A prediction rule to identify severe cases among adult patients hospitalized with pandemic influenza A (H1N1) 2009

The purpose of this study was to establish a prediction rule for severe illness in adult patients hospitalized with pandemic influenza A (H1N1) 2009. At the time of initial presentation, the baseline characteristics of those with severe illness (i.e., admission to intensive care unit, mechanical ventilation, or death) were compared to those of patients with non-severe illnesses. A total of 709 adults hospitalized with pandemic influenza A (H1N1) 2009 were included: 75 severe and 634 non-severe cases. The multivariate analysis demonstrated that altered mental status, hypoxia (PaO(2)/FiO(2) ≤ 250), bilateral lung infiltration, and old age (≥ 65 yr) were independent risk factors for severe cases (all P < 0.001). The area under the ROC curve (0.834 [95% CI, 0.778-0.890]) of the number of risk factors were not significantly different with that of APACHE II score (0.840 [95% CI, 0.790-0.891]) (P = 0.496). The presence of ≥ 2 risk factors had a higher sensitivity, specificity, positive predictive value and negative predictive value than an APACHE II score of ≥ 13. As a prediction rule, the presence of ≥ 2 these risk factors is a powerful and easy-to-use predictor of the severity in adult patients hospitalized with pandemic influenza A (H1N1) 2009.     

Influenza A(H1N1)2009 in the French Pacific territories: assessment of the epidemic wave during the austral winter

The three French territories in the Pacific (New Caledonia [NC], French Polynesia [FP] and Wallis and Futuna [WF]) have been affected by an outbreak of influenza A(H1N1)2009 during the austral winter of 2009. This wave of influenza-like illness was characterized by a short duration (approximately 8 weeks) and high attack rates: 16–18% in NC and FP, 28% in Wallis and 38% in Futuna. The number of infected patients requiring hospitalization in critical care services and the number of deaths were, respectively, 21 and 10 in NC and 13 and 7 in FP (none in WF). Diabetes, cardiac and pulmonary diseases, obesity in adults, neuromuscular diseases in children, and Oceanic origin were frequently observed among severe cases and deaths. A significant proportion of the population remains susceptible to A(H1N1)2009, making the occurrence of a second wave likely. A state of preparedness and control efforts must be implemented, based on preventive measures (immunization), as well as combined clinical and virological surveillance and health organization.     

Differential diagnosis of pandemic (H1N1) 2009 infection by detection of haemagglutinin with an enzyme-linked immunoassay

A sensitive and convenient immunoassay that can directly differentiate pandemic (H1N1) 2009 (pH1N1) virus from seasonal influenza virus can play an important role in the clinic. In the presented study, a double-sandwich ELISA (pH1N1 ELISA), based on two monoclonal antibodies against haemagglutinin (HA) of the pH1N1 virus, was developed. After laboratory determination of the sensitivity and specificity characteristics, the performance of this assay was evaluated in a cohort of 904 patients with influenza-like illness. All seven strains of pH1N1 virus tested were positive by pH1N1 ELISA, with an average lower detection limit of 10^{3.0 ± 0.4} tissue culture infective dose (TCID)₅₀/mL (or 0.009 ± 0.005 HA titre). Cross-reaction of the assay with seasonal influenza virus and other common respiratory pathogens was rare. In pH1N1-infected patients, the sensitivity of the pH1N1 ELISA was 92.3% (84/91, 95% CI 84.8–96.9%), which is significantly higher than that of the BD Directigen EZ Flu A + B test (70.3%, p <0.01). The specificity of pH1N1 ELISA in seasonal influenza A patients was 100.0% (171/171, 95% CI 97.9–100.0%), similar to that in non-influenza A patients (640/642, 99.7%, 95% CI 98.9–100.0%). The positive predictive value for pH1N1 ELISA was 97.7% and the negative predictive value was 99.1% in this study population with a pH1N1 prevalence of 10.1%. In conclusion, detection of HA of pH1N1 virus by immunoassay appears to be a convenient and reliable method for the differential diagnosis of pH1N1 from other respiratory pathogens, including seasonal influenza virus.     

Pathologic study of pandemic influenza A (H1N1) 2009 cases from India

The pandemic influenza A (H1N1) 2009 originated in Mexico and rapidly spread to the United States and many other countries. India reported the first pandemic influenza case in May 2009. Autopsy studies describing the pathology of pandemic influenza infection in humans have appeared in the literature and most of these were from Western countries. We present the clinicopathologic features in 46 fatal cases with confirmed pandemic influenza A (H1N1) 2009 virus infection during August 2009 to October 2010. Postmortem needle biopsy tissues were examined for histopathological changes and distribution of virus antigen by immunohistochemistry. The results are comparable with previous autopsy studies. Diffuse alveolar damage was the consistent finding in the lung tissues. However, underlying medical conditions were not noted in the cases from present study. Consistent presence of viral antigen was noted in the bronchiolar epithelium without any reference to the duration of illness. This study also emphasizes the use of the postmortem needle biopsy technique whenever an autopsy is not possible.     

Prolonged viral shedding in pandemic influenza A(H1N1): clinical significance and viral load analysis in hospitalized patients

The clinical significance of prolonged viral shedding (PVS) and viral load (VL) dynamics has not been sufficiently assessed in hospitalized patients with pandemic 2009 influenza A(H1N1). We performed a prospective study of adults with confirmed influenza A(H1N1) virus infection admitted to our hospital from 20 September 2009 to 31 December 2009. Consecutive nasopharyngeal swabs were collected every 2 days during the first week after diagnosis, and then every week or until viral detection was negative. Relative VL was measured on the basis of haemagglutinin and RNaseP gene analysis. PVS was defined as positive detection of influenza A(H1N1) virus by real-time RT-PCR at day 7 after diagnosis. We studied 64 patients: 16 (25%) presented PVS. The factors associated with PVS were admission to the intensive-care unit (69% vs. 33%, p 0.02), purulent expectoration (75% vs. 44%, p 0.04), higher dosage of oseltamivir (62.5% vs. 27%, p 0.016), corticosteroid treatment (50% vs. 21%, p 0.05), mechanical ventilation (MV) (50% vs. 12.5%, p 0.004), and longer stay (34 vs. 7 median days, p 0.003). Multivariate analysis revealed the factors independently associated with PVS to be immunosuppression (OR 5.15; 95% CI 1.2–22.2; p 0.03) and the need for MV (OR 11.7; 95% CI 2.5–54.4; p 0.002). VL at diagnosis correlated negatively with age and septic shock. VL dynamics of patients with acute respiratory distress syndrome and/or mortality were very different from those of other patients. PVS was detected in 25% of hospitalized patients with pandemic 2009 influenza A(H1N1) and was strongly associated with immunosuppression and the need for MV. Diagnostic VL and viral clearance varied with the clinical course.     

Rhinoviruses delayed the circulation of the pandemic influenza A (H1N1) 2009 virus in France

In contrast to the experience in other European countries, the onset of the A(H1N1)2009 influenza virus epidemic was unexpectedly slow in France during the first part of autumn 2009. Our objective was to test the hypothesis that intense circulation of rhinoviruses might have reduced the probability of infection by A(H1N1)2009 virus at the beginning of autumn 2009. Systematic analysis for the detection of A(H1N1)2009 (H1N1) and human rhinovirus (HRV) was performed by RT-PCR from week 36 to week 48 on respiratory samples sent to the diagnostic laboratory by the paediatric hospital (n = 2121). Retrospective analysis of the obtained data, using 2 × 2 contingency tables with Fisher's exact test, revealed evidence of an inverse relationship between HRV and H1N1 detection. Between weeks 36 and 48 of 2009, both HRV and H1N1 were detected but in different time frames. HRV dispersed widely during early September, peaking at the end of the month, whereas the H1N1 epidemic began during mid-October and was still active at the end of this survey. During the co-circulation period of these two respiratory viruses (weeks 43–46), HRV detection appeared to reduce the likelihood of H1N1 detection in the same sample (OR = 0.08–0.24 p <0.0001). These results support the hypothesis that HRV infections can reduce the probability of A(H1N1) infection. This viral interference between respiratory viruses could have affected the spread of the H1N1 viruses and delayed the influenza pandemic at the beginning of autumn in France.     

Sero‐immunity and serologic response to pandemic influenza A (H1N1) 2009 virus in Hong Kong

To study the serologic response to the new pandemic influenza A (H1N1) 2009 virus in Hong Kong, the level of immunity was measured before and after the occurrence of the outbreak, and the titer of antibody to the pandemic influenza A (H1N1) 2009 virus in serum samples of laboratory confirmed cases. The presence of pre‐outbreak pandemic influenza A (H1N1) 2009 virus antibodies in 37% of individuals older than >65 years suggested previous exposures to heterologous virus strains may have elicited cross‐reacting antibody. Following large outbreaks of pandemic influenza A 2009 virus that peaked in September 2009, there is a change in immunity level in various age groups consistent with the attack rates among population in Hong Kong. Among individuals with mild clinical presentation, the antibody response to pandemic influenza A (H1N1) 2009 virus was stronger in those individuals aged ≤24 years but took more time to reach a titer of 40 when compared with those aged >24 years; however, the antibody level declined slower among individuals aged ≤24 years. Regardless of age, the antibody response rose rapidly and reached much higher titer among individuals with severe clinical presentation. Further study is required to collect additional data on antibody persistence and determine how much protection is conferred by previous exposure to seasonal influenza A (H1N1) viruses. J. Med. Virol. 82:1809–1815, 2010. © 2010 Wiley‐Liss, Inc.     

2009 H1N1 influenza and experience in three critical care units

Aim: We describe futures of ICU admission, demographic characteristics, treatment and outcome for critically ill patients with laboratory-confirmed and suspected infection with the H1N1 virus admitted to the three different critical care departments in Turkey.Methods: Retrospective study of critically ill patients with 2009 influenza A(H1N1) at ICU. Demographic data, symptoms, comorbid conditions, and clinical outcomes were collected using a case report form.Results: Critical illness occurred in 61 patients admitted to an ICU with confirmed (n=45) or probable and suspected 2009 influenza A(H1N1). Patients were young (mean, 41.5 years), were female (54%). Fifty-six patients, required mechanical ventilation (14 invasive, 27 noninvasive, 15 both) during the course of ICU. On admission, mean APACHE II score was 18.7±6.3 and median PaO₂/FIO₂ was 127.9±70.4. 31 patients (50.8%) was die. There were no significant differences in baseline PaO₂/FIO₂ and ventilation strategies between survivors and nonsurvivors. Patients who survived were more likely to have NIMV use at the time of admission to the ICU.Conclusion: Critical illness from 2009 influenza A(H1N1) in ICU predominantly affects young patients with little major comorbidity and had a high case-fatality rate. NIMV could be used in 2009 influenza A (H1N1) infection-related hypoxemic respiratory failure.     

2009甲型H1N1流感大流行期间北京儿童的流感监测

目的 了解2009年甲型H1N1流感大流行期间北京地区儿童中流感流行的情况.方法 采用WHO推荐的实时荧光定量RT-PCR和国家流感中心推荐的分型方法,对2009年甲型H1N1流感大流行期间因流感样症状来首都儿科研究所附属儿童医院就诊患儿的咽拭子标本进行流感病毒核酸检测.结果 2009年6月1日至2010年2月28日期间共检测了4363份咽拭子标本,其中623例为甲型H1N1阳性,阳性率为14.3%,657例为其他甲型流感病毒阳性(15.1%),所有甲型流感病毒的总阳性率为29.3%.623例中有23例为危重症病例(占阳性患者的3.7%),其中5例死亡.618例信息完整的甲型H1N1病例中,患儿年龄为14天～16岁,性别比例为男比女为1.3:1.1～3岁儿童占25.2%,3～6岁学龄前儿童和6～12岁学龄儿童所占比例相近,各约占30%.在监测期间,仅呈现了一个甲型H1N1的流行波.2009年11月达到最高峰,随后减弱,2010年2月快速下降至2.7%.对监测期间每周20～30份临床标本同时进行季节性流感的监测显示,季节性H3N2、甲型H1N1和乙型流感交替流行.呼吸道合胞病毒(RSV)在甲型H1N1流行趋势减缓后逐渐流行成为流行优势株.结论 2009年6月至2010年2月北京地区儿童中出现甲型H1N1的流行,主要累及学龄前和学龄儿童.季节性流感和RSV与甲型H1N1交替流行.     

Characteristics of hospitalized children with 2009 pandemic influenza A (H1N1): a multicenter study in Korea

The majority of Korean patients with pandemic influenza A (H1N1) during the 2009 epidemic were under 20 yr of age. The limited data on the clinical characteristics of these children led us to conduct a case note-based investigation of children admitted to 6 university hospitals with 2009 H1N1 influenza. A total of 804 children was enrolled. The median age was 5 yr; 63.8% were males; and 22.4% had at least one chronic underlying disease. Ninety-five of the patients (11.8%) were critically ill and they suffered more from shortness of breath, dyspnea and lymphopenia than the other patients. Among all the patients, 98.8% were treated with antivirals and 73% received treatment within 48 hr of illness onset. All the enrolled patients are alive and appear to have had good outcomes, probably due to the early intervention and antiviral treatment. This study deals with hospitalized children whose diagnoses of influenza A (H1N1) were confirmed, and therefore provides important new information about the clinical patterns of children with influenza A (H1N1) in Korea.     

Changes in epidemiology,clinical features and severity of influenza A (H1N1) 2009 pneumonia in the first post-pandemic influenza season

Although the influenza A (H1N1) 2009 virus is expected to circulate as a seasonal virus for some years after the pandemic period, its behaviour cannot be predicted. We analysed a prospective cohort study of hospitalized adults with influenza A (H1N1) 2009 pneumonia at 14 teaching hospitals in Spain to compare the epidemiology, clinical features and outcomes of influenza A (H1N1) 2009 pneumonia between the pandemic period and the first post-pandemic influenza season. A total of 348 patients were included: 234 during the pandemic period and 114 during the first post-pandemic influenza season. Patients during the post-pandemic period were older and more likely to have chronic obstructive pulmonary disease, chronic kidney disease and cancer than the others. Septic shock, altered mental status and respiratory failure on arrival at hospital were significantly more common during the post-pandemic period. Time from illness onset to receipt of antiviral therapy was also longer during this period. Early antiviral therapy was less frequently administered to patients during the post-pandemic period (22.9% versus 10.9%; p 0.009). In addition, length of stay was longer, and need for mechanical ventilation and intensive-care unit admission were significantly higher during the post-pandemic period. In-hospital mortality (5.1% versus 21.2%; p <0.001) was also greater during this period. In conclusion, significant epidemiological changes and an increased severity of influenza A (H1N1) 2009 pneumonia were found in the first post-pandemic influenza season. Physicians should consider influenza A (H1N1) 2009 when selecting microbiological testing and treatment in patients with pneumonia in the upcoming influenza season.     

Interim report on the A/H1N1 influenza virus pandemic in Marseille,France, April-November 2009

We report here the results of a 7-month survey of the influenza A/H1N1 pandemic in the Virology laboratory of the public hospitals of Marseille (April–November 2009). In total, 8 587 samples were analysed during this period, of which 1 974 (23%) were positive for the novel influenza variant. The analysis of results obtained using rapid influenza diagnostic tests (RIDTs) revealed a global sensitivity of 49.4% (vs. molecular qRT-PCR detection), strongly correlated with age groups (varying from 30% to 58% for patients >40 age and <10, respectively), indicating that RIDTs can be helpful in accelerating the management of suspected cases. Epidemiological analysis showed that the winter influenza wave began in October in Marseille (i.e. 2 to 3 months earlier than usual seasonal influenza outbreaks) and that the majority of autochthonous cases were observed in patients younger than 20 years old, with a low number of cases in patients over 60 years old. In November 2009, 22.2% (167/754) of patients with a laboratory diagnosis of influenza A/H1N1 infection were hospitalized, of which 9% (15/167) were admitted to an intensive care unit (ICU). Patients in the extreme age groups (>40 years old and <1) were significantly more often hospitalized than others, and 2.4% of hospitalized patients died. During the last 3 weeks of the period, the average number of bed-days attributable to H1N1sw-positive patients was 31.4, of which 5.9 were in ICUs.     

Predictors of mortality and length of stay in hospitalized cases of 2009 influenza A (H1N1): Experiences of a tertiary care center

Aim:

To study the clinical characteristics and outcome of admitted patients of H1N1 (hemagglutinin -H neuraminidase -N) influenza in a tertiary level hospital, from Oct 2009 to Dec 2010.

Materials and Methods:

A retrospective analysis of 77 confirmed patients admitted in this unit with H1N1 infection.

Results:

Of the 77 patients studied, 33 (42.8%) were female. Mean age was 40.88 ± 13.45 years, majority (70.13%) being less than 50 years. Thirty eight (49.3%) patients had at least one co-morbidity, diabetes mellitus being the most common (n = 15, 19.5%). The most common presenting symptom was fever in 75 (97.4%) patients, cough in 67 (87%) and dyspnoea in 59 (76.6%) patients. At admission, mean PaO2/FiO2 ratio was 213.16 ± 132.75 mmHg (n = 60) while mean PaCO₂ was 40.14 ± 14.86 mmHg. One or more organ failure was present in 45 (58.4%) patients. Nineteen (24.60%) patients required invasive mechanical ventilation. Circulatory failure was observed in 10 (13%) patients while 2 patients required hemodialysis. Overall, 13% mortality (n = 10) was observed. PaCO₂ level at admission (OR 1.093; 95% confidence interval: 1.002-1.193; P = 0.044) and number of organ failure (OR 8.089; 95% confidence interval: 1.133-57.778; P = 0.037) were identified as independent risk- factors for mortality.

Conclusion:

Increased duration of dyspnoea prior to admission, pneumonia, low PaO₂/FiO₂ ratio at admission and 24 hours later, higher PaCO₂ values on admission, higher O₂ requirement, number of organ failures and use of corticosteroids and delay in specialized treatment were associated with a poorer outcome.     

Classical swine H1N1 influenza viruses confer cross protection from swine-origin 2009 pandemic H1N1 influenza virus infection in mice and ferrets

The hemagglutinin of the 2009 pandemic H1N1 influenza virus is a derivative of and is antigenically related to classical swine but not to seasonal human H1N1 viruses. We compared the A/California/7/2009 (CA/7/09) virus recommended by the WHO as the reference virus for vaccine development, with two classical swine influenza viruses A/swine/Iowa/31 (sw/IA/31) and A/New Jersey/8/1976 (NJ/76) to establish the extent of immunologic cross-reactivity and cross-protection in animal models. Primary infection with 2009 pandemic or NJ/76 viruses elicited antibodies against the CA/7/09 virus and provided complete protection from challenge with this virus in ferrets; the response in mice was variable and conferred partial protection. Although ferrets infected with sw/IA/31 virus developed low titers of cross-neutralizing antibody, they were protected from pulmonary replication of the CA/7/09 virus. The data suggest that prior exposure to antigenically related H1N1 viruses of swine-origin provide some protective immunity against the 2009 pandemic H1N1 virus.