Multicenter evaluation of the Alere™ i influenza A&B assay using respiratory specimens collected in viral transport media.

Rapid and accurate detection of influenza virus is critical for proper patient management. The Alere™ i Influenza A&B assay is an isothermal nucleic acid amplification test capable of detecting influenza A and B viruses directly from respiratory specimens. In this multicenter clinical trial conducted in the US, we evaluated the clinical performance of the Alere™ i Influenza A&B assay against that of the Prodesse ProFlu+ assay. A total of 1243 fresh, leftover nasal or nasopharyngeal swabs eluted in viral transport medium were tested by both assays. Sensitivity and specificity of the Alere™ i Influenza A&B assay were 97.8% (95% CI 94.6-99.2) and 96.6% (95% CI 95.2-97.5) for influenza A and 92.9% (95% CI 85.5-96.9) and 98.3% (95% CI 97.4-98.0) for influenza B. The Alere™ i Influenza A&B assay is an ideal molecular assay for influenza virus detection due to its high sensitivity and specificity with minimal hands-on and turn-around-time.

Mucosal antibody responses are directed by viral burden in children with acute influenza infection.

BACKGROUND: Influenza infection causes excess hospitalizations and deaths in younger patients, but susceptibility to severe disease is poorly understood. While mucosal antibodies can limit influenza-associated infection and disease, little is known about acute mucosal antibody responses to influenza infection. OBJECTIVES: These studies characterize mucosal antiviral antibody production in children during lower respiratory infection (LRI) with H1N1 influenza versus other viral LRI and examine the relationship between mucosal antiviral antibodies and protection against severe disease. METHODS: B lymphocytes were assessed by immunohistochemistry in lung tissue from infants with fatal acute seasonal influenza infection. Nasopharyngeal secretions (NPS) were obtained at presentation from children with acute respiratory illness, including H1N1 (2009) influenza infection. Total and antiviral antibodies, and inflammatory and immune mediators, were quantified by ELISA. Neutralizing activity in NPS was detected using a pseudotyped virus assay. Viral burden was assessed by qPCR. RESULTS AND CONCLUSIONS: B lymphocytes were abundant in lung tissue of infants with fatal acute influenza LRI. Among surviving children with H1N1 infection, only a small subset (11%) demonstrated H1N1 neutralizing activity in NPS. H1N1 neutralizing activity coincided with high local levels of antiviral IgM, IgG and IgA, greater detection of inflammatory mediators, and higher viral burden (P = 0·016). Patients with mucosal antiviral antibody responses demonstrated more severe respiratory symptoms including greater hypoxia (P = 0·0018) and pneumonia (P = 0·038). These patients also trended toward younger age, longer duration of illness and longer hospital stays. Prophylaxis strategies that heighten neutralizing antibody production in the mucosa are likely to benefit both older and younger children.

Do pediatricians manage influenza differently than internists?

BACKGROUND: Little is known about how pediatricians or internists manage influenza symptoms. Recent guidelines on antiviral prescribing by the Centers for Disease Control and Prevention (CDC) make almost no distinction between adults and children. Our objective was to describe how pediatricians in two large academic medical institutions manage influenza and compare them to internists. METHODS: At the end of the 2003-4 influenza season, we conducted a cross sectional on-line survey of physician knowledge, attitudes and practices regarding rapid diagnostic testing and use of antiviral therapy for influenza at two large academic medical centers, one in Massachusetts and the other in Texas. We collected data on self-reported demographics, test use, prescribing practices, and beliefs about influenza and anti-influenza drugs. RESULTS: A total of 107 pediatricians and 103 internists completed the survey (response rate of 53%). Compared to internists, pediatricians were more likely to perform rapid testing (74% vs. 47%, p < 0.0001), to use amantadine (88% vs. 48%, p < 0.0001), to restrict their prescribing to high-risk patients (86% vs. 53%, p < 0.0001), and to believe that antiviral therapy could decrease mortality (38% vs. 22%, p = 0.01). Other beliefs about antiviral therapy did not differ statistically between the specialties. Internists were more likely to be unfamiliar with rapid testing or not to have it available. CONCLUSION: Pediatricians and internists manage influenza differently. Evidence-based guidelines addressing the specific concerns of each group would be helpful.

Comparison of the MChip to viral culture, reverse transcription-PCR, and the QuickVue influenza A+B test for rapid diagnosis of influenza.

The performance of a diagnostic microarray (the MChip assay) for influenza was compared in a blind study to that of viral culture, reverse transcription (RT)-PCR, and the QuickVue Influenza A+B test. The patient sample data set was composed of 102 respiratory secretion specimens collected between 29 December 2005 and 2 February 2006 at Scott & White Hospital and Clinic in Temple, Texas. Samples were collected from a wide range of age groups by using direct collection, nasal/nasopharyngeal swabs, or nasopharyngeal aspiration. Viral culture and the QuickVue assay were performed at the Texas site at the time of collection. Aliquots for each sample, identified only by study numbers, were provided to the University of Colorado and Vanderbilt University teams for blinded analysis. When referenced to viral culture, the MChip exhibited a clinical sensitivity of 98% and a clinical specificity of 98%. When referenced to RT-PCR, the MChip assay exhibited a clinical sensitivity of 92% and a clinical specificity of 98%. While the MChip assay currently requires 7 to 8 h to complete the analysis, a significant advantage of the test for influenza virus-positive samples is simultaneous detection and full subtype identification for the two subtypes currently circulating in humans (A/H3N2 and A/H1N1) and avian (A/H5N1) viruses.

Effects of local variation, specialty, and beliefs on antiviral prescribing for influenza.

In 2004, we conducted a survey of physician knowledge, attitudes, and practices regarding influenza diagnosis and treatment at Baystate Medical Center in Massachusetts and Scott & White Hospital and Clinic in Texas. Of the 579 physicians we contacted, 336 completed the survey. Sixty-one percent of the respondents prescribed antivirals, and 62% used rapid testing. Prescribing practices were associated with location, practice size, use of rapid testing, and belief in the efficacy of antivirals.

Impact of the rapid diagnosis of influenza on physician decision-making and patient management in the pediatric emergency department: results of a randomized, prospective, controlled trial.

OBJECTIVE: To determine the impact of the rapid diagnosis of influenza on physician decision-making and patient management, including laboratory tests and radiographs ordered, patient charges associated with these tests, antibiotics/antivirals prescribed, and length of time to patient discharge from the emergency department. METHODS: Patients aged 2 months to 21 years presenting to an urban children's teaching hospital emergency department were screened for fever and cough, coryza, myalgias, headache, and/or malaise. After obtaining informed consent, patients were randomized to 1 of 2 groups: 1) physician receives (physician aware of) the rapid influenza test result; or 2) physician does not receive (physician unaware of) the result. For patients in the physician aware group, nasopharyngeal swabs were obtained, immediately tested with the FluOIA test for influenza A and B, and the result was placed on the chart before patient evaluation by the attending physician. For the physician unaware group, nasopharyngeal swabs were obtained, stored according to manufacturer's directions, and tested within 24 hours. Results for the physician unaware group were not disclosed to the treating physicians at any time. The 2 resultant influenza-positive groups (aware and unaware) were compared for laboratory and radiograph studies and their associated patient charges, antibiotic/antiviral prescriptions, and length of stay in the emergency department. RESULTS: A total of 418 patients were enrolled, and 391 completed the study. Of these, 202 tested positive for influenza. Comparison of the 96 influenza-positive patients whose physician was aware of the result with the 106 influenza-positive patients whose physician was unaware of the result revealed significant reductions among the former group in: 1) numbers of complete blood counts, blood cultures, urinalyses, urine cultures, and chest radiographs performed; 2) charges associated with these tests; 3) antibiotics prescribed; and 4) length of stay in the emergency department. The number of influenza-positive patients who received prescriptions for antiviral drugs was significantly higher among those whose physician was aware of the result. CONCLUSIONS: Physician awareness of a rapid diagnosis of influenza in the pediatric emergency department significantly reduced the number of laboratory tests and radiographs ordered and their associated charges, decreased antibiotic use, increased antiviral use, and decreased length of time to discharge.