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

Chlamydiae as pathogens: new species and new issues.

The recognition of genital chlamydial infection as an important public health problem was made first by the recognition of its role in acute clinical syndromes, as well as in serious reproductive and ocular complications, and secondly by our awareness of its prevalence when diagnostic tests became widely accessible. The recent availability of effective single dose oral antimicrobial therapy and sensitive molecular amplification tests that allow the use of noninvasive specimens for diagnosis and screening is expected to have a major impact in reducing the prevalence of disease in the next decade. Clinical manifestations associated with Chlamydia pneumoniae infection continue to emerge beyond respiratory illness. In particular, its association with atherosclerosis deserves further investigation. Chlamydia pecorum, a pathogen of ruminants, was recently recognized as a new species. The continued application of molecular techniques will likely elucidate an expanding role for chlamydiae in human and animal diseases, delineate the phylogenetic relationships among chlamydial species and within the eubacteria domain, and provide tools for detection and control of chlamydial infections

Advancing prevention of sexually transmitted infections through point-of-care testing : target product profiles and landscape analysis

Objectives: Advancing the field of point-of-care testing (POCT) for STIs can rapidly and substantially improve STI control and prevention by providing targeted, essential STI services (case detection and screening). POCT enables definitive diagnosis and appropriate treatment in a single visit and home and community-based testing. Methods: Since 2014, the WHO Department of Reproductive Health and Research, in collaboration with technical partners, has completed four landscape analyses of promising diagnostics for use at or near the point of patient care to detect syphilis, Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis and the human papillomavirus. The analyses comprised a literature review and interviews. Two International Technical Consultations on STI POCTs (2014 and 2015) resulted in the development of target product profiles (TPP). Experts in STI microbiology, laboratory diagnostics, clinical management, public health and epidemiology participated in the consultations with representation from all WHO regions. Results: The landscape analysis identified diagnostic tests that are either available on the market, to be released in the near future or in the pipeline. The TPPs specify 28 analytical and operational characteristics of POCTs for use in different populations for surveillance, screening and case management. None of the tests that were identified in the landscape analysis met all of the targets of the TPPs. Conclusion: More efforts of the global health community are needed to accelerate access to affordable quality-assured STI POCTs, particularly in low-and middle-income countries, by supporting the development of new diagnostic platforms as well as strengthening the validation and implementation of existing diagnostics according to internationally endorsed standards and the best available evidence

Improving access to new diagnostics through harmonised regulation: priorities for action.

A new generation of diagnostic tests is being developed for use at the point of care that could save lives and reduce the spread of infectious diseases through early detection and treatment. It is important that patients in developing countries have access to these products at affordable prices and without delay. Regulation of medical products is intended to ensure safety and quality whilst balancing the need for timely access to beneficial new products. Current regulatory oversight of diagnostic tests in developing countries is highly variable and weak regulation allows poor-quality tests to enter the market. However, inefficient or overzealous regulation results in unnecessary delays, increases costs and acts as a barrier to innovation and market entry. Setting international standards and streamlining the regulatory process could reduce these barriers. Four priority activities have been identified where convergence of standards and protocols or joint review of data would be advantageous: (1) adoption of a common registration file for pre-market approval; (2) convergence of quality standards for manufacturing site inspections; (3) use of common evaluation protocols, as well as joint review of data, to reduce unnecessary duplication of lengthy and costly clinical performance studies; and (4) use of networks of laboratories for post-market surveillance in order to monitor ongoing quality of diagnostic devices. The adoption and implementation of such measures in developing countries could accelerate access to new diagnostic tests that are safe and affordable

The trade-off between accuracy and accessibility of syphilis screening assays.

The availability of rapid and sensitive methods to diagnose syphilis facilitates screening of pregnant women, which is one of the most cost-effective health interventions available. We have evaluated two screening methods in Tanzania: an enzyme immunoassay (EIA), and a point-of-care test (POCT). We evaluated the performance of each test against the Treponema pallidum particle agglutination assay (TPPA) as the reference method, and the accessibility of testing in a rural district of Tanzania. The POCT was performed in the clinic on whole blood, while the other assays were performed on plasma in the laboratory. Samples were also tested by the rapid plasma Reagin (RPR) test. With TPPA as reference assay, the sensitivity and specificity of EIA were 95.3% and 97.8%, and of the POCT were 59.6% and 99.4% respectively. The sensitivity of the POCT and EIA for active syphilis cases (TPPA positive and RPR titer ≥ 1/8) were 82% and 100% respectively. Only 15% of antenatal clinic attenders in this district visited a health facility with a laboratory capable of performing the EIA. Although it is less sensitive than EIA, its greater accessibility, and the fact that treatment can be given on the same day, means that the use of POCT would result in a higher proportion of women with syphilis receiving treatment than with the EIA in this district of Tanzania

The costs of accessible quality assured syphilis diagnostics: informing quality systems for rapid syphilis tests in a Tanzanian setting.

OBJECTIVES: To determine the costs of Rapid Syphilis Test (RSTs) as compared with rapid plasma reagin (RPR) when implemented in a Tanzanian setting, and to determine the relative impact of a quality assurance (QA) system on the cost of RST implementation. METHODS: The incremental costs for RPR and RST screening programmes in existing antenatal care settings in Geita District, Tanzania were collected for 9 months in subsequent years from nine health facilities that varied in size, remoteness and scope of antenatal services. The costs per woman tested and treated were estimated for each facility. A sensitivity analysis was constructed to determine the impact of parameter and model uncertainty. FINDINGS: In surveyed facilities, a total of 6362 women were tested with RSTs compared with 224 tested with RPR. The range of unit costs was $1.76-$3.13 per woman screened and $12.88-$32.67 per woman treated. Unit costs for the QA system came to $0.51 per woman tested, of which 50% were attributed to salaries and transport for project personnel. CONCLUSIONS: Our results suggest that rapid syphilis diagnostics are very inexpensive in this setting and can overcome some critical barriers to ensuring universal access to syphilis testing and treatment. The additional costs for implementation of a quality system were found to be relatively small, and could be reduced through alterations to the programme design. Given the potential for a quality system to improve quality of diagnosis and care, we recommend that QA activities be incorporated into RST roll-out

The future of viral hepatitis testing: innovations in testing technologies and approaches.

A large burden of undiagnosed hepatitis virus cases remains globally. Despite the 257 million people living with chronic hepatitis B virus infection, and 71 million with chronic viraemic HCV infection, most people with hepatitis remain unaware of their infection. Advances in rapid detection technology have created new opportunities for enhancing access to testing and care, as well as monitoring of treatment. This article examines a range of other technological innovations that can be leveraged to provide more affordable and simplified approaches to testing for HBV and HCV infection and monitoring of treatment response. These include improved access to testing through alternative sampling methods (use of dried blood spots, oral fluids, self-testing) and combination rapid diagnostic tests for detection of HIV, HBV and HCV infection; more affordable options for confirmation of virological infection (HBV DNA and HCV RNA) such as point-of-care molecular assays, HCV core antigen and multi-disease polyvalent molecular platforms that make use of existing centralised laboratory based or decentralised TB and HIV instrumentation for viral hepatitis testing; and finally health system improvements such as integration of laboratory services for procurement and sample transportation and enhanced data connectivity to support quality assurance and supply chain management

Rapid Syphilis Tests as Catalysts for Health Systems Strengthening: A Case Study from Peru.

OBJECTIVES: Untreated maternal syphilis leads to adverse pregnancy outcomes. The use of point of care tests (POCT) offers an opportunity to improve screening coverage for syphilis and other aspects of health systems. Our objective is to present the experience of the introduction of POCT for syphilis in Peru and describe how new technology can catalyze health system strengthening. METHODS: The study was implemented from September 2009-November 2010 to assess the feasibility of the use of a POCT for syphilis for screening pregnant women in Lima, Peru. Outcomes measured included access to syphilis screening, treatment coverage, partner treatment, effect on patient flow and service efficiency, acceptability among providers and patients, and sustainability. RESULTS: Before the introduction of POCT, a pregnant woman needed 6 visits to the health center in 27 days before she received her syphilis result. We trained 604 health providers and implemented the POCT for syphilis as the "two for one strategy", offering with one finger stick both syphilis and HIV testing. Implementation of the POCT resulted in testing and treatment on the first visit. Screening and treatment coverages for syphilis improved significantly compared with the previous year. Implementation of POCT has been scaled up nationally since the study ended, and coverages for screening, treatment and partner treatment have remained over 92%. CONCLUSIONS: Implementation of POCT for syphilis proved feasible and acceptable, and led to improvement in several aspects of health services. For the process to be effective we highlight the importance of: (1) engaging the authorities; (2) dissipating tensions between providers and identifying champions; (3) training according to the needs; (4) providing monitoring, supervision, support and recognition; (5) sharing results and discussing actions together; (6) consulting and obtaining feedback from users; and (7) integrating with other services such as with rapid HIV testing