Background Seasonal influenza virus is a common cause of acute lower respiratory infection (ALRI) in young children. In 2008, we estimated that 20 million influenza-virus-associated ALRI and 1 million influenza-virus-associated severe ALRI occurred in children under 5 years globally. Despite this substantial burden, only a few low-income and middleincome countries have adopted routine influenza vaccination policies for children and, where present, these have achieved only low or unknown levels of vaccine uptake. Moreover, the influenza burden might have changed due to the emergence and circulation of influenza A/H1N1pdm09. We aimed to incorporate new data to update estimates of the global number of cases, hospital admissions, and mortality from influenza-virus-associated respiratory infections in children under 5 years in 2018.Methods We estimated the regional and global burden of influenza-associated respiratory infections in children under 5 years from a systematic review of 100 studies published between Jan 1, 1995, and Dec 31, 2018, and a further 57 high-quality unpublished studies. We adapted the Newcastle-Ottawa Scale to assess the risk of bias. We estimated incidence and hospitalisation rates of influenza-virus-associated respiratory infections by severity, case ascertainment, region, and age. We estimated in-hospital deaths from influenza virus ALRI by combining hospital admissions and in-hospital case-fatality ratios of influenza virus ALRI. We estimated the upper bound of influenza virus-associated ALRI deaths based on the number of in-hospital deaths, US paediatric influenza-associated death data, and populationbased childhood all-cause pneumonia mortality data in six sites in low-income and lower-middle-income countries.Findings In 2018, among children under 5 years globally, there were an estimated 109•5 million influenza virus episodes (uncertainty range [UR] 63•1-190•6), 10•1 million influenza-virus-associated ALRI cases (6•8-15•1); 870 000 influenza-virus-associated ALRI hospital admissions (543 000-1 415 000), 15 300 in-hospital deaths (5800-43 800), and up to 34 800 (13 200-97 200) overall influenza-virus-associated ALRI deaths. Influenza virus accounted for 7% of ALRI cases, 5% of ALRI hospital admissions, and 4% of ALRI deaths in children under 5 years. About 23% of the hospital admissions and 36% of the in-hospital deaths were in infants under 6 months. About 82% of the in-hospital deaths occurred in low-income and lower-middle-income countries.Interpretation A large proportion of the influenza-associated burden occurs among young infants and in low-income and lower middle-income countries. Our findings provide new and important evidence for maternal and paediatric influenza immunisation, and should inform future immunisation policy particularly in low-income and middleincome countries.Funding WHO; Bill & Melinda Gates Foundation.

Background Understanding the risk factors for poor outcomes among COVID-19 patients could help identify vulnerable populations who would need prioritisation in prevention and treatment for COVID-19. We aimed to critically appraise and synthesise published evidence on the risk factors for poor outcomes in hospitalised COVID-19 patients. Methods We searched PubMed, medRxiv and the WHO COVID-19 literature database for studies that reported characteristics of COVID-19 patients who required hospitalisation. We included studies published between January and May 2020 that reported adjusted effect size of any demographic and/or clinical factors for any of the three poor outcomes: mortality, intensive care unit (ICU) admission, and invasive mechanical ventilation. We appraised the quality of the included studies using Joanna Briggs Institute appraisal tools and quantitatively synthesised the evidence through a series of random-effect meta-analyses. To aid data interpretation, we further developed an interpretation framework that indicated strength of the evidence, informed by both quantity and quality of the evidence. Results We included a total of 40 studies in our review. Most of the included studies (29/40, 73%) were assessed as “good quality”, with assessment scores of 80 or more. We found that male sex (pooled odds ratio (OR) = 1.32 (95% confidence interval (CI) = 1.18-1.48; 20 studies), older age (OR = 1.05, 95% CI = 1.04-1.07, per one year of age increase; 10 studies), obesity (OR = 1.59, 95% CI = 1.02-2.48; 4 studies), diabetes (OR = 1.25, 95% CI = 1.11-1.40; 11 studies) and chronic kidney diseases (6 studies; OR = 1.57, 95% CI = 1.27-1.93) were associated with increased risks for mortality with the greatest strength of evidence based on our interpretation framework. We did not find increased risk of mortality for several factors including chronic obstructive pulmonary diseases (5 studies), cancer (4 studies), or current smoker (5 studies); however, this does not indicate absence of risk due to limited data on each of these factors. Conclusion Male sex, older age, obesity, diabetes and chronic kidney diseases are important risk factors of COVID-19 poor outcomes. Our review provides not only an appraisal and synthesis of evidence on the risk factors of COVID-19 poor outcomes, but also a data interpretation framework that could be adopted by relevant future research.

Background Bronchiolitis is the commonest cause of respiratory related hospital admissions in young children. This study aimed to describe temporal trends in bronchiolitis admissions for children under 2 years of age in Scotland by patient characteristics, socioeconomic deprivation, and duration of admission. Methods The national hospital admissions database for Scotland was used to extract data on all bronchiolitis admissions (International Classification of Disease, Tenth Revision, code J21) in children <2 years of age from 2001 to 2016. Deprivation quintiles were classified using the 2011 Scottish Index of Multiple Deprivation. Results Over the 15-year study period, admission rates for children under 2 years old increased 2.20-fold (95% confidence interval [CI], 1.4–3.6-fold) from 17.2 (15.9–18.5) to 37.7 (37.4–38.1) admissions per 1000 children per year. Admissions peaked in infants aged 1 month, and in those born in the 3 months preceding the peak bronchiolitis month—September, October, and November. Admissions from the most-deprived quintile had the highest overall rate of admission, at 40.5 per 1000 children per year (95% CI, 39.5–41.5) compared with the least-deprived quintile, at 23.0 admissions per 1000 children per year (22.1–23.9). The most-deprived quintile had the greatest increase in admissions over time, whereas the least-deprived quintile had the lowest increase. Zero-day admissions, defined as admission and discharge within the same calendar date, increased 5.3-fold (5.1–5.5) over the study period, with the highest increase in patients in the most-deprived quintile. Conclusions This study provides baseline epidemiological data to aid policy makers in the strategic planning of preventative interventions. With the majority of bronchiolitis caused by respiratory syncytial virus (RSV), and several RSV vaccines and monoclonal antibodies currently in clinical trials, understanding national trends in bronchiolitis admissions is an important proxy for determining potential RSV vaccination strategies.

Typhoid fever remains an important public health problem in low-and middle-income countries, with large outbreaks reported from Africa and Asia. Although the WHO recommends typhoid vaccination for control of confirmed outbreaks, there are limited data on the epidemiologic characteristics of outbreaks to inform vaccine use in outbreak settings. We conducted a literature review for typhoid outbreaks published since 1990. We found 47 publications describing 45,215 cases in outbreaks occurring in 25 countries from 1989 through 2018. Outbreak characteristics varied considerably by WHO region, with median outbreak size ranging from 12 to 1,101 cases, median duration from 23 to 140 days, and median case fatality ratio from 0% to 1%. The largest number of outbreaks occurred in WHO Southeast Asia, 13 (28%), and African regions, 12 (26%). Among 43 outbreaks reporting a mode of disease transmission, 24 (56%) were waterborne, 17 (40%) were foodborne, and two (5%) were by direct contact transmission. Among the 34 outbreaks with antimicrobial resistance data, 11 (32%) reported Typhi non-susceptible to ciprofloxacin, 16 (47%) reported multidrug-resistant (MDR) strains, and one reported extensively drug-resistant strains. Our review showed a longer median duration of outbreaks caused by MDR strains (148 days versus 34 days for susceptible strains), although this difference was not statistically significant. Control strategies focused on water, sanitation, and food safety, with vaccine use described in only six (13%) outbreaks. As typhoid conjugate vaccines become more widely used, their potential role and impact in outbreak control warrant further evaluation.

Background Statistical modelling studies based on excess morbidity and mortality are important for understanding RSV disease burden for age groups that are less frequently tested for RSV. We aimed to understand the full age spectrum of RSV morbidity and mortality burden based on statistical modelling studies, as well as the value of modelling studies in RSV disease burden estimation. Methods The databases Medline, Embase and Global Health were searched to identify studies published between January 1, 1995, and December 31, 2021, reporting RSV-associated excess hospitalisation or mortality rates of any case definitions using a modelling approach. All reported rates were summarised using median, IQR (Interquartile range) and range by age group, outcome and country income group; where applicable, a random-effects meta-analysis was conducted to combine the reported rates. We further estimated the proportion of RSV hospitalisations that could be captured in clinical databases. Results A total of 32 studies were included, with 26 studies from high-income countries. RSV-associated hospitalisation and mortality rates both showed a U-shape age pattern. Lowest and highest RSV acute respiratory infection (ARI) hospitalisation rates were found in 5–17 years (median: 1.6/100,000 population, IQR: 1.3–18.5) and < 1 year (2235.7/100,000 population, 1779.1–3552.5), respectively. Lowest and highest RSV mortality rates were found in 18–49 years (0.1/100,000 population, 0.06–0.2) and ≥ 75 years (80.0/100,000 population, 70.0–90.0) for high-income countries, respectively, and in 18–49 years (0.3/100,000 population, 0.1–2.4) and < 1 year (143.4/100,000 population, 143.4–143.4) for upper-middle income countries. More than 70% of RSV hospitalisations in children < 5 years could be captured in clinical databases whereas less than 10% of RSV hospitalisations could be captured in adults, especially for adults ≥ 50 years. Using pneumonia and influenza (P&I) mortality could potentially capture half of all RSV mortality in older adults but only 10–30% of RSV mortality in children. Conclusions Our study provides insights into the age spectrum of RSV hospitalisation and mortality. RSV disease burden using laboratory records alone could be substantially severely underreported for age groups ≥ 5 years. Our findings confirm infants and older adults should be prioritised for RSV immunisation programmes. Trial registration PROSPERO CRD42020173430.