Negative Rapid Influenza Diagnostic Tests Research Articles

Assessment of potential factors associated with the sensitivity and specificity of Sofia Influenza A+B Fluorescent Immunoassay in an ambulatory care setting.

Seasonal influenza leads to an increase in outpatient clinic visits. Timely, accurate, and affordable testing could facilitate improved treatment outcomes. Rapid influenza diagnostic tests (RIDTs) provide results in as little as 15 minutes and are relatively inexpensive, but have reduced sensitivity when compared to RT-PCR. The contributions of multiple factors related to test performance are not well defined for ambulatory care settings. We assessed clinical and laboratory factors that may affect the sensitivity and specificity of Sofia Influenza A+B Fluorescence Immunoassay. We performed a post-hoc assessment of surveillance data amassed over seven years from five primary care clinics. We analyzed 4,475 paired RIDT and RT-PCR results from specimens collected from patients presenting with respiratory symptoms and examined eleven potential factors with additional sub-categories that could affect RIDT sensitivity. In an unadjusted analysis, greater sensitivity was associated with the presence of an influenza-like illness (ILI), no other virus detected, no seasonal influenza vaccination, younger age, lower cycle threshold value, fewer days since illness onset, nasal discharge, stuffy nose, and fever. After adjustment, presence of an ILI, younger age, fewer days from onset, no co-detection, and presence of a nasal discharge maintained significance. Clinical and laboratory factors may affect RIDT sensitivity. Identifying potential factors during point-of-care testing could aid clinicians in appropriately interpreting negative influenza RIDT results.

Correlation between Negative Rapid Influenza Diagnostic Test and Severe Disease in Hospitalized Adults with Laboratory-Confirmed Influenza Virus Infection.

.False-negative rapid influenza diagnostic test (RIDT) results could mislead physicians to exclude an influenza diagnosis. We sought to evaluate the association between negative RIDT and intensive care unit (ICU) admission. We reviewed data from hospitalized adults with laboratory-confirmed influenza virus infections in a tertiary referral hospital in Taiwan from July 2009 to February 2011. The diagnosis was documented by real-time PCR or virus culture. Of 134 hospitalized adults infected with influenza virus, 38 (28%) were admitted to the ICU. Compared with RIDT-positive patients, the percentage of ICU admission was significantly higher among RIDT-negative patients (46% versus 13%, P < 0.001). The RIDT-negative patients had higher percentages of lower respiratory symptoms and more chest radiograph infiltrates. The time interval between the RIDT and antiviral treatment was longer in RIDT-negative than RIDT-positive patients (1.94 days versus 0.03 days, P < 0.001). Among patients presenting with mild illness, only a negative RIDT and delayed antiviral treatment were associated with ICU admission after adjusting for potential confounding factors. To conclude, patients with a negative RIDT were more likely to have severe disease and a delay in initiating antiviral treatment. Our findings should help improve treatment outcomes of hospitalized patients with influenza infection.

Clinical Impact of Rapid Point-of-Care PCR Influenza Testing in an Urgent Care Setting: a Single-Center Study.

Seasonal influenza virus causes significant morbidity and mortality each year. Point-of-care (POC) testing using rapid influenza diagnostic tests (RIDTs), immunoassays that detect viral antigens, are often used for diagnosis by physician offices and urgent care centers. These tests are rapid but lack sensitivity, which is estimated to be 50 to 70%. Testing by PCR is highly sensitive and specific, but historically these assays have been performed in centralized clinical laboratories necessitating specimen transport and increasing the time to result. Recently, Clinical Laboratory Improvement Amendments (CLIA)-waived, POC PCR influenza assays have been developed with >95% sensitivity and specificity compared to centralized PCR assays. To determine the clinical impact of a POC PCR test for influenza, we compared antimicrobial prescribing patterns of one urgent care location using the Cobas LIAT Influenza A/B assay (LIAT assay; Roche Diagnostics, Indianapolis, IN) to other urgent care centers in our health system using traditional RIDT, with negative specimens being reflexed to PCR. Antiviral prescribing was lower in patients with a negative LIAT PCR result (2.3%) than in patients with a negative RIDT result (25.3%; P < 0.005). Antivirals were prescribed more often in patients that tested positive by LIAT PCR (82.4%) than in those testing positive by either RIDT or reflex PCR (69.9%; P < 0.05). Antibacterial prescriptions for patients testing negative by LIAT PCR were higher (44.5%) than for those testing negative by RIDT (37.7%), although the difference was not statistically significant. In conclusion, having results from a PCR POC test during the clinic visit improved antiviral prescribing practices compared to having rapid results from an RIDT.

Outcomes of a Negative Rapid Influenza Diagnostic Test in Pregnant Women.

The objective of this study was to evaluate the negative predictive value (NPV) of a rapid influenza diagnostic test (RIDT) compared with polymerase chain reaction (PCR) in pregnant women. Retrospective cohort study of pregnant women with a negative RIDT followed by confirmatory PCR for influenza A, H1N1, and B during the influenza seasons from 2012 to 2015. The NPV of the RIDT was 85.4% (211 of 247), 93.5% (231 of 247), and 97.9% (242 of 247) for influenza A, H1N1, and B, respectively. Antiviral treatment was administered to 47.2% (17 of 36) of women with a false-negative RIDT for influenza A compared with 9.0% (19 of 211) of women with a true-negative RIDT (p< 0.001). Patients were more likely to receive antiviral treatment if they were feverish (adjusted odds ratio [aOR]: 6.05, 95% confidence interval [CI]: 1.83-20.03), had cough (aOR: 6.43, 95% CI: 1.06-39.26), dyspnea (aOR: 6.41, 95% CI: 1.63-25.29), or had a subsequently positive PCR (aOR: 9.41, 95% CI: 3.13-28.31). Up to 14.5% of women with a negative RIDT in pregnancy had positive influenza A by PCR of whom more than half did not receive antiviral treatment.

22: Outcomes of a negative rapid influenza diagnostic test among pregnant women

22: Outcomes of a negative rapid influenza diagnostic test among pregnant women

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

BackgroundThe clinical diagnosis of influenza is difficult in the younger children. ObjectivesEvaluate the impact of rapid influenza diagnostic test (RIDT) on clinicians’ estimation of the clinical probability of influenza in children. Study designThis 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. Results170 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). ConclusionsThe 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.

Effect of rapid influenza diagnostic testing on antiviral treatment decisions for patients with influenza-like illness: southwestern U.S., May-December 2009.

Rapid influenza diagnostic tests (RIDTs) had low test sensitivity for detecting 2009 pandemic influenza A (H1N1pdm09) infection, causing public health authorities to recommend that treatment decisions be based primarily upon risk for influenza complications. We used multivariate Poisson regression analysis to estimate the contribution of RIDT results and risk for H1N1pdm09 complications to receipt of early antiviral (AV) treatment among 290 people with influenza-like illness (ILI) who received an RIDT ≤48 hours after symptom onset from May to December 2009 at four southwestern U.S. facilities. RIDT results had a stronger association with receipt of early AVs (rate ratio [RR] = 3.3, 95% confidence interval [CI] 2.4, 4.6) than did the presence of risk factors for H1N1pdm09 complications (age <5 years or high-risk medical conditions) (RR=1.9, 95% CI 1.3, 2.7). Few at-risk people (28/126, 22%) who had a negative RIDT received early AVs, suggesting the need for sustained efforts by public health to influence clinician practices.

Clinical diagnosis of pandemic A(H1N1) 2009 influenza in children with negative rapid influenza diagnostic test by lymphopenia and lower C‐reactive protein levels

BackgroundThe sensitivity of rapid influenza diagnostic test (RIDT) of children with influenza-like illness (ILI) remains low.ObjectiveWe compare the parameters between pandemic A(H1N1) 2009 influenza with negative RIDT and ILI not H1N1 for improving the low sensitivity of RIDT for children with ILI.MethodsIn a cohort of consecutive laboratory-confirmed H1N1 influenza, we identified 150 H1N1 children with positive RIDT, 152 H1N1 children with negative RIDT, and 75 children with ILI not H1N1. Viral load in throat, complete blood count (CBC), and C-reactive protein (CRP) levels between H1N1 children with negative RIDT and children with ILI not H1N1 were assessed.ResultsThe diagnostic sensitivity of the RIDT was 45·5%. An analysis of CBC and CRP levels indicated that H1N1 children with negative RIDT had lower total leukocyte, neutrophil, lymphocyte, and basophil counts, and serum CRP levels (P < 0·01). Lymphocyte counts less than 1500 cells/mm3 and CRP levels <15 mg/l, determined by a receiver operating characteristic curve, showed a diagnostic sensitivity of 52·5% and 80·7%, respectively. Combining the lymphocyte counts and CRP levels provided a diagnostic sensitivity of 91·5%. Moreover, H1N1 children with negative RIDT had a lower viral load than those with positive RIDT (3·33 versus 4·48 log10 copies/ml, P < 0·001); the viral load was negatively correlated to the lymphocyte count (P < 0·001).ConclusionsA combination of a low lymphocyte count and a low CRP level could, in the early disease phase, provide a useful screening for H1N1 children with false-negative RIDT, potentially facilitating differential diagnoses.

Estimating the Influenza Vaccine Effectiveness against Medically Attended Influenza in Clinical Settings: A Hospital-Based Case-Control Study with a Rapid Diagnostic Test in Japan

BackgroundInfluenza vaccine effectiveness (VE) studies are usually conducted by specialized agencies and require time and resources. The objective of this study was to estimate the influenza VE against medically attended influenza using a test-negative case-control design with rapid influenza diagnostic tests (RIDT) in a clinical setting.MethodsA prospective study was conducted at a community hospital in Nagasaki, western Japan during the 2010/11 influenza season. All outpatients aged 15 years and older with influenza-like illnesses (ILI) who had undergone RIDT were enrolled. A test-negative case-control design was applied to estimate the VEs: the cases were ILI patients with positive RIDT results and the controls were ILI patients with negative RIDT results. Information on patient characteristics, including vaccination histories, was collected using questionnaires and medical records.ResultsBetween December 2010 and April 2011, 526 ILI patients were tested with RIDT, and 476 were eligible for the analysis. The overall VE estimate against medically attended influenza was 47.6%, after adjusting for the patients' age groups, presence of chronic conditions, month of visit, and smoking and alcohol use. The seasonal influenza vaccine reduced the risk of medically attended influenza by 60.9% for patients less than 50 years of age, but a significant reduction was not observed for patients 50 years of age and older. A sensitivity analysis provided similar figures.ConclusionThe test-negative case-control study using RIDT provided moderate influenza VE consistent with other reports. Utilizing the commonly used RIDT to estimate VE provides rapid assessment of VE; however, it may require validation with more specific endpoint.

Symptomatic Predictors for 2009 Influenza A Virus (H1N1) Infection with an Emphasis for Patients with a Negative Rapid Diagnostic Test

BackgroundThe clinical diagnosis of influenza is difficult because it shares nonspecific symptoms with a variety of diseases. Emergency departments and clinics were overwhelmed by a surge of anxious patients during the 2009 influenza A virus (H1N1) outbreak. Our objective was to identify symptomatic predictors of influenza virus infection for patients with a negative rapid diagnostic test.Methodology/Principal FindingsWe conducted a retrospective review of 805 patients who presented at Chang Gung Memorial Hospital, from August 1, 2009, to September 30, 2009. Respiratory specimens from these patients were subjected to rapid influenza tests and reverse-transcription polymerase chain reactions. In total, 36% of 308 children and 23% of 497 adults were positive for 2009 influenza A virus (H1N1) infection by polymerase chain reaction or virus culture. For pediatric patients, sore throat and influenza-like illness significantly increased the odds of having 2009 influenza A virus (H1N1) infection, by more than 3-fold (95% confidence interval (CI): 1.9–7.3) and 7-fold (95% CI: 4.00–14.2), respectively. For adult patients, cough and constitutional symptoms increased the odds of having 2009 influenza A virus (H1N1) by greater than 5-fold (95% CI: 3.1–10.2) and 3-fold (95% CI: 2.1–6.7), respectively. The negative likelihood ratio of the combination of fever and cough was 0.096 (95% CI: 0.01–0.69) for children with negative results of rapid influenza diagnostic tests.Conclusion/SignificanceIn influenza epidemic settings, clinicians should be aware that rapid influenza diagnostic tests are relatively insensitive for the diagnosis of influenza virus infection. For patients with negative rapid influenza diagnostic tests, those lacking fever and cough have a low probability of influenza virus infection. The management strategy should be made individually and depend on the severity of illness.

Severity of pandemic H1N1 2009 influenza virus infection may not be directly correlated with initial viral load in upper respiratory tract

Please cite this paper as: Wu et al. (2012) Severity of pandemic H1N1 2009 influenza virus infection may not be directly correlated with initial viral load in upper respiratory tract. Influenza and Other Respiratory Viruses 6(5), 367–373. Background Recent studies have demonstrated that rapid influenza diagnostic tests (RIDTs) have a relatively low sensitivity in detecting severe cases of pandemic H1N1 2009 influenza virus (pH1N1) infection. We hypothesized that viral load in upper respiratory specimens obtained on presentation may not be correlated with disease severity. Methods We conducted a prospective study to compare patterns of viral shedding using nasopharyngeal swab specimens, according to the number of days of post‐symptom onset and post‐antiviral therapy, between patients with and without complications. Results From July 15, 2009 through July 23, 2010, we collected and processed a total of 141 nasopharyngeal swab specimens from 64 inpatients and outpatients with laboratory‐confirmed pH1N1 infection. These included 46 patients without any complications (uncomplicated group) and 18 patients who required hospital admission (complicated group). The mean initial viral load was higher in the uncomplicated group than in the complicated group (3·4 ± 1·6 log10 copies/μl versus 1·9 ± 1·7, P = 0·02). However, prolonged viral shedding was only detected in the complicated group (44% by day 7 of antiviral therapy). By multivariate analysis, we found that age (OR, 1·1; 95% CI, 1·0–1·1) and initial nasopharyngeal viral load (OR, 0·5; 95% CI, 0·3–0·8) were significant factors associated with complications. Conclusion Given that patients with severe pH1N1 infection may have relatively lower initial viral load in the upper respiratory tract, cautious interpretation of negative RIDT results is particularly warranted in this patient population.

Severe swine influenza A (H1N1) versus severe human seasonal influenza A (H 3N 2): Clinical comparisons

At the beginning of the swine influenza (H1N1) pandemic in the spring of 2009, there were still stories of human seasonal influenza A circulating in the New York area. Adult patients admitted with influenza-like illnesses (ILIs) (fever > 102°F, dry cough, and myalgias) presented diagnostic problems. First, clinicians had to differentiate ILIs from influenza, and then differentiate human seasonal influenza A from H1N1 in hospitalized adults with ILIs and negative chest films (no focal segmental/lobar infiltrates). Human seasonal influenza A was diagnosed by rapid influenza diagnostic tests (RIDTs), but H1N1 was often RIDT negative. Reverse transcriptase-polymerase chain reaction for H1N1 was restricted or not available. The Winthrop-University Hospital Infectious Disease Division developed clinical diagnostic criteria (a diagnostic weighted point score system) to rapidly and clinically diagnose H1N1 in patients with negative RIDTs. The point score system was modified and shortened for ease of use, that is, the diagnostic H1N1 triad (any 3 of 4) (ILI, see above) plus thrombocytopenia, relative lymphopenia, elevated serum transaminases, or an elevated creatine phosphokinase. Our clinical experience during the pandemic allowed us to develop the swine diagnostic H1N1 triad. In the process, similarities and differences between human seasonal influenza A and H1N1 were noted. We present 2 illustrative cases of severe influenza, one due to human seasonal influenza A and one due to H1N1, for clinical consideration reflective of our experiences early in the H1N1 pandemic in 2009.

Human parainfluenza virus type 3 (HPIV 3) viral community-acquired pneumonia (CAP) mimicking swine influenza (H1N1) during the swine flu pandemic

Background The swine influenza (H1N1) pandemic began in Mexico in 2009 and quickly spread worldwide. During the H1N1 pandemic, many patients were admitted to the Winthrop-University Hospital with influenza-like illnesses (ILIs). Many hospitalized adults had H1N1 pneumonia diagnosed by laboratory or clinical criteria. However, the laboratory diagnosis of H1N1 was problematic. The rapid influenza (QuickVue A/B [Quidel, San Diego, CA]) test frequently showed false-negative results. Reverse transcriptase-polymerase chain reaction (RT-PCR), the definitive test for H1N1, was restricted or unavailable, or results were reported after they were clinically relevant. Because of difficulties making a laboratory diagnosis of H1N1, Winthrop-University Hospital’s Infectious Disease Division developed clinical criteria to diagnose H1N1 when rapid influenza diagnostic test (RIDT) results were negative. It also became clear that some patients with negative RIDT and RT-PCR H1N1 clearly had H1N1 pneumonia on a clinical basis. There have been patients who died of H1N1 pneumonia with negative RIDT and RT-PCR H1N1 but had postmortem lung specimens positive for H1N1 by RT-PCR. Methods During the flu pandemic, the main diagnostic and infection control problems were to differentiate ILIs from H1N1. Unlike admitted adults hospitalized with ILIs, clinical H1N1 pneumonia patients with negative RIDT results but had dry cough, myalgias, temperatures greater than 102°F, and a negative chest x-ray without focal segmental/lobar infiltrates. With the use of the Winthrop-University Hospital’s Infectious Disease Division diagnostic H1N1 triad, patients with H1N1 had the above plus 3 of the following 4 laboratory abnormalities: relative lymphopenia, thrombocytopenia, elevated serum transaminases, or elevated creatine phosphokinase. It was important to rapidly and accurately diagnose H1N1 to place such patients on proper precautions and initiate oseltamivir therapy. Results As the H1N1 pandemic progressed, it became clear that there were some infectious diseases that mimicked H1N1 pneumonia (eg, Legionnaires’ disease). We describe the case of a 61-year-old man who presented with an ILI with dry cough, fever, myalgias, and shortness of breath. His rapid influenza A test result was negative, and specimens for RT-PCR for H1N1 were ordered. On admission, he had relative lymphopenia, thrombocytopenia, and an elevated creatine phosphokinase. His chest x-ray showed no focal segmental or lobar infiltrates. The patient was placed on influenza precautions and administered oseltamivir. During the patient’s hospital course, the RT-PCR for H1N1 was reported negative. His respiratory fluorescent antibody viral panel was negative for influenza A, influenza B, metapneumoviruses, respiratory syncytial virus, and adenoviruses but positive for human parainfluenza virus type 3 (HPIV 3). Conclusions Clinicians should be aware of other causes of community-acquired pneumonia that may mimic H1N1 pneumonia. In our experience, the most common mimics of H1N1 pneumonia are Legionnaires’ disease or HPIV 3 in adults, and metapneumovirus or respiratory syncytial virus in children. In adult patients who present with an ILI and negative RIDT results, we suggest that respiratory secretions specimens be obtained for respiratory fluorescent antibody viral testing pending RT-PCR for H1N1 results. HPIV 3, known to be an important community-acquired pneumonia pathogen in transplant recipients and immunosuppressed patients, is also an important pathogen in immunocompetent adults. In normal adult hosts, the clinical presentation of HPIV 3 pneumonia may clinically closely mimic H1N1 pneumonia.

Rapid clinical diagnosis of Legionnaires' disease during the “herald wave” of the swine influenza (H1N1) pandemic: The Legionnaires' disease triad

BackgroundIn adults hospitalized with atypical community-acquired pneumonia (CAP), Legionnaires' disease is not uncommon. Legionnaire's disease can be differentiated from typical CAPs and from other atypical CAPs based on its characteristic pattern of extrapulmonary organ involvement. The first clinically useful diagnostic weighted point score system for the clinical diagnosis of Legionnaires' disease was developed by the Infectious Disease Division at Winthrop-University Hospital in the 1980s. It has proven to be diagnostically accurate and useful for more than two decades, but was time-consuming. Because Legionella spp. diagnostic tests are time-dependent and problematic, a need was perceived for a rapid, simple way to render a clinical, syndromic diagnosis of Legionnaires' disease pending Legionella test results. During the “herald wave” of the swine influenza (H1N1) pandemic in the New York area, our hospital, like others, was inundated with patients who presented to the Emergency Department with influenza-like illnesses (ILIs) for H1N1 testing/evaluation. Most patients with ILIs did not have swine influenza. Hospitalized patients with ILIs who tested positive with rapid influenza diagnostic tests (RIDTs) were placed on influenza precautions and treated with oseltamivir. Unfortunately, approximately 30% of adult patients admitted with an ILI had negative RIDTs. Because the definitive laboratory diagnosis of H1N1 pneumonia by reverse transcription-polymerase chain reaction(RT-PCR), testing was restricted by health departments, resulted in clinical and infection control dilemmas in determining which RIDT-negative patients did, in fact, have H1N1 pneumonia.ObjectiveAccordingly, a diagnostic weighted point score system was developed for H1N1 pneumonia patients, based on RT-PCR positivity by the Infectious Disease Division at Winthrop-University Hospital. This diagnostic point score system for hospitalized adults with negative RIDTs was time-consuming. As the pandemic progressed, a simplified diagnostic swine influenza (H1N1) triad was developed for the rapid clinical diagnosis of probable H1N1 pneumonia, which also differentiated it from its mimics as well as from bacterial pneumonia, eg, Legionnaires' disease. During the “herald wave” of the H1N1 pandemic, we noticed an unexplained increase in Legionnaires' disease CAPs. Because clinical resources were stressed to the maximum during the pandemic, it was critically important to rapidly identify patients rapidly with Legionnaire's disease who did not require influenza precautions or oseltamivir, but who did require anti-Legionella antimicrobial therapy.MethodsBased on the Winthrop-University Hospital Infectious Disease Division's diagnostic weighted point score system for Legionnaires' disease (modified), key indicators were identified and became the basis for the diagnostic Legionnaires' disease triad. The diagnostic Legionnaires' disease triad was used to make a clinical diagnosis of Legionnaires' disease until the results of Legionella diagnostic tests were reported. The diagnostic Legionnaires' disease triad diagnosed Legionnaires' disease in hospitalized adults with CAPs with extrapulmonary findings (atypical CAP) and relative bradycardia, accompanied by any three (ie, a triad) of the following: otherwise unexplained relative lymphopenia, early/mildly elevated serum transaminases (SGOT/SGPT), highly increased ferritin levels (≥2 × n), or hypophosphatemia. The diagnostic Legionnaires' disease triad provides clinicians with a rapid way to clinically diagnose Legionnaires' disease, pending Legionella test results.ResultsThe accuracy of the diagnostic Legionnaires' disease triad was confirmed in our 9 cases of Legionnaires' disease by subsequent Legionella diagnostic testing.ConclusionsThe diagnostic Legionnaires' disease triad is particularly useful in situations where a rapid clinical syndromic diagnosis is needed, ie, during an H1N1 pandemic.

Clinical Management of Pandemic 2009 Influenza A(H1N1) Infection

Antiviral therapy and vaccination are important strategies for controlling pandemic 2009 influenza A(H1N1) but efficacy depends on the timing of administration and is often limited by supply shortage. Patients with dyspnea, tachypnea, evidence of hypoxemia, and pulmonary infiltrates on chest radiograph should be hospitalized. Patients with severe illness or underlying medical conditions that increase the risk of more severe disease should be treated with oseltamivir or zanamivir as soon as possible, without waiting for the results of laboratory tests. Lung-protective ventilation strategy with a low tidal volume and adequate pressure, in addition to a conservative fluid management approach, is recommended when treating adult patients with ARDS. Extracorporeal membrane oxygenation has emerged as an important rescue therapy for critically ill patients. Use of systemic steroids was associated with delayed viral clearance in severe acute respiratory syndrome and H3N2 infection. Low-dose corticosteroids may be considered in the treatment of refractory septic shock. Passive immunotherapy in the form of convalescent plasma or hyperimmune globulin may be explored as rescue therapy. More data are needed to explore the potential role of IV gamma globulin and other drugs with immunomodulating properties, such as statins, gemfibrozil, and N-acetyl-cysteine. Health-care workers must apply strict standard and droplet precautions when dealing with suspected and confirmed case and upgrade to airborne precautions when performing aerosol-generating procedures. Nonpharmacologic measures, such as early case isolation, household quarantine, school/workplace closure, good community hygiene, and restrictions on travel are useful measures in controlling an influenza pandemic at its early phase.

Performance of a Rapid Influenza Test in Children During the H1N1 2009 Influenza A Outbreak

To evaluate the performance of a rapid influenza diagnostic test (RIDT) in detecting H1N1 2009 influenza A virus in respiratory samples from pediatric patients in comparison to that of real-time reverse-transcriptase polymerase chain reaction (rRT-PCR) and viral culture. Methodology. This was a cross-sectional diagnostic-accuracy study conducted at a tertiary care children's hospital. Patients for whom the RIDT (BinaxNOW [Binax, Inc, Portland, ME]), viral culture, and rRT-PCR results were known were included. Sensitivity, specificity, and likelihood ratios (LRs) were calculated. A total of 3030 specimens had RIDT results paired with both rRT-PCR and viral culture results. With rRT-PCR as the reference, overall test sensitivity was 45% (95% confidence interval [CI]: 43.3%-46.3%) and specificity was 98.6% (95% CI: 98.1%-99%). Positive and negative LRs were 32.9 (95% CI: 22.9-45.4) and 0.56 (95% CI: 0.54-0.58), respectively. RIDT sensitivity was significantly higher in young infants and children younger than 2 years than in older children. Using viral culture as the reference standard, RIDT sensitivity was 55.5% (95% CI: 51.9%-95.6%) and specificity was 95.6% (95% CI: 95%-96.1%). The positive and negative LRs were 12.6 and 0.47, respectively. The RIDT had relatively poor sensitivity but excellent specificity in this consecutive series of respiratory specimens obtained from pediatric patients. Although a positive RIDT result was highly accurate in predicting infection with influenza type A H1N1 2009 in children, a negative RIDT result did not preclude a child having H1N1. Therefore, for children at high risk with influenza-like illnesses during high-prevalence periods of influenza, empiric initiation of antiviral therapy should be considered for patients with a negative RIDT result.

Rapid clinical diagnosis in fatal swine influenza (H1N1) pneumonia in an adult with negative rapid influenza diagnostic tests (RIDTs): Diagnostic swine influenza triad

BackgroundThe “herald wave” of the H1N1 pandemic spread from Mexico to the United States in spring 2009. Initially, the epicenter of H1N1 in the United States was in the New York area. Our hospital, like others, was inundated with large numbers of patients who presented at the Emergency Department (ED) with influenza-like illnesses (ILIs) for swine influenza testing and evaluation.MethodsThe Winthrop-University Hospital ED used rapid influenza (QuickVue A/B) tests to screen for H1N1 infection. Patients who were rapid influenza A test-positive were also reverse transcription-polymerase chain reaction (RT-PCR) positive for H1N1. In our ED, 30% of patients with ILIs and possible H1N1 pneumonia had negative rapid influenza A screening tests. Because H1N1 RT-PCR testing was restricted, there was no laboratory test to confirm or rule out H1N1. Other rapid influenza diagnostic tests (RIDTs), e.g., the respiratory fluorescent antibody (FA) viral panel test, were used to identify H1N1 patients with negative RIDTs.ResultsUnfortunately, there was not a good correlation between RIDT results and RT-PCR results. There was a critical need to develop a clinical syndromic approach for diagnosing hospitalized adults with probable H1N1 pneumonia with negative RIDTs. Early in the pandemic, the Winthrop-University Hospital Infectious Disease Division developed a diagnostic weighted point score system to diagnose H1N1 pneumonia clinically in RIDT-negative adults. The point score system worked well, but was time-consuming. As the “herald wave” of the pandemic progressed, our ED staff needed a rapid, simplified method to diagnose probable H1N1 pneumonia in hospitalized adults with negative RIDTs. A rapid and simplified diagnosis was based on the diagnostic weighted point score system, which we simplified into a triad of key, nonspecific laboratory indicators. In adults hospitalized with an ILI, a fever >102°F with severe myalgias, and a chest x-ray without focal segmental/lobar infiltrates, the presence of three indicators, i.e., otherwise unexplained relative lymphopenia, elevated serum transaminases, and an elevated creatinine phosphokinase, constituted the diagnostic swine influenza triad. The Infectious Disease Division's diagnostic swine flu triad was used effectively as the pandemic progressed, and was not only useful in correctly diagnosing probable H1N1 pneumonia in hospitalized adults with negative RIDTs, but was also in ruling out mimics of swine influenza, e.g., exacerbations of chronic bronchitis, asthma, or congestive heart failure, as well as bacterial community-acquired pneumonias (CAPs), e.g., legionnaire's disease.ConclusionClinicians can use the Winthrop-University Hospital Infectious Disease Division's Diagnostic swine influenza triad to make a rapid clinical diagnosis of probable H1N1 pneumonia in hospitalized adult patients with negative RIDTs.

H1N1 Influenza: Contact Investigation Burden because of Failure to Institute Influenza Precautions in Patients with Negative Rapid Influenza Diagnostic Test Results

H1N1 Influenza: Contact Investigation Burden because of Failure to Institute Influenza Precautions in Patients with Negative Rapid Influenza Diagnostic Test Results

Diagnostic Testing for 2009 Pandemic Influenza A (H1N1) Virus Infection in Hospitalized Patients

Establishing a diagnosis of 2009 pandemic influenza A (H1N1) virus infection in hospitalized patients can be challenging, especially in patients presenting late in their clinical course. Although real-time reverse-transcriptase polymerase chain reaction (RT-PCR) is the most sensitive testing method to detect 2009 H1N1 virus in respiratory specimens,1 results are not accessible right away. Influenza antigen–detection tests produce quick results, but reported sensitivities of rapid influenza diagnostic tests (RIDTs) to detect 2009 H1N1 virus infection in upper respiratory specimens as compared with real-time RT-PCR range from 10 to 70%; therefore, false negative RIDT results are common2 and also occur with direct . . .

Winthrop-University Hospital Infectious Disease Division's swine influenza (H1N1) pneumonia diagnostic weighted point score system for hospitalized adults with influenza-like illnesses (ILIs) and negative rapid influenza diagnostic tests (RIDTs)

BackgroundIn spring 2009, a novel strain of influenza A originating in Veracruz, Mexico, quickly spread to the United States and throughout the world. This influenza A virus was the product of gene reassortment of 4 different genetic elements: human influenza, swine influenza, avian influenza, and Eurasian swine influenza. In the United States, New York was the epicenter of the swine influenza (H1N1) pandemic. Hospital emergency departments (EDs) were inundated with patients with influenza-like illnesses (ILIs) requesting screening for H1N1. Our ED screening, as well as many others, used a rapid screening test for influenza A (QuickVue A/B) because H1N1 was a variant of influenza A. The definitive laboratory test i.e., RT-PCR for H1N1 was developed by the Centers for Disease Control (Atlanta, GA) and subsequently distributed to health departments. Because of the extraordinary volume of test requests, health authorities restricted reverse transcription polymerase chain reaction (RT-PCR) testing. Hence most EDs, including our own, were dependent on rapid influenza diagnostic tests (RIDTs) for swine influenza. A positive rapid influenza A test was usually predictive of RT-PCR H1N1 positivity, but the rapid influenza A screening test (QuickVue A/B) was associated with 30% false negatives. The inability to rely on RIDTs for H1N1 diagnosis resulted in underdiagnosing H1N1. Confronted with adults admitted with ILIs, negative RIDTs, and restricted RT-PCR testing, there was a critical need to develop clinical criteria to diagnose probable swine influenza H1N1 pneumonia.MethodsDuring the pandemic, the Infectious Disease Division at Winthrop-University Hospital developed clinical criteria for adult admitted patients with ILIs and negative RIDTs. Similar to the one developed for the clinical diagnosis of legionnaire's disease. The Winthrop-University Hospital Infectious Disease Division's diagnostic weighted point score system for swine influenza H1N1 pneumonia is based on key clinical and laboratory features.ResultsDuring the “herald” wave of the swine influenza H1N1 pandemic, the diagnostic weighted point score system accurately identified probable swine influenza H1N1 pneumonia and accurately differentiated swine influenza H1N1 pneumonia from ILIs and other viral and bacterial community-acquired pneumonias.ConclusionIn hospitalized adults with ILIs and negative RIDTs, the diagnostic weighted diagnostic point score system, may be used to make a presumptive clinical diagnosis of swine influenza H1N1 pneumonia.