Real world outcomes of distributing Lucira Check-It® COVID self-tests in Ontario, Canada: the GetaKit COVID study.

BACKGROUND: In Ontario, Canada we developed and implemented an online screening algorithm for the distribution of HIV self-tests, known as GetaKit. During the COVID pandemic, we adapted the GetaKit algorithm to screen for COVID based on population and infection data and distributed COVID rt-LAMP self-tests (using the Lucira Check-It®) to eligible participants. METHODS: GetaKit/COVID was a prospective observational study that occurred over a 7-month period from September 2021 to April 2022. All potential participants completed an online registration and risk assessment, including demographic information, COVID symptoms and risk factors, and vaccination status. Bivariate comparisons were performed for three outcomes: results reporting status, vaccination status, and COVID diagnosis status. Data were analysed using Chi-Square for categorial covariates and Independent Samples T-Test and Mann-Whitney U test for continuous covariates. Bivariate logistic regression models were applied to examine associations between the covariates and outcomes. RESULTS: During the study period, we distributed 6469 COVID self-tests to 4160 eligible participants; 46% identified as Black, Indigenous or a Person of Colour (BIPOC). Nearly 70% of participants reported their COVID self-test results; 304 of which were positive. Overall, 91% also reported being vaccinated against COVID. Statistical analysis found living with five or fewer people, having tested for COVID previously, and being fully vaccinated were positive factors in results reporting. For COVID vaccination, people from large urban centers, who identified their ethnicity as white, and who reported previous COVID testing were more likely to be fully vaccinated. Finally, being identified as a contact of someone who had tested positive for COVID and the presence of COVID-related symptoms were found to be positive factors in diagnosis. CONCLUSIONS: While most participants who accessed this service were vaccinated against COVID and the majority of diagnoses were identified in participants who had symptoms of, or an exposure to, COVID, our program was able to appropriately link participants to recommended follow-up based on reported risks and results. These findings highlight the utility of online screening algorithms to provide health services, particularly for persons with historical barriers to healthcare access, such as BIPOC or lower-income groups.

Alone But Supported: A Qualitative Study of an HIV Self-testing App in an Observational Cohort Study in South Africa.

HIV self-testing has the potential to improve test access and uptake, but concerns remain regarding counselling and support during and after HIV self-testing. We investigated an oral HIV self-testing strategy together with a mobile phone/tablet application to see if and how it provided counselling and support, and how it might impact test access. This ethnographic study was nested within an ongoing observational cohort study in Cape Town, South Africa. Qualitative data was collected from study participants and study staff using 33 semi-structured interviews, one focus group discussion, and observation notes. The app provided information and guidance while also addressing privacy concerns. The flexibility and support provided by the strategy gave participants more control in choosing whom they included during testing. Accessibility concerns included smartphone access and usability issues for older and rural users. The adaptable access and support of this strategy could aid in expanding test access in South Africa.

Rapid and point-of-care tests for the diagnosis of Trichomonas vaginalis in women and men.

BACKGROUND: Trichomonasvaginalis (TV) is a highly prevalent parasitic infection worldwide. It is associated with many adverse reproductive health outcomes. Many infections are asymptomatic and syndromic management leads to underdetection of TV. Traditional methods of TV detection such as wet preparation are insensitive. New rapid, point-of-care (POC) tests can enhance the diagnosis of trichomoniasis. METHODS: The authors reviewed the literature and discuss older POC tests for TV detection, as well as the OSOM lateral flow test, the AmpliVue test, the Solana test and the GeneXpert test as well as the limitations of wet preparation and culture for detection of TV. RESULTS: The OSOM test is easy to perform, compared with other POC tests, and is Clinical Laboratory Improvement Amendments (CLIA)-waived, equipment-free, has sensitivities of 83%-86% compared with nucleic acid amplification tests (NAATs) and can be performed in 15 min. The AmpliVue and the Solana tests are not CLIA waived and require small pieces of equipment. They are molecular amplified assays and can be completed in <1 hour. AmpliVue demonstrated a sensitivity for vaginal swabs of 100% compared with wet preparation/culture and 90.7% compared with NAATs. Solana demonstrated a sensitivity of 98.6%-100% for vaginal swabs and 92.9%-98% for female urines, compared with wet preparation/culture. Compared with other NAATs, the sensitivity for Solana was 89.7% for swabs and 100% for urine. The GeneXpert TV test for women and men is a moderately complex test, requires a small platform and can be performed in <1 hour. The sensitivity compared with wet preparation/culture for self-collected vaginal swabs was 96.4%, 98.9% for endocervical specimens and 98.4% for female urine. For men, sensitivity for urines was excellent (97.2%). The specificity for all assays was excellent. CONCLUSIONS: Several rapid POC tests have the potential to rapidly diagnose trichomoniasis in women and one is available for detection of TV in men.

Point-of-Care Sexually Transmitted Infection Diagnostics: Proceedings of the STAR Sexually Transmitted Infection-Clinical Trial Group Programmatic Meeting.

The goal of the point-of-care (POC) sexually transmitted infection (STI) Diagnostics meeting was to review the state-of-the-art research and develop recommendations for the use of POC STI diagnostics. Experts from academia, government, nonprofit, and industry discussed POC diagnostics for STIs such as Chlamydia trachomatis, human papillomavirus, Neisseria gonorrhoeae, Trichomonas vaginalis, and Treponema pallidum. Key objectives included a review of current and emerging technologies, clinical and public health benefits, POC STI diagnostics in developing countries, regulatory considerations, and future areas of development. Key points of the meeting are as follows: (i) although some rapid point-of-care tests are affordable, sensitive, specific, easy to perform, and deliverable to those who need them for select sexually transmitted infections, implementation barriers exist at the device, patient, provider, and health system levels; (ii) further investment in research and development of point-of-care tests for sexually transmitted infections is needed, and new technologies can be used to improve diagnostic testing, test uptake, and treatment; (iii) efficient deployment of self-testing in supervised (ie, pharmacies, clinics, and so on) and/or unsupervised (ie, home, offices, and so on) settings could facilitate more screening and diagnosis that will reduce the burden of sexually transmitted infections; (iv) development of novel diagnostic technologies has outpaced the generation of guidance tools and documents issued by regulatory agencies; and (v) questions regarding quality management are emerging including the mechanism by which poor-performing diagnostics are removed from the market and quality assurance of self-testing is ensured.

Strategies to increase the demand for childhood vaccination in low- and middle-income countries: a systematic review and meta-analysis.

OBJECTIVE: To investigate which strategies to increase demand for vaccination are effective in increasing child vaccine coverage in low- and middle-income countries. METHODS: We searched MEDLINE, EMBASE, Cochrane library, POPLINE, ECONLIT, CINAHL, LILACS, BDSP, Web of Science and Scopus databases for relevant studies, published in English, French, German, Hindi, Portuguese and Spanish up to 25 March 2014. We included studies of interventions intended to increase demand for routine childhood vaccination. Studies were eligible if conducted in low- and middle-income countries and employing a randomized controlled trial, non-randomized controlled trial, controlled before-and-after or interrupted time series design. We estimated risk of bias using Cochrane collaboration guidelines and performed random-effects meta-analysis. FINDINGS: We identified 11 studies comprising four randomized controlled trials, six cluster randomized controlled trials and one controlled before-and-after study published in English between 1996 and 2013. Participants were generally parents of young children exposed to an eligible intervention. Six studies demonstrated low risk of bias and five studies had moderate to high risk of bias. We conducted a pooled analysis considering all 11 studies, with data from 11,512 participants. Demand-side interventions were associated with significantly higher receipt of vaccines, relative risk (RR): 1.30, (95% confidence interval, CI: 1.17-1.44). Subgroup analyses also demonstrated significant effects of seven education and knowledge translation studies, RR: 1.40 (95% CI: 1.20-1.63) and of four studies which used incentives, RR: 1.28 (95% CI: 1.12-1.45). CONCLUSION: Demand-side interventions lead to significant gains in child vaccination coverage in low- and middle-income countries. Educational approaches and use of incentives were both effective strategies.

Compounding diagnostic delays: a qualitative study of point-of-care testing in South Africa.

OBJECTIVES: Successful point-of-care (POC) testing (completion of test-and-treat cycle in one patient encounter) has immense potential to reduce diagnostic and treatment delays, and improve patient and public health outcomes. We explored what tests are done and how in public/private, rural/urban hospitals and clinics in South Africa and whether they can ensure successful POC testing. METHODS: This qualitative research study examined POC testing across major diseases in Cape Town, Durban and Eastern Cape. We conducted 101 semi-structured interviews and seven focus group discussions with doctors, nurses, community health workers, patients, laboratory technicians, policymakers, hospital managers and diagnostic manufacturers. RESULTS: In South Africa, diagnostics are characterised by a centralised system. Most tests conducted on the spot can be made to work successfully as POC tests. The majority of public/private clinics and smaller hospitals send samples via couriers to centralised laboratories and retrieve results the same way, via internet, fax or phone. The main challenge to POC testing lies in transporting samples and results, while delays risk patient loss from diagnostic/treatment pathways. Strategies to deal with associated delays create new problems, such as artificially prolonged turnaround times, strains on human resources and quality of testing, compounding additional diagnostic and treatment delays. CONCLUSIONS: For POC testing to succeed, particular characteristics of diagnostic ecosystems and adaptations of professional practices to overcome associated challenges must be taken into account.

Point-of-care testing in India: missed opportunities to realize the true potential of point-of-care testing programs.

BACKGROUND: The core objective of any point-of-care (POC) testing program is to ensure that testing will result in an actionable management decision (e.g. referral, confirmatory test, treatment), within the same clinical encounter (e.g. POC continuum). This can but does not have to involve rapid tests. Most studies on POC testing focus on one specific test and disease in a particular healthcare setting. This paper describes the actors, technologies and practices involved in diagnosing major diseases in five Indian settings - the home, community, clinics, peripheral laboratories and hospitals. The aim was to understand how tests are used and fit into the health system and with what implications for the POC continuum. METHODS: The paper reports on a qualitative study including 78 semi-structured interviews and 13 focus group discussions with doctors, nurses, patients, lab technicians, program officers and informal providers, conducted between January and June 2013 in rural and urban Karnataka, South India. Actors, diseases, tests and diagnostic processes were mapped for each of the five settings and analyzed with regard to whether and how POC continuums are being ensured. RESULTS: Successful POC testing hardly occurs in any of the five settings. In hospitals and public clinics, most of the rapid tests are used in laboratories where either the single patient encounter advantage is not realized or the rapidity is compromised. Lab-based testing in a context of manpower and equipment shortages leads to delays. In smaller peripheral laboratories and private clinics with shorter turn-around-times, rapid tests are unavailable or too costly. Here providers find alternative measures to ensure the POC continuum. In the home setting, patients who can afford a test are not/do not feel empowered to use those devices. CONCLUSION: These results show that there is much diagnostic delay that deters the POC continuum. Existing rapid tests are currently not translated into treatment decisions rapidly or are not available where they could ensure shorter turn-around times, thus undermining their full potential. To ensure the success of POC testing programs, test developers, decision-makers and funders need to account for such ground realities and overcome barriers to POC testing programs.

Diagnostic yield as an important metric for the evaluation of novel tuberculosis tests: rationale and guidance for future research.

Better access to tuberculosis testing is a key priority for fighting tuberculosis, the leading cause of infectious disease deaths in people. Despite the roll-out of molecular WHO-recommended rapid diagnostics to replace sputum smear microscopy over the past decade, a large diagnostic gap remains. Of the estimated 10·6 million people who developed tuberculosis globally in 2022, more than 3·1 million were not diagnosed. An exclusive focus on improving tuberculosis test accuracy alone will not be sufficient to close the diagnostic gap for tuberculosis. Diagnostic yield, which we define as the proportion of people in whom a diagnostic test identifies tuberculosis among all people we attempt to test for tuberculosis, is an important metric not adequately explored. Diagnostic yield is particularly relevant for subpopulations unable to produce sputum such as young children, people living with HIV, and people with subclinical tuberculosis. As more accessible non-sputum specimens (eg, urine, oral swabs, saliva, capillary blood, and breath) are being explored for point-of-care tuberculosis testing, the concept of yield will be of growing importance. Using the example of urine lipoarabinomannan testing, we illustrate how even tests with limited sensitivity can diagnose more people with tuberculosis if they enable increased diagnostic yield. Using tongue swab-based molecular tuberculosis testing as another example, we provide definitions and guidance for the design and conduct of pragmatic studies that assess diagnostic yield. Lastly, we show how diagnostic yield and other important test characteristics, such as cost and implementation feasibility, are essential for increased effective population coverage, which is required for optimal clinical care and transmission impact. We are calling for diagnostic yield to be incorporated into tuberculosis test evaluation processes, including the WHO Grading of Recommendations, Assessment, Development, and Evaluations process, providing a crucial real-life implementation metric that complements traditional accuracy measures.

How much does HIV self-testing cost in low and middle income countries? A systematic review of evidence from economic studies.

Objectives: HIV self-testing (HIVST) has been proposed as an innovative strategy to diagnose human immunodeficiency virus (HIV). While HIVST offers the potential to broaden accessibility of early HIV diagnosis and treatment initiation, this testing strategy incurs additional cost and requires confirmatory testing and treatment. We have conducted the first systematic review to summarize the current economic literature for HIVST in low- and middle-income countries (LMICs). Design: A search strategy was developed including key terms for HIV, self-testing and cost-effectiveness and was conducted in Medline and Embase databases. Studies were included that reported costs per outcome and included both cost-effectiveness and cost-utility outcome measures. The search strategy identified publications up until August 15, 2023 were included. Abstract and full text screening was conducted and a standardized data abstraction form was used for included studies. Costs are reported in USD, 2020. Results: Our search strategy identified 536 total titles from the search strategy, which were screened down to 25 relevant studies that provided both cost and outcome data on HIVST. There was significant heterogeneity in the HIVST intervention, study population, costs and outcomes reported among included studies. Cost per person tested ranged from $1.09-155. Cost per case diagnosed ranged from $20-1,277. Cost-utility estimates ranged from cost-saving to $1846 per DALY averted. Higher cost-effectiveness estimates were associated with more expensive testing algorithms with increased support for linkage to care and post-test counseling. Conclusion: All studies considered HIVST cost-effective although major drivers were identified included underlying HIV prevalence, testing cost and linkage to care. HIVST is likely to be cost-effective in a LMIC context, however policy makers should be aware of the drivers of cost-effectiveness when implementing HIVST programs as these underlying factors can impact the overall cost-effectiveness of HIVST.

Rapid point-of-care first-line screening tests for hepatitis B infection: a meta-analysis of diagnostic accuracy (1980-2010).

OBJECTIVES: Three-hundred fifty million people worldwide are chronically infected with Hepatitis B, with four million acute infections annually. With infection concentrated in hard-to-reach populations and low resource settings, rapid point-of-care (POC) tests offer an efficient screening alternative to laboratory tests. We conducted a meta-analysis to evaluate accuracy of rapid POC tests screening for Hepatitis B. METHODS: Two reviewers searched four databases, critiqued quality. A hierarchical Bayesian meta-analysis correcting for imperfect reference standards was used. Based on components of the antigen-antibody response, 17 studies were stratified into three subgroups: (i) Hepatitis B surface antigen (HBsAg) tests; (ii) anti-HBsAg tests, and (iii) HBs+eAg tests. Further, we pooled estimates on individual tests with sufficient data. RESULTS: In subgroup 1, the pooled sensitivity (Sn) was 94.76% (95% credible interval (CrI): 90.08-98.23%) and specificity (Sp) was 99.54% (95% CrI: 99.03-99.95%). The Determine test reported a pooled Sn 98.2% (95% CrI: 94.7, 99.9) and Sp 99.9% (95% CrI: 99.3, 100); in subgroup 2, Sn 93.2% (95% CrI: 85.1, 98.5), Sp 93.1% (95% CrI: 81.9, 99.9); and in subgroup 3, the Binax test showed Sn 95.5% (95% CrI: 88.9, 99.4), Sp 99.8% (95% CrI: 99.3, 100). CONCLUSIONS: HBsAg tests, including Determine, and the HBs+eAg test, Binax showed high accuracy. Improvements in sensitivity of antibody-based tests will enhance their potential for global first-line screening.

Incidence of acute hepatitis C virus infection among men who have sex with men with and without HIV infection: a systematic review.

BACKGROUND: A recent increase in reports of acute hepatitis C virus infection (HCV) in HIV-infected and HIV-uninfected men who have sex with men (MSM), with the sole risk factor being sexual exposure, has led to routine screening and targeted prevention requests for this population; current evidence for this necessity is unclear. OBJECTIVE: A systematic review was conducted to assess the incidence of HCV infection among studies conducted in HIV-positive and/or HIV-negative MSM to explore the implications for routine HCV screening. DATA SOURCES: The MEDLINE, EMBASE and BIOSYS databases were searched for the period January 2000 to May 2012, yielding 21 studies. Six conferences were hand-searched for the same period yielding four abstracts. STUDY SELECTION: Only studies in English presenting incidence rates of HCV and specifying HIV status were included. DATA ABSTRACTION: Data were abstracted by two authors using predefined data fields. The STROBE checklist was used to assess study quality. DATA SYNTHESIS: Data were divided into HIV-negative MSM and HIV-positive MSM subgroups, and HCV incidence density measurements were pooled. Using a DerSimonian-Laird random effects model, pooled incidence was 1.48/1000 person-years (95% CI 0.75 to 2.21) for the HIV-negative MSM subgroup. The HIV-positive MSM subgroup was at 4.1 times higher risk of acquiring HCV at 6.08/1000 person-years (95% CI 5.18 to 6.99). Studies directly comparing subgroups estimated a pooled risk difference of 3.45/1000 person-years (95% CI 1.63 to 5.27). CONCLUSION: HIV-positive MSM were at higher risk for acute HCV infection than HIV-negative MSM, substantiating the need for routine screening initiatives. Insufficient evidence exists to warrant routine screening of HIV-negative MSM, except on a case-by-case basis, such as high-risk sexual behaviour.

Multiplexed rapid technologies for sexually transmitted infections: a systematic review.

Multiplexed technologies for sexually transmitted infections offer a convenient diagnostics option to screen, confirm, and treat multiple pathogens simultaneously. Due to scarce published real-world diagnostic performance data, we did a systematic review. Two reviewers searched major databases for data published between Jan 1, 2009, and April 20, 2020, and abstracted and analysed sensitivity and specificity data from 24 studies, which assessed 17 multiplex rapid nucleic acid amplification test platforms and seven multiplex immunochromatographic devices. Overall, these studies evaluated 19 sexually transmitted infections in 26 126 individuals. High sensitivity and specificity were shown for rapid nucleic acid amplification platform tests and immunochromatographic devices, with performance varying by pathogen, device, seropositivity, and subpopulation screened. As most devices yielded more than 95% sensitivity and specificity, immunochromatographic tests and rapid nucleic acid amplification test platforms can be advised for screening and confirmatory use. These highly accurate devices are appropriate for integrated, rapid screening initiatives for sexually transmitted infections to screen and treat many of these infections simultaneously, for antimicrobial stewardship, and for disease elimination programmes.

HIV self-testing with digital supports as the new paradigm: A systematic review of global evidence (2010-2021).

BACKGROUND: HIV self-testing (HIVST) is recommended by the WHO as an innovative strategy to reach UNAIDS targets to end HIV by 2030. HIVST with digital supports is defined as the use of digital interventions (e.g., website-based, social media, mobile HIVST applications (apps), text messaging (SMS), digital vending machines (digital VMs)) to improve the efficiency and impact of HIVST. HIVST deployment and integration in health services is an emerging priority. We conducted a systematic review aiming to close the gap in evidence that summarizes the impact of digitally supported HIVST and to inform policy recommendations. METHODS: We searched PubMed and Embase for articles and abstracts on HIVST with digital supports published during the period February 1st, 2010 to June 15th, 2021, following Cochrane guidelines and PRISMA methodology. We assessed feasibility, acceptability, preference, and impact outcomes across all populations and study designs. Metrics reported were willingness to use HIVST, preferences for HIVST delivery, proportion of first-time testers, HIVST uptake, HIVST kit return rate, and linkage to care. Heterogeneity of the interventions and reported metrics precluded us from conducting a meta-analysis. FINDINGS: 46 studies were narratively synthesized, of which 72% were observational and 28% were RCTs. Half of all studies (54%, 25/46) assessed web-based innovations (e.g., study websites, videos, chatbots), followed by social media (26%, 12/46), HIVST-specific apps (7%, 3/46), SMS (9%, 4/46), and digital VMs (4%, 2/46). Web-based innovations were found to be acceptable (77-97%), preferred over in-person and hybrid options by more first-time testers (47-48%), highly feasible (93-95%), and were overall effective in supporting linkage to care (53-100%). Social media and app-based innovations also had high acceptability (87-95%) and linkage to care proportions (80-100%). SMS innovations increased kit return rates (54-94%) and HIVST uptake among hard-to-reach groups. Finally, digital VMs were highly acceptable (54-93%), and HIVST uptake was six times greater when using digital VMs compared to distribution by community workers. INTERPRETATION: HIVST with digital supports was deemed feasible, acceptable, preferable, and was shown to increase uptake, engage first-time testers and hard-to-reach populations, and successfully link participants to treatment. Findings pave the way for greater use of HIVST interventions with digital supports globally.

Modern diagnostic technologies for HIV.

Novel diagnostic technologies, including nanotechnology, microfluidics, -omics science, next-generation sequencing, genomics big data, and machine learning, could contribute to meeting the UNAIDS 95-95-95 targets to end the HIV epidemic by 2030. Novel technologies include multiplexed technologies (including biomarker-based point-of-care tests and molecular platform technologies), biomarker-based combination antibody and antigen technologies, dried-blood-spot testing, and self-testing. Although biomarker-based rapid tests, in particular antibody-based tests, have dominated HIV diagnostics since the development of the first HIV test in the mid-1980s, targets such as nucleic acids and genes are now used in nanomedicine, biosensors, microfluidics, and -omics to enable early diagnosis of HIV. These novel technologies show promise as they are associated with ease of use, high diagnostic accuracy, rapid detection, and the ability to detect HIV-specific markers. Additional clinical and implementation research is needed to generate evidence for use of novel technologies and a public health approach will be required to address clinical and operational challenges to optimise their global deployment.

Diagnostic Infectious Diseases Testing Outside Clinics: A Global Systematic Review and Meta-analysis.

BACKGROUND: Most people around the world do not have access to facility-based diagnostic testing, and the gap in availability of diagnostic tests is a major public health challenge. Self-testing, self-sampling, and institutional testing outside conventional clinical settings are transforming infectious disease diagnostic testing in a wide range of low- and middle-income countries (LMICs). We examined the delivery models of infectious disease diagnostic testing outside clinics to assess the impact on test uptake and linkage to care. METHODS: We conducted a systematic review and meta-analysis, searching 6 databases and including original research manuscripts comparing testing outside clinics with conventional testing. The main outcomes were test uptake and linkage to care, delivery models, and adverse outcomes. Data from studies with similar interventions and outcomes within thematic areas of interest were pooled, and the quality of evidence was assessed using GRADE. This study was registered in PROSPERO (CRD42019140828).We identified 10 386 de-duplicated citations, and 76 studies were included. Data from 18 studies were pooled in meta-analyses. Studies focused on HIV (48 studies), chlamydia (8 studies), and multiple diseases (20 studies). HIV self-testing increased test uptake compared with facility-based testing (9 studies: pooled odds ratio [OR], 2.59; 95% CI, 1.06-6.29; moderate quality). Self-sampling for sexually transmitted infections increased test uptake compared with facility-based testing (7 studies: pooled OR, 1.74; 95% CI, 0.97-3.12; moderate quality). Conclusions. Testing outside of clinics increased test uptake without significant adverse outcomes. These testing approaches provide an opportunity to expand access and empower patients. Further implementation research, scale-up of effective service delivery models, and policies in LMIC settings are needed.