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    Robert e. Black

    The research was carried out to study the rate of population-based hospital admissions due to acute lower respiratory infections (ALRIs) and bacterial aetiology of ALRIs in children aged less than five years in Bangladesh. A cohort of... more
    The research was carried out to study the rate of population-based hospital admissions due to acute lower respiratory infections (ALRIs) and bacterial aetiology of ALRIs in children aged less than five years in Bangladesh. A cohort of children aged less than five years in a rural surveillance population in Matlab, Bangladesh, was studied for two years. Cases were children admitted to the Matlab Hospital of ICDDR,B with a diagnosis of severe ALRIs. Bacterial aetiology was determined by blood culture. Antimicrobial resistance patterns of Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae (Spn) isolates were determined using the disc-diffusion method. In total, 18,983 children aged less than five years contributed to 24,902 child-years of observation (CYO). The incidence of ALRI-related hospital admissions was 50.2 per 1,000 CYO. The incidences of ALRI were 67% higher in males than in females and were higher in children aged less than two years than in older children. Abo...
    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... more
    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 pre...
    Lack of surveillance systems and accurate data impede evidence-based decisions on treatment and prevention of enteric fever, caused by Salmonella Typhi/Paratyphi. The WHO coordinates a global Invasive Bacterial-Vaccine Preventable... more
    Lack of surveillance systems and accurate data impede evidence-based decisions on treatment and prevention of enteric fever, caused by Salmonella Typhi/Paratyphi. The WHO coordinates a global Invasive Bacterial-Vaccine Preventable Diseases (IB-VPD) surveillance network but does not monitor enteric fever. We evaluated the feasibility and sustainability of integrating enteric fever surveillance into the ongoing IB-VPD platform. The IB-VPD surveillance system uses WHO definitions to enroll 2-59 month children hospitalized with possible pneumonia, sepsis or meningitis. We expanded this surveillance system to additionally capture suspect enteric fever cases during 2012-2016, in two WHO sentinel hospitals of Bangladesh, by adding inclusion criteria of fever ≥102°F for ≥3 days, irrespective of other manifestations. Culture-positive enteric fever cases from in-patient departments (IPD) detected in the hospital laboratories but missed by the expanded surveillance, were also enrolled to asses...
    Objectives To estimate small for gestational age birth prevalence and attributable neonatal mortality in low and middle income countries with the INTERGROWTH-21(st) birth weight standard.Design Secondary analysis of data from the Child... more
    Objectives To estimate small for gestational age birth prevalence and attributable neonatal mortality in low and middle income countries with the INTERGROWTH-21(st) birth weight standard.Design Secondary analysis of data from the Child Health Epidemiology Reference Group (CHERG), including 14 birth cohorts with gestational age, birth weight, and neonatal follow-up. Small for gestational age was defined as infants weighing less than the 10th centile birth weight for gestational age and sex with the multiethnic, INTERGROWTH-21(st) birth weight standard. Prevalence of small for gestational age and neonatal mortality risk ratios were calculated and pooled among these datasets at the regional level. With available national level data, prevalence of small for gestational age and population attributable fractions of neonatal mortality attributable to small for gestational age were estimated.Setting CHERG birth cohorts from 14 population based sites in low and middle income countries.Main o...
    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... more
    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...
    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... more
    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. Hemog...
    National estimates for the numbers of babies born small for gestational age and the comorbidity with preterm birth are unavailable. We aimed to estimate the prevalence of term and preterm babies born small for gestational age (term-SGA... more
    National estimates for the numbers of babies born small for gestational age and the comorbidity with preterm birth are unavailable. We aimed to estimate the prevalence of term and preterm babies born small for gestational age (term-SGA and preterm-SGA), and the relation to low birthweight (<2500 g), in 138 countries of low and middle income in 2010. Small for gestational age was defined as lower than the 10th centile for fetal growth from the 1991 US national reference population. Data from 22 birth cohort studies (14 low-income and middle-income countries) and from the WHO Global Survey on Maternal and Perinatal Health (23 countries) were used to model the prevalence of term-SGA births. Prevalence of preterm-SGA infants was calculated from meta-analyses. In 2010, an estimated 32·4 million infants were born small for gestational age in low-income and middle-income countries (27% of livebirths), of whom 10·6 million infants were born at term and low birthweight. The prevalence of ...
    Objectives.To describe breastfeeding practices and investigate the influence of exclusive breastfeeding in early infancy on the risk of infant deaths, especially those attributable to respiratory infections (ARI) and diarrhea.Methods.A... more
    Objectives.To describe breastfeeding practices and investigate the influence of exclusive breastfeeding in early infancy on the risk of infant deaths, especially those attributable to respiratory infections (ARI) and diarrhea.Methods.A prospective observational study was conducted on a birth cohort of 1677 infants who were born in slum areas of Dhaka in Bangladesh and followed from birth to 12 months of age. After enrollment at birth, the infants were visited 5 more times by 12 months of age. Verbal autopsy, based on a structured questionnaire, was used to assign a cause to the 180 reported deaths. Proportional hazards regression models were used to estimate the effect of breastfeeding practices, introduced as a time-varying variable, after accounting for other variables, including birth weight. Overall neonatal, postneonatal and infant mortality, and mortality attributable to ARI and diarrhea were measured.Results.The proportion of infants who were breastfed exclusively was only 6%...
    The turnaround time (TAT) for Salmonella enterica serovar Typhi identification and reporting of the antibiotic susceptibility profile was determined for 391 cases of typhoid fever, using the lysis direct plating or lysis centrifugation... more
    The turnaround time (TAT) for Salmonella enterica serovar Typhi identification and reporting of the antibiotic susceptibility profile was determined for 391 cases of typhoid fever, using the lysis direct plating or lysis centrifugation method of blood culture along with rapid antimicrobial susceptibility testing. The TAT was more rapid (TAT for 90% of the patients [TAT 90 ] = 30 h; TAT 100 ≤ 67 h) than was possible with conventional methodologies and was equivalent to that reported previously using more advanced, costly technologies that are largely unavailable in developing countries. Antibiotic susceptibility profiles, determined by the rapid antimicrobial susceptibility testing method, of randomly selected 60 S. enterica serovar Typhi isolates were identical to those determined by overnight conventional testing. Preliminary assessment of the impact of the reduced TAT on physician practices revealed that initial empirical therapy was prescribed at the time of presentation in most ...
    The nasopharyngeal carriage of Streptococcus pneumoniae is thought to pose a risk for invasive pneumococcal diseases, and the evaluation of carriage strains is thus often used to inform antibiotic treatment and vaccination strategies for... more
    The nasopharyngeal carriage of Streptococcus pneumoniae is thought to pose a risk for invasive pneumococcal diseases, and the evaluation of carriage strains is thus often used to inform antibiotic treatment and vaccination strategies for these diseases. In this study, the age-specific prevalences, resistance to antibiotics, and serotype distributions of 1,340 carriage strains were analyzed and compared to 71 pneumococcal strains isolated from the cerebrospinal fluid of children under 5 years old with meningitis. Overall, the nasal carriage rate was 47%. One-fourth (26%) of the infants under 1 month of age and one-half (48%) of the infants under 12 months of age were colonized with S. pneumoniae . Rural children were colonized earlier than those from urban areas. Approximately one-fourth and one-half of the cases of pneumococcal meningitis occurred in the first 3 and 6 months of life, respectively. The respective rates of resistance for carriage and meningitis strains to penicillin (...
    The objective of the study was to determine the prevalence of smear-positive tuberculosis (TB) in a rural area in Bangladesh at Matlab. A TB surveillance system was established among 106000 people in rural Bangladesh at Matlab. Trained... more
    The objective of the study was to determine the prevalence of smear-positive tuberculosis (TB) in a rural area in Bangladesh at Matlab. A TB surveillance system was established among 106000 people in rural Bangladesh at Matlab. Trained field workers interviewed all persons aged [ges ]15 years to detect suspected cases of TB (cough>21 days) and sputum specimens of suspected cases were examined for acid-fast bacilli (AFB). Of 59395 persons interviewed, 4235 (7·1%) had a cough for >21 days. Sputum specimens were examined for AFB from 3834 persons, 52 (1·4%) of them were positive for AFB. The prevalence of chronic cough and sputum positivity were significantly higher among males compared to females (P<0·001). The population-based prevalence rate of smear-positive TB cases was 95/100000 among persons aged [ges ]15 years. Cases of TB clustered geographically (relative risk 5·53, 95% CI 3·19–9·59). The high burden of TB among rural population warrants appropriate measures to contr...
    Background The World Health Organization recommends dry cord care for newborns but this recommendation may not be optimal in low resource settings where most births take place in an unclean environment and infections account for up to... more
    Background The World Health Organization recommends dry cord care for newborns but this recommendation may not be optimal in low resource settings where most births take place in an unclean environment and infections account for up to half of neonatal deaths. A previous trial in Nepal indicated that umbilical cord cleansing with 4.0% chlorhexidine could substantially reduce mortality and omphalitis risk, but policy changes await additional community-based data. Methods The Projahnmo Chlorhexidine study was a three-year, cluster-randomized, community-based trial to assess the impact of three cord care regimens on neonatal mortality and omphalitis. Women were recruited mid-pregnancy, received a basic package of maternal and neonatal health promotion messages, and were followed to pregnancy outcome. Newborns were visited at home by local village-based workers whose areas were randomized to either 1) single- or 2) 7-day cord cleansing with 4.0% chlorhexidine, or 3) promotion of dry cord...
    In a community-based double-blind randomized trial in children aged 6–35 months, both intervention and control groups received a multi-vitamin syrup containing vitamin A, while the intervention group had zinc gluconate (equivalent to 10... more
    In a community-based double-blind randomized trial in children aged 6–35 months, both intervention and control groups received a multi-vitamin syrup containing vitamin A, while the intervention group had zinc gluconate (equivalent to 10 mg of elemental zinc) additional in the syrup. There was a significant decrease in diarrhoea and pneumonia in the intervention group. This study was undertaken to investigate if addition of zinc to vitamin A had improved plasma retinol levels, which, in turn, was responsible for the effects observed in the intervention group. In a randomly-selected subsample of 200 children—100 each from the intervention and the control group, plasma retinol levels after 120 days of supplementation were measured. There was no difference in the mean plasma retinol levels [the difference in the mean 0.46 μg/dL (95% confidence interval -1.42–2.36)] between the two groups following supplementation. No difference in plasma retinol levels was observed in the subgroups base...
    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... more
    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.
    In 2013, an estimated 2.8 million newborns died and 2.7 million were stillborn. A much greater number suffer from long term impairment associated with preterm birth, intrauterine growth restriction, congenital anomalies, and perinatal or... more
    In 2013, an estimated 2.8 million newborns died and 2.7 million were stillborn. A much greater number suffer from long term impairment associated with preterm birth, intrauterine growth restriction, congenital anomalies, and perinatal or infectious causes. With the approaching deadline for the achievement of the Millennium Development Goals (MDGs) in 2015, there was a need to set the new research priorities on newborns and stillbirth with a focus not only on survival but also on health, growth and development. We therefore carried out a systematic exercise to set newborn health research priorities for 2013-2025. We used adapted Child Health and Nutrition Research Initiative (CHNRI) methods for this prioritization exercise. We identified and approached the 200 most productive researchers and 400 program experts, and 132 of them submitted research questions online. These were collated into a set of 205 research questions, sent for scoring to the 600 identified experts, and were assess...
    Iron and zinc are essential micronutrients for human health. Deficiencies in these 2 nutrients remain a global problem, especially among women and children in developing countries. Supplementation with iron and zinc as single... more
    Iron and zinc are essential micronutrients for human health. Deficiencies in these 2 nutrients remain a global problem, especially among women and children in developing countries. Supplementation with iron and zinc as single micronutrients enhances distinct and unique biochemical and functional outcomes. These micronutrients have the potential to interact when given together; thus, it is important to assess the biochemical and functional evidence from clinical trials before supplementation policies are established. We reviewed randomized trials that assessed the effects of iron and zinc supplementation on iron and zinc status. On the basis of this review, zinc supplementation alone does not appear to have a clinically important negative effect on iron status. However, when zinc is given with iron, iron indicators do not improve as greatly as when iron is given alone. In most of the studies, iron supplementation did not affect the biochemical status of zinc, but the data are not cle...
    Evidence for an effect of zinc supplementation on growth and morbidity in very young infants in developing countries is scarce and inconsistent. We assessed the effect of zinc supplementation on growth and morbidity in poor Bangladeshi... more
    Evidence for an effect of zinc supplementation on growth and morbidity in very young infants in developing countries is scarce and inconsistent. We assessed the effect of zinc supplementation on growth and morbidity in poor Bangladeshi infants aged 4-24 wk. Infants from Dhaka slums were enrolled at 4 wk of age and randomly assigned to receive 5 mg elemental Zn/d (n = 152) or placebo (n = 149) until 24 wk of age. They were followed weekly for information on compliance and morbidity; anthropometric measurements were performed monthly. Serum zinc was assessed at baseline and at 24 wk of age. At 24 wk of age, serum zinc concentrations were higher in the zinc than in the placebo group (13.3 +/- 3.8 and 10.7 +/- 2.9 micro mol/L, respectively; P < 0.001). Significantly greater weight gains were observed in the zinc than in the placebo group for 43 infants who were zinc deficient (< 9.18 micro mol/L) at baseline (3.15 +/- 0.77 and 2.66 +/- 0.80 kg, respectively; P < 0.04). In the o...
    Multidrug resistance (MDR), specifically to ampicillin and chloramphenicol, has complicated the treatment of Haemophilus influenzae type b (Hib) meningitis. This is worsened by use of prior antibiotics, which limits identification of the... more
    Multidrug resistance (MDR), specifically to ampicillin and chloramphenicol, has complicated the treatment of Haemophilus influenzae type b (Hib) meningitis. This is worsened by use of prior antibiotics, which limits identification of the causative agent by culture and increases reliance on antigen detection. We aimed to develop a PCR assay for detecting the family of Haemophilus integrating and conjugative elements (ICEs) represented by ICEHin1056 among antibiotic resistant Hib, and then apply this directly to CSF to diagnose Hib meningitis and predict organism susceptibility, irrespective of culture results. Primers specific for orf 51 of ICEHin1056 were designed and multiplexed with Bex primers, specific for H. influenzae, and tested on culture positive and negative cases. Of 73 Hib isolates, orf 51 PCR amplicons, predicting the presence of ICEs, were found in all 33 MDR isolates while only in 1 of 33 sensitive strains. The remaining 7 ampicillin susceptible, chloramphenicol and tetracycline resistant strains did not produce a PCR product to orf 51. PCR amplification from CSF specimens of these culture positive cases produced identical results with 100% and 97% positive and negative predictive values, respectively. Multiplex PCR to detect Bex and orf 51 identified another 16 MDR Hib cases among 81 culture-negative CSF samples. Direct PCR for orf 51 in CSF identified resistance pattern of 51% more Hib strains than culture alone (110 versus 73). The ability to detect MDR, in culture negative Hib meningitis cases has significant implications for better directing antibiotic treatment of meningitis cases and thus for preventing disability and death.
    Studies from Asia have suggested that zinc supplementation can reduce morbidity and mortality in children, but evidence from malarious populations in Africa has been inconsistent. Our aim was to assess the effects of zinc supplementation... more
    Studies from Asia have suggested that zinc supplementation can reduce morbidity and mortality in children, but evidence from malarious populations in Africa has been inconsistent. Our aim was to assess the effects of zinc supplementation on overall mortality in children in Pemba, Zanzibar. We enrolled 42,546 children aged 1-36 months, contributing a total of 56,507 child-years in a randomised, double-blind, placebo-controlled trial in Pemba, Zanzibar. Randomisation was by household. 21 274 children received daily supplementation with zinc 10 mg (5 mg in children younger than 12 months) for mean 484.7 days (SD 306.6). 21,272 received placebo. The primary endpoint was overall mortality, and analysis was by intention to treat. This study is registered as an International Standard Randomised Clinical Trial, number ISRCTN59549825. Overall, there was a non-significant 7% (95% CI -6% to 19%; p=0.29) reduction in the relative risk of all-cause mortality associated with zinc supplementation. We believe that a meta-analysis of all studies of mortality and morbidity, will help to make evidence-based recommendations for the role of zinc supplementation in public health policy to improve mortality, morbidity, growth, and development in young children.

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