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Background With the future epidemiology and evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uncertain, the use of safe and effective coronavirus disease 2019 (COVID-19) vaccines in pediatric populations remains important. Methods We report data from two open-label substudies of an ongoing phase 1/2/3 master study (NCT05543616) investigating the safety and immunogenicity of a variant-adapted bivalent COVID-19 vaccine encoding ancestral and Omicron BA.4/BA.5 spike proteins (bivalent BNT162b2). The open-label groups presented here evaluate dose 4 with bivalent BNT162b2 in 6-month- to <12-year-olds who previously received three original (monovalent) BNT162b2 doses. In 6-month- to <5-year-olds, primary immunogenicity objectives were to demonstrate superiority (neutralizing titer) and noninferiority (seroresponse rate) to Omicron BA.4/BA.5 and noninferiority (neutralizing titer and seroresponse rate) to SARS-CoV-2 ancestral strains in participants who received bivalent BNT162b2 dose 4 compared with a matched group who received three doses of original BNT162b2 in the pivotal pediatric study (NCT04816643). In 5- to <12-year-olds, primary immunogenicity comparisons were descriptive. Reactogenicity and safety following vaccination were evaluated. Results In 6-month- to <5-year-olds, dose 4 with bivalent BNT162b2 met predefined immunogenicity superiority and noninferiority criteria against Omicron BA.4/BA.5 and ancestral strains when compared with dose 3 of original BNT162b2. In 5- to <12-year-olds, bivalent BNT162b2 induced robust Omicron BA.4/BA.5 and ancestral strain neutralizing titers comparable with dose 3 of original BNT162b2. The safety profile for dose 4 of bivalent BNT162b2 given as dose 4 was consistent with that of original BNT162b2 in 6-month- to <12-year-olds. Reactogenicity events were generally mild to moderate. No adverse events led to discontinuation. Conclusions These safety and immunogenicity data support a favorable benefit-risk profile for a variant-adapted BNT162b2 in children <12 years old. [ABSTRACT FROM AUTHOR]

Background The objective was to report critical respiratory syncytial virus (RSV)–related epidemiological and healthcare resource utilization measures among Japanese children stratified by gestational and chronological age groups. Methods The JMDC (formerly the Japan Medical Data Center) was used to retrospectively identify infants with or without RSV infection (beginning between 1 February 2011 and 31 January 2016, with follow-up through 31 December 2017). The incidence of RSV medically attended lower respiratory tract infection (MALRI) was captured by flagging hospitalizations, outpatient, and emergency department/urgent care visits with an RSV diagnosis code during the season. Results Of 113 529 infants and children identified, 17 022 (15%) had an RSV MALRI (14 590 during the season). The RSV MALRI and hospitalization rates in the first 5 months were 14.3/100 child-years (CY) and 6.0/100 CY, respectively (13.4/100 and 5.8/100 CY for full-term infants and 20/100 and 6.8/100 CY for late preterm infants, respectively). Among those with ≥1 type of MALRI event during the RSV season, >80% of children had it by 24 months of chronological age, although this observation differed by prematurity status. Sixty percent of healthcare resource utilization measures started in the outpatient setting. Conclusions This study emphasizes the RSV burden in young children and critically highlights the data needed to make decisions about new preventive strategies. [ABSTRACT FROM AUTHOR]

Background Infants covered by Medicaid have higher respiratory syncytial virus (RSV) hospitalization rates than those with commercial insurance, but findings are limited to the inpatient setting. This birth cohort study describes healthcare encounters for RSV across all settings among infants covered by Medicaid and the Children's Health Insurance Program. Methods Medicaid claims for infants born and residing in Arizona (AZ), California (CA), Florida (FL), Michigan (MI), North Carolina (NC), New York (NY), and Texas (TX) were analyzed for first diagnosis of RSV in 2016–2018 using International Classification of Diseases, Tenth Revision codes. Encounters on the day of first diagnosis were examined by setting in 7 states and by setting and race in CA, FL, and NC. Results A total of 80 945 infants were diagnosed with RSV in 7 states in 2016–2018. The highest encounter rates for first RSV diagnosis were in the emergency department (ED) in 5 states (11.0–33.4 per 1000 in AZ, CA, FL, MI, and NY) and outpatient setting in 2 states (54.8 and 68.5 per 1000 in TX and NC). Significantly higher outpatient encounter rates were found in CA and NC for White infants compared to non-White infants. In NC, ED encounter rates were significantly higher for non-White infants than White infants, whereas in CA, the rates were comparable. In these 2 states, hospitalization rates were similar across groups. In FL, compared with White infants, non-White infants had significantly higher encounter rates in each setting on the day of first RSV diagnosis. Conclusions This is the first study to describe the burden of RSV by setting and race. Medicaid infants who are newly diagnosed with RSV have the highest burden in ED and outpatient settings. [ABSTRACT FROM AUTHOR]

Background Recent studies explored which pathogens drive the global burden of pneumonia hospitalizations among young children. However, the etiology of broader acute lower respiratory tract infections (ALRIs) remains unclear. Methods Using a multicountry study (Albania, Jordan, Nicaragua, and the Philippines) of hospitalized infants and non-ill community controls between 2015 and 2017, we assessed the prevalence and severity of viral infections and coinfections. We also estimated the proportion of ALRI hospitalizations caused by 21 respiratory pathogens identified via multiplex real-time reverse transcription polymerase chain reaction with bayesian nested partially latent class models. Results An overall 3632 hospitalized infants and 1068 non-ill community controls participated in the study and had specimens tested. Among hospitalized infants, 1743 (48.0%) met the ALRI case definition for the etiology analysis. After accounting for the prevalence in non-ill controls, respiratory syncytial virus (RSV) was responsible for the largest proportion of ALRI hospitalizations, although the magnitude varied across sites—ranging from 65.2% (95% credible interval, 46.3%–79.6%) in Albania to 34.9% (95% credible interval, 20.0%–49.0%) in the Philippines. While the fraction of ALRI hospitalizations caused by RSV decreased as age increased, it remained the greatest driver. After RSV, rhinovirus/enterovirus (range, 13.4%–27.1%) and human metapneumovirus (range, 6.3%–12.0%) were the next-highest contributors to ALRI hospitalizations. Conclusions We observed substantial numbers of ALRI hospitalizations, with RSV as the largest source, particularly in infants aged <3 months. This underscores the potential for vaccines and long-lasting monoclonal antibodies on the horizon to reduce the burden of ALRI in infants worldwide. [ABSTRACT FROM AUTHOR]

Background Understanding respiratory syncytial virus (RSV) global epidemiology is important to inform future prevention strategies. Methods Hospitalized infants <1-year-old with acute illness were enrolled prospectively in Albania, Jordan, Nicaragua, and Philippines during respiratory seasons in 2015–2017. Medical chart review, parental interview, and post-discharge follow up were conducted. Respiratory specimens were tested using real-time RT-PCR for RSV. Infant characteristics associated with very severe illness (intensive care unit [ICU] admission or receipt of supplemental oxygen) were assessed using logistic regression to adjust for potential confounders (age, sex, study site, and preterm birth). Results Of 3634 enrolled hospitalized infants, 1129 (31%) tested positive for RSV. The median age of RSV-positive infants was 2.7 (IQR: 1.4–6.1) months and 665 (59%) were male. Very severe illness in 583 (52%) RSV-positive infants was associated with younger age (aOR 4.1, 95% CI: 2.6–6.5 for 0–2 compared to 9–11-months; P <.01), low weight-for-age z -score (aOR 1.9, 95% CI: 1.2–2.8; P <.01), ICU care after birth (aOR 1.6, 95% CI: 1.0–2.5; P =.048), and cesarean delivery (aOR 1.4, 95% CI: 1.0–1.8; P =.03). RSV subgroups A and B co-circulated at all sites with alternating predominance by year; subgroup was not associated with severity (aOR 1.0, 95% CI: 0.8–1.4). Nine (0.8%) RSV-positive infants died during admission or within ≤30 days of discharge, of which 7 (78%) were <6-months-old. Conclusions RSV was associated with nearly a third of infant acute illness hospitalizations in four middle-income countries during the respiratory season, where, in addition to young age, factors including low weight-for-age might be important predictors of severity. RSV prevention strategies targeting young infants could substantially reduce RSV-associated hospitalizations in middle-income countries. [ABSTRACT FROM AUTHOR]

In this ongoing study, substantially increased ancestral SARS-CoV-2 neutralizing responses were observed 1 month after a third 10-µg BNT162b2 dose given to 5 to 11-year olds versus neutralizing responses post-dose 2. After dose 3, increased neutralizing responses against Omicron BA.1 and BA.4/BA.5 strains were also observed. The safety/tolerability profile was acceptable. (NCT04816643) [ABSTRACT FROM AUTHOR]

In the United States, a retrospective examination of the National Inpatient Sample (NIS) estimates that between October 2015 and December 2019, hospitalizations directly related to RSV accounted for 9.3% of all infant hospitalizations and were the most common cause of infant hospitalizations outside the birth hospitalization [[17]]. Keywords: costs; epidemiology; hospitalization; mortality EN costs epidemiology hospitalization mortality S143 S147 5 08/18/22 20220803 NES 220803 Although pediatricians have long recognized that respiratory syncytial virus (RSV) is the single most important cause of lower respiratory tract infection (LRTI) in infants and young children, the most important cause of acute illness visits to their clinics, and the most important cause of hospitalizations during the respiratory season, we have been resigned for the last 4 decades to patiently waiting while other viral and bacterial diseases have been conquered by successful vaccines [[1]]. It was estimated that in the 2020 birth cohort, there were approximately 80 000 RSV hospitalizations in the first 6 months of life [[23]], a rate closer to the estimates of 100 000 RSV hospitalizations in the first year of life using the NIS data [[19]]. In summary, we have learned from this series of articles that the burden of RSV hospitalization in US children is significant, causing between 9% and 12% of all nonbirth hospitalizations and resulting in between 80, 000 and 100, 000 hospitalizations annually and almost 3 times that number of visits to the ED. [Extracted from the article]

Comparison of the safety and immunogenicity of 2 respiratory syncytial virus (RSV) vaccines: nonadjuvanted vaccine or vaccine adjuvanted with alum - given concomitantly with influenza vaccine to high-risk elderly individuals. Even cost-effective analyses of RSV prevention increasingly find that the healthcare resource utilization costs following RSV are an important contributor to the overall burden of RSV disease [[50]]. This analysis showed that RSV-specific antibody appeared to protect mice from RSV disease but not cows from bovine RSV. Keywords: hospitalization; epidemiology; RSV prevention; vaccines; costs EN hospitalization epidemiology RSV prevention vaccines costs S1 S9 9 08/18/22 20220802 NES 220802 Soon after the discovery that respiratory syncytial virus (RSV) was the major cause of bronchiolitis in infants, in 1956 [[1]], vaccines were developed to try and prevent both infection and severe disease caused by the virus, but such early preventive efforts failed [[2]]. [Extracted from the article]

Background Estimating real-world vaccine effectiveness is challenging as a variety of population factors can impact vaccine effectiveness. We aimed to assess the population-level reduction in cumulative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cases, hospitalizations, and mortality due to the BNT162b2 mRNA coronavirus disease 2019 (COVID-19) vaccination campaign in Israel during January–February 2021. Methods A susceptible-infected-recovered/removed (SIR) model and a Dynamic Survival Analysis (DSA) statistical approach were used. Daily counts of individuals who tested positive and of vaccine doses administered, obtained from the Israeli Ministry of Health, were used to calibrate the model. The model was parameterized using values derived from a previous phase of the pandemic during which similar lockdown and other preventive measures were implemented in order to take into account the effect of these prevention measures on COVID-19 spread. Results Our model predicted for the total population a reduction of 648 585 SARS-CoV-2 cases (75% confidence interval [CI], 25 877–1 396 963) during the first 2 months of the vaccination campaign. The number of averted hospitalizations for moderate to severe conditions was 16 101 (75% CI, 2010–33 035), and reduction of death was estimated at 5123 (75% CI, 388–10 815) fatalities. Among children aged 0–19 years, we estimated a reduction of 163 436 (75% CI, 0–433 233) SARS-CoV-2 cases, which we consider to be an indirect effect of the vaccine. Conclusions Our results suggest that the rapid vaccination campaign prevented hundreds of thousands of new cases as well as thousands of hospitalizations and fatalities and has probably averted a major health care crisis. [ABSTRACT FROM AUTHOR]

Background: Although global reviews of infant respiratory syncytial virus (RSV) burden exist, none have summarized data from the United States or evaluated how RSV burden estimates are influenced by variations in study design.Methods: We performed a systematic literature review and meta-analysis of studies describing RSV-associated hospitalization rates among US infants and examined the impact of key study characteristics on these estimates.Results: We reviewed 3328 articles through 14 August 2020 and identified 25 studies with 31 unique estimates of RSV-associated hospitalization rates. Among US infants <1 year of age, annual rates ranged from 8.4 to 40.8 per 1000 with a pooled rate of 19.4 (95% confidence interval [CI], 17.9-20.9). Study type influenced RSV-associated hospitalization rates (P = .003), with active surveillance studies having pooled rates (11.0; 95% CI, 9.8-12.2) that were half that of studies based on administrative claims (21.4; 19.5-23.3) or modeling approaches (23.2; 20.2-26.2).Conclusions: Applying our pooled rates to the 2020 US birth cohort suggests that 79 850 (95% CI, 73 680-86 020) RSV-associated infant hospitalizations occur each year. The full range of RSV-associated hospitalization rates identified in our review can better inform future evaluations of RSV prevention strategies. More research is needed to better understand differences in estimated RSV burden across study design. [ABSTRACT FROM AUTHOR]

Background: Immunoglobulin A (IgA) is an important component of the early immune response to SARS-CoV-2. Prior serosurveys in high-risk groups employing IgG testing alone have provided discordant estimates. The potential added benefit of IgA in serosurveys has not been established.Methods: Longitudinal serosurvey of first responders (police, emergency medical service providers, fire fighters, and other staff) employing 3 serologic tests (anti-spike IgA, anti-spike IgG, and anti-nucleocapsid IgG) correlated with surveys assessing occupational and nonoccupational risk, exposure to COVID-19, and illnesses consistent with COVID-19.Results: Twelve percent of first responders in Colorado at baseline and 22% at follow-up were assessed as having SARS-CoV-2 infection. Five percent at baseline and 6% at follow-up were seropositive only for IgA. Among those IgA positive only at baseline, the majority (69%) had a positive antibody at follow-up; 45% of those infected at baseline and 33% at follow-up were asymptomatic. At all time points, the estimated cumulative incidence in our study was higher than that in the general population.Conclusions: First responders are at high risk of infection with SARS-CoV-2. IgA testing identified a significant portion of cases missed by IgG testing and its use as part of serologic surveys may improve retrospective identification of asymptomatic infection. [ABSTRACT FROM AUTHOR]

Background Benefits of school reopening must be weighed against the morbidity and mortality risks and the impact of enhancing spread of coronavirus disease 2019 (COVID-19). We investigated the effects of school reopening and easing of social-distancing restrictions on dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in Israel between March and July 2020. Methods We examined the nationwide age-wise weekly incidence, prevalence, SARS-CoV-2 polymerase chain reaction tests, their positivity, COVID-19 hospitalizations, and associated mortality. Temporal differences in these parameters following school reopening, school ending, and following easing of restrictions such as permission of large-scale gatherings were examined. Results Incidence of SARS-CoV-2 infections gradually increased following school reopening in all age groups, with a significantly higher increase in adults than children. Higher rate ratios (RRs) of sample positivity rates 21–27 days following school reopening relative to positivity rates prior to openings were found for the age groups 40–59 (RR, 4.72; 95% CI, 3.26–6.83) and 20–39 (RR, 3.37 [2.51–4.53]) years, but not for children aged 0–9 (RR, 1.46 [.85–2.51]) and 10–19 (RR,.93 [.65–1.34]) years. No increase was observed in COVID-19–associated hospitalizations and deaths following school reopening. In contrast, permission of large-scale gatherings was accompanied by increases in incidence and positivity rates of samples for all age groups, and increased hospitalizations and mortality. Conclusions This analysis does not support a major role of school reopening in the resurgence of COVID-19 in Israel. Easing restrictions on large-scale gatherings was the major influence on this resurgence. [ABSTRACT FROM AUTHOR]

Background Respiratory syncytial virus (RSV) is a major cause of childhood medically attended respiratory infection (MARI). Methods We conducted a randomized, double-blind, placebo-controlled phase 3 trial in 1154 preterm infants of 1 or 2 doses of suptavumab, a human monoclonal antibody that can bind and block a conserved epitope on RSV A and B subtypes, for the prevention of RSV MARI. The primary endpoint was proportion of subjects with RSV-confirmed hospitalizations or outpatient lower respiratory tract infection (LRTI). Results There were no significant differences between primary endpoint rates (8.1%, placebo; 7.7%, 1-dose; 9.3%, 2-dose). Suptavumab prevented RSV A infections (relative risks,.38; 95% confidence interval [CI],.14–1.05 in the 1-dose group and.39 [95% CI,.14–1.07] in the 2-dose group; nominal significance of combined suptavumab group vs placebo; P =.0499), while increasing the rate of RSV B infections (relative risk 1.36 [95% CI,.73–2.56] in the 1-dose group and 1.69 [95% CI,.92–3.08] in the 2-dose group; nominal significance of combined suptavumab group vs placebo; P =.12). Sequenced RSV isolates demonstrated no suptavumab epitope changes in RSV A isolates, while all RSV B isolates had 2–amino acid substitution in the suptavumab epitope that led to loss of neutralization activity. Treatment emergent adverse events were balanced across treatment groups. Conclusions Suptavumab did not reduce overall RSV hospitalizations or outpatient LRTI because of a newly circulating mutant strain of RSV B. Genetic variation in circulating RSV strains will continue to challenge prevention efforts. Clinical Trials Registration NCT02325791. [ABSTRACT FROM AUTHOR]

Background Although respiratory syncytial virus (RSV) is the most important viral cause of lower respiratory tract infection deaths in infants, there are few data on infant community deaths caused by RSV. Methods This was an active surveillance of children younger than 2 years of age in 93 villages, 5 primary health centers, and 3 hospitals serving these villages. Village health workers and counselors at the health facilities monitored all lower respiratory tract infections (LRTIs) in consented subjects. Children with severe, or very severe LRTIs and all who died, had nasopharyngeal swabs collected for detection of RSV by molecular methods. Results In the 12 134 subjects, there were 2064 episodes of severe LRTIs and 1732 of very severe LRTIs, of which 271 and 195, respectively, had RSV. Fifteen of 16 (94%) children with RSV died of LRTIs, 14 in the community and 1 in the hospital. The case fatality ratios for severe RSV LRTIs in the first 6 months of life were 3/52 (7.1%) and 1/36 (2.8%) in the community and hospital, respectively. Of those with very severe LRTIs in the community, 17.6% died. There were no very severe RSV LRTI hospital deaths. The adjusted RSV LRTI mortality rates ranged from 1.0 to 3.0/1000 child-years (CY) overall, and 2.0 to 6.1/1000 CY, accounting for 20% of the LRTI deaths and 10% of the postneonatal infant mortality. Conclusions Community deaths from RSV account for the majority of RSV LRTI deaths, and efforts at prevention should be preferentially directed at populations where access to care is limited. [ABSTRACT FROM AUTHOR]

Background Globally, respiratory syncytial virus (RSV) is a common cause of acute lower tract infection (LRTI) in children younger than 2 years of age, but there are scant population-based studies on the burden of RSV illness in rural communities and no community studies in preterm infants. Methods Active surveillance of LRTI was performed in the community and hospital setting for the population of 93 tribal villages in Melghat, Central India, over 4 respiratory seasons. A nasopharyngeal swab was obtained from cases presenting as a severe LRTI for molecular analysis of respiratory pathogens including RSVA and B. Results High rates of RSV-associated LRTI were found in preterm and term infants beyond 6 months of age, extending into the second year of life. Community severe RSV LRTI rates for 0–11 months of age was 22.4 (18.6–27.0)/1000 child-years (CY) and the hospital-associated rate was 14.1 (11.1–17.8)/1000 CY. For preterm infants, these rates were 26.2 (17.8–38.5)/1000 CY and 12.6 (7.2–22.0)/1000 CY. Comparable rates in the first 6 months were 15.9 (11.8–21.4)/1000 CY and 12.9 (9.3–18.0)/1000 CY in term infants and 26.3 (15.4–45.0)/1000 CY and 10.1 (4.2–24.2)/1000 CY for preterms. The single RSV B season had higher incidences of RSV LRTI in every age group than the 2 RSV A seasons in both preterm and term infants. There were 11 deaths, all term infants. Conclusions Studies restricted to the healthcare settings significantly underestimate the burden of RSV LRTI and preterm and term infants have comparable burdens of disease in this rural community. [ABSTRACT FROM AUTHOR]

Background: Respiratory syncytial virus (RSV) is the primary cause of respiratory tract infections in infants; however, current burden estimates report only the short-term effects of acute infection.Methods: Infants with RSV infection and ≥24 months of continuous enrollment were retrospectively identified from the Truven MarketScan database (1 January 2004-30 September 2015). Exposed infants (n = 38 473) were propensity score matched to nonexposed controls (n = 76 825) by baseline characteristics and gestational age. Five-year cumulative all-cause, asthma/wheezing, and respiratory event-related hospitalization rates and physician and emergency department healthcare-resource utilization rates were assessed.Results: During follow-up, RSV-infected cohorts had higher average all-cause cumulative hospitalization rates, compared with controls, with values of 79.9 hospitalizations/100 patient-years (95% confidence interval [CI], 41.7-118.2) for 213 early premature infants (P < .001), 18.2 hospitalizations/100 patient-years (95% CI, .8-35.7) for 397 premature infants (P = .04), 34.2 hospitalizations/100 patient-years (95% CI, 29.1-39.2) for 4446 late premature infants (P < .001), and 16.1 hospitalizations/100 patient-years (95% CI, 14.9-17.4) for 33 417 full-term infants (P < .001). Cumulative rates of physician and emergency department visits were also higher for RSV-infected infants. Asthma/wheezing accounted for 10%-18% of total 5-year physician visits.Conclusions: Infant RSV infection has a significant long-term healthcare-resource utilization impact across gestational ages for at least 5 years after infection, most of it in the first 2 years. Systematically collecting healthcare-resource utilization data will be important for cost-effectiveness evaluations of RSV interventions in planned or ongoing trials. [ABSTRACT FROM AUTHOR]

Background This study evaluates the long-term respiratory syncytial virus (RSV) burden among preterm and full-term infants in the United States. Methods Infants with birth hospitalization claims and ≥24 months of continuous enrollment were retrospectively identified in the Truven MarketScan Commercial Claims and Encounters database for the period 1 January 2004–30 September 2015. Infants with RSV infection in the first year of life (n = 38 473) were matched to controls (n = 76 825), and remaining imbalances in the number of individuals in each group were adjusted using propensity score methods. All-cause, respiratory-related, and asthma/wheezing-related 5-year average cumulative costs were measured. Results Early premature (n = 213), premature (n = 397), late premature (n = 4446), and full-term (n = 33 417) RSV-infected infants were matched to 424, 791, 8875, and 66 735 controls, respectively. After 2 years since RSV diagnosis, all-cause cumulative costs for RSV-infected infants as compared to those for controls increased by $22 081 (95% confidence interval [CI], −$5800-$42 543) for early premature infants, by $14 034 (95% CI, $5095– $22 973) for premature infants, by $10 164 (95% CI, $8835–$11 493) for late premature infants, and by $5404 (95% CI, $5110–$5698) for full-term infants. The 5-year RSV burden increased to $39 490 (95% CI, $18 217–$60 764), $23 160 (95% CI, $13 002–$33 317),$13 755 (95% CI, $12 097–$15 414), and $6631 (95% CI, $6060–$7202), respectively. The RSV burden was higher when stratified by inpatient and outpatient setting and respiratory-related and asthma/wheezing-related costs. Conclusions The RSV burden extends across cost domains and prematurity, with the greatest burden incurred by the second year of follow-up. Findings are useful in determining the cost-effectiveness of RSV therapies in development. [ABSTRACT FROM AUTHOR]

We evaluated whether Denver neighborhoods with elevated rates of adult hospitalizations for laboratory-confirmed influenza had lower adult coverage with influenza vaccine. Overall vaccine coverage was low. Hospitalization rates were associated with demographic and socioeconomic characteristics. Active immunization of at-risk neighborhoods may be necessary to address disparities in influenza hospitalization rates. [ABSTRACT FROM AUTHOR]

The article presents a study which investigated respiratory syncytial virus (RSV) neutralizing antibody levels in HIV-infected/exposed and HIV-uninfected mother-newborn dyads. Topics discussed include the burden of RSV acute lower respiratory tract infection (LRT1) hospitalizations in HIV-infected children, overall RSV neutralizing antibody cord-to-maternal ratio (CMR), and mechanisms that may be involved in reducing transfer efficiency.

Background. Influenza immunization of pregnant women protects their young infants against laboratory-confirmed influenza infection. Influenza infection might predispose to subsequent bacterial infections that cause severe pneumonia. In a secondary analysis of a randomized clinical trial (RCT), we evaluated the effect of maternal vaccination on infant hospitalizations for all-cause acute lower respiratory tract infection (ALRI). Methods. Infants born to women who participated in a double-blind placebo-controlled RCT in 2011 and 2012 on the efficacy of trivalent inactivated influenza vaccine (IIV) during pregnancy were followed during the first 6 months of life. Results. The study included 1026 infants born to IIV recipients and 1023 born to placebo recipients. There were 52 ALRI hospitalizations (median age, 72 days). The incidence (per 1000 infant-months) of ALRI hospitalizations was lower in infants born to IIV recipients (3.4 [95% confidence interval {CI}, 2.2-5.4]; 19 cases) compared with placebo recipients (6.0 [95% CI, 4.3-8.5]; 33 cases) with a vaccine efficacy of 43.1% (P = .050). Thirty of the ALRI hospitalizations occurred during the first 90 days of life, 9 in the IIV group (3.0 [95% CI, 1.6-5.9]) and 21 in the placebo group (7.2 [95% CI, 4.7-11.0]) (incidence rate ratio, 0.43 [95% CI, .19-.93]) for a vaccine efficacy of 57.5% (P = .032). The incidence of ALRI hospitalizations was similar in the IIV and placebo group for infants >3 months of age. Forty-four of the hospitalized infants were tested for influenza virus infection and 1 tested positive. Conclusions. Using an RCT as a vaccine probe, influenza vaccination during pregnancy decreased all-cause ALRI hospitalization during the first 3 months of life, suggesting possible protection against subsequent bacterial infections that influenza infection might predispose to. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) causes lower respiratory tract illness frequently. No effective antivirals or vaccines for RSV are approved for use in the United States; however, there are at least 50 vaccines and monoclonal antibody products in development, with those targeting older adults and pregnant women (to protect young infants) in phase 2 and 3 clinical trials. Unanswered questions regarding RSV epidemiology need to be identified and addressed prior to RSV vaccine introduction to guide the measurement of impact and future recommendations. The Centers for Disease Control and Prevention (CDC) convened a technical consultation to gather input from external subject matter experts on their individual perspectives regarding evidence gaps in current RSV epidemiology in the United States, potential studies and surveillance platforms needed to fill these gaps, and prioritizing efforts. Participants articulated their individual views, and CDC staff synthesized individuals’ input into this report. [ABSTRACT FROM AUTHOR]

Background. The utility of serologic testing to evaluate vaccine efficacy of seasonal inactivated influenza vaccine (IIV) is controversial. We aimed to evaluate the efficacy of IIV against serologically diagnosed influenza infection (SDI) and reverse-transcription polymerase chain reaction–confirmed influenza illness (PCR-CI) in women vaccinated during pregnancy. Methods. We undertook a post hoc analysis of 2 randomized clinical trials evaluating IIV efficacy among human immunodeficiency virus (HIV)–uninfected and HIV-infected pregnant women. SDI was defined as ≥4-fold increase in paired hemagglutinin antibody inhibition titers from 1 month postvaccination until end-of-study participation. PCR-CI was defined as molecular diagnostic evidence of influenza virus in pharyngeal specimens collected during clinical illness. Results. Among placebo recipients, the respective incidence of PCR-CI and SDI was 5.6% and 35.0% in HIV-uninfected women and 20.5% and 43.6% among HIV-infected women. Vaccine efficacy in HIV-uninfected women was similar for PCR-CI (66.9%; 95% confidence interval [CI], –20.1% to 90.9%) and SDI (59.2%; 95% CI, 37.0%–73.5%); however, fewer women required vaccination to prevent 1 episode of SDI (5; 95% CI, 3–9) than PCR-CI (27; 95% CI, 12–∞). Also, vaccine efficacy was similar for PCR-CI (61.2%; 95% CI, 10.7%–83.2%) and SDI (60.9%; 95% CI, 33.9%–76.9%) in HIV-infected women, with 2-fold fewer women needing to be vaccinated to prevent SDI (4; 95% CI, 3–8) than PCR-CI (8; 95% CI, 4–52). Conclusions. Although vaccine efficacy was similar when measured for PCR-CI or SDI, IIV vaccination prevented a greater number of SDI than PCR-CI; the clinical relevance of the former warrants interrogation. [ABSTRACT FROM AUTHOR]

Background: Both vaccine trials and surveillance studies typically use passive surveillance systems to monitor study outcomes, which may lead to under-reporting of study outcomes in areas with poor access to care. This detection bias can have an adverse effect on conventional estimates of pneumonia risk derived from vaccine trials.Methods: We conducted a secondary analysis of a randomized, placebo-controlled, double-blind vaccine trial that examined the efficacy of an 11-valent pneumococcal vaccine (PCV) among children less than 2 years of age in Bohol, Philippines. Trial data were linked to the residential location of each participant using a geographical information system. The study was conducted using 11 729 children who received three doses of any study vaccine (PCV11) or placebo. Multivariate Cox proportional hazards models were used to examine major risk factors for pneumonia diagnosis and the relationship between distance to Bohol Regional Hospital (BRH) and vaccination with PCV with risk for pneumonia diagnosis.Results: There was a significant interaction effect between distance from BRH and vaccination with PCV11 on pneumonia risk. Among children living 12 km from BRH, vaccination with PCV11 was associated with a decreased hazard ratio for radiographic pneumonia, compared with vaccination with the study placebo [0.57, 95% confidence interval (CI) 0.37-0.86). However, for children living 1 km from BRH, there was little difference in risk of radiographic pneumonia diagnosis between children vaccinated with PCV11 and those given the study placebo.Conclusion: Children living close to BRH had no documented reduction in the primary study outcome from PCV11, whereas those at greater distance experienced a substantial reduction. Because of detection bias caused by distance to BRH, in spatial analysis of vaccine trial results it may be necessary to adjust estimates of pneumonia risk and vaccine efficacy. Failure to consider the geographical dimension of trials may lead to underestimates of efficacy which might influence public health planning efforts. [ABSTRACT FROM AUTHOR]

Background. The goal of this study was to obtain representative Kenyan data on the point prevalence of acute otitis media (AOM) and its sequelae (otitis media with effusion [OME] and chronic suppurative otitis media [CSOM]), a major cause of preventable hearing loss in children in developing countries. In Africa, there are limited studies on the prevalence of AOM and its sequelae in children. Methods. Study subjects were children aged 2 to 15 years and were enrolled from randomly selected preprimary and primary schools. After parental or guardian consent, subjects had a questionnaire administered, otoscopy and tympanometry were done, and audiometry was performed on those with ear problems detected on these examinations. Results. A total of 9825 (75%) children was from rural schools. The prevalence of CSOM was 15 of 1000, OME was 15 of 1000, and AOM was 7 of 1000 children. Rural Rift Valley schoolchildren had the highest prevalence of CSOM (24 of 1000) compared with other regions (12 of 1000; P < .0001). Ear discharge occurred before 3.5 years in 50% of 901 children with ear discharge. A history of ear discharge was associated with abnormal tympanograms (odds ratio [OR], 11.9-19.2) and mild-to-severe hearing loss (OR, 21.6-38.6), even in children without ear disease (OR, 10.7-24.4). Conclusions. The burden of AOM sequelae in Kenyan preschool and schoolchildren is significant, and it occurs mostly in the first 4 years of life. By preventing early recurrent AOM, pneumococcal vaccination might partly avert nonreversible sequelae. [ABSTRACT FROM AUTHOR]

An editorial is presented on the outpatient burden of Respiratory Syncytial Virus infection in children aged more than 5 years. It also states that the children who were already having influenza-like illness (ILI) have numerous estimates of burden of RSV infectious. Topic discussed includes polymerase chain reaction (PCR) based test, respiratory tract infections and epidemiology.

Background. Little is known about how chronic conditions other than prematurity, heart disease, and Down syndrome affect the risk and severity of hospitalization for respiratory syncytial virus (RSV). We assess the risk and severity of RSV hospitalization in children with chronic conditions in this register-based, population-based cohort study. Methods. Data on RSV tests, maternal smoking, siblings, single parenthood, mode of delivery, gestational age at birth, major surgery, asthma diagnosis, chronic conditions, and hospitalization and discharge dates were obtained from the Danish RSV database, the National Patient and Birth Registries, and the Civil Registration System. Statistics. Cox regression models were used to estimate incidence rate ratios (IRRs) for RSV hospitalization between groups stratified by sex and date of birth. Duration of RSV hospitalization was analyzed in a linear regression and reported as geometric mean ratios. Results. A total of 391 983 children aged 0-23 months were included in the analysis. A total of 10 616 (2.7%) had a diagnosis for chronic disease. IRRs (95% confidence intervals) for RSV hospitalization in children with any congenital or acquired chronic condition were 2.18 (2.01-2.36) and 2.25 (1.94-2.61), respectively. Several new risk factors for RSV hospitalization, including malformations, interstitial lung disease, neuromuscular disease, liver disease, chromosomal abnormalities, congenital immunodeficiencies, and inborn errors of metabolism, were identified. Duration of RSV hospitalization was increased in many chronic conditions. Conclusions. Chronic disease per se is an important risk factor for RSV hospitalization. [ABSTRACT FROM AUTHOR]

Background. We aimed to define the excess morbidity associated with bloodstream infections (BSIs), imposed by pandemic H1N1 influenza during 2009-2010 (pH1N1/2009-2010) and seasonal influenza. Methods. Eight hospitals, accounting for 33% of hospitalizations in Israel, provided data on BSI during 2006- 2010. The age-specific incidence of BSI due to Streptococcus pneumoniae, Staphylococcus aureus, and Streptococcus pyogenes was determined. BSI incidence rate ratios (IRRs) during seasonal and pH1N1 influenza seasons were assessed. Results. Regular influenza seasons were characterized by increased rates of S. pneumoniae BSI but with no increase in S. aureus and S. pyogenes BSI rates. The pH1N1/2009-2010 influenza outbreak was characterized by (1) higher rates of S. pneumoniae bacteremia among children but not among adults (IRRs for S. pneumoniae BSI among children aged 0-4 years during the summer and winter of 2009-2010 were 14.8 [95% confidence interval {CI}, 5-43.7] and 6.5 [95% CI, 3.6-11.8], compared with 2006-2009 summers and influenza-active winter weeks, respectively [P < .0001]), higher rates of S. aureus BSI in all age groups (IRRs during the summer and winter of 2009-2010 were 1.6 [95% CI, 1.4-1.9] and 1.5 [95% CI, 1.2-1.7], compared with 2006-2009 summers and influenza-active weeks, respectively [P < .0001]), higher rates of S. pyogenes BSI during 2009-2010 influenza season (IRR 2.7 [95% CI, 1.6-4.6] and 3.3 [95% CI, 1.9-5.8] during the summer and winter of 2009-2010, compared with 2006-2009 summers and influenza-active weeks, respectively [P < .0001]). Conclusions. pH1N1 influenza seasons were characterized by marked increases in invasive S. aureus and S. pyogenes infections among children and adults, with the highest increase in S. pneumoniae BSI among children. [ABSTRACT FROM AUTHOR]

Background. Respiratory syncytial virus (RSV) has been recognized recently as an important adult pathogen. Methods. This randomized, double-blind, placebo-controlled study was designed to compare humoral responses to licensed trivalent influenza vaccine given concomitantly with 1 of 2 RSV vaccine formulations in persons ⩾65 years old with cardiopulmonary disease. Hemagglutinin-inhibition assays and neutralization assays were used to measure levels of antibody to influenza and RSV, respectively. Subjects with respiratory illnesses during subsequent winters were tested for RSV and influenza by reverse-transcriptase polymerase chain reaction and serologic analysis. Results. Neither RSV vaccine formulation had an effect on the humoral response to influenza vaccination, and both RSV vaccines were well tolerated by 1169 participants. The immunogenicity of the nonadjuvanted vaccine was judged superior on the basis of mean postvaccination neutralizing antibody titers (12.5 vs. 12.1) and the percentage of subjects for whom ⩾4-fold increases in neutralizing titer were observed when acute-phase and convalescent-phase serum samples were compared (168 [44%] of 383 vs. 129 [33%] of 400). In year 1, the percentage of illnesses due to RSV was 7% (36 of 492 illnesses) and that due to influenza was 8%(40 of 492), compared with 6% (11 of 189) due to RSV and 11% (20 of 189) due to influenza in year 2. The incidence of RSV infection was not significantly different in the RSV vaccine and placebo groups. Conclusions. Although the safety and immunogenicity data of these RSV vaccines are encouraging, low rates of infection make it challenging to design efficacy trials. [ABSTRACT FROM AUTHOR]

Background: This study evaluates the long-term respiratory syncytial virus (RSV) burden among preterm and full-term infants in the United States.Methods: Infants with birth hospitalization claims and ≥24 months of continuous enrollment were retrospectively identified in the Truven MarketScan Commercial Claims and Encounters database for the period 1 January 2004-30 September 2015. Infants with RSV infection in the first year of life (n = 38 473) were matched to controls (n = 76 825), and remaining imbalances in the number of individuals in each group were adjusted using propensity score methods. All-cause, respiratory-related, and asthma/wheezing-related 5-year average cumulative costs were measured.Results: Early premature (n = 213), premature (n = 397), late premature (n = 4446), and full-term (n = 33 417) RSV-infected infants were matched to 424, 791, 8875, and 66 735 controls, respectively. After 2 years since RSV diagnosis, all-cause cumulative costs for RSV-infected infants as compared to those for controls increased by $22 081 (95% confidence interval [CI], -$5800-$42 543) for early premature infants, by $14 034 (95% CI, $5095- $22 973) for premature infants, by $10 164 (95% CI, $8835-$11 493) for late premature infants, and by $5404 (95% CI, $5110-$5698) for full-term infants. The 5-year RSV burden increased to $39 490 (95% CI, $18 217-$60 764), $23 160 (95% CI, $13 002-$33 317),$13 755 (95% CI, $12 097-$15 414), and $6631 (95% CI, $6060-$7202), respectively. The RSV burden was higher when stratified by inpatient and outpatient setting and respiratory-related and asthma/wheezing-related costs.Conclusions: The RSV burden extends across cost domains and prematurity, with the greatest burden incurred by the second year of follow-up. Findings are useful in determining the cost-effectiveness of RSV therapies in development. [ABSTRACT FROM AUTHOR]

Two meetings, one sponsored by the Wellcome Trust in 2012 and the other by the Global Virology Foundation in 2013, assembled academic, public health and pharmaceutical industry experts to assess the challenges and opportunities for developing antivirals for the treatment of respiratory syncytial virus (RSV) infections. The practicalities of clinical trials and establishing reliable outcome measures in different target groups were discussed in the context of the regulatory pathways that could accelerate the translation of promising compounds into licensed agents. RSV drug development is hampered by the perceptions of a relatively small and fragmented market that may discourage major pharmaceutical company investment. Conversely, the public health need is far too large for RSV to be designated an orphan or neglected disease. Recent advances in understanding RSV epidemiology, improved point-of-care diagnostics, and identification of candidate antiviral drugs argue that the major obstacles to drug development can and will be overcome. Further progress will depend on studies of disease pathogenesis and knowledge provided from controlled clinical trials of these new therapeutic agents. The use of combinations of inhibitors that have different mechanisms of action may be necessary to increase antiviral potency and reduce the risk of resistance emergence. [ABSTRACT FROM AUTHOR]