A review of adult mortality due to 2009 pandemic (H1N1) influenza A in California.
ABSTRACT: BACKGROUND: While children and young adults had the highest attack rates due to 2009 pandemic (H1N1) influenza A (2009 H1N1), studies of hospitalized cases noted high fatality in older adults. We analyzed California public health surveillance data to better characterize the populations at risk for dying due to 2009 H1N1. METHODS AND FINDINGS: A case was an adult ?20 years who died with influenza-like symptoms and laboratory results indicative of 2009 H1N1. Demographic and clinical data were abstracted from medical records using a standardized case report form. From April 3, 2009-August 10, 2010, 541 fatal cases ?20 years with 2009 H1N1 were reported. Influenza fatality rates per 100,000 population were highest in persons 50-59 years (3.5; annualized rate?=?2.6) and 60-69 years (2.3; annualized rate?=?1.7) compared to younger and older age groups (0.4-1.9; annualized rates?=?0.3-1.4). Of 486 cases hospitalized prior to death, 441 (91%) required intensive care unit (ICU) admission. ICU admission rates per 100,000 population were highest in adults 50-59 years (8.6). ICU case-fatality ratios among adults ranged from 24-42%, with the highest ratios in persons 70-79 years. A total of 425 (80%) cases had co-morbid conditions associated with severe seasonal influenza. The prevalence of most co-morbid conditions increased with increasing age, but obesity, pregnancy and obstructive sleep apnea decreased with age. Rapid testing was positive in 97 (35%) of 276 tested. Of 482 cases with available data, 384 (80%) received antiviral treatment, including 49 (15%) of 328 within 48 hours of symptom onset. CONCLUSIONS: Adults aged 50-59 years had the highest fatality due to 2009 H1N1; older adults may have been spared due to pre-existing immunity. However, once infected and hospitalized in intensive care, case-fatality ratios were high for all adults, especially in those over 60 years. Vaccination of adults older than 50 years should be encouraged.
Project description:In April 2009, 2009 pandemic influenza A H1N1 (2009 H1N1) was first identified in Mexico but did not cause widespread transmission in neighboring Guatemala until several weeks later.Using a population-based surveillance system for hospitalized pneumonia and influenza-like illness ongoing before the 2009 H1N1 pandemic began, we tracked the onset of 2009 H1N1 infection in Guatemala. We identified 239 individuals infected with influenza A (2009 H1N1) between May and December 2009, of whom 76 were hospitalized with pneumonia and 11 died (case fatality proportion: 4.6%, 95% confidence interval [CI] 2.3-8.1%). The median age of patients infected with 2009 H1N1 was 8.8 years, the median age of those hospitalized with pneumonia was 4.2 years, and five (45.5%) deaths occurred in children <5 years old. Crude rates of hospitalization between May and December 2009 were highest for children <5 years old. Twenty-one (27.6%) of the patients hospitalized with 2009 H1N1 were admitted to the intensive care unit and eight (10.5%) required mechanical ventilation. Underlying chronic conditions were noted in 14 (18.4%) of patients with pneumonia hospitalized with 2009 H1N1 infection.Chronic illnesses may be underdiagnosed in Guatemala, making it difficult to identify this risk group for vaccination. Children 6 months to 5 years old should be among priority groups for vaccination to prevent serious consequences because of 2009 H1N1 infection.
Project description:OBJECTIVE: To describe the clinical course and outcome of adults hospitalized with the 2009 H1N1 influenza infection. PATIENTS AND METHODS: In this retrospective study, we reviewed the electronic medical records of patients with H1N1 influenza infection treated at Mayo Clinic in Rochester, MN, from May 1, 2009, through December 31, 2009. RESULTS: We identified 1053 patients with H1N1 influenza infection; this study consists of 66 hospitalized adults (6%). Patients' mean +/- SD age was 46.9+/-17.8 years. The 3 most common comorbidities were hypertension in 31 patients (47%), obesity in 29 (44%), and diabetes mellitus in 21 (32%). The most common symptoms were cough in 58 patients (88%), fever or chills in 55 (83%), and dyspnea in 47 (71%). Twenty-nine patients (44%) were admitted to the intensive care unit (ICU). Dyspnea and thrombocytopenia were more common in the ICU patients. The hospital, 28-day, and 90-day mortality rates were 8% (5/66), 11% (7/66), and 14% (9/66), respectively. Among the 29 ICU patients, 23 (79%) received mechanical ventilation, and 16 (55%) developed acute lung injury or acute respiratory distress syndrome. Rescue therapy for refractory respiratory failure was provided for 6 patients (21%). Of the 29 ICU patients, 10 (34%) required vasopressor support, and 4 (14%) required acute renal replacement therapy. CONCLUSION: Hospitalized adults with H1N1 influenza infection are relatively young, and a significant number require treatment in the ICU. Among the patients who require ICU admission, most develop acute lung injury or acute respiratory distress syndrome and require mechanical ventilator support.
Project description: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.
Project description:Data from prospectively planned cohort studies on risk of major clinical outcomes and prognostic factors for patients with influenza A(H1N1)pdm09 virus are limited. In 2009, in order to assess outcomes and evaluate risk factors for progression of illness, two cohort studies were initiated: FLU 002 in outpatients and FLU 003 in hospitalized patients.Between October 2009 and December 2012, adults with influenza-like illness (ILI) were enrolled; outpatients were followed for 14 days and inpatients for 60 days. Disease progression was defined as hospitalization and/or death for outpatients, and hospitalization for >28 days, transfer to intensive care unit (ICU) if enrolled from general ward, and/or death for inpatients. Infection was confirmed by RT-PCR. 590 FLU 002 and 392 FLU 003 patients with influenza A (H1N1)pdm09 were enrolled from 81 sites in 17 countries at 2 days (IQR 1-3) and 6 days (IQR 4-10) following ILI onset, respectively. Disease progression was experienced by 29 (1 death) outpatients (5.1%; 95% CI: 3.4-7.2%) and 80 inpatients [death (32), hospitalization >28 days (43) or ICU transfer (20)] (21.6%; 95% CI: 17.5-26.2%). Disease progression (death) for hospitalized patients was 53.1% (26.6%) and 12.8% (3.8%), respectively, for those enrolled in the ICU and general ward. In pooled analyses for both studies, predictors of disease progression were age, longer duration of symptoms at enrollment and immunosuppression. Patients hospitalized during the pandemic period had a poorer prognosis than in subsequent seasons.Patients with influenza A(H1N1)pdm09, particularly when requiring hospital admission, are at high risk for disease progression, especially if they are older, immunodeficient, or admitted late in infection. These data reinforce the need for international trials of novel treatment strategies for influenza infection and serve as a reminder of the need to monitor the severity of seasonal and pandemic influenza epidemics globally.ClinicalTrials.gov Identifiers: FLU 002--NCT01056354, FLU 003--NCT01056185.
Project description:Background:Outcome data from prospective follow-up studies comparing infections with different influenza virus types/subtypes are limited. Methods:Demographic, clinical characteristics and follow-up outcomes for adults with laboratory-confirmed influenza A(H1N1)pdm09, A(H3N2), or B virus infections were compared in 2 prospective cohorts enrolled globally from 2009 through 2015. Logistic regression was used to compare outcomes among influenza virus type/subtypes. Results:Of 3952 outpatients, 1290 (32.6%) had A(H1N1)pdm09 virus infection, 1857 (47.0%) had A(H3N2), and 805 (20.4%) had influenza B. Of 1398 inpatients, 641 (45.8%) had A(H1N1)pdm09, 532 (38.1%) had A(H3N2), and 225 (16.1%) had influenza B. Outpatients with A(H1N1)pdm09 were younger with fewer comorbidities and were more likely to be hospitalized during the 14-day follow-up (3.3%) than influenza B (2.2%) or A(H3N2) (0.7%; P < .0001). Hospitalized patients with A(H1N1)pdm09 (20.3%) were more likely to be enrolled from intensive care units (ICUs) than those with A(H3N2) (11.3%) or B (9.8%; P < .0001). However, 60-day follow-up of discharged inpatients showed no difference in disease progression (P = .32) or all-cause mortality (P = .30) among influenza types/subtypes. These findings were consistent after covariate adjustment, in sensitivity analyses, and for subgroups defined by age, enrollment location, and comorbidities. Conclusions:Outpatients infected with influenza A(H1N1)pdm09 or influenza B were more likely to be hospitalized than those with A(H3N2). Hospitalized patients infected with A(H1N1)pdm09 were younger and more likely to have severe disease at study entry (measured by ICU enrollment), but did not have worse 60-day outcomes.
Project description: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.
Project description:The aim of this systematic review was to summarise the clinical and epidemiological features of the pandemic influenza A (H1N1) 2009. We did a systematic search of published literature reporting clinical features of laboratory-confirmed pandemic influenza A (H1N1) 2009 from 1 April 2009 to 31 January 2010. Forty-four articles met our inclusion criteria for the review. The calculated weighted mean age of confirmed cases was 18·1 years, with the median ranging from 12 to 44 years. Cough (84·9%), fever (84·7%), headache (66·5%), runny nose (60·1%) and muscle pain (58·1%) were the most common symptoms of confirmed cases. One or more pre-existing chronic medical conditions were found in 18·4% of cases. Almost two-thirds (64%) of cases were aged between 10 and 29 years, 5·1% were aged over 50 years and only 1·1% were aged over 60 years. The confirmed case fatality ratio was 2·9% (95% CI 0·0-6·7%), an extracted average from 12 of 42 studies reporting fatal cases (937 fatal cases among 31,980 confirmed cases), which gives an overall estimated infected case fatality ratio of 0·02%. Early in the pandemic, disease occurred overwhelmingly in children and younger adults, with cough and fever as the most prevalent clinical symptoms of the confirmed cases. A high infection rate in children and young adults, with sparing of the elderly population, has implications for pandemic influenza management and control policies.
Project description:Indoleamine-2,3-dioxygenase (IDO) mediated tryptophan (TRP) depletion has antimicrobial and immuno-regulatory effects. Increased kynurenine (KYN)-to-TRP (KT) ratios, reflecting increased IDO activity, have been associated with poorer outcomes from several infections.We performed a case-control (1:2; age and sex matched) analysis of adults hospitalized with influenza A(H1N1)pdm09 with protocol-defined disease progression (died/transferred to ICU/mechanical ventilation) after enrollment (cases) or survived without progression (controls) over 60 days of follow-up. Conditional logistic regression was used to analyze the relationship between baseline KT ratio and other metabolites and disease progression.We included 32 cases and 64 controls with a median age of 52 years; 41% were female, and the median durations of influenza symptoms prior to hospitalization were 8 and 6 days for cases and controls, respectively (P = .04). Median baseline KT ratios were 2-fold higher in cases (0.24 mM/M; IQR, 0.13-0.40) than controls (0.12; IQR, 0.09-0.17; P ? .001). When divided into tertiles, 59% of cases vs 20% of controls had KT ratios in the highest tertile (0.21-0.84 mM/M). When adjusted for symptom duration, the odds ratio for disease progression for those in the highest vs lowest tertiles of KT ratio was 9.94 (95% CI, 2.25-43.90).High KT ratio was associated with poor outcome in adults hospitalized with influenza A(H1N1)pdm09. The clinical utility of this biomarker in this setting merits further exploration.NCT01056185.
Project description:OBJECTIVE: We sought to determine the range and extent of neurologic complications due to pandemic influenza A (H1N1) 2009 infection (pH1N1'09) in children hospitalized with influenza. METHODS: Active hospital-based surveillance in 6 Australian tertiary pediatric referral centers between June 1 and September 30, 2009, for children aged <15 years with laboratory-confirmed pH1N1'09. RESULTS: A total of 506 children with pH1N1'09 were hospitalized, of whom 49 (9.7%) had neurologic complications; median age 4.8 years (range 0.5-12.6 years) compared with 3.7 years (0.01-14.9 years) in those without complications. Approximately one-half (55.1%) of the children with neurologic complications had preexisting medical conditions, and 42.8% had preexisting neurologic conditions. On presentation, only 36.7% had the triad of cough, fever, and coryza/runny nose, whereas 38.7% had only 1 or no respiratory symptoms. Seizure was the most common neurologic complication (7.5%). Others included encephalitis/encephalopathy (1.4%), confusion/disorientation (1.0%), loss of consciousness (1.0%), and paralysis/Guillain-Barré syndrome (0.4%). A total of 30.6% needed intensive care unit (ICU) admission, 24.5% required mechanical ventilation, and 2 (4.1%) died. The mean length of stay in hospital was 6.5 days (median 3 days) and mean ICU stay was 4.4 days (median 1.5 days). CONCLUSIONS: Neurologic complications are relatively common among children admitted with influenza, and can be life-threatening. The lack of specific treatment for influenza-related neurologic complications underlines the importance of early diagnosis, use of antivirals, and universal influenza vaccination in children. Clinicians should consider influenza in children with neurologic symptoms even with a paucity of respiratory symptoms.
Project description:This case-control study was carried out to estimate risk factors associated with hospitalizations and severe outcomes [intensive care unit (ICU) admission or death] among patients with illness because of laboratory-confirmed 2009 pandemic A/H1N1 virus (pH1N1) during the first wave of pH1N1 activity in the province of Quebec, Canada.We collected epidemiologic information by phone using a standardized questionnaire from patients with laboratory-confirmed pH1N1 illness during the first spring/summer pandemic wave in Quebec, Canada. Risk factors associated with hospitalization were assessed by comparing hospitalized to community cases and for ICU admission or death through comparison with hospitalized cases.Cases (321 hospitalized patients including 47 ICU admissions and 15 deaths) were compared to controls (395 non-hospitalized patients) by using multivariable logistic regression adjusted for gender, age, education, being a health care worker, smoking, seasonal influenza vaccination, delay to consultation, antiviral use before admission, pregnancy, underlying medical conditions, and obesity. Age <5 years, underlying medical conditions (neuromuscular, cardiac, pulmonary, and renal conditions, diabetes, asthma, and other), and delayed consultation were associated with hospitalization. The strongest association with hospitalization was observed for neuromuscular disorders. Antiviral medication before hospital admission protected against severe disease. Association of obesity with hospitalization was not significant after adjustment in multivariable analysis. Among hospitalized patients, age ≥60 years and immune suppression were associated with death.Previously identified risk factors for seasonal influenza were also associated with increased risk of severe pH1N1 outcomes. The independent role of obesity needs to be further defined.