pH1N1 Infection Research Articles

Serologic Survey of the Pandemic H1N1 2009 Virus in Guangdong Province, China: A Cross Sectional Study

BackgroundRelying on surveillance of clinical cases limits the ability to understand the full impact and severity of an epidemic, which urges a deep insight into the serological evidence of infection and transmission feature of pandemic H1N1 2009 (pH1N1) virus in Guangdong province.MethodsIn this cross-sectional serological survey, serum samples were collected by multi-stage stratified random sampling in Jan 2010. Antibody titers were measured by hemagglutination inhibition (HI) assay. Age-specific and region-specific prevalence were calculated based on the results of HI assay (positive, HI titer≥1∶40).ResultsA total of 4,319 serum samples had been collected from subjects without vaccination with pH1N1 vaccine. The seroprevalence was 22.82% (985/4,319). By contrast, there was a marked spatial heterogeneity in prevalence. The seroprevalence was 27.3% in large city, 21.4% in medium cities, higher than that of 20.2% in rural areas. The seroprevalence was highest in 11–20 age group (32.8%), however, in those above 60 years of age group, which was 12.6%, lower than other age groups. On the other hand, antibody titers to pH1N1 virus were highest in school children, which were followed by a gradual decrease in adult. However, in the elderly groups from cities, especially from large city, the antibody titer to pH1N1 increased significantly and reached a much higher level.ConclusionOur results showed that the prevalence for pH1N1 was correlated with age and population density. Preexisting antibody may have protected the very old from pH1N1 infection, while original antigenic sin and immunosenescence may have contributed to greater severity once infected. These should be considered when studying the pathogenesis and transmission of influenza virus and formulating strategies on vaccination and treatment.

Early Use of Glucocorticoids Was a Risk Factor for Critical Disease and Death From pH1N1 Infection

Glucocorticoids increase the risk of developing critical disease from viral infections. However, primary care practitioners in China use them as antipyretics, potentially exposing hundreds of millions to this risk. We enrolled all patients with confirmed pandemic influenza A (pH1N1) virus infection aged ≥3 years with available medical records at 4 Shenyang City hospitals from 20 October to 30 November 2009. A critical patient was any confirmed, hospitalized pH1N1 patient who developed ≥1 of the following: death, respiratory failure, septic shock, failure or insufficiency of ≥2 nonpulmonary organs, mechanical ventilation, or ICU admission. In a retrospective cohort study, we evaluated the risk of developing critical illness in relation to early (≤72 hours of influenza-like illness [ILI] onset) glucocorticoids treatment. Of the 83 hospitalized case-patients, 46% developed critical illness, 17% died, and 37% recovered and were discharged. Critically ill and other patients did not differ by underlying conditions and severity, median temperature at first clinic visit, and other measured risk factors. Of 17 patients who received early glucocorticoid treatment, 71% subsequently developed critical disease compared with 39% of 66 patients who received late (>72 hours) or no glucocorticoid treatment (RR(M-H) = 1.8, 95% CI = 1.2-2.8, after adjusting for 2 summary variables; ie, presence of underlying diseases and presence of underlying risk factors). Proportional hazards modeling showed that use of glucocorticoids tripled the hazard of developing critical disease (hazard ratio [HR] = 2.9, 95% CI = 1.3-6.2, after adjusting for the same summary variables). Early use of parenteral glucocorticoids therapy for fever reduction and pneumonia prevention increases the risk for critical disease or death from pH1N1 infection. We recommend that guidelines on glucocorticoid use be established and enforced.

Comparison of Pandemic and Seasonal Influenza in the Pediatric Emergency Department

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. 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. 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). 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.

Cost-effectiveness of 2009 pandemic influenza A(H1N1) vaccination in the United States.

BackgroundPandemic influenza A(H1N1) (pH1N1) was first identified in North America in April 2009. Vaccination against pH1N1 commenced in the U.S. in October 2009 and continued through January 2010. The objective of this study was to evaluate the cost-effectiveness of pH1N1 vaccination.MethodologyA computer simulation model was developed to predict costs and health outcomes for a pH1N1 vaccination program using inactivated vaccine compared to no vaccination. Probabilities, costs and quality-of-life weights were derived from emerging primary data on pH1N1 infections in the US, published and unpublished data for seasonal and pH1N1 illnesses, supplemented by expert opinion. The modeled target population included hypothetical cohorts of persons aged 6 months and older stratified by age and risk. The analysis used a one-year time horizon for most endpoints but also includes longer-term costs and consequences of long-term sequelae deaths. A societal perspective was used. Indirect effects (i.e., herd effects) were not included in the primary analysis. The main endpoint was the incremental cost-effectiveness ratio in dollars per quality-adjusted life year (QALY) gained. Sensitivity analyses were conducted.ResultsFor vaccination initiated prior to the outbreak, pH1N1 vaccination was cost-saving for persons 6 months to 64 years under many assumptions. For those without high risk conditions, incremental cost-effectiveness ratios ranged from $8,000–$52,000/QALY depending on age and risk status. Results were sensitive to the number of vaccine doses needed, costs of vaccination, illness rates, and timing of vaccine delivery.ConclusionsVaccination for pH1N1 for children and working-age adults is cost-effective compared to other preventive health interventions under a wide range of scenarios. The economic evidence was consistent with target recommendations that were in place for pH1N1 vaccination. We also found that the delays in vaccine availability had a substantial impact on the cost-effectiveness of vaccination.

Delayed oseltamivir treatment is associated with longer viral shedding of pandemic (H1N1) 2009 virus

During the early phase of the influenza pandemic in 2009, all cases of laboratory-confirmed pandemic (H1N1) 2009 (pH1N1) infection required compulsory isolation in hospital. These cases were offered oseltamivir treatment and only allowed to be discharged from the hospital when three consecutive respiratory specimens were negative for the virus by reverse transcription-polymerase chain reaction (RT-PCR). We reviewed the case records of these patients to assess the viral shedding kinetics of the pH1N1 virus. We defined viral shedding duration as the interval from illness onset date to the date of collection of the last positive specimen from the patients. Fifty-six patients were included in the study, of whom 96% received oseltamivir. The median viral shedding duration of pH1N1 virus by viral culture and RT-PCR were 3 days and 4 days, respectively. Patients who started oseltamivir treatment >48 h after onset had a significantly longer median viral shedding duration by viral culture than those who started treatment within 48 h of onset (4 days vs. 2 days, P=0·014).

Comparison of Hospitalized Solid Organ Transplant Recipients and Nonimmunocompromised Patients With Pandemic H1N1 Infection: A Retrospective Cohort Study

Pandemic H1N1 influenza has been associated with a worldwide outbreak of febrile respiratory illness. Although impaired cell mediated immunity, such as that caused by transplant immunosuppression, has been identified as a risk factor for severe infection with this virus, the course of this infection has not been adequately characterized in solid organ transplant (SOT) recipients in comparison with nontransplanted controls. We report our experience with severe pH1N1 infection in transplant recipients and compare this group with nonimmunosuppressed patients. Data were retrospectively collected on all patients admitted to our institution with proven pH1N1 infection. Clinical characteristics, treatments, and outcomes were compared between SOT recipients and nonimmunocompromised controls. Seventeen SOT recipients and 49 controls were identified. The control group had higher baseline rates of asthma (P = 0.02) and smoking (P = 0.05) at baseline. No difference in clinical features of H1N1 infection was detected except for a greater prevalence of wheeze in the non-SOT group (P = 0.02). No statistical differences in outcomes could be detected between the groups. Several markers of severity, including use of high frequency oscillatory ventilation, extracorporeal membrane oxygenation, and death were slightly more frequent in the control group. SOT recipients admitted to hospital with pH1N1 infection did not have significantly more severe outcomes of their infection compared with their nonimmunocompromised counterparts, despite their immune suppressed status.

Factors associated with infection by 2009 pandemic H1N1 influenza virus during different phases of the epidemic

The focus of this study was to ascertain the factors associated with 2009 pandemic influenza H1N1 (pH1N1) infection during different phases of the epidemic. In central Taiwan, 306 persons from households with schoolchildren were followed sequentially and serum samples were taken at three sampling time-points starting in the fall of 2008, shortly after influenza vaccination. Participants who seroconverted between two consecutive blood samplings were considered as having serological evidence of infection. A generalized estimation equation (GEE) with a logistic link to account for household correlations was applied to identify factors associated with pH1N1 infections during the pre-epidemic (April-June) and epidemic (September-October) periods. The results showed that receiving an inactivated seasonal influenza vaccine (ISIV) and having a hemagglutination inhibition assay (HI) titer of 40 or higher resulted in a significantly lower likelihood of pH1N1 infection during the pre-epidemic period only, for both children and adults (adjusted odds ratio (OR) 0.3, 95% confidence interval (CI) 0.12-0.9). Having a previous infection by pH1N1 with a baseline titer of 20 or higher resulted in a significantly lower likelihood of infection by pH1N1 during the epidemic period (adjusted OR 0.06, 95% CI 0.02-0.16). Our results provide the first serological evidence to suggest a protection effect from receiving an ISIV against pH1N1 infection only when the HI titer reaches 40 or higher during the pre-epidemic period. This study gives an important insight into the control and intervention measures required for preventing infections during future influenza epidemics.

Age- Matched Comparison of Children Hospitalized for 2009 Pandemic H1N1 Influenza with Those Hospitalized for Seasonal H1N1 and H3N2

BackgroundA wide spectrum of clinical manifestation ranging from deaths to a mild course of disease has been reported in children infected with the 2009 pandemic H1N1 (pH1N1) influenza.Methodology/Major FindingsWe conducted an age-matched control study comparing children hospitalized for pH1N1 with historic controls infected with seasonal H1N1 and H3N2 influenza to correct for the effect of age on disease susceptibility and clinical manifestations. We also compared children with pH1N1 to children concurrently admitted for seasonal influenza during the pandemic period to adjust for differences in health-seeking behavior during the pandemic or other potential bias associated with historic controls. There was no death or intensive care admission. Children with pH1N1 were more likely to have at least one risk condition for influenza, an underlying chronic pulmonary condition, more likely to have asthma exacerbation and to be treated with oseltamivir. There was no difference in other aspects of the clinical course or outcome.ConclusionDisease manifestation of children hospitalized for pH1N1 infection was mild in our patient population.

Investigation of an Outbreak of 2009 Pandemic Influenza A Virus (H1N1) Infections among Healthcare Personnel in a Chicago Hospital

In May 2009, we investigated a hospital outbreak of pandemic H1N1 (pH1N1) infection among healthcare personnel (HCP). Thirteen (65%) of 20 HCP with pH1N1 infection had healthcare-associated cases, which were primarily attributed to transmission among HCP. Eleven (55%) of HCP with pH1N1 infection worked for 1 day or more after the onset of illness. Personnel working with mild illness may have contributed to transmission among HCP.

Study of respiratory influenza A H1N1 Virus (pH1N1) in hospitalized children in the pandemic year. Experience in 34 centers in Argentina

In Argentina, pandemic influenza pH1N1 caused nearly 10,000 confirmed cases with high impact in pediatrics. To describe clinical and epidemiological characteristics and analyse the risk factor of lethality in children hospitalized with infection pH1N1 confirmed by PCR. We identifed all suspected cases (according to Ministry of health) in 34 centers and we included all the confirmed cases of 0-18 years from 1/4/09 to 31/8/09 in a retrospective cohort study. The viral diagnosis was confirmed by RT-PCR method. Data are expressed in percentages, average, median, standard deviation, and range (IQR) as appropriate; and as a measure of association, relative risk (RR), with 95% confidence interval (95%CI). Multiple logistic regression was conducted to determine the independent risk predictors. Total number of suspected cases were: 2367; PCR was performed to 47.8% (n: 1131) being positive for pH1N1 65.5% (n: 741/1131); 57.2% males; 61.5% <24 months, median age: 14 months (IQR 6-46 months); 45.1% with underlying disease; more frequent clinical pictures were: pneumonia (39,7%) and bronchiolitis 25.8%; Case-fatality rate: 5.9% (44/741). Mortality risk factors were [RR (95%CI)]: neurological disease [5.00 (2.84-8.81)], genetic disease [3.67 (1.58-8.52)], malnutrition [3,07 (1.46-6.48)] and prematurity [2.28 (1.14-4.56)]. Independent mortality predictor: neurological disease [3.84 (1.81-8.14)]. No significant association between age, chronic respiratory disease, immunosuppression and viral co-infection with lethality was observed. Almost half of children with pH1N1 infection had underlying disease; the neurological condition was a separate CFR predictor.

Radiological prognostic factors in patients with pandemic H1N1 (pH1N1) infection requiring hospital admission

The aim of this study was to determine the radiologic findings associated with admission to the intensive care unit (ICU) and the development of acute respiratory distress syndrome (ARDS) in patients with pH1N1 infection. One hundred and four patients (15–96 years) with laboratory-confirmed pH1N1 infection seen at the Emergency Department from July to December 2009 who underwent chest radiographs were studied. Radiographs were evaluated for consolidation, ground-glass opacities, interstitial patterns, distribution, and extent of findings. Eighty-seven (83.7%) of the patients were managed in the ward, and 17 (16.3%) patients eventually required admission to the ICU. All patients admitted to the ICU showed abnormalities on the initial radiograph. The presence of consolidation, multifocal, diffuse, and bilateral involvement on the initial radiograph was associated with a statistically higher risk of requiring ICU admission (p < 0.001). There were no significant differences regarding age, sex, and presence of underlying comorbidities. Evolution to ARDS was found in eight cases that necessitated ICU care. All of them had on the initial radiograph patchy multifocal consolidations (p < 0.001) with bilateral lesions in six cases. A higher number of lung zones involved and consolidation on the initial chest radiograph as well as a rapid progression of the radiological abnormalities were identified in patients requiring ICU admission and development of ARDS. Initial chest radiographs show acute abnormalities in all patients with severe disease. The findings of a multifocal patchy consolidation pattern with bilateral or diffuse lung involvement on admission should alert of the impending severity of disease and the risk of necessitating ICU admission

Complications and Outcomes of Pandemic 2009 Influenza A (H1N1) Virus Infection in Hospitalized Adults: How Do They Differ From Those in Seasonal Influenza?

It is unclear whether pandemic 2009 influenza A (pH1N1) infection caused more significant disease among hospitalized adults than seasonal influenza. A prospective, observational study was conducted in adults hospitalized with polymerase chain reaction-confirmed pH1N1 infection in 2 acute-care general hospitals from June 2009 to May 2010 (n = 382). Complications and outcomes were described and compared with those in a seasonal influenza cohort (2007-2008, same hospitals; n = 754). Hospitalized patients with pH1N1 influenza were younger than those with seasonal influenza (mean age ± standard deviation, 47 ± 20 vs 70 ± 19 years) and fewer had comorbid conditions (48% vs 64%). The rate of positive immunofluorescence assay results was low (54% vs 84%), and antiviral use was frequent (96% vs 52%). Most patients in both cohorts developed complicated illnesses (67.8% vs 77.1%), but patients with pH1N1 influenza had higher rates of extrapulmonary complications (23% vs 16%; P = .004) and intensive care unit admission and/or death (patient age <35 years, 2.3% vs 0%; 35-65 years, 12.4% vs 3.2%; >65 years, 13.5% vs 8.5%; adjusted odds ratio [OR] 2.13; 95% confidence interval [CI], 1.25-3.62; P = .005). Patients who received antiviral treatment within 96 h after onset had better survival (log-rank test, P < .001). However, without timely treatment, the mortality risk was higher with pH1N1 infection (9.0% vs 5.8% for seasonal influenza; adjusted OR, 6.85; 95% CI, 1.64-28.65; P = .008]. Bacterial superinfection worsened outcomes. Adults hospitalized for pH1N1 influenza had significant complications and mortality despite being younger than patients with seasonal influenza. Antiviral treatment within 96 h may improve survival.

Influenza A (pH1N1) infection in children admitted to a pediatric intensive care unit: Differences with other respiratory viruses*

To describe the clinical features of patients admitted to the pediatric intensive care unit (PICU) with acute lower respiratory tract infection (LRTI) attributable to influenza A pH1N1 virus and compare them with those admitted with LRTI due to other viral pathogens. Retrospective, observational, comparative study. PICU in a university-affiliated, tertiary-care, pediatric hospital. Patients aged >1 month with acute viral LRTI admitted to the PICU who met the following criteria: 1) influenza A pH1N1 virus infection detected between June 1, 2009 and July 16, 2009; and 2) patients with LRTI due to other viral pathogens infection detected in the same period of the year 2008 plus patients with 2009 influenza A non-pH1N1 infection. None. We evaluated age, weight, gender, length of hospital stay before PICU admission, length of PICU stay, underlying disease, clinical diagnosis, severity, complications, treatment, risk of death, mortality, and cause of death. We identified 30 patients with acute LRTI due to influenza A pH1N1 virus (group 1) and 62 patients with LRTI due to other viral pathogens (group 2). Relevant characteristics in group 1: 59% of patients were aged >2 yrs. Median length of PICU stay was 15 days. An underlying condition was present in 83% of the patients. None of them had bronchiolitis on PICU admission; 12 (40%) had bilateral pneumonia; 15 (50%) had acute respiratory distress syndrome; and nine (30%) had shock. Twenty-nine patients required mechanical ventilation (96.6%); only one required extracorporeal membrane oxygenation; and 19 (63%) had respiratory complications. Six (20%) children died. When both groups were compared, patients with influenza A pH1N1 infection were older; pneumonia, acute respiratory distress syndrome, and shock were more frequently seen at the time of PICU admission, although length of stay and mortality were similar. Patients with influenza A pH1N1 respiratory virus infection presented with more severe illness. Outcomes were similar in both groups.

Age as an Independent Risk Factor for Intensive Care Unit Admission or Death Due to 2009 Pandemic Influenza A(H1N1) Virus Infection

This study evaluated risk factors for intensive care unit (ICU) admission or death among people hospitalized with 2009 pandemic influenza A (pH1N1) virus infection. We based analyses on data collected in Washington State from April 27 to September 18, 2009, on deceased or hospitalized people with laboratory-confirmed pH1N1 infection reported by health-care providers and hospitals as part of enhanced public health surveillance. We used bivariate analyses and multivariable logistic regression to identify risk factors associated with ICU admission or death due to pH1N1. We identified 123 patients admitted to the hospital but not an ICU and 61 patients who were admitted to an ICU or died. Independent of high-risk medical conditions, both older age and delayed time to hospital admission were identified as risk factors for ICU admission or death due to pH1N1. Specifically, the odds of ICU admission or death were 4.44 times greater among adults aged 18-49 years (95% confidence interval [CI] 1.97, 10.02) and 5.93 times greater among adults aged 50-64 years (95% CI 2.24, 15.65) compared with pediatric patients < 18 years of age. Likewise, hospitalized cases admitted more than two days after illness onset had 2.17 times higher odds of ICU admission or death than those admitted within two days of illness onset (95% CI 1.10, 4.25). Although certain medical conditions clearly influence the need for hospitalization among people infected with pH1N1 virus, older age and delayed time to admission each played an independent role in the progression to ICU admission or death among hospitalized patients.

Severe 2009 A/H1N1v influenza in pregnant women in Spain*

To describe the severity of the 2009 influenza A/H1N1v illness among pregnant women admitted to Spanish intensive care units. Prospective, observational, multicenter study conducted in 148 Spanish intensive care units. We reviewed demographic and clinical data from the Spanish Society of Intensive Care Medicine database reported from April 23, 2009, to February 15, 2010. We included women of reproductive age (15-44 yrs) with confirmed A/H1N1v infection admitted to intensive care units. Two hundred thirty-four women of reproductive age were admitted to intensive care units, 50 (21.4%) of them pregnant. Seven deaths were recorded in pregnant and 22 in nonpregnant women. Among intensive care unit admissions, there were no statistically significant differences between pregnant women and nonpregnant in Acute Physiology and Chronic Health Evaluation II, Sequential Organ Failure Assessment scores, chest x-rays, inotrope requirement, or need for mechanical ventilation or steroid therapy. Mortality risk was significantly associated with Acute Physiology and Chronic Health Evaluation II, Sequential Organ Failure Assessment, and obesity. Viral pneumonia was more frequent in pregnant women than in nonpregnant women, with an odds ratio (adjusted for asthma, time from onset influenza symptoms to hospital admission and obesity) of 4.9 (95% confidence interval: 1.4-17.2). The development of primary viral pneumonia in women of reproductive age appeared to be related to the time of commencement of antiviral treatment, the lowest rates being reported with initiation of antiviral therapy within 48 hrs of symptom onset (63.6% vs. 82.6%, p = .03). However, antiviral therapy was started within this time span in only 14% of pregnant women. More than 20% of women of reproductive age admitted to intensive care unit for pH1N1 infection were pregnant. Pregnancy was significantly associated with primary viral pneumonia. Pregnant women should receive prompt treatment with oseltamivir within 48 hrs of the onset of influenza symptoms.

The Seroprevalence of Pandemic Influenza H1N1 (2009) Virus in China

BackgroundMainland China experienced pandemic influenza H1N1 (2009) virus (pH1N1) with peak activity during November-December 2009. To understand the geographic extent, risk factors, and attack rate of pH1N1 infection in China we conducted a nationwide serological survey to determine the prevalence of antibodies to pH1N1.Methodology/Principal FindingsStored serum samples (n = 2,379) collected during 2006-2008 were used to estimate baseline serum reactogenicity to pH1N1. In January 2010, we used a multistage-stratified random sampling method to select 50,111 subjects who met eligibility criteria and collected serum samples and administered a standardized questionnaire. Antibody response to pH1N1 was measured using haemagglutination inhibition (HI) assay and the weighted seroprevalence was calculated using the Taylor series linearization method. Multivariable logistic regression analyses were used to examine risk factors for pH1N1 seropositivity. Baseline seroprevalence of pH1N1 antibody (HI titer ≥40) was 1.2%. The weighted seroprevalence of pH1N1 among the Chinese population was 21.5%(vaccinated: 62.0%; unvaccinated: 17.1%). Among unvaccinated participants, those aged 6-15 years (32.9%) and 16-24 years (30.3%) had higher seroprevalence compared with participants aged 25–59 years (10.7%) and ≥60 years (9.9%, P<0.0001). Children in kindergarten and students had higher odds of seropositivity than children in family care (OR: 1.36 and 2.05, respectively). We estimated that 207.7 million individuals (15.9%) experienced pH1N1 infection in China.Conclusions/SignificanceThe Chinese population had low pre-existing immunity to pH1N1 and experienced a relatively high attack rate in 2009 of this virus. We recommend routine control measures such as vaccination to reduce transmission and spread of seasonal and pandemic influenza viruses.

Seroprevalence of antibody to pandemic influenza A (H1N1) 2009 among healthcare workers after the first wave in Hong Kong

SummaryDuring the first wave of an influenza pandemic prior to the availability of an effective vaccine, healthcare workers (HCWs) may be at particular risk of infection with the novel influenza strain. We conducted a cross-sectional study of the prevalence of antibody to pandemic influenza A (H1N1) 2009 (pH1N1) among HCWs in Hong Kong in February–March 2010 following the first pandemic wave. Sera collected from HCWs were tested for antibody to pH1N1 influenza virus by viral neutralisation (VN). We assessed factors associated with higher antibody titres, and we compared antibody titres in HCWs with those in a separate community study. In total we enrolled 703 HCWs. Among 599 HCWs who did not report receipt of pH1N1 vaccine, 12% had antibody titre ≥1:40 by VN. There were no significant differences in the age-specific proportions of unvaccinated HCWs with antibody titre ≥1:40 compared with the general community following the first wave of pH1N1. Under good adherence to infection control guidelines, potential occupational exposures in the hospital setting did not appear to be associated with any substantial excess risk of pH1N1 infection in HCWs. Most HCWs had low antibody titres following the first pandemic wave.

Influenza A Pandemic (H1N1) 2009 Virus Outbreak in a Cat Colony in Italy

In April 2009, a novel H1N1 influenza A virus (pH1N1) was recognized as the cause of the flu pandemic in humans. Here, we report the isolation of pH1N1 virus from the lung homogenates of two cats, which died after severe respiratory symptoms. The cats belonged to a cat colony consisting of 90 caged cats and were found dead following a 2-week period of respiratory and gastrointestinal diseases in the colony. During the outbreak, 25 cats died and 50% of the animal colony showed anorexia, depression, respiratory and gastrointestinal symptoms. Histological examination of the lungs of the two tested cats displayed lesions centred on terminal airways with epithelial bronchiolar hyperplasia and alveolar necrosis. Influenza A virus was detected in the lung tissues by immunohistochemistry and real-time RT-PCR (rRT-PCR). Partial sequences of haemagglutinin (HA) genes and complete sequences of neuraminidase (NA) genes of the two isolates displayed high similarity to the pH1N1 viruses circulating in humans (99% for HA gene and 100% for NA gene). To determine whether the pandemic virus had circulated among cats, serum samples and pharyngeal swabs were collected from 38 cats of the colony. Serum samples were tested by ELISA to detect antibodies against pH1N1 nucleoprotein and by hemagglutination-inhibition test, while pharyngeal swabs were examined by pH1N1 specific rRT-PCR. Twenty-one (55%) of the tested cats carried antibodies against the isolated strain and two swabs were positive for the presence of pH1N1 RNA. Our results confirm that the pH1N1 virus was able to infect cats and raise the hypothesis of the circulation of the virus within the colony being due to cat-to-cat transmission. The case reported here provides, to the best of the authors' knowledge, the first description of the pH1N1 infection involving numerous cats that lived in a restricted area with limited contact with humans.

Fatal outcome of pandemic H1N1 2009 influenza infection is associated with neutrophil and macrophage lung infiltration but not enhanced viral burden in pregnant mice. (111.3)

Abstract Pandemic H1N1 2009 Influenza A virus (pH1N1) infection in pregnant or postpartum women is quite severe. The immunological mechanisms that affect infection outcome in these populations are not well understood. To address this, pregnant Balb/c and non-pregnant mice were inoculated with a wild-type pH1N1 virus. We determined that early cytokine responses were impaired in pregnant mouse lungs. Moreover, pulmonary infiltration of neutrophils and macrophages strongly correlated with an increase in mortality in pregnant mice. Increased mortality in pregnant animals was not associated with higher virus load because equivalent viral burden (virus titers and immunohistochemical staining) was observed in the nasal cavities and lower respiratory tracts of all mice. Pregnancy altered innate responses despite the presence of similar viral burden. Also, pregnant mice demonstrated equivalent influenza-specific activation of pulmonary CD8+ T lymphocytes however; they displayed elevated T-regulator lymphocyte (Tregs) responses in the lung and mediastinal lymph nodes. Despite these immunologic alterations, pregnant animals mounted equivalent hemagglutinin inhibition and IgG subclass titers in response to virus or immunization with monovalent inactivated pH1N1 vaccine. Therefore, the severity of pH1N1 in pregnant mice is associated with pulmonary neutrophil and macrophage invasion, dysregulated cytokine responses but not increased viral load.

Pandemic (H1N1) 2009 influenza virus induces weaker host immune responses in vitro: a possible mechanism of high transmissibility

BackgroundThe world has recently overcome the first influenza pandemic of the 21st century caused by a novel H1N1 virus (pH1N1) which is a triple reassortant comprising genes derived from avian, human, and swine influenza viruses and antigenically quite different from seasonal H1N1 strains. Although the case fatality rates have decreased in many developed countries, the situation is still alarming in many developing countries including India where considerable numbers of new cases are appearing everyday. There is still a high morbidity and mortality of susceptible adult as well as young population without having underlying health issues due to the influenza infection.ResultsTo achieve a better understanding of the risk posed by the pH1N1 and to understand its pathogenicity, we studied the host gene expression response to Indian isolate of pH1N1 infection and compared it with seasonal H1N1 infection. The response was studied at four different time points (4, 8, 16 and 24 h) post infection (hpi) in A549 cells using microarray platform. We found that pH1N1 induces immune response earlier than seasonal H1N1 viruses, but at the later stages of infection there is a suppression of host immune responses. The infection with pH1N1 resulted in considerable decrease in the expression of cytokine and other immune genes namely IL8, STAT1, B2 M and IL4 compared to seasonal H1N1.ConclusionWe propose that the inability to induce strong innate immune response could be a reason for the high transmissibility, pathogenicity and mortality caused by pH1N1 virus.