Hospitalized children with 2009 pandemic influenza A (H1N1): comparison to seasonal influenza and risk factors for admission to the ICU

Background

Limited data are available describing the clinical presentation and risk factors for admission to the intensive care unit for children with 2009 H1N1 infection.

Methods

We conducted a retrospective chart review of all hospitalized children with 2009 influenza A (H1N1) and 2008–09 seasonal influenza at The Children''s Hospital, Denver, Colorado.

Results

Of the 307 children identified with 2009 H1N1 infections, the median age was 6 years, 61% were male, and 66% had underlying medical conditions. Eighty children (26%) were admitted to the ICU. Thirty-two (40%) of the ICU patients required intubation and 17 (53%) of the intubated patients developed acute respiratory distress syndrome (ARDS). Four patients required extracorporeal membrane oxygenation. Eight (3%) of the hospitalized children died. Admission to the ICU was significantly associated with older age and underlying neurological condition. Compared to the 90 children admitted during the 2008–09 season, children admitted with 2009 H1N1 influenza were significantly older, had a shorter length of hospitalization, more use of antivirals, and a higher incidence of ARDS.

Conclusions

Compared to the 2008–09 season, hospitalized children with 2009 H1N1 influenza were much older and had more severe respiratory disease. Among children hospitalized with 2009 H1N1 influenza, risk factors for admission to the ICU included older age and having an underlying neurological condition. Children under the age of 2 hospitalized with 2009 H1N1 influenza were significantly less likely to require ICU care compared to older hospitalized children.     

The epidemiological and molecular aspects of influenza H5N1 viruses at the human-animal interface in Egypt

With 119 confirmed cases between March 2006 and December 2010, Egypt ranks second among countries reporting human H5N1 influenza virus infections. In 2009–2010, Egypt reported 68 new human cases and became the new epicenter for H5N1 infections. We conducted an epidemiological and molecular analysis in order to better understand the situation in Egypt. The onset of new cases peaked annually during the winter and spring months, with majority of cases reported in the Nile Delta region. Most cases were less than 18 years old (62%) and females (60%). The overall case-fatality rate was 34% and significantly increased by age. There was a significant difference between the case-fatality rates among females and males. We observed a significant drop (p = 0.004) in case fatality rate in 2009 (10%) as compared to higher rates (36%–56%) in other years. Hospitalization within 2 or 3 days after onset of symptoms significantly decreased mortality. Molecular analysis showed that variations do occur among viruses isolated from birds as well as from humans in Egypt, and these mutations were especially noted in 2009 viruses. As the epidemiological profile of Egyptian cases differs from other countries, there is an urgent need to conduct prospective studies to enhance our understanding of incidence, prevalence, and determinants of virulence of human infections with avian H5N1 influenza viruses.     

Risk factors for severe outcomes following 2009 influenza A (H1N1) infection: a global pooled analysis

Background

Since the start of the 2009 influenza A pandemic (H1N1pdm), the World Health Organization and its member states have gathered information to characterize the clinical severity of H1N1pdm infection and to assist policy makers to determine risk groups for targeted control measures.

Methods and Findings

Data were collected on approximately 70,000 laboratory-confirmed hospitalized H1N1pdm patients, 9,700 patients admitted to intensive care units (ICUs), and 2,500 deaths reported between 1 April 2009 and 1 January 2010 from 19 countries or administrative regions—Argentina, Australia, Canada, Chile, China, France, Germany, Hong Kong SAR, Japan, Madagascar, Mexico, the Netherlands, New Zealand, Singapore, South Africa, Spain, Thailand, the United States, and the United Kingdom—to characterize and compare the distribution of risk factors among H1N1pdm patients at three levels of severity: hospitalizations, ICU admissions, and deaths. The median age of patients increased with severity of disease. The highest per capita risk of hospitalization was among patients <5 y and 5–14 y (relative risk [RR] = 3.3 and 3.2, respectively, compared to the general population), whereas the highest risk of death per capita was in the age groups 50–64 y and ≥65 y (RR = 1.5 and 1.6, respectively, compared to the general population). Similarly, the ratio of H1N1pdm deaths to hospitalizations increased with age and was the highest in the ≥65-y-old age group, indicating that while infection rates have been observed to be very low in the oldest age group, risk of death in those over the age of 64 y who became infected was higher than in younger groups. The proportion of H1N1pdm patients with one or more reported chronic conditions increased with severity (median = 31.1%, 52.3%, and 61.8% of hospitalized, ICU-admitted, and fatal H1N1pdm cases, respectively). With the exception of the risk factors asthma, pregnancy, and obesity, the proportion of patients with each risk factor increased with severity level. For all levels of severity, pregnant women in their third trimester consistently accounted for the majority of the total of pregnant women. Our findings suggest that morbid obesity might be a risk factor for ICU admission and fatal outcome (RR = 36.3).

Conclusions

Our results demonstrate that risk factors for severe H1N1pdm infection are similar to those for seasonal influenza, with some notable differences, such as younger age groups and obesity, and reinforce the need to identify and protect groups at highest risk of severe outcomes. Please see later in the article for the Editors'' Summary     

Sero-prevalence and incidence of A/H1N1 2009 influenza infection in Scotland in winter 2009-2010

Background

Sero-prevalence is a valuable indicator of prevalence and incidence of A/H1N1 2009 infection. However, raw sero-prevalence data must be corrected for background levels of cross-reactivity (i.e. imperfect test specificity) and the effects of immunisation programmes.

Methods and Findings

We obtained serum samples from a representative sample of 1563 adults resident in Scotland between late October 2009 and April 2010. Based on a microneutralisation assay, we estimate that 44% (95% confidence intervals (CIs): 40–47%) of the adult population of Scotland were sero-positive for A/H1N1 2009 influenza by 1 March 2010. Correcting for background cross-reactivity and for recorded vaccination rates by time and age group, we estimated that 34% (27–42%) were naturally infected with A/H1N1 2009 by 1 March 2010. The central estimate increases to >40% if we allow for imperfect test sensitivity. Over half of these infections are estimated to have occurred during the study period and the incidence of infection in late October 2009 was estimated at 4.3 new infections per 1000 people per day (1.2 to 7.2), falling close to zero by April 2010. The central estimate increases to over 5.0 per 1000 if we allow for imperfect test specificity. The rate of infection was higher for younger adults than older adults. Raw sero-prevalences were significantly higher in more deprived areas (likelihood ratio trend statistic = 4.92,1 df, P = 0.03) but there was no evidence of any difference in vaccination rates.

Conclusions

We estimate that almost half the adult population of Scotland were sero-positive for A/H1N1 2009 influenza by early 2010 and that the majority of these individuals (except in the oldest age classes) sero-converted as a result of natural infection with A/H1N1 2009. Public health planning should consider the possibility of higher rates of infection with A/H1N1 2009 influenza in more deprived areas.     

Characterizing the epidemiology of the 2009 influenza A/H1N1 pandemic in Mexico

Background

Mexico''s local and national authorities initiated an intense public health response during the early stages of the 2009 A/H1N1 pandemic. In this study we analyzed the epidemiological patterns of the pandemic during April–December 2009 in Mexico and evaluated the impact of nonmedical interventions, school cycles, and demographic factors on influenza transmission.

Methods and Findings

We used influenza surveillance data compiled by the Mexican Institute for Social Security, representing 40% of the population, to study patterns in influenza-like illness (ILIs) hospitalizations, deaths, and case-fatality rate by pandemic wave and geographical region. We also estimated the reproduction number (R) on the basis of the growth rate of daily cases, and used a transmission model to evaluate the effectiveness of mitigation strategies initiated during the spring pandemic wave. A total of 117,626 ILI cases were identified during April–December 2009, of which 30.6% were tested for influenza, and 23.3% were positive for the influenza A/H1N1 pandemic virus. A three-wave pandemic profile was identified, with an initial wave in April–May (Mexico City area), a second wave in June–July (southeastern states), and a geographically widespread third wave in August–December. The median age of laboratory confirmed ILI cases was ∼18 years overall and increased to ∼31 years during autumn (p<0.0001). The case-fatality ratio among ILI cases was 1.2% overall, and highest (5.5%) among people over 60 years. The regional R estimates were 1.8–2.1, 1.6–1.9, and 1.2–1.3 for the spring, summer, and fall waves, respectively. We estimate that the 18-day period of mandatory school closures and other social distancing measures implemented in the greater Mexico City area was associated with a 29%–37% reduction in influenza transmission in spring 2009. In addition, an increase in R was observed in late May and early June in the southeast states, after mandatory school suspension resumed and before summer vacation started. State-specific fall pandemic waves began 2–5 weeks after school reopened for the fall term, coinciding with an age shift in influenza cases.

Conclusions

We documented three spatially heterogeneous waves of the 2009 A/H1N1 pandemic virus in Mexico, which were characterized by a relatively young age distribution of cases. Our study highlights the importance of school cycles on the transmission dynamics of this pandemic influenza strain and suggests that school closure and other mitigation measures could be useful to mitigate future influenza pandemics. Please see later in the article for the Editors'' Summary     

Epidemiological characteristics of 2009 (H1N1) pandemic influenza based on paired sera from a longitudinal community cohort study

Background

While patterns of incidence of clinical influenza have been well described, much uncertainty remains over patterns of incidence of infection. The 2009 pandemic provided both the motivation and opportunity to investigate patterns of mild and asymptomatic infection using serological techniques. However, to date, only broad epidemiological patterns have been defined, based on largely cross-sectional study designs with convenience sampling frameworks.

Methods and Findings

We conducted a paired serological survey of a cohort of households in Hong Kong, recruited using random digit dialing, and gathered data on severe confirmed cases from the public hospital system (>90% inpatient days). Paired sera were obtained from 770 individuals, aged 3 to 103, along with detailed individual-level and household-level risk factors for infection. Also, we extrapolated beyond the period of our study using time series of severe cases and we simulated alternate study designs using epidemiological parameters obtained from our data. Rates of infection during the period of our study decreased substantially with age: for 3–19 years, the attack rate was 39% (31%–49%); 20–39 years, 8.9% (5.3%–14.7%); 40–59 years, 5.3% (3.5%–8.0%); and 60 years or older, 0.77% (0.18%–4.2%). We estimated parameters for a parsimonious model of infection in which a linear age term and the presence of a child in the household were used to predict the log odds of infection. Patterns of symptom reporting suggested that children experienced symptoms more often than adults. The overall rate of confirmed pandemic (H1N1) 2009 influenza (H1N1pdm) deaths was 7.6 (6.2–9.5) per 100,000 infections. However, there was substantial and progressive increase in deaths per 100,000 infections with increasing age from 0.66 (0.65–0.86) for 3–19 years up to 220 (50–4,000) for 60 years and older. Extrapolating beyond the period of our study using rates of severe disease, we estimated that 56% (43%–69%) of 3–19 year olds and 16% (13%–18%) of people overall were infected by the pandemic strain up to the end of January 2010. Using simulation, we found that, during 2009, larger cohorts with shorter follow-up times could have rapidly provided similar data to those presented here.

Conclusions

Should H1N1pdm evolve to be more infectious in older adults, average rates of severe disease per infection could be higher in future waves: measuring such changes in severity requires studies similar to that described here. The benefit of effective vaccination against H1N1pdm infection is likely to be substantial for older individuals. Revised pandemic influenza preparedness plans should include prospective serological cohort studies. Many individuals, of all ages, remained susceptible to H1N1pdm after the main 2009 wave in Hong Kong. Please see later in the article for the Editors'' Summary     

Characteristics of Hospitalized Cases with Influenza A (H1N1)pdm09 Infection during First Winter Season of Post-Pandemic in China

Background

Influenza A (H1N1)pdm09 (2009 H1N1) re-circulated as the predominant virus from January through February 2011 in China. National surveillance of 2009 H1N1 as a notifiable disease was maintained to monitor potential changes in disease severity from the previous season.

Methodology/Principal Findings

To describe the characteristics of hospitalized cases with 2009 H1N1 infection and analyze risk factors for severe illness during the 2010–2011winter season in China, we obtained surveillance data from hospitalized cases with 2009 H1N1 infection from November 2010 through May 2011, and reviewed medical records from 701 hospitalized cases. Age-standardized risk ratios were used to compare the age distribution of patients that were hospitalized and died due to 2009 H1N1 between the 2010–2011winter season to those during the 2009–2010 pandemic period. During the 2010–2011 winter season, children less than 5 years of age had the highest relative risk of hospitalization and death, followed by adults aged 65 years or older. Additionally, the relative risk of hospitalized cases aged 5–14 and 15–24 years was lower compared to children less than 5 years of age. During the winter season of 2010–2011, the proportions of adults aged 25 years or older for hospitalization and death were significantly higher than those during the 2009–2010 pandemic period. Being male, having a chronic medical condition, delayed hospital admission (≥3 days from onset) or delayed initiation of antiviral treatment (≥5 days from onset) were associated with severe illness among non-pregnant patients ≥2 years of age.

Conclusions/Significance

We observed a change in high risk groups for hospitalization for 2009 H1N1 during the winter months immediately following the pandemic period compared to the high risk groups identified during the pandemic period. Our nationally notifiable disease surveillance system enabled us to understand the evolving epidemiology of 2009 H1N1 infection after the pandemic period.     

H1N1pdm influenza infection in hospitalized cancer patients: clinical evolution and viral analysis

Background

The novel influenza A pandemic virus (H1N1pdm) caused considerable morbidity and mortality worldwide in 2009. The aim of the present study was to evaluate the clinical course, duration of viral shedding, H1N1pdm evolution and emergence of antiviral resistance in hospitalized cancer patients with severe H1N1pdm infections during the winter of 2009 in Brazil.

Methods

We performed a prospective single-center cohort study in a cancer center in Rio de Janeiro, Brazil. Hospitalized patients with cancer and a confirmed diagnosis of influenza A H1N1pdm were evaluated. The main outcome measures in this study were in-hospital mortality, duration of viral shedding, viral persistence and both functional and molecular analyses of H1N1pdm susceptibility to oseltamivir.

Results

A total of 44 hospitalized patients with suspected influenza-like illness were screened. A total of 24 had diagnosed H1N1pdm infections. The overall hospital mortality in our cohort was 21%. Thirteen (54%) patients required intensive care. The median age of the studied cohort was 14.5 years (3–69 years). Eighteen (75%) patients had received chemotherapy in the previous month, and 14 were neutropenic at the onset of influenza. A total of 10 patients were evaluated for their duration of viral shedding, and 5 (50%) displayed prolonged viral shedding (median 23, range = 11–63 days); however, this was not associated with the emergence of a resistant H1N1pdm virus. Viral evolution was observed in sequentially collected samples.

Conclusions

Prolonged influenza A H1N1pdm shedding was observed in cancer patients. However, oseltamivir resistance was not detected. Taken together, our data suggest that severely ill cancer patients may constitute a pandemic virus reservoir with major implications for viral propagation.     

Safety and immunogenicity following administration of a live, attenuated monovalent 2009 H1N1 influenza vaccine to children and adults in two randomized controlled trials

Background

The safety, tolerability, and immunogenicity of a monovalent intranasal 2009 A/H1N1 live attenuated influenza vaccine (LAIV) were evaluated in children and adults.

Methods/Principal Findings

Two randomized, double-blind, placebo-controlled studies were completed in children (2–17 y) and adults (18–49 y). Subjects were assigned 4∶1 to receive 2 doses of H1N1 LAIV or placebo 28 days apart. The primary safety endpoint was fever ≥38.3°C during days 1–8 after the first dose; the primary immunogenicity endpoint was the proportion of subjects experiencing a postdose seroresponse. Solicited symptoms and adverse events were recorded for 14 days after each dose and safety data were collected for 180 days post-final dose. In total, 326 children (H1N1 LAIV, n = 261; placebo, n = 65) and 300 adults (H1N1 LAIV, n = 240; placebo, n = 60) were enrolled. After dose 1, fever ≥38.3°C occurred in 4 (1.5%) pediatric vaccine recipients and 1 (1.5%) placebo recipient (rate difference, 0%; 95% CI: –6.4%, 3.1%). No adults experienced fever following dose 1. Seroresponse rates in children (H1N1 LAIV vs. placebo) were 11.1% vs. 6.3% after dose 1 (rate difference, 4.8%; 95% CI: –9.6%, 13.8%) and 32.0% vs. 14.5% after dose 2 (rate difference, 17.5%; 95% CI: 5.5%, 27.1%). Seroresponse rates in adults were 6.1% vs. 0% (rate difference, 6.1%; 95% CI: –5.6%, 12.6%) and 14.9% vs. 5.6% (rate difference, 9.3%; 95% CI: –0.8%, 16.3%) after dose 1 and dose 2, respectively. Solicited symptoms after dose 1 (H1N1 LAIV vs. placebo) occurred in 37.5% vs. 32.3% of children and 41.7% vs. 31.7% of adults. Solicited symptoms occurred less frequently after dose 2 in adults and children. No vaccine-related serious adverse events occurred.

Conclusions/Significance

In subjects aged 2 to 49 years, two doses of H1N1 LAIV have a safety and immunogenicity profile similar to other previously studied and efficacious formulations of seasonal trivalent LAIV.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00946101","term_id":"NCT00946101"}}NCT00946101, {"type":"clinical-trial","attrs":{"text":"NCT00945893","term_id":"NCT00945893"}}NCT00945893     

Risk factors and immunity in a nationally representative population following the 2009 influenza A(H1N1) pandemic

Background

Understanding immunity, incidence and risk factors of the 2009 influenza A(H1N1) pandemic (2009 H1N1) through a national seroprevalence study is necessary for informing public health interventions and disease modelling.

Methods and Findings

We collected 1687 serum samples and individual risk factor data between November-2009 to March-2010, three months after the end of the 2009 H1N1 wave in New Zealand. Participants were randomly sampled from selected general practices countrywide and hospitals in the Auckland region. Baseline immunity was measured from 521 sera collected during 2004 to April-2009. Haemagglutination inhibition (HI) antibody titres of ≥1∶40 against 2009 H1N1 were considered seroprotective as well as seropositive. The overall community seroprevalence was 26.7% (CI:22.6–29.4). The seroprevalence varied across age and ethnicity. Children aged 5–19 years had the highest seroprevalence (46.7%;CI:38.3–55.0), a significant increase from the baseline (14%;CI:7.2–20.8). Older adults aged ≥60 had no significant difference in seroprevalence between the serosurvey (24.8%;CI:18.7–30.9) and baseline (22.6%;CI:15.3–30.0). Pacific peoples had the highest seroprevalence (49.5%;CI:35.1–64.0). There was no significant difference in seroprevalence between both primary (29.6%;CI:22.6–36.5) and secondary healthcare workers (25.3%;CI:20.8–29.8) and community participants. No significant regional variation was observed. Multivariate analysis indicated age as the most important risk factor followed by ethnicity. Previous seasonal influenza vaccination was associated with higher HI titres. Approximately 45.2% of seropositive individuals reported no symptoms.

Conclusions

Based on age and ethnicity standardisation to the New Zealand Population, about 29.5% of New Zealanders had antibody titers at a level consistent with immunity to 2009 H1N1. Around 18.3% of New Zealanders were infected with the virus during the first wave including about one child in every three. Older people were protected due to pre-existing immunity. Age was the most important factor associated with infection followed by ethnicity. Healthcare workers did not appear to have an increased risk of infection compared with the general population.     

Seroprevalence and severity of 2009 pandemic influenza A H1N1 in Taiwan

Background

This study is to determine the seroprevalence of the pandemic influenza A H1N1 virus (pH1N1) in Taiwan before and after the 2009 pandemic, and to estimate the relative severity of pH1N1 infections among different age groups.

Methodology/Principal Findings

A total of 1544 and 1558 random serum samples were collected from the general population in Taiwan in 2007 and 2010, respectively. Seropositivity was defined by a hemagglutination inhibition titer to pH1N1 (A/Taiwan/126/09) ≥1:40. The seropositivity rate of pH1N1 among the unvaccinated subjects and national surveillance data were used to compare the proportion of infections that led to severe diseases and fatalities among different age groups. The overall seroprevalence of pH1N1 was 0.91% (95% confidence interval [CI] 0.43–1.38) in 2007 and significantly increased to 29.9% (95% CI 27.6–32.2) in 2010 (p<0.0001), with the peak attack rate (55.4%) in 10–17 year-old adolescents, the lowest in elderly ≥65 years (14.1%). The overall attack rates were 20.6% (188/912) in unvaccinated subjects. Among the unvaccinated but infected populations, the estimated attack rates of severe cases per 100,000 infections were significantly higher in children aged 0–5 years (54.9 cases, odds ratio [OR] 4.23, 95% CI 3.04–5.90) and elderly ≥ 65years (22.4 cases, OR 2.76, 95% CI 1.99–3.83) compared to adolescents aged 10–17 years (13.0 cases). The overall case-fatality rate was 0.98 per 100,000 infections without a significant difference in different age groups.

Conclusions/Significance

Pre-existing immunity against pH1N1 was rarely identified in Taiwanese at any age in 2007. Young children and elderly – the two most lower seroprotection groups showed the greatest vulnerability to clinical severity after the pH1N1 infections. These results imply that both age groups should have higher priority for immunization in the coming flu season.     

A comparison of clinical and epidemiological characteristics of fatal human infections with H5N1 and human influenza viruses in Thailand, 2004-2006

Background

The National Avian Influenza Surveillance (NAIS) system detected human H5N1 cases in Thailand from 2004–2006. Using NAIS data, we identified risk factors for death among H5N1 cases and described differences between H5N1 and human (seasonal) influenza cases.

Methods and Findings

NAIS identified 11,641 suspect H5N1 cases (e.g. persons with fever and respiratory symptoms or pneumonia, and exposure to sick or dead poultry). All suspect H5N1 cases were tested with polymerase chain reaction (PCR) assays for influenza A(H5N1) and human influenza viruses. NAIS detected 25 H5N1 and 2074 human influenza cases; 17 (68%) and 22 (1%) were fatal, respectively. We collected detailed information from medical records on all H5N1 cases, all fatal human influenza cases, and a sampled subset of 230 hospitalized non-fatal human influenza cases drawn from provinces with ≥1 H5N1 case or human influenza fatality.Fatal versus non-fatal H5N1 cases were more likely to present with low white blood cell (p = 0.05), lymphocyte (p<0.02), and platelet counts (p<0.01); have elevated liver enzymes (p = 0.05); and progress to circulatory (p<0.001) and respiratory failure (p<0.001). There were no differences in age, medical conditions, or antiviral treatment between fatal and non-fatal H5N1 cases. Compared to a sample of human influenza cases, all H5N1 cases had direct exposure to sick or dead birds (60% vs. 100%, p<0.05). Fatal H5N1 and fatal human influenza cases were similar clinically except that fatal H5N1 cases more commonly: had fever (p<0.001), vomiting (p<0.01), low white blood cell counts (p<0.01), received oseltamivir (71% vs. 23%, p<.001), but less often had ≥1 chronic medical conditions (p<0.001).

Conclusions

In the absence of diagnostic testing during an influenza A(H5N1) epizootic, a few epidemiologic, clinical, and laboratory findings might provide clues to help target H5N1 control efforts. Severe human influenza and H5N1 cases were clinically similar, and both would benefit from early antiviral treatment.     

Post-pandemic seroprevalence of pandemic influenza A (H1N1) 2009 infection (swine flu) among children <18 years in Germany

Background

We determined antibodies to the pandemic influenza A (H1N1) 2009 virus in children to assess: the incidence of (H1N1) 2009 infections in the 2009/2010 season in Germany, the proportion of subclinical infections and to compare titers in vaccinated and infected children.

Methodology/Principal Findings

Eight pediatric hospitals distributed over Germany prospectively provided sera from in- or outpatients aged 1 to 17 years from April 1^st to July 31^st 2010. Vaccination history, recall of infections and sociodemographic factors were ascertained. Antibody titers were measured with a sensitive and specific in-house hemagglutination inhibition test (HIT) and compared to age-matched sera collected during 6 months before the onset of the pandemic in Germany. We analyzed 1420 post-pandemic and 300 pre-pandemic sera. Among unvaccinated children aged 1–4 and 5–17 years the prevalence of HI titers (≥1∶10) was 27.1% (95% CI: 23.5–31.3) and 53.5% (95% CI: 50.9–56.2) compared to 1.7% and 5.5%, respectively, for pre-pandemic sera, accounting for a serologically determined incidence of influenza A (H1N1) 2009 during the season 2009/2010 of 25,4% (95% CI : 19.3–30.5) in children aged 1–4 years and 48.0% (95% CI: 42.6–52.0) in 5–17 year old children. Of children with HI titers ≥1∶10, 25.5% (95% CI: 22.5–28.8) reported no history of any infectious disease since June 2009. Among vaccinated children, 92% (95%-CI: 87.0–96.6) of the 5–17 year old but only 47.8% (95%-CI: 33.5–66.5) of the 1–4 year old children exhibited HI titers against influenza A virus (H1N1) 2009.

Conclusion

Serologically determined incidence of influenza A (H1N1) 2009 infections in children indicates high infection rates with older children (5–17 years) infected twice as often as younger children. In about a quarter of the children with HI titers after the season 2009/2010 subclinical infections must be assumed. Low HI titers in young children after vaccination with the AS03_B-adjuvanted split virion vaccine need further scrutiny.     

Prevalence of 2009 pandemic influenza A (H1N1) virus antibodies, Tampa Bay Florida--November-December, 2009

Background

In 2009, a novel influenza virus (2009 pandemic influenza A (H1N1) virus (pH1N1)) caused significant disease in the United States. Most states, including Florida, experienced a large fall wave of disease from September through November, after which disease activity decreased substantially. We determined the prevalence of antibodies due to the pH1N1 virus in Florida after influenza activity had peaked and estimated the proportion of the population infected with pH1N1 virus during the pandemic.

Methods

During November-December 2009, we collected leftover serum from a blood bank, a pediatric children''s hospital and a pediatric outpatient clinic in Tampa Bay Florida. Serum was tested for pH1N1 virus antibodies using the hemagglutination-inhibition (HI) assay. HI titers ≥40 were considered seropositive. We adjusted seroprevalence results to account for previously established HI assay specificity and sensitivity and employed a simple statistical model to estimate the proportion of seropositivity due to pH1N1 virus infection and vaccination.

Results

During the study time period, the overall seroprevalence in Tampa Bay, Florida was 25%, increasing to 30% after adjusting for HI assay sensitivity and specificity. We estimated that 5.9% of the population had vaccine-induced seropositivity while 25% had seropositivity secondary to pH1N1 virus infection. The highest cumulative incidence of pH1N1 virus infection was among children aged 5–17 years (53%) and young adults aged 18–24 years (47%), while adults aged ≥50 years had the lowest cumulative incidence (11–13%) of pH1N1 virus infection.

Conclusions

After the peak of the fall wave of the pandemic, an estimated one quarter of the Tampa Bay population had been infected with the pH1N1 virus. Consistent with epidemiologic trends observed during the pandemic, the highest burdens of disease were among school-aged children and young adults.     

Estimating the disease burden of 2009 pandemic influenza A(H1N1) from surveillance and household surveys in Greece

Background

The aim of this study was to assess the disease burden of the 2009 pandemic influenza A(H1N1) in Greece.

Methodology/Principal Findings

Data on influenza-like illness (ILI), collected through cross-sectional nationwide telephone surveys of 1,000 households in Greece repeated for 25 consecutive weeks, were combined with data from H1N1 virologic surveillance to estimate the incidence and the clinical attack rate (CAR) of influenza A(H1N1). Alternative definitions of ILI (cough or sore throat and fever>38°C [ILI-38] or fever 37.1–38°C [ILI-37]) were used to estimate the number of symptomatic infections. The infection attack rate (IAR) was approximated using estimates from published studies on the frequency of fever in infected individuals. Data on H1N1 morbidity and mortality were used to estimate ICU admission and case fatality (CFR) rates. The epidemic peaked on week 48/2009 with approximately 750–1,500 new cases/100,000 population per week, depending on ILI-38 or ILI-37 case definition, respectively. By week 6/2010, 7.1%–15.6% of the population in Greece was estimated to be symptomatically infected with H1N1. Children 5–19 years represented the most affected population group (CAR:27%–54%), whereas individuals older than 64 years were the least affected (CAR:0.6%–2.2%). The IAR (95% CI) of influenza A(H1N1) was estimated to be 19.7% (13.3%, 26.1%). Per 1,000 symptomatic cases, based on ILI-38 case definition, 416 attended health services, 108 visited hospital emergency departments and 15 were admitted to hospitals. ICU admission rate and CFR were 37 and 17.5 per 100,000 symptomatic cases or 13.4 and 6.3 per 100,000 infections, respectively.

Conclusions/Significance

Influenza A(H1N1) infected one fifth and caused symptomatic infection in up to 15% of the Greek population. Although individuals older than 65 years were the least affected age group in terms of attack rate, they had 55 and 185 times higher risk of ICU admission and CFR, respectively.     

Seroprevalence Following the Second Wave of Pandemic 2009 H1N1 Influenza in Pittsburgh,PA, USA

Background

In April 2009, a new pandemic strain of influenza infected thousands of persons in Mexico and the United States and spread rapidly worldwide. During the ensuing summer months, cases ebbed in the Northern Hemisphere while the Southern Hemisphere experienced a typical influenza season dominated by the novel strain. In the fall, a second wave of pandemic H1N1 swept through the United States, peaking in most parts of the country by mid October and returning to baseline levels by early December. The objective was to determine the seroprevalence of antibodies against the pandemic 2009 H1N1 influenza strain by decade of birth among Pittsburgh-area residents.

Methods and Findings

Anonymous blood samples were obtained from clinical laboratories and categorized by decade of birth from 1920–2009. Using hemagglutination-inhibition assays, approximately 100 samples per decade (n = 846) were tested from blood samples drawn on hospital and clinic patients in mid-November and early December 2009. Age specific seroprevalences against pandemic H1N1 (A/California/7/2009) were measured and compared to seroprevalences against H1N1 strains that had previously circulated in the population in 2007, 1957, and 1918. (A/Brisbane/59/2007, A/Denver/1/1957, and A/South Carolina/1/1918). Stored serum samples from healthy, young adults from 2008 were used as a control group (n = 100). Seroprevalences against pandemic 2009 H1N1 influenza varied by age group, with children age 10–19 years having the highest seroprevalence (45%), and persons age 70–79 years having the lowest (5%). The baseline seroprevalence among control samples from 18–24 year-olds was 6%. Overall seroprevalence against pandemic H1N1 across all age groups was approximately 21%.

Conclusions

After the peak of the second wave of 2009 H1N1, HAI seroprevalence results suggest that 21% of persons in the Pittsburgh area had become infected and developed immunity. Extrapolating to the entire US population, we estimate that at least 63 million persons became infected in 2009. As was observed among clinical cases, this sero-epidemiological study revealed highest infection rates among school-age children.     

Clinical characteristics of 26 human cases of highly pathogenic avian influenza A (H5N1) virus infection in China

Background

While human cases of highly pathogenic avian influenza A (H5N1) virus infection continue to increase globally, available clinical data on H5N1 cases are limited. We conducted a retrospective study of 26 confirmed human H5N1 cases identified through surveillance in China from October 2005 through April 2008.

Methodology/Principal Findings

Data were collected from hospital medical records of H5N1 cases and analyzed. The median age was 29 years (range 6–62) and 58% were female. Many H5N1 cases reported fever (92%) and cough (58%) at illness onset, and had lower respiratory findings of tachypnea and dyspnea at admission. All cases progressed rapidly to bilateral pneumonia. Clinical complications included acute respiratory distress syndrome (ARDS, 81%), cardiac failure (50%), elevated aminotransaminases (43%), and renal dysfunction (17%). Fatal cases had a lower median nadir platelet count (64.5×10⁹ cells/L vs 93.0×10⁹ cells/L, p = 0.02), higher median peak lactic dehydrogenase (LDH) level (1982.5 U/L vs 1230.0 U/L, p = 0.001), higher percentage of ARDS (94% [n = 16] vs 56% [n = 5], p = 0.034) and more frequent cardiac failure (71% [n = 12] vs 11% [n = 1], p = 0.011) than nonfatal cases. A higher proportion of patients who received antiviral drugs survived compared to untreated (67% [8/12] vs 7% [1/14], p = 0.003).

Conclusions/Significance

The clinical course of Chinese H5N1 cases is characterized by fever and cough initially, with rapid progression to lower respiratory disease. Decreased platelet count, elevated LDH level, ARDS and cardiac failure were associated with fatal outcomes. Clinical management of H5N1 cases should be standardized in China to include early antiviral treatment for suspected H5N1 cases.     

Field effectiveness of pandemic and 2009-2010 seasonal vaccines against 2009-2010 A(H1N1) influenza: estimations from surveillance data in France

Background

In this study, we assess how effective pandemic and trivalent 2009-2010 seasonal vaccines were in preventing influenza-like illness (ILI) during the 2009 A(H1N1) pandemic in France. We also compare vaccine effectiveness against ILI versus laboratory-confirmed pandemic A(H1N1) influenza, and assess the possible bias caused by using non-specific endpoints and observational data.

Methodology and Principal Findings

We estimated vaccine effectiveness by using the following formula: VE  =  (PPV-PCV)/(PPV(1-PCV)) × 100%, where PPV is the proportion vaccinated in the population and PCV the proportion of vaccinated influenza cases. People were considered vaccinated three weeks after receiving a dose of vaccine. ILI and pandemic A(H1N1) laboratory-confirmed cases were obtained from two surveillance networks of general practitioners. During the epidemic, 99.7% of influenza isolates were pandemic A(H1N1). Pandemic and seasonal vaccine uptakes in the population were obtained from the National Health Insurance database and by telephonic surveys, respectively. Effectiveness estimates were adjusted by age and week. The presence of residual biases was explored by calculating vaccine effectiveness after the influenza period. The effectiveness of pandemic vaccines in preventing ILI was 52% (95% confidence interval: 30–69) during the pandemic and 33% (4–55) after. It was 86% (56–98) against confirmed influenza. The effectiveness of seasonal vaccines against ILI was 61% (56–66) during the pandemic and 19% (−10–41) after. It was 60% (41–74) against confirmed influenza.

Conclusions

The effectiveness of pandemic vaccines in preventing confirmed pandemic A(H1N1) influenza on the field was high, consistently with published findings. It was significantly lower against ILI. This is unsurprising since not all ILI cases are caused by influenza. Trivalent 2009-2010 seasonal vaccines had a statistically significant effectiveness in preventing ILI and confirmed pandemic influenza, but were not better in preventing confirmed pandemic influenza than in preventing ILI. This lack of difference might be indicative of selection bias.