Independent clinic-based evaluation of point-of-care testing for the screening of Chlamydia trachomatis, Neisseria gonorrhoea and Trichomonas vaginalis in women-at-risk in Australia, Guatemala, Morocco, and South Africa.

BACKGROUND: In 2018, the World Health Organization commenced a multi-country validation study of the Cepheid GeneXpert for a range of molecular-based point-of-care (POC) tests in primary care settings. One study arm focused on the evaluation of POC tests for screening 'women at risk' for chlamydia (CT), gonorrhoea (NG) and trichomonas (TV) in four countries - Australia, Guatemala, Morocco and South Africa. METHODS: Study participants completed a pre-test questionnaire which included demographics, clinical information and general questions on POC testing (POCT). Two vaginal swab samples (either self-collected or clinician collected) from each patient were tested on the GeneXpert at the POC and at a reference laboratory using quality-assured nucleic acid amplification tests (NAATs). RESULTS: One thousand three hundred and eighty-three women were enrolled: 58.6% from South Africa, 29.2% from Morocco, 6.2% from Guatemala, and 6.0% from Australia. 1296 samples for CT/NG and 1380 samples for TV were tested by the GeneXpert and the reference NAAT. The rate of unsuccessful tests on the GeneXpert was 1.9% for CT, 1.5% for NG and 0.96% for TV. The prevalence of CT, NG and TV was 31%, 13% and 23%, respectively. 1.5% of samples were positive for all three infections; 7.8% were positive for CT and NG; 2.4% were positive for NG and TV; and 7.3% were positive for CT and TV. Compared to reference NAATs, pooled estimates of sensitivity for the GeneXpert tests were 83.7% (95% confidence intervals 69.2-92.1) for CT, 90.5% (85.1-94.1) for NG and 64.7% (58.1-70.7) for TV (although estimates varied considerably between countries). Estimates for specificity were ≥96% for all three tests both within- and between-countries. Pooled positive and negative likelihood ratios were: 32.7 ([CI] 21.2-50.5) and 0.17 (0.08-0.33) for CT; 95.3 (36.9-245.7) and 0.10 (0.06-0.15) for NG; and 56.5 (31.6-101.1) and 0.35 (0.27-0.47) for TV. CONCLUSION: This multi-country evaluation is the first of its kind world-wide. Positive likelihood ratios, as well as specificity estimates, indicate the GeneXpert POC test results for CT, NG and TV were clinically acceptable for ruling in the presence of disease. However, negative likelihood ratios and variable sensitivity estimates from this study were poorer than expected for ruling out these infections, particularly for TV. TRIAL REGISTRATION: Ethics approval to conduct the ProSPeRo study was granted by the WHO Ethics Review Committee, as well as local ethics committees from all participating countries.

Quality control and external quality assessment for the independent clinic-based evaluation of point-of-care testing to detect Chlamydia trachomatis, Neisseria gonorrhoeae and Trichomonas vaginalis in eight countries.

BACKGROUND: Sexually transmitted infections caused by Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and Trichomonas vaginalis (TV) remain significant global health problems. The World Health Organization (WHO) has recently conducted a multi-faceted, multi-country validation study (ProSPeRo), which included an evaluation of the Xpert CT/NG and Xpert TV assays on the GeneXpert system (Cepheid, Sunnyvale, Ca., USA) in clinic-based settings across eight countries. To support the study, a training and quality management system was implemented and evaluated. METHODS: A comprehensive training program for the study was developed. Quality control (QC) and external quality assessment (EQA) samples were provided by an accredited quality assurance provider. QC testing was conducted at 14 point-of-care testing (POCT) clinics, while EQA samples were tested by the POCT sites and a reference laboratory supporting each clinic. RESULTS: For QC testing, concordance with the expected results for CT and NG was > 99% and rates of unsuccessful tests were < 4%. For TV testing, concordance was similar (97%), but rates of unsuccessful tests were high (18%), particularly in the 'TV negative' sample. For EQA testing initially conducted in 2018, concordance was 100% for CT and NG, and 90% for TV for the reference laboratory group (which used non-GeneXpert systems). Concordance for the POCT group was also high (> 94%) for all analytes, but this cohort (which used GeneXpert systems) exhibited a high rate of unsuccessful TV tests. All but one of these unsuccessful tests was subcategorised as 'invalid'. CONCLUSIONS: The high level of concordance for QC and EQA testing confirm that the trained operators at the POC clinical sites were competent to conduct POC testing and that the training and quality systems implemented for the ProSPeRo study were effective. The quality materials used were satisfactory for CT and NG but exhibited poor performance for TV testing on the GeneXpert system. The WHO should continue to work with industry and EQA providers to provide improved materials that are reliable, stable and cost effective for quality management, as it seeks to rollout molecular-based STI POCT in non-laboratory-based settings. TRIAL REGISTRATION: Ethics approval to conduct the ProSPeRo study was granted by the WHO Ethics Review Committee.

Flexible and Innovative Connectivity Solution to Support National Decentralized Infectious Diseases Point-of-Care Testing Programs in Primary Health Services: Descriptive Evaluation Study.

BACKGROUND: Molecular point-of-care (POC) testing for Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and Trichomonas vaginalis (TV) has been available in regional and remote primary health services in Australia as part of a decentralized POC testing program since 2016 and for SARS-CoV-2 from 2020. As there was no suitable existing connectivity infrastructure to capture and deliver POC test results to a range of end users, a new system needed to be established. OBJECTIVE: The aim of the study is to design, implement, and optimize a connectivity system to meet clinical management, analytical quality management, and public health surveillance needs. METHODS: We used commercially available e-messaging technology coupled with adapted proprietary software to integrate a decentralized molecular POC testing platform (GeneXpert) in primary health services and interface with end-user databases. This connectivity infrastructure was designed to overcome key barriers to the implementation, integration, and monitoring of these large multijurisdictional infectious disease POC testing networks. Test result messages were tailored to meet end-user needs. Using centrally captured deidentified data, we evaluated the time to receipt of test results and completeness of accompanying demographic data. RESULTS: From January 2016 to April 2020, we operationalized the system at 31 health services across 4 jurisdictions and integrated with 5 different patient management systems to support the real-time delivery of 29,356 CT/NG and TV test results to designated recipients (patient management system and local clinical and central program databases). In 2019, 12,105 CT/NG and TV results were delivered, and the median time to receipt of results was 3.2 (IQR 2.2-4.6) hours, inclusive of test runtime. From May 2020 to August 2022, we optimized the system to support rapid scale-up of SARS-CoV-2 testing (105 services; 6 jurisdictions; 71,823 tests) and additional sexually transmissible infection testing (16,232 tests), including the electronic disease-specific notifications to jurisdictional health departments and alerts for connectivity disruption and positive results. In 2022, 19,355 results were delivered with an overall median transmission time of 2.3 (IQR 1.4-3.1) hours, 2.2 (IQR 1.2-2.3) hours for SARS-CoV-2 (n=16,066), 3.0 (IQR 2.0-4.0) hours for CT/NG (n=1843), and 2.6 (IQR 1.5-3.8) hours for TV (n=1446). Demographic data (age, sex, and ethnicity) were completed for 99.5% of test results in 2022. CONCLUSIONS: This innovative connectivity system designed to meet end-user needs has proven to be sustainable, flexible, and scalable. It represents the first such system in Australia established independent of traditional pathology providers to support POC testing in geographically dispersed remote primary health services. The system has been optimized to deliver real-time test results and has proven critical for clinical, public health, and quality management. The system has significantly supported equitable access to rapid diagnostics for infectious diseases across Australia, and its design is suitable for onboarding other POC tests and testing platforms in the future.

Scaling up sexually transmissible infections point-of-care testing in remote Aboriginal and Torres Strait Islander communities: healthcare workers' perceptions of the barriers and facilitators.

BACKGROUND: Sexually transmissible infections (STIs), such as gonorrhoea and chlamydia, are highly prevalent, particularly in remote Aboriginal and Torres Strait Islander communities in Australia. In these settings, due to distance to centralised laboratories, the return of laboratory test results can take a week or longer, and many young people do not receive treatment, or it is considerably delayed. Point-of-care testing (POCT) provides an opportunity for same day diagnosis and treatment. Molecular POC testing for STIs was available at 31 regional or remote primary health care clinic sites through the Test-Treat-And-GO (TANGO2) program. This qualitative study sought to identify barriers and facilitators to further scaling up STI POCT in remote Aboriginal communities within Australia. METHODS: A total of 15 healthcare workers (including nurses and Aboriginal health practitioners) and five managers (including clinic coordinators and practice managers) were recruited from remote health services involved in the TTANGO2 program to participate in semi-structured in-depth interviews. Health services' clinics were purposively selected to include those with high or low STI POCT uptake. Personnel participants were selected via a hybrid approach including nomination by clinic managers and purposive sampling to include those in roles relevant to STI testing and treatment and those who had received TTANGO2 training for POCT technology. Milat's scaling up guide informed the coding framework and analysis. RESULTS: Acceptability of STI POCT technology among healthcare workers and managers was predominantly influenced by self-efficacy and perceived effectiveness of POCT technology as well as perceptions of additional workload burden associated with POCT. Barriers to integration of STI POCT included retention of trained staff to conduct POCT. Patient reach (including strategies for patient engagement) was broadly considered an enabler for STI testing scale up using POCT technology. CONCLUSIONS: Remote healthcare clinics should be supported by both program and clinic management throughout scaling up efforts to ensure broad acceptability of STI POCT as well as addressing local health systems' issues and identifying and enhancing opportunities for patient engagement.

A decentralised point-of-care testing model to address inequities in the COVID-19 response.

The COVID-19 pandemic is growing rapidly, with over 37 million cases and more than 1 million deaths reported by mid-October, 2020, with true numbers likely to be much higher in the many countries with low testing rates. Many communities are highly vulnerable to the devastating effects of COVID-19 because of overcrowding in domestic settings, high burden of comorbidities, and scarce access to health care. Access to testing is crucial to globally recommended control strategies, but many communities do not have adequate access to timely laboratory services. Geographic dispersion of small populations across islands and other rural and remote settings presents a key barrier to testing access. In this Personal View, we describe a model for the implementation of decentralised COVID-19 point-of-care testing in remote locations by use of the GeneXpert platform, which has been successfully scaled up in remote Aboriginal and Torres Strait Islander communities across Australia. Implementation of the decentralised point-of-care testing model should be considered for communities in need, especially those that are undertested and socially vulnerable. The decentralised testing model should be part of the core global response towards suppressing COVID-19.

The Benefits and Challenges of Point-of-Care Testing in Rural and Remote Primary Care Settings in Australia.

CONTEXT.­: Point-of-care (POC) testing has significant potential application in rural and remote Australian communities where access to laboratory-based pathology testing is often poor and the burden of chronic, acute, and infectious disease is high. OBJECTIVE.­: To explore the clinical, operational, cultural, and cost benefits of POC testing in the Australian rural and remote health sector and describe some of the current challenges and limitations of this technology. DATA SOURCES.­: Evidence-based research from established POC testing networks for chronic, acute, and infectious disease currently managed by the International Centre for Point-of-Care Testing at Flinders University are used to highlight the experience gained and the lessons learned from these networks and, where possible, describe innovative solutions to address the current barriers to the uptake of POC testing, which include governance, staff turnover, maintaining training and competency, connectivity, quality testing, sustainable funding mechanisms, and accreditation. CONCLUSIONS.­: Point-of-care testing can provide practical and inventive opportunities to revolutionize the delivery of pathology services in rural and remote sectors where clinical need for this technology is greatest. However, many barriers to POC testing still exist in these settings, and the full potential of POC testing cannot be realized until these limitations are addressed and resolved.