Summary Background Rotavirus vaccine has proved effective for prevention of severe rotavirus gastroenteritis in infants in developed countries, but no efficacy studies have been done in developing ...countries in Asia. We assessed the clinical efficacy of live oral pentavalent rotavirus vaccine for prevention of severe rotavirus gastroenteritis in infants in Bangladesh and Vietnam. Methods In this multicentre, double-blind, placebo-controlled trial, undertaken in rural Matlab, Bangladesh, and urban and periurban Nha Trang, Vietnam, infants aged 4–12 weeks without symptoms of gastrointestinal disorders were randomly assigned (1:1) to receive three oral doses of pentavalent rotavirus vaccine 2 mL or placebo at around 6 weeks, 10 weeks, and 14 weeks of age, in conjunction with routine infant vaccines including oral poliovirus vaccine. Randomisation was done by computer-generated randomisation sequence in blocks of six. Episodes of gastroenteritis in infants who presented to study medical facilities were reported by clinical staff and from parent recollection. The primary endpoint was severe rotavirus gastroenteritis (Vesikari score ≥11) arising 14 days or more after the third dose of placebo or vaccine to end of study (March 31, 2009; around 21 months of age). Analysis was per protocol; infants who received scheduled doses of vaccine or placebo without intervening laboratory-confirmed naturally occurring rotavirus disease earlier than 14 days after the third dose and had complete clinical and laboratory results were included in the analysis. This study is registered with ClinicalTrials.gov , number NCT00362648. Findings 2036 infants were randomly assigned to receive pentavalent rotavirus vaccine (n=1018) or placebo (n=1018). 991 infants assigned to pentavalent rotavirus vaccine and 978 assigned to placebo were included in the per-protocol analysis. Median follow up from 14 days after the third dose of placebo or vaccine until final disposition was 498 days (IQR 480–575). 38 cases of severe rotavirus gastroenteritis (Vesikari score ≥11) were reported during more than 1197 person-years of follow up in the vaccine group, compared with 71 cases in more than 1156 person years in the placebo group, resulting in a vaccine efficacy of 48·3% (95% CI 22·3–66·1) against severe disease (p=0·0005 for efficacy >0%) during nearly 2 years of follow-up. 25 (2·5%) of 1017 infants assigned to receive vaccine and 20 (2·0%) of 1018 assigned to receive placebo had a serious adverse event within 14 days of any dose. The most frequent serious adverse event was pneumonia (vaccine 12 1·2%; placebo 15 1·5%). Interpretation In infants in developing countries in Asia, pentavalent rotavirus vaccine is safe and efficacious against severe rotavirus gastroenteritis, and our results support expanded WHO recommendations to promote its global use. Funding PATH (GAVI Alliance grant) and Merck.
Summary Background Influenza causes substantial morbidity and mortality worldwide. Few data exist for the efficacy of neuraminidase inhibitors, which are the only readily available influenza ...treatment options, especially in low-income settings. We assessed the efficacy of treatment with the neuraminidase inhibitor oseltamivir to reduce patient illness and viral shedding in people with influenza, in whom treatment was started within 5 days of symptom onset, in an urban setting in Bangladesh. Methods We undertook a double-blind, randomised, controlled trial between May, 2008, and December, 2010. Patients with a positive rapid influenza test identified by surveillance of households in Kamalapur, Bangladesh were randomly allocated on a 1:1 basis to receive oseltamivir or placebo twice daily for 5 days. Randomisation lists for individuals enrolled less than 48 h and 48 h or longer since illness onset were generated with permuted blocks of variable length between two and eight. Participants and study staff were masked to treatment group. Participants provided nasal wash specimens at enrolment and 2, 4, and 7 days later, and were visited daily to record symptoms. All specimens were tested for influenza with reverse-transcriptase PCR, and if the result was positive, we isolated the virus. The primary endpoints were duration of clinical illness and viral shedding in patients treated less than and more than 48 h since illness onset and the frequency of oseltamivir resistance during treatment. Analyses were intention to treat unless otherwise specified. This trial is registered with ClinicalTrials.gov , number NCT00707941. Findings Overall, 1190 people with a median age of 5 years (IQR 2–9) were enrolled: 794 (67%) less than 48 h since symptom onset and 396 (33%) 48 h or longer since symptom onset. 592 participants were assigned to placebo and 598 to oseltamivir. The median duration of symptoms was shorter in the oseltamivir group (3 days, IQR 1–5) than in the placebo group (4 days, 1–6; p=0·01). When stratified by timing of treatment initiation, in participants enrolled 48 h or longer since illness onset, the median duration of symptoms was similar in both groups (oseltamivir 3 days IQR 2–5, placebo 3 days 1–5; p=0·04). The median duration of symptoms was reduced by 1 day in the group given oseltamivir who were enrolled less than 48 h since symptom onset compared with those given placebo, but this difference was not significant. In those with all swab specimens (n=1134), oseltamivir significantly reduced virus isolation on days 2 (placebo 374 66% vs oseltamivir 321 56%; difference 15·2%, 95% CI 9·5–20·8, p=0·0004), 4 (241 43% vs 174 30%; difference 30·2%, 95% CI 24·6–35·8, p<0·0001), and 7 (68 12% vs 36 6%; difference 47·5%, 95% CI 44·2–50·8, p=0·0009). In participants enrolled 48 h or longer since illness onset, oseltamivir treatment significantly reduced virus isolation on days 2 and 4, but not day 7. In participants enrolled less than 48 h since illness onset, oseltamivir treatment significantly reduced virus isolation on days 2, 4, and 7. The emergency of resistance to oseltamivir during treatment was rare overall (<1%) and in influenza A H1N1pdm09 viruses (3·9%). Interpretation Oseltamivir treatment resulted in a modest reduction in the duration of symptoms and virus shedding in people with uncomplicated influenza infections, even when treatment was started 48 h or longer after illness onset. Funding Centers for Disease Control and Prevention (in agreement with the International Centre for Diarrhoeal Disease Research, Bangladesh).
Poor nutrition and exposure to faecal contamination are associated with diarrhoea and growth faltering, both of which have long-term consequences for child health. We aimed to assess whether water, ...sanitation, handwashing, and nutrition interventions reduced diarrhoea or growth faltering.
The WASH Benefits cluster-randomised trial enrolled pregnant women from villages in rural Kenya and evaluated outcomes at 1 year and 2 years of follow-up. Geographically-adjacent clusters were block-randomised to active control (household visits to measure mid-upper-arm circumference), passive control (data collection only), or compound-level interventions including household visits to promote target behaviours: drinking chlorinated water (water); safe sanitation consisting of disposing faeces in an improved latrine (sanitation); handwashing with soap (handwashing); combined water, sanitation, and handwashing; counselling on appropriate maternal, infant, and young child feeding plus small-quantity lipid-based nutrient supplements from 6–24 months (nutrition); and combined water, sanitation, handwashing, and nutrition. Primary outcomes were caregiver-reported diarrhoea in the past 7 days and length-for-age Z score at year 2 in index children born to the enrolled pregnant women. Masking was not possible for data collection, but analyses were masked. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01704105.
Between Nov 27, 2012, and May 21, 2014, 8246 women in 702 clusters were enrolled and randomly assigned an intervention or control group. 1919 women were assigned to the active control group; 938 to passive control; 904 to water; 892 to sanitation; 917 to handwashing; 912 to combined water, sanitation, and handwashing; 843 to nutrition; and 921 to combined water, sanitation, handwashing, and nutrition. Data on diarrhoea at year 1 or year 2 were available for 6494 children and data on length-for-age Z score in year 2 were available for 6583 children (86% of living children were measured at year 2). Adherence indicators for sanitation, handwashing, and nutrition were more than 70% at year 1, handwashing fell to less than 25% at year 2, and for water was less than 45% at year 1 and less than 25% at year 2; combined groups were comparable to single groups. None of the interventions reduced diarrhoea prevalence compared with the active control. Compared with active control (length-for-age Z score −1·54) children in nutrition and combined water, sanitation, handwashing, and nutrition were taller by year 2 (mean difference 0·13 95% CI 0·01–0·25 in the nutrition group; 0·16 0·05–0·27 in the combined water, sanitation, handwashing, and nutrition group). The individual water, sanitation, and handwashing groups, and combined water, sanitation, and handwashing group had no effect on linear growth.
Behaviour change messaging combined with technologically simple interventions such as water treatment, household sanitation upgrades from unimproved to improved latrines, and handwashing stations did not reduce childhood diarrhoea or improve growth, even when adherence was at least as high as has been achieved by other programmes. Counselling and supplementation in the nutrition group and combined water, sanitation, handwashing, and nutrition interventions led to small growth benefits, but there was no advantage to integrating water, sanitation, and handwashing with nutrition. The interventions might have been more efficacious with higher adherence or in an environment with lower baseline sanitation coverage, especially in this context of high diarrhoea prevalence.
Bill & Melinda Gates Foundation, United States Agency for International Development.
Background Family caregivers are integral to patient care in Bangladeshi public hospitals. This study explored family caregivers' activities and their perceptions and practices related to disease ...transmission and prevention in public hospitals. Methods Trained qualitative researchers conducted a total of 48 hours of observation in 3 public tertiary care hospitals and 12 in-depth interviews with family caregivers. Results Family caregivers provided care 24 hours a day, including bedside nursing, cleaning care, and psychologic support. During observations, family members provided 2,065 episodes of care giving, 75% (1,544) of which involved close contact with patients. We observed family caregivers washing their hands with soap on only 4 occasions. The majority of respondents said diseases are transmitted through physical contact with surfaces and objects that have been contaminated with patient secretions and excretions, and avoiding contact with these contaminated objects would help prevent disease. Conclusion Family caregivers are at risk for hospital-acquired infection from their repeated exposure to infectious agents combined with their inadequate hand hygiene and knowledge about disease transmission. Future research should explore potential strategies to improve family caregivers' knowledge about disease transmission and reduce family caregiver exposures, which may be accomplished by improving care provided by health care workers.
Summary Background The provision of several doses of monovalent type 1 oral poliovirus vaccine (mOPV1) and bivalent OPV1 and 3 (bOPV) vaccines through campaigns is essential to stop the circulation ...of remaining wild polioviruses. Our study aimed to assess the shortening of intervals between campaigns with bOPV and mOPV1 and to assess the immunogenicity of bOPV in routine immunisation schedules. Methods We did an open-label, non-inferiority, five-arm, randomised controlled trial in Bangladesh. We recruited healthy infants aged 6 weeks at 42 immunisation clinics and randomly assigned them (with blocks of 15, three per group) to receive a short three-dose schedule of bOPV (bOPV short) or mOPV1 (mOPV1 short) with the first dose given at age 6 weeks, the second at age 8 weeks, and the third at age 10 weeks; or to a standard three-dose schedule of bOPV (bOPV standard) or mOPV1 (mOPV1 standard) or trivalent OPV (tOPV standard) with the first dose given at age 6 weeks, the second at 10 weeks, and the third at age 14 weeks. The primary outcome was the proportion of infants with antibody seroconversion for type 1, type 2, and type 3 polioviruses. The primary, modified intention-to-treat analysis included all patients who had testable serum samples before and after receiving at least one OPV dose. We used a 10% margin to establish non-inferiority for bOPV groups versus mOPV1 groups in seroconversion for type 1 poliovirus, and for bOPV1 short versus bOPV1 standard for types 1 and 3. This trial is registered at ClinicalTrials.gov , number NCT01633216 , and is closed to new participants. Findings Between May 13, 2012, and Jan 21, 2013, we randomly assigned 1000 infants to our study groups. 927 completed all study visits and were included in the primary analysis. Seroconversion for type-1 poliovirus was recorded in 183 (98%, 95% CI 95–100) of 186 infants given bOPV short, 179 (97%, 94–99) of 184 given bOPV standard, 180 (96%, 92–98) of 188 given mOPV short, 178 (99%, 97–100) of 179 given mOPV1 standard, and 175 (92%, 87–96) of 190 given tOPV standard. Seroconversion for type 2 was noted in 16 infants (9%, 5–14) on bOPV short, 29 (16%, 11–22) on bOPV standard, 19 (10%, 7–15) on mOPV short, 33 (18%, 13–25) on mOPV1 standard, and 182 (96%, 92–98) on tOPV standard. Seroconversion for type 3 was noted in 175 infants (94%, 90–97) on bOPV short, 176 (96%, 92–98) on bOPV standard, 18 (10%, 6–15) on mOPV short, 25 (14%, 10–20) on mOPV1 standard, and 167 (88%, 83–92) on tOPV standard. The short schedules for mOPV1 and bOPV elicited a non-inferior antibody response compared with the bOPV standard schedule. 104 adverse events were reported in 100 infants during follow up. 36 of these events needed admission to hospital (32 were pneumonia, two were vomiting or feeding disorders, one was septicaemia, and one was diarrhoea with severe malnutrition). One of the infants admitted to hospital for pneumonia died 5 days after admission. No adverse event was attributed to the vaccines. Interpretation Our trial showed that three doses of mOPV1 or bOPV with a short schedule of 2 week intervals between doses induces an immune response similar to that obtained with the standard schedule of giving doses at 4 week intervals. These findings support the use of these vaccines in campaigns done at short intervals to rapidly increase population immunity against polioviruses to control outbreaks or prevent transmission in high-risk areas. Funding Centers for Disease Control and Prevention and UNICEF.
Objectives Some Asian countries have been reluctant to adopt Haemophilus influenzae type b (Hib) conjugate vaccination because of uncertainty over disease burden. We assessed the impact of ...introduction of Hib conjugate vaccine into the Expanded Program on Immunization in Bangladesh on purulent and laboratory-confirmed H influenzae meningitis. Study design Within a well-defined catchment area around 2 surveillance hospitals in Dhaka, Bangladesh, we compared the incidence of Hib meningitis confirmed by culture, latex agglutination, and polymerase chain reaction assay among infants 1 year before and 1 year after introduction of Hib conjugate vaccine. We adjusted the incidence rate for the proportion of children who sought care at the surveillance hospitals. Results Among infants, the incidence of confirmed Hib meningitis decreased from 92-16 cases per 100 000 within 1 year of vaccine introduction (vaccine preventable incidence = 76; 95% CI 18, 135 per 100 000). The incidence of purulent meningitis decreased from 1659-1159 per 100 000 (vaccine preventable incidence = 500; 95% CI: 203, 799 per 100 000). During the same time period, there was no significant difference in the incidence of meningitis due to Streptococcus pneumoniae. Conclusions Introduction of conjugate Hib conjugate vaccine into Bangladesh Expanded Program on Immunization markedly reduced the burden of Hib and purulent meningitis.
Abstract Background Drinking water salinity has contributed to scarcity of potable water in southwest coastal Bangladesh. Drinking saline water has been associated with high blood pressure among ...communities in southwest coastal Bangladesh, but the effect of water salinity on kidney health is unknown. We aimed to understand the association between drinking water salinity and urinary protein excretion from the baseline findings of a community-based stepped-wedge randomised trial. Methods We collected 24-h urine from 1185 participants from 532 households and 16 communities in three districts (Khulna, Satkhira, and Bagerhat) of southwest coastal Bangladesh between Nov 17, and Dec 21, 2016, and measured urinary sodium and total protein. We measured electrical conductivity in sampled households' stored drinking water. We estimated water chloride concentration by using a published conversion factor and then estimated daily sodium intake by drinking water assuming sodium ions will be coupled with chloride in water. Among normotensive participants who reported exclusively drinking household stored water, and did not report kidney or heart diseases or diabetes, we determined the effects of daily sodium intake by water and urinary sodium on total protein using hierarchical models accounting for household and community level clustering, and adjusted for age, sex and, weight. Findings Mean urinary sodium was 164 mmoL/24 h and total protein was 402 mg/24 h. Mean sodium intake through drinking water was 17 mmoL per day. For each 1000 μS/cm higher in drinking water electrical conductivity, there was a 8·2 mmoL/24 h (95% CI 5·3–11·1) higher excretion of 24-h urinary sodium. For each 10 mmoL increase in estimated daily sodium intake through drinking water, there was a 15·9 mg/24 h (95% CI 0·3–31·6) increase in total protein. We estimated a 62·9 mg/24 h (95% CI 29·7–96·1) increase in total protein for each 100 mmoL/24 h increase urinary sodium. We identified 37% participants that had mild proteinuria (total protein: 300–500 mg/24 h) and 20% had moderate or substantial proteinuria (total protein: >500 mg/24 h). Interpretation Drinking water sodium and urinary sodium were associated with increased protein excretion—a powerful marker for progressive kidney disease—in southwest coastal Bangladesh. Interventions aimed at lowering drinking water salinity could provide benefit to kidney health. Funding Wellcome Trust, UK.
We conducted a cluster-randomized trial to measure the effect of community-level mask distribution and promotion on symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections ...in rural Bangladesh from November 2020 to April 2021 (
= 600 villages,
= 342,183 adults). We cross-randomized mask type (cloth versus surgical) and promotion strategies at the village and household level. Proper mask-wearing increased from 13.3% in the control group to 42.3% in the intervention arm (adjusted percentage point difference = 0.29; 95% confidence interval = 0.26, 0.31). The intervention reduced symptomatic seroprevalence (adjusted prevalence ratio = 0.91 0.82, 1.00), especially among adults ≥60 years old in villages where surgical masks were distributed (adjusted prevalence ratio = 0.65 0.45, 0.85). Mask distribution with promotion was a scalable and effective method to reduce symptomatic SARS-CoV-2 infections.
A regulated stress response is essential for healthy child growth and development trajectories. We conducted a cluster-randomized trial in rural Bangladesh (funded by the Bill & Melinda Gates ...Foundation, ClinicalTrials.gov NCT01590095) to assess the effects of an integrated nutritional, water, sanitation, and handwashing intervention on child health. We previously reported on the primary outcomes of the trial, linear growth and caregiver-reported diarrhea. Here, we assessed additional prespecified outcomes: physiological stress response, oxidative stress, and DNA methylation (N = 759, ages 1-2 years). Eight neighboring pregnant women were grouped into a study cluster. Eight geographically adjacent clusters were block-randomized into the control or the combined nutrition, water, sanitation, and handwashing (N + WSH) intervention group (receiving nutritional counseling and lipid-based nutrient supplements, chlorinated drinking water, upgraded sanitation, and handwashing with soap). Participants and data collectors were not masked, but analyses were masked. There were 358 children (68 clusters) in the control group and 401 children (63 clusters) in the intervention group. We measured four F2-isoprostanes isomers (iPF(2α)-III; 2,3-dinor-iPF(2α)-III; iPF(2α)-VI; 8,12-iso-iPF(2α)-VI), salivary alpha-amylase and cortisol, and methylation of the glucocorticoid receptor (NR3C1) exon 1F promoter including the NGFI-A binding site. Compared with control, the N + WSH group had lower concentrations of F2-isoprostanes isomers (differences ranging from -0.16 to -0.19 log ng/mg of creatinine, P < 0.01), elevated post-stressor cortisol (0.24 log µg/dl; P < 0.01), higher cortisol residualized gain scores (0.06 µg/dl; P = 0.023), and decreased methylation of the NGFI-A binding site (-0.04; P = 0.037). The N + WSH intervention enhanced adaptive responses of the physiological stress system in early childhood.
Started in 2007, the Sanitation Hygiene Education and Water Supply in Bangladesh (SHEWA-B) project aims to improve the hygiene, sanitation and water supply for 20 million people in Bangladesh, and ...thus reduce disease among this population. This paper assesses the effectiveness of SHEWA-B on changing behaviors and reducing diarrhea and respiratory illness among children < 5 years of age. We assessed behaviors at baseline in 2007 and after 6 months and 18 months by conducting structured observation of handwashing behavior in 500 intervention and 500 control households. In addition we conducted spot checks of water and sanitation facilities in 850 intervention and 850 control households. We also collected monthly data on diarrhea and respiratory illness from 500 intervention and 500 control households from October 2007 to September 2009. Participants washed their hands with soap < 3% of the time around food related events in both intervention and control households at baseline and after 18 months. Washing both hands with soap or ash after cleaning a child's anus increased from 22% to 36%, and no access to a latrine decreased from 10% to 6.8% from baseline to 18 months. The prevalence of diarrhea and respiratory illness, among children <5 years of age were similar in intervention and control communities throughout the study. This large scale sanitation, hygiene and water improvement programme resulted in improvements in a few of its targeted behaviors, but these modest behavior changes have not yet resulted in a measurable reduction in childhood diarrhea and respiratory illness.
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