SummaryBackgroundWe have previously estimated that respiratory syncytial virus (RSV) was associated with 22% of all episodes of (severe) acute lower respiratory infection (ALRI) resulting in 55 000 to 199 000 deaths in children younger than 5 years in 2005. In the past 5 years, major research activity on RSV has yielded substantial new data from developing countries. With a considerably expanded dataset from a large international collaboration, we aimed to estimate the global incidence, hospital admission rate, and mortality from RSV-ALRI episodes in young children in 2015.MethodsWe estimated the incidence and hospital admission rate of RSV-associated ALRI (RSV-ALRI) in children younger than 5 years stratified by age and World Bank income regions from a systematic review of studies published between Jan 1, 1995, and Dec 31, 2016, and unpublished data from 76 high quality population-based studies. We estimated the RSV-ALRI incidence for 132 developing countries using a risk factor-based model and 2015 population estimates. We estimated the in-hospital RSV-ALRI mortality by combining in-hospital case fatality ratios with hospital admission estimates from hospital-based (published and unpublished) studies. We also estimated overall RSV-ALRI mortality by identifying studies reporting monthly data for ALRI mortality in the community and RSV activity.FindingsWe estimated that globally in 2015, 33·1 million (uncertainty range [UR] 21·6–50·3) episodes of RSV-ALRI, resulted in about 3·2 million (2·7–3·8) hospital admissions, and 59 600 (48 000–74 500) in-hospital deaths in children younger than 5 years. In children younger than 6 months, 1·4 million (UR 1·2–1·7) hospital admissions, and 27 300 (UR 20 700–36 200) in-hospital deaths were due to RSV-ALRI. We also estimated that the overall RSV-ALRI mortality could be as high as 118 200 (UR 94 600–149 400). Incidence and mortality varied substantially from year to year in any given population.InterpretationGlobally, RSV is a common cause of childhood ALRI and a major cause of hospital admissions in young children, resulting in a substantial burden on health-care services. About 45% of hospital admissions and in-hospital deaths due to RSV-ALRI occur in children younger than 6 months. An effective maternal RSV vaccine or monoclonal antibody could have a substantial effect on disease burden in this age group.FundingThe Bill & Melinda Gates Foundation.

BackgroundRespiratory syncytial virus (RSV) is the most common pathogen identified in young children with acute lower respiratory infection (ALRI) as well as an important cause of hospital admission. The high incidence of RSV infection and its potential severe outcome make it important to identify and prioritise children who are at higher risk of developing RSV–associated ALRI. We aimed to identify risk factors for RSV–associated ALRI in young children.MethodsWe carried out a systematic literature review across 4 databases and obtained unpublished studies from RSV Global Epidemiology Network (RSV GEN) collaborators. Quality of all eligible studies was assessed according to modified GRADE criteria. We conducted meta–analyses to estimate odds ratios with 95% confidence intervals (CI) for individual risk factors.ResultsWe identified 20 studies (3 were unpublished data) with “good quality” that investigated 18 risk factors for RSV–associated ALRI in children younger than five years old. Among them, 8 risk factors were significantly associated with RSV–associated ALRI. The meta–estimates of their odds ratio (ORs) with corresponding 95% confidence intervals (CI) are prematurity 1.96 (95% CI 1.44–2.67), low birth weight 1.91 (95% CI 1.45–2.53), being male 1.23 (95% CI 1.13–1.33), having siblings 1.60 (95% CI 1.32–1.95), maternal smoking 1.36 (95% CI 1.24–1.50), history of atopy 1.47 (95% CI 1.16–1.87), no breastfeeding 2.24 (95% CI 1.56–3.20) and crowding 1.94 (95% CI 1.29–2.93). Although there were insufficient studies available to generate a meta–estimate for HIV, all articles (irrespective of quality scores) reported significant associations between HIV and RSV–associated ALRI.ConclusionsThis study presents a comprehensive report of the strength of association between various socio–demographic risk factors and RSV–associated ALRI in young children. Some of these amenable risk factors are similar to those that have been identified for (all cause) ALRI and thus, in addition to the future impact of novel RSV vaccines, national action against ALRI risk factors as part of national control programmes can be expected to reduce burden of disease from RSV. Further research which identifies, accesses and analyses additional unpublished RSV data sets could further improve the precision of these estimates.

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.

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We have characterized the mutations in 1050 carriers of the beta-thalassemia gene and analyzed their regional distribution in India. The majority of beta-thalassemia carriers were migrants from Pakistan and their pattern of mutations differed from the rest. The frequency of the 619-bp deletion was 33.3% among the migrants from Pakistan, 8-17% in the northern states, and less than 5% in the other states. Among non-migrant subjects, the predominant mutation was IVS-I-5 (G-->C), varying from 85% in the southern states and 66-70% in the eastern states to 47-60% in the northern states. The mutation IVS-I-1 (G-->T) was observed at high frequency among the migrants from Pakistan (26.2%), but with very low/zero frequency in the other states. Mutations at codons 8/9 (+G) and codons 41/42 (-CTTT) were distributed in all regions of India with a frequency varying from 3% to 15%. Only eight of 12 published rare mutations were observed in subjects from different parts of India. Mutations of codon 5 (-CT) and codons 47/48 (+ATCT) were found exclusively in migrants from Pakistan, and mutation -88 (C-->T) was detected only in subjects from Punjab, Haryana, and Uttar Pradesh. Using the amplification refractory mutation system technique, mutations were successfully identified in 98.2% of subjects. Overall, 91.8% of the subjects had one of the five commonest mutations [IVS-I-5 (G-->C), 34.1%; 619-bp deletion, 21.0%; IVS-I-1 (G-->T) 15.8%; codons 8/9 (+G), 12.1%, and codons 41/42 (-CTTT), 8.7%], 5.9% of the subjects had a less common mutation, while 1.8% of the carriers remained uncharacterized. The application of this knowledge has helped to successfully establish a program of genetic counselling and prenatal diagnosis of beta-thalassemia in order to reduce the burden of this disease in India.

Background The Cholera-Hospital-Based-Intervention-for-7-Days (CHoBI7) is a handwashing with soap and water treatment intervention program delivered by a health promoter bedside in a health facility and through home visits to diarrhea patients and their household members during the 7 days after admission to a health facility. In a randomized controlled trial among cholera patient households in Bangladesh, the 7-day CHoBI7 program resulted in a significant reduction in cholera among household members of cholera patients and sustained improvements in drinking water quality and handwashing with soap practices 12 months post-intervention. In an effort to take this intervention to scale across Bangladesh in partnership with the Bangladesh Ministry of Health and Family Welfare, this study evaluates the feasibility and acceptability of mobile health (mHealth) programs as a low-cost, scalable approach for CHoBI7 program delivery. Methods Formative research for the development of the CHoBI7 mHealth intervention included 40 semi-structured interviews, 4 mHealth workshops, 2 group discussions, and a pilot study of 52 households to assess the feasibility and acceptability of the developed mHealth program. Thematic analysis of the interviews and group discussions was conducted by two individuals separately based on emergent themes, and then themes were compared and discussed. Results A theory- and evidence-based approach using qualitative research methods was implemented to design the CHoBI7 mHealth program. Semi-structured interviews with government stakeholders identified perceptions and preferences for scaling the CHoBI7 mHealth program. Group discussions and semi-structured interviews with diarrhea patients and their family members identified beneficiary perceptions of mHealth and preferences for CHoBI7 mHealth program delivery. mHealth workshops were conducted as an interactive approach to draft and refine mobile message content based on stakeholder preferences. The pilot findings indicate that the CHoBI7 mHealth program has high user acceptability and is feasible to deliver to diarrhea patients that present at health facilities for treatment in Bangladesh. Both text and voice messages were recommended for program delivery. Dr. Chobi, the sender of mHealth messages, was viewed as a credible source of information that could be shared with others. Conclusion This study presents a theory- and evidence-based approach that can be implemented for the development of future water, sanitation, and hygiene mHealth programs in low-resource settings. Electronic supplementary material The online version of this article (10.1186/s12889-019-7144-z) contains supplementary material, which is available to authorized users.

Background: During the time a diarrhea patient presents at a health facility, the household members of the patient are at higher risk of developing diarrheal diseases (> 100 times for cholera) than the general population. The Cholera-Hospital-based-Intervention-for-7-Days (CHoBI7) is a health facility-initiated water treatment and handwashing with soap intervention designed to reduce transmission of diarrheal diseases between patients and their household members. The present research aimed to (1) develop a scalable approach to integrate the CHoBI7 intervention program into services provided at government and private health facilities in Bangladesh; and (2) tailor the intervention program for the household members of all diarrhea patients, irrespective of the etiology of disease. Methods: We conducted 8 months of formative research, including 60 semi-structured interviews, 2 group discussions, and a pilot study. Thirty-two interviews were conducted with diarrhea patients and their family caregivers, government stakeholders, and health care providers both to explore existing WASH and diarrhea patient care practices in health facilities and to identify considerations for scaling the CHoBI7 program. Fifty-two diarrhea patient households participated in a pilot study of a modified version of the CHoBI7 intervention program for tailoring. Twenty-eight interviews and 2 group discussions were conducted with pilot households to explore experiences with and recommendations for intervention delivery.

Elevated exposure to arsenic disproportionately affects populations relying on private well water in the United States (US). This includes many American Indian (AI) communities where naturally occurring arsenic is often above 10 µg/L, the current US Environmental Protection Agency safety standard. The Strong Heart Water Study is a randomized controlled trial aiming to reduce arsenic exposure to private well water users in AI communities in North Dakota and South Dakota. In preparation for this intervention, 371 households were included in a community water arsenic testing program to identify households with arsenic ≥10 µg/L by inductively coupled plasma mass spectrometry (ICP-MS). Arsenic ≥10 µg/L was found in 97/371 (26.1%) households; median water arsenic concentration was 6.3 µg/L, ranging from <1-198 µg/L. Silica was identified as a water quality parameter that could impact the efficacy of arsenic removal devices to be installed. A low-range field rapid arsenic testing kit evaluated in a small number of households was found to have low accuracy; therefore, not an option for the screening of affected households in this setting. In a pilot study of the effectiveness of a point-of-use adsorptive media water filtration device for arsenic removal, all devices installed removed arsenic below 1 µg/L at both installation and 9 months post-installation. This study identified a relatively high burden of arsenic in AI study communities as well as an effective water filtration device to reduce arsenic in these communities. The long-term efficacy of a community based arsenic mitigation program in reducing arsenic exposure and preventing arsenic related disease is being tested as part of the Strong Heart Water Study.