zithromax and Yaws

Mass drug administration (MDA) is a strategy to improve health at the population level through widespread delivery of medicine in a community. We surveyed the literature to summarize the benefits and potential risks associated with MDA of antibacterials, focusing predominantly on azithromycin as it has the greatest evidence base.. High-quality evidence from randomized controlled trials (RCTs) indicate that MDA-azithromycin is effective in reducing the prevalence of infection due to yaws and trachoma. In addition, RCTs suggest that MDA-azithromycin reduces under-five mortality in certain low-resource settings that have high childhood mortality rates at baseline. This reduction in mortality appears to be sustained over time with twice-yearly MDA-azithromycin, with the greatest effect observed in children < 1 year of age. In addition, observational data suggest that infections such as skin and soft tissue infections, rheumatic heart disease, acute respiratory illness, diarrheal illness, and malaria may all be treated by azithromycin and thus incidentally impacted by MDA-azithromycin. However, the mechanism by which MDA-azithromycin reduces childhood mortality remains unclear. Verbal autopsies performed in MDA-azithromycin childhood mortality studies have produced conflicting data and are underpowered to answer this question. In addition to benefits, there are several important risks associated with MDA-azithromycin. Direct adverse effects potentially resulting from MDA-azithromycin include gastrointestinal side effects, idiopathic hypertrophic pyloric stenosis, cardiovascular side effects, and increase in chronic diseases such as asthma and obesity. Antibacterial resistance is also a risk associated with MDA-azithromycin and has been reported for both gram-positive and enteric organisms. Further, there is the risk for cross-resistance with other antibacterial agents, especially clindamycin.. Evidence shows that MDA-azithromycin programs may be beneficial for reducing trachoma, yaws, and mortality in children < 5 years of age in certain under-resourced settings. However, there are significant potential risks that need to be considered when deciding how, when, and where to implement these programs. Robust systems to monitor benefits as well as adverse effects and antibacterial resistance are warranted in communities where MDA-azithromycin programs are implemented.

Topics: Anti-Bacterial Agents; Azithromycin; Child; Humans; Mass Drug Administration; Risk Assessment; Trachoma; Yaws

Yaws, caused by Treponema pallidum ssp. pertenue, is endemic in parts of West Africa, Southeast Asia and the Pacific. The WHO has launched a campaign based on mass treatment with azithromycin, to eradicate yaws by 2020.. We reviewed published data, surveillance data and data presented at yaws eradication meetings.. Azithromycin is now the preferred agent for treating yaws. Point-of-care tests have demonstrated their value in yaws.. There is limited data from 76 countries, which previously reported yaws. Different doses of azithromycin are used in community mass treatment for yaws and trachoma.. Yaws eradication appears an achievable goal. The programme will require considerable support from partners across health and development sectors.. Studies to complete baseline mapping, integrate diagnostic tests into surveillance and assess the impact of community mass treatment with azithromycin are ongoing.

Topics: Anti-Bacterial Agents; Azithromycin; Cost-Benefit Analysis; Disease Eradication; Humans; Program Development; Sentinel Surveillance; Treponema pallidum; Yaws

Yaws is endemic in west Africa, southeast Asia, and the Pacific region. To eradicate yaws by 2020, WHO has launched a campaign of mass treatment with azithromycin. Progress has been made towards achievement of this ambitious goal, including the validation of point-of-care and molecular diagnostic tests and piloting of the strategy in several countries, including Ghana, Vanuatu, and Papua New Guinea. Gaps in knowledge need to be addressed to allow refinement of the eradication strategy. Studies exploring determinants of the spatial distribution of yaws are needed to help with the completion of baseline mapping. The finding that Haemophilus ducreyi causes lesions similar to yaws is particularly important and further work is needed to assess the effect of azithromycin on these lesions. The integration of diagnostic tests into different stages of the eradication campaign needs investigation. Finally, studies must be done to inform the optimum mass-treatment strategy for sustainable interruption of transmission.

Topics: Africa, Western; Anti-Bacterial Agents; Asia, Southeastern; Azithromycin; Diagnostic Tests, Routine; Disease Eradication; Endemic Diseases; Humans; Pacific Islands; Topography, Medical; Yaws

Topics: Anti-Bacterial Agents; Azithromycin; Global Health; Humans; Trachoma; Yaws

Yaws, a chronic and debilitating infectious disease caused by Treponema pallidum subsp. pertenue, and closely related to syphilis, although transmitted by skin-to-skin contact, remains an important public health challenge, causing a significant burden of morbidity in children in certain areas of the Pacific and Africa. Recent advances in its diagnosis and treatment have led to an enthusiastic upsurge of activities related to its control, and exciting perspectives of global eradication. Although possibly considered among the most neglected of all neglected diseases during decades, there seems to be now agreement that massive drug administration of the antibiotic azithromycin, coupled with adequate surveillance of foci of transmission could result in its eradication. In this review, we summarize current knowledge regarding the therapeutics of yaws and its diagnosis.

Topics: Africa; Anti-Bacterial Agents; Azithromycin; Child; Disease Eradication; Drug Administration Schedule; Forecasting; Humans; Neglected Diseases; Papua New Guinea; Treatment Outcome; Treponema pallidum; Yaws

Yaws is an infection that mainly affects the poorest populations living in humid tropical areas. We reviewed the literature on yaws, the most common non-venereal treponemal infection, using the standard Prescrire methodology. Yaws is often transmitted directly from person to person. It starts as a single lesion, later leading to multiple contagious lesions. Yaws mainly affects children. The infection remains asymptomatic for several years. In about 10% of cases, late reactivation leads to bone lesions, deformities and disability. Diagnosis of yaws is based on the clinical and epidemiological context. Serological tests cannot distinguish between yaws and syphilis or other non-venereal treponematoses. Curative treatment consists of a single injection of benzathine benzylpenicillin. The results of a randomised trial suggest that a single oral dose of azithromycin is as effective as penicillin. In India, yaws was successfully eradicated through a programme based on providing information to the population at risk, screening and treatment.

Topics: Anti-Bacterial Agents; Azithromycin; Communicable Disease Control; Developing Countries; Disease Eradication; Endemic Diseases; Humans; Humidity; India; Penicillin G; Poverty; Treatment Outcome; Treponema pallidum; Tropical Climate; Yaws

In an open-label, cluster-randomized, community-based trial conducted in a yaws-endemic area of Papua New Guinea, we randomly assigned 38 wards (i.e., clusters) to receive one round of mass administration of azithromycin followed by two rounds of target treatment of active cases (control group) or three rounds of mass administration of azithromycin (experimental group); round 1 was administered at baseline, round 2 at 6 months, and round 3 at 12 months. The coprimary end points were the prevalence of active cases of yaws, confirmed by polymerase-chain-reaction assay, in the entire trial population and the prevalence of latent yaws, confirmed by serologic testing, in a subgroup of asymptomatic children 1 to 15 years of age; prevalences were measured at 18 months, and the between-group differences were calculated.. Of the 38 wards, 19 were randomly assigned to the control group (30,438 persons) and 19 to the experimental group (26,238 persons). A total of 24,848 doses of azithromycin were administered in the control group (22,033 were given to the participants at round 1 and 207 and 2608 were given to the participants with yaws-like lesions and their contacts, respectively, at rounds 2 and 3 [combined]), and 59,852 doses were administered in the experimental group. At 18 months, the prevalence of active yaws had decreased from 0.46% (102 of 22,033 persons) at baseline to 0.16% (47 of 29,954 persons) in the control group and from 0.43% (87 of 20,331 persons) at baseline to 0.04% (10 of 25,987 persons) in the experimental group (relative risk adjusted for clustering, 4.08; 95% confidence interval [CI], 1.90 to 8.76). The prevalence of other infectious ulcers decreased to a similar extent in the two treatment groups. The prevalence of latent yaws at 18 months was 6.54% (95% CI, 5.00 to 8.08) among 994 children in the control group and 3.28% (95% CI, 2.14 to 4.42) among 945 children in the experimental group (relative risk adjusted for clustering and age, 2.03; 95% CI, 1.12 to 3.70). Three cases of yaws with resistance to macrolides were found in the experimental group.. The reduction in the community prevalence of yaws was greater with three rounds of mass administration of azithromycin at 6-month intervals than with one round of mass administration of azithromycin followed by two rounds of targeted treatment. Monitoring for the emergence and spread of antimicrobial resistance is needed. (Funded by Fundació "la Caixa" and others; ClinicalTrials.gov number, NCT03490123.).

Topics: Adolescent; Anti-Bacterial Agents; Azithromycin; Child; Child, Preschool; Drug Resistance, Bacterial; Female; Haemophilus ducreyi; Humans; Infant; Male; Mass Drug Administration; Papua New Guinea; Polymerase Chain Reaction; Prevalence; Skin Ulcer; Treponema; Yaws

WHO and its partners aim to interrupt yaws transmission in countries of endemicity and to certify others as being yaws-free. Transmission can be assessed using rapid plasma reagin (RPR) tests, reflecting current or recent infection, but RPR is operationally impractical. We evaluated changes in antibody levels against two recombinant treponemal antigens, rp17 (also known as Tp17) and TmpA, after antibiotic treatment given as part of a randomized controlled trial for yaws in Ghana and Papua New Guinea. Paired serum samples from children aged 6 to 15 years with confirmed yaws, collected before and after treatment, were tested for antibodies to rp17 and TmpA using a semiquantitative bead-based immunoassay. Of 344 baseline samples, 342 tested positive for anti-rp17 antibodies and 337 tested positive for anti-TmpA antibodies. Six months after treatment, the median decrease in anti-rp17 signal was 3.2%, whereas the median decrease in anti-TmpA was 53.8%. The magnitude of change in the anti-TmpA response increased with increasing RPR titer fold change. These data demonstrate that responses to TmpA decrease markedly within 6 months of treatment whereas (as expected) those to rp17 do not. Incorporating responses to TmpA as a marker of recent infection within an integrated sero-surveillance platform could provide a way to prioritize areas for yaws mapping.

Topics: Antibody Formation; Azithromycin; Child; Ghana; Humans; Papua New Guinea; Treponema pallidum; Yaws

A dose of 30 mg/kg of azithromycin is recommended for treatment of yaws, a disease targeted for global eradication. Treatment with 20 mg/kg of azithromycin is recommended for the elimination of trachoma as a public health problem. In some settings, these diseases are co-endemic. We aimed to determine the efficacy of 20 mg/kg of azithromycin compared with 30 mg/kg azithromycin for the treatment of active and latent yaws.. We did a non-inferiority, open-label, randomised controlled trial in children aged 6-15 years who were recruited from schools in Ghana and schools and the community in Papua New Guinea. Participants were enrolled based on the presence of a clinical lesion that was consistent with infectious primary or secondary yaws and a positive rapid diagnostic test for treponemal and non-treponemal antibodies. Participants were randomly assigned (1:1) to receive either standard-dose (30 mg/kg) or low-dose (20 mg/kg) azithromycin by a computer-generated random number sequence. Health-care workers assessing clinical outcomes in the field were not blinded to the patient's treatment, but investigators involved in statistical or laboratory analyses and the participants were blinded to treatment group. We followed up participants at 4 weeks and 6 months. The primary outcome was cure at 6 months, defined as lesion healing at 4 weeks in patients with active yaws and at least a four-fold decrease in rapid plasma reagin titre from baseline to 6 months in patients with active and latent yaws. Active yaws was defined as a skin lesion that was positive for Treponema pallidum ssp pertenue in PCR testing. We used a non-inferiority margin of 10%. This trial was registered with ClinicalTrials.gov, number NCT02344628.. Between June 12, 2015, and July 2, 2016, 583 (65·1%) of 895 children screened were enrolled; 292 patients were assigned a low dose of azithromycin and 291 patients were assigned a standard dose of azithromycin. 191 participants had active yaws and 392 had presumed latent yaws. Complete follow-up to 6 months was available for 157 (82·2%) of 191 patients with active yaws. In cases of active yaws, cure was achieved in 61 (80·3%) of 76 patients in the low-dose group and in 68 (84·0%) of 81 patients in the standard-dose group (difference 3·7%; 95% CI -8·4 to 15·7%; this result did not meet the non-inferiority criterion). There were no serious adverse events reported in response to treatment in either group. The most commonly reported adverse event at 4 weeks was gastrointestinal upset, with eight (2·7%) participants in each group reporting this symptom.. In this study, low-dose azithromycin did not meet the prespecified non-inferiority margin compared with standard-dose azithromycin in achieving clinical and serological cure in PCR-confirmed active yaws. Only a single participant (with presumed latent yaws) had definitive serological failure. This work suggests that 20 mg/kg of azithromycin is probably effective against yaws, but further data are needed.. Coalition for Operational Research on Neglected Tropical Diseases.

Topics: Adolescent; Anti-Bacterial Agents; Azithromycin; Child; Dose-Response Relationship, Drug; Female; Ghana; Humans; Male; Papua New Guinea; Treatment Outcome; Yaws

Yaws is a treponemal infection that was almost eradicated fifty years ago; however, the disease has re-emerged in a number of countries including Ghana. A single-dose of intramuscular benzathine penicillin has been the mainstay of treatment for yaws. However, intramuscular injections are painful and pose safety and logistical constraints in the poor areas where yaws occurs. A single center randomized control trial (RCT) carried out in Papua New Guinea in 2012 demonstrated the efficacy of a single-dose of oral azithromycin for the treatment of yaws. In this study, we also compared the efficacy of a single oral dose of azithromycin as an alternative to intramuscular benzathine penicillin for the treatment of the disease in another geographic setting.. We conducted an open-label, randomized non-inferiority trial in three neighboring yaws-endemic districts in Southern Ghana. Children aged 1-15 years with yaws lesions were assigned to receive either 30mg/kg of oral azithromycin or 50,000 units/kg of intramuscular benzathine penicillin. The primary end point was clinical cure rate, defined as a complete or partial resolution of lesions 3 weeks after treatment. The secondary endpoint was serological cure, defined as at least a 4-fold decline in baseline RPR titre 6 months after treatment. Non- inferiority of azithromycin treatment was determined if the upper bound limit of a 2 sided 95% CI was less than 10%.. The mean age of participants was 9.5 years (S.D.3.1, range: 1-15 years), 247(70%) were males. The clinical cure rates were 98.2% (95% CI: 96.2-100) in the azithromycin group and 96.9% (95% CI: 94.1-99.6) in the benzathine penicillin group. The serological cure rates at 6 months were 57.4% (95% CI: 49.9-64.9) in the azithromycin group and 49.1% (95% CI: 41.2-56.9) in the benzathine penicillin group, thus achieving the specified criteria for non-inferiority.. A single oral dose of azithromycin, at a dosage of 30mg/kg, was non-inferior to a single dose of intramuscular benzathine penicillin for the treatment of early yaws among Ghanaian patients, and provides additional support for the WHO policy for use of oral azithromycin for the eradication of yaws in resource-poor settings.. Pan African Clinical Trials Registry PACTR2013030005181 http://www.pactr.org/.

Topics: Administration, Oral; Adolescent; Anti-Bacterial Agents; Azithromycin; Child; Child, Preschool; Female; Ghana; Humans; Infant; Injections, Intramuscular; Male; Penicillin G Benzathine; Treatment Outcome; Treponema pallidum; Yaws

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.. 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.. 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.. 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.).

Topics: Adolescent; Adult; Age Distribution; Anti-Bacterial Agents; Azithromycin; Chancroid; Child; Child, Preschool; Cross-Sectional Studies; Drug Resistance, Bacterial; Endemic Diseases; Haemophilus ducreyi; Humans; Infant; Papua New Guinea; Polymerase Chain Reaction; Prevalence; Treponema pallidum; Yaws; Young Adult

Yaws--an endemic treponematosis and, as such, a neglected tropical disease--is re-emerging in children in rural, tropical areas. Oral azithromycin is effective for syphilis. We assessed the efficacy of azithromycin compared with intramuscular long-acting penicillin to treat patients with yaws.. We did an open-label, non-inferiority, randomised trial at Lihir Medical Centre, Papua New Guinea, between Sept 1, 2010, and Feb 1, 2011. Children aged 6 months to 15 years with a serologically confirmed diagnosis of yaws were randomly allocated, by a computer-generated randomisation sequence, to receive either one 30 mg/kg oral dose of azithromycin or an intramuscular injection of 50,000 units per kg benzathine benzylpenicillin. Investigators were masked to group assignment. The primary endpoint was treatment efficacy, with cure rate defined serologically as a decrease in rapid plasma reagin titre of at least two dilutions by 6 months after treatment, and, in participants with primary ulcers, also by epithelialisation of lesions within 2 weeks. Non-inferiority was shown if the upper limit of the two-sided 95% CI for the difference in rates was lower than 10%. The primary analysis was per protocol. This trial is registered with ClinicalTrials.gov, number NCT01382004.. We allocated 124 patients to the azithromycin group and 126 to the benzathine benzylpenicillin group. In the per-protocol analysis, after 6 months of follow-up, 106 (96%) of 110 patients in the azithromycin group were cured, compared with 105 (93%) of 113 in the benzathine benzylpenicillin group (treatment difference -3·4%; 95% CI -9·3 to 2·4), thus meeting prespecified criteria for non-inferiority. The number of drug-related adverse events (all mild or moderate) was similar in both treatment groups (ten [8%] in the azithromycin group vs eight [7%] in the benzathine benzylpenicillin group).. A single oral dose of azithromycin is non-inferior to benzathine benzylpenicillin and avoids the need for injection equipment and medically trained personnel. A change to the simpler azithromycin treatment regimen could enable yaws elimination through mass drug administration programmes.. International SOS and Newcrest Mining.

Topics: Administration, Oral; Adolescent; Anti-Bacterial Agents; Azithromycin; Child; Child, Preschool; Female; Humans; Infant; Injections, Intramuscular; Male; Papua New Guinea; Penicillin G Benzathine; Yaws

Yaws is a chronic infection that affects mainly the skin, bone and cartilage and spreads mostly between children. The new approval of a medication as treatment in 2012 has revived eradication efforts and now only few known localized foci of infection remain. The World Health Organization strategy mandates an initial round of total community treatment (TCT) with single-dose azithromycin followed either by further TCT or by total targeted treatment (TTT), an active case-finding and treatment of cases and their contacts. We develop the compartmental ODE model of yaws transmission and treatment for these scenarios. We solve for disease-free and endemic equilibria and also perform the stability analysis. We calibrate the model and validate its predictions on the data from Lihir Island in Papua New Guinea. We demonstrate that TTT strategy is efficient in preventing outbreaks but, due to the presence of asymptomatic latent cases, TTT will not eliminate yaws within a reasonable time frame. To achieve the 2030 eradication target, TCT should be applied instead.

Topics: Anti-Bacterial Agents; Azithromycin; Child; Humans; Papua New Guinea; Skin; Yaws

Yaws is targeted for eradication by 2030, using a strategy based on mass drug administration (MDA) with azithromycin. New diagnostics are needed to aid eradication. Serology is currently the mainstay for yaws diagnosis; however, inaccuracies associated with current serological tests makes it difficult to fully assess the need for and impact of eradication campaigns using these tools. Under the recommendation of the WHO Diagnostic Technical Advisory Group (DTAG) for Neglected Tropical Diseases(NTDs), a working group was assembled and tasked with agreeing on priority use cases for developing target product profiles (TPPs) for new diagnostics tools.. The working group convened three times and established two use cases: identifying a single case of yaws and detecting azithromycin resistance. One subgroup assessed the current diagnostic landscape for yaws and a second subgroup determined the test requirements for both use cases. Draft TPPs were sent out for input from stakeholders and experts. Both TPPs considered the following parameters: product use, design, performance, configuration, cost, access and equity. To identify a single case of yaws, the test should be able to detect an analyte which confirms an active infection with at least 95% sensitivity and 99.9% specificity. The high specificity was deemed important to avoid a high false positive rate which could result in unnecessary continuation or initiation of MDA campaigns. If used in settings where the number of suspected cases is low, further testing could be considered to compensate for imperfect sensitivity and to improve specificity. The test to detect azithromycin resistance should be able to detect known genetic resistance mutations with a minimum sensitivity and specificity of 95%, with the caveat that all patients with suspected treatment failure should be treated as having resistant yaws and offered alternative treatment.. The TPPs developed will provide test developers with guidance to ensure that novel diagnostic tests meet identified public health needs.

Topics: Anti-Bacterial Agents; Azithromycin; Humans; Mass Drug Administration; Neglected Diseases; Treponema pallidum; Yaws

In yaws-endemic areas, two-thirds of exudative cutaneous ulcers (CU) are associated with Treponema pallidum subsp. pertenue (TP) and Haemophilus ducreyi (HD); one-third are classified as idiopathic ulcers (IU). A yaws eradication campaign on Lihir Island in Papua New Guinea utilizing mass drug administration (MDA) of azithromycin initially reduced but failed to eradicate yaws; IU rates remained constant throughout the study. Using 16S rRNA gene sequencing, we previously determined that Streptococcus pyogenes was associated with some cases of IU. Here, we applied shotgun metagenomics to the same samples we analyzed previously by 16S rRNA sequencing to verify this result, identify additional IU-associated microorganisms, and determine why S. pyogenes-associated IU might have persisted after MDA of azithromycin.. We sequenced DNA extracted from 244 CU specimens separated into four groups based upon microorganism-specific PCR results (HD+, TP+, TP+HD+, and TP-HD- or IU). S. pyogenes was enriched in IU (24.71% relative abundance [RA]) specimens compared to other ulcer sub-groups, confirming our prior results. We bioinformatically identified the emm (M protein gene) types found in the S. pyogenes IU specimens and found matches to emm156 and emm166. Only ~39% of IU specimens contained detectable S. pyogenes, suggesting that additional organisms could be associated with IU. In the sub-set of S. pyogenes-negative IU specimens, Criibacterium bergeronii, a member of the Peptostreptococcaceae, and Fusobacterium necrophorum (7.07% versus 0.00% RA and 2.18% versus 0.00% RA, respectively), were enriched compared to the S. pyogenes-positive sub-set. Although a broad range of viruses were detected in the CU specimens, none were specifically associated with IU.. Our observations confirm the association of S. pyogenes with IU in yaws-endemic areas, and suggest that additional anaerobic bacteria, but not other microorganisms, may be associated with this syndrome. Our results should aid in the design of diagnostic tests and selective therapies for CU.

Topics: Anaerobiosis; Azithromycin; Bacteria, Anaerobic; Child; Haemophilus ducreyi; Humans; RNA, Ribosomal, 16S; Skin Ulcer; Streptococcus pyogenes; Treponema pallidum; Ulcer; Yaws

Yaws is a disabling bacterial infection found primarily in warm and humid tropical areas. The World Health Organization strategy mandates an initial round of total community treatment (TCT) with single-dose azithromycin followed either by further TCT or active case-finding and treatment of cases and their contacts (the Morges strategy). We sought to investigate the effectiveness of the Morges strategy. We employed a stochastic household model to study the transmission of infection using data collected from a pre-TCT survey conducted in the Solomon Islands. We used this model to assess the proportion of asymptomatic infections that occurred in households without active cases. This analysis indicated that targeted treatment of cases and their household contacts would miss a large fraction of asymptomatic infections (65%-100%). This fraction was actually higher at lower prevalences. Even assuming that all active cases and their households were successfully treated, our analysis demonstrated that at all prevalences present in the data set, up to 90% of (active and asymptomatic) infections would not be treated under household-based contact tracing. Mapping was undertaken as part of the study "Epidemiology of Yaws in the Solomon Islands and the Impact of a Trachoma Control Programme," in September-October 2013.

Topics: Anti-Bacterial Agents; Azithromycin; Communicable Disease Control; Contact Tracing; Female; Humans; Male; Melanesia; Models, Statistical; Yaws

Topics: Azithromycin; Humans; Macrolides; Treponema pallidum; Yaws

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.. 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.. 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<0·0001), but the infection began to re-emerge after 24 months with a significant increase to 0·4% at 42 months (difference from 18 months 0·3%, 95% CI 0·1 to 0·4; p<0·0001). At each timepoint after baseline, more than 70% of the total community burden of yaws was found in individuals who had not had the mass treatment or as new infections in non-travelling residents. At months 36 and 42, five cases of active yaws, all from the same village, showed clinical failure following azithromycin treatment, with PCR-detected mutations in the 23S ribosomal RNA genes conferring resistance to azithromycin. A sustained decrease in the prevalence of high-titre latent yaws from 13·7% to <1·5% in asymptomatic children aged 1-5 years old and of genetic diversity of yaws strains from 0·139 to less than 0·046 between months 24 and 42 indicated a reduction in transmission of infection.. 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.. ISDIN laboratories, Newcrest Mining Limited, and US Public Health Service National Institutes of Health.

Topics: Adolescent; Anti-Bacterial Agents; Azithromycin; Child; Child, Preschool; Communicable Diseases, Emerging; Disease Eradication; Drug Resistance, Bacterial; Female; Genetic Variation; Humans; Infant; Longitudinal Studies; Male; Mass Drug Administration; Papua New Guinea; Polymerase Chain Reaction; Prevalence; RNA, Ribosomal, 23S; Treatment Outcome; Treponema pallidum; Yaws

Topics: Anti-Bacterial Agents; Azithromycin; Humans; Treponema pallidum; Yaws

The WHO yaws eradication strategy consists of one round of total community treatment (TCT) of single-dose azithromycin with coverage of > 90%.The efficacy of the strategy to reduce the levels on infection has been demonstrated previously in isolated island communities in the Pacific region. We aimed to determine the efficacy of a single round of TCT with azithromycin to achieve a decrease in yaws prevalence in communities that are endemic for yaws and surrounded by other yaws-endemic areas.. Surveys for yaws seroprevalence and prevalence of skin lesions were conducted among schoolchildren aged 5-15 years before and one year after the TCT intervention in the Abamkrom sub-district of Ghana. We used a cluster design with the schools as the primary sampling unit. Among 20 eligible primary schools in the sub district, 10 were assigned to the baseline survey and 10 to the post-TCT survey. The field teams conducted a physical examination for skin lesions and a dual point-of-care immunoassay for non-treponemal and treponemal antibodies of all children present at the time of the visit. We also undertook surveys with non-probabilistic sampling to collect lesion swabs for etiology and macrolide resistance assessment.. At baseline 14,548 (89%) of 16,287 population in the sub-district received treatment during TCT. Following one round of TCT, the prevalence of dual seropositivity among all children decreased from 10.9% (103/943) pre-TCT to 2.2% (27/1211) post-TCT (OR 0.19; 95%CI 0.09-0.37). The prevalence of serologically confirmed skin lesions consistent with active yaws was reduced from 5.7% (54/943) pre-TCT to 0.6% (7/1211) post-TCT (OR 0.10; 95% CI 0.25-0.35). No evidence of resistance to macrolides against Treponema pallidum subsp. pertenue was seen.. A single round of high coverage TCT with azithromycin in a yaws affected sub-district adjoining other endemic areas is effective in reducing the prevalence of seropositive children and the prevalence of early skin lesions consistent with yaws one year following the intervention. These results suggest that national yaws eradication programmes may plan the gradual expansion of mass treatment interventions without high short-term risk of reintroduction of infection from contiguous untreated endemic areas.

Topics: Adolescent; Anti-Bacterial Agents; Antibodies, Bacterial; Azithromycin; Child; Child, Preschool; Community Medicine; Disease Eradication; Drug Resistance, Bacterial; Female; Ghana; Humans; Immunoassay; Male; Pilot Projects; Prevalence; Seroepidemiologic Studies; Skin; Treponema pallidum; World Health Organization; Yaws

Haemophilus ducreyi and Treponema pallidum subsp. pertenue are major causes of leg ulcers in children in Africa and the Pacific Region. We investigated the presence of DNA (PCR positivity) from these bacteria on asymptomatic people, flies, and household linens in an endemic setting.. We performed a cross-sectional study in rural villages of Lihir Island, Papua New Guinea during a yaws elimination campaign. Participants were asymptomatic subjects recruited from households with cases of leg ulcers, and from households without cases of leg ulcers. We rubbed swabs on the intact skin of the leg of asymptomatic individuals, and collected flies and swabs of environmental surfaces. All specimens were tested by PCR for H. ducreyi and T. p. pertenue DNA. Of 78 asymptomatic participants that had an adequate specimen for DNA detection, H. ducreyi-PCR positivity was identified in 16 (21%) and T. p. pertenue-PCR positivity in 1 (1%). In subgroup analyses, H. ducreyi-PCR positivity did not differ in participants exposed or not exposed to a case of H. ducreyi ulcer in the household (24% vs 18%; p = 0.76). Of 17 cultures obtained from asymptomatic participants, 2 (12%) yielded a definitive diagnosis of H. ducreyi, proving skin colonization. Of 10 flies tested, 9 (90%) had H. ducreyi DNA and 5 (50%) had T. p. pertenue DNA. Of 6 bed sheets sampled, 2 (33%) had H. ducreyi DNA and 1 (17%) had T. p. pertenue DNA.. This is the first time that H. ducreyi DNA and colonization has been demonstrated on the skin of asymptomatic children and that H. ducreyi DNA and T. p. pertenue DNA has been identified in flies and on fomites. The ubiquity of H. ducreyi in the environment is a contributing factor to the spread of the organism.

Topics: Adolescent; Animals; Anti-Bacterial Agents; Asymptomatic Diseases; Azithromycin; Chancroid; Child; Child, Preschool; Cross-Sectional Studies; Diptera; DNA, Bacterial; Female; Fomites; Haemophilus ducreyi; Humans; Leg Ulcer; Logistic Models; Male; Papua New Guinea; Polymerase Chain Reaction; Skin; Treponema pallidum; Yaws

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.. This population-based cohort study included children (age <20 years) living on Lihir Island, Papua New Guinea, with high-titre (rapid plasma reagin titre ≥1:8) latent or active yaws, between April, 2013, and May, 2015. Latent yaws was defined as lack of suspicious skin lesions or presence of ulcers negative for 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.. 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.. 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.. Newcrest Mining Limited and ISDIN laboratories.

Topics: Adolescent; Anti-Bacterial Agents; Azithromycin; Child; Child, Preschool; Cohort Studies; Female; Humans; Longitudinal Studies; Male; Papua New Guinea; Polymerase Chain Reaction; Treponema pallidum; Yaws

Topics: Anti-Bacterial Agents; Azithromycin; Humans; Treponema pallidum; Yaws

Yaws is targeted for eradication by 2020. The mainstay of the eradication strategy is mass treatment followed by case finding. Modeling has been used to inform programmatic requirements for other neglected tropical diseases and could provide insights into yaws eradication. We developed a model of yaws transmission varying the coverage and number of rounds of treatment. The estimated number of cases arising from an index case (basic reproduction number [R

Topics: Anti-Bacterial Agents; Azithromycin; Computer Simulation; Disease Eradication; Female; Humans; Male; Markov Chains; Models, Statistical; Neglected Diseases; Recurrence; Treponema pallidum; Tropical Climate; Yaws

Topics: Anti-Bacterial Agents; Azithromycin; Child, Preschool; DNA, Bacterial; Humans; Leg; Male; Periosteum; Periostitis; Tomography, X-Ray Computed; Treatment Outcome; Treponema pallidum; Wrist; Yaws

The management of yaws has changed in recent years. Mass treatment with oral azithromycin has replaced intramuscular benzathine benzylpenicillin. Treponemal and non-treponemal serology (equivalent to TPHA and RPR) point-of-care blood testing is now available. In addition, recent studies in yaws endemic regions have shown that a significant number of leg ulcers in children which are clinically suggestive of yaws are caused by Haemophilus ducreyi. It is noteworthy that the World Health Organization has also set the ambitious goal to eliminate yaws by 2020.

Topics: Anti-Bacterial Agents; Azithromycin; Child; Disease Eradication; Humans; Leg Ulcer; Penicillin G Benzathine; Point-of-Care Systems; Treponema pallidum; Vanuatu; Yaws

In 2012 WHO declared a target to eradicate yaws by 2020. The cornerstone of this strategy is community mass treatment with azithromycin. Initial studies suggest this is a very effective tool that may be capable of interrupting transmission. Alongside this there has been progress in the development and validation of diagnostic tests for yaws. Several new challenges have also emerged, in particular, evidence that Haemophilus ducreyi can cause phenotypically similar ulcers in yaws endemic communities, and evidence for a possible non-human primate reservoir. The 2020 eradication target remains ambitious and more challenges should be expected on the journey.

Topics: Animals; Anti-Bacterial Agents; Azithromycin; Diagnostic Tests, Routine; Disease Eradication; Disease Reservoirs; Endemic Diseases; Haemophilus ducreyi; Humans; Primates; Treponema pallidum; Ulcer; World Health Organization; Yaws

Both yaws and trachoma are endemic in the Pacific. Mass treatment with azithromycin is the mainstay of the WHO strategy for both the eradication of yaws and the elimination of trachoma as a public health problem, but the dose recommended for trachoma is lower than that for yaws. In countries where both diseases are endemic, there is a potential for synergy between yaws and trachoma control programs if mass treatment with the lower dose of azithromycin was shown to be effective for the treatment of yaws. In an earlier study, we demonstrated a profound reduction in the clinical and serological prevalence of yaws following a single round of mass treatment with azithromycin 20 mg/kg undertaken for the purposes of trachoma elimination.. This survey was conducted 18 months following a single round of azithromycin mass treatment in the same communities in which we had conducted our previous six-month follow-up survey. We examined children aged 1-14 years and took blood and lesion samples for yaws diagnosis using the Treponema pallidum particle agglutination assay (TPPA) and the non-treponemal Rapid Plasma Reagin (RPR) test.. A total of 1,284 children were enrolled in the study. Amongst children aged 5-14 years, 223 had a positive TPPA (27.5%, 95% CI 13.6-47.7%). The TPPA seroprevalence amongst this age group did not differ significantly from either our pre-mass treatment survey or our initial follow-up survey. Thirty-five children had positive TPPA and positive RPR (4.3%, 95% CI 2.1-8.7%), and this did not differ significantly from our initial post-mass drug administration (MDA) follow-up survey (4.3% versus 3.5%, p = 0.43) but remained significantly lower than our initial pre-MDA survey (4.3% vs 21.7%, p <0.0001). Village-level MDA coverage was strongly associated with dual-seropositivity (p = 0.005). Amongst children aged 1-4 years, 16 had a positive TPPA (3.5%, 95% CI 1.6-7.1%). This did not differ significantly from the seroprevalence in this age group that had been predicted based on our previous surveys (3.5% vs 5%, p = 0.11). Fourteen children (1.1%) were considered to have a skin lesion clinically consistent with yaws, but none of these individuals was seropositive for yaws. Of nine cases where a swab could be collected for PCR, all were negative for Treponema pallidum subsp. pertenue DNA.. In this study we have shown that the benefit of a single round of mass treatment with azithromycin 20mg/kg appears to extend to 18 months without any further intervention. The lack of a significant change in seroprevalence from 6 to 18 months after mass treatment might suggest that interventions could be spaced at yearly intervals without a significant loss of impact, and that this might facilitate integration of yaws eradication with other neglected tropical disease (NTD) control programmes. MDA coverage above 90% was associated with significantly better outcomes than coverages lower than this threshold, and strategies to improve coverage at all stages of yaws eradication efforts should be investigated.

Topics: Adolescent; Agglutination Tests; Anti-Bacterial Agents; Azithromycin; Child; Child, Preschool; Female; Follow-Up Studies; Humans; Infant; Logistic Models; Male; Melanesia; Seroepidemiologic Studies; Trachoma; Treponema pallidum; Yaws

Topics: Anti-Bacterial Agents; Azithromycin; Humans; Yaws

Topics: Anti-Bacterial Agents; Azithromycin; Humans; Yaws

Topics: Anti-Bacterial Agents; Azithromycin; Humans; Yaws

We developed a TaqMan-based real-time quadriplex polymerase chain reaction (PCR) to simultaneously detect Treponema pallidum subspecies pallidum, T. pallidum subsp. pertenue, and T. pallidum subsp. endemicum, the causative agents of venereal syphilis, yaws, and bejel, respectively. The PCR assay was applied to samples from skin ulcerations of clinically presumptive yaws cases among children on Tanna Island, Vanuatu. Another real-time triplex PCR was used to screen for the point mutations in the 23S rRNA genes that have previously been associated with azithromycin resistance in T. pallidum subsp. pallidum strains. Seropositivity by the classical syphilis serological tests was 35.5% among children with skin ulcerations clinically suspected with yaws, whereas the presence of T. pallidum subsp. pertenue DNA was only found in lesions from 15.5% of children. No evidence of T. pallidum subsp. pertenue infection, by either PCR or serology was found in ∼59% of cases indicating alternative causes of yaws-like lesions in this endemic area.

Topics: Adolescent; Anti-Bacterial Agents; Azithromycin; Base Sequence; Child; DNA Primers; Humans; Multiplex Polymerase Chain Reaction; Philippines; Real-Time Polymerase Chain Reaction; Skin Ulcer; Treponema pallidum; Yaws

Yaws, caused by Treponema pallidum ssp. pertenue, is reportedly endemic in Ghana. Mass distribution of azithromycin is now the cornerstone of the WHO yaws eradication campaign. Mass distribution of azithromycin at a lower target dose was previously undertaken in two regions of Ghana for the control of trachoma. Ongoing reporting of yaws raises the possibility that resistance may have emerged in T. pallidum pertenue, or that alternative infections may be responsible for some of the reported cases. We conducted a cross-sectional survey in thirty communities in two districts of Ghana where MDA for trachoma had previously been conducted. Children aged 5-17 years with ulcerative lesions compatible with yaws were enrolled. Samples for treponemal serology and lesion PCR were collected from all children. 90 children with 98 lesions were enrolled. Syphilis serology was negative in all of them. PCR for T. pallidum ssp pertenue was negative in all children, but Haemophilus ducreyi DNA was detected in 9 lesions. In these communities, previously treated for trachoma, we found no evidence of ongoing transmission of yaws. H. ducreyi was associated with a proportion of skin lesions, but the majority of lesions remain unexplained. Integration of diagnostic testing into both pre and post-MDA surveillance systems is required to better inform yaws control programmes.

Topics: Adolescent; Anti-Bacterial Agents; Azithromycin; Child; Child, Preschool; Cross-Sectional Studies; Female; Ghana; Humans; Male; Trachoma; Yaws

Topics: Anti-Bacterial Agents; Azithromycin; Humans; Treponema pallidum; Yaws

Treponema pallidum ssp. pallidum (TPA) causes over 10 million new cases of syphilis worldwide whereas T. pallidum ssp. pertenue (TPE), the causative agent of yaws, affects about 2.5 million people. Although penicillin remains the drug of choice in the treatment of syphilis, in penicillin-allergic patients, macrolides have been used in this indication since the 1950s. Failures of macrolides in syphilis treatment have been well documented in the literature and since 2000, there has been a dramatic increase in a number of clinical samples with macrolide-resistant TPA. Scarce data regarding the genetics of macrolide-resistant mutations in TPA suggest that although macrolide-resistance mutations have emerged independently several times, the increase in the proportion of TPA strains resistant to macrolides is mainly due to the spread of resistant strains, especially in developed countries. The emergence of macrolide resistance in TPA appears to require a two-step process including either A2058G or A2059G mutation in one copy of the 23S rRNA gene and a subsequent gene conversion unification of both rRNA genes. Given the enormous genetic similarity that was recently revealed between TPA and TPE strains, there is a low but reasonable risk of emergence and spread of macrolide-resistant yaws strains following azithromycin treatment.

Topics: Anti-Bacterial Agents; Azithromycin; Drug Resistance, Bacterial; Humans; Macrolides; Mutation; Operon; RNA, Ribosomal, 23S; Syphilis; Treatment Failure; Treponema pallidum; Yaws

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.. 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.. 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.. 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.

Topics: Adolescent; Anti-Bacterial Agents; Azithromycin; Child; Child, Preschool; Female; Humans; Male; Melanesia; Prevalence; Seasons; Trachoma; Yaws

Topics: Anti-Bacterial Agents; Azithromycin; Female; Humans; Male; Penicillin G Benzathine; Yaws

Recent reports from the island of Tanna in Vanuatu suggest that yaws has resurged. We carried out a serological and clinical survey to determine the prevalence and clinical presentation of yaws on the island. A total of 306 random serum samples were tested for rapid plasma reagin and rapid diagnostic determine syphilis: 31.04% were positive for one or both tests; 39.8% of children surveyed in three schools had skin lesions consistent with yaws; and there were only two cases of secondary yaws osteitis and no cases of tertiary yaws. These results confirm that the disease has resurged but appears to be attenuated. Intramuscular benzathine penicillin is the currently recommended treatment for yaws. We suggest that a stat dose of oral azithromycin would be a more accessible treatment as it could be prescribed by village health workers and therefore enable yaws control to be more easily incorporated into other primary health-care programmes.

Topics: Administration, Oral; Anti-Bacterial Agents; Azithromycin; Cluster Analysis; Disease Outbreaks; Drug Administration Schedule; Female; Humans; Prevalence; Rural Health Services; Seroepidemiologic Studies; Vanuatu; Yaws