Risk Analysis of Respiratory Syncytial Virus Among Infants in the United States by Birth Month.

BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of morbidity and mortality among U.S. infants. A child's calendar birth month determines their age at first exposure(s) to RSV. We estimated birth month-specific risk of medically attended (MA) RSV lower respiratory tract infection (LRTI) among infants during their first RSV season and first year of life. METHODS: We analyzed infants born in the USA between July 2016 and February 2020 using three insurance claims databases (two commercial, one Medicaid). We classified infants' first MA RSV LRTI episode by highest level of care incurred (outpatient, emergency department, or inpatient), employing specific and sensitive diagnostic coding algorithms to define index RSV diagnoses. In our main analysis we focused on infants' first RSV season. In our secondary analysis we compared the risk of MA RSV LRTI during infants' first RSV season to that of their first year of life. RESULTS: Infants born from May through September generally had the highest risk of first-season MA RSV LRTI-approximately 6%-10% under the specific RSV index diagnosis definition and 16%-26% under the sensitive. Infants born between October and December had the highest risk of RSV-related hospitalization during their first season. The proportion of MA RSV LRTI events classified as inpatient ranged from 9%-54% (specific) and 5%-33% (sensitive) across birth month and comorbidity group. Through the first year of life, the overall risk of MA RSV LRTI is comparable across birth months within each claims database (6%-11% under the specific definition, 17%-30% under the sensitive), with additional cases progressing to care at outpatient or ED settings. CONCLUSIONS: Our data support recent national recommendations for the use of nirsevimab in the USA. For infants born at the tail end of an RSV season who do not receive nirsevimab, a dose administered prior to the onset of their second RSV season could reduce the incidence of outpatient and ED-related events.

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.

Comparing performance of year-round and campaign-mode influenza vaccination strategies among children aged 6-23 months in Kenya: 2019-2021.

INTRODUCTION: In 2016, the Kenya National Immunization Technical Advisory Group requested additional programmatic and cost effectiveness data to inform the choice of strategy for a national influenza vaccination program among children aged 6-23 months of age. In response, we conducted an influenza vaccine demonstration project to compare the performance of a year-round versus campaign-mode vaccination strategy. Findings from this demonstration project will help identify essential learning lessons for a national program. METHODS: We compared two vaccine delivery strategies: (i) a year-round vaccination strategy where influenza vaccines were administered throughout the year at health facilities. This strategy was implemented in Njoro sub-county in Nakuru (November 2019 to October 2021) and Jomvu sub-county in Mombasa (December 2019 to October 2021), (ii) a campaign-mode vaccination strategy where vaccines were available at health facilities over four months. This strategy was implemented in Nakuru North sub-county in Nakuru (June to September 2021) and Likoni sub-county in Mombasa (July to October 2021). We assessed differences in coverage, dropout rates, vaccine wastage, and operational needs. RESULTS: We observed similar performance between strategies in coverage of the first dose of influenza vaccine (year-round strategy 59.7 %, campaign strategy 63.2 %). The coverage obtained in the year-round sub-counties was similar (Njoro 57.4 %; Jomvu 63.1 %); however, more marked differences between campaign sub-counties were observed (Nakuru North 73.4 %; Likoni 55.2 %). The campaign-mode strategy exceeded the cold chain capacity of participating health facilities, requiring thrice monthly instead of once monthly deliveries, and was associated with a two-fold increase in workload compared to the year-round strategy (168 vaccines administered per day in the campaign strategy versus 83 vaccines administered per day in the year-round strategy). CONCLUSION: Although both strategies had similar coverage levels, the campaign-mode strategy was associated with considerable operational needs that could significantly impact the immunization program.

Genetic and potential antigenic evolution of influenza A(H1N1)pdm09 viruses circulating in Kenya during 2009-2018 influenza seasons.

Influenza viruses undergo rapid evolutionary changes, which requires continuous surveillance to monitor for genetic and potential antigenic changes in circulating viruses that can guide control and prevention decision making. We sequenced and phylogenetically analyzed A(H1N1)pdm09 virus genome sequences obtained from specimens collected from hospitalized patients of all ages with or without pneumonia between 2009 and 2018 from seven sentinel surveillance sites across Kenya. We compared these sequences with recommended vaccine strains during the study period to infer genetic and potential antigenic changes in circulating viruses and associations of clinical outcome. We generated and analyzed a total of 383 A(H1N1)pdm09 virus genome sequences. Phylogenetic analyses of HA protein revealed that multiple genetic groups (clades, subclades, and subgroups) of A(H1N1)pdm09 virus circulated in Kenya over the study period; these evolved away from their vaccine strain, forming clades 7 and 6, subclades 6C, 6B, and 6B.1, and subgroups 6B.1A and 6B.1A1 through acquisition of additional substitutions. Several amino acid substitutions among circulating viruses were associated with continued evolution of the viruses, especially in antigenic epitopes and receptor binding sites (RBS) of circulating viruses. Disease severity declined with an increase in age among children aged < 5 years. Our study highlights the necessity of timely genomic surveillance to monitor the evolutionary changes of influenza viruses. Routine influenza surveillance with broad geographic representation and whole genome sequencing capacity to inform on prioritization of antigenic analysis and the severity of circulating strains are critical to improved selection of influenza strains for inclusion in vaccines.

Correcting for measurement error in assessing gestational age in a low-resource setting: a regression calibration approach.

Introduction: Measurement error in gestational age (GA) may bias the association of GA with a health outcome. Ultrasound-based GA is considered the gold standard and is not readily available in low-resource settings. We corrected for measurement error in GA based on fundal height (FH) and date of last menstrual period (LMP) using ultrasound from the sub-cohort and adjusted for the bias in associating GA with neonatal mortality and low birth weight (< 2,500 grams, LBW). Methods: We used data collected from 01/2015 to 09/2019 from pregnant women enrolled at two public hospitals in Siaya county, Kenya (N = 2,750). We used regression calibration to correct for measurement error in FH- and LMP-based GA accounting for maternal and child characteristics. We applied logistic regression to associate GA with neonatal mortality and low birth weight, with and without calibrating FH- and LMP-based GA. Results: Calibration improved the precision of LMP (correlation coefficient, ρ from 0.48 to 0.57) and FH-based GA (ρ from 0.82 to 0.83). Calibrating FH/LMP-based GA eliminated the bias in the mean GA estimates. The log odds ratio that quantifies the association of GA with neonatal mortality increased by 29% (from -0.159 to -0.205) by calibrating FH-based GA and by more than twofold (from -0.158 to -0.471) by calibrating LMP-based GA. Conclusion: Calibrating FH/LMP-based GA improved the accuracy and precision of GA estimates and strengthened the association of GA with neonatal mortality/LBW. When assessing GA, neonatal public health and clinical interventions may benefit from calibration modeling in settings where ultrasound may not be fully available.

Age Differences in Comorbidities, Presenting Symptoms, and Outcomes of Influenza Illness Requiring Hospitalization: A Worldwide Perspective From the Global Influenza Hospital Surveillance Network.

Background: The Global Influenza Hospital Surveillance Network (GIHSN) was established in 2012 to conduct coordinated worldwide influenza surveillance. In this study, we describe underlying comorbidities, symptoms, and outcomes in patients hospitalized with influenza. Methods: Between November 2018 and October 2019, GIHSN included 19 sites in 18 countries using a standardized surveillance protocol. Influenza infection was laboratory-confirmed with reverse-transcription polymerase chain reaction. A multivariate logistic regression model was utilized to analyze the extent to which various risk factors predict severe outcomes. Results: Of 16 022 enrolled patients, 21.9% had laboratory-confirmed influenza; 49.2% of influenza cases were A/H1N1pdm09. Fever and cough were the most common symptoms, although they decreased with age (P < .001). Shortness of breath was uncommon among those <50 years but increased with age (P < .001). Middle and older age and history of underlying diabetes or chronic obstructive pulmonary disease were associated with increased odds of death and intensive care unit (ICU) admission, and male sex and influenza vaccination were associated with lower odds. The ICU admissions and mortality occurred across the age spectrum. Conclusions: Both virus and host factors contributed to influenza burden. We identified age differences in comorbidities, presenting symptoms, and adverse clinical outcomes among those hospitalized with influenza and benefit from influenza vaccination in protecting against adverse clinical outcomes. The GIHSN provides an ongoing platform for global understanding of hospitalized influenza illness.

High-Dose Influenza Vaccine Is Associated With Reduced Mortality Among Older Adults With Breakthrough Influenza Even When There Is Poor Vaccine-Strain Match.

BACKGROUND: High-dose (HD) influenza vaccine offers improved protection from influenza virus infection among older adults compared with standard-dose (SD) vaccine. Here, we explored whether HD vaccine attenuates disease severity among older adults with breakthrough influenza. METHODS: This was a retrospective cohort study of US claims data for influenza seasons 2016-2017, 2017-2018, and 2018-2019, defined as 1 October through 30 April, among adults aged ≥65 years. After adjusting the different cohorts for the probability of vaccination conditional on patients' characteristics, we compared 30-day mortality rate post-influenza among older adults who experienced breakthrough infection after receipt of HD or SD influenza vaccines and among those not vaccinated (NV). RESULTS: We evaluated 44 456 influenza cases: 23 109 (52%) were unvaccinated, 15 037 (33.8%) received HD vaccine, and 6310 (14.2%) received SD vaccine. Significant reductions in mortality rates among breakthrough cases were observed across all 3 seasons for HD vs NV, ranging from 17% to 29% reductions. A significant mortality reduction of 25% was associated with SD vaccination vs NV in the 2016-2017 season when there was a good match between circulating influenza viruses and selected vaccine strains. When comparing HD vs SD cohorts, mortality reductions were higher among those who received HD in the last 2 seasons when mismatch between vaccine strains and circulating H3N2 viruses was documented, albeit not significant. CONCLUSIONS: HD vaccination was associated with lower post-influenza mortality among older adults with breakthrough influenza, even during seasons when antigenically drifted H3N2 circulated. Improved understanding of the impact of different vaccines on attenuating disease severity is warranted when assessing vaccine policy recommendations.

Healthcare-seeking behavior for respiratory illnesses in Kenya: implications for burden of disease estimation.

BACKGROUND: Understanding healthcare-seeking patterns for respiratory illness can help improve estimation of disease burden and target public health interventions to control acute respiratory disease in Kenya. METHODS: We conducted a cross-sectional survey to determine healthcare utilization patterns for acute respiratory illness (ARI) and severe pneumonia in four diverse counties representing urban, peri-urban, rural mixed farmers, and rural pastoralist communities in Kenya using a two-stage (sub-locations then households) cluster sampling procedure. Healthcare seeking behavior for ARI episodes in the last 14 days, and severe pneumonia in the last 12 months was evaluated. Severe pneumonia was defined as reported cough and difficulty breathing for > 2 days and report of hospitalization or recommendation for hospitalization, or a danger sign (unable to breastfeed/drink, vomiting everything, convulsions, unconscious) for children < 5 years, or report of inability to perform routine chores. RESULTS: From August through September 2018, we interviewed 28,072 individuals from 5,407 households. Of those surveyed, 9.2% (95% Confidence Interval [CI] 7.9-10.7) reported an episode of ARI, and 4.2% (95% CI 3.8-4.6) reported an episode of severe pneumonia. Of the reported ARI cases, 40.0% (95% CI 36.8-43.3) sought care at a health facility. Of the74.2% (95% CI 70.2-77.9) who reported severe pneumonia and visited a medical health facility, 28.9% (95% CI 25.6-32.6) were hospitalized and 7.0% (95% CI 5.4-9.1) were referred by a clinician to the hospital but not hospitalized. 21% (95% CI 18.2-23.6) of self-reported severe pneumonias were hospitalized. Children aged < 5 years and persons in households with a higher socio-economic status were more likely to seek care for respiratory illness at a health facility. CONCLUSION: Our findings suggest that hospital-based surveillance captures less than one quarter of severe pneumonia in the community. Multipliers from community household surveys can account for underutilization of healthcare resources and under-ascertainment of severe pneumonia at hospitals.

Global and national influenza-associated hospitalisation rates: Estimates for 40 countries and administrative regions.

Background: WHO estimates that seasonal influenza epidemics result in three to five million cases of severe illness (hospitalisations) every year. We aimed to improve the understanding of influenza-associated hospitalisation estimates at a national and global level. Methods: We performed a systematic literature review of English- and Chinese-language studies published between 1995 and 2020 estimating influenza-associated hospitalisation. We included a total of 127 studies (seven in Chinese) in the meta-analysis and analyzed their data using a logit-logistic regression model to understand the influence of five study factors and produce national and global estimates by age groups. The five study factors assessed were: 1) the method used to calculate the influenza-associated hospitalisation estimates (rate- or time series regression-based), 2) the outcome measure (divided into three envelopes: narrow, medium, or wide), 3) whether every case was laboratory-confirmed or not, 4) whether the estimates were national or sub-national, 5) whether the rates were based on a single year or multiple years. Results: The overall pooled influenza-associated hospitalisation rate was 40.5 (95% confidence interval (CI) = 24.3-67.4) per 100 000 persons, with rates varying substantially by age: 224.0 (95% CI = 118.8-420.0) in children aged 0-4 years and 96.8 (95% CI = 57.0-164.3) in the elderly aged >65 years. The overall pooled hospitalisation rates varied by calculation method; for all ages, the rates were significantly higher when they were based on rate-based methods or calculated on a single season and significantly lower when cases were laboratory-confirmed. The national hospitalisation rates (all ages) varied considerably, ranging from 11.7 (95% CI = 3.8-36.3) per 100 000 in New Zealand to 122.1 (95% CI = 41.5-358.4) per 100 000 in India (all age estimates). Conclusions: Using the pooled global influenza-associated hospitalisation rate, we estimate that seasonal influenza epidemics result in 3.2 million cases of severe illness (hospitalisations) per annum. More extensive analyses are required to assess the influence of other factors on the estimates (e.g. vaccination and dominant virus (sub)types) and efforts to harmonize the methods should be encouraged. Our study highlights the high rates of influenza-associated hospitalisations in children aged 0-4 years and the elderly aged 65+ years.

Global, regional and national estimates of influenza-attributable ischemic heart disease mortality.

Background: Influenza virus infection is associated with incident ischemic heart disease (IHD) events. Here, we estimate the global, regional, and national IHD mortality burden attributable to influenza. Methods: We used vital registration data from deaths in adults ≥50 years (13.2 million IHD deaths as underlying cause) to assess the relationship between influenza activity and IHD mortality in a non-linear meta-regression framework from 2010 to 2019. This derived relationship was then used to estimate the global influenza attributable IHD mortality. We estimated the population attributable fraction (PAF) of influenza for IHD deaths based on the relative risk associated with a given level of weekly influenza test positivity rate and multiplied PAFs by IHD mortality from the Global Burden of Disease study. Findings: Influenza activity was associated with increased risk of IHD mortality across all countries analyzed. The mean PAF of influenza for IHD mortality was 3.9% (95% uncertainty interval [UI] 2.5-5.3%), ranging from <1% to 10%, depending on country and year. Globally, 299,858 IHD deaths (95% UI 191,216-406,809) in adults ≥50 years could be attributed to influenza, with the highest rates per 100,000 population in the Central Europe, Eastern Europe and Central Asia Region (32.3; 95% UI 20.6-43.8), and in the North Africa and Middle East Region (26.7; 95% UI 17-36.2). Interpretation: Influenza may contribute substantially to the burden of IHD. Our results suggest that if there were no influenza, an average of 4% of IHD deaths globally would not occur. Funding: Collaborative study funded by Sanofi Vaccines.

Seasonal influenza, its complications and related healthcare resource utilization among people 60 years and older: A descriptive retrospective study in Japan.

Evidence suggests that older people aged ≥65 years and those aged 60-64 years with chronic medical conditions are at higher risk of developing severe complications due to influenza virus infection when compared with young, healthy adults. Although seasonal influenza is monitored through a nationwide passive surveillance in Japan, influenza related outcomes and medical resource consumption have not been fully documented. This retrospective database study aimed to describe the epidemiological and clinical characteristics of medically attended influenza cases aged ≥60 years and the associated medical resource consumption in Japan. We used clinically diagnosed influenza (CDI) based on the international classification of disease codes, and laboratory-confirmed influenza (LCI) based on influenza test results, to identify the patient population during a total of nine seasons (2010/2011 to 2018/2019). A total of 372,356 CDI and 31,122 LCI cases were identified from 77 medical institutions. The highest numbers of medically-attended influenza episodes were in patients aged 65-74 years and 75-84 years. On average, across seasons, 5.9% of all-cause hospitalizations were attributable to CDI and 0.4% were LCI. Influenza viruses type A and B co-circulated annually in varying degree of intensity and were associated with similar level of complications, including cardiovascular-related. Oxygen therapy increased with age; by contrast, mechanical ventilation, dialysis, blood transfusion, and intensive care unit admission were higher in the younger groups. In-hospital mortality for inpatients aged ≥ 85 years with CDI and LCI were 18.6% and 15.5%, respectively. Considering the burden associated with medically-attended influenza in this population, influenza prevention, laboratory confirmation and clinical management should be emphasized by general practicians and specialists like cardiologists to protect this aging population.

Inequalities in Health Impact of Alternative Reimbursement Pathways for Nirsevimab in the United States.

The target populations and financing mechanisms for a new health technology may affect health inequalities in access and impact. We projected the distributional consequences of introducing nirsevimab for prevention of respiratory syncytial virus in a US birth cohort of infants through alternative reimbursement pathway scenarios. Using the RSV immunization impact model, we estimated that a vaccine-like reimbursement pathway would cover 32% more infants than a pharmaceutical pathway. The vaccine pathway would avert 30% more hospitalizations and 39% more emergency room visits overall, and 44% and 44%, respectively, in publicly insured infants. The vaccine pathway would benefit infants from poorer households.

Medically Attended Illness due to Respiratory Syncytial Virus Infection Among Infants Born in the United States Between 2016 and 2020.

BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of infant hospitalization in the United States. Preterm infants and those with select comorbidities are at highest risk of RSV-related complications. However, morbidity due to RSV infection is not confined to high-risk infants. We estimated the burden of medically attended (MA) RSV-associated lower respiratory tract infection (LRTI) among infants in the United States. METHODS: We analyzed commercial (MarketScan Commercial [MSC], Optum Clinformatics [OC]), and Medicaid (MarketScan Medicaid [MSM]) insurance claims data for infants born between April 2016 and February 2020. Using both specific and sensitive definitions of MA RSV LRTI, we estimated the burden of MA RSV LRTI during infants' first RSV season, stratified by gestational age, comorbidity status, and highest level of medical care associated with the MA RSV LRTI diagnosis. RESULTS: According to the specific definition 75.0% (MSC), 78.6% (MSM), and 79.6% (OC) of MA RSV LRTI events during infants' first RSV season occurred among term infants without known comorbidities. CONCLUSIONS: Term infants without known comorbidities account for up to 80% of the MA RSV LRTI burden in the United States during infants' first RSV season. Future prevention efforts should consider all infants.

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.

Looking Back on 50 Years of Literature to Understand the Potential Impact of Influenza on Extrapulmonary Medical Outcomes.

We conducted a scoping review of the epidemiological literature from the past 50 years to document the contribution of influenza virus infection to extrapulmonary clinical outcomes. We identified 99 publications reporting 243 associations using many study designs, exposure and outcome definitions, and methods. Laboratory confirmation of influenza was used in only 28 (12%) estimates, mostly in case-control and self-controlled case series study designs. We identified 50 individual clinical conditions associated with influenza. The most numerous estimates were of cardiocirculatory diseases, neurological/neuromuscular diseases, and fetal/newborn disorders, with myocardial infarction the most common individual outcome. Due to heterogeneity, we could not generate summary estimates of effect size, but of 130 relative effect estimates, 105 (81%) indicated an elevated risk of extrapulmonary outcome with influenza exposure. The literature is indicative of systemic complications of influenza virus infection, the requirement for more effective influenza control, and a need for robust confirmatory studies.

Development of effective messages to promote maternal immunization in Kenya.

OBJECTIVES: This study evaluated messages and communication approaches for maternal immunization uptake in Kenya. We identified persuasive communication aspects that would inform maternal immunization attitudes, intent, and vaccine uptake. METHODS: We conducted a two-phased mixed methods study with pregnant women and their male partners in three regions of Kenya. Discussions were conducted in English and Swahili languages by trained focus group moderators. Baseline measures included a survey and discussions about potential messages and accompanying visuals. Follow-up focus groups with the same participants included a survey about previously discussed messages, visuals, and communication impressions. The second round of focus groups focused on message preferences developed from the first round, along with rank order discussion for final message selection. Following transcription of focus group discussions, we conducted analyses using NVivo software. Quantitative data analyses included frequencies, factor analyses, reliability assessment, regression modeling, and comparative assessment of rank order. RESULTS: The sample (N = 118) included pregnant women (n = 91) and their partners (n = 27) from diverse Kenyan regions (Bondo/Lwak/Siaya, Mombasa, and Nairobi). A four-factor solution resulted from factor analyses that included subscales "positive ad attitudes" (n = 5 items, α = 0.82), "negative ad attitudes" (n = 4 items, α = 0.75), "ad indifference" (n = 2 items, α = 0.52), and "ad motivation" (n = 4 items, α = 0.71). Overall, the positive ad attitudes factor (ß = 0.61, p = 0.03) was the only significant component in the overall model examining message selections (χ2(6) = 262.87, p = 0.17). Among the tested concepts, we found that source and situational cues had a strong influence on women's attitude formation and intention to obtain recommended maternal vaccinations. With self-acknowledged variations in knowledge, participants were particularly attuned to images of relatable women, providers, and depictions in realistic or actual Kenyan clinical settings. CONCLUSIONS: The results indicated that positive attitudes were shaped by incorporating highly relatable factors in messages. Implications for subsequent campaigns and research directions are discussed.

Efficiency of transplacental transfer of respiratory syncytial virus (RSV) specific antibodies among pregnant women in Kenya.

Background: Maternal immunisation to boost respiratory syncytial virus (RSV) antibodies in pregnant women, is a strategy being considered to enhance infant protection from severe RSV associated disease. However, little is known about the efficiency of transplacental transfer of RSV-specific antibodies in a setting with a high burden of malaria and HIV, to guide the implementation of such a vaccination program. Methods: Using a plaque reduction neutralization assay, we screened 400 pairs of cord and maternal serum specimens from pregnant women for RSV-specific antibodies. Participants were pregnant women of two surveillance cohorts: 200 participants from a hospital cohort in Kilifi, Coastal Kenya and 200 participants from a surveillance cohort in Siaya, Western Kenya. Transplacental transfer efficiency was determined by the cord to maternal transfer ratio (CMTR). Logistic regression was used to determine independent predictors of impaired transplacental transfer of RSV-specific antibodies. Results: A total of 800 samples were screened from the 400 participants. At enrollment the median age was 25 years (Interquartile range (IQR): 21-31). Overall, transplacental transfer was efficient and did not differ between Kilifi and Siaya cohort (1.02 vs. 1.02; p=0.946) but was significantly reduced among HIV-infected mothers compared to HIV-uninfected mothers (mean CMTR: 0.98 vs 1.03; p=0.015). Prematurity <33 weeks gestation (Odds ratio [OR]: 0.23, 95% confidence interval [CI] 0.06-0.85; p=0.028), low birth weight <2.5 kgs (OR: 0.25, 95% CI: 0.07-0.94; p=0.041) and HIV infection (OR: 0.47, 95% CI:0.23-0.98; p=0.045) reduced efficiency of transplacental transfer among these women. Conclusions: Transplacental transfer of RSV-specific antibodies among pregnant women in Kenya is efficient. A consideration to integrate other preventive interventions with maternal RSV vaccination targeting infants born premature (<33 weeks gestation), with low birth weight <2.5 kgs, or HIV-infected mothers is likely to improve vaccine outcomes in this setting.

Predictors of influenza severity among hospitalized adults with laboratory confirmed influenza: Analysis of nine influenza seasons from the Valencia region, Spain.

PURPOSE: Influenza hospitalizations contribute substantially to healthcare disruption. We explored the impact of ageing, comorbidities and other risk factors to better understand associations with severe clinical outcomes in adults hospitalized with influenza. METHODS: We analysed multi-season data from adults ≥18 years, hospitalized with laboratory-confirmed influenza in Valencia, Spain. Severity was defined as intensive care unit (ICU) admission, assisted ventilation and/or death. Generalized estimating equations were used to estimate associations between risk factors and severity. Rate of hospital discharge was analysed with a cumulative incidence function. RESULTS: Only 26% of influenza patients had their primary discharge diagnosis coded as influenza. Comorbidities were associated with severity among adults aged 50-79 years, with the highest odds ratio (OR) in patients with ≥3 comorbidities aged 50-64 years (OR = 6.7; 95% CI: 1.0-44.6). Morbid obesity and functional dependencies were also identified risk factors (ORs varying from 3 to 5 depending on age). The presence of increasing numbers of comorbidities was associated with prolonged hospital stay. CONCLUSIONS: Influenza clinical outcomes are aggravated by the presence of comorbidities and ageing. Increased awareness of influenza among hospitalized patients could prompt clinical and public health interventions to reduce associated burden.

Severe acute respiratory illness surveillance for influenza in Kenya: Patient characteristics and lessons learnt.

BACKGROUND: We describe the epidemiology and clinical features of Kenyan patients hospitalized with laboratory-confirmed influenza compared with those testing negative and discuss the potential contribution of severe acute respiratory illness (SARI) surveillance in monitoring a broader range of respiratory pathogens. METHODS: We described demographic and clinical characteristics of SARI cases among children (<18 years) and adults, separately. We compared disease severity (clinical features and treatment) of hospitalized influenza positive versus negative cases and explored independent predictors of death among SARI cases using a multivariable logistic regression model. RESULTS: From January 2014 to December 2018, 11,166 persons were hospitalized with SARI and overall positivity for influenza was ~10%. There were 10,742 (96%) children (<18 years)-median age of 1 year, interquartile range (IQR = 6 months, 2 years). Only 424 (4%) of the SARI cases were adults (≥18 years), with median age of 38 years (IQR 28 years, 52 years). There was no difference in disease severity comparing influenza positive and negative cases among children. Children hospitalized with SARI who had an underlying illness had greater odds of in-hospital death compared with those without (adjusted odds ratio 2.11 95% CI 1.09-4.07). No further analysis was done among adults due to the small sample size. CONCLUSION: Kenya's sentinel surveillance for SARI mainly captures data on younger children. Hospital-based platforms designed to monitor influenza viruses and associated disease burden may be adapted and expanded to other respiratory viruses to inform public health interventions. Efforts should be made to capture adults as part of routine respiratory surveillance.