Introducing new diagnostics into STI control programmes: the importance of programme science.

Many innovative diagnostic technologies will become commercially available over the next 5-10 years. These tests can potentially transform the diagnosis of sexually transmitted infections but their introduction into control programmes can be hampered by health system constraints, and political, cultural, socioeconomic and behavioural factors. We used the introduction of syphilis rapid tests to illustrate the importance of programme science to address the gap between accruing evidence of acceptable test performance and the complexity of programme design, implementation and evaluation of test deployment to address public health needs and improve patient-important outcomes

Endemic treponemal diseases.

The endemic treponemal diseases, consisting of yaws, bejel (endemic syphilis) and pinta, are non-venereal infections closely related to syphilis, and are recognized by WHO as neglected tropical diseases (NTDs). Despite previous worldwide eradication efforts the prevalence of yaws has rebounded in recent years and the disease is now a major public health problem in 14 countries. Adequate data on the epidemiology of bejel and pinta is lacking. Each disease is restricted to a specific ecological niche but all predominantly affect poor, rural communities. As with venereal syphilis, the clinical manifestations of the endemic treponemal diseases are variable and can be broken down in to early stage and late stage disease. Current diagnostic techniques are unable to distinguish the different causative species but newer molecular techniques are now making this possible. Penicillin has long been considered the mainstay of treatment for the endemic treponemal diseases but the recent discovery that azithromycin is effective in the treatment of yaws has renewed interest in these most neglected of the NTDs, and raised hopes that global eradication may finally be possible

Yaws.

INTRODUCTION: 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. SOURCES OF DATA: We reviewed published data, surveillance data and data presented at yaws eradication meetings. AREAS OF AGREEMENT: Azithromycin is now the preferred agent for treating yaws. Point-of-care tests have demonstrated their value in yaws. AREAS OF CONTROVERSY: 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. GROWING POINTS: Yaws eradication appears an achievable goal. The programme will require considerable support from partners across health and development sectors. AREAS TIMELY FOR DEVELOPING RESEARCH: Studies to complete baseline mapping, integrate diagnostic tests into surveillance and assess the impact of community mass treatment with azithromycin are ongoing

Yaws

Introduction 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. Sources of data We reviewed published data, surveillance data and data presented at yaws eradication meetings. Areas of agreement Azithromycin is now the preferred agent for treating yaws. Point-of-care tests have demonstrated their value in yaws. Areas of controversy 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. Growing points Yaws eradication appears an achievable goal. The programme will require considerable support from partners across health and development sectors. Areas timely for developing research Studies to complete baseline mapping, integrate diagnostic tests into surveillance and assess the impact of community mass treatment with azithromycin are ongoin

Support and performance improvement for primary health care workers in low- and middle-income countries: a scoping review of intervention design and methods.

Primary health care workers (HCWs) in low- and middle-income settings (LMIC) often work in challenging conditions in remote, rural areas, in isolation from the rest of the health system and particularly specialist care. Much attention has been given to implementation of interventions to support quality and performance improvement for workers in such settings. However, little is known about the design of such initiatives and which approaches predominate, let alone those that are most effective. We aimed for a broad understanding of what distinguishes different approaches to primary HCW support and performance improvement and to clarify the existing evidence as well as gaps in evidence in order to inform decision-making and design of programs intended to support and improve the performance of health workers in these settings. We systematically searched the literature for articles addressing this topic, and undertook a comparative review to document the principal approaches to performance and quality improvement for primary HCWs in LMIC settings. We identified 40 eligible papers reporting on interventions that we categorized into five different approaches: (1) supervision and supportive supervision; (2) mentoring; (3) tools and aids; (4) quality improvement methods, and (5) coaching. The variety of study designs and quality/performance indicators precluded a formal quantitative data synthesis. The most extensive literature was on supervision, but there was little clarity on what defines the most effective approach to the supervision activities themselves, let alone the design and implementation of supervision programs. The mentoring literature was limited, and largely focused on clinical skills building and educational strategies. Further research on how best to incorporate mentorship into pre-service clinical training, while maintaining its function within the routine health system, is needed. There is insufficient evidence to draw conclusions about coaching in this setting, however a review of the corporate and the business school literature is warranted to identify transferrable approaches. A substantial literature exists on tools, but significant variation in approaches makes comparison challenging. We found examples of effective individual projects and designs in specific settings, but there was a lack of comparative research on tools across approaches or across settings, and no systematic analysis within specific approaches to provide evidence with clear generalizability. Future research should prioritize comparative intervention trials to establish clear global standards for performance and quality improvement initiatives. Such standards will be critical to creating and sustaining a well-functioning health workforce and for global initiatives such as universal health coverage

Prevalence of Active and Latent Yaws in the Solomon Islands 18 Months after Azithromycin Mass Drug Administration for Trachoma.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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

Targeted treatment of yaws with 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

Failure of PCR to Detect Treponema pallidum ssp. pertenue DNA in Blood in Latent Yaws.

Yaws, caused by Treponema pallidum ssp. pertenue, is a neglected tropical disease closely related to venereal syphilis and is targeted for eradication by 2020. Latent yaws represents a diagnostic challenge, and current tools cannot adequately distinguish between individuals with true latent infection and individuals who are serofast following successful treatment. PCR on blood has previously been shown to detect T. pallidum DNA in patients with syphilis, suggesting that this approach may be of value in yaws. We performed real-time PCR for Treponema pallidum ssp. pertenue on blood samples from 140 children with positive T. pallidum Particle Agglutination (TPPA) and Rapid Plasma Reagin (RPR) tests and 7 controls (negative serology), all collected as part of a prospective study of yaws in the Solomon Islands. All samples were also tested by a nested PCR for T. pallidum. 12 patients had clinical evidence of active yaws whilst 128 were considered to have latent yaws. 43 children had high titre rapid plasma reagins (RPRs) of ≥1:32. PCR testing with both assays gave negative results in all cases. It is possible that the failure to detect T. pallidum ssp. pertenue in blood reflects lower loads of organism in latent yaws compared to those in latent infection with T. pallidum ssp. pertenue, and/or a lower propensity for haematogenous dissemination in yaws than in syphilis. As the goal of the yaws control programme is eradication, a tool that can differentiate true latent infection from individuals who are serofast would be of value; however, PCR of blood is not that tool