that the performance of TTT is improved when there is little mixing between subpopulations and when there is spatial heterogeneity in transmissibility, but even in these settings, our model suggests that MDA will still outperform TTT. Significance Statement Yaws is a neglected tropical disease that causes skin lesions. Eradicating Yaws is challenging because people can be infected but not show any signs or symptoms for years. Using simulations, we found that targeting antibiotics to people with active Yaws and to their neighbors is a good way to combat active Yaws, but treating entire populations is a better way to get rid of all infections, including the hidden ones. Also, targeted treatment works better in populations in which people do not move around much and in which how easily the disease is transmitted varies from place to place. Overall, a targeted treatment strategy uses fewer antibiotics but takes longer than mass treatment to achieve results.
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Advances in the Treatment of Yaws.
Tropical medicine and infectious disease, 2018Co-Authors: Michael MarksAbstract:Yaws is one of the three endemic treponematoses and is recognised by the World Health Organization as a neglected tropical disease. Yaws is currently reported in 15 countries in the Pacific, South-East Asia, West and Central Africa, predominantly affects children, and results in destructive lesions of the skin and soft tissues. For most of the twentieth century penicillin-based treatment was the standard of care and resistance to penicillin has still not been described. Recently, oral azithromycin has been shown to be an effective treatment for Yaws, facilitating renewed Yaws eradication efforts. Resistance to azithromycin is an emerging threat and close surveillance will be required as Yaws eradication efforts are scaled up globally.
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Knowledge, attitudes and practices towards Yaws and Yaws-like skin disease in Ghana.
PLoS neglected tropical diseases, 2017Co-Authors: Michael Marks, Oriol Mitjà, Cynthia Kwakye-maclean, Rachel Doherty, Paul Adwere, Abdul Aziz Abdulai, Fredrick Duah, Sally-ann Ohene, Blanche Oguti, Anthony W. SolomonAbstract:Introduction Yaws is endemic in Ghana. The World Health Organization (WHO) has launched a new global eradication campaign based on total community mass treatment with azithromycin. Achieving high coverage of mass treatment will be fundamental to the success of this new strategy; coverage is dependent, in part, on appropriate community mobilisation. An understanding of community knowledge, attitudes and practices related to Yaws in Ghana and other endemic countries will be vital in designing effective community engagement strategies. Methods A verbally administered questionnaire was administered to residents in 3 districts in the Eastern region of Ghana where a randomised trial on the treatment of Yaws was being conducted. The questionnaire combined both quantitative and qualitative questions covering perceptions of the cause and mechanisms of transmission of Yaws-like lesions, the providers from which individuals would seek healthcare for Yaws-like lesions, and what factors were important in reaching decisions on where to seek care. Chi-square tests and logistic regression were used to assess relationships between reported knowledge, attitudes and practices, and demographic variables. Thematic analysis of qualitative data was used to identify common themes. Results A total of 1,162 individuals participated. The majority of individuals (n = 895, 77%) reported that “germs” were the cause of Yaws lesions. Overall 13% (n = 161) of respondents believed that the disease was caused by supernatural forces. Participants frequently mentioned lack of personal hygiene, irregular and inefficient bathing, and washing with dirty water as fundamental to both the cause and the prevention of Yaws. A majority of individuals reported that they would want to take an antibiotic to prevent the development of Yaws if they were asymptomatic (n = 689, 61.2%), but a substantial minority reported they would not want to do so. A majority of individuals (n = 839, 72.7%) reported that if they had a Yaws-like skin lesion they would seek care from a doctor or nurse. Both direct and indirect costs of treatment were reported as key factors affecting where participants reported they would seek care. Discussion This is the first study that has explored community knowledge, attitudes and practices in relation to Yaws in any endemic population. The belief that ‘germs’ are in some way related to disease through a variety of transmission routes including both contact and dirty water are similar to those reported for other skin diseases in Ghana. The prominent role of private healthcare providers is an important finding of this study and suggests engagement with this sector will be important in Yaws eradication efforts. Strategies to address the substantial minority of individuals who reported they would not take treatment for Yaws if they were currently asymptomatic will be needed to ensure the success of Yaws eradication efforts. The data collected will be of value to the Ghana Health Service and also to WHO and other partners, who are currently developing community mobilisation tools to support Yaws eradication efforts worldwide.
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integrated mapping of Yaws and trachoma in the five northern most provinces of vanuatu
PLOS Neglected Tropical Diseases, 2017Co-Authors: Fasihah Taleo, Michael Marks, Oliver Sokana, Colin K Macleod, Rebecca Willis, Mackline Garae, Annie Bong, Brian K Chu, Paul Courtright, Jacob L KoolAbstract:Yaws and trachoma are targeted for eradication and elimination as public health problems. In trachoma-endemic populations mass administration of azithromycin can simultaneously treat Yaws. We conducted a population-based prevalence survey in the five northernmost provinces of Vanuatu, where trachoma and Yaws are suspected to be co-endemic. Clinical signs of trachoma were evaluated using the WHO simplified grading system, and skin examination with a serological rapid diagnostic test used to identify Yaws. We enrolled 1004 households in 59 villages over 16 islands, and examined 3650 individuals of all ages for trachoma. The overall adjusted prevalence of trachomatous inflammation-follicular (TF) in 1-9 year-olds was 12.0% (95% Confidence Interval: 8.1-16.7%), and the overall adjusted prevalence of TT in those aged 15 years and greater was 0.04% (95% CI 0-0.14%). In multivariate analysis, the odds of children having TF was 2.6 (95% CI = 1.5-4.4) times higher in households with unimproved latrines, and independently associated with the number of children in the household (OR 1.3, 95% CI = 1.0-1.6 for each additional child). We examined the skin of 821 children aged 5-14 years. Two children had Yaws, giving an estimated prevalence of active Yaws in those aged 5-14 years of 0.2% (95% CI = 0.03-0.9%). Mass treatment with azithromycin is recommended in these provinces. Given the apparent low burden of Yaws, integration of Yaws and trachoma control programmes is likely to be useful and cost-effective to national programmes.
Anthony W. Solomon - One of the best experts on this subject based on the ideXlab platform.
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Knowledge, attitudes and practices towards Yaws and Yaws-like skin disease in Ghana.
PLoS neglected tropical diseases, 2017Co-Authors: Michael Marks, Oriol Mitjà, Cynthia Kwakye-maclean, Rachel Doherty, Paul Adwere, Abdul Aziz Abdulai, Fredrick Duah, Sally-ann Ohene, Blanche Oguti, Anthony W. SolomonAbstract:Introduction Yaws is endemic in Ghana. The World Health Organization (WHO) has launched a new global eradication campaign based on total community mass treatment with azithromycin. Achieving high coverage of mass treatment will be fundamental to the success of this new strategy; coverage is dependent, in part, on appropriate community mobilisation. An understanding of community knowledge, attitudes and practices related to Yaws in Ghana and other endemic countries will be vital in designing effective community engagement strategies. Methods A verbally administered questionnaire was administered to residents in 3 districts in the Eastern region of Ghana where a randomised trial on the treatment of Yaws was being conducted. The questionnaire combined both quantitative and qualitative questions covering perceptions of the cause and mechanisms of transmission of Yaws-like lesions, the providers from which individuals would seek healthcare for Yaws-like lesions, and what factors were important in reaching decisions on where to seek care. Chi-square tests and logistic regression were used to assess relationships between reported knowledge, attitudes and practices, and demographic variables. Thematic analysis of qualitative data was used to identify common themes. Results A total of 1,162 individuals participated. The majority of individuals (n = 895, 77%) reported that “germs” were the cause of Yaws lesions. Overall 13% (n = 161) of respondents believed that the disease was caused by supernatural forces. Participants frequently mentioned lack of personal hygiene, irregular and inefficient bathing, and washing with dirty water as fundamental to both the cause and the prevention of Yaws. A majority of individuals reported that they would want to take an antibiotic to prevent the development of Yaws if they were asymptomatic (n = 689, 61.2%), but a substantial minority reported they would not want to do so. A majority of individuals (n = 839, 72.7%) reported that if they had a Yaws-like skin lesion they would seek care from a doctor or nurse. Both direct and indirect costs of treatment were reported as key factors affecting where participants reported they would seek care. Discussion This is the first study that has explored community knowledge, attitudes and practices in relation to Yaws in any endemic population. The belief that ‘germs’ are in some way related to disease through a variety of transmission routes including both contact and dirty water are similar to those reported for other skin diseases in Ghana. The prominent role of private healthcare providers is an important finding of this study and suggests engagement with this sector will be important in Yaws eradication efforts. Strategies to address the substantial minority of individuals who reported they would not take treatment for Yaws if they were currently asymptomatic will be needed to ensure the success of Yaws eradication efforts. The data collected will be of value to the Ghana Health Service and also to WHO and other partners, who are currently developing community mobilisation tools to support Yaws eradication efforts worldwide.
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ducreyi Associated with Skin Ulcers among Children, Solomon Islands
2016Co-Authors: Michael Marks, Ventis Vahi, Oliver Sokana, Alex Pavluck, Anthony W. Solomon, Kaihua Chi, Cheng Y Chen, Allan Pillay, David C. Mabey, Solomon IslandsAbstract:During a survey of Yaws prevalence in the Solomon Is-lands, we collected samples from skin ulcers of 41 children. Using PCR, we identified Haemophilus ducreyi infection in 13 (32%) children. PCR-positive and PCR-negative ulcers were phenotypically indistinguishable. Emergence of H. du-creyi as a cause of nongenital ulcers may affect the World Health Organization’s Yaws eradication program. Bacterial ulcerative skin diseases are a common cause of illness in the developing world (1). Some of these diseases, including Buruli ulcer, caused by Mycobacterium ulcerans, and Yaws, caused by Treponema pallidum sub-species pertenue, occur only in tropical and subtropical climates. Yaws is endemic in the Solomon Islands, where ≈15,000 cases per year are reported (2). In 2012, the World Health Organization (WHO) launched a worldwide Yaws eradication program based on treatment by mass distribu-tion of azithromycin and monitoring for skin ulcers (3). Reports suggest that Haemophilus ducreyi, the caus-ative organism of chancroid, a sexually transmitted infec-tion, may be associated with nonsexual transmission of nongenital ulcers of the skin in persons from the Pacific region (4,5). If this organism is a common cause of skin ulcers in the region, this factor has crucial implications for the Yaws eradication strategy. PCR has been shown to be highly sensitive and specific for diagnosing chancroid (6). We used real-time PCR to detect H. ducreyi in skin ulcer samples collected during a survey for Yaws in th
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trachoma and Yaws common ground
PLOS Neglected Tropical Diseases, 2015Co-Authors: Anthony W. Solomon, Oriol Mitjà, Kingsley Asiedu, Michael Marks, Diana L Martin, Alexei Mikhailov, Rebecca M Flueckiger, Jean Jannin, Dirk EngelsAbstract:Trachoma is an important cause of blindness. The causative organism is an intracellular bacterium, Chlamydia trachomatis, which is susceptible to single-dose azithromycin [1]. A World Health Organization (WHO)-led program aims to eliminate trachoma as a public health problem globally by 2020 [2]. Yaws is a cause of skin, bone, and cartilage disease. The causative organism is a spirochaete bacterium, Treponema pallidum ssp. pertenue, which is susceptible to single-dose azithromycin [3]. A WHO-led program aims to eradicate Yaws globally by 2020 [4]. These diseases are both found in hard-to-reach populations—they affect the poorest people living in the most remote areas of the countries where they’re found—and have some apparent similarity in the methods recommended to counter them. Maximum synergy between programs is possible only if the two diseases affect the same communities, and if program goals permit alignment of work. Trachoma’s elimination as a public health problem means “the reduction of disease incidence, prevalence, morbidity or mortality to a locally acceptable level as a result of deliberate efforts” [5], whereas Yaws eradication requires “permanent reduction to zero of the worldwide incidence of infection caused by a specific agent as a result of deliberate efforts” [5]—a quite different goal. This symposium reviews the extent to which the epidemiologies of and management strategies for these diseases actually overlap, to determine areas for mutually beneficial collaboration.
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impact of community mass treatment with azithromycin for trachoma elimination on the prevalence of Yaws
PLOS Neglected Tropical Diseases, 2015Co-Authors: Michael Marks, Ventis Vahi, Oliver Sokana, Elliot Puiahi, Tenneth Dalipanda, Christian Bottomley, Kaihua Chi, Allan Pillay, Georgina Kilua, Anthony W. SolomonAbstract:BACKGROUND: Community mass treatment with 30 mg/kg azithromycin is central to the new WHO strategy for eradicating Yaws. Both Yaws and trachoma--which is earmarked for elimination by 2020 using a strategy that includes mass treatment with 20 mg/kg azithromycin--are endemic in the Pacific, raising the possibility of an integrated approach to disease control. Community mass treatment with azithromycin for trachoma elimination was conducted in the Solomon Islands in 2014. METHODS: We conducted a study to assess the impact of mass treatment with 20 mg/kg azithromycin on Yaws. We examined children aged 5-14 years and took blood and lesion samples for Yaws diagnosis. RESULTS: We recruited 897 children, 6 months after mass treatment. There were no cases of active Yaws. Serological evidence of current infection was found in 3.6% (95% CI= 2.5-5.0%). This differed significantly between individuals who had and had not received azithromycin (2.8% vs 6.5%, p=0.015); the prevalence of positive serology in 5-14 year-olds had been 21.7% (95% CI=14.6%-30.9%) 6 months prior to mass treatment. Not receiving azithromycin was associated with an odds of 3.9 for infection (p=0.001). National figures showed a 57% reduction in reported cases of Yaws following mass treatment. DISCUSSION: Following a single round of treatment we did not identify any cases of active Yaws in a previously endemic population. We found a significant reduction in latent infection. Our data support expansion of the WHO eradication strategy and suggest an integrated approach to the control of Yaws and trachoma in the Pacific may be viable.
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failure of pcr to detect treponema pallidum ssp pertenue dna in blood in latent Yaws
PLOS Neglected Tropical Diseases, 2015Co-Authors: Michael Marks, Ventis Vahi, David Mabey, Anthony W. Solomon, Samantha S Katz, Kaihua Chi, Yongcheng Sun, Cheng Y Chen, Allan PillayAbstract:Yaws, caused by Treponema pallidum ssp. pertenue, is a neglected tropical disease closely related to venereal syphilis and is targeted for eradication by 2020. Latent Yaws represents a diagnostic challenge, and current tools cannot adequately distinguish between individuals with true latent infection and individuals who are serofast following successful treatment. PCR on blood has previously been shown to detect T. pallidum DNA in patients with syphilis, suggesting that this approach may be of value in Yaws. We performed real-time PCR for Treponema pallidum ssp. pertenue on blood samples from 140 children with positive T. pallidum Particle Agglutination (TPPA) and Rapid Plasma Reagin (RPR) tests and 7 controls (negative serology), all collected as part of a prospective study of Yaws in the Solomon Islands. All samples were also tested by a nested PCR for T. pallidum. 12 patients had clinical evidence of active Yaws whilst 128 were considered to have latent Yaws. 43 children had high titre rapid plasma reagins (RPRs) of ≥1:32. PCR testing with both assays gave negative results in all cases. It is possible that the failure to detect T. pallidum ssp. pertenue in blood reflects lower loads of organism in latent Yaws compared to those in latent infection with T. pallidum ssp. pertenue, and/or a lower propensity for haematogenous dissemination in Yaws than in syphilis. As the goal of the Yaws control programme is eradication, a tool that can differentiate true latent infection from individuals who are serofast would be of value; however, PCR of blood is not that tool.
Wendy Houinei - One of the best experts on this subject based on the ideXlab platform.
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re emergence of Yaws after single mass azithromycin treatment followed by targeted treatment a longitudinal study
The Lancet, 2018Co-Authors: Oriol Mitjà, Charmie Godornes, Wendy Houinei, Haina Abel, August Kapa, Raymond Paru, Camila Gonzalezbeiras, Sibauk BiebAbstract:Summary Background Yaws is a substantial cause of chronic disfiguring ulcers in children in at least 14 countries in the tropics. WHO's newly adopted strategy for Yaws eradication uses a single round of mass azithromycin treatment followed by targeted treatment programmes, and data from pilot studies have shown a short-term significant reduction of Yaws. We assessed the long-term efficacy of the WHO strategy for Yaws eradication. Methods Between April 15, 2013, and Oct 24, 2016, we did a longitudinal study on a Papua New Guinea island (Lihir; 16 092 population) in which Yaws was endemic. In the initial study, the participants were followed for 12 months; in this extended follow-up study, clinical, serological, and PCR surveys were continued every 6 months for 42 months. We used genotyping and travel history to identify importation events. Active Yaws confirmed by PCR specific for Treponema pallidum was the primary outcome indicator. The study is registered with ClinicalTrials.gov, number NCT01955252. Findings Mass azithromycin treatment (coverage rate of 84%) followed by targeted treatment programmes reduced the prevalence of active Yaws from 1·8% to a minimum of 0·1% at 18 months (difference from baseline −1·7%, 95% CI, −1·9 to −1·4; p Interpretation The implementation of the WHO strategy did not, in the long-term, achieve elimination in a high-endemic community mainly due to the individuals who were absent at the time of mass treatment in whom Yaws reactivated; repeated mass treatment might be necessary to eliminate Yaws. To our knowledge, this is the first report of the emergence of azithromycin-resistant T p pertenue and spread within one village. Communities' surveillance should be strengthened to detect any possible treatment failure and biological markers of resistance. Funding ISDIN laboratories, Newcrest Mining Limited, and US Public Health Service National Institutes of Health.
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Effectiveness of single-dose azithromycin to treat latent Yaws: a longitudinal comparative cohort study
The Lancet. Global health, 2017Co-Authors: Oriol Mitjà, Camila González-beiras, Charmie Godornes, Reman Kolmau, Wendy Houinei, Haina Abel, August Kapa, Raymond Paru, Sibauk Bieb, James WangiAbstract:Summary Background Treatment of latent Yaws is a crucial component of the WHO Yaws eradication strategy to prevent relapse and the resulting transmission to uninfected children. We assessed the effectiveness of single-dose azithromycin to treat patients with latent Yaws. Methods This population-based cohort study included children (age Treponema pallidum subsp pertenue on PCR, and active Yaws was defined as ulcers positive for T pertenue on PCR. All children received one oral dose of 30 mg/kg azithromycin. The primary endpoint was serological cure, defined as a two-dilution decrease in rapid plasma reagin titre by 24 months after treatment. Treatment of latent Yaws was taken to be non-inferior to that of active Yaws if the lower limit of the two-sided 95% CI for the difference in rates was higher than or equal to −10%. This study is registered with ClinicalTrials.gov, number NCT01955252. Findings Of 311 participants enrolled, 273 (88%; 165 with latent Yaws and 108 with active Yaws) completed follow-up. The primary endpoint was achieved in 151 (92%) participants with latent Yaws and 101 (94%) with active Yaws (risk difference −2·0%, 95% CI −8·3 to 4·3), meeting the prespecified criteria for non-inferiority. Interpretation On the basis of decline in serological titre, oral single-dose azithromycin was effective in participants with latent Yaws. This finding supports the WHO strategy for the eradication of Yaws based on mass administration of the entire endemic community irrespective of clinical status. Funding Newcrest Mining Limited and ISDIN laboratories.
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Mass Treatment with Single-Dose Azithromycin for Yaws
The New England journal of medicine, 2015Co-Authors: Oriol Mitjà, Wendy Houinei, August Kapa, Raymond Paru, Sibauk Bieb, Penias Moses, Russell Hays, Sheila A. Lukehart, Charmine Godornes, Tim A. GriceAbstract:Mass treatment with azithromycin is a central component of the new World Health Organization (WHO) strategy to eradicate Yaws. Empirical data on the effectiveness of the strategy are required as a prerequisite for worldwide implementation of the plan. METHODS We performed repeated clinical surveys for active Yaws, serologic surveys for latent Yaws, and molecular analyses to determine the cause of skin ulcers and identify macrolide-resistant mutations before and 6 and 12 months after mass treatment with azithromycin on a Papua New Guinean island on which Yaws was endemic. Primary-outcome indicators were the prevalence of serologically confirmed active infectious Yaws in the entire population and the prevalence of latent Yaws with high-titer seroreactivity in a subgroup of children 1 to 15 years of age. RESULTS At baseline, 13,302 of 16,092 residents (82.7%) received one oral dose of azithromycin. The prevalence of active infectious Yaws was reduced from 2.4% before mass treatment to 0.3% at 12 months (difference, 2.1 percentage points; P
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mass treatment with single dose azithromycin for Yaws
The New England Journal of Medicine, 2015Co-Authors: Oriol Mitjà, Wendy Houinei, August Kapa, Raymond Paru, Sibauk Bieb, Penias Moses, Russell Hays, Sheila A. Lukehart, Charmine Godornes, Tim A. GriceAbstract:Mass treatment with azithromycin is a central component of the new World Health Organization (WHO) strategy to eradicate Yaws. Empirical data on the effectiveness of the strategy are required as a prerequisite for worldwide implementation of the plan. METHODS We performed repeated clinical surveys for active Yaws, serologic surveys for latent Yaws, and molecular analyses to determine the cause of skin ulcers and identify macrolide-resistant mutations before and 6 and 12 months after mass treatment with azithromycin on a Papua New Guinean island on which Yaws was endemic. Primary-outcome indicators were the prevalence of serologically confirmed active infectious Yaws in the entire population and the prevalence of latent Yaws with high-titer seroreactivity in a subgroup of children 1 to 15 years of age. RESULTS At baseline, 13,302 of 16,092 residents (82.7%) received one oral dose of azithromycin. The prevalence of active infectious Yaws was reduced from 2.4% before mass treatment to 0.3% at 12 months (difference, 2.1 percentage points; P<0.001). The prevalence of high-titer latent Yaws among children was reduced from 18.3% to 6.5% (difference, 11.8 percentage points; P<0.001) with a near-absence of high-titer seroreactivity in children 1 to 5 years of age. Adverse events identified within 1 week after administration of the medication occurred in approximately 17% of the participants, included nausea, diarrhea, and vomiting, and were mild in severity. No evidence of emergence of resistance to macrolides against Treponema pallidum subspecies pertenue was seen. CONCLUSIONS The prevalence of active and latent Yaws infection fell rapidly and substantially 12 months after high-coverage mass treatment with azithromycin, with the reduction perhaps aided by subsequent activities to identify and treat new cases of Yaws. Our results support the WHO strategy for the eradication of Yaws. (Funded by Newcrest Mining and International SOS; YESA-13 ClinicalTrials.gov number, NCT01955252.)
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Global epidemiology of Yaws : a systematic review
The Lancet. Global health, 2015Co-Authors: Oriol Mitjà, Camila González-beiras, Wendy Houinei, Michael Marks, Diby Jean Paul Konan, Gilbert Adjimon Ayelo, Bernard Boua, Yiragnima Kobara, Earnest Njih Tabah, Agana NsiireAbstract:Summary Background To achieve Yaws eradication, the use of the new WHO strategy of initial mass treatment with azithromycin and surveillance twice a year needs to be extended everywhere the disease occurs. However, the geographic scope of the disease is unknown. We aimed to synthesise published and unpublished work to update the reported number of people with Yaws at national and subnational levels and to estimate at-risk populations. Methods We searched PubMed and WHO databases to identify published data for prevalence of active and latent Yaws from Jan 1, 1990, to Dec 31, 2014. We also searched for ongoing or recently completed unpublished studies from the WHO Yaws surveillance network. We estimated Yaws prevalence (and 95% CIs). We collected Yaws incidence data from official national surveillance programmes at the first administrative level from Jan 1, 2010, to Dec 31, 2013, and we used total population data at the second administrative level to estimate the size of at-risk populations. Findings We identified 103 records, of which 23 published articles describing 27 studies and four unpublished studies met the inclusion criteria. Prevalence of active disease ranged from 0·31% to 14·54% in Yaws-endemic areas, and prevalence of latent Yaws ranged from 2·45% to 31·05%. During 2010–13, 256 343 Yaws cases were reported to WHO from 13 endemic countries, all of which are low-income and middle-income countries. 215 308 (84%) of 256 343 cases reported to WHO were from three countries—Papua New Guinea, Solomon Islands, and Ghana. We estimated that, in 2012, over 89 million people were living in Yaws-endemic districts. Interpretation Papua New Guinea, Solomon Islands, and Ghana should be the focus of initial efforts at implementing the WHO Yaws eradication strategy. Community-based mapping and active surveillance must accompany the implementation of Yaws eradication activities. Funding None.
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re emergence of Yaws after single mass azithromycin treatment followed by targeted treatment a longitudinal study
The Lancet, 2018Co-Authors: Oriol Mitjà, Charmie Godornes, Wendy Houinei, Haina Abel, August Kapa, Raymond Paru, Camila Gonzalezbeiras, Sibauk BiebAbstract:Summary Background Yaws is a substantial cause of chronic disfiguring ulcers in children in at least 14 countries in the tropics. WHO's newly adopted strategy for Yaws eradication uses a single round of mass azithromycin treatment followed by targeted treatment programmes, and data from pilot studies have shown a short-term significant reduction of Yaws. We assessed the long-term efficacy of the WHO strategy for Yaws eradication. Methods Between April 15, 2013, and Oct 24, 2016, we did a longitudinal study on a Papua New Guinea island (Lihir; 16 092 population) in which Yaws was endemic. In the initial study, the participants were followed for 12 months; in this extended follow-up study, clinical, serological, and PCR surveys were continued every 6 months for 42 months. We used genotyping and travel history to identify importation events. Active Yaws confirmed by PCR specific for Treponema pallidum was the primary outcome indicator. The study is registered with ClinicalTrials.gov, number NCT01955252. Findings Mass azithromycin treatment (coverage rate of 84%) followed by targeted treatment programmes reduced the prevalence of active Yaws from 1·8% to a minimum of 0·1% at 18 months (difference from baseline −1·7%, 95% CI, −1·9 to −1·4; p Interpretation The implementation of the WHO strategy did not, in the long-term, achieve elimination in a high-endemic community mainly due to the individuals who were absent at the time of mass treatment in whom Yaws reactivated; repeated mass treatment might be necessary to eliminate Yaws. To our knowledge, this is the first report of the emergence of azithromycin-resistant T p pertenue and spread within one village. Communities' surveillance should be strengthened to detect any possible treatment failure and biological markers of resistance. Funding ISDIN laboratories, Newcrest Mining Limited, and US Public Health Service National Institutes of Health.
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Effectiveness of single-dose azithromycin to treat latent Yaws: a longitudinal comparative cohort study
The Lancet. Global health, 2017Co-Authors: Oriol Mitjà, Camila González-beiras, Charmie Godornes, Reman Kolmau, Wendy Houinei, Haina Abel, August Kapa, Raymond Paru, Sibauk Bieb, James WangiAbstract:Summary Background Treatment of latent Yaws is a crucial component of the WHO Yaws eradication strategy to prevent relapse and the resulting transmission to uninfected children. We assessed the effectiveness of single-dose azithromycin to treat patients with latent Yaws. Methods This population-based cohort study included children (age Treponema pallidum subsp pertenue on PCR, and active Yaws was defined as ulcers positive for T pertenue on PCR. All children received one oral dose of 30 mg/kg azithromycin. The primary endpoint was serological cure, defined as a two-dilution decrease in rapid plasma reagin titre by 24 months after treatment. Treatment of latent Yaws was taken to be non-inferior to that of active Yaws if the lower limit of the two-sided 95% CI for the difference in rates was higher than or equal to −10%. This study is registered with ClinicalTrials.gov, number NCT01955252. Findings Of 311 participants enrolled, 273 (88%; 165 with latent Yaws and 108 with active Yaws) completed follow-up. The primary endpoint was achieved in 151 (92%) participants with latent Yaws and 101 (94%) with active Yaws (risk difference −2·0%, 95% CI −8·3 to 4·3), meeting the prespecified criteria for non-inferiority. Interpretation On the basis of decline in serological titre, oral single-dose azithromycin was effective in participants with latent Yaws. This finding supports the WHO strategy for the eradication of Yaws based on mass administration of the entire endemic community irrespective of clinical status. Funding Newcrest Mining Limited and ISDIN laboratories.
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Mass Treatment with Single-Dose Azithromycin for Yaws
The New England journal of medicine, 2015Co-Authors: Oriol Mitjà, Wendy Houinei, August Kapa, Raymond Paru, Sibauk Bieb, Penias Moses, Russell Hays, Sheila A. Lukehart, Charmine Godornes, Tim A. GriceAbstract:Mass treatment with azithromycin is a central component of the new World Health Organization (WHO) strategy to eradicate Yaws. Empirical data on the effectiveness of the strategy are required as a prerequisite for worldwide implementation of the plan. METHODS We performed repeated clinical surveys for active Yaws, serologic surveys for latent Yaws, and molecular analyses to determine the cause of skin ulcers and identify macrolide-resistant mutations before and 6 and 12 months after mass treatment with azithromycin on a Papua New Guinean island on which Yaws was endemic. Primary-outcome indicators were the prevalence of serologically confirmed active infectious Yaws in the entire population and the prevalence of latent Yaws with high-titer seroreactivity in a subgroup of children 1 to 15 years of age. RESULTS At baseline, 13,302 of 16,092 residents (82.7%) received one oral dose of azithromycin. The prevalence of active infectious Yaws was reduced from 2.4% before mass treatment to 0.3% at 12 months (difference, 2.1 percentage points; P
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mass treatment with single dose azithromycin for Yaws
The New England Journal of Medicine, 2015Co-Authors: Oriol Mitjà, Wendy Houinei, August Kapa, Raymond Paru, Sibauk Bieb, Penias Moses, Russell Hays, Sheila A. Lukehart, Charmine Godornes, Tim A. GriceAbstract:Mass treatment with azithromycin is a central component of the new World Health Organization (WHO) strategy to eradicate Yaws. Empirical data on the effectiveness of the strategy are required as a prerequisite for worldwide implementation of the plan. METHODS We performed repeated clinical surveys for active Yaws, serologic surveys for latent Yaws, and molecular analyses to determine the cause of skin ulcers and identify macrolide-resistant mutations before and 6 and 12 months after mass treatment with azithromycin on a Papua New Guinean island on which Yaws was endemic. Primary-outcome indicators were the prevalence of serologically confirmed active infectious Yaws in the entire population and the prevalence of latent Yaws with high-titer seroreactivity in a subgroup of children 1 to 15 years of age. RESULTS At baseline, 13,302 of 16,092 residents (82.7%) received one oral dose of azithromycin. The prevalence of active infectious Yaws was reduced from 2.4% before mass treatment to 0.3% at 12 months (difference, 2.1 percentage points; P<0.001). The prevalence of high-titer latent Yaws among children was reduced from 18.3% to 6.5% (difference, 11.8 percentage points; P<0.001) with a near-absence of high-titer seroreactivity in children 1 to 5 years of age. Adverse events identified within 1 week after administration of the medication occurred in approximately 17% of the participants, included nausea, diarrhea, and vomiting, and were mild in severity. No evidence of emergence of resistance to macrolides against Treponema pallidum subspecies pertenue was seen. CONCLUSIONS The prevalence of active and latent Yaws infection fell rapidly and substantially 12 months after high-coverage mass treatment with azithromycin, with the reduction perhaps aided by subsequent activities to identify and treat new cases of Yaws. Our results support the WHO strategy for the eradication of Yaws. (Funded by Newcrest Mining and International SOS; YESA-13 ClinicalTrials.gov number, NCT01955252.)
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haemophilus ducreyi as a cause of skin ulcers in children from a Yaws endemic area of papua new guinea a prospective cohort study
The Lancet Global Health, 2014Co-Authors: Oriol Mitjà, Charmie Godornes, August Kapa, Penias Moses, Sheila A. Lukehart, Gideon Pokowas, Jennifer Robson, Sarah G Cherian, Wendy HouineiAbstract:Summary Background Skin infections with ulceration are a major health problem in countries of the south Pacific region. Yaws, caused by Treponema pallidum subspecies pertenue and diagnosed by the presence of skin ulcers and a reactive syphilis serology, is one major cause, but this infection can be confused clinically with ulcers due to other causative agents. We investigated T pallidum pertenue and another bacterium known to cause skin infections in the Pacific islands— Haemophilus ducreyi —as causes of skin ulceration in a Yaws-endemic region. Additionally, we identified specific signs and symptoms associated with these causative agents of cutaneous ulcers and compared these findings with laboratory-based diagnoses. Methods We did a prospective cohort study of five Yaws-endemic villages (total population 3117 people) during a Yaws elimination campaign in Papua New Guinea in April, 2013. We enrolled all consenting patients with chronic moist or exudative skin ulcers. We undertook a detailed dermatological assessment, syphilis serology, and PCR on lesional swabs to detect the presence of T pallidum pertenue and H ducreyi . Patients with PCR-confirmed bacterial infections were included in a comparative analysis of demographics and clinical features. Findings Full outcome data were available for 90 people with skin ulcers. Of these patients, 17 (19%) had negative results in all molecular tests and were therefore excluded from the comparative analyses. A bacterial cause was identified in 73 (81%) participants—either H ducreyi (n=42), T pallidum pertenue (Yaws; n=19), or coinfection with both organisms (dual infection; n=12). The demographic characteristics of the patients infected with Yaws and with H ducreyi were similar. Skin lesions in patients with Yaws and in those with dual infection were larger than those in patients infected with H ducreyi (p=0·071). The lesions in patients with Yaws and dual infection were more circular in shape (79% and 67%) than in those infected with H ducreyi (21%; p vs 14%; p vs 31%; p=0·0003). The prevalence of reactive combined serology (positive T pallidum haemagglutination test and rapid plasmin reagin titre of ≥1:8) was higher in cases of Yaws (63%) and dual infections (92%) than in H ducreyi infections (29%; p Interpretation In this Yaws-endemic community, H ducreyi is an important and previously unrecognised cause of chronic skin ulceration. Reactive syphilis serology caused by latent Yaws can occur in ulcers with the presence of H ducreyi alone. The introduction of PCR for ulcer surveillance could improve the accuracy of diagnosis in countries with Yaws eradication campaigns. Funding Newcrest Mining Company.
