Search

Objective: To examine how maternal depressive symptoms are related to infant development among low-income infants in rural Bangladesh and to examine how the relationship is affected by maternal perceptions of infant irritability and observations of caregiving practices. Methods: Development was measured among 221 infants at 6 and 12 months with the Bayley Scales II. Mothers reported on their depressive symptoms and on perceptions of their infant's temperament, and a home visit was made to complete the HOME Inventory. Results: Half (52%) the mothers reported depressive symptoms. In bivariate analyses, maternal depressive symptoms were related to low scores on the Bayley Scales. Infants whose mothers reported depressive symptoms and perceived their infants to be irritable acquired fewer cognitive, motor, and Orientation/Engagement skills between 6-12 months than infants whose mothers reported neither or only one condition. The relationship linking maternal depressive symptoms and perceived infant irritability with infant cognitive skills was partially mediated by parental responsiveness and opportunities for play in the home. Conclusions: The intergenerational risks of maternal depressive symptoms on infant development extend to rural Bangladesh and are accentuated when mothers perceive their infants as irritable. Mothers who report depressive symptoms and infant irritability may lack the capacity to provide responsive, developmentally-oriented caregiving environments.

Background: Children in resource-limited settings remain vulnerable to zinc deficiency and its consequences.Objectives: To evaluate the effects of different doses, durations, and frequencies of zinc supplementation on the incidence of diarrhea and change in linear growth among young children.Methods: We conducted a randomized, partially double-blind, controlled, 6-arm, community-based efficacy trial in Dhaka, Bangladesh. Children aged 9-11 mo were randomly assigned to receive 1 of the following interventions for 24 wk: 1) standard micronutrient powder (MNP) containing 4.1 mg zinc and 10 mg iron, daily; 2) high-zinc (10 mg), low-iron (6 mg) (HiZn LoFe) MNP, daily; 3) HiZn (10 mg) LoFe (6 mg)/HiZn (10 mg), no-iron MNPs on alternating days; 4) dispersible zinc tablet (10 mg), daily; 5) dispersible zinc tablet (10 mg), daily for 2 wk at enrollment and 12 wk; 6) placebo powder, daily. Primary outcomes were incidence of diarrhea and change in length-for-age z-score (LAZ) over the 24-wk intervention period. Home visits were conducted twice weekly to assess diarrhea and other morbidity. Incidence and prevalence outcomes were compared among groups with Poisson regression; continuous outcomes were compared using ANCOVA.Results: A total of 2886 children were enrolled between February 2018 and July 2019. The mean incidence and prevalence of diarrhea among all participants was 1.21 episodes per 100 d and 3.76 d per 100 d, respectively. There were no differences in the incidence or prevalence of diarrhea across intervention groups. The decline in LAZ was slightly smaller among children in the daily HiZn LoFe MNP group compared with the placebo powder group (P < 0.05).Conclusions: The dose of zinc in MNPs as well as the duration and frequency of supplementation evaluated in this trial were not effective in reducing diarrhea; however, the daily HiZn LoFe MNP formulation offered modest improvements in linear growth among young children. This trial was registered at clinicaltrials.gov as NCT03406793. [ABSTRACT FROM AUTHOR]

Background: Informal health care providers particularly "village doctors" are the first point of care for under-five childhood illnesses in rural Bangladesh. We engaged village doctors as part of the Multi-Country Evaluation (MCE) of Integrated Management of Childhood Illness (IMCI) and assessed their management of sick under-five children before and after a modified IMCI training, supplemented with ongoing monitoring and supportive supervision.Methods: In 2003-2004, 144 village doctors across 131 IMCI intervention villages in Matlab Bangladesh participated in a two-day IMCI training; 135 of which completed pre- and post-training evaluation tests. In 2007, 38 IMCI-trained village doctors completed an end-of-project knowledge retention test. Village doctor prescription practices for sick under-five children were examined through household surveys, and routine monitoring visits. In-depth interviews were done with mothers seeking care from village doctors.Results: Village doctors' knowledge on the assessment and management of childhood illnesses improved significantly after training; knowledge of danger signs of pneumonia and severe pneumonia increased from 39% to 78% (P < 0.0001) and from 17% to 47% (P < 0.0001) respectively. Knowledge on the correct management of severe pneumonia increased from 62% to 84% (P < 0.0001), and diarrhoea management improved from 65% to 82% (P = 0.0005). Village doctors retained this knowledge over three years except for home management of pneumonia. No significant differences were observed in prescribing practices for diarrhoea and pneumonia management between trained and untrained village doctors. Village doctors were accessible to communities; 76% had cell phones; almost all attended home calls, and did not charge consultation fees. Nearly all (91%) received incentives from pharmaceutical representatives.Conclusions: Village doctors have the capacity to learn and retain knowledge on the appropriate management of under-five illnesses. Training alone did not improve inappropriate antibiotic prescription practices. Intensive monitoring and efforts to target key actors including pharmaceutical companies, which influence village doctors dispensing practices, and implementation of mechanisms to track and regulate these providers are necessary for future engagement in management of under-five childhood illnesses. [ABSTRACT FROM AUTHOR]

Abstract: Agriculture is the mainstay of livelihoods of the rural Bangladeshi population with the majority involved in the staple rice production which is subjected to seasonal variation. Rice production is invariably related to food insecurity which translates to the food shortage or lean periods. In order to have a comprehensive view on food insecurity in Bangladesh, it is necessary to assess the seasonality of food insecurity status and the factors associated with it. The objective of this paper is to compare the effect of two major rice harvest seasons and the post‐aus rice harvest period on household food insecurity along with the contribution of relevant household characteristics. Data was collected during Bangladeshi aman harvest (November–January) and boro harvest (April–June) seasons and post‐aus harvest (September–October) period. Information of 47,239 households from February 2011 to November 2013 was subjected to bivariate and multivariate analyses and statistical significance was declared when p < 0.05. Around 27%, 47%, and 26% of households were food insecure during aman harvest, boro harvest, and post‐aus harvest period respectively. The aman harvest [adjusted OR (aOR): 0.54 [95% CI: 0.40–0.74; p < 0.001] and post‐aus [aOR: 0.59 [95% CI: 0.44–0.80; p < 0.001] period had a lower odds of being food insecure when compared to boro harvest season except for the northern Rangpur region. Contrary to expectation, the prevalence of household food insecurity in the defined seasons is less during post‐aus harvest period (the perceived lean period) and aman harvest season in comparison to the boro harvest season when food and work is more readily available in rural Bangladesh. There are several statistically significant household characteristics, namely household head being a farmer, educational status of household head, and household monthly income to have higher impact on food insecurity. [ABSTRACT FROM AUTHOR]

The World Health Organization (WHO) currently coordinates rotavirus diarrhea and invasive bacterial disease (IBD) surveillance at 178 sentinel sites in 60 countries. However, only 78 sites participate in both surveillance systems using a common sentinel site. Here, we explored the feasibility of extending a WHO-IBD surveillance platform to generate data on the burden of rotaviral diarrhea and its epidemiological characteristics to prepare the countries to measure the impact of rotaviral vaccine. A six-month (July to December, 2012) surveillance, managed by IBD team, collected stool samples and clinical data from under-five children with acute watery diarrhea at an IBD sentinel site. Samples were tested for rotavirus antigen by ELISA and genotyped by PCR at the regional reference laboratory (RRL). Specimens were collected from 79% (n = 297) of eligible cases (n = 375); 100% of which were tested for rotavirus by ELISA and 54% (159/297) of them were positive. At RRL, all the cases were confirmed by PCR and genotyped (99%; 158/159). The typing results revealed the predominance of G12 (40%; 64/159) genotype, followed by G1 (31%; 50/159) and G9 (19%; 31/159). All in all, this exploratory surveillance collected the desired demographic and epidemiological data and achieved almost all the benchmark indicators of WHO, starting from enrollment number to quality assurance through a number of case detection, collection, and testing of specimens and genotyping of strains at RRL. The success of this WHO-IBD site in achieving these benchmark indicators of WHO can be used by WHO as a proof-of-concept for considering integration of rotavirus surveillance with WHO-IBD platforms, specifically in countries with well performing IBD site and no ongoing rotavirus surveillance. [ABSTRACT FROM AUTHOR]

Background The Integrated Management of Childhood Illness (IMCI) strategy includes guidelines for the management of sick children at first-level facilities. These guidelines intend to improve quality of care by ensuring a complete assessment of the child’s health and by providing algorithms that combine presenting symptoms into a set of illness classifications for management by IMCI-trained service providers at first-level facilities.Objectives To investigate the sustainability of improvements in under-five case management by two cadres of first-level government service providers with different levels of pre-service training following implementation of IMCI training and supportive supervision.Methods Twenty first-level health facilities in the rural sub-district of Matlab in Bangladesh were randomly assigned to IMCI intervention or comparison groups. Health workers in IMCI facilities received training in case management and monthly supportive supervision that involved observations of case management and reinforcement of skills by trained physicians. Health workers in comparison facilities were supervised according to Government of Bangladesh standards. Health facility surveys involving observations of case management were carried out at baseline (2000) and at two points (2003 and 2005) after implementation of IMCI in intervention facilities.Findings Improvement in the management of sick under-five children by IMCI trained service providers with only 18 months of pre-service training was equivalent to that of service providers with 4 years of pre-service training. The improvements in quality of care were sustained over a 2-year period across both cadres of providers in intervention facilities.Conclusion IMCI training coupled with regular supervision can sustain improvements in the quality of child health care in first-level health facilities, even among workers with minimal pre-service training. These findings can guide government policy makers and provide further evidence to support the scale-up of regular supervision and task shifting the management of sick under-five children to lower-level service providers. [ABSTRACT FROM AUTHOR]

Background: Interventions providing foods fortified with multiple micronutrients can be a cost-effective and sustainable strategy to improve micronutrient status and physical growth of school children. We evaluated the effect of micronutrient-fortified yoghurt on the biochemical status of important micronutrients (iron, zinc, iodine, vitamin A) as well as growth indicators among school children in Bogra district of Bangladesh. Methods: In a double-masked randomized controlled trial (RCT) conducted in 4 primary schools, 1010 children from classes 1-4 (age 6-9 years) were randomly allocated to receive either micronutrient fortified yoghurt (FY, n = 501) or non-fortified yoghurt (NFY, n = 509). For one year, children were fed with 60 g yoghurt everyday providing 30% RDA for iron, zinc, iodine and vitamin A. Anthropometric measurements and blood/urine samples were collected at base-, mid- and end-line. All children (FY, n = 278, NFY, n = 293) consenting for the end-line blood sample were included in the present analyses. Results: Both groups were comparable at baseline for socio-economic status variables, micronutrient status markers and anthropometry measures. Compliance was similar in both the groups. At baseline 53.4% of the population was anemic; 2.1% was iron deficient (ferritin <15.0 μg/L and TfR > 8.3 mg/L). Children in the FY group showed improvement in Hb (mean difference: 1.5; 95% CI: 0.4-2.5; p = 0.006) as compared to NFY group. Retinol binding protein (mean diff: 0.05; 95% CI: 0.002-0.09; p = 0.04) and iodine levels (mean difference: 39.87; 95% CI: 20.39-59.35; p < 0.001) decreased between base and end-line but the decrease was significantly less in the FY group. Compared to NFY, the FY group had better height gain velocity (mean diff: 0.32; 95% CI: 0.05-0.60; p = 0.02) and height-for-age z-scores (mean diff: 0.18; 95% CI: 0.02-0.33; p = 0.03). There was no difference in weight gain velocity, weight-for-age z-scores or Body Mass Index z-scores. Conclusion: In the absence of iron deficiency at baseline the impact on iron status would not be expected to be observed and hence cannot be evaluated. Improved Hb concentrations in the absence of a change in iron status suggest improved utilization of iron possibly due to vitamin A and zinc availability. Fortification improved height gain without affecting weight gain. Trial registration: ClinicalTrial.gov: NCT00980733 [ABSTRACT FROM AUTHOR]

Background: Streptococcus pneumoniae is a leading cause of meningitis in countries where pneumococcal conjugate vaccines (PCV) targeting commonly occurring serotypes are not routinely used. However, effectiveness of PCV would be jeopardized by emergence of invasive pneumococcal diseases (IPD) caused by serotypes which are not included in PCV. Systematic hospital based surveillance in Bangladesh was established and progressively improved to determine the pathogens causing childhood sepsis and meningitis. This also provided the foundation for determining the spectrum of serotypes causing IPD. This article reports an unprecedented upsurge of serotype 2, an uncommon pneumococcal serotype, without any known intervention. Methods and Findings: Cases with suspected IPD had blood or cerebrospinal fluid (CSF) collected from the beginning of 2001 till 2009. Pneumococcal serotypes were determined by capsular swelling of isolates or PCR of culture-negative CSF specimens. Multicenter national surveillance, expanded from 2004, identified 45,437 patients with suspected bacteremia who were blood cultured and 10,618 suspected meningitis cases who had a lumber puncture. Pneumococcus accounted for 230 culture positive cases of meningitis in children <5 years. Serotype-2 was the leading cause of pneumococcal meningitis, accounting for 20.4% (45/221; 95% CI 15%-26%) of cases. Ninety eight percent (45/46) of these serotype-2 strains were isolated from meningitis cases, yielding the highest serotype-specific odds ratio for meningitis (29.6; 95% CI 3.4-256.3). The serotype-2 strains had three closely related pulsed field gel electrophoresis types. Conclusions: S. pneumoniae serotype-2 was found to possess an unusually high potential for causing meningitis and was the leading serotype-specific cause of childhood meningitis in Bangladesh over the past decade. Persisting disease occurrence or progressive spread would represent a major potential infection threat since serotype-2 is not included in PCVs currently licensed or under development. [ABSTRACT FROM AUTHOR]

Background To validate a clinical algorithm for community health workers (CHWs) during routine household surveillance for neonatal illness in rural Bangladesh. Methods Surveillance was conducted in the intervention arm of a trial of newborn interventions. CHWs assessed 7587 neonates on postnatal days 0, 2, 5 and 8 and identified neonates with very severe disease (VSD) using an 11-sign algorithm. A nested prospective study was conducted to validate the algorithm (n=395). Physicians evaluated neonates to determine whether newborns with VSD needed referral. The authors calculated algorithm sensitivity and specificity in identifying (1) neonates needing referral and (2) mortality during the first 10 days of life. Results The 11-sign algorithm had sensitivity of 50.0% (95% CI 24.7% to 75.3%) and specificity of 98.4% (96.6% to 99.4%) for identifying neonates needing referral-level care. A simplified 6-sign algorithm had sensitivity of 81.3% (54.4% to 96.0%) and specificity of 96.0% (93.6% to 97.8%) for identifying referral need and sensitivity of 58.0% (45.5% to 69.8%) and specificity of 93.2% (92.5% to 93.7%) for screening mortality. Compared to our 6-sign algorithm, the Young Infant Study 7-sign (YIS7) algorithm with minor modifications had similar sensitivity and specificity. Conclusion Community-based surveillance for neonatal illness by CHWs using a simple 6-sign clinical algorithm is a promising strategy to effectively identify neonates at risk of mortality and needing referral to hospital. The YIS7 algorithm was also validated with high sensitivity and specificity at community level, and is recommended for routine household surveillance for newborn illness. [ABSTRACT FROM AUTHOR]

We conducted a randomized, double-blind placebo controlled, community trial in rural Bangladesh in children 4-59 mo of age to compare the efficacy of a 5- and 10-d course of zinc therapy on the incidence and duration of diarrhea over the subsequent 90-d follow-up after initial treatment for an acute childhood diarrheal (ACD) episode. Children (n = 1622) with ACD were randomly allocated to either 5 or 10 d of zinc treatment. Female field workers visited each child daily, supervised the administration of zinc, recorded the duration of current episode, and the occurrence and duration of diarrhea over the subsequent 3 mo. The incidence of diarrhea over the 90 d of follow-up did not differ between the 5-d (1.08 ± 1.38 episodesl and 10-d 11.02 ± 1.35 episodesl groups (P = 0.35). Children in both groups experienced a comparable duration of diarrheal episodes (3.1 ± 5.6 d vs. 2.9 ± 5.6 d, 5-d vs. 10-d, respectively; P= 0.64) with a mean difference between groups within the defined range of equivalence. Time to onset of the first episode and the proportion children experiencing diarrhea during the 90-d follow-up also did not differ between groups. These findings suggest that among Bangladeshi children, a 5-d zinc treatment for ACD is as efficacious as 10 d in preventing diarrhea in the subsequent 3 mo. [ABSTRACT FROM AUTHOR]

Background: Lack of data is a critical barrier to addressing the problem of stillbirth in countries with the highest stillbirth burden. Our study objective was to estimate the levels, types, and causes of stillbirth in rural Sylhet district of Bangladesh. Methods: A complete pregnancy history was taken from all women (n = 39 998) who had pregnancy outcomes during 2003-2005 in the study area. Verbal autopsy data were obtained for all identified stillbirths during the period. We used pre-defined case definitions and computer programs to assign causes of stillbirth for selected causes containing specific signs and symptoms. Both non-hierarchical and hierarchical approaches were used to assign causes of stillbirths. Results: A total of 1748 stillbirths were recorded during 2003-2005 from 48,192 births (stillbirth rate: 36.3 per 1000 total births). About 60% and 40% of stillbirths were categorized as antepartum and intrapartum, respectively. Maternal conditions, including infections, hypertensive disorders, and anemia, contributed to about 29% of total antepartum stillbirths. About 50% of intrapartum stillbirths were attributed to obstetric complications. Maternal infections and hypertensive disorders contributed to another 11% of stillbirths. A cause could not be assigned in nearly half (49%) of stillbirths. Conclusion: The stillbirth rate is high in rural Bangladesh. Based on algorithmic approaches using verbal autopsy data, a substantial portion of stillbirths is attributable to maternal conditions and obstetric complications. Programs need to deliver community-level interventions to prevent and manage maternal complications, and to develop strategies to improve access to emergency obstetric care. Improvements in care to avert stillbirth can be accomplished in the context of existing maternal and child health programs. Methodological improvements in the measurement of stillbirths, especially causes of stillbirths, are also needed to better define the burden of stillbirths in low-resource settings. [ABSTRACT FROM AUTHOR]

Background Effective and scalable community-based strategies are needed for identification and management of serious neonatal illness. [ABSTRACT FROM PUBLISHER]

Background: To evaluate a delivery strategy for newborn interventions in rural Bangladesh. Methods: A cluster-randomized controlled trial was conducted in Mirzapur, Bangladesh. Twelve unions were randomized to intervention or comparison arm. All women of reproductive age were eligible to participate. In the intervention arm, community health workers identified pregnant women; made two antenatal home visits to promote birth and newborn care preparedness; made four postnatal home visits to negotiate preventive care practices and to assess newborns for illness; and referred sick neonates to a hospital and facilitated compliance. Primary outcome measures were antenatal and immediate newborn care behaviours, knowledge of danger signs, care seeking for neonatal complications, and neonatal mortality. Findings: A total of 4616 and 5241 live births were recorded from 9987 and 11153 participants in the intervention and comparison arm, respectively. High coverage of antenatal (91% visited twice) and postnatal (69% visited on days 0 or 1) home visitations was achieved. Indicators of care practices and knowledge of maternal and neonatal danger signs improved. Adjusted mortality hazard ratio in the intervention arm, compared to the comparison arm, was 1.02 (95% CI: 0.80-1.30) at baseline and 0.87 (95% CI: 0.68-1.12) at endline. Primary causes of death were birth asphyxia (49%) and prematurity (26%). No adverse events associated with interventions were reported. Conclusion: Lack of evidence for mortality impact despite high program coverage and quality assurance of implementation, and improvements in targeted newborn care practices suggests the intervention did not adequately address risk factors for mortality. The level and cause-structure of neonatal mortality in the local population must be considered in developing interventions. Programs must ensure skilled care during childbirth, including management of birth asphyxia and prematurity, and curative postnatal care during the first two days of life, in addition to essential newborn care and infection prevention and management. Trial Registration: Clinicaltrials.gov NCT00198627 [ABSTRACT FROM AUTHOR]

Copyright of Tropical Medicine & International Health is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background. To devise treatment strategies for neonatal infections, the population-level incidence and antibiotic susceptibility of pathogens must be defined. Methods. Surveillance for suspected neonatal sepsis was conducted in Mirzapur, Bangladesh, from February 2004 through November 2006. Community health workers assessed neonates on postnatal days 0, 2, 5, and 8 and referred sick neonates to a hospital, where blood was collected for culture from neonates with suspected sepsis. We estimated the incidence and pattern of community-acquired neonatal bacteremia and determined the antibiotic susceptibility profile of pathogens. Results. The incidence rate of community-acquired neonatal bacteremia was 3.0 per 1000 person-neonatal periods. Among the 30 pathogens identified, the most common was Staphylococcus aureus (np10); half of all isolates were gram positive. Nine were resistant to ampicillin and gentamicin or to ceftiaxone, and 13 were resistant to cotrimoxazole. Conclusion. S. aureus was the most common pathogen to cause community-acquired neonatal bacteremia. Nearly 40% of infections were identified on days 0-3, emphasizing the need to address maternal and environmental sources of infection. The combination of parenteral procaine benzyl penicillin and an aminoglycoside is recommended for the first-line treatment of serious community-acquired neonatal infections in rural Bangladesh, which has a moderate level of neonatal mortality. Additional population-based data are needed to further guide national and global strategies. Trial registration. ClinicalTrials.gov identifier: NCT00198627. [ABSTRACT FROM AUTHOR]

Objective To assess the effect of the timing of first postnatal home visit by community health workers on neonatal mortality. Design Analysis of prospectively collected data using time varying discrete hazard models to estimate hazard ratios for neonatal mortality according to day of first postnatal home visit. Data source Data from a community based trial of neonatal care interventions conducted in Bangladesh during 2004-5. Main outcome measure Neonatal mortality. Results 9211 live births were included. Among infants who survived the first day of life, neonatal mortality was 67% lower in those who received a visit on day one than in those who received no visit (adjusted hazard ratio 0.33, 95% confidence interval 0.23 to 0.46; P<0.001). For those infants who survived the first two days of life, receiving the first visit on the second day was associated with a 64% lower neonatal mortality than in those who did not receive a visit (adjusted hazard ratio 0.36, 0.23 to 0.55; P<0.001). First visits on any day after the second day of life were not associated with reduced mortality. Conclusions In developing countries, especially where home delivery with unskilled attendants is common, postnatal home visits within the first two days of life by trained community health workers can significantly reduce neonatal mortality. [ABSTRACT FROM AUTHOR]

The benefit of zinc for the treatment of diarrhoea in a cluster-randomized trial of children, aged 3-59 months, living in rural Bangladesh was previously reported. Here, the benefits of zinc stratified by age--3-5 months, 6-11 months, and 12-59 months--are reported. Although the sample sizes in the stratified groups were too small to detect statistical significance in the 3-5-month and 6-11-month age-groups, the trends suggest that there may be a benefit of zinc for the treatment of diarrhoea on the duration of diarrhoea and on subsequent morbidity and mortality. Additional research is needed to better understand the effect of zinc for the treatment of diarrhoea among infants aged less than six months. [ABSTRACT FROM AUTHOR]

The benefit of zinc for the treatment of diarrhoea in a cluster-randomized trial of children, aged 3-59 months, living in rural Bangladesh was previously reported. Here, the benefits of zinc stratified by age--3-5 months, 6-11 months, and 12-59 months--are reported. Although the sample sizes in the stratified groups were too small to detect statistical significance in the 3-5-month and 6-11-month age-groups, the trends suggest that there may be a benefit of zinc for the treatment of diarrhoea on the duration of diarrhoea and on subsequent morbidity and mortality. Additional research is needed to better understand the effect of zinc for the treatment of diarrhoea among infants aged less than six months. [ABSTRACT FROM AUTHOR]

Because infants and young children in many developing countries are deficient in both iron and zinc, and zinc can affect iron metabolism, evaluation of optimum strategies to simultaneously supplement iron and zinc is an important public health priority. This study evaluated the efficacy of weekly supplementation of iron or zinc or both on iron, zinc, and copper status in Bangladeshi infants. In a double-blind, randomized, controlled community trial, 6-mo-old infants were assigned to receive weekly supplements of I mg riboflavin (control, n = 82) or 1 mg riboflavin + 20 mg iron (n = 83), 20 mg zinc (n = 83), or both (n = 85) for 6 mo. Hemoglobin, serum ferritin, transferrin receptor, zinc, and copper concentrations were measured at baseline and at the end of intervention. Serum Zn increased in both groups receiving zinc; the increase was greatest among children with low baseline serum zinc concentration. Iron status indicators did not differ among the groups before or after 6 mo of supplementation. Supplementation with either zinc or iron decreased serum copper after 6 mo. Joint supplementation did not alter the individual effects of iron or zinc supplementation in these Bangladeshi children. However, the dosing regimen may not have been adequate to achieve the desired biochemical effects. [ABSTRACT FROM AUTHOR]

OBJECTIVE:: The skin is a potential source for invasive infections in neonates from developing countries such as Bangladesh, where the level of environmental contamination is exceedingly high. A randomized controlled trial was conducted from 1998 to 2003 in the Special Care Nursery of a tertiary hospital in Bangladesh to test the effectiveness of topical emollient therapy in enhancing the skin barrier of preterm neonates less than 33 weeks of gestational age. In the initial months of the study, the infection and mortality rates were noted to be unacceptably high. Therefore, an infection control program was introduced early in the trial to reduce the rate of nosocomial infections. STUDY DESIGN:: After a comprehensive review of neonatal care practices and equipment to identify sources of nosocomial infections, a simple but comprehensive infection control program was introduced that emphasized education of staff and caregivers about measures to decrease risk of contamination, particularly hand-washing, proper disposal of infectious waste, and strict asepsis during procedures, as well as prudent use of antibiotics. RESULTS:: Infection control efforts resulted in declines in episodes of suspected sepsis (47%), cases of culture-proven (61%) sepsis, patients with a clinical diagnosis of sepsis (79%), and deaths with clinical (82%) or culture-proven sepsis (50%). CONCLUSION:: The infection control program was shown to be a simple, low-cost, low-technology intervention to reduce substantially the incidence of septicemia and mortality in the nursery.Journal of Perinatology (2005) 25, 331-335. doi:10.1038/sj.jp.7211283 Published online 17 February 2005 [ABSTRACT FROM AUTHOR]

Given the high prevalence of micronutrient deficiencies and infectious diseases in infants in developing countries, an evaluation of the efficacy of different micronutrient formulations on infant morbidity is a priority. The efficacy of weekly supplementation of four different micronutrient formulations on diarrhea and acute lower respiratory infection (ALRI) morbidity was evaluated in Bangladeshi infants. In a double-blind, randomized, controlled community trial, 799 infants aged 6 mo were randomly assigned to one of the following 5 groups: 1) 20 mg elemental iron with 1 mg riboflavin, 2) 20 mg elemental zinc with 1 mg riboflavin, 3) 20 mg iron and 20 mg zinc with 1 mg riboflavin, 4) a micronutrient mix (MM) containing 20 mg iron, 20 mg zinc, 1 mg riboflavin along with other minerals and vitamins and 5) a control treatment, 1 mg riboflavin only. Health workers visited each infant weekly until age 12 mo to feed the supplement and to collect data on diarrhea and ALRI morbidity. Hemoglobin, serum ferritin and serum zinc levels of a sample of infants were measured at 6 and 12 mo. Compared with the control group, at 12 mo, serum ferritin levels were higher in the iron + zinc group, and serum zinc levels were higher in the zinc and iron + zinc groups. Simultaneous supplementation with iron + zinc was associated with lower risk of severe diarrhea, 19% lower in all infants and 30% lower in less well-nourished infants with weight-for-age Z-score below -1. Iron + zinc supplementation was also associated with 40% lower risk of severe ALRI in less well-nourished infants. MM supplementation was associated with a 15% higher risk of diarrhea in all infants and 22% higher risk in less well-nourished infants. Intermittent simultaneous supplementation with iron + zinc seems promising; it will be useful to determine whether higher doses would provide greater benefits. [ABSTRACT FROM AUTHOR]

Abstract Objective: To evaluate the effect on morbidity and mortality of providing daily zinc for 14 days to children with diarrhoea. Design: Cluster randomised comparison. Setting: Matlab field site of International Center for Diarrhoeal Disease Research, Bangladesh. Participants: 8070 children aged 3-59 months contributed 11 881 child years of observation during a two year period. Intervention: Children with diarrhoea in the intervention clusters were treated with zinc (20 mg per day for 14 days); all children with diarrhoea were treated with oral rehydration therapy. Main outcome measures: Duration of episode of diarrhoea, incidence of diarrhoea and acute lower respiratory infections, admission to hospital for diarrhoea or acute lower respiratory infections, and child mortality. Results: About 40% (399/1007) of diarrhoeal episodes were treated with zinc in the first four months of the trial; the rate rose to 67% (350/526) in month 5 and to > 80% (364/434) in month 7 and was sustained at that level. Children in the intervention cluster received zinc for about seven days on average during each episode of diarrhoea. They had a shorter duration (hazard ratio 0.76, 95% confidence interval 0.65 to 0.90) and lower incidence of diarrhoea (rate ratio 0.85, 0.76 to 0.96) than children in the comparison group. Incidence of acute lower respiratory infection was reduced in the intervention group but not in the comparison group. Admission to hospital of children with diarrhoea was lower in the intervention group than in the comparison group (0.76, 0.59 to 0.98). Admission for acute lower respiratory infection was lower in the intervention group, but this was not statistically significant (0.81, 0.53 to 1.23). The rate of non-injury deaths in the intervention clusters was considerably lower (0.49, 0.25 to 0.94). Conclusions: The lower rates of child morbidity and mortality with zinc treatment represent substantial benefits from a simple and inexpensive intervention that... [ABSTRACT FROM AUTHOR]

Describes infant growth patterns and their relations to birth weight, intrauterine growth retardation and prematurity in Dhaka, Bangladesh. General and baseline characteristics of the sample; Body weight at follow-up visits; Nutritional status at birth; Implications for developing interventions to reduce undernutrition in infancy and later childhood.

Abstract. Village-based surveillance data from longitudinal studies in rural Bangladesh have been used to evaluate the nutritional consequences of infectious diseases, including diarrhea due to specific pathogens. The prevalences of specific illnesses were related to the ponderal and linear growth of young children for 2-month and 1-year periods. Of the common illnesses, only diarrhea had a significant inverse relationship with increments of weight during 2-month periods and of length during 1 year. Diarrhea accounted for 20% of the difference in linear growth between the study children and the international reference population during the first 5 years of life. Diarrhea associated with enterotoxigenic Escherichia coli had a significant negative effect on the bimonthly weight gain of children in this community and shigellosis had the strongest negative effect on bimonthly and annual linear growth. Control of diarrhea due to enterotoxigenic E coli and Shigella would not only substantially diminish diarrheal morbidity but would also improve the growth of children and thereby reduce the prevalence of protein-energy malnutrition. [ABSTRACT FROM AUTHOR]

ABSTRACT. The use of oral rehydration solutions containing essential electrolytes and either glucose or sucrose of equal osmolality was compared in a double-blind sequential trial of 784 children with rotavirus-associated diarrhea treated at a center in rural Bangladesh. The oral fluid failure rate was 11.5% for the sucrose-containing solution group and 7.3% for the glucose-containing group (P = NS), Vomiting was a significantly more common cause of failure for the group treated with sucrose-containing oral rehydration solution and was associated with an increased rate of intake of the sweeter sucrose-containing solution. The purging rate was not different for the two groups. The oral fluid failure rates for children in the most underweight category (<60% of expected weight for age) were not different from those for other groups, although, as assessed by purging rate and initial dehydration, the stool losses of members of this group constituted a greater proportion of their body weight. Glucose is the preferred carbohydrate for oral electrolyte solutions, although sucrose can be substituted with only minimum loss of efficacy. [ABSTRACT FROM AUTHOR]

A community-based longitudinal study was carried out at Matlab, Bangladesh, to investigate the magnitude of the problem of persistent diarrhea; 705 children aged < 5 y were followed, yielding 7300 child-months of observation in 1 y. Morbidity data were collected every fourth day by home visit, anthropometric status was determined monthly, and cell-mediated immune status was assessed every 3 mo. The incidence of persistent diarrhea was 34 episodes per 100 child-years; rates were highest in infancy and declined through the remainder of childhood. In a logistic-regression model, weight-for-height status and immune status were significant predictors of persistent diarrhea. Compared with those at zero Z score, children with weight-for-height at -2 would have a 3.5 times increased risk of persistent diarrhea. Compared with immunocompetent children, immunodeficient children had about twice the risk of developing persistent diarrhea. Thus, nutritional status and cell-mediated immune status were important independent risk factors for persistent diarrhea. [ABSTRACT FROM AUTHOR]

The authors comment on the article "MINIMat Study Team: Effects of prenatal micronutrient and early food supplementation on maternal hemoglobin, birth weight, and infant mortality among children in Bangladesh: The MINIMat randomized trial," by L.A. Persson and colleagues, published within the issue of the "Journal of the American Medical Association." They examine whether the results are plausible or simply due to chance. They suggest further study on the timing of nutritional interventions.

Background: Measles vaccination effectiveness studies showed dramatic decreases in all-cause mortality in excess of what would be expected from the prevention of measles disease alone. This invited speculation that measles infection may increase the risk of diarrhea morbidity and mortality subsequent to the acute phase of the disease. The aim of the present systematic review is to summarize the existing evidence in the publically available literature pertaining to the putative causal link between measles and diarrhea in the period 4-26 weeks following measles rash onset.Methods: We searched the PubMed, Embase, Open Grey and Grey Literature Report databases for relevant literature using broad search terms. Prospective, retrospective and case-control studies in low- and middle-income countries involving children under five wherein relevant evidence were presented were included. Data were extracted from the articles and summarized.Results: Fifty abstracts retrieved through the database searches met the initial screening criteria. Twelve additional documents were identified by review of the references of the documents found in the initial searches. Six documents representing five unique studies that presented evidence relevant to the research question were found. Four of the included studies took place in Bangladesh. One of the included studies took place in Sudan. Some measles vaccine effectiveness studies show lower diarrhea morbidity and mortality among the vaccinated. However, children who received vaccine may have differed in important ways from children who did not, such as health service utilization. Additionally, cohort studies following unvaccinated children showed no difference in diarrhea morbidity and mortality between cases and controls more than 4 weeks after measles rash onset. One study showed some evidence that severe measles may predispose children to gastroenteritis, but was not able to show a corresponding increase in the risk of diarrhea mortality.Conclusions: The available evidence suggests that the risk of measles-associated diarrhea mortality is largely limited to the 5-week period 1 week prior to and 4 weeks after measles rash onset, and that there is no increased risk of diarrhea mortality in the longer-term caused by measles. [ABSTRACT FROM AUTHOR]

Globally, undernutrition affects nearly half of all children aged less than 5 years. It is more prominent in low- and middle-income countries. This study aimed to identify the age-specific risk factors for different categories of undernutrition among Bangladeshi children aged less than 2 years. Data of 10,291 children aged less than 2 years were collected between October 2011 to November 2013 through the Food Security Nutritional Surveillance Project in Bangladesh. Simple logistic regression established bivariate relationships between the categories of undernutrition and the relevant risk factors. Multiple logistic regression constructed the age-specific regression models depicting the independent association and effect size of the risk factors contributing to the various categories of undernutrition among study population. Stunting was prevalent among 30.9% of the study children, whereas 9.7% were wasted and 24.9% were underweight. Being a male child, increase in age, maternal body mass index and education, and household food insecurity were the strongest predictors for all categories of undernutrition in terms of effect size. Our study shows that the different categories of childhood undernutrition have different age-specific risk factors. Maternal body mass index and household food insecurity were the common age-specific risk factors for all categories of undernutrition. We expect our findings to enhance the existing evidence base for the risk factors of undernutrition among children aged less than 2 years. [ABSTRACT FROM AUTHOR]

Objective To evaluate and compare the cost-effectiveness of two strategies for neonatal care in Sylhet division, Bangladesh. Methods In a cluster-randomized controlled trial, two strategies for neonatal care -- known as home care and community care -- were compared with existing services. For each study arm, economic costs were estimated from a societal perspective, inclusive of programme costs, provider costs and household out-of-pocket payments on care-seeking. Neonatal mortality in each study arm was determined through household surveys. The incremental cost-effectiveness of each strategy -- compared with that of the pre-existing levels of maternal and neonatal care -- was then estimated. The levels of uncertainty in our estimates were quantified through probabilistic sensitivity analysis. Findings The incremental programme costs of implementing the home-care package were 2939 (95% confidence interval, CI: 1833-7616) United States dollars (US$) per neonatal death averted and US$ 103.49 (95% CI: 64.72-265.93) per disability-adjusted life year (DALY) averted. The corresponding total societal costs were US$ 2971 (95% CI: 1844-7628) and US$ 104.62 (95% CI: 65.15-266.60), respectively. The home-care package was cost-effective -- with 95% certainty -- if healthy life years were valued above US$ 214 per DALY averted. In contrast, implementation of the community-care strategy led to no reduction in neonatal mortality and did not appear to be cost-effective. Conclusion The home-care package represents a highly cost-effective intervention strategy that should be considered for replication and scale-up in Bangladesh and similar settings elsewhere. [ABSTRACT FROM AUTHOR]

The article presents a study which assesses the effectiveness of single or daily umbilical cord cleaning regimens with the promotion of dry cord care in neonatal mortality prevention. It states that the study was a community-based, parallel cluster-randomised trial in Sylhet, Bangladesh. It concludes that though umbilical cord cleaning with Chlorhexidine can save lives, determining the best treatment frequency requires further studies.

Abstract: In double-blind trials in Bangladesh, 88 adults, and 79 children (8–10 years) were randomized to receive either a single oral dose of 1×104, 1×105 or 1×106 CFU of SC602 (a live, attenuated Shigella flexneri 2a strain vaccine) or placebo. In the adult outpatient 1×106 CFU group, severe joint pain and body aches were reported by one and two vaccinees respectively. In the adult inpatient trial, SC602 was isolated from 3 volunteers, pre-vaccination antibody titers were high, and fourfold increases in serum IgG anti-LPS responses were observed in 2 of 5 subjects of the 1×106 CFU group. None of the volunteers developed diarrhea. Overall, SC602 was found to be associated with minimal vaccine shedding, minimal reactogenicity, no transmission risk, and low immune stimulation. [ABSTRACT FROM AUTHOR]

The validity of three methods (last menstrual period [LPM], Ballard and Dubowitz scores) for assessment of gestational age for premature infants in a low-resource setting was assessed, using antenatal ultrasound as the gold standard. It was hypothesized that LMP and other methods would perform similarly in determining postnatal gestational age. Concordance analysis was applied to data on 355 neonates of <33 weeks gestational age enrolled in a topical skin-therapy trial in a tertiary-care children's hospital in Bangladesh. The concordance coefficient for LMP, Ballard, and Dubowitz was 0.878, 0.914, and 0.886 respectively. LMP and Ballard underestimated gestational age by one day (±11) and 2.9 days (±7.8) respectively while Dubowitz overestimated gestational age by 3.9 days (±7.1) compared to ultrasound finding. LMP in a low-resource setting was a more reliable measure of gestational age than previously thought for estimation of postnatal gestational age of preterm infants. Ballard and Dubowitz scores are slightly more reliable but require more technical skills to perform. Additional prospective trials are warranted to examine LMP against antenatal ultrasound for primary assessment of neonatal gestational age in other low-resource settings. [ABSTRACT FROM AUTHOR]

Objective To estimate the validity (sensitivity, specificity, and positive and negative predictive values) of a clinical algorithm as used by community health workers (CHWs) to detect and classify neonatal illness during routine household visits in rural Bangladesh. Methods CHWs evaluated breastfeeding and symptoms and signs of illness in 395 neonates selected randomly from neonatal illness surveillance during household visits on postnatal days 0, 2, 5 and 8. Neonates classified with very severe disease (VSD) were referred to a community-based hospital. Within 12 hours of CHW assessments, physicians independently evaluated all neonates seen in a given day by one CHW, randomly chosen from among 36 project CHWs. Physicians recorded symptoms and signs of illness, classified the illness, and determined whether the newborn needed referral-level care at the hospital. Physicians' identification and classification were used as the gold standard in determining the validity of CHWs' identification of symptoms and signs of illness and its classification. Findings CHWs' classification of VSD showed a sensitivity of 73%, a specificity of 98%, a positive predictive value of 57% and a negative predictive value of 99%. A maternal report of any feeding problem as ascertained by physician questioning was significantly associated (P < 0.001) with "not sucking at all" and "not attached at all" or "not well attached" as determined clinically by CHWs during feeding assessment. Conclusion CHWs identified with high validity the neonates with severe illness needing referral-level care. Home-based illness recognition and management, including referral of neonates with severe illness by CHWs, is a promising strategy for improving neonatal health and survival in low-resource developing country settings. [ABSTRACT FROM AUTHOR]

This article discusses research into the efficacy of the World Health Organisation guidelines on the integrated management of childhood illness (IMCI) in the treatment of pediatric pneumonia in Bangladesh. Low levels of Patient compliance with hospitalisation orders in cases of childhood pneumonia are noted, leading researchers to recommend a shift to treatment in first-level care facilities. This research was conducted in Matlab, a rural section of Bangladesh. The modification of IMCI guidelines in this region is presented as an example of the potential benefits of adapting treatments to cross cultural and financial barriers.

The article presents research assessing the effectiveness of community-based intervention programs to advance the health of newborns and prevent neonatal mortality in the Sylhet district of Bangladesh. The methods and design of the study involving a comparison of intervention programs that promoted birth and newborn-care preparedness and postnatal home-visits from female community health workers in an attempt to reduce neonatal mortality are described. Researchers concluded that a home-care strategy of preventative and curative newborn care is effective in reducing neonatal mortality in communities with a weak health system.

This paper reports on a population-based sample survey of 2,289 children aged less than five years (under-five children) conducted in 2000 as a baseline for the Bangladesh component of the Multi-country Evaluation (MCE) of the Integrated Management of Childhood Illness strategy. Of interest were rates and differentials by sex and socioeconomic status for three aspects of child health in rural Bangladesh: morbidity and hospitalizations, including severity of illness; care-seeking for childhood illness; and home-care for illness. The survey was carried out among a population of about 380,000 in Matlab upazila (subdistrict). Generic MCE Household Survey tools were adapted, translated, and pretested. Trained interviewers conducted the survey in the study areas. In total, 2,289 under-five children were included in the survey. Results showed a very high prevalence of illness among Bangladeshi children, with over two-thirds reported to have had at least one illness during the two weeks preceding the survey. Most sick children in this population had multiple symptoms, suggesting that the use of the IMCI clinical guidelines will lead to improved quality of care. Contrary to expectations, there were no significant differences in the prevalence of illness either by sex or by socioeconomic status. About one-third of the children with a reported illness did not receive any care outside the home. Of those for whom outside care was sought, 42% were taken to a village doctor. Only 8% were taken to an appropriate provider, i.e. a health facility, a hospital, a doctor, a paramedic, or a community-based health worker. Poorer children than less-poor children were less likely to be taken to an appropriate healthcare provider. The findings indicated that children with severe illness in the least poor households were three times more likely to seek care from a trained provider than children in the poorest households. Any evidence of gender inequities in child healthcare, either in terms of prevalence of illness or care-seeking patterns, was not found. Care-seeking patterns were associated with the perceived severity of illness, the presence of danger signs, and the duration and number of symptoms. The results highlight the challenges that will need to be addressed as IMCI is implemented in health facilities and extended to address key family and community practices, including extremely low rates of use of the formal health sector for the management of sick children. Child health planners and researchers must find ways to address the apparent population preference for untrained and traditional providers which is determined by various factors, including the actual and perceived quality of care, and the differentials in care-seeking practices that discriminate against the poorest households. [ABSTRACT FROM AUTHOR]

OBJECTIVE. Skin barrier therapy during the neonatal period, when the skin barrier is most highly compromised and the risk of death is greatest, has been shown to have a number of potential benefits, including reduced risk of nosocomial sepsis. Topical application of emollients that augment skin barrier function was evaluated as a strategy for improving survival rates among hospitalized preterm infants in Bangladesh. METHODS, A prospective, randomized, controlled, clinical trial was conducted in the special care nursery at Dhaka Shishu (Children) Hospital, the largest tertiary care children's hospital in Bangladesh. Preterm infants (gestational age: ≤33 weeks; N = 497) received daily topical applications of sunflower seed oil or Aquaphor ointment. Neonatal mortality rates were compared in an intent-to-treat analysis with a control group that did not receive emollient therapy. RESULTS. Treatment with sunflower seed oil resulted in a statistically significant 26% reduction in mortality rates, compared with infants not receiving topical emollient therapy. Aquaphor therapy also significantly reduced mortality rates, by 32%. CONCLUSIONS. Topical therapy with skin barrier-enhancing emollients improved survival rates among preterm hospitalized infants in Bangladesh. This study provides strong evidence for the implementation of topical therapy for high-risk preterm neonates in developing countries. [ABSTRACT FROM AUTHOR]

Abstract: Background: Zinc deficiency is known to impair immunologic functions. However, the effect of zinc supplementation on immune response to polysaccharide vaccines is not known. Objective: To determine the immunogenicity of the heptavalent Pneumococcal protein conjugate (PNC) vaccine in poor Bangladeshi infants and to assess the effect of zinc supplementation on immune response to the PNC vaccine. Design: We immunized a sub-cohort of 241 infants who had previously received three doses of a Hib conjugate vaccine with three doses of the heptavalent PNC vaccine at 4 weeks intervals beginning at 18±1 weeks of age. The infants were supplemented with daily 5mg zinc or placebo from 4 to 33 weeks of age. Response to each of the seven PNC serotypes were assessed at 4, 24 and 33 weeks of age. Results: After three doses of PNC, at 29 weeks of age, geometric mean titres for the pneumococcal serotypes ranged from 3.68 to 13.34μg/ml. Titres were significantly higher for infants who had received PNC compared to infants who had only received DTP-Hib. Zinc supplementation resulted in higher titres for serotype 9V (4.09μg/ml; [95% CI: 3.27; 5.10] and 3.33μg/ml; [95% CI: 2.79; 3.96] for zinc and placebo group, respectively; p <0.05) after three doses but had no effect on other serotypes. Conclusions: A heptavalent PNC vaccine proved to be safe and immunogenic in Bangladeshi infants. Zinc supplementation enhanced the immune response to only one of the serotypes (9V). However, there was no effect on other serotypes. [Copyright &y& Elsevier]

Abstract: Background: Accidental death in people with epilepsy (PWE) has been described in high income settings where the relative risk of death is known to be higher than in the standard population. Population-based studies of injury deaths among PWE in developing countries are uncommon. Methods: A population-based verbal autopsy study in Matlab, Bangladesh, performed at a health and demographic surveillance system site (mean population 223,886 in 142 villages), was used to assess the possible causes of all deaths. All cases of accidental injury (2005–2008) were evaluated and compared between people with and without a diagnosis of epilepsy. Results: There were 12 accidental deaths among PWE (8 females, age range 12–58years old) out of a total of 316 deaths due to accidental injuries (3.8% of all injury deaths). Causes of mortality were drowning (n=10) and burns (n=2). The proportion of deaths due to drowning among PWE was significantly higher than that of the standard population (83% (10/12) vs. 7% (21/304), relative risk 12.6 (95% CI, 7.7–20.7, p<0.0001)). Mortality due to injury in PWE occurred at a younger age compared to people without epilepsy (mean difference 20.7years (95% CI 6.7, 34.3), p<0.004). Conclusions: There is a high proportion of accidental deaths due to drowning in PWE in Bangladesh compared to the standard population. Given the risk of seasonal flooding and low level of formal education, programs targeting water safety for PWE at all ages should be emphasized, appropriate for level of ability. [Copyright &y& Elsevier]

Young children in resource-constrained settings are susceptible to zinc deficiency and its deleterious health effects. The objective of this secondary analysis was to evaluate the effects of the following six interventions on biomarkers of iron and zinc status among a subgroup of young children in Dhaka, Bangladesh, who participated in the Zinc in Powders Trial (ZiPT): (1) standard micronutrient powders (MNPs) containing 4.1 mg zinc and 10 mg iron, daily; (2) high-zinc (10 mg) and low-iron (6 mg) (HiZn LoFe) MNP, daily; (3) HiZn (10 mg) and LoFe (6 mg)/HiZn (10 mg) and no-iron MNPs on alternating days; (4) dispersible zinc tablet (10 mg), daily; (5) dispersible zinc tablet (10 mg), daily for 2 weeks at enrollment and at 12 weeks; (6) placebo powder, daily. At the end of the 24 week intervention period, children in the daily dispersible zinc tablet group exhibited a mean serum zinc concentration (SZC) of 92.5 μg/dL, which was significantly higher than all other groups except the HiZn LoFe MNP alternating group (81.3 μg/dL). MNPs containing 10 mg and 6 mg of iron had a similar impact on biomarkers of iron status, with no evidence of an adverse interaction with zinc.

Preventive zinc supplementation provided as a stand-alone dispersible tablet, or via home fortification as multiple micronutrient powders (MNPs), has been considered a potential strategy to prevent zinc deficiency and improve health (including immune) outcomes among children in low- and middle-income countries. However, the impact of zinc supplementation on immune profiles has not been well characterized. We sought to define the effect of zinc supplementation on peripheral blood gene expression and cytokine levels among young children in Dhaka, Bangladesh. In a sub-study of a large randomized, controlled, community-based efficacy trial where children 9-11 months of age received one of the following interventions on a daily basis for 24 weeks: (1) MNPs containing 10 mg of zinc; (2) dispersible tablet containing 10 mg zinc; or (3) placebo powder, we used RNA sequencing to profile the peripheral blood gene expression, as well as highly sensitive multiplex assays to detect cytokine profiles. We profiled samples from 100 children enrolled in the parent trial (zinc MNPs 28, zinc tablets 39, placebo 33). We did not detect an effect from either zinc intervention on differential peripheral blood gene expression at the end of the intervention, or an effect from the intervention on changes in gene expression from baseline. We also did not detect an effect from either intervention on cytokine concentrations. Exploratory analysis did not identify an association between undernutrition (defined as stunting, underweight or wasting) and peripheral blood gene expression. Zinc interventions in children did not produce a gene expression or cytokine signature in the peripheral blood. However, this study demonstrates a proof of principle that sensitive multi-omic techniques can be applied to samples collected in field studies.

Background: Climate change threatens to undermine recent progress in reducing global deaths from diarrhoeal disease in children. However, the scarcity of evidence about how individual environmental factors affect transmission of specific pathogens makes prediction of trends under different climate scenarios challenging. We aimed to model associations between daily estimates of a suite of hydrometeorological variables and rotavirus infection status ascertained through community-based surveillance., Methods: For this analysis of multisite cohort data, rotavirus infection status was ascertained through community-based surveillance of infants in the eight-site MAL-ED cohort study, and matched by date with earth observation estimates of nine hydrometeorological variables from the Global Land Data Assimilation System: daily total precipitation volume (mm), daily total surface runoff (mm), surface pressure (mbar), wind speed (m/s), relative humidity (%), soil moisture (%), solar radiation (W/m 2 ), specific humidity (kg/kg), and average daily temperatures (°C). Lag relationships, independent effects, and interactions were characterised by use of modified Poisson models and compared with and without adjustment for seasonality and between-site variation. Final models were created with stepwise selection of main effects and interactions and their validity assessed by excluding each site in turn and calculating Tjur's Coefficients of Determination., Findings: All nine hydrometeorological variables were significantly associated with rotavirus infection after adjusting for seasonality and between-site variation over multiple consecutive or non-consecutive lags, showing complex, often non-linear associations that differed by symptom status and showed considerable mutual interaction. The final models explained 5·9% to 6·2% of the variability in rotavirus infection in the pooled data and their predictions explained between 0·0% and 14·1% of the variability at individual study sites., Interpretation: These results suggest that the effect of climate on rotavirus transmission was mediated by four independent mechanisms: waterborne dispersal, airborne dispersal, virus survival on soil and surfaces, and host factors. Earth observation data products available at a global scale and at subdaily resolution can be combined with longitudinal surveillance data to test hypotheses about routes and drivers of transmission but showed little potential for making predictions in this setting., Funding: Bill & Melinda Gates Foundation; Foundation for the National Institutes of Health, National Institutes of Health, Fogarty International Center; Sherrilyn and Ken Fisher Center for Environmental Infectious Diseases, Johns Hopkins School of Medicine; and NASA's Group on Earth Observations Work Programme., (Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Zinc is essential to supporting growth in young children especially for tissues undergoing rapid cellular differentiation and turnover, such as those in the immune system and gastrointestinal tract. Therapeutic zinc supplementation has been initiated in low-income countries as part of diarrhea treatment programs to support these needs for young children, but the effects of preventive supplemental zinc as a tablet or as a multiple micronutrient powder (MNP) on child growth and diarrheal disease are mixed and pose programmatic uncertainties. Thus, a randomized, double-blind community-based efficacy trial of five different doses, forms, and frequencies of preventive zinc supplementation vs. a placebo was designed for a study in children aged 9⁻11 months in an urban community in Dhaka, Bangladesh. The primary outcomes of this 24-week study are incidence of diarrheal disease and linear growth. Study workers will conduct in-home morbidity checks twice weekly; anthropometry will be measured at baseline, 12 weeks and 24 weeks. Serum zinc and other related biomarkers will be measured in a subsample along with an estimate of the exchangeable zinc pool size using stable isotope techniques in a subgroup. Therapeutic zinc will be provided as part of diarrhea treatment, in accordance with Bangladesh's national policy. Therefore, the proposed study will determine the additional benefit of a preventive zinc supplementation intervention. The protocol has been approved by the Institutional Review Boards (IRBs) of icddr,b and Children's Hospital Oakland Research Institute (CHORI). The IRB review process is underway at the University of Colorado Denver as well., Competing Interests: The authors declare no conflict of interest.

Background: The etiology of >90% of cases of suspected neonatal infection remains unknown. We conducted community-based surveillance in conjunction with hospital-based surveillance in a rural region in Bangladesh from June 2006 to September 2007 to assess the incidence and etiology of community-acquired viral infections among neonates., Methods: Community health workers (CHWs) assessed neonates at home on days 0, 2, 5 and 8 after birth and referred cases of suspected illness to the hospital (CHW surveillance). Among neonates with clinically suspected upper respiratory tract infection (URTI), pneumonia, sepsis and/or meningitis, virus identification studies were conducted on nasal wash, cerebrospinal fluid and/or blood specimens. In the hospital-based surveillance, similar screening was conducted among all neonates (referred by CHWs and self-referred) who were admitted to the hospital., Results: CHW surveillance found an incidence rate of 15.6 neonatal viral infections per 1000 live births with 30% of infections identified on the day of birth. Among neonates with suspected sepsis, a viral etiology was identified in 36% of cases, with enterovirus accounting for two-thirds of those infections. Respiratory syncytial virus was the most common etiologic agent among those with viral pneumonia (91%) and URTI (68%). There was a low incidence (1.2%) of influenza in this rural population., Conclusion: Viral infections are commonly associated with acute newborn illness, even in the early neonatal period. The estimated incidence was 5-fold greater than reported previously for bacterial infections. Low-cost preventive measures for neonatal viral infections are urgently needed.

Background: We estimate the effect of antibiotics given in the intrapartum period on early-onset neonatal sepsis in Dhaka, Bangladesh using propensity score techniques., Methods: We followed 600 mother-newborn pairs as part of a cohort study at a maternity center in Dhaka. Some pregnant women received one dose of intravenous antibiotics during labor based on clinician discretion. Newborns were followed over the first seven days of life for early-onset neonatal sepsis defined by a modified version of the World Health Organization Young Infants Integrated Management of Childhood Illnesses criteria.Using propensity scores we matched women who received antibiotics with similar women who did not. A final logistic regression model predicting sepsis was run in the matched sample controlling for additional potential confounders., Results: Of the 600 mother-newborn pairs, 48 mothers (8.0%) received antibiotics during the intrapartum period. Seventy-seven newborns (12.8%) were classified with early-onset neonatal sepsis. Antibiotics appeared to be protective (odds ratio 0.381, 95% confidence interval 0.115-1.258), however this was not statistically significant. The results were similar after adjusting for prematurity, wealth status, and maternal colonization status (odds ratio 0.361, 95% confidence interval 0.106-1.225)., Conclusions: Antibiotics administered during the intrapartum period may reduce the risk of early-onset neonatal sepsis in high neonatal mortality settings like Dhaka.

Objective: To estimate the risk of early-onset neonatal sepsis among newborns of mothers with chorioamnionitis and/or bacterial colonisation in Dhaka., Methods: We conducted a cohort study at a maternity centre following 600 mother-newborn pairs. Women with a positive bacterial vaginal culture or positive Group B streptococcus (GBS) rectal culture during labour were classified as colonised. Women with placental histopathology demonstrating signs of maternal or foetal inflammation were classified as having chorioamnionitis. Newborns were followed over the first 7 days of life. The primary outcome measure was physician or community health worker diagnosis of neonatal sepsis following modified World Health Organization Integrated Management of Childhood Illnesses criteria. Survival analysis was conducted with non-parametric, parametric and semiparametric models., Results: Of the 600 mother-newborn pairs, 12.8% of newborns were diagnosed with early-onset sepsis. Five hundred and forty-three women had both colonisation and chorioamnionitis data, 55.4% of mothers were non-exposed, 31.7% were only colonised and 12.9% had chorioamnionitis regardless of colonisation status. After adjusting for birthweight, sex, maternal characteristics and wealth, newborns of only colonised mothers developed sepsis 63% faster and had a 71% higher risk of developing sepsis than their non-exposed counterparts (RT = 0.37, 95% CI 0.14-1.03; RH = 1.71, 95% CI 1.00-2.94). Newborns of mothers with chorioamnionitis developed sepsis 74% faster and had a 111% higher risk of developing sepsis (RT = 0.26, 95% CI 0.07-0.94; RH = 2.11, 95% CI 1.06-4.21)., Conclusions: Newborns born to mothers with colonisation or chorioamnionitis developed sepsis faster and were at higher risk of developing sepsis in Dhaka., (© 2013 John Wiley & Sons Ltd.)

Background: Because access to care is limited in settings with high mortality, exclusive reliance on the current recommendation of 7-10 days of parenteral antibiotic treatment is a barrier to provision of adequate treatment of newborn infections., Methods: We are conducting a trial to determine if simplified antibiotic regimens with fewer injections are as efficacious as the standard course of parenteral antibiotics for empiric treatment of young infants with clinical signs suggestive of severe infection in 4 urban hospitals and in a rural surveillance site in Bangladesh. The reference regimen of intramuscular procaine-benzyl penicillin and gentamicin given once daily for 7 days is being compared with (1) intramuscular gentamicin once daily and oral amoxicillin twice daily for 7 days and (2) intramuscular penicillin and gentamicin once daily for 2 days followed by oral amoxicillin twice daily for additional 5 days. All regimens are provided in the infant's home. The primary outcome is treatment failure (death or lack of clinical improvement) within 7 days of enrolment. The sample size is 750 evaluable infants enrolled per treatment group, and results will be reported at the end of 2013., Discussion: The trial builds upon previous studies of community case management of clinical severe infections in young infants conducted by our research team in Bangladesh. The approach although effective was not widely accepted in part because of feasibility concerns about the large number of injections. The proposed research that includes fewer doses of parenteral antibiotics if shown efficacious will address this concern.

Introduction: The burden of disease resulting from neonatal conditions is substantial in developing countries. From 2003 to 2005, the Projahnmo I programme delivered community-based interventions for maternal and newborn health in Sylhet, Bangladesh. This analysis quantifies burden of disability and incorporates non-fatal outcomes into cost-effectiveness analysis of interventions delivered in the Projahnmo I programme., Methods: A decision tree model was created to predict disability resulting from preterm birth, neonatal meningitis and intrapartum-related hypoxia ('birth asphyxia'). Outcomes were defined as the years lost to disability (YLD) component of disability-adjusted life years (DALYs). Calculations were based on data from the Projahnmo I trial, supplemented with values from published literature and expert opinion where data were absent., Results: 195 YLD per 1000 neonates [95% confidence interval (CI): 157-241] were predicted in the main calculation, sensitive to different DALY assumptions, disability weights and alternative model structures. The Projahnmo I home care intervention may have averted 2.0 (1.3-2.8) YLD per 1000 neonates. Compared with calculations based on reductions in mortality alone, the cost-effectiveness ratio decreased by only 0.6% from $105.23 to $104.62 ($65.15-$266.60) when YLD were included, with 0.6% more DALYs averted [total 338/1000 (95% CI: 131-542)]., Discussion: A significant burden of disability results from neonatal conditions in Sylhet, Bangladesh. Adding YLD has very little impact on recommendations based on cost-effectiveness, even at the margin of programme adoption. This model provides guidance for collecting data on disabilities in new settings.

A pharmacokinetic study was conducted to assess the biochemical dose-response and tolerability of high-dose prenatal vitamin D3 supplementation in Dhaka, Bangladesh (23°N). Pregnant women at 27-30 weeks gestation (n = 28) were randomized to 70,000 IU once + 35,000 IU/week vitamin D3 (group PH: pregnant, higher dose) or 14,000 IU/week vitamin D3 (PL: pregnant, lower dose) until delivery. A group of non-pregnant women (n = 16) was similarly administered 70,000 IU once + 35,000 IU/week for 10 weeks (NH: non-pregnant, higher-dose). Rise (∆) in serum 25-hydroxyvitamin D concentration ([25(OH)D]) above baseline was the primary pharmacokinetic outcome. Baseline mean [25(OH)D] were similar in PH and PL (35 nmol/L vs. 31 nmol/L, p = 0.34). A dose-response effect was observed: ∆[25(OH)D] at modeled steady-state was 19 nmol/L (95% CI, 1 to 37) higher in PH vs. PL (p = 0.044). ∆[25(OH)D] at modeled steady-state was lower in PH versus NH but the difference was not significant (-15 nmol/L, 95% CI -34 to 5; p = 0.13). In PH, 100% attained [25(OH)D] ≥ 50 nmol/L and 90% attained [25(OH)D] ≥ 80 nmol/L; in PL, 89% attained [25(OH)D] ≥ 50 nmol/L but 56% attained [25(OH)D] ≥ 80 nmol/L. Cord [25(OH)D] (n = 23) was slightly higher in PH versus PL (117 nmol/L vs. 98 nmol/L; p = 0.07). Vitamin D3 was well tolerated; there were no supplement-related serious adverse clinical events or hypercalcemia. In summary, a regimen of an initial dose of 70,000 IU and 35,000 IU/week vitamin D3 in the third trimester of pregnancy was non-hypercalcemic and attained [25(OH)D] ≥ 80 nmol/L in virtually all mothers and newborns. Further research is required to establish the safety of high-dose vitamin D3 in pregnancy and to determine if supplement-induced [25(OH)D] elevations lead to maternal-infant health benefits.