Encourage target discovery

Participants suggested the development of a TPP for POCTs specifically for the elimination of mother-to-child transmission of syphilis. There is a need for a novel marker of active syphilis that can be detected using easy, low-tech, low-cost and effective technologies to replace the detection of non-treponemal antibody (reagin) as a proxy of active syphilis, given the dilemma whether to repeat treatment for patients with persistent non-treponemal antibody. Identifying new markers for active syphilis is a high-risk undertaking, it should however not be neglected by developers, as it is a critical tool for the elimination of mother-to-child transmission of syphilis and management of the ‘serofast’ patient. Both the utility of absolute titres and comparison of titres over time, and between the baby versus the mother, should be considered.

Participants recommended the identification of genetic markers to predict gonococcal resistance/susceptibility, including nucleic acid targets, against recommended therapeutic agents for gonorrhoea. The frequency of potential diagnostic targets in different gonococcal genotypes and populations should be investigated. Current technologies are complicated, requiring multiple steps, trained personnel and may take more than 48 hours to perform. The novel resistance markers should be incorporated into a POCT to track resistance.

Encourage integration and miniaturisation of sample preparation and target detection

As was pointed out in the landscape of POCTs in this supplement, sample preparation and target detection are two key processes in diagnostics. ‘Next-generation’ technologies, such as microfluidics and nanotechnology, enabling the integration and miniaturisation of both processes, should be fully supported to overcome these barriers.12 Although miniaturisation allows complex technologies to be used at POC, it should be noted that the smaller sample size required for these nanoscale reactions poses a risk that test sensitivity would be poor unless the diagnostic target is present in ample amounts.13

The AMR opinion paper in this supplement shows that microfluidic and nanotechnology platforms provide a basis to develop molecular POC–AMR diagnostics. However, particularly for gonorrhoea, more knowledge is required to assess which antibiotic classes lend themselves to a genotypic POC–AMR approach. It is difficult to estimate the potential clinical and epidemiological impact of using a genotypic approach when genotypic–phenotypic relationships for N. gonorrhoeae are not well understood.14

It could be beneficial to improve and promote non-invasive sample collection where possible, for example, urine among men and women in the case of urethrogenital infections, and saliva in case of systemic infections like syphilis, without jeopardising the analytical performance of STI POCTs. Diagnostic platforms should be calibrated according to the quantity of pathogen targets in samples in order to ensure acceptable levels of sensitivity and specificity.

Promote international and multisectorial research cooperation

To enable research in low-resource settings, participants suggested the creation of biobanks to gather available well-characterised specimens that can be accessed by various stakeholders.

The knowledge of conserved diagnostic target sequences across the globe could be improved by expanding genomic sequence databases.

Although the field of STI POCTs is advancing, initiatives to prompt the uptake of novel technologies have been scarce compared to the POCT field in other areas in clinical medicine.15 A literature review should be conducted to identify promising crossover initiatives, both for STIs and emerging infectious diseases.

Prioritise the development of miniaturised multiplexable STI POCT platforms

The development of a POCT that simultaneously screens for multiple pathogens from a single specimen should be prioritised because the same clinical symptoms can be caused by infections by many aetiological agents and mixed infections are common.12 Moreover, disease and therapeutic response often involve interplay between many biological processes.13 Multiplexing could also potentially increase throughput and data generation while simplifying formats and decreasing the time and cost required to operate tests, which makes them more fit for use in low- and middle-income settings than current POCT platforms.

The IEG stressed the need for further developing next-generation platforms and prototypes to miniaturise the products, their footprints and turnaround time and combining them to achieve multiplexing optimisation. Target combinations should be optimised to improve global strain coverage while reducing any signal interference. The possibility of having a multiplex pregnancy/HIV/syphilis POCT was raised.

One of the very promising prototypes uses microfluidics and lab-on-chip technology, capable of detecting major causes of STIs simultaneously at very low cost per test.17 It is, however, not yet commercially available nor widely evaluated. Another promising approach, which combines both spatial and spectral multiplexing, uses quantum dots, potentially increasing the multiplexing capabilities of immunoassays.13 Recent developments in paper-based microfluidic assays together with novel assay formats have also unprecedentedly expanded the number and complexity of tests that can be conducted using low-cost and disposable POCT kits, particularly in the developing world.18 A more comprehensive overview of the next-generation technologies can be found in the landscape article in this supplement.

Include researchers, manufacturers and end-users in the translational phase of POCTs

The meeting participants acknowledged that in most settings, few appropriate tests are available. Part of the reason being that the scientists and engineers who design these tests, and the companies who develop and market them, are usually based in affluent countries and are often unaware of settings and the real needs of the end-users in the developing world.19 Bringing them together with end-users, providers and patients, in the translational stage of POCT development creates an opportunity for proactive problem-solving, discussions about trade-offs and device design.20 21 In addition, used to working with few resources and local healthcare professionals might come up with simple yet innovative solutions to challenges around cost-effectiveness.

The IEG stressed the need for more qualitative studies in different settings and populations, to assess end-users’ requirements.22

Capitalise on the advances in connectivity for STI-surveillance, testing uptake and quality control of STI POCTs

If an STI POCT comes with a reader and is introduced in a whole region or country, connectivity may be used for STI surveillance purpose.23

Quality control is not often included in the translation stage of POCT development. Reader devices should be an asset for enhancing quality control programmes. If data are not coming in, programme managers can immediately investigate the reason (personnel, supplies, treatment stock-outs, etc) and initiate corrective action. Connectivity solutions can be leveraged to turn system stresses into increasing efficiency.

The meeting participants agreed on the need of AMR—research in N. gonorrhoeae to capitalise on the fact that mobile phones are widespread globally, even in low- and middle-income settings, although not all. Mobile phones and smartphone applications could facilitate reading POCT test results, promote uptake and increase follow-up. STI apps might lead to more testing.24 The fact that current STI apps have a marked variation in content, quality and accuracy, some even contain potentially harmful information,25 calls for the need to invest in a free, good quality e-health approach to sexual health and well-being, which could complement and reinforce the introduction of STI POCTs.

The IEG also emphasised the need of making TTPs for self-administered, home-based STI diagnostic tools, which can be purchased online or through apps.26

Promote standardised high-quality laboratory, clinic-based and utility evaluations of STI POCTs

The IEG welcomed the initiative of WHO to prepare core protocols for laboratory, clinic-based and utility evaluation of STI POCTs and indicated those STIs for which POCTs are most urgent and the populations in greatest need of them. The research priorities for diagnostic tests in a public health setting are based on the main challenging areas in terms of STI control from a diagnostic perspective. Linking the discussion on STI POCTs to STI case management as well as STI control and prevention in key populations, the following priorities were identified:

• Chlamydia/trichomoniasis: high prevalence, understanding the purpose of regular screening in women at risk;

• Gonorrhoea: increase of resistance in N. gonorrhoeae, increasing the need for scaling up regular screening of women at high risk;

• Chlamydia/gonorrhoea/trichomoniasis: case management vaginal discharge syndrome needs to optimise case management through introduction of testing;

• Chlamydia/gonorrhoea: screening in men who have sex with men (MSM) in extragenital anatomic sites: using pharyngeal and anorectic swabs;

• Dual HIV/syphilis: screening in antenatal care (ANC) as well as sex workers and MSM.

These protocols have in the mean time been approved by the Research Project Review Panel of the Reproductive Health and Research Department (RHR) and the Research Ethics Review Committee of WHO. The protocols are freely available on the WHO website. Building on these achievements, RHR plans to conduct independent multicountry evaluations of existing promising tests and technologies starting from 2017, as an essential next step to advance the understanding of performance, feasibility, acceptability and utility of existing STI POCTs, to develop an investment case for the implementation of STI POCTs within national STI control and prevention programmes and to inform and promote the development of appropriate STI POC diagnostic platforms.

High-quality evaluations in laboratory and real-world settings include evaluating sensitivity and specificity, and predictive values, and determining optimal operational characteristics of STI POCTs in sample sets from high-prevalence and low-prevalence clinical settings and in a variety of populations, for both screening for asymptomatic STIs and for case management.28 The clinical utility should be comprehensively evaluated, by morbidity/mortality and adverse event profiles of the target infections.

The IEG emphasised that the required level of sensitivity depends on the context of the site, including among others access, laboratory infrastructure and quality assurance. The evaluations should be carried out opportunistically and take advantage of having a rapid turnaround time for test results to determine whether the POCT can be used to streamline patient pathways and improve the efficiency of the healthcare system.29 30 The ecology of the site should be comprehensively assessed. The paper on clinic-based evaluation of syphilis POCTs in Verona, included in this supplement, suggested that despite low sensitivity, lower than the minimum set in the TPPs, predictive values can still be acceptable for rolling out POCT testing.

Specifically for syphilis POCTs, the experts suggested that the results of evaluations in ANC should be used to reconsider the treatment algorithm. In some settings, the patients might not come back for the result of the reference test and consequent treatment. If the risk of missing to treat a syphilis case is high, then presumptive treatment should be considered. The IEG also raised the issue of including the partners of pregnant women in the evaluations.

The evaluations should also help to clarify what the minimal time should be between the POCT and the (potential) infection and when to retest after risk or treatment.

To accelerate the introduction of promising tests, they should be evaluated before they become commercially available.

Lastly, the IEG noted that conducting POCT evaluations can be a vehicle to assess the quality of participating laboratories and provide capacity building if needed.

Determine local preferences and perceptions of patients and providers towards STI POCTs

The IEG called for more studies to determine local preferences and perceptions on the use of STI POCTs in clinic-based and community-based outreach settings. Qualitative studies should assess attitudes, the perceived usefulness and changes in the management of STIs, which might result in more timely and targeted treatment, earlier commencement of partner notification and reduced follow-up efforts. Providers should be questioned about their confidence in POCT results and consequent treatment decisions and changes in job satisfaction. As shown in figure 2, even though POCTs can shorten episodes of care, managing positive test results in a shorter time frame can also be challenging.31

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Figure 2

Potential influences on acceptability of a POCT to operators in remote health services. Reprinted from “I Do Feel Like a Scientist at Times”: A Qualitative Study of the Acceptability of Molecular Point-Of-Care Testing for Chlamydia and Gonorrhoea to Primary Care Professionals in a Remote High STI Burden, by Natoli et al. 31 All PLOS content is available under CC BY (Creative Commons Attribution).

Accelerate the development of STI POCT guidelines and harmonisation of regulatory approval

If POCTs are to be effective STI diagnostics of the future in primary care centres in low- and middle-income countries, there should be a regularly updated set of easy-to-use guidelines and recommendations for use of POCTs for STI case management, screening of asymptomatic infections and surveillance.

WHO has recently published an information note on the use of dual HIV/syphilis rapid diagnostic tests with the main focus on antenatal services.34 This is an important step towards the integration of dual HIV/syphilis POCTs into guidelines for management of syphilis in pregnant women, aiming to advance the dual elimination of HIV/syphilis.

The IEG suggested a review to determine the regulatory approval frameworks, procurement mechanisms and distributors in settings of interest around the world, this could be informative for both the evaluation of POCTs as for the manufacturers.

Plan for introduction in advance

The approach to introducing POCTs to healthcare systems should consider all its aspects in advance of product introduction, including patient information, experiences, ideas for uptake, and the clinic and social systems in the local area. Crowdsourcing and using non-traditional ways to include populations in STI POCT provision35 might increase community engagement, essential for successful implementation of an STI POCT strategy.36

I mplementation studies should be conducted to determine staff training needs and inform the development of general and context-specific and population-specific trainings.

Anticipate potential tensions of STI POCT introduction by modelling the impact on health systems

The technological innovations of POCTs allow for a shift in the health system towards more decentralisation. Decentralised testing has tremendous advantages in accessibility of the services and follow-up, but places considerable pressure on health systems, particularly in terms of personnel, infrastructure and ensuring quality of service.37

Moving towards decentralisation of testing could be seen as a concern for future stability by laboratories, as some of their tasks regarding STI-testing would disappear. The EIG suggested assessing the capability and willingness of laboratories to accept a new role: they should monitor and evaluate STI testing both during and after the shift to POCTs. The laboratory should become both a command and training centre for POCTs and their providers.38

Harmonisation of critical elements of new pathways to deliver STI POCTs, particularly over-the-counter, should be anticipated. Different public health programmes, for both communicable and non-communicable diseases, should collaborate to harmonise delivery systems for a large spectrum of existing and upcoming POCTs, reducing potential tensions between different parties involved in procurement, delivery, use and postmarket monitoring and evaluation.

If connectivity is adequately implemented, a big part of the disruptive potential of POCT introduction can be minimised. Health systems could improve their efficiency through connectivity solutions, facilitating supply chain management to avoid stock-outs and wastage, and enabling ongoing monitoring of test results, the performance of devices and the competency of the operators from each POCT-site in a country.37 The IEG suggested to develop mentorship programmes for both policy makers and programme coordinators.

The IEG acknowledged that the technologies are rapidly changing and opportunities need to be catalysed if manufacturers are to produce the STI POCTs that are needed. Experts urged WHO to bring manufacturers and the wider clinical community together, to guide development, condition funding and negotiate the cost.

Notwithstanding the relative scarcity of available STI POCTs, few companies have commercialised products developed by scientists in academia and industry. Clinicians and industry have different perceptions about the limitations of current tests. Therefore, industry needs to be more mindful of the requirements of clinicians to introduce marketable tests.13

The cost-effectiveness of introducing a new POCT and the potential gains in public health and economic gains should be modelled, considering downstream sequelae. Opportunities for investments and potential returns from investments in STI POCTs should be identified. The development of an investment case should be prioritised as an essential step to engage relevant stakeholders throughout all phases of the diagnostic development cycle. Public health authorities should be engaged to build support for sustainable funding of POCTs as a programmatic goal to strengthen their health system.30 The IEG stressed the importance for countries to have a generic, crosscutting STI POCT policy, avoiding ad hoc decisions.

In various countries, home-grown solutions are being developed, and should be encouraged, as small to medium enterprises can address challenges such as importation and national distribution.

Encourage investment in STI POCTs

The IEG expressed the urgent need to communicate the need for POCTs. The global health sector strategy on STIs, endorsed at the 2016 World Health Assembly, creates a unique opportunity to amplify all elements of the current roadmap through a strong call for innovation in STI control and prevention.1 Development of partnerships in the STI POCT field and identifying groups or organisations that can be strong champions could work towards the goal of advancing a clear and compelling message for the need for STI POCT investment.