Modeling Treatment Strategies to Inform Yaws Eradication.
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ABSTRACT:
SUBMITTER: Holmes A
PROVIDER: S-EPMC7588528 | biostudies-literature | 2020 Nov
REPOSITORIES: biostudies-literature
Publications
Modeling Treatment Strategies to Inform Yaws Eradication.
Holmes Alex A Tildesley Michael J MJ Solomon Anthony W AW Mabey David C W DCW Sokana Oliver O Marks Michael M Dyson Louise L
Emerging infectious diseases 20201101 11
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 cl ...[more]
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Project description: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.
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Project description: Not available
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Project description:BackgroundTreponema pallidum subspecies pertenue causes yaws. Strategies to better control, eliminate, and eradicate yaws are needed.MethodsIn 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.ResultsOf 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.ConclusionsThe 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.).
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Project description:BackgroundYaws 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.Methodology and principal findingsThe 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.ConclusionsThe TPPs developed will provide test developers with guidance to ensure that novel diagnostic tests meet identified public health needs.
| S-EPMC9473620 | biostudies-literature
Project description:Large reductions in the global malaria burden have been achieved, but plateauing funding poses a challenge for progressing towards the ultimate goal of malaria eradication. Using previously published mathematical models of Plasmodium falciparum and Plasmodium vivax transmission incorporating insecticide-treated nets (ITNs) as an illustrative intervention, we sought to identify the global funding allocation that maximized impact under defined objectives and across a range of global funding budgets. The optimal strategy for case reduction mirrored an allocation framework that prioritizes funding for high-transmission settings, resulting in total case reductions of 76% and 66% at intermediate budget levels, respectively. Allocation strategies that had the greatest impact on case reductions were associated with lesser near-term impacts on the global population at risk. The optimal funding distribution prioritized high ITN coverage in high-transmission settings endemic for P. falciparum only, while maintaining lower levels in low-transmission settings. However, at high budgets, 62% of funding was targeted to low-transmission settings co-endemic for P. falciparum and P. vivax. These results support current global strategies to prioritize funding to high-burden P. falciparum-endemic settings in sub-Saharan Africa to minimize clinical malaria burden and progress towards elimination, but highlight a trade-off with 'shrinking the map' through a focus on near-elimination settings and addressing the burden of P. vivax.
| S-EPMC10957170 | biostudies-literature
Project description:BackgroundPre-exposure prophylaxis (PrEP) is essential to ending HIV. Yet, uptake remains uneven across racial and ethnic groups. We aimed to estimate the impacts of alternative PrEP implementation strategies in Los Angeles County.SettingMen who have sex with men, residing in Los Angeles County.MethodsWe developed a microsimulation model of HIV transmission, with inputs from key local stakeholders. With this model, we estimated the 15-year (2021-2035) health and racial and ethnic equity impacts of 3 PrEP implementation strategies involving coverage with 9000 additional PrEP units annually, above the Status-quo coverage level. Strategies included PrEP allocation equally (strategy 1), proportionally to HIV prevalence (strategy 2), and proportionally to HIV diagnosis rates (strategy 3), across racial and ethnic groups. We measured the degree of relative equalities in the distribution of the health impacts using the Gini index (G) which ranges from 0 (perfect equality, with all individuals across all groups receiving equal health benefits) to 1 (total inequality).ResultsHIV prevalence was 21.3% in 2021 [Black (BMSM), 31.1%; Latino (LMSM), 18.3%, and White (WMSM), 20.7%] with relatively equal to reasonable distribution across groups (G, 0.28; 95% confidence interval [CI], 0.26 to 0.34). During 2021-2035, cumulative incident infections were highest under Status-quo (n = 24,584) and lowest under strategy 3 (n = 22,080). Status-quo infection risk declined over time among all groups but remained higher in 2035 for BMSM (incidence rate ratio, 4.76; 95% CI: 4.58 to 4.95), and LMSM (incidence rate ratio, 1.74; 95% CI: 1.69 to 1.80), with the health benefits equally to reasonably distributed across groups (G, 0.32; 95% CI: 0.28 to 0.35). Relative to Status-quo, all other strategies reduced BMSM-WMSM and BMSM-LMSM disparities, but none reduced LMSM-WMSM disparities by 2035. Compared to Status-quo, strategy 3 reduced the most both incident infections (% infections averted: overall, 10.2%; BMSM, 32.4%; LMSM, 3.8%; WMSM, 3.5%) and HIV racial inequalities (G reduction, 0.08; 95% CI: 0.02 to 0.14).ConclusionsMicrosimulation models developed with early, continuous stakeholder engagement and inputs yield powerful tools to guide policy implementation.
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Project description:IntroductionA disabling and disfiguring disease that "begins where the road ends", yaws is targeted by WHO for eradication by the year 2020. The global campaign is not yet financed. To evaluate yaws eradication within the context of the post-2015 development agenda, we perform a somewhat allegorical cost-effectiveness analysis of eradication, comparing it to a counterfactual in which we simply wait for more roads (the end of poverty).MethodsWe use evidence from four yaws eradication pilot sites and other mass treatment campaigns to set benchmarks for the cost of eradication in 12 known endemic countries. We construct a compartmental model of long-term health effects to 2050. Conservatively, we attribute zero cost to the counterfactual and allow for gradual exit of the susceptible (at risk) population by road (poverty reduction). We report mean, 5th and 95th centile estimates to reflect uncertainty about costs and effects.ResultsOur benchmark for the economic cost of yaws eradication is uncertain but not high -US$ 362 (75-1073) million in 12 countries. Eradication would cost US$ 26 (4.2-78) for each year of life lived without disability or disfigurement due to yaws, or US$ 324 (47-936) per disability-adjusted life year (DALY). Excluding drugs, existing staff and assets, the financial cost benchmark is US$ 213 (74-522) million. The real cost of waiting for more roads (poverty reduction) would be 13 (7.3-20) million years of life affected by early-stage yaws and 2.3 (1.1-4.2) million years of life affected by late-stage yaws.DiscussionEndemic countries need financing to begin implementing and adapting global strategy to local conditions. Donations of drugs and diagnostics could reduce cost to the public sector and catalyze financing. Resources may be harnessed from the extractive industries. Yaws eradication should be seen as complementary to universal health coverage and shared prosperity on the post-2015 development agenda.
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Project description:Due to security, access, and programmatic challenges in areas of Pakistan and Afghanistan, both countries continue to sustain indigenous wild poliovirus (WPV) transmission and threaten the success of global polio eradication and oral poliovirus vaccine (OPV) cessation. We fitted an existing differential-equation-based poliovirus transmission and OPV evolution model to Pakistan and Afghanistan using four subpopulations to characterize the well-vaccinated and undervaccinated subpopulations in each country. We explored retrospective and prospective scenarios for using inactivated poliovirus vaccine (IPV) in routine immunization or supplemental immunization activities (SIAs). The undervaccinated subpopulations sustain the circulation of serotype 1 WPV and serotype 2 circulating vaccine-derived poliovirus. We find a moderate impact of past IPV use on polio incidence and population immunity to transmission mainly due to (1) the boosting effect of IPV for individuals with preexisting immunity from a live poliovirus infection and (2) the effect of IPV-only on oropharyngeal transmission for individuals without preexisting immunity from a live poliovirus infection. Future IPV use may similarly yield moderate benefits, particularly if access to undervaccinated subpopulations dramatically improves. However, OPV provides a much greater impact on transmission and the incremental benefit of IPV in addition to OPV remains limited. This study suggests that despite the moderate effect of using IPV in SIAs, using OPV in SIAs remains the most effective means to stop transmission, while limited IPV resources should prioritize IPV use in routine immunization.
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Project description: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.
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Project description:Nursing home residents and staff were included in the first phase of COVID-19 vaccination in the United States. Because the primary trial endpoint was vaccine efficacy (VE) against symptomatic disease, there are limited data on the extent to which vaccines protect against SARS-CoV-2 infection and the ability to infect others (infectiousness). Assumptions about VE against infection and infectiousness have implications for possible changes to infection prevention guidance for vaccinated populations, including testing strategies. We use a stochastic agent-based SEIR model of a nursing home to simulate SARS-CoV-2 transmission. We model three scenarios, varying VE against infection, infectiousness, and symptoms, to understand the expected impact of vaccination in nursing homes, increasing staff vaccination coverage, and different screening testing strategies under each scenario. Increasing vaccination coverage in staff decreases total symptomatic cases in each scenario. When there is low VE against infection and infectiousness, increasing staff coverage reduces symptomatic cases among residents. If vaccination only protects against symptoms, but asymptomatic cases remain infectious, increased staff coverage increases symptomatic cases among residents through exposure to asymptomatic but infected staff. High frequency testing is needed to reduce total symptomatic cases if the vaccine has low efficacy against infection and infectiousness, or only protects against symptoms. Encouraging staff vaccination is not only important for protecting staff, but might also reduce symptomatic cases in residents if a vaccine confers at least some protection against infection or infectiousness. The extent of efficacy of SARS-CoV-2 vaccines against infection, infectiousness, or disease, impacts strategies for vaccination and testing in nursing homes. If vaccines confer some protection against infection or infectiousness, encouraging vaccination in staff may reduce symptomatic cases in residents.
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