Jesse Papenburg

Emergence of oseltamivir-resistant pandemic H1N1 virus during prophylaxis.

To the Editor: Neuraminidase inhibitors (oseltamivir and zanamivir) are recommended for treatment of severe illness caused by the 2009 pandemic influenza A (H1N1) virus, and their use has also been advocated for postexposure prophylaxis in high-risk persons.1 We report the emergence of an oseltamivir-resistant virus in a familial cluster of infections with the 2009 H1N1 virus. In a 13-year-old boy with asthma, infection with the 2009 H1N1 virus developed and was confirmed by reverse-transcriptase polymerase-chain-reaction (RT-PCR) testing of a nasopharyngeal aspirate. Administration of oseltamivir (60 mg twice a day for 5 days for this boy who weighed 32 kg) was .xa0.xa0.

Risk factors for hospitalization and severe outcomes of 2009 pandemic H1N1 influenza in Quebec, Canada.

Please cite this paper as: Gilca et al. (2011) Risk Factors for Hospitalization and Severe Outcomes of 2009 Pandemic H1N1 Influenza in Quebec, Canada. Influenza and Other Respiratory Viruses 5(4), 247–255

Presence of Oseltamivir-Resistant Pandemic A/H1N1 Minor Variants Before Drug Therapy With Subsequent Selection and Transmission

A small proportion (1%-1.5%) of 2009 pandemic influenza A/H1N1 virus strains (A[H1N1]pdm09) are oseltamivir resistant, almost exclusively because of a H275Y mutation in the neuraminidase protein. However, many individuals infected with resistant strains had not received antivirals. Whether drug-resistant viruses are initially present as minor variants in untreated individuals before they emerge as the dominant strain in a virus population is of great importance for predicting the speed at which resistance will arise. To address this issue, we used ultra-deep sequencing of viral populations from serial nasopharyngeal specimens from an immunocompromised child and from 2 individuals in a household outbreak. We observed that the Y275 mutation was present as a minor variant in infected hosts before the onset of therapy. We also found evidence for the transmission of this drug-resistant variant with drug-susceptible viruses. These observations provide important information on the relative fitness of the Y275 mutation in the absence of oseltamivir treatment.

Human metapneumovirus viral load is an important risk factor for disease severity in young children

BACKGROUNDnThe role of viral load in human metapneumovirus (HMPV) disease severity has not yet been clearly determined.nnnOBJECTIVEnWe evaluated the importance of viral load along with other factors in HMPV disease severity among children aged <3 years old.nnnSTUDY DESIGNnHMPV-positive cases were selected from a cohort of outpatients and hospitalized children with lower respiratory tract infections. HMPV groups (A or B) and viral loads were determined in their nasopharyngeal aspirates. Disease severity was defined by assessing risk for hospitalization and by using two validated clinical severity scores.nnnRESULTSnOf the 118 HMPV cases detected over 4 years for which viral load could be determined, 60 belonged to genotype A and 58 to genotype B. Baseline characteristics were similar in HMPV-A and HMPV-B mono-infected patients. In multivariate analysis, HMPV hospitalization was associated with viral load ≥1000 copies/10(4)cells (OR, 3.2; 95%CI, 1.4-7.4), age <6 months (OR, 3.1; 95%CI, 1.2-8.6) and presence of ≥3 children in the household (OR, 2.7; 95%CI, 1.04-6.9). A high HMPV viral load was also associated with pulmonary rales (p=.03), use of bronchodilators (p=.02) and inhaled corticosteroids (p=.01).nnnCONCLUSIONnHMPV viral load is associated with disease severity in young children along with young age and household crowding.

Pediatric injuries from needles discarded in the community: epidemiology and risk of seroconversion.

OBJECTIVES. Although anxiety exists concerning the perceived risk of transmission of bloodborne viruses after community-acquired needlestick injuries, seroconversion seems to be rare. The objectives of this study were to describe the epidemiology of pediatric community-acquired needlestick injuries and to estimate the risk of seroconversion for HIV, hepatitis B virus, and hepatitis C virus in these events. METHODS. The study population included all of the children presenting with community-acquired needlestick injuries to the Montreal Childrens Hospital between 1988 and 2006 and to Hôpital Sainte-Justine between 1995 and 2006. Data were collected prospectively at Hôpital Sainte-Justine from 2001 to 2006. All of the other data were reviewed retrospectively by using a standardized case report form. RESULTS. A total of 274 patients were identified over a period of 19 years. Mean age was 7.9 ± 3.4 years. A total of 176 (64.2%) were boys. Most injuries occurred in streets (29.2%) or parks (24.1%), and 64.6% of children purposely picked up the needle. Only 36 patients (13.1%) noted blood on the device. Among the 230 patients not known to be immune for hepatitis B virus, 189 (82.2%) received hepatitis B immunoglobulin, and 213 (92.6%) received hepatitis B virus vaccine. Prophylactic antiretroviral therapy was offered beginning in 1997. Of the 210 patients who presented thereafter, 82 (39.0%) received chemoprophylaxis, of whom 69 (84.1%) completed a 4-week course of therapy. The use of a protease inhibitor was not associated with a significantly higher risk of adverse effects or early discontinuation of therapy. At 6 months, 189 were tested for HIV, 167 for hepatitis B virus, and 159 for hepatitis C virus. There were no seroconversions. CONCLUSIONS. We observed no seroconversions in 274 pediatric community-acquired needlestick injuries, thereby confirming that the risk of transmission of bloodborne viruses in these events is very low.

Molecular evolution of respiratory syncytial virus fusion gene, Canada, 2006-2010.

To assess molecular evolution of the respiratory syncytial virus (RSV) fusion gene, we analyzed RSV-positive specimens from 123 children in Canada who did or did not receive RSV immunoprophylaxis (palivizumab) during 2006–2010. Resistance-conferring mutations within the palivizumab binding site occurred in 8.7% of palivizumab recipients and none of the nonrecipients.

Global respiratory syncytial virus-associated mortality in young children (RSV GOLD): a retrospective case series

Summary Background Respiratory syncytial virus (RSV) infection is an important cause of pneumonia mortality in young children. However, clinical data for fatal RSV infection are scarce. We aimed to identify clinical and socioeconomic characteristics of children aged younger than 5 years with RSV-related mortality using individual patient data. Methods In this retrospective case series, we developed an online questionnaire to obtain individual patient data for clinical and socioeconomic characteristics of children aged younger than 5 years who died with community-acquired RSV infection between Jan 1, 1995, and Oct 31, 2015, through leading research groups for child pneumonia identified through a comprehensive literature search and existing research networks. For the literature search, we searched PubMed for articles published up to Feb 3, 2015, using the key terms “RSV”, “respiratory syncytial virus”, or “respiratory syncytial viral” combined with “mortality”, “fatality”, “death”, “died”, “deaths”, or “CFR” for articles published in English. We invited researchers and clinicians identified to participate between Nov 1, 2014, and Oct 31, 2015. We calculated descriptive statistics for all variables. Findings We studied 358 children with RSV-related in-hospital death from 23 countries across the world, with data contributed from 31 research groups. 117 (33%) children were from low-income or lower middle-income countries, 77 (22%) were from upper middle-income countries, and 164 (46%) were from high-income countries. 190 (53%) were male. Data for comorbidities were missing for some children in low-income and middle-income countries. Available data showed that comorbidities were present in at least 33 (28%) children from low-income or lower middle-income countries, 36 (47%) from upper middle-income countries, and 114 (70%) from high-income countries. Median age for RSV-related deaths was 5·0 months (IQR 2·3–11·0) in low-income or lower middle-income countries, 4·0 years (2·0–10·0) in upper middle-income countries, and 7·0 years (3·6–16·8) in high-income countries. Interpretation This study is the first large case series of children who died with community-acquired RSV infection. A substantial proportion of children with RSV-related death had comorbidities. Our results show that perinatal immunisation strategies for children aged younger than 6 months could have a substantial impact on RSV-related child mortality in low-income and middle-income countries. Funding Bill & Melinda Gates Foundation.

Comparison of pandemic and seasonal influenza in the pediatric emergency department.

Background: Emergency department (ED) presentation of pediatric pandemic H1N1 (pH1N1) infection is not well characterized. Our objective was to describe the clinical manifestations of pH1N1 in the pediatric ED. We also compared these characteristics to seasonal influenza A, and explored risk factors for pH1N1 hospitalization. Methods: We conducted a retrospective cohort study at a pediatric hospital in Quebec City, Canada. Subjects were ED patients aged 0 to 17 years with laboratory-confirmed pH1N1 (April–July 2009) or seasonal influenza A (June 2006–March 2009). Clinical and laboratory data were analyzed by univariate and multivariate log-binomial regression. Results: A total of 127 pH1N1 cases and 110 seasonal influenza cases were identified. pH1N1 patients were older (9.5 vs. 5.6 years; P < 0.0001) and presented more rapidly (2.8 vs. 3.5 days; P = 0.02). Clinical manifestations were similar, although gastrointestinal findings were less frequent in pH1N1 (relative risk [RR]: 0.49; 95% confidence interval [CI]: 0.37–0.65). Hospitalization risk was similar (RR: 1.12; 95% CI: 0.81–1.55), but hospitalized pH1N1 subjects were more frequently diagnosed with pneumonia (RR: 2.41; 95% CI: 1.16–5.00). In a multivariable model, age <2 years was independently associated with pH1N1 hospitalization (RR: 3.17; 95% CI: 1.78–5.65), whereas the absence of significant comorbidities decreased its risk (RR: 0.51; 95% CI: 0.31–0.85). Conclusions: After adjustment for age and delay to presentation, clinical manifestations and 21-day outcomes of pediatric pH1N1 were similar to those of seasonal influenza. pH1N1 patients with previously established risk factors for severe seasonal influenza experienced increased hospitalization risk. Our results suggest that pH1N1 clinical diagnosis and management in the pediatric ED can be performed in a manner similar to seasonal influenza.

Multiplex Respiratory Virus Testing for Antimicrobial Stewardship: A Prospective Assessment of Antimicrobial Use and Clinical Outcomes Among Hospitalized Adults

Positivity for influenza virus leads to appropriate antiviral management and shorter duration of hospitalization, but positivity for other viruses does not lead to changes in antimicrobial management. Multiplex respiratory virus testing might not, by itself, be a useful tool for antimicrobial stewardship.

Seroconversion to Seasonal Influenza Viruses after A(H1N1)pdm09 Virus Infection, Quebec, Canada

We looked for cross-reactive antibodies in 122 persons with paired serum samples collected during the 2009 pandemic of influenza virus A(H1N1)pdm09. Eight (12%) of 67 persons with A(H1N1)pdm09 infection confirmed by reverse transcription PCR and/or serology also seroconverted to the seasonal A/Brisbane/59/2007 (H1N1) virus, compared with 1 (2%) of 55 A(H1N1)pdm09-negative persons (p<0.05).