Surveillance for laboratory-confirmed influenza-associated pediatric deaths since 2004 has shown that most deaths occur in unvaccinated children. We assessed whether influenza vaccination reduced the ...risk of influenza-associated death in children and adolescents.
We conducted a case-cohort analysis comparing vaccination uptake among laboratory-confirmed influenza-associated pediatric deaths with estimated vaccination coverage among pediatric cohorts in the United States. Case vaccination and high-risk status were determined by case investigation. Influenza vaccination coverage estimates were obtained from national survey data or a national insurance claims database. We estimated odds ratios from logistic regression comparing odds of vaccination among cases with odds of vaccination in comparison cohorts. We used Bayesian methods to compute 95% credible intervals (CIs) for vaccine effectiveness (VE), calculated as (1 - odds ratio) × 100.
From July 2010 through June 2014, 358 laboratory-confirmed influenza-associated pediatric deaths were reported among children aged 6 months through 17 years. Vaccination status was determined for 291 deaths; 75 (26%) received vaccine before illness onset. Average vaccination coverage in survey cohorts was 48%. Overall VE against death was 65% (95% CI, 54% to 74%). Among 153 deaths in children with underlying high-risk medical conditions, 47 (31%) were vaccinated. VE among children with high-risk conditions was 51% (95% CI, 31% to 67%), compared with 65% (95% CI, 47% to 78%) among children without high-risk conditions.
Influenza vaccination was associated with reduced risk of laboratory-confirmed influenza-associated pediatric death. Increasing influenza vaccination could prevent influenza-associated deaths among children and adolescents.
Infection with influenza viruses, including seasonal, avian and pandemic viruses, remains a worldwide public health problem. Although influenza virus infection is both vaccine preventable and drug ...treatable, high rates of mutation and reassortment of viruses can result in reduced effectiveness of vaccines or drugs. Currently, two classes of drugs, adamantanes (M2 blockers) and neuraminidase (NA) inhibitors (NAIs), are available for treatment and chemoprophylaxis of influenza infections. Given these limited antiviral therapy options, resistance to anti-influenza drugs is a constant concern. The emergence and global spread of adamantane-resistant H3N2 viruses in 2003-2004 and oseltamivir-resistant seasonal H1N1 viruses in 2007-2009 demonstrated the ability of drug-resistant variants to rapidly become predominant worldwide. Since the 2009 H1N1 pandemic, all influenza viruses circulating in humans are M2-blocker-resistant and, in general, NAI-susceptible. However, pandemic H1N1 viruses with resistance to the NAI oseltamivir have been reported. 'Permissive' drift mutations and reassortment of viral gene segments have been proposed as mechanisms underlying the retained replicative fitness of resistant viruses. Nevertheless, the precise role of these genetic changes in the efficient transmission and maintenance of resistant viruses in the absence of drug pressure remains poorly understood. In this review, we summarize NAI resistance in influenza viruses and discuss recent challenges in laboratory testing methods. Close monitoring of antiviral resistance among all influenza viruses, both locally and globally, are essential to inform public health strategies for the control of influenza infections.
The anti-influenza therapeutic baloxavir targets cap-dependent endonuclease activity of polymerase acidic (PA) protein. We monitored baloxavir susceptibility in the United States with next generation ...sequencing analysis supplemented by phenotypic one-cycle infection assay. Analysis of PA sequences of 6,891 influenza A and B viruses collected during 2016/17 and 2017/18 seasons showed amino acid substitutions: I38L (two A(H1N1)pdm09 viruses), E23G (two A(H1N1)pdm09 viruses) and I38M (one A(H3N2) virus); conferring 4-10-fold reduced susceptibility to baloxavir.
CONTEXT Early data on pandemic 2009 influenza A(H1N1) suggest pregnant women are at increased risk of hospitalization and death. OBJECTIVE To describe the severity of 2009 influenza A(H1N1) illness ...and the association with early antiviral treatment among pregnant women in the United States. DESIGN, SETTING, AND PATIENTS Surveillance of 2009 influenza A(H1N1) in pregnant women reported to the Centers for Disease Control and Prevention (CDC) with symptom onset from April through December 2009. MAIN OUTCOME MEASURES Severity of illness (hospitalizations, intensive care unit ICU admissions, and deaths) due to 2009 influenza A(H1N1) among pregnant women, stratified by timing of antiviral treatment and pregnancy trimester at symptom onset. RESULTS We received reports on 788 pregnant women in the United States with 2009 influenza A(H1N1) with symptom onset from April through August 2009. Among those, 30 died (5% of all reported 2009 influenza AH1N1 influenza deaths in this period). Among 509 hospitalized women, 115 (22.6%) were admitted to an ICU. Pregnant women with treatment more than 4 days after symptom onset were more likely to be admitted to an ICU (56.9% vs 9.4%; relative risk RR, 6.0; 95% confidence interval CI, 3.5-10.6) than those treated within 2 days after symptom onset. Only 1 death occurred in a patient who received treatment within 2 days of symptom onset. Updating these data with the CDC's continued surveillance of ICU admissions and deaths among pregnant women with symptom onset through December 31, 2009, identified an additional 165 women for a total of 280 women who were admitted to ICUs, 56 of whom died. Among the deaths, 4 occurred in the first trimester (7.1%), 15 in the second (26.8%), and 36 in the third (64.3%); CONCLUSIONS Pregnant women had a disproportionately high risk of mortality due to 2009 influenza A(H1N1). Among pregnant women with 2009 influenza A(H1N1) influenza reported to the CDC, early antiviral treatment appeared to be associated with fewer admissions to an ICU and fewer deaths.
Abstract
Background
Vaccination is the best way to prevent influenza; however, greater benefits could be achieved. To help guide research and policy agendas, we aimed to quantify the magnitude of ...influenza disease that would be prevented through targeted increases in vaccine effectiveness (VE) or vaccine coverage (VC).
Methods
For 3 influenza seasons (2011–12, 2015–16, and 2017–18), we used a mathematical model to estimate the number of prevented influenza-associated illnesses, medically attended illnesses, and hospitalizations across 5 age groups. Compared with estimates of prevented illness during each season, given observed VE and VC, we explored the number of additional outcomes that would have been prevented from a 5% absolute increase in VE or VC or from achieving 60% VE or 70% VC.
Results
During the 2017–18 season, compared with the burden already prevented by influenza vaccination, a 5% absolute VE increase would have prevented an additional 1 050 000 illnesses and 25 000 hospitalizations (76% among those aged ≥65 years), while achieving 60% VE would have prevented an additional 190 000 hospitalizations. A 5% VC increase would have resulted in 785 000 fewer illnesses (56% among those aged 18–64 years) and 11 000 fewer hospitalizations; reaching 70% would have prevented an additional 39 000 hospitalizations.
Conclusions
Small, attainable improvements in effectiveness or VC of the influenza vaccine could lead to substantial additional reductions in the influenza burden in the United States. Improvements in VE would have the greatest impact in reducing hospitalizations in adults aged ≥65 years, and VC improvements would have the largest benefit in reducing illnesses in adults aged 18–49 years.
Mathematical modeling demonstrated how increases in influenza vaccine effectiveness or coverage during influenza seasons of varying severity would result in substantial reductions to influenza-associated illnesses, medically attended illnesses, and hospitalizations in the United States.
Better understanding the etiology-specific incidence of severe acute respiratory infections (SARIs) in resource-poor, rural settings will help further develop and prioritize prevention strategies. To ...address this gap in knowledge, we conducted a longitudinal study to estimate the incidence of SARIs among children in rural Bangladesh.
During June through October 2010, we followed children aged <5 years in 67 villages to identify those with cough, difficulty breathing, age-specific tachypnea and/or danger signs in the community or admitted to the local hospital. A study physician collected clinical information and obtained nasopharyngeal swabs from all SARI cases and blood for bacterial culture from those hospitalized. We tested swabs for respiratory syncytial virus (RSV), influenza viruses, human metapneumoviruses, adenoviruses and human parainfluenza viruses 1-3 (HPIV) by real-time reverse transcription polymerase chain reaction. We calculated virus-specific SARI incidence by dividing the number of new illnesses by the person-time each child contributed to the study.
We followed 12,850 children for 279,029 person-weeks (pw) and identified 141 SARI cases; 76 (54%) at their homes and 65 (46%) at the hospital. RSV was associated with 7.9 SARI hospitalizations per 100,000 pw, HPIV3 2.2 hospitalizations/100,000 pw, and influenza 1.1 hospitalizations/100,000 pw. Among non-hospitalized SARI cases, RSV was associated with 10.8 illnesses/100,000 pw, HPIV3 1.8/100,000 pw, influenza 1.4/100,000 pw, and adenoviruses 0.4/100,000 pw.
Respiratory viruses, particularly RSV, were commonly associated with SARI among children. It may be useful to explore the value of investing in prevention strategies, such as handwashing and respiratory hygiene, to reduce respiratory infections among young children in such settings.
In an outbreak of Covid-19 at a summer camp, 224 confirmed cases in children and adolescents 7 to 19 years of age were identified. After the campers returned home, transmission of SARS-CoV-2 occurred ...in 35 of 194 households (18%), with a secondary attack rate of 45% among household members.
The epidemiology of pneumonia has likely evolved in recent years, reflecting an aging population, changes in population immunity, and socioeconomic disparities.
Using the National (Nationwide) ...Inpatient Sample, estimated numbers and rates of pneumonia-associated hospitalizations for 2001-2014 were calculated. A pneumonia-associated hospitalization was defined as one in which the discharge record listed a principal diagnosis of pneumonia or a secondary diagnosis of pneumonia if the principal diagnosis was respiratory failure or sepsis.
There were an estimated 20,361,181 (SE, 95,601) pneumonia-associated hospitalizations in the United States during 2001-2014 (average annual age-adjusted pneumonia-associated hospitalization rate of 464.8 per 100,000 population 95% CI, 462.5-467.1). The average annual age-adjusted pneumonia-associated hospitalization rate decreased over the study period (P < .0001). In-hospital death occurred in 7.4% (SE, 0.03) of pneumonia-associated hospitalizations. Non-Hispanic American Indian/Alaskan Natives and non-Hispanic blacks had the highest average annual age-adjusted rates of pneumonia-associated hospitalization of all race/ethnicities at 439.2 (95% CI, 415.9-462.5) and 438.6 (95% CI, 432.5-444.7) per 100,000 population, respectively. During 2001-2014, the proportion of pneumonia-associated hospitalizations colisting an immunocompromising condition increased from 18.7% (SE, 0.2) in 2001 to 29.9% (SE, 0.2) in 2014. Total charges for pneumonia-associated hospitalizations in 2014 were over $84 billion.
Pneumonia is a major cause of morbidity and mortality in the United States. Differences in rates and outcomes of pneumonia-associated hospitalizations between sociodemographic groups warrant further investigation. The immunocompromised population has emerged as a group experiencing a disproportionate burden of pneumonia-associated hospitalizations.
To assess the stability of improvements in global respiratory virus surveillance in countries supported by the United States Centers for Disease Control and Prevention (CDC) after reductions in CDC ...funding and with the stress of the coronavirus disease 2019 (COVID-19) pandemic.
We assessed whether national influenza surveillance systems of CDC-funded countries: (i) continued to analyse as many specimens between 2013 and 2021; (ii) participated in activities of the World Health Organization's (WHO) Global Influenza Surveillance and Response System; (iii) tested enough specimens to detect rare events or signals of unusual activity; and (iv) demonstrated stability before and during the COVID-19 pandemic. We used CDC budget records and data from the WHO Global Influenza Surveillance and Response System.
While CDC reduced per-country influenza funding by about 75% over 10 years, the number of specimens tested annually remained stable (mean 2261). Reporting varied substantially by country and transmission zone. Countries funded by CDC accounted for 71% (range 61-75%) of specimens included in WHO consultations on the composition of influenza virus vaccines. In 2019, only eight of the 17 transmission zones sent enough specimens to WHO collaborating centres before the vaccine composition meeting to reliably identify antigenic variants.
Great progress has been made in the global understanding of influenza trends and seasonality. To optimize surveillance to identify atypical influenza viruses, and to integrate molecular testing, sequencing and reporting of severe acute respiratory syndrome coronavirus 2 into existing systems, funding must continue to support these efforts.
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