Performance of BioFire array or QuickVue influenza A + B test versus a validation qPCR assay for detection of influenza A during a volunteer A/California/2009/H1N1 challenge study.

BACKGROUND: Influenza places a significant burden on global health and economics. Individual case management and public health efforts to mitigate the spread of influenza are both strongly impacted by our ability to accurately and efficiently detect influenza viruses in clinical samples. Therefore, it is important to understand the performance characteristics of available assays to detect influenza in a variety of settings. We provide the first report of relative performance between two products marketed to streamline detection of influenza virus in the context of a highly controlled volunteer influenza challenge study. METHODS: Nasopharyngeal swab samples were collected during a controlled A/California/2009/H1N1 influenza challenge study and analyzed for detection of virus shedding using a validated qRT-PCR (qPCR) assay, a sample-to-answer qRT-PCR device (BioMerieux BioFire FilmArray RP), and an immunoassay based rapid test kit (Quidel QuickVue Influenza A + B Test). RESULTS: Relative to qPCR, the sensitivity and specificity of the BioFire assay was 72.1% [63.7-79.5%, 95% confidence interval (CI)] and 93.5% (89.3-96.4%, 95% CI) respectively. For the QuickVue rapid test the sensitivity was 8.5% (4.8-13.7%, 95% CI) and specificity was 99.2% (95.6-100%, 95% CI). CONCLUSION: Relative to qPCR, the BioFire assay had superior performance compared to rapid test in the context of a controlled influenza challenge study.

Detection of Influenza A and B Viruses and Respiratory Syncytial Virus by Use of Clinical Laboratory Improvement Amendments of 1988 (CLIA)-Waived Point-of-Care Assays: a Paradigm Shift to Molecular Tests.

An accurate laboratory diagnosis of influenza, respiratory syncytial virus (RSV), and other respiratory viruses can help to guide patient management, antiviral therapy, infection prevention strategies, and epidemiologic monitoring. Influenza has been the primary driver of rapid laboratory testing due to its morbidity and mortality across all ages, the availability of antiviral therapy, which must be given early to have an effect, and the constant threat of new pandemic strains. Over the past 30 years, there has been an evolution in viral diagnostic testing, from viral culture to rapid antigen detection, and more recently, to highly sensitive nucleic acid amplification tests (NAAT), as well as a trend to testing at the point of care (POC). Simple rapid antigen immunoassays have long been the mainstay for POC testing for influenza A and B viruses and respiratory syncytial virus (RSV) but have been faulted for low sensitivity. In 2015, the first POC NAAT for the detection of influenza was approved by the Food and Drug Administration (FDA), ushering in a new era. In 2017, the FDA reclassified rapid influenza diagnostic tests (RIDTs) from class I to class II devices with new minimum performance standards and a requirement for annual reactivity testing. Consequently, many previously available RIDTs can no longer be purchased in the United States. In this review, recent developments in Clinical Laboratory Improvement Amendments of 1988 (CLIA)-waived testing for respiratory virus infections will be presented, with the focus on currently available FDA-cleared rapid antigen and molecular tests primarily for influenza A and B viruses and RSV.

Practice patterns and perceptions of influenza testing amongst pediatric urgent care providers.

INTRODUCTION: Despite a sensitivity of 50% to 70% the rapid influenza diagnostic test (RIDT) continues to play an important role in clinical decision-making due to its quick turn-around time, high specificity, relative simplicity of use, and low cost. METHODS: A quantitative study using a web-based survey was distributed to 110 members of the Society of Pediatric Urgent Care aimed to assess RIDT use for diagnosis and management of influenza in outpatient pediatric patients. RESULTS: Responses from 61 providers were received. Forty-two percent (95% CI 29.5-54.5%) of respondents report higher confidence in their diagnosis of influenza with the aid of a positive RIDT. 28% of respondents (95% CI 16.6-39.4%) report a higher likelihood of prescribing antiviral medications to low-risk patients if an RIDT is positive than without laboratory confirmation. CONCLUSION: Most pediatric urgent care respondents reported higher confidence in their diagnosis and higher likelihood of prescribing antivirals with a positive RIDT rather than by clinical symptoms alone.

A narrative review of nine commercial point of care influenza tests: an overview of methods, benefits, and drawbacks to rapid influenza diagnostic testing.

CONTEXT: Rapid influenza diagnostic tests (RIDTs) are becoming increasingly accurate, available, and reliable as the first line of testing when suspecting influenza infections, although the global burden of influenza infections remains high. Rapid diagnosis of influenza infections has been shown to reduce improper or delayed treatment and to increase access to diagnostic measures in public health, primary care, and hospital-based settings. OBJECTIVES: As the use of RIDTs continues to expand in all healthcare settings, there is a multitude of molecular techniques being employed by these various testing platforms. With this in mind, we compare the sensitivity, specificity, and time to diagnosis for nine highly utilized commercial RIDTs. METHODS: Nine commercially available RIDTs were identified from the US Centers for Disease Control and Prevention (CDC) website, which were also referenced on PubMed by name within the title or abstract of peer-reviewed publications examining the sensitivity and specificity of each test against a minimum of three influenza A virus (IAV) strains as well as seasonal influenza B virus (IBV). Data from the peer-reviewed publications and manufacturers' websites were combined to discuss the sensitivity, specify, and time to diagnosis associated with each RIDT. RESULTS: The sensitivity and specificity across the examined RIDTs were greater than 85.0% for both IAV and IBV across all platforms, with the reverse transcriptase-polymerase chain reaction (RT-PCR) assays maintaining sensitivity and specificity greater than 95.0% for all viruses tested. However, the RT-PCR platforms were the longest in time to diagnosis when compared to the other molecular methods utilized in the examined RIDTs. CONCLUSIONS: Herein, we discussed the benefits and limitations of nine commercially available RIDTs and the molecular techniques upon which they are based, showing the relative accuracy and speed of each test for IAV and IBV detection as reported by the peer-reviewed literature and commercial manufacturers.

Point-of-Care and Rapid Tests for the Etiological Diagnosis of Respiratory Tract Infections in Children: A Systematic Review and Meta-Analysis.

Fever is one of the most common causes of medical evaluation of children, and early discrimination between viral and bacterial infection is essential to reduce inappropriate prescriptions. This study aims to systematically review the effects of point-of-care tests (POCTs) and rapid tests for respiratory tract infections on changing antibiotic prescription rate, length of stay, duration of therapy, and healthcare costs. Embase, MEDLINE, and Cochrane Library databases were systematically searched. All randomized control trials and non-randomized observational studies meeting inclusion criteria were evaluated using the NIH assessment tool. A meta-analysis was performed to assess the effects of rapid influenza diagnostic tests and film-array respiratory panel implementation on selected outcomes. From a total of 6440 studies, 57 were eligible for the review. The analysis was stratified by setting and POCT/rapid test type. The most frequent POCTs or rapid tests implemented were the Rapid Influenza Diagnostic Test and film-array and for those types of test a separate meta-analysis assessed a significant reduction in antibiotic prescription and an improvement in oseltamivir prescription. Implementing POCTs and rapid tests to discriminate between viral and bacterial infections for respiratory pathogens is valuable for improving appropriate antimicrobial prescriptions. However, more studies are needed to assess these findings in pediatric settings.

Performance Evaluation of Alere i Influenza A&B in Detecting Influenza Viruses A and B.

OBJECTIVE: Alere i Influenza A&B is an isothermal nucleic acid amplification-based integrated system used for detecting and differentiating between influenza virus A and influenza virus B. We evaluated the clinical performances of Alere i Influenza A&B compared to that of real-time PCR, multiplex real-time PCR, and two rapid influenza diagnostic kits. METHODS: Nasopharyngeal aspiration specimens (n=315) from patients with signs of acute respiratory infection were collected between 2015 and 2016. Samples were tested using real-time PCR, the multiplex RT-PCR Anyplex II RV16 Detection kit, Alere i Influenza A&B, BD Veritor™ System Flu A+B, and the Sofia Influenza A+B Fluorescence Immunoassay. Positive influenza specimens detected by the Anyplex II RV16 Detection kit were tested by real-time PCR. RESULTS: Compared to that of multiplex RT-PCR (influenza A, n=88; influenza B, n=82; influenza-negative, n=145), the sensitivities of Alere i, Sofia, and Veritor for influenza A were 97.7%, 72.7%, and 71.6%, respectively, whereas for influenza B, the sensitivities were 96.3%, 80.4%, and 75.6%, respectively. The specificity of Alere i, Sofia, and Veritor was 100.0%. CONCLUSIONS: The clinical performance of Alere i Influenza A&B is satisfactory, with the advantage of a significantly shorter test time than other molecular assays. It is suitable for point-of-care testing and rapid influenza diagnostic tests because of its high sensitivity and specificity.

Influenza Management During the COVID-19 Pandemic: A Review of Recent Innovations in Antiviral Therapy and Relevance to Primary Care Practice.

Seasonal influenza requires appropriate management to protect public health and resources. Decreasing the burden of influenza will depend primarily on increasing vaccination rates as well as prompt initiation of antiviral therapy within 48 hours of symptom onset, especially in the context of the current coronavirus disease 2019 pandemic. A careful approach is required to prevent health services from being overwhelmed by a surge in demand that could exceed capacity. This review highlights the societal burden of influenza and discusses the prevention, diagnosis, and treatment of influenza as a complicating addition to the challenges of the coronavirus disease 2019 pandemic. The importance of vaccination for seasonal influenza and the role of antiviral therapy in the treatment and prophylaxis of seasonal influenza, including the most up-to-date recommendations from the Centers for Disease Control and Prevention for influenza management, will also be reviewed.

The Importance of Rapid Influenza Testing in Pediatric Primary Care: Experience During Three Consecutive Influenza Seasons (2016-2019) in Barcelona (Catalonia, Spain).

Clinical diagnosis of influenza has low sensitivity in infants and children. Signs and symptoms are non-specific and similar to those of other respiratory viruses. Rapid influenza diagnostic tests (RIDTs) with adequate sensitivity and specificity used at the point of care can be useful for an etiologic diagnosis of influenza in primary care. This should have an impact on better management of these patients. We conducted a study during three consecutive influenza seasons (2016-2017, 2017-2018, and 2018-2019) in pediatric primary care settings collecting data from influenza point-of-care tests (POCTs)-confirmed ≤ 6-year-old patients. During the first two influenza seasons, antibiotic prescriptions and additional visits from influenza POCT-confirmed patients (Group_1) were compared to patients with influenza-like illness (ILI) (Group_2), or fever (2016 ICD-10 code R50) with no other signs of influenza (Group_3). Group_1 had 0.19 (2016-2017) and 0.23 (2017-2018) additional visits compared to 0.48 (2016-2017) and 0.49 (2017-2018) Group_2 p < 0.001 and 1.01 (2016-2017) and 0.80 (2017-2018) Group_3 p < 0.001. Antibiotic prescription was lower in Group_1 (10.2%) vs. Group_3 (17.2%) p < 0.002, difference statistically significant only for the 2017-2018 season. During the third season (2018-2019), RIDTs results were transmitted in real time to the reference laboratory ia the cloud, which strengthens the monitoring of circulating influenza viruses in the community. In our experience, the use of POCTs has a great potential in primary care specially in infants and young children in which the diagnosis maybe missed due to non-specific signs and symptoms.

Seasonal influenza among children diagnosed by their guardians: a small pilot study in Japan.

AIM: We aimed to elucidate the accuracy and optimal cut-off point of the self-diagnosis of influenza and the associated clinical symptoms of children by their guardians, compared with those of the rapid influenza diagnostic test (RIDT). BACKGROUND: Seasonal influenza is a common outpatient problem during the winter season. A paediatric influenza epidemic has socio-economic impacts like temporary school closure, school event cancellations, and unscheduled work absences among parents. Hence, early identification and assessment of influenza to prevent its spread is important from a societal perspective. METHOD: We performed a cross-sectional observational study in a rural clinic in Japan every winter season from December 2013 to March 2016. We retrospectively extracted information from the medical records and pre-examination checklists of 24 patients aged <12 years (mean age, 5.4 years; men, 54.2%). The data extracted from the medical records and pre-examination checklist included the baseline characteristics (age, sex and past medical history of influenza), clinical signs and symptoms, diagnosis by guardians (%) and RIDT results. FINDINGS: The optimal cut-off point of the self-diagnosis of influenza by guardians was 80%, with a sensitivity and specificity of 63.6% (95% confidence interval: 30.8-89.1) and 92.3% (64.0-99.8). At a 50% cut-off point, the sensitivity and specificity were 90.9% (58.7-99.8) and 53.8% (25.1-80.8). The accuracy of feeling severely sick, as estimated by the guardians showed a sensitivity and specificity of 90.9% (58.7-99.8) and 69.2% (38.6-90.9). Our study indicates that the diagnosis of seasonal influenza by guardians to their children would be useful in the establishment of both confirmatory diagnoses when it has high probability above the optimal cut-off point (80%), and exclusion diagnosis when it has low probability (50%). Not feeling severely sick, estimated by the guardians might be a useful indicator for the exclusion of paediatric influenza.

Are Rapid Influenza Antigen Tests Still Clinically Useful in Today's Molecular Diagnostics World?

Influenza virus infection and disease historically contribute to widespread cases of seasonal morbidity and in some cases mortality. Prompt and accurate diagnosis is crucial for optimal patient management. Rapid influenza direct antigen testing (RIDT) offers a faster turn-around-time for results but test performance (ie, sensitivity and specificity) varies widely. Nucleic acid amplification testing (NAAT) can offer a viable alternative. The objective of this retrospective study was to compare the test performance of RIDT with NAAT. RIDT testing included the Directigen EZ Flu A+B or the Veritor System for Rapid Detection of Flu A+B. NAAT employed the SimplexaTM Flu A/B™ RSV assay. A total of 5,795 specimens collected from October to March for the 2012/2013 (n=953), 2013/2014 (n=2060) and 2014/2015 (n=2783) seasons were co-tested by RIDT and NAAT. Using NAAT as the gold standard, RIDT tests had a sensitivity range of 0 to 15.7% and a specificity of 98.2 to 100% for influenza type A. For influenza type B, RIDT tests had a sensitivity of 0 to 33.3% and a specificity of 98.9 to 100%. These findings suggest that RIDT has unacceptably low sensitivity for both influenza A and influenza B, despite high specificity. The key advantage of RIDT in previous years (faster turnaround time) has been challenged by newer NAAT technology that provides results in a turn-around-time comparable to RIDT, but with superior test performance.

Rapid Influenza Testing in an Austere Setting, Mongolia.

In 2015-2017, we helped rural Mongolian clinicians with poor infrastructure adopt rapid influenza diagnostic tests (RIDTs). In their hands, the Quidel Sofia Influenza A Test was both sensitive (75%) and specific (100%). If made widely available, such RIDTs would have the potential to markedly reduce influenza morbidity and mortality in Mongolia.

Variability in the diagnostic performance of a bedside rapid diagnostic influenza test over four epidemic seasons in a pediatric emergency department.

We wanted to determine the diagnostic performance of a rapid influenza diagnostic test (RIDT) used bedside in a pediatric emergency department (PED). This was a prospective study over four consecutive winters (2009-2013), comparing the results of a RIDT (QuickVue®) with RT-PCR in children admitted to a PED. Among the 764 children included, we did not observe any significant differences in the diagnostic performance of RIDT except during the H1N1 pandemic. The overall sensitivity of the test was 0.82; the specificity 0.98; the positive and negative likelihood ratios 37.8 and 0.19. The positive and negative post-test probabilities of infection were 98% and 17%. The diagnostic performance was increased for influenza B cases (P = 0.03). RIDTs are suitable for use every winter with few differences in its diagnostic value, except during specific pandemic periods. This test could limit unnecessary complementary exams and guide the prescription of antivirals during influenza epidemic periods in PEDs.

GENEDIA Multi Influenza Ag Rapid Test for detection and H1, H3, and H5 subtyping of influenza viruses.

BACKGROUND: Rapid identification and subtype determination of influenza virus is important in managing infected patients. Rapid influenza diagnostic tests (RIDTs) are widely used in this manner, but most can only detect influenza A and B viruses without subtyping. A new RIDT, GENEDIA Multi Influenza Ag Rapid Test (GENEDIA), was developed for detection of influenza A and B viruses and also subtyping of influenza A to H1, H3, H5 which has not been possible with other RIDTs. OBJECTIVES: Assess the performance of GENEDIA. STUDY DESIGN: Nasopharyngeal swabs were collected from 274 clinically suspected patients (influenza A/H1N1/2009 (n=50), influenza A/H3 (n=50), influenza B (n=73) and influenza-negative (n=101)) and analyzed with the real-time RT-PCR, GENEDIA, SD Bioline Influenza Ag, and Alere BinaxNow Influenza A&B Card. Also, 46 fecal specimens (H5N2 (n=3), H5N3 (n=3)) of spot-billed duck were analyzed with RT-PCR and GENEDIA. RESULTS: Compared to real-time RT-PCR, the sensitivities of GENEDIA, SD Bioline Influenza Ag, and Alere BinaxNow Influenza A&B Card were 73.0%, 57.0%, 58.0% for influenza A, respectively, and 68.5%, 65.8%, 57.5% for influenza B, respectively. Specifically, the sensitivity of GENEDIA was 70.0% for influenza A/H1N1/2009 and 76.0% for influenza A/H3. From the avian influenza samples, GENEDIA detected all six H5 subtype without any cross-reactions. CONCLUSION: The GENEDIA Multi Influenza Ag Rapid Test was sensitive in detecting influenza viruses compared with other commercial RIDTs and also useful for rapid subtype determination of influenza A.

Impact of rapid influenza diagnostic test on physician estimation of viral infection probability in paediatric emergency department during epidemic period.

BACKGROUND: The clinical diagnosis of influenza is difficult in the younger children. OBJECTIVES: Evaluate the impact of rapid influenza diagnostic test (RIDT) on clinicians' estimation of the clinical probability of influenza in children. STUDY DESIGN: This prospective study included children aged from 1 month to 5 years who were admitted in a university paediatric emergency department during an influenza epidemic period and presented with fever without source. The RIDT Quickvue(®) was performed on nasopharyngeal aspiration and results were confirmed with immunofluorescence and/or PCR. The clinical probability of influenza and serious bacterial infection (SBI) was evaluated for each child before and after the physician(s) was informed of the RIDT results. RESULTS: 170 children were included from January 15th through March 18th, 2013. After the only clinical examination, the overall clinical probability of influenza was 66.0% [CI 95%: 63.04-68.4], and was significantly increased at 92.4% [CI 95%: 89.5-95.3] in case of positive RIDT and significantly decreased at 30.8% [CI 95%: 29.0-32.5] in case of negative RIDT without knowing the results of laboratory tests. Whereas the initial clinical probability of influenza were appropriate regarding the prevalence (66.0% vs. 57.0%), the probability of SBI was overestimated (30.2% vs. 8.8%). The RIDT result positive enabled a significant decrease in orders for chest X-rays (64,4% vs. 45.8%, p<0,05) and laboratory tests (71,1% vs. 41.1%, p<0,05). CONCLUSIONS: The RIDT seems to be a useful diagnostic tool for ED clinicians in epidemic conditions. Improving clinician estimation of flu probability would reduce orders for imaging and testing.

Evaluation of 3 rapid influenza diagnostic tests during the 2012-2013 epidemic: influences of subtype and viral load.

This article evaluates the performance of 3 rapid influenza diagnostic tests (RIDTs), in correlation with the influenza subtypes and the viral load. A total of 236 samples were prospectively analyzed with BinaxNOW Influenza A/B, Directigen EZ Flu A and B, and bioNexia Influenza A+B. The results were compared to cell cultures and real-time polymerase chain reaction. Positive samples were further subtyped. Thirty-seven samples were positive for influenza A, and 57, for influenza B. For A(H1N1), the sensitivities were 71.42% for BinaxNOW, 78.57% for Directigen, and 67.85% for bioNexia. Eight samples were positive for A(H3N2), and only the bioNexia test had 1 false-negative result. Lowest sensitivities were observed for influenza B/Yamagata, (56.86% for BinaxNOW and Directigen and 39.21% for bioNexia). The 3 evaluated RIDTs were more efficient at detecting influenza A(H3N2) than for A(H1N1) and B/Yamagata. Highest viral loads in the samples were associated with better rate of detection.

Evaluation of a rapid immunodiagnostic rabies field surveillance test on samples collected from military operations in Africa, Europe, and the Middle East.

The Anigen Rapid Rabies Antigen Test Kit (Bionote, Inc, Hwaseong, Korea) was evaluated using 80 clinical samples collected by US military veterinary units. Samples for the study were obtained from brain specimens of domestic and wildlife animals that were submitted to the US Army Public Health Command's Veterinary Laboratory Europe in Landstuhl, Germany, for rabies testing with the direct fluorescent antibody test. The rapid immunodiagnostic test was able to detect rabies virus antigen in clinical samples of brain tissue. The rapid immunodiagnostic test had an overall sensitivity of 96.9% and specificity of 100% when compared to the direct fluorescent antibody test. The rapid immunodiagnostic test for rabies virus antigen detection is a straightforward test that can be run under field conditions and without a microscope or electricity, and yield results in 5 to 10 minutes. This rapid immunodiagnostic test is a quick, inexpensive, and easy to use surveillance tool that can identify rabies positive animals and help focus targeted control measures with the goal of reducing the rabies burden.

Patients Hospitalized with pH1N1 Influenza in an Academic Community Medical Center.

BACKGROUND: The emergence of a novel strain of pandemic influenza (pH1N1) in 2009 presented significant challenges to health care facilities worldwide. In our academic community medical center in suburban Philadelphia, we noted our first pH1N1 diagnosis in September 2009. We sought to assess the impact of pH1N1 disease on our hospitalized patient population. METHODS: We prospectively collected clinical and epidemiological data on 29 consecutive patients that were admitted to our hospital with a primary or secondary diagnosis of influenza from October 1-November 30, 2009. Data were obtained through care of the patients and chart review. RESULTS: Prominent symptoms on admission included fever, hypoxia, cough, myalgias, and diarrhea, with leukocytosis and neutrophilia. Pre-existing medical conditions included asthma, pregnancy, immunosuppressive therapy, and sickle cell disease. All but 5 of the patients were under 60 years of age. Three patients had culture-documented bacterial or mycoplasma infections. All but two of the patients received oseltamivir. Six required admission to the intensive care unit but only one patient died. CONCLUSIONS: Our population of hospitalized patients with novel pH1N1 influenza demonstrated many of the features that have been associated with pH1N1 disease in other populations. Most of the patients were women and none of the patients died directly as a complication of influenza. We observed a cluster of patients with a tetrad of features comprising a history of asthma, obesity, female gender, and African-American race. Individuals with this constellation of factors should be specifically targeted for pH1N1 vaccination.

<b>Development of A Decision Making Model for the Management of Influenza. A Proposal of Diagnostic Policy </b><b>Based on Phenomena and Therapeutics. </b> / 日本東洋医学雑誌

The management of influenza has dramatically changed since the introduction of the rapid influenza diagnostic test, or RIDT, and neuraminidase inhibitors (NI). However, it is still far from optimal due to low RIDT sensitivity and problems involving NI such as side effects and the potential emergence of resistant virus.Therefore, we developed a decision-making model for the management of influenza, which includes Kampo medicines in its strategies. First, the severity of patients is evaluated. If a patient is judged at severe or high-risk, intravenous NI would be the main component of treatment. If a patient has neither a severe condition nor is at high-risk, the patient would be asked to choose either NI or Kampo medicine. In the former, RIDT would be used if pretest probability was less than 50%, but it would not be used if it was more than 50%, based on the lack of influence on the post-test probability. For the latter, RIDT would be not used in general as Kampo targets “phenomena”, not the virus <i>per se</i>. This model enables us to optimize the use of RIDT by appropriately selecting patients based on the characteristics of RIDT, and by avoiding unnecessary tests and their misinterpretation.