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IntroductionScreening for G6PD deficiency can inform disease management including malaria. Treatment with the antimalarial drugs primaquine and tafenoquine can be guided by point-of-care testing for G6PD deficiency.Methods and FindingsData from similar clinical studies evaluating the performance of the STANDARD™G6PD Test (SD Biosensor, South Korea) conducted in Bangladesh, Brazil, Ethiopia, India, Thailand, the United Kingdom, and the United States were pooled. Test performance was assessed in a retrospective analysis on capillary and venous specimens. All study sites used spectrophotometry for reference G6PD testing, and either the HemoCue or complete blood count for reference hemoglobin measurement.The sensitivity of the STANDARD™G6PD Test using the manufacturer thresholds for G6PD deficient and intermediate cases in capillary specimens from 4212 study participants was 100% (95% Confidence Interval (CI): 97.5%–100%) for G6PD deficient cases with 60% on the reference assay. Negative predictive values for females with G6PD activity >60% was 99.6% (95% CI 99.1%–99.8%) on capillary specimens. Test sensitivity among 396P. vivaxmalaria cases was 100% (69.2%–100.0%) for both deficient and intermediate cases. In the study population, a high proportion of those classified as G6PD deficient or intermediate resulted from true normal cases. Despite this, the majority cases would receive the correct medication and no true G6PD deficient cases would be treated inappropriately.ConclusionsThe STANDARD G6PD Test enables safe access to drugs which are contraindicated for individuals with G6PD deficiency. Operational considerations will inform test uptake in specific settings.

The relationship between N-antigen concentration and viral load within a specimen and across different specimens is essential for interpretation of rapid diagnostic tests (RDT) clinical performance in different use cases. A prospective study was conducted in Porto Velho, Brazil, to investigate RDT performance in different specimen types as a function of the correlation between antigen concentration and viral load. The study included 214 close contacts with recent exposures to confirmed cases, aged 12 years and older and with various levels of vaccination. Antigen concentration was measured in nasopharyngeal swab (NPS), anterior nares swab (ANS), and saliva specimens. Reverse transcriptase (RT)–PCR was conducted on the NPS and saliva specimens, and two RDTs were conducted on ANS and one on saliva. Antigen concentration correlated with viral load when measured in the same specimen type but not across specimen types. Antigen levels were higher in symptomatic cases compared to asymptomatic/oligosymptomatic cases and lower in saliva compared to NPS and ANS samples. Discordant results between the RDTs conducted on ANS and the RT-PCR on NPS were resolved by antigen concentration values. The analytical limit-of-detection of RDTs can be used to predict the performance of the tests in populations for which the antigen concentration is known. The antigen dynamics across different sample types observed in SARS-CoV-2 disease progression support use of RDTs in nasal samples. Given lower antigen concentrations in saliva, tests using saliva is expected to require improved analytical sensitivity to achieve clinical sensitivity similar to testing of nasal samples.

Background Point-of-care and decentralized testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical to inform public health responses. Performance evaluations in priority use cases such as contact tracing can highlight trade-offs in test selection and testing strategies. Methods A prospective diagnostic accuracy study was conducted among close contacts of coronavirus disease 2019 (COVID-19) cases in Brazil. Two anterior nares swabs (ANS), a nasopharyngeal swab (NPS), and saliva were collected at all visits. Vaccination history and symptoms were assessed. Household contacts were followed longitudinally. Three rapid antigen tests and 1 molecular method were evaluated for usability and performance against reference reverse-transcription polymerase chain reaction (RT-PCR) on nasopharyngeal swab specimens. Results Fifty index cases and 214 contacts (64 household) were enrolled. Sixty-five contacts were RT-PCR positive during ≥1 visit. Vaccination did not influence viral load. Gamma variants were most prevalent; Delta variants emerged increasingly during implementation. The overall sensitivity of evaluated tests ranged from 33% to 76%. Performance was higher among symptomatic cases and those with cycle threshold (Ct) values 70% and almost 90% after 4 days. Conclusions The near-immediate time to results for antigen tests significantly offsets lower analytical sensitivity in settings where RT-PCR results are delayed or unavailable.

BackgroundPoint-of-care and decentralized testing for SARS-CoV-2 is critical to inform public health responses. Performance evaluations in priority use cases such as contact tracing can highlight trade-offs in test selection and testing strategies.MethodsA prospective diagnostic accuracy study was conducted among close contacts of COVID-19 cases in Brazil. Two anterior nares swabs (ANS), a nasopharyngeal swab (NPS), and saliva were collected at all visits. Vaccination history and symptoms were assessed. Household contacts were followed longitudinally. Three rapid antigen tests and one molecular method were evaluated for usability and performance against reference RT-PCR on NPS.ResultsFifty index cases and 214 contacts (64 household) were enrolled. Sixty-five contacts were RT-PCR positive during at least one visit. Vaccination did not influence viral load. Gamma variants were most prevalent; Delta emerged increasingly during implementation. Overall sensitivity of evaluated tests ranged from 33%–76%. Performance was higher among symptomatic cases and cases with Ct70% and almost 90% after four days.ConclusionsThe near immediate time-to-result for antigen tests significantly offsets lower analytical sensitivity in settings where RT-PCR results are delayed or unavailable.

Background Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common enzyme deficiency, prevalent in many malaria-endemic countries. G6PD-deficient individuals are susceptible to hemolysis during oxidative stress, which can occur from exposure to certain medications, including 8-aminoquinolines used to treat Plasmodium vivax malaria. Accordingly, access to point-of-care (POC) G6PD testing in Brazil is critical for safe treatment of P. vivax malaria. Methodology/Principal findings This study evaluated the performance of the semi-quantitative, POC STANDARD G6PD Test (SD Biosensor, Republic of Korea). Participants were recruited at clinics and through an enriched sample in Manaus and Porto Velho, Brazil. G6PD and hemoglobin measurements were obtained from capillary samples at the POC using the STANDARD and HemoCue 201+ (HemoCue AB, Sweden) tests. A thick blood slide was prepared for malaria microscopy. At the laboratories, the STANDARD and HemoCue tests were repeated on venous samples and a quantitative spectrophotometric G6PD reference assay was performed (Pointe Scientific, Canton, MI). G6PD was also assessed by fluorescent spot test. In Manaus, a complete blood count was performed. Samples were analyzed from 1,736 participants. In comparison to spectrophotometry, the STANDARD G6PD Test performed equivalently in determining G6PD status in venous and capillary specimens under varied operating temperatures. Using the manufacturer-recommended reference value thresholds, the test’s sensitivity at the, Author summary G6PD deficiency affects an estimated 500 million people worldwide and is prevalent in many malaria-endemic settings. People with G6PD deficiency are at risk of hemolysis when exposed to certain medications, including 8-aminoquinoline drugs used to treat Plasmodium vivax malaria. Increased access to testing for G6PD deficiency at or near the point of care is critical for expanding the safe treatment of P. vivax malaria. In this study, we aimed to evaluate the performance of a point-of-care, semi-quantitative test for G6PD deficiency, the STANDARD G6PD Test, in a malaria-endemic setting in Brazil. The test was evaluated on both capillary and venous blood samples across a broad range of operating temperatures. The findings show that the STANDARD G6PD Test performed equivalently to the reference test in its ability to diagnose G6PD deficiency at the point of care. The STANDARD G6PD Test is a promising tool to aid in detecting G6PD deficiency at the point of care in Brazil.

Background Point-of-care glucose-6-phosphate dehydrogenase (G6PD) testing has the potential to make the use of radical treatment for vivax malaria safer and more effective. Widespread use of G6PD tests as part of malaria case management has been limited, in part due to due concerns regarding product usability, user training, and supervision. This study seeks to assess how well end users can understand the Standard™ G6PD Test (SD Biosensor, Suwon, South Korea) workflow, result output, and label after training. This will ultimately help inform test registration and introduction. Methods Potential G6PD test users who provide malaria case management at three sites in Brazil, Ethiopia, and India were trained on the use of the SD Biosensor Standard G6PD Test and assessed based on their ability to understand the test workflow and interpret results. The assessment was done through a questionnaire, designed to assess product usability against key technical product specifications and fulfill regulatory evidence requirements. Any participant who obtained 85% or above correct responses to the questionnaire was considered to adequately comprehend how to use and interpret the test. Results Forty-five participants, including malaria microscopists, laboratory staff, nurses, and community health workers took part in the study. Seventy-eight percent of all participants in the study (35/45) obtained passing scores on the assessment with minimal training. Responses to the multiple-choice questions indicate that most participants understood well the test intended use, safety claims, and warnings. The greatest source of error regarding the test was around the correct operating temperature. Most test results were also read and interpreted correctly, with the haemoglobin measurement being a more problematic output to interpret than the G6PD measurement. Conclusions These data results show how a standardized tool can be used to assess a user’s ability to run a point-of-care diagnostic and interpret results. When applied to the SD Biosensor Standard G6PD Test, this tool demonstrates that a range of users across multiple contexts can use the test and suggests improvements to the test instructions and training that can improve product usability, increase user comprehension, and ultimately contribute to more widespread effective use of point-of-care G6PD tests. Trial registration: NCT04033640