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Pneumonia is the leading cause of death among children younger than 5 years. In this study, we estimated causes of pneumonia in young African and Asian children, using novel analytical methods applied to clinical and microbiological findings. We did a multi-site, international case-control study in nine study sites in seven countries: Bangladesh, The Gambia, Kenya, Mali, South Africa, Thailand, and Zambia. All sites enrolled in the study for 24 months. Cases were children aged 1–59 months admitted to hospital with severe pneumonia. Controls were age-group-matched children randomly selected from communities surrounding study sites. Nasopharyngeal and oropharyngeal (NP-OP), urine, blood, induced sputum, lung aspirate, pleural fluid, and gastric aspirates were tested with cultures, multiplex PCR, or both. Primary analyses were restricted to cases without HIV infection and with abnormal chest x-rays and to controls without HIV infection. We applied a Bayesian, partial latent class analysis to estimate probabilities of aetiological agents at the individual and population level, incorporating case and control data. Between Aug 15, 2011, and Jan 30, 2014, we enrolled 4232 cases and 5119 community controls. The primary analysis group was comprised of 1769 (41·8% of 4232) cases without HIV infection and with positive chest x-rays and 5102 (99·7% of 5119) community controls without HIV infection. Wheezing was present in 555 (31·7%) of 1752 cases (range by site 10·6–97·3%). 30-day case-fatality ratio was 6·4% (114 of 1769 cases). Blood cultures were positive in 56 (3·2%) of 1749 cases, and Streptococcus pneumoniae was the most common bacteria isolated (19 [33·9%] of 56). Almost all cases (98·9%) and controls (98·0%) had at least one pathogen detected by PCR in the NP-OP specimen. The detection of respiratory syncytial virus (RSV), parainfluenza virus, human metapneumovirus, influenza virus, S pneumoniae, Haemophilus influenzae type b (Hib), H influenzae non-type b, and Pneumocystis jirovecii in NP-OP specimens was associated with case status. The aetiology analysis estimated that viruses accounted for 61·4% (95% credible interval [CrI] 57·3–65·6) of causes, whereas bacteria accounted for 27·3% (23·3–31·6) and Mycobacterium tuberculosis for 5·9% (3·9–8·3). Viruses were less common (54·5%, 95% CrI 47·4–61·5 vs 68·0%, 62·7–72·7) and bacteria more common (33·7%, 27·2–40·8 vs 22·8%, 18·3–27·6) in very severe pneumonia cases than in severe cases. RSV had the greatest aetiological fraction (31·1%, 95% CrI 28·4–34·2) of all pathogens. Human rhinovirus, human metapneumovirus A or B, human parainfluenza virus, S pneumoniae, M tuberculosis, and H influenzae each accounted for 5% or more of the aetiological distribution. We observed differences in aetiological fraction by age for Bordetella pertussis, parainfluenza types 1 and 3, parechovirus–enterovirus, P jirovecii, RSV, rhinovirus, Staphylococcus aureus, and S pneumoniae, and differences by severity for RSV, S aureus, S pneumoniae, and parainfluenza type 3. The leading ten pathogens of each site accounted for 79% or more of the site's aetiological fraction. In our study, a small set of pathogens accounted for most cases of pneumonia requiring hospital admission. Preventing and treating a subset of pathogens could substantially affect childhood pneumonia outcomes. Bill & Melinda Gates Foundation.

Typhoid fever remains a major cause of morbidity and mortality in low-income and middle-income countries. Vi-tetanus toxoid conjugate vaccine (Vi-TT) is recommended by WHO for implementation in high-burden countries, but there is little evidence about its ability to protect against clinical typhoid in such settings. We did a participant-masked and observer-masked cluster-randomised trial preceded by a safety pilot phase in an urban endemic setting in Dhaka, Bangladesh. 150 clusters, each with approximately 1350 residents, were randomly assigned (1:1) to either Vi-TT or SA 14-14-2 Japanese encephalitis (JE) vaccine. Children aged 9 months to less than 16 years were invited via parent or guardian to receive a single, parenteral dose of vaccine according to their cluster of residence. The study population was followed for an average of 17·1 months. Total and overall protection by Vi-TT against blood culture-confirmed typhoid were the primary endpoints assessed in the intention-to-treat population of vaccinees or all residents in the clusters. A subset of approximately 4800 participants was assessed with active surveillance for adverse events. The trial is registered at www.isrctn.com, ISRCTN11643110. 41 344 children were vaccinated in April–May, 2018, with another 20 412 children vaccinated at catch-up vaccination campaigns between September and December, 2018, and April and May, 2019. The incidence of typhoid fever (cases per 100 000 person-years) was 635 in JE vaccinees and 96 in Vi-TT vaccinees (total Vi-TT protection 85%; 97·5% CI 76 to 91, p<0·0001). Total vaccine protection was consistent in different age groups, including children vaccinated at ages under 2 years (81%; 95% CI 39 to 94, p=0·0052). The incidence was 213 among all residents in the JE clusters and 93 in the Vi-TT clusters (overall Vi-TT protection 57%; 97·5% CI 43 to 68, p<0·0001). We did not observe significant indirect vaccine protection by Vi-TT (19%; 95% CI −12 to 41, p=0·20). The vaccines were well tolerated, and no serious adverse events judged to be vaccine-related were observed. Vi-TT provided protection against typhoid fever to children vaccinated between 9 months and less than 16 years. Longer-term follow-up will be needed to assess the duration of protection and the need for booster doses. The study was funded by the Bill & Melinda Gates Foundation.

Novel oral poliovirus vaccine type 2 (nOPV2) was developed by modifying the Sabin strain to increase genetic stability and reduce risk of seeding new circulating vaccine-derived poliovirus type 2 outbreaks. Bivalent oral poliovirus vaccine (bOPV; containing Sabin types 1 and 3) is the vaccine of choice for type 1 and type 3 outbreak responses. We aimed to assess immunological interference between nOPV2 and bOPV when administered concomitantly. We conducted an open-label, non-inferiority, randomised, controlled trial at two clinical trial sites in Dhaka, Bangladesh. Healthy infants aged 6 weeks were randomly assigned (1:1:1) using block randomisation, stratified by site, to receive nOPV2 only, nOPV2 plus bOPV, or bOPV only, at the ages of 6 weeks, 10 weeks, and 14 weeks. Eligibility criteria included singleton and full term (≥37 weeks’ gestation) birth and parents intending to remain in the study area for the duration of study follow-up activities. Poliovirus neutralising antibody titres were measured at the ages of 6 weeks, 10 weeks, 14 weeks, and 18 weeks. The primary outcome was cumulative immune response for all three poliovirus types at the age of 14 weeks (after two doses) and was assessed in the modified intention-to-treat population, which was restricted to participants with adequate blood specimens from all study visits. Safety was assessed in all participants who received at least one dose of study product. A non-inferiority margin of 10% was used to compare single and concomitant administration. This trial is registered with ClinicalTrials.gov, NCT04579510. Between Feb 8 and Sept 26, 2021, 736 participants (244 in the nOPV2 only group, 246 in the nOPV2 plus bOPV group, and 246 in the bOPV only group) were enrolled and included in the modified intention-to-treat analysis. After two doses, 209 (86%; 95% CI 81–90) participants in the nOPV2 only group and 159 (65%; 58–70) participants in the nOPV2 plus bOPV group had a type 2 poliovirus immune response; 227 (92%; 88–95) participants in the nOPV2 plus bOPV group and 229 (93%; 89–96) participants in the bOPV only group had a type 1 response; and 216 (88%; 83–91) participants in the nOPV2 plus bOPV group and 212 (86%; 81–90) participants in the bOPV only group had a type 3 response. Co-administration was non-inferior to single administration for types 1 and 3, but not for type 2. There were 15 serious adverse events (including three deaths, one in each group, all attributable to sudden infant death syndrome); none were attributed to vaccination. Co-administration of nOPV2 and bOPV interfered with immunogenicity for poliovirus type 2, but not for types 1 and 3. The blunted nOPV2 immunogenicity we observed would be a major drawback of using co-administration as a vaccination strategy. The US Centers for Disease Control and Prevention.

Development of an easily deployable cholera vaccine for both endemic and epidemic disease is a high priority. In this report from Bangladesh, a single dose of an inactivated oral vaccine is assessed in a setting where cholera is endemic. Cholera remains a serious global health problem despite advances in the understanding of its pathogenesis and treatment 1 , 2 and despite the placement of improved water quality and sanitation at the forefront of global development priorities. 3 Killed oral vaccines against cholera have been under active development since the 1970s. In 2009, a public–private partnership in India developed and licensed a new killed whole-cell-only oral cholera vaccine (Shanchol, Shantha Biotechnics), which was modified from an earlier oral cholera vaccine produced in Vietnam and which is currently priced affordably for the public sector, at $1.85 per dose. In a trial conducted in Kolkata, . . .

Influenza infection causes significant morbidity in pregnant woman and neonates. In this randomized study of 340 pregnant women in Bangladesh, influenza vaccination during pregnancy was found to decrease laboratory-proven influenza infection in neonates by 63% and febrile respiratory illness in the mothers by more than a third. In pregnant women in Bangladesh, influenza vaccination during pregnancy was found to decrease laboratory-proven influenza infection in neonates by 63% and febrile respiratory illness in the mothers by more than a third. Infection with influenza virus is associated with serious illness and hospitalization among pregnant women 1 – 3 and young infants, including neonates. 4 – 6 Maternal influenza infection has been associated with an increased risk of maternal hospitalization, fetal malformation, and other illnesses. 7 , 8 Influenza infection in young infants often prompts hospitalization and can predispose the infants to bacterial pneumonia or otitis media. 9 , 10 Studies from North America 11 and Hong Kong 12 have shown high rates of hospitalization among infants with influenza, especially those under 6 months of age. 13 The rate of hospitalization for such infants is higher than that for other high-risk groups. A . . .

More than 100 countries have implemented pictorial health warnings on cigarette packages. However, few studies have compared how consumers from different geographic and cultural contexts respond to health warning content. The current study compares perceptions of warnings among adult smokers and youth in seven countries, to examine the efficacy of different health warning themes and images. Between 2010 and 2012, online and face-to-face surveys were conducted with ~500 adult smokers and ~500 youth (age 16-18) smokers and nonsmokers in each of Mexico, United States, China, Germany, India, Bangladesh, and Republic of Korea (total N = 8182). Respondents were randomized to view and rate sets of 5-7 health warnings (each set for a different health effect); each set included a text-only warning and various types (ie, themes) of pictorial warnings, including graphic health effects, \"lived experience,\" symbolic images, and personal testimonials. Mixed-effects models were utilized to examine perceived effectiveness of warning themes, and between-country differences in responses. Overall, pictorial warnings were rated as more effective than text-only warnings (p < .001). Among pictorial themes, \"graphic\" health effects were rated as more effective than warnings depicting \"lived experience\" (p < .001) or \"symbolic\" images (p < .001). Pictorial warnings with personal testimonials were rated as more effective than the same images with didactic text (p < .001). While the magnitude of differences between warning themes varied across countries, the pattern of findings was generally consistent. The findings support the efficacy of graphic pictorial warnings across diverse geographic and cultural contexts, and support sharing health warning images across jurisdictions. Although over 100 countries have implemented pictorial health warnings on cigarette packages, there is little research on the most effective types of message content across geographic and cultural contexts. The current study examined perceived effectiveness of text and pictorial health warnings featuring different message content-graphic health effects, \"lived experience,\" personal testimonials, and symbolic imagery-among more than 8000 adults and youth in Mexico, United States, China, Germany, India, Bangladesh, and Korea. Across countries, \"graphic\" pictorial messages were rated as most effective. Consistencies across countries in rating message content suggests there may be \"globally effective\" themes and styles for designing effective health warnings.

Many diarrhea-causing pathogens are climate-sensitive, and populations with the lowest socioeconomic position (SEP) are often most vulnerable to climate-related transmission. Household Water, Sanitation, and Handwashing (WASH) interventions constitute one potential effective strategy to reduce child diarrhea, especially among low-income households. Capitalizing on a cluster randomized trial population (360 clusters, 4941 children with 8440 measurements) in rural Bangladesh, one of the world’s most climate-sensitive regions, we show that improved WASH substantially reduces diarrhea risk with largest benefits among children with lowest SEP and during the monsoon season. We extrapolated trial results to rural Bangladesh regions using high-resolution geospatial layers to identify areas most likely to benefit. Scaling up a similar intervention could prevent an estimated 734 (95% CI 385, 1085) cases per 1000 children per month during the seasonal monsoon, with marked regional heterogeneities. Here, we show how to extend large-scale trials to inform WASH strategies among climate-sensitive and low-income populations. Household water, sanitation, and handwashing (WASH) interventions can reduce diarrhoea-related morbidity in young children. Here, the authors report findings from a pre-specified secondary analysis of a cluster-randomised trial assessing how WASH impacts vary by socioeconomic position and season.

Cholera is endemic in Bangladesh with epidemics occurring each year. The decision to use a cheap oral killed whole-cell cholera vaccine to control the disease depends on the feasibility and effectiveness of vaccination when delivered in a public health setting. We therefore assessed the feasibility and protective effect of delivering such a vaccine through routine government services in urban Bangladesh and evaluated the benefit of adding behavioural interventions to encourage safe drinking water and hand washing to vaccination in this setting. We did this cluster-randomised open-label trial in Dhaka, Bangladesh. We randomly assigned 90 clusters (1:1:1) to vaccination only, vaccination and behavioural change, or no intervention. The primary outcome was overall protective effectiveness, assessed as the risk of severely dehydrating cholera during 2 years after vaccination for all individuals present at time of the second dose. This study is registered with ClinicalTrials.gov, number NCT01339845. Of 268 896 people present at baseline, we analysed 267 270: 94 675 assigned to vaccination only, 92 539 assigned to vaccination and behavioural change, and 80 056 assigned to non-intervention. Vaccine coverage was 65% in the vaccination only group and 66% in the vaccination and behavioural change group. Overall protective effectiveness was 37% (95% CI lower bound 18%; p=0·002) in the vaccination group and 45% (95% CI lower bound 24%; p=0·001) in the vaccination and behavioural change group. We recorded no vaccine-related serious adverse events. Our findings provide the first indication of the effect of delivering an oral killed whole-cell cholera vaccine to poor urban populations with endemic cholera using routine government services and will help policy makers to formulate vaccination strategies to reduce the burden of severely dehydrating cholera in such populations. Bill & Melinda Gates Foundation.

ObjectiveTo assess the prevalence of and factors associated with depression among adolescent boys and girls.DesignWe conducted a nationwide cross-sectional study.SettingThis study was carried out in 82 randomly selected clusters (57 rural, 15 non-slum urban and 10 slums) from eight divisions of Bangladesh.ParticipantsWe interviewed 4907 adolescent boys and 4949 adolescent girls.Primary and secondary outcome measuresThe primary outcome measure was ‘any depression’ and the secondary outcome measures were types of depression: no or minimal, mild, moderate, moderately severe and severe.ResultsThe overall prevalence of no or minimal, mild, moderate, moderately severe and severe depression was 75.5%, 17.9%, 5,4%, 1.1% and 0.1%, respectively. Across most of the sociodemographic, lifestyle and anthropometric strata, the prevalence of any depression was higher among adolescent girls. In both sexes, depression was associated with higher age, higher maternal education, paternal occupation e.g., business, absence of a 6–9-year-old member in the household, food insecurity, household consumption of unfortified oil, household use of non-iodised salt, insufficient physical activity (adjusted odds ratio, AOR: 1.24 for boys, 1.44 for girls) and increased television viewing time e.g., ≥121 minute/day (AOR: 1.95 for boys, 1.99 for girls). Only among boys, depression was also associated with higher paternal education e.g., complete secondary and above (AOR: 1.42), absence of another adolescent member in the household (AOR: 1.34), household use of solid biomass fuel (AOR: 1.39), use of any tobacco products (AOR: 2.17), and consumption of processed food (AOR: 1.24). Only among girls, non-slum urban residence, Muslim religion, and household size ≤4 were also associated with depression.ConclusionThe prevalence of depression among adolescent boys and girls is high in Bangladesh. In most sociodemographic, lifestyle and anthropometric strata, the prevalence is higher among girls. In this age group, depression is associated with a number of sociodemographic and lyfestyle factors. The government of Bangladesh should consider these findings while integrating adolescent mental health in the existing and future programmes.