Analysis of the risk and pre-emptive control of viral outbreaks accounting for within-host dynamics: SARS-CoV-2 as a case study.

In the era of living with COVID-19, the risk of localised SARS-CoV-2 outbreaks remains. Here, we develop a multiscale modelling framework for estimating the local outbreak risk for a viral disease (the probability that a major outbreak results from a single case introduced into the population), accounting for within-host viral dynamics. Compared to population-level models previously used to estimate outbreak risks, our approach enables more detailed analysis of how the risk can be mitigated through pre-emptive interventions such as antigen testing. Considering SARS-CoV-2 as a case study, we quantify the within-host dynamics using data from individuals with omicron variant infections. We demonstrate that regular antigen testing reduces, but may not eliminate, the outbreak risk, depending on characteristics of local transmission. In our baseline analysis, daily antigen testing reduces the outbreak risk by 45% compared to a scenario without antigen testing. Additionally, we show that accounting for heterogeneity in within-host dynamics between individuals affects outbreak risk estimates and assessments of the impact of antigen testing. Our results therefore highlight important factors to consider when using multiscale models to design pre-emptive interventions against SARS-CoV-2 and other viruses.

Prostate-specific antigen testing patterns and prostate cancer stage at diagnosis in older Ohio cancer patients.

BACKGROUND: Prostate cancer (PCa) screening recommendations do not support prostate-specific antigen (PSA) screening for older men. Such screening often occurs, however. It is, therefore, important to understand how frequently and among which subgroups screening occurs, and the extent of distant stage PCa diagnoses among screened older men. METHODS: Using the 2014-2016 linked Ohio Cancer Incidence Surveillance System (OCISS) and Medicare administrative database, we identified men 68 and older diagnosed with PCa and categorized their PSA testing in the three years preceding diagnosis as screening or diagnostic. We conducted multivariable logistic regression analysis to identify correlates of screening PSA and to determine whether screening PSA is independently associated with distant stage disease. RESULTS: Our study population included 3034 patients (median age: 73 years). 62.1% of PCa patients underwent at least one screening-based PSA in the three years preceding diagnosis. Older age (75-84 years: aOR [95% CI]: 0.84 [0.71, 0.99], ≥ 85: aOR: 0.27 [0.19, 0.38]), and frailty (aOR: 0.51 [0.37, 0.71]) were associated with lower screening. Screening was associated with decreased odds of distant stage disease (aOR: 0.55 [0.42, 0.71]). However, older age (75-84 years: aOR: 2.43 [1.82, 3.25], ≥ 85: aOR: 10.57 [7.05, 15.85]), frailty (aOR: 5.00 [2.78, 9.31]), and being separated or divorced (aOR: 1.64 [1.01, 2.60]) were associated with increased distant stage PCa. CONCLUSION: PSA screening in older men is common, though providers appear to curtail PSA screening as age and frailty increase. Screened older men are diagnosed at earlier stages, but the harms of screening cannot be assessed.

Implementation and Performance of a Point-of-Care COVID-19 Test Program in 4000 California Schools.

OBJECTIVE: To evaluate the feasibility and accuracy of an unprecedented COVID-19 antigen testing program in schools, which required a healthcare provider order, laboratory director, a Clinical Laboratory Improvement Amendments certificate of waiver, as well as training of school personnel. STUDY DESIGN: Descriptive report of a point-of-care, school-based antigen testing program in California from August 1st, 2021 through May 30, 2022, in which participants grades K-12 self-swabbed and school personnel performed testing. Participants included 944 009 students, personnel, and community members from 4022 California kindergarten through high schools. Outcomes measured include sensitivity and specificity (with polymerase chain reaction [PCR] as comparator) of the Abbott BinaxNOW antigen test, number of tests performed, and active infections identified. RESULTS: Of 102 022 paired PCR/antigen tests, the overall sensitivity and specificity for the antigen test was 81.2% (95% CI: 80.5%-81.8%) and 99.6% (95% CI: 99.5%-99.6%), respectively, using cycle threshold values <30. During January through March 2022, the highest prevalence period, the positive predictive value of antigen testing was 94.7% and the negative predictive value was 94.2%. Overall, 4022 school sites were enrolled and 3 987 840 million antigen tests were performed on 944 009 individuals. A total of 162 927 positive antigen tests were reported in 135 163 individuals (14.3% of persons tested). CONCLUSIONS: Rapidly implementing a school-based testing program in thousands of schools is feasible. Self-swabbing and testing by school personnel can yield accurate results. On-site COVID-19 testing is no longer necessary in schools, but this model provides a framework for future infectious disease threats.

The use of intracellular dyes to create a multiplexed flow cytometry-based red blood cell phenotyping assay.

BACKGROUND AND OBJECTIVES: Flow cytometry can be used to phenotype red blood cell antigens, allowing for high-throughput testing while using low reagent volumes. This article utilizes intracellular dyes to pre-label red blood cells to further multiplex flow cytometry-based red blood cell antigen phenotyping. MATERIALS AND METHODS: Red blood cells were pre-labelled using the intracellular dyes V450 and Oregon Green. These dyes are detected fluorescently via flow cytometry. Four combinations of intracellular staining were used to allow four patient or donor red blood cells to be analysed in a single test well. Antigen phenotyping was then performed via flow cytometry using a previously described method. RESULTS: The intracellular dyes showed uniform staining when measured in mean fluorescence intensity and allowed the red blood cells to be clearly distinguished from one another. The presence or absence of red blood cell antigens was determined with 100% accuracy. CONCLUSION: The use of intracellular dyes allowed a fourfold increase in the throughput of our previously described flow cytometry-based red blood cell antigen phenotyping method. The described method allows up to 48 patients to be simultaneously phenotyped using a single 96-well microplate. Furthermore, additional fluorescent dyes could potentially increase the throughput exponentially.

A nanogap-enhanced SERS nanotag-based lateral flow assay for ultrasensitive and simultaneous monitoring of SARS-CoV-2 S and NP antigens.

A lateral flow assay (LFA) strip based on dual 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB)-encoded satellite Fe3O4@Au (Mag@Au) SERS tags with nanogap is reported for  ultrasensitive and simultaneous diagnosis of two SARS-CoV-2 functional proteins. Composed of Fe3O4 core, satellite gold shell with nanogaps, and double-layer DTNB, the Mag@Au nanoparticles with an average size of 238 nm were designed as multifunctional tags to efficiently enrich the target SARS-CoV-2 protein from complex samples, significantly enhancing the SERS signal of the LFA strip and provide quantitative SERS detection of analyte on test lines. The developed dual DTNB-encoded satellite Mag@Au-based LFA allowed simultaneous quantification of spike (S) protein and nucleocapsid (NP) protein with detection limits of 23 pg mL-1 and 2 pg mL-1, respectively, lower than commercial ELISA kits and reported SERS-LFA detection system-based Au NPs and Fe3O4@3 nm Au MNPs. This magnetic SERS-LFA also showed high performance of multi-variant strain detection and further distinguished clinical samples of Omicron variant infection, demonstrating the potential of in situ detection of respiratory virus diseases.

Assessment of DNA/RNA Defend Pro: An Inactivating Sample Collection Buffer for Enhanced Stability, Extraction-Free PCR, and Rapid Antigen Testing of Nasopharyngeal Swab Samples.

This study comprehensively evaluated the DNA/RNA Defend Pro (DRDP) sample collection buffer, designed to inactivate and stabilize patient samples. The primary objectives were to assess DRDP's efficacy in ensuring sample stability, facilitating extraction-free polymerase chain reaction (PCR), and ensuring compatibility with rapid antigen testing (RAT). Ninety-five diagnostic nasopharyngeal swab samples tested for influenza virus (influenza A), respiratory syncytial virus (RSV A), and/or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were 10-fold diluted with DRDP and anonymized. Initial characterization and retesting of these samples using cobas Liat confirmed 88 samples as positive, validating the presence of viral targets. Results from rapid antigen testing showed lower sensitivity compared to nucleic acid amplification testing (NAAT) but maintained perfect specificity, with 40 out of 88 positive samples by cobas Liat also testing positive for RAT. Direct RT-qPCR of DRDP-diluted samples demonstrated robust compatibility, with 72 out of 88 samples positive for cobas Liat also testing positive by direct RT-qPCR. Non-concordant results could be explained by the 200-fold lower input of extraction-free NAAT. Stability testing involved incubating 31 positive samples at 4 °C, 20 °C, and 37 °C for 7 days, with extraction-free NAAT. DRDP guaranteed viral RNA stability at all temperatures for influenza A, SARS-CoV-2, and RSV A, showing stability up to 7 days at 4 °C. In conclusion, DRDP is an effective stabilizing medium compatible with direct RT-qPCR and rapid antigen testing and shows great potential for optimizing diagnostic processes, particularly in resource-limited or time-sensitive scenarios.

Prospective study of three saliva qualitative antigen testing kits for the detection of SARS-CoV-2 among mainly symptomatic patients in Japan.

INTRODUCTION: Rapid qualitative antigen testing has been widely used for the laboratory diagnosis of COVID-19 with nasopharyngeal samples. Saliva samples have been used as alternative samples, but the analytical performance of those samples for qualitative antigen testing has not been sufficiently evaluated. METHODS: A prospective observational study evaluated the analytical performance of three In Vitro Diagnostics (IVD) approved COVID-19 rapid antigen detection kits for saliva between June 2022 and July 2022 in Japan using real-time reverse transcription polymerase chain reaction (RT-qPCR) as a reference. A nasopharyngeal sample and a saliva sample were simultaneously obtained, and RT-qPCR was performed. RESULTS: In total, saliva samples and nasopharyngeal samples were collected from 471 individuals (RT-qPCR-positive, n = 145) for the analysis. Of these, 96.6% were symptomatic. The median copy numbers were 1.7 × 106 copies/mL for saliva samples and 1.2 × 108 copies/mL for nasopharyngeal samples (p < 0.001). Compared with the reference, the sensitivity and specificity were 44.8% and 99.7% for ImunoAce SARS-CoV-2 Saliva, 57.2% and 99.1% for Espline SARS-CoV-2 N, and 60.0% and 99.1% for QuickChaser Auto SARS-CoV-2, respectively. The sensitivities of all antigen testing kit were 100% for saliva samples with a high viral load (>107 copies/mL), whereas the sensitivities were <70% for high-viral-load nasopharyngeal samples (>107 copies/mL). CONCLUSION: COVID-19 rapid antigen detection kits with saliva showed high specificity, but the sensitivity varied among kits, and were also insufficient for the detection of symptomatic COVID-19 patients.

A population-based study of the trend in SARS-CoV-2 diagnostic modalities from the beginning of the pandemic to the Omicron surge in Kyoto City, Kyoto, Japan.

BACKGROUND: The coronavirus disease 2019 (COVID-19) presents critical diagnostic challenges for managing the pandemic. We investigated the 30-month changes in COVID-19 testing modalities and functional testing sites from the early period of the pandemic to the most recent Omicron surge in 2022 in Kyoto City, Japan. METHODS: This is a retrospective-observational study using a local anonymized population database that included patients' demographic and clinical information, testing methods and facilities from January 2020 to June 2022, a total of 30 months. We computed the distribution of symptomatic presentation, testing methods, and testing facilities among cases. Differences over time were tested using chi-square tests of independence. RESULTS: During the study period, 133,115 confirmed COVID-19 cases were reported, of which 90.9% were symptomatic. Although nucleic acid amplification testing occupied 68.9% of all testing, the ratio of lateral flow devices (LFDs) rapidly increased in 2022. As the pandemic continued, the testing capability was shifted from COVID-19 designated facilities to general practitioners, who became the leading testing providers (57.3% of 99,945 tests in 2022). CONCLUSIONS: There was a dynamic shift in testing modality during the first 30 months of the pandemic in Kyoto City. General practitioners increased their role substantially as the use of LFDs spread dramatically in 2022. By comprehending and documenting the evolution of testing methods and testing locations, it is anticipated that this will contribute to the establishment of an even more efficient testing infrastructure for the next pandemic.

Equitable access to COVID-19 diagnostics: factors associated with the uptake of rapid antigen testing in Victoria, Australia, January - February 2022.

BACKGROUND: Accessible and accurate diagnostics are critical to control communicable diseases. Uptake of COVID-19 rapid antigen (RA) testing requires physical and financial access to tests, knowledge about usage, motivation, and ability to report results. We sought to understand patterns of and factors associated with RA test uptake in Victoria during a period of high caseload, RA test promotion, and difficulty accessing RA and PCR testing. We hypothesise RA test uptake is indicated by the ratio of cases diagnosed by RA test (probable) to those diagnosed using PCR (confirmed) (p:c). METHODS: Analysing case records, trends in p:c were assessed, between regions, sex, age groups, socio-economic strata and cultural diversity. Logistic regression assessed associations between case classification, and median age, postcode-level socio-economic disadvantage, and proportion overseas-born. RESULTS: We included 591,789 cases. Mean p:c was lower in socio-economically disadvantaged areas (decile 1 + 2: 0.90 vs. decile 9 + 10: 1.10), and in postcodes where the overseas-born population was above the Victorian average (0.83 vs. 1.05). Conversely, p:c was higher in younger age groups; with no difference between sexes overall. In metropolitan Melbourne, odds of RA test usage increased as socio-economic disadvantage decreased (decile 9 + 10, aOR 1.40, 95%CI 1.37-1.43, vs. decile 1 + 2; p < .001), decreased for cases from areas with a higher overseas-born population (aOR 0.85, 0.83-0.86, p < .001), and with older age. CONCLUSIONS: Reduced uptake of RA tests in Victoria is associated with socio-economic disadvantage, cultural diversity, and older age. Equitable access to COVID-19 diagnostics requires elimination of financial barriers, and greater engagement with culturally diverse and older groups. Inequitable RA test uptake may lead to case under-ascertainment, affecting resource allocation, effective control strategy development, in turn impacting COVID-19 morbidity and mortality, and could indicate relative engagement with response initiatives.

Knowledge and willingness toward SARS-CoV-2 rapid antigen testing among older adults in China: a nationwide cross-sectional study.

BACKGROUND AND AIMS: The end of the zero-COVID-19 policy placed a large number of older adults in China at increased risk of COVID-19 infection. SARS-CoV-2 rapid antigen testing (RAT) is a promising tool for scaling up testing and ensuring that patient management and public health measures can be implemented without delay. We aimed to understand the knowledge and willingness of RAT, and its correlates among older adults in China. METHODS: A nationwide cross-sectional survey on knowledge and willingness about RAT among older adults in China was conducted between January 14 and 28, 2023, shortly after the end of the zero-COVID-19 policy. An online questionnaire was used to collect information on sociodemographic characteristics, health characteristics, sources to access RAT information, and attitudes toward COVID-19 and its RAT. Logistic regression was used to assess correlates of knowledge of RAT and willingness to take RAT among older adults. RESULTS: A total of 1030 older adults (494 women and 536 men, mean age 68.7 ± 7.0 years) were recruited. 49.4% of the participants had a high level of RAT knowledge. After adjusting for sociodemographic characteristics, chronic diseases (0.70, 0.49-0.99), learning RAT from new media (5.46, 3.48-8.68) and traditional media (3.35, 2.13-5.34), and perceiving RAT as convenient (4.03, 2.80-5.85) were associated with levels of RAT knowledge. 53.3% of the participants were willing to take RAT. After adjusting for sociodemographic characteristics, learning RAT from new media (8.46, 5.26-14.0) and traditional media (1.63, 1.04-2.55), perceiving RAT as convenient (2.97, 2.10-4.22), and worrying about (re)infection with COVID-19 (2.12, 1.55-2.92) were associated with willingness to take RAT. CONCLUSION: The levels of RAT knowledge and willingness to take RAT among older adults in China may hinder the scale-up of RAT. Health education about RAT should be strengthened among older adults. Special efforts should be made to integrate traditional and new media to promote RAT among older adults, specifically, for virus susceptibility and the convenience of RAT. Given the reopening of society, our study could inform our response to future novel infectious diseases and aid in the timely scale-up of RAT.

Incidental Prostate Cancer: A 23-Year Review Of A Tertiary Care Hospital.

Prostate cancer is the second most commonly diagnosed malignancy in men worldwide. The prevalence has been increasing with significant differences between regions. This study assesses the prevalence of incidental prostate cancer detected in specimens removed during bladder outlet obstruction operation. A retrospective analysis of the records of patients who had either endoscopic or open prostatectomy from January 1998 to December 2021 was conducted. The variables analysed were age, procedure, date of surgery, and Gleason score. A total of 2,842 patients underwent surgery on the prostate gland during the study period. Most of the patients, i.e. 2,733 (96.2%), were pathologically diagnosed with benign prostatic hyperplasia, while only 110 (3.9%) had prostate cancer. The frequency of incidental prostate cancer following surgery for bladder outlet obstruction has decreased over the last two decades at our centre, possibly because of an increase in PSA testing.

Choice of SARS-CoV-2 diagnostic test: challenges and key considerations for the future.

A plethora of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnostic tests are available, each with different performance specifications, detection methods, and targets. This narrative review aims to summarize the diagnostic technologies available and how they are best selected to tackle SARS-CoV-2 infection as the pandemic evolves. Seven key settings have been identified where diagnostic tests are being deployed: symptomatic individuals presenting for diagnostic testing and/or treatment of COVID-19 symptoms; asymptomatic individuals accessing healthcare for planned non-COVID-19-related reasons; patients needing to access emergency care (symptom status unknown); patients being discharged from healthcare following hospitalization for COVID-19; healthy individuals in both single event settings (e.g. airports, restaurants, hotels, concerts, and sporting events) and repeat access settings (e.g. workplaces, schools, and universities); and vaccinated individuals. While molecular diagnostics remain central to SARS-CoV-2 testing strategies, we have offered some discussion on the considerations for when other tools and technologies may be useful, when centralized/point-of-care testing is appropriate, and how the various additional diagnostics can be deployed in differently resourced settings. As the pandemic evolves, molecular testing remains important for definitive diagnosis, but increasingly widespread point-of-care testing is essential to the re-opening of society.

ß-1,3-d-Glucan and Galactomannan as Biomarkers for the Detection of Invasive Geotrichum and Magnusiomyces Infections: a Retrospective Evaluation.

Magnusiomyces and Geotrichum species are ascomycetous yeasts that can cause potentially life-threatening invasive fungal infections commonly referred to as geotrichosis. In this study, we aimed to estimate the incidence and mortality of these infections in a German tertiary care center. Furthermore, we evaluated the suitability of the fungal biomarkers galactomannan (GM) and ß-1,3-d-glucan (BDG), which are both recommended as surrogate markers for Magnusiomyces capitatus infection by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and the European Confederation of Medical Mycology (ECMM) joint clinical guidelines for the diagnosis and management of rare invasive yeast infections for detection of invasive geotrichosis. Cases meeting the inclusion criteria for invasive Magnusiomyces/Geotrichum infection were retrospectively identified. Serum samples and culture supernatants were analyzed with two commercially available fungal antigen tests (Platelia Aspergillus Ag EIA and Wako ß-glucan test). For a control cohort, outpatient samples sent for lues testing were included. Thirty-eight cases of Magnusiomyces/Geotrichum infection were identified over an 11-year observation period. In the majority of cases, the fungus was isolated from intra-abdominal specimens of patients with a history of abdominal surgery/procedures (n = 32). All cases of fungemia occurred exclusively in haemato-oncologic patients (n = 14). Thirty-day survival was 42% in the fungemia and 43% in the intra-abdominal geotrichosis group. Serum samples were available for 23 patients (14 bloodstream and nine intra-abdominal infections). While BDG sensitivity was 65%, none of the sera was GM positive. This finding was supported by in vitro experiments analyzing fungal culture supernatants: M. capitatus secretes significant amounts of BDG but not GM. Specificity was 96% for BDG and 100% for GM. Magnusiomyces and Geotrichum infections are not limited to haemato-oncologic patients. Contrasting the current ESCMID/ECMM recommendation, our results indicate that GM is no suitable biomarker for the diagnosis of Magnusiomyces infection. Contrarily, BDG sensitivity is comparable to that of candidemia.

Evaluation of a new "all in one" SARS-CoV-2 antigen-detecting rapid diagnostic test and self-test: Diagnostic performance and usability in child and adult populations.

The control of the COVID-19 epidemics has been one global health priorities for the last 2 years. To that end, more reliable and easy-to-use, regardless of age, diagnostic tests are necessary. Considering that, we evaluated an innovative two-step self-test, the AAZ COVID-VIRO ALL IN®, switching from the classic nasal swab to a nasal sponge. We performed a multicenter study, on 124 adults and children, in a point-of-care setting. Sensitivity, specificity and overall acceptance of the COVID-VIRO ALL IN® self-test compared to reverse transcriptase polymerase chain reaction (RT-PCR) on nasopharyngeal samples were of 93.0%, 100%, and 97.5%, respectively. We then performed a multicenter, usability study to evaluate the ease of use of COVID-VIRO ALL IN® on 68 laypersons adults. A vast majority of participants correctly executed and interpreted the test. The usability was then specifically investigated on 40 children and teenagers, comparing COVID-VIRO® first generation to the new COVID-VIRO ALL IN®. They all found COVID-VIRO ALL IN® more comfortable and easier to use. For young children, the new self-test seems safer (less risk of trauma and no liquid exposure), and faster than saliva-based RT-PCR. Moreover, the COVID-VIRO ALL IN® can easily be adapted as a multiplex self-test for other respiratory viruses, opening new perspectives of simultaneous, rapid and massive detection of respiratory infections, especially among vulnerable populations like children and elderly people.

Evaluation of Five Commercial SARS-CoV-2 Antigen Tests in a Clinical Setting.

BACKGROUND: Point-of-care antigen tests (AgTs) for the detection of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) enable the rapid testing of infected individuals and are easy-to-use. However, there are few studies evaluating their clinical use. OBJECTIVE: The present study aimed to evaluate and compare the clinical performance characteristics of various commercial SARS-CoV-2 AgTs. DESIGN: The sensitivity of five AgTs, comprising four rapid antigen tests (RAT; AMP Rapid Test SARS-CoV-2 Ag, NADAL COVID-19 Antigen Rapid Test, CLINITEST Rapid COVID-19 Antigen Test, and Roche SARS-CoV-2 Rapid Antigen Test) and one sandwich chemiluminescence immunoassay (CLIA; LIAISON SARS-CoV-2 Assay), were evaluated in 300 nasopharyngeal (NP) swabs. Reverse transcriptase (RT) polymerase chain reaction (PCR) was used as a reference method. PARTICIPANTS: NP swabs were collected from patients admitted to hospital due to COVID-19. KEY RESULTS: Sensitivities of the AgTs ranged from 64.9 to 91.7% for samples with RT-PCR cycle threshold (Ct) values lower than 30 and were 100% for cycle threshold (Ct) values lower than 20. The highest sensitivity was observed for CLINITEST Rapid COVID-19 Antigen Test, and Roche SARS-CoV-2 rapid antigen test. Multivariate analysis using time from symptom onset and the Ct value for AgT sensitivity showed an inverse correlation. Further, the female sex was an independent factor of lower RAT sensitivity. CONCLUSIONS: Antigen tests from NP swab samples show high sensitivity in patients with a Ct value < 20. The best clinical sensitivity can be obtained using AgTs within the first 6 days after symptom onset.

Optimal diagnostic test allocation strategy during the COVID-19 pandemic and beyond.

Timely diagnostic testing for active SARS-CoV-2 viral infections is key to controlling the spread of the virus and preventing severe disease. A central public health challenge is defining test allocation strategies with limited resources. In this paper, we provide a mathematical framework for defining an optimal strategy for allocating viral diagnostic tests. The framework accounts for imperfect test results, selective testing in certain high-risk patient populations, practical constraints in terms of budget and/or total number of available tests, and the purpose of testing. Our method is not only useful for detecting infections, but can also be used for long-time surveillance to detect new outbreaks. In our proposed approach, tests can be allocated across population strata defined by symptom severity and other patient characteristics, allowing the test allocation plan to prioritize higher risk patient populations. We illustrate our framework using historical data from the initial wave of the COVID-19 outbreak in New York City. We extend our proposed method to address the challenge of allocating two different types of diagnostic tests with different costs and accuracy, for example, the RT-PCR and the rapid antigen test (RAT), under budget constraints. We show how this latter framework can be useful to reopening of college campuses where university administrators are challenged with finite resources for community surveillance. We provide a R Shiny web application allowing users to explore test allocation strategies across a variety of pandemic scenarios. This work can serve as a useful tool for guiding public health decision-making at a community level and adapting testing plans to different stages of an epidemic. The conceptual framework has broader relevance beyond the current COVID-19 pandemic.

Lower beta-1,3-D-glucan testing cut-offs increase sensitivity for non-albicans Candida species bloodstream infections.

PURPOSE: Fungal biomarkers support early diagnosis of invasive fungal infections. In this study, we evaluated the impact of a recent update to the manufacturer-recommended cut-off for beta-1,3-D-glucan (BDG) testing (Fujifilm Wako BDG assay) on sensitivity and specificity for the detection of candidemia. Additionally, we compared the performance with tests for Candida antigen (Ag by Serion ELISA antigen Candida, Virion\Serion) and anti-mannan antibodies (Ab by Hemkit Candida IHA, Ravo Diagnostika). METHODS: Sera of 82 patients with candidemia, which were sampled with a maximum distance of ±14 days from the date of sampling of the corresponding positive blood cultures, were retrospectively analysed for BDG, Ag and Ab. Results of BDG testing were compared with results from sera of 129 patients with candidemia from a different hospital. RESULTS: Sensitivity of BDG testing (47%) was higher than for Ag (17%) or Ab (20%). By combining Ag and Ab testing, sensitivity was raised to 32%. Lowering the cut-off of BDG from 11 pg/ml to the newly recommended cut-off of 7 pg/ml resulted in a significant increase in sensitivity (47% vs 58%, p = .01 and 63% vs 71% p < .01). At both centres, the increase was significant in NAC but not in C. albicans candidemia. No significant effects on specificity were observed. CONCLUSION: BDG testing outperformed Ag and Ab testing and its combination. Lowering the BDG cut-off had no significant impact on specificity. The increase in sensitivity can be mainly attributed to a gain in sensitivity for non-albicans Candida species bloodstream infections.

Throat infections and use of streptococcal antigen test and antibiotic treatment in general practice; a web-based survey.

OBJECTIVE: The aim of this study was to investigate the use of streptococcal antigen tests and antibiotic prescription in general practice in Norway in relation to the national guidelines for sore throat. DESIGN: This study was based on a web-based survey. SETTING: Norwegian general practice. SUBJECTS: 4700 members of the Norwegian College of General Practice received the survey by E-mail. MAIN OUTCOME MEASURES: General practitioner (GP) adherence to national guidelines. RESULTS: In total, 807 GPs responded and were included in the study. According to the guidelines, 20% and 30% of the GPs would perform unnecessary streptococcal antigen testing when presented with mild and severe infections respectively, while 52% would not perform the test at moderate infection. Phenoxymethylpenicillin was recommended by 95% of the GPs. CONCLUSION: In this survey of self-selected GPs, we identified some non-adherence to National guidelines for streptococcal antigen testing and antibiotic prescribing. However, when antibiotic treatment was offered, the correct antibiotics were prescribed.Key pointsNorwegian guidelines for diagnosis and treatment of throat infections include the use of Centor criteria as a clinical tool to limit the unnecessary use of antibiotics. In this web-based survey, we investigated the use of streptococcal antigen tests and antibiotic prescription in general practice in relation to the national guidelines.•Streptococcal antigen tests were not always performed according to Norwegian guidelines, causing inappropriate antibiotic prescribing.•National guidelines were followed in the choice of antibiotics for sore throat.

[Safety of blood and blood products: test methods for the detection of hepatitis B, C, and E virus]. / Sicherheit von Blut und Blutprodukten: Testmethoden zum Nachweis der Hepatitisviren B, C und E.

Infections with hepatitis B, C, and E virus (HBV, HCV, and HEV) can be transmitted via blood and cause severe acute or chronic liver infections. To ensure the safety of blood donations and protect recipients from virus transmissions, blood donations in Germany are tested for viral genomes using nucleic acid amplification techniques (NATs) as well as for viral antigens and antibodies by serological testing. This article describes the relevant regulations on the safety of blood and blood products in Germany and the various screening methods. The safety of blood products is assessed.Currently used NAT methods for detection of hepatitis viruses are based either on polymerase chain reaction (PCR) or isothermal methods such as transcription-mediated amplification (TMA), which enable a highly sensitive detection of viral infections and thereby contribute to the reduction of the diagnostic window. Antigen tests for the detection of viral surface protein of hepatitis B virus in blood donations were introduced in the 1970s in order to prevent potential transmissions. Since the introduction of mandatory testing for HCV-specific antibodies in 1992, HCV NAT testing in 1999, anti-HBc antibody testing in 2006, and the non-mandatory HBV NAT, which is voluntarily performed by most of the blood establishments, blood safety has increased tremendously. Only a few isolated cases of transfusion-transmitted infections in the early window period have been reported since. The success of the recent introduction of mandatory HEV NAT testing in 2020 will have to be assessed in the upcoming years. Besides blood donor screening, the system for blood safety in Germany is supplemented by additional measures for donor selection and pathogen inactivation.

Longitudinal Assessment of Diagnostic Test Performance Over the Course of Acute SARS-CoV-2 Infection.

BACKGROUND: Serial screening is critical for restricting spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by facilitating timely identification of infected individuals to interrupt transmission. Variation in sensitivity of different diagnostic tests at different stages of infection has not been well documented. METHODS: In a longitudinal study of 43 adults newly infected with SARS-CoV-2, all provided daily saliva and nasal swabs for quantitative reverse transcription polymerase chain reaction (RT-qPCR), Quidel SARS Sofia antigen fluorescent immunoassay (FIA), and live virus culture. RESULTS: Both RT-qPCR and Quidel SARS Sofia antigen FIA peaked in sensitivity during the period in which live virus was detected in nasal swabs, but sensitivity of RT-qPCR tests rose more rapidly prior to this period. We also found that serial testing multiple times per week increases the sensitivity of antigen tests. CONCLUSIONS: RT-qPCR tests are more effective than antigen tests at identifying infected individuals prior to or early during the infectious period and thus for minimizing forward transmission (given timely results reporting). All tests showed >98% sensitivity for identifying infected individuals if used at least every 3 days. Daily screening using antigen tests can achieve approximately 90% sensitivity for identifying infected individuals while they are viral culture positive.