Predictors of Severity of Influenza-Related Hospitalizations: Results From the Global Influenza Hospital Surveillance Network (GIHSN).

BACKGROUND: The Global Influenza Hospital Surveillance Network (GIHSN) has since 2012 provided patient-level data on severe influenza-like-illnesses from >100 participating clinical sites worldwide based on a core protocol and consistent case definitions. METHODS: We used multivariable logistic regression to assess the risk of intensive care unit admission, mechanical ventilation, and in-hospital death among hospitalized patients with influenza and explored the role of patient-level covariates and country income level. RESULTS: The data set included 73 121 patients hospitalized with respiratory illness in 22 countries, including 15 660 with laboratory-confirmed influenza. After adjusting for patient-level covariates we found a 7-fold increase in the risk of influenza-related intensive care unit admission in lower middle-income countries (LMICs), compared with high-income countries (P = .01). The risk of mechanical ventilation and in-hospital death also increased by 4-fold in LMICs, though these differences were not statistically significant. We also find that influenza mortality increased significantly with older age and number of comorbid conditions. Across all severity outcomes studied and after controlling for patient characteristics, infection with influenza A/H1N1pdm09 was more severe than with A/H3N2. CONCLUSIONS: Our study provides new information on influenza severity in underresourced populations, particularly those in LMICs.

The Use of Death Certificate Data to Characterize Mortality Associated With Respiratory Syncytial Virus, Unspecified Bronchiolitis, and Influenza in the United States, 1999-2018.

BACKGROUND: Death certificate data can improve our understanding of the mortality burden associated with respiratory syncytial virus (RSV) and influenza. METHODS: We used International Classification of Diseases, Tenth Revision codes listed on death certificates to characterize deaths from 1999 to 2018 as RSV, influenza, and unspecified bronchiolitis. We described the distribution of each cause of death by age, sex, race/ethnicity, place of death, and contributing causes of death. RESULTS: Over the 20-year study period, RSV, bronchiolitis, and influenza were listed as the underlying causes of death on 932, 1046, and 52 293 death certificates, respectively. Children <1 year of age accounted for 39% of RSV and bronchiolitis deaths, while 72% of influenza deaths were in adults ≥65 years. Children <1 year were more likely to die outside of the hospital from RSV, bronchiolitis, or influenza compared to all causes (P < .01), and black infants had the highest mortality rate for all 3 causes. Most infants dying from RSV did not have a high-risk condition listed on the death certificate. Death certificates captured 20%-60% of estimated excess RSV-attributable mortality in infants and <1% in seniors. CONCLUSIONS: Thorough reporting on death certificates is an important public health goal, especially as new therapeutics become available. Infants had higher odds of dying out of hospital from respiratory pathogens compared to other causes, and race/ethnicity alone did not explain this disparity.

Examining the relationships between early childhood experiences and adolescent and young adult health status in a resource-limited population: A cohort study.

BACKGROUND: Adolescence is a critical point in the realization of human capital, as health and educational decisions with long-term impacts are made. We examined the role of early childhood experiences on health, cognitive abilities, and educational outcomes of adolescents followed up from a longitudinal cohort study in Pakistan, hypothesizing that early childhood experiences reflecting poverty would manifest in reduced health and development in adolescence. METHODS AND FINDINGS: Adolescents/young adults previously followed as children aged under 5 years were interviewed. Childhood data were available on diarrhea, pneumonia, and parental/household characteristics. New data were collected on health, anthropometry, education, employment, and languages spoken; nonverbal reasoning was assessed. A multivariable Bayesian network was constructed to explore structural relationships between variables. Of 1,868 children originally enrolled, 1,463 (78.3%) were interviewed as adolescents (range 16.0-29.3 years, mean age 22.6 years); 945 (65%) lived in Oshikhandass. While 1,031 (70.5%) of their mothers and 440 (30.1%) of their fathers had received no formal education, adolescents reported a mean of 11.1 years of education. Childhood diarrhea (calculated as episodes/child-year) had no association with nonverbal reasoning score (an arc was supported in just 4.6% of bootstrap samples), health measures (with BMI, 1% of bootstrap samples; systolic and diastolic blood pressure, 0.1% and 1.6% of bootstrap samples, respectively), education (0.7% of bootstrap samples), or employment (0% of bootstrap samples). Relationships were found between nonverbal reasoning and adolescent height (arc supported in 63% of bootstrap samples), age (84%), educational attainment (100%), and speaking English (100%); speaking English was linked to the childhood home environment, mediated through maternal education and primary language. Speaking English (n = 390, 26.7% of adolescents) was associated with education (100% of bootstrap samples), self-reported child health (82%), current location (85%) and variables describing childhood socioeconomic status. The main limitations of this study were the lack of parental data to characterize the home setting (including parental mental and physical health, and female empowerment) and reliance on self-reporting of health status. CONCLUSIONS: In this population, investments in education, especially for females, are associated with an increase in human capital. Against the backdrop of substantial societal change, with the exception of a small and indirect association between childhood malnutrition and cognitive scores, educational opportunities and cultural language groups have stronger associations with aspects of human capital than childhood morbidity.

Impacts of human mobility on the citywide transmission dynamics of 18 respiratory viruses in pre- and post-COVID-19 pandemic years.

Many studies have used mobile device location data to model SARS-CoV-2 dynamics, yet relationships between mobility behavior and endemic respiratory pathogens are less understood. We studied the effects of population mobility on the transmission of 17 endemic viruses and SARS-CoV-2 in Seattle over a 4-year period, 2018-2022. Before 2020, visits to schools and daycares, within-city mixing, and visitor inflow preceded or coincided with seasonal outbreaks of endemic viruses. Pathogen circulation dropped substantially after the initiation of COVID-19 stay-at-home orders in March 2020. During this period, mobility was a positive, leading indicator of transmission of all endemic viruses and lagging and negatively correlated with SARS-CoV-2 activity. Mobility was briefly predictive of SARS-CoV-2 transmission when restrictions relaxed but associations weakened in subsequent waves. The rebound of endemic viruses was heterogeneously timed but exhibited stronger, longer-lasting relationships with mobility than SARS-CoV-2. Overall, mobility is most predictive of respiratory virus transmission during periods of dramatic behavioral change and at the beginning of epidemic waves.

Mortality Associated With Influenza and Respiratory Syncytial Virus in the US, 1999-2018.

IMPORTANCE: Respiratory syncytial virus (RSV) mortality estimates have not been updated since 2009, and no study has assessed changes in influenza mortality after the 2009 pandemic. Updated burden estimates are needed to characterize long-term changes in the epidemiology of these viruses. OBJECTIVE: To evaluate excess mortality from RSV and influenza in the US from 1999 to 2018. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used data from 50.3 million US death certificates from 1999 to 2018 to create age-specific linear regression models and assess weekly mortality fluctuations above a seasonal baseline associated with RSV and influenza. Statistical analysis was performed for 1043 weeks from January 3, 1999, to December 29, 2018. MAIN OUTCOMES AND MEASURES: Excess mortality associated with RSV and influenza estimated from the difference between observed and expected underlying respiratory mortality each season. RESULTS: There were 50.3 million death certificates (50.1% women and 49.9% men; mean [SD] age at death, 72.7 [18.6] years) included in this analysis, 1.0% for children younger than 1 year and 73.4% for adults aged 65 years or older. A mean of 6549 (95% CI, 6140-6958) underlying respiratory deaths were associated with RSV annually, including 96 (95% CI, 92-99) deaths among children younger than 1 year. For influenza, there were 10 171 (95% CI, 9652-10 691) underlying respiratory deaths per year, with 23 deaths (95% CI, 19-27) among children younger than 1 year. The highest mean mortality rate per 100 000 population for both viruses was among adults aged 65 years or older at 14.7 (95% CI, 13.8-15.5) for RSV and 20.5 (95% CI, 19.4-21.5) for influenza. A lower proportion of influenza deaths occurred among those aged 65 years or older compared with earlier estimates (75.1% [95% CI, 67.4%-82.8%]). Influenza mortality was highest among those aged 65 years or older in seasons when A/H3N2 predominated (18 739 [95% CI, 16 616-21 336] deaths in 2017-2018) and among those aged 5 to 49 years when A/H1N1pdm2009 predominated (1683 [95% CI, 1583-1787] deaths in 2013-2014). Results were sensitive to the choice of mortality outcome and method, with the broadest outcome associated with annual means of 23 352 (95% CI, 21 814-24 891) excess deaths for RSV and 27 171 (95% CI, 25 142-29 199) for influenza. CONCLUSIONS AND RELEVANCE: This study suggests that RSV poses a greater risk than influenza to infants, while both are associated with substantial mortality among elderly individuals. Influenza has large interannual variability, affecting different age groups depending on the circulating virus. The emergence of the influenza A/H1N1pdm2009 pandemic virus in 2009 shifted mortality toward middle-aged adults, a trend still observed to date. This study's estimates provide a benchmark to evaluate the mortality benefits associated with interventions against respiratory viruses, including new or improved immunization strategies.

Determinants of vaccine coverage and timeliness in a northern Pakistani village.

The incidence of vaccine preventable disease in Pakistan remains high despite a long-standing Expanded Program on Immunization (EPI). We describe vaccine completeness, timeliness and determinants of coverage from a remote rural cohort (2012-2014). Vaccination histories were taken from EPI records. Vaccination was complete if all doses were received according to the EPI schedule and timely if doses were not ≥3 days early or ≥ 28 days late. Three models are presented: a multivariable logistic regression of household demographic and socioeconomic factors associated with complete vaccination, a multivariable mixed effects logistic regression assessing whether or not the vaccine was administered late (versus on-time), and a mixed effects multivariable Poisson regression model analysing the interval (in days) between vaccine doses. Of 959 enrolled children with full vaccination histories, 88.2 and 65.1% were fully vaccinated following either the pentavalent or DPT/HBV schedules if measles was excluded; coverage dropped to 50.0 and 27.1% when both doses of measles were included. Sixty-four (6.7%) were unvaccinated. Coverage and timeliness declined with subsequent doses. Migrating into the village after 1995 (95%CI 1.88 to 5.17) was associated with late vaccination. Being male, having an older father, and having parents with at least some formal education reduced the likelihood of a late dose. The interval between doses was consistent at 5 weeks (compared with the 4 weeks recommended by EPI). None of the socio-demographic variables were related to the likelihood of receiving full coverage. Vaccine coverage in Oshikhandass was higher than national averages. Measles vaccine coverage and timeliness were low; special consideration should be paid to this vaccine. The local vaccination schedule differed from the EPI, but the consistency suggests good local administration.