Trial of Three Rounds of Mass Azithromycin Administration for Yaws Eradication.

BACKGROUND: Treponema pallidum subspecies pertenue causes yaws. Strategies to better control, eliminate, and eradicate yaws are needed. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.).

Rapid Serologic Test for Diagnosis of Yaws in Patients with Suspicious Skin Ulcers.

The Chembio DPP (Dual Path Platform) Syphilis Screen & Confirm kit (https://chembio.com) is a rapid serologic test that can be used to diagnose yaws. We evaluated its capacity to detect patients with ulcers that tested PCR positive for Treponema pallidum subsp. pertenue. DPP detected 84% of ulcers that were positive by PCR.

Evolutionary Processes in the Emergence and Recent Spread of the Syphilis Agent, Treponema pallidum.

The incidence of syphilis has risen worldwide in the last decade in spite of being an easily treated infection. The causative agent of this sexually transmitted disease is the bacterium Treponema pallidum subspecies pallidum (TPA), very closely related to subsp. pertenue (TPE) and endemicum (TEN), responsible for the human treponematoses yaws and bejel, respectively. Although much focus has been placed on the question of the spatial and temporary origins of TPA, the processes driving the evolution and epidemiological spread of TPA since its divergence from TPE and TEN are not well understood. Here, we investigate the effects of recombination and selection as forces of genetic diversity and differentiation acting during the evolution of T. pallidum subspecies. Using a custom-tailored procedure, named phylogenetic incongruence method, with 75 complete genome sequences, we found strong evidence for recombination among the T. pallidum subspecies, involving 12 genes and 21 events. In most cases, only one recombination event per gene was detected and all but one event corresponded to intersubspecies transfers, from TPE/TEN to TPA. We found a clear signal of natural selection acting on the recombinant genes, which is more intense in their recombinant regions. The phylogenetic location of the recombination events detected and the functional role of the genes with signals of positive selection suggest that these evolutionary processes had a key role in the evolution and recent expansion of the syphilis bacteria and significant implications for the selection of vaccine candidates and the design of a broadly protective syphilis vaccine.

Improved rapid diagnostic tests to detect syphilis and yaws: a systematic review and meta-analysis.

BACKGROUND: Current rapid tests for syphilis and yaws can detect treponemal and non-treponemal antibodies. We aimed to critically appraise the literature for rapid diagnostic tests (RDTs) which can better distinguish an active infection of syphilis or yaws. METHODS: We conducted a systematic review and meta-analysis, searching five databases between January 2010 and October 2021 (with an update in July 2022). A generalised linear mixed model was used to conduct a bivariate meta-analysis for the pooled sensitivity and specificity. Heterogeneity was assessed using the I2 statistic. We used the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) to assess the risk of bias and Grading of Recommendations, Assessment, Development and Evaluations (GRADE) to evaluate the certainty of evidence. RESULTS: We included 17 studies for meta-analyses. For syphilis, the pooled sensitivity and specificity of the treponemal component were 0.93 (95% CI: 0.86 to 0.97) and 0.98 (95% CI: 0.96 to 0.99), respectively. For the non-treponemal component, the pooled sensitivity and specificity were 0.90 (95% CI: 0.82 to 0.95) and 0.97 (95% CI: 0.92 to 0.99), respectively. For yaws, the pooled sensitivity and specificity of the treponemal component were 0.86 (95% CI: 0.66 to 0.95) and 0.97 (95% CI: 0.94 to 0.99), respectively. For the non-treponemal component, the pooled sensitivity and specificity were 0.80 (95% CI: 0.55 to 0.93) and 0.96 (95% CI: 0.92 to 0.98), respectively. CONCLUSIONS: RDTs that can differentiate between active and previously treated infections could optimise management by providing same-day treatment and reducing unnecessary treatment. PROSPERO REGISTRATION NUMBER: CRD42021279587.

Epidemiologic and Genomic Reidentification of Yaws, Liberia.

We confirmed endemicity and autochthonous transmission of yaws in Liberia after a population-based, community-led burden estimation (56,825 participants). Serologically confirmed yaws was rare and focal at population level (24 cases; 2.6 [95% CI 1.4-3.9] cases/10,000 population) with similar clinical epidemiology to other endemic countries in West Africa. Unsupervised classification of spatially referenced case finding data indicated that yaws was more likely to occur in hard-to-reach communities; healthcare-seeking was low among communities, and clinical awareness of yaws was low among healthcare workers. We recovered whole bacterial genomes from 12 cases and describe a monophyletic clade of Treponema pallidum subspecies pertenue, phylogenetically distinct from known TPE lineages, including those affecting neighboring nonhuman primate populations (Taï Forest, Côte d'Ivoire). Yaws is endemic in Liberia but exhibits low focal population prevalence with evidence of a historical genetic bottleneck and subsequent local expansion. Reporting gaps appear attributable to challenging epidemiology and low disease awareness.

Antibody Responses to Two Recombinant Treponemal Antigens (rp17 and TmpA) before and after Azithromycin Treatment for Yaws in Ghana and Papua New Guinea.

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.

Yaws Disease Caused by Treponema pallidum subspecies pertenue in Wild Chimpanzee, Guinea, 2019.

Yaws-like lesions are widely reported in wild African great apes, yet the causative agent has not been confirmed in affected animals. We describe yaws-like lesions in a wild chimpanzee in Guinea for which we demonstrate infection with Treponema pallidum subsp. pertenue. Assessing the conservation implications of this pathogen requires further research.

Modeling Treatment Strategies to Inform Yaws Eradication.

Yaws is a neglected tropical disease targeted for eradication by 2030. To achieve eradication, finding and treating asymptomatic infections as well as clinical cases is crucial. The proposed plan, the Morges strategy, involves rounds of total community treatment (i.e., treating the whole population) and total targeted treatment (TTT) (i.e., treating clinical cases and contacts). However, modeling and empirical work suggests asymptomatic infections often are not found in the same households as clinical cases, reducing the utility of household-based contact tracing for a TTT strategy. We use a model fitted to data from the Solomon Islands to predict the likelihood of elimination of transmission under different intervention schemes and levels of systematic nontreatment resulting from the intervention. Our results indicate that implementing additional treatment rounds through total community treatment is more effective than conducting additional rounds of treatment of at-risk persons through TTT.

Multiplex Mediator Displacement Loop-Mediated Isothermal Amplification for Detection of Treponema pallidum and Haemophilus ducreyi.

Yaws, a neglected tropical disease caused by the bacterium Treponema pallidum subspecies pertenue, manifests as ulcerative skin lesions. Nucleic acid amplification tests, like loop-mediated isothermal amplification (LAMP), are versatile tools to distinguish yaws from infections that cause similar skin lesions, primarily Haemophilus ducreyi. We developed a novel molecular test to simultaneously detect T. pallidum and H. ducreyi based on mediator displacement LAMP. We validated the T. pallidum and H. ducreyi LAMP (TPHD-LAMP) by testing 293 clinical samples from patients with yaws-like lesions. Compared with quantitative PCR, the TPHD-LAMP demonstrated high sensitivity and specificity for T. pallidum (84.7% sensitivity, 95.7% specificity) and H. ducreyi (91.6% sensitivity, 84.8% specificity). This novel assay provided rapid molecular confirmation of T. pallidum and H. ducreyi DNA and might be suitable for use at the point of care. TPHD-LAMP could support yaws eradication by improving access to molecular diagnostic tests at the district hospital level.

Serosurvey of Treponema pallidum infection among children with skin ulcers in the Tarangire-Manyara ecosystem, northern Tanzania.

BACKGROUND: The first yaws eradication campaign reduced the prevalence of yaws by 95%. In recent years, however, yaws has reemerged and is currently subject to a second, ongoing eradication campaign. Yet, the epidemiological status of Tanzania and 75 other countries with a known history of human yaws is currently unknown. Contrary to the situation in humans in Tanzania, recent infection of nonhuman primates (NHPs) with the yaws bacterium Treponema pallidum subsp. pertenue (TPE) have been reported. In this study, we consider a One Health approach to investigate yaws and describe skin ulcers and corresponding T. pallidum serology results among children living in the Tarangire-Manyara ecosystem, an area with increasing wildlife-human interaction in northern Tanzania. METHODS: To investigate human yaws in Tanzania, we conducted a cross-sectional study to screen and interview skin-ulcerated children aged 6 to 15 years, who live in close proximity to two national parks with high numbers of naturally TPE-infected monkeys. Serum samples from children with skin ulcers were tested for antibodies against the bacterium using a treponemal (Treponema pallidum Particle Agglutination assay) and a non-treponemal (Rapid Plasma Reagin) test. RESULTS: A total of 186 children aged between 6 and 15 years (boys: 10.7 ± 2.1 (mean ± SD), N = 132; girls: 10.9 ± 2.0 (mean ± SD), N = 54) were enrolled. Seven children were sampled at health care facilities and 179 at primary schools. 38 children (20.4%) reported active participation in bushmeat hunting and consumption and 26 (13.9%) reported at least one physical contact with a NHP. None of the lesions seen were pathognomonic for yaws. Two children tested positive for treponemal antibodies (1.2%) in the treponemal test, but remained negative in the non-treponemal test. CONCLUSIONS: We found no serological evidence of yaws among children in the Tarangire-Manyara ecosystem. Nevertheless, the close genetic relationship of human and NHPs infecting TPE strains should lead to contact prevention with infected NHPs. Further research investigations are warranted to study the causes and possible prevention measures of spontaneous chronic ulcers among children in rural Tanzania and to certify that the country is free from human yaws.

Integrated approach in the control and management of skin neglected tropical diseases in three health districts of Côte d'Ivoire.

BACKGROUND: Neglected tropical diseases (NTDs) comprise 20 communicable diseases that are prevalent in rural poor and remote communities with less access to the health system. For effective and efficient control, the WHO recommends that affected countries implement integrated control interventions that take into account the different co-endemic NTDs in the same community. However, implementing these integrated interventions involving several diseases with different etiologies, requiring different control approaches and driven by different vertical programs, remains a challenge. We report here the results and lessons learned from a pilot test of this integrated approach based on integrated screening of skin diseases in three co-endemic health districts of Côte d'Ivoire, a West African country endemic for Buruli ulcer, leprosy and yaw. METHOD: This cross-sectional study took place from April 2016 to March 2017 in 3 districts of Côte d'Ivoire co-endemic for BU, leprosy and yaws. The study was carried out in 6 stages: identification of potentially co-endemic communities; stakeholder training; social mobilization; mobile medical consultations; case detection and management; and a review meeting. RESULTS: We included in the study all patients with skin signs and symptoms at the screening stage who voluntarily accepted screening. In total, 2310 persons screened had skin lesions at the screening stage. Among them, 07 cases were diagnosed with Buruli ulcer. There were 30 leprosy cases and 15 yaws detected. Other types of ulcerations and skin conditions have been identified and represent the majority of cases detected. We learned from this pilot experience that integration can be successfully implemented in co-endemic communities in Côte d'Ivoire. Health workers are motivated and available to implement integrated interventions instead of interventions focused on a single disease. However, it is essential to provide capacity building, a minimum of drugs and consumables for the care of the patients identified, as well as follow-up of identified patients, including those with other skin conditions. CONCLUSIONS: The results of this study show that the integration of activities can be successfully implemented in co-endemic communities under the condition of staff capacity building and minimal care of identified patients.

Congenital Syphilis in Honiara, Solomon Islands.

INTRODUCTION: Congenital syphilis remains a significant cause of newborn mortality and long-term neurodevelopmental problems in some low- and middle-income countries. This study was done in Honiara, Solomon Islands to determine the incidence of babies born to mothers with a positive venereal disease research laboratory (VDRL) test and a positive Treponema pallidum haemagglutination assay (TPHA); to determine the VDRL status of newborns and features of congenital syphilis; and to estimate the proportion of stillbirths associated with syphilis. METHODOLOGY: All neonates born to VDRL-positive mothers, including stillbirths were included between April and July 2019. Neonates were examined, investigated and treated. RESULTS: Among 1534 consecutive births, 1469 were live births and 65 (4.2%) were stillbirths. One hundred and forty-three neonates were born to VDRL-positive mothers: 130 (90.1%) were live infants and 13 (8.9%) stillbirths. Of the 130 VDRL-exposed live-born infants, 72 (55%) had reactive VDRL and a positive TPHA and 7 (9.7%) had clinical signs of congenital syphilis. Five of the infants with clinical signs of syphilis infection had a 4-fold higher VDRL titre than their mother. Four infants of VDRL-positive mothers died during admission, all of whom had clinical signs of syphilis. Ninety percent of affected infants were born to mothers who were not treated or only partially treated during pregnancy. CONCLUSIONS: In this study, 1:210 live-born babies had clinical and serological evidence of congenital syphilis, and evidence of Treponema infection was found disproportionately in stillbirths. In a setting where Treponema infections are common, an empirical approach to prevention may be needed.

Endemicity of Yaws and Seroprevalence of Treponema pallidum Antibodies in Nonhuman Primates, Kenya.

Human yaws has historically been endemic to Kenya, but current epidemiologic data are lacking. We report seroprevalence for Treponema pallidum antibodies in olive baboons (Papio anubis) and vervet monkeys (Chlorocebus pygerythrus) in Laikipia County, Kenya. Our results suggest endemicity of the yaws bacterium in monkeys, posing a possible zoonotic threat to humans.

Re-emergence of yaws after single mass azithromycin treatment followed by targeted treatment: a longitudinal study.

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<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. 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.

Diagnostics for Yaws Eradication: Insights From Direct Next-Generation Sequencing of Cutaneous Strains of Treponema pallidum.

Background: Yaws-like chronic ulcers can be caused by Treponema pallidum subspecies pertenue, Haemophilus ducreyi, or other, still-undefined bacteria. To permit accurate evaluation of yaws elimination efforts, programmatic use of molecular diagnostics is required. The accuracy and sensitivity of current tools remain unclear because our understanding of T. pallidum diversity is limited by the low number of sequenced genomes. Methods: We tested samples from patients with suspected yaws collected in the Solomon Islands and Ghana. All samples were from patients whose lesions had previously tested negative using the Centers for Disease Control and Prevention (CDC) diagnostic assay in widespread use. However, some of these patients had positive serological assays for yaws on blood. We used direct whole-genome sequencing to identify T. pallidum subsp pertenue strains missed by the current assay. Results: From 45 Solomon Islands and 27 Ghanaian samples, 11 were positive for T. pallidum DNA using the species-wide quantitative polymerase chain reaction (PCR) assay, from which we obtained 6 previously undetected T. pallidum subsp pertenue whole-genome sequences. These show that Solomon Islands sequences represent distinct T. pallidum subsp pertenue clades. These isolates were invisible to the CDC diagnostic PCR assay, due to sequence variation in the primer binding site. Conclusions: Our data double the number of published T. pallidum subsp pertenue genomes. We show that Solomon Islands strains are undetectable by the PCR used in many studies and by health ministries. This assay is therefore not adequate for the eradication program. Next-generation genome sequence data are essential for these efforts.

Widespread Treponema pallidum Infection in Nonhuman Primates, Tanzania.

We investigated Treponema pallidum infection in 8 nonhuman primate species (289 animals) in Tanzania during 2015-2017. We used a serologic treponemal test to detect antibodies against the bacterium. Infection was further confirmed from tissue samples of skin-ulcerated animals by 3 independent PCRs (polA, tp47, and TP_0619). Our findings indicate that T. pallidum infection is geographically widespread in Tanzania and occurs in several species (olive baboons, yellow baboons, vervet monkeys, and blue monkeys). We found the bacterium at 11 of 14 investigated geographic locations. Anogenital ulceration was the most common clinical manifestation; orofacial lesions also were observed. Molecular data show that nonhuman primates in Tanzania are most likely infected with T. pallidum subsp. pertenue-like strains, which could have implications for human yaws eradication.

Targeted Treatment of Yaws With Household Contact Tracing: How Much Do We Miss?

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.

Mass treatment with single-dose azithromycin for yaws.

BACKGROUND: 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.).

Mathematical Modeling of Programmatic Requirements for Yaws Eradication.

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 [R0]) ranged from 1.08 to 3.32. To have 80% probability of achieving eradication, 8 rounds of treatment with 80% coverage were required at low estimates of R0 (1.45). This requirement increased to 95% at high estimates of R0 (2.47). Extending the treatment interval to 12 months increased requirements at all estimates of R0. At high estimates of R0 with 12 monthly rounds of treatment, no combination of variables achieved eradication. Models should be used to guide the scale-up of yaws eradication.

Metaanalysis of the Performance of a Combined Treponemal and Nontreponemal Rapid Diagnostic Test for Syphilis and Yaws.

BACKGROUND: The human treponematoses are important causes of disease. Mother-to-child transmission of syphilis remains a major cause of stillbirth and neonatal death. There are also almost 100 000 cases of endemic treponemal disease reported annually, predominantly yaws. Rapid diagnostic tests (RDTs) would improve access to screening for these diseases. Most RDTs cannot distinguish current and previous infection. The Dual Path Platform (DPP) Syphilis Screen & Confirm test includes both a treponemal (T1) and nontreponemal (T2) component and may improve the accuracy of diagnosis. METHODS: We conducted a metaanalysis of published and unpublished evaluations of the DPP-RDT for the diagnosis of syphilis and yaws. We calculated the sensitivity, specificity, and overall agreement of the test compared with reference laboratory tests. RESULTS: Nine evaluations, including 7267 tests, were included. Sensitivity was higher in patients with higher titer rapid plasma reagin (≥1:16) for both the T1 (98.2% vs 90.1%, P < .0001) and the T2 component (98.2% vs 80.6%, P < .0001). Overall agreement between the DPP test and reference serology was 85.2% (84.4%-86.1%). Agreement was highest for high-titer active infection and lowest for past infection. CONCLUSIONS: The RDT has good sensitivity and specificity of the treponemal and nontreponemal components both in cases of suspected syphilis and yaws, although the sensitivity is decreased at lower antibody titers.