Reliability of HIV rapid diagnostic tests for self-testing compared with testing by health-care workers: a systematic review and meta-analysis.

BACKGROUND: The ability of individuals to use HIV self-tests correctly is debated. To inform the 2016 WHO recommendation on HIV self-testing, we assessed the reliability and performance of HIV rapid diagnostic tests when used by self-testers. METHODS: In this systematic review and meta-analysis, we searched PubMed, PopLine, and Embase, conference abstracts, and additional grey literature between Jan 1, 1995, and April 30, 2016, for observational and experimental studies reporting on HIV self-testing performance. We excluded studies evaluating home specimen collection because patients did not interpret their own test results. We extracted data independently, using standardised extraction forms. Outcomes of interest were agreement between self-testers and health-care workers, sensitivity, and specificity. We calculated κ to establish the level of agreement and pooled κ estimates using a random-effects model, by approach (directly assisted or unassisted) and type of specimen (blood or oral fluid). We examined heterogeneity with the I2 statistic. FINDINGS: 25 studies met inclusion criteria (22 to 5662 participants). Quality assessment with QUADAS-2 showed studies had low risk of bias and incomplete reporting in accordance with the STARD checklist. Raw proportion of agreement ranged from 85·4% to 100%, and reported κ ranged from fair (κ 0·277, p<0·001) to almost perfect (κ 0·99, n=25). Pooled κ suggested almost perfect agreement for both types of approaches (directly assisted 0·98, 95% CI 0·96-0·99 and unassisted 0·97, 0·96-0·98; I2=34·5%, 0-97·8). Excluding two outliers, sensitivity and specificity was higher for blood-based rapid diagnostic tests (4/16) compared with oral fluid rapid diagnostic tests (13/16). The most common error that affected test performance was incorrect specimen collection (oral swab or finger prick). Study limitations included the use of different reference standards and no disaggregation of results by individuals taking antiretrovirals. INTERPRETATION: Self-testers can reliably and accurately do HIV rapid diagnostic tests, as compared with trained health-care workers. Errors in performance might be reduced through the improvement of rapid diagnostic tests for self-testing, particularly to make sample collection easier and to simplify instructions for use. FUNDING: The Bill & Melinda Gates Foundation and Unitaid

Laboratory evaluation of RealStar Yellow Fever Virus RT-PCR kit 1.0 for potential use in the global yellow fever laboratory network

Background Early detection of human yellow fever (YF) infection in YF-endemic regions is critical to timely outbreak mitigation. African National Laboratories chiefly rely on serological assays that require confirmation at Regional Reference Laboratories, thus delaying results, which themselves are not always definitive often due to antibody cross-reactivity. A positive molecular test result is confirmatory for YF; therefore, a standardized YF molecular assay would facilitate immediate confirmation at National Laboratories. The WHO-coordinated global Eliminate Yellow Fever Epidemics Laboratory Technical Working Group sought to independently evaluate the quality and performance of commercial YF molecular assays relevant to use in countries with endemic YF, in the absence of stringent premarket assessments. This report details a limited laboratory WHO-coordinated evaluation of the altona Diagnostics RealStar Yellow Fever Virus RT-PCR kit 1.0. Methodology and principal findings Specific objectives were to assess the assay’s ability to detect YF virus strains in human serum from YF-endemic regions, determine the potential for interference and cross-reactions, verify the performance claims as stated by the manufacturer, and assess usability. RNA extracted from normal human serum spiked with YF virus showed the assay to be precise with minimal lot-to-lot variation. The 95% limit of detection calculated was approximately 1,245 RNA copies/ml [95% confidence interval 497 to 1,640 copies/ml]. Positive results were obtained with spatially and temporally diverse YF strains. The assay was specific for YF virus, was not subject to endogenous or exogenous interferents, and was clinically sensitive and specific. A review of operational characteristics revealed that a positivity cutoff was not defined in the instructions for use, but otherwise the assay was user-friendly. Conclusions and significance The RealStar Yellow Fever Virus RT-PCR kit 1.0 has performance characteristics consistent with the manufacturer’s claims and is suitable for use in YF-endemic regions. Its use is expected to decrease YF outbreak detection times and be instrumental in saving lives.Peer Reviewe

Lateral flow test engineering and lessons learned from COVID-19

The acceptability and feasibility of large-scale testing with lateral flow tests (LFTs) for clinical and public health purposes has been demonstrated during the COVID-19 pandemic. LFTs can detect analytes in a variety of samples, providing a rapid read-out, which allows self-testing and decentralized diagnosis. In this Review, we examine the changing LFT landscape with a focus on lessons learned from COVID-19. We discuss the implications of LFTs for decentralized testing of infectious diseases, including diseases of epidemic potential, the ‘silent pandemic’ of antimicrobial resistance, and other acute and chronic infections. Bioengineering approaches will play a key part in increasing the sensitivity and specificity of LFTs, improving sample preparation, incorporating nucleic acid amplification and detection, and enabling multiplexing, digital connection and green manufacturing, with the aim of creating the next generation of high-accuracy, easy-to-use, affordable and digitally connected LFTs. We conclude with recommendations, including the building of a global network of LFT research and development hubs to facilitate and strengthen future diagnostic resilience

COVID-19 Serological Tests: How Well Do They Actually Perform?

In only a few months after initial discovery in Wuhan, China, SARS-CoV-2 and the associated coronavirus disease 2019 (COVID-19) have become a global pandemic causing significant mortality and morbidity and implementation of strict isolation measures. In the absence of vaccines and effective therapeutics, reliable serological testing must be a key element of public health policy to control further spread of the disease and gradually remove quarantine measures. Serological diagnostic tests are being increasingly used to provide a broader understanding of COVID-19 incidence and to assess immunity status in the population. However, there are discrepancies between claimed and actual performance data for serological diagnostic tests on the market. In this study, we conducted a review of independent studies evaluating the performance of SARS-CoV-2 serological tests. We found significant variability in the accuracy of marketed tests and highlight several lab-based and point-of-care rapid serological tests with high levels of performance. The findings of this review highlight the need for ongoing independent evaluations of commercialized COVID-19 diagnostic tests

COVID-19 Point-of-Care Diagnostics That Satisfy Global Target Product Profiles

COVID-19 pandemic will continue to pose a major public health threat until vaccination-mediated herd immunity is achieved. Most projections predict vaccines will reach a large subset of the population late in 2021 or early 2022. In the meantime, countries are exploring options to remove strict lockdown measures and allow society and the economy to return to normal function. One possibility is to expand on existing COVID-19 testing strategies by including large-scale rapid point-of-care diagnostic tests (POCTs). Currently, there is significant variability in performance and features of available POCTs, making selection and procurement of an appropriate test for specific use case difficult. In this review, we have used the World Health Organization’s (WHO) recently published target product profiles (TPPs) for specific use cases of COVID-19 diagnostic tests to screen for top-performing POCTs on the market. Several POCTs, based on clinical sensitivity/specificity, the limit of detection, and time to results, which meet WHO TPP criteria for direct detection of SARS-CoV-2 (acute infection) or indirect diagnosis of past infection (host antibodies), are highlighted here.</jats:p

COVID-19 Point-of-Care Diagnostics That Satisfy Global Target Product Profiles

COVID-19 pandemic will continue to pose a major public health threat until vaccination-mediated herd immunity is achieved. Most projections predict vaccines will reach a large subset of the population late in 2021 or early 2022. In the meantime, countries are exploring options to remove strict lockdown measures and allow society and the economy to return to normal function. One possibility is to expand on existing COVID-19 testing strategies by including large-scale rapid point-of-care diagnostic tests (POCTs). Currently, there is significant variability in performance and features of available POCTs, making selection and procurement of an appropriate test for specific use case difficult. In this review, we have used the World Health Organization’s (WHO) recently published target product profiles (TPPs) for specific use cases of COVID-19 diagnostic tests to screen for top-performing POCTs on the market. Several POCTs, based on clinical sensitivity/specificity, the limit of detection, and time to results, which meet WHO TPP criteria for direct detection of SARS-CoV-2 (acute infection) or indirect diagnosis of past infection (host antibodies), are highlighted here

COVID-19 Serological Tests: How Well Do They Actually Perform?

In only a few months after initial discovery in Wuhan, China, SARS-CoV-2 and the associated COVID-19 disease has become a global pandemic causing significant mortality and morbidity. In the absence of vaccines and effective therapeutics, reliable serological testing can be a key element of public health policy to control further spread of the disease and gradually ease quarantine measures. However, prior to launch of large-scale seroprevalence studies to assess herd immunity, it is critical to understand the limits and potential of current SARS-CoV-2 serological tests on the market. In this study, we provide an overview of serological testing and conduct a systematic review of independent evaluations of SARS-CoV-2 serological tests performance. Our findings show significant variability in the accuracy of marketed tests and highlight several lab-based and point-of-care rapid diagnostic tests with high performance level in detecting SRAS-CoV-2 specific antibodies. The findings of this review highlight the need for ongoing independent evaluations of commercialized COVID-19 diagnostic tests.</jats:p

COVID-19 Serological Tests: How Well Do They Actually Perform?

In only a few months after initial discovery in Wuhan, China, SARS-CoV-2 and the associated coronavirus disease 2019 (COVID-19) have become a global pandemic causing significant mortality and morbidity and implementation of strict isolation measures. In the absence of vaccines and effective therapeutics, reliable serological testing must be a key element of public health policy to control further spread of the disease and gradually remove quarantine measures. Serological diagnostic tests are being increasingly used to provide a broader understanding of COVID-19 incidence and to assess immunity status in the population. However, there are discrepancies between claimed and actual performance data for serological diagnostic tests on the market. In this study, we conducted a review of independent studies evaluating the performance of SARS-CoV-2 serological tests. We found significant variability in the accuracy of marketed tests and highlight several lab-based and point-of-care rapid serological tests with high levels of performance. The findings of this review highlight the need for ongoing independent evaluations of commercialized COVID-19 diagnostic tests.</jats:p

COVID-19 Serological Tests: How Well Do They Actually Perform?

In only a few months after initial discovery in Wuhan, China, SARS-CoV-2 and the associated coronavirus disease 2019 (COVID-19) have become a global pandemic causing significant mortality and morbidity and implementation of strict isolation measures. In the absence of vaccines and effective therapeutics, reliable serological testing must be a key element of public health policy to control further spread of the disease and gradually remove quarantine measures. Serological diagnostic tests are being increasingly used to provide a broader understanding of COVID-19 incidence and to assess immunity status in the population. However, there are discrepancies between claimed and actual performance data for serological diagnostic tests on the market. In this study, we conducted a review of independent studies evaluating the performance of SARS-CoV-2 serological tests. We found significant variability in the accuracy of marketed tests and highlight several lab-based and point-of-care rapid serological tests with high levels of performance. The findings of this review highlight the need for ongoing independent evaluations of commercialized COVID-19 diagnostic tests

COVID-19 Point-of-Care Diagnostics that Satisfy Global Target Product Profiles

COVID-19 pandemic will continue to pose a major public health threat until vaccination-mediated herd immunity is achieved. Most projections predict vaccine will reach a large subset of the population late in 2021 or early 2022. In the meantime, countries are exploring options to remove strict lockdown measures and allow for society and the economy to return to normal function. One possibility is to expand on existing COVID-19 testing strategies by including large-scale rapid point of care diagnostic tests (POCTs). Currently, there is significant variability in performance and features of available POCTs, making selection and procurement of appropriate test for specific use case difficult. In this review, we have used the World Health Organization&amp;rsquo;s (WHO) recently published Target Product Profiles (TPPs) for specific use cases of COVID-19 diagnostic tests to screen for top-performing POCTs on the market. Several top-performing POCTs, based on clinical sensitivity/specificity, the limit of detection, and time to results, that meet WHO TPP criteria for direct detection of SARS-CoV-2 (acute infection), or indirect diagnosis of past infection (host antibodies) are highlighted here.</jats:p