Pathogens Associated With Linear Growth Faltering in Children With Diarrhea and Impact of Antibiotic Treatment: The Global Enteric Multicenter Study.

BACKGROUND: The association between childhood diarrheal disease and linear growth faltering in developing countries is well described. However, the impact attributed to specific pathogens has not been elucidated, nor has the impact of recommended antibiotic treatment. METHODS: The Global Enteric Multicenter Study enrolled children with moderate to severe diarrhea (MSD) seeking healthcare at 7 sites in sub-Saharan Africa and South Asia. At enrollment, we collected stool samples to identify enteropathogens. Length/height was measured at enrollment and follow-up, approximately 60 days later, to calculate change in height-for-age z scores (ΔHAZ). The association of pathogens with ΔHAZ was tested using linear mixed effects regression models. RESULTS: Among 8077 MSD cases analyzed, the proportion with stunting (HAZ below -1) increased from 59% at enrollment to 65% at follow-up (P < .0001). Pathogens significantly associated with linear growth decline included Cryptosporidium (P < .001), typical enteropathogenic Escherichia coli (P = .01), and untreated Shigella (P = .009) among infants (aged 0-11 months) and enterotoxigenic E. coli encoding heat-stable toxin (P < .001) and Cryptosporidium (P = .03) among toddlers (aged 12-23 months). Shigella-infected toddlers given antibiotics had improved linear growth (P = .02). CONCLUSIONS: Linear growth faltering among children aged 0-23 months with MSD is associated with specific pathogens and can be mitigated with targeted treatment strategies, as demonstrated for Shigella.

Otitis media guidelines for Australian Aboriginal and Torres Strait Islander children: summary of recommendations.

INTRODUCTION: The 2001 Recommendations for clinical care guidelines on the management of otitis media in Aboriginal and Torres Islander populations were revised in 2010. This 2020 update by the Centre of Research Excellence in Ear and Hearing Health of Aboriginal and Torres Strait Islander Children used for the first time the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. MAIN RECOMMENDATIONS: We performed systematic reviews of evidence across prevention, diagnosis, prognosis and management. We report ten algorithms to guide diagnosis and clinical management of all forms of otitis media. The guidelines include 14 prevention and 37 treatment strategies addressing 191 questions. CHANGES IN MANAGEMENT AS A RESULT OF THE GUIDELINES: A GRADE approach is used. Targeted recommendations for both high and low risk children. New tympanostomy tube otorrhoea section. New Priority 5 for health services: annual and catch-up ear health checks for at-risk children. Antibiotics are strongly recommended for persistent otitis media with effusion in high risk children. Azithromycin is strongly recommended for acute otitis media where adherence is difficult or there is no access to refrigeration. Concurrent audiology and surgical referrals are recommended where delays are likely. Surgical referral is recommended for chronic suppurative otitis media at the time of diagnosis. The use of autoinflation devices is recommended for some children with persistent otitis media with effusion. Definitions for mild (21-30 dB) and moderate (> 30 dB) hearing impairment have been updated. New "OMapp" enables free fast access to the guidelines, plus images, animations, and multiple Aboriginal and Torres Strait Islander language audio translations to aid communication with families.

Validity of a tool designed to assess the preventability of potentially preventable hospitalizations for chronic conditions.

BACKGROUND: Potentially preventable hospitalizations (PPH) are defined as unplanned hospital admissions which could potentially have been prevented with the provision of effective, timely outpatient care. To better understand and ultimately reduce rates of PPH, a means of identifying those which are actually preventable is required. The Preventability Assessment Tool (PAT) was designed for use by hospital clinicians to assess the preventability of unplanned admissions for chronic conditions. OBJECTIVE: The present study examined the ability of the PAT to distinguish between those unplanned admissions which are preventable and those which are not, compared to the assessments of an Expert Panel. METHODS: Data were collected between November 2014 and June 2017 at three hospitals in NSW, Australia. Participants were community-dwelling patients with unplanned hospital admissions for congestive heart failure, chronic obstructive pulmonary disease, diabetes complications or angina pectoris. A nurse and a doctor caring for the patient made assessments of the preventability of the admission using the PAT. Expert Panels made assessments of the preventability of each admission based on a comprehensive case report and consensus process. RESULTS: There was little concordance between the hospital doctors and nurses regarding the preventability of admissions, nor between the assessments of the Expert Panel and the hospital nurse or the Expert Panel and the hospital doctor. CONCLUSIONS: The PAT demonstrated poor concurrent validity and is not a valid tool for assessing the preventability of unplanned hospital admissions. The use of Expert Panels provides a more rigorous approach to assessing the preventability of such admissions.

Maternal alcohol consumption during pregnancy and its association with offspring renal function at 30 years: Observation from a birth cohort study.

AIM: Prenatal exposure to alcohol has adverse ramifications on foetal development resulting in developmental abnormalities and major congenital anomalies. Experimental studies have documented effects on kidney structure and function among offspring exposed to alcohol during foetal life; however, human evidence is scarce. Thus, the present study aimed to determine the development of CKD among a cohort of 30-year-old Australian offspring whose mothers reported consumption of alcohol during pregnancy. METHODS: The study sample comprised 1626 offspring of the Australia cohort study (MUSP) whose serum creatinine was assessed at 30 years of age and CKD was categorized from stage 1 to stage 5 based on their level of eGFR following the CKD-EPI definition. RESULTS: Seven percent (n = 111) of offspring had mild (stage 2) CKD at 30 years. The overall adjusted odds of CKD were 2.10 (95% CI 1.02 to 4.33) for offspring of moderate to heavy drinking mothers in late pregnancy, 1.59 (0.69 to 3.66) for early pregnancy and 1.23 (0.75 to 2.04) for pre-pregnancy. The association was higher for female offspring-2.84 (1.07 to 7.54) for late pregnancy and 2.94 (1.10 to 7.88) for early pregnancy. Higher but insignificant odds were found for male offspring at late pregnancy 1.51 (0.49 to 4.73) only. CONCLUSION: Maternal alcohol exposure during early and late pregnancy is associated with development of mild CKD in their offspring at 30 years. This association is stronger for female than male offspring.

A Nutrition Education Program in Rural Bangladesh Was Associated with Improved Feeding Practices but Not with Child Growth.

Background: Childhood undernutrition is a major public health problem in Bangladesh. Evaluating child nutrition programs is a priority.Objective: The objective of this study was to evaluate a community-based nutrition education program (implemented from 2011 to 2013) aimed at improving infant and young child feeding (IYCF) practices and growth in rural Bangladesh.Methods: A cohort-based evaluation was conducted that included 2400 women (1200 from Karimganj, the intervention subdistrict, and 1200 from Katiadi, the control subdistrict) enrolled at 28-31 wk gestation in 3 waves between January and October 2011. Follow-up occurred at 3, 9, 16, and 24 mo of offspring age. The main outcomes were exclusive breastfeeding (EBF), measured at 3 mo, timing of complementary feeding (CF) initiation and minimum acceptable diet (MAD), measured at 9 mo, and child growth [assessed via length-for-age z score (LAZ) and weight-for-length z score], measured at all follow-ups. The main exposures were subdistrict of residence and wave of enrollment. For IYCF practices as outcome, logistic regressions were used. Generalized estimating equations were used for child growth as outcome.Results: EBF rates at 3 mo remained unchanged between waves 1 and 3 in Karimganj (55.6% compared with 57.3%), but the proportion of infants receiving timely CF initiation and MAD at 9 mo increased significantly (CF: 27.1-54.7%; MAD: 8.4-35.3%). Mean LAZ at 24 mo remained unchanged between waves 1 and 3 in Karimganj (-2.18 compared with -1.98).Conclusions: The program was successful in improving the quality of infant diet at 9 mo and timely CF initiation, but not EBF at 3 mo or LAZ. These findings support the case for implementing simple messages in all programs aimed at improving infant diet, especially in settings in which supplementing overall household diet may not be feasible.

Household food security and infant feeding practices in rural Bangladesh.

OBJECTIVE: To determine the association between household food security and infant complementary feeding practices in rural Bangladesh. DESIGN: Prospective, cohort study using structured home interviews during pregnancy and 3 and 9 months after delivery. We used two indicators of household food security at 3-months' follow-up: maternal Food Composition Score (FCS), calculated via the World Food Programme method, and an HHFS index created from an eleven-item food security questionnaire. Infant feeding practices were characterized using WHO definitions. SETTING: Two rural sub-districts of Kishoreganj, Bangladesh. SUBJECTS: Mother-child dyads (n 2073) who completed the 9-months' follow-up. RESULTS: Complementary feeding was initiated at age ≤4 months for 7 %, at 5-6 months for 49 % and at ≥7 months for 44 % of infants. Based on 24 h dietary recall, 98 % of infants were still breast-feeding at age 9 months, and 16 % received ≥4 food groups and ≥4 meals (minimally acceptable diet) in addition to breast milk. Mothers' diet was more diverse than infants'. The odds of receiving a minimally acceptable diet for infants living in most food-secure households were three times those for infants living in least food-secure households (adjusted OR=3·0; 95 % CI 2·1, 4·3). Socio-economic status, maternal age, literacy, parity and infant sex were not associated with infant diet. CONCLUSIONS: HHFS and maternal FCS were significant predictors of subsequent infant feeding practices. Nevertheless, even the more food-secure households had poor infant diet. Interventions aimed at improving infant nutritional status need to focus on both complementary food provision and education.

Maternal prenatal attitudes and postnatal breast-feeding behaviours in rural Bangladesh.

OBJECTIVE: To assess the relationships between maternal breast-feeding intention, attitudes, self-efficacy and knowledge at 7 months' gestation with exclusive or full breast-feeding at 3 months postpartum. DESIGN: Prospective cohort study with structured home interviews during pregnancy and 3 months after delivery. SETTING: Two rural sub-districts of Kishoreganj district, Bangladesh. SUBJECTS: Mother-infant dyads. RESULTS: Over 80 % of 2178 pregnant women intended to exclusively breast-feed (EBF). Maternal positive attitudes, self-efficacy and knowledge about breast-feeding were positively associated with EBF intention (all P<0.05). All mothers except one reported initiating breast-feeding and 99.6 % of children were still breast-fed at 3 months. According to 24 h dietary recalls, we categorized 985 (45.2 %) infants as EBF at 3 months (47.8 % among mothers with EBF intention; 31.7 % among mothers with no EBF intention; P<0.05) and 551 (25.3 %) infants as predominantly breast-fed at 3 months (24.2 % among mothers with EBF intention; 30.8 % among mothers with no EBF intention; P<0.05). Prenatal EBF intention was associated with EBF (OR=1.48, 95 % CI 1.14, 1.91) and with full breast-feeding (OR=1.34, 95 % CI 1.04, 1.72) at age 3 months. EBF at age 3 months was not associated with maternal breast-feeding knowledge, attitudes or self-efficacy. CONCLUSIONS: Despite widespread expressed maternal EBF intention and universal breast-feeding initiation, prevalence of both exclusive and full breast-feeding at 3 months remains lower than WHO recommendations. EBF intention predicts breast-feeding behaviours, suggesting the importance of prenatal counselling to improve infant feeding behaviours.

Maternal knowledge, attitudes and self-efficacy in relation to intention to exclusively breastfeed among pregnant women in rural Bangladesh.

Achieving optimal exclusive breastfeeding (EBF) remains a challenge. Because intention is a precursor of practice, we examined factors associated with EBF intention during pregnancy in two rural sub-districts of Kishoreganj district, Bangladesh. We studied 2,400 pregnant women in their third trimester (26-32 weeks gestation). We assessed knowledge (6 items, scale range 0-6), attitudes (15 items, scale range 15-75) and self-efficacy (6 items, scale range 6-30) by interview using a standardized questionnaire. 83.9 % of pregnant women reported EBF intention. Mean breastfeeding knowledge was 3.5 (SD 1.3), mean attitude was 55.8 (SD 8.1) and mean self-efficacy was 25.6 (SD 3.4). Knowledge was associated with EBF intention (OR 2.47, 95 % CI 1.74, 3.51), attitudes toward EBF (OR 1.68, 95 % CI 1.31, 2.16) and self-efficacy (OR 1.72, 95 % CI 1.23, 2.40) were independently associated with EBF intention in the model in which all three constructs were entered simultaneously. Receipt of breastfeeding counseling during pregnancy and being literate were each associated with EBF knowledge and EBF intention (all p < 0.05). Increasing maternal knowledge, positive attitudes, and self-efficacy regarding EBF were associated with prenatal EBF intention. These results reinforce the importance of appropriate counseling to increase EBF prevalence .

Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): a prospective, case-control study.

BACKGROUND: Diarrhoeal diseases cause illness and death among children younger than 5 years in low-income countries. We designed the Global Enteric Multicenter Study (GEMS) to identify the aetiology and population-based burden of paediatric diarrhoeal disease in sub-Saharan Africa and south Asia. METHODS: The GEMS is a 3-year, prospective, age-stratified, matched case-control study of moderate-to-severe diarrhoea in children aged 0-59 months residing in censused populations at four sites in Africa and three in Asia. We recruited children with moderate-to-severe diarrhoea seeking care at health centres along with one to three randomly selected matched community control children without diarrhoea. From patients with moderate-to-severe diarrhoea and controls, we obtained clinical and epidemiological data, anthropometric measurements, and a faecal sample to identify enteropathogens at enrolment; one follow-up home visit was made about 60 days later to ascertain vital status, clinical outcome, and interval growth. FINDINGS: We enrolled 9439 children with moderate-to-severe diarrhoea and 13,129 control children without diarrhoea. By analysing adjusted population attributable fractions, most attributable cases of moderate-to-severe diarrhoea were due to four pathogens: rotavirus, Cryptosporidium, enterotoxigenic Escherichia coli producing heat-stable toxin (ST-ETEC; with or without co-expression of heat-labile enterotoxin), and Shigella. Other pathogens were important in selected sites (eg, Aeromonas, Vibrio cholerae O1, Campylobacter jejuni). Odds of dying during follow-up were 8·5-fold higher in patients with moderate-to-severe diarrhoea than in controls (odd ratio 8·5, 95% CI 5·8-12·5, p<0·0001); most deaths (167 [87·9%]) occurred during the first 2 years of life. Pathogens associated with increased risk of case death were ST-ETEC (hazard ratio [HR] 1·9; 0·99-3·5) and typical enteropathogenic E coli (HR 2·6; 1·6-4·1) in infants aged 0-11 months, and Cryptosporidium (HR 2·3; 1·3-4·3) in toddlers aged 12-23 months. INTERPRETATION: Interventions targeting five pathogens (rotavirus, Shigella, ST-ETEC, Cryptosporidium, typical enteropathogenic E coli) can substantially reduce the burden of moderate-to-severe diarrhoea. New methods and accelerated implementation of existing interventions (rotavirus vaccine and zinc) are needed to prevent disease and improve outcomes. FUNDING: The Bill & Melinda Gates Foundation.

Prevalence, clinical predictors, and outcome of hypocalcaemia in severely-malnourished under-five children admitted to an urban hospital in Bangladesh: a case-control study.

Hypocalcaemia is common in severely-malnourished children and is often associated with fatal outcome. There is very limited information on the clinical predicting factors of hypocalcaemia in hospitalized severely-malnourished under-five children. Our objective was to evaluate the prevalence, clinical predicting factors, and outcome of hypocalcaemia in such children. In this case-control study, all severely-malnourished under-five children (n=333) admitted to the Longer Stay Ward (LSW), High Dependency Unit (HDU), and Intensive Care Unit (ICU) of the Dhaka Hospital of icddr,b between April 2011 and April 2012, who also had their total serum calcium estimated, were enrolled. Those who presented with hypocalcaemia (serum calcium <2.12 mmol/L) constituted the cases (n=87), and those admitted without hypocalcaemia (n=246) constituted the control group in our analysis. The prevalence of hypocalcaemia among severely-malnourished under-five children was 26% (87/333). The fatality rate among cases was significantly higher than that in the controls (17% vs 5%; p < 0.001). Using logistic regression analysis, after adjusting for potential confounders, such as vomiting, abdominal distension, and diastolic hypotension, we identified acute watery diarrhoea (AWD) (OR 2.19, 95% CI 1.08-4.43, p = 0.030), convulsion on admission (OR 21.86, 95% CI 2.57-185.86, p = 0.005), and lethargy (OR 2.70, 95% CI 1.633-5.46, p = 0.006) as independent predictors of hypocalcaemia in severely-malnourished children. It is concluded, severely-malnourished children presenting with hypocalcaemia have an increased risk of death than those without hypocalcaemia. AWD, convulsion, and lethargy assessed on admission to hospital are the clinical predictors of hypocalcaemia in such children. Presence of these features in hospitalized children with severe acute malnutrition (SAM) should alert clinicians about the possibility of hypocalcaemia and may help undertake potential preventive measures, such as calcium supplementation, in addition to other aspects of management of such children, especially in the resource-poor settings.

Diarrhoeal disease and subsequent risk of death in infants and children residing in low-income and middle-income countries: analysis of the GEMS case-control study and 12-month GEMS-1A follow-on study.

BACKGROUND: The Global Enteric Multicenter Study (GEMS) was a 3-year case-control study that measured the burden, aetiology, and consequences of moderate-to-severe diarrhoea (MSD) in children aged 0-59 months. GEMS-1A, a 12-month follow-on study, comprised two parallel case-control studies, one assessing MSD and the other less-severe diarrhoea (LSD). In this report, we analyse the risk of death with each diarrhoea type and the specific pathogens associated with fatal outcomes. METHODS: GEMS was a prospective, age-stratified, matched case-control study done at seven sites in Africa and Asia. Children aged 0-59 months with MSD seeking care at sentinel health centres were recruited along with one to three randomly selected matched community control children without diarrhoea. In the 12-month GEMS-1A follow-on study, children with LSD and matched controls, in addition to children with MSD and matched controls, were recruited at six of the seven sites; only cases of MSD and controls were enrolled at the seventh site. We compared risk of death during the period between enrolment and one follow-up household visit done about 60 days later (range 50-90 days) in children with MSD and LSD and in their respective controls. Approximately 50 pathogens were detected using, as appropriate, classic bacteriology, immunoassays, gel-based PCR and reverse transcriptase PCR, and quantitative real-time PCR (qPCR). Specimens from a subset of GEMS cases and controls were also tested by a TaqMan Array Card that compartmentalised probe-based qPCR for 32 enteropathogens. FINDINGS: 223 (2·0%) of 11 108 children with MSD and 43 (0·3%) of 16 369 matched controls died between study enrolment and the follow-up visit at about 60 days (hazard ratio [HR] 8·16, 95% CI 5·69-11·68, p<0·0001). 12 (0·4%) of 2962 children with LSD and seven (0·2%) of 4074 matched controls died during the follow-up period (HR 2·78, 95% CI 0·95-8·11, p=0·061). Risk of death was lower in children with dysenteric MSD than in children with non-dysenteric MSD (HR 0·20, 95% CI 0·05-0·87, p=0·032), and lower in children with LSD than in those with non-dysenteric MSD (HR 0·29, 0·14-0·59, p=0·0006). In children younger than 24 months with MSD, infection with typical enteropathogenic Escherichia coli, enterotoxigenic E coli encoding heat-stable toxin, enteroaggregative E coli, Shigella spp (non-dysentery cases), Aeromonas spp, Cryptosporidium spp, and Entamoeba histolytica increased risk of death. Of 61 deaths in children aged 12-59 months with non-dysenteric MSD, 31 occurred among 942 children qPCR-positive for Shigella spp and 30 deaths occurred in 1384 qPCR-negative children (HR 2·2, 95% CI 1·2-3·9, p=0·0090), showing that Shigella was strongly associated with increased risk of death. INTERPRETATION: Risk of death is increased following MSD and, to a lesser extent, LSD. Considering there are approximately three times more cases of LSD than MSD in the population, more deaths are expected among children with LSD than in those with MSD. Because the major attributable LSD-associated and MSD-associated pathogens are the same, implementing vaccines and rapid diagnosis and treatment interventions against these major pathogens are rational investments. FUNDING: Bill & Melinda Gates Foundation.

The incidence, aetiology, and adverse clinical consequences of less severe diarrhoeal episodes among infants and children residing in low-income and middle-income countries: a 12-month case-control study as a follow-on to the Global Enteric Multicenter Study (GEMS).

BACKGROUND: Diarrheal diseases remain a leading cause of illness and death among children younger than 5 years in low-income and middle-income countries. The Global Enteric Multicenter Study (GEMS) has described the incidence, aetiology, and sequelae of medically attended moderate-to-severe diarrhoea (MSD) among children aged 0-59 months residing in censused populations in sub-Saharan Africa and south Asia, where most child deaths occur. To further characterise this disease burden and guide interventions, we extended this study to include children with episodes of less-severe diarrhoea (LSD) seeking care at health centres serving six GEMS sites. METHODS: We report a 1-year, multisite, age-stratified, matched case-control study following on to the GEMS study. Six sites (Bamako, Mali; Manhiça, Mozambique; Basse, The Gambia; Mirzapur, Bangladesh; Kolkata, India; and Bin Qasim Town, Karachi, Pakistan) participated in this study. Children aged 0-59 months at each site who sought care at a sentinel hospital or health centre during a 12-month period were screened for diarrhoea. New (onset after ≥7 diarrhoea-free days) and acute (onset within the previous 7 days) episodes of diarrhoea in children who had sunken eyes, whose skin lost turgor, who received intravenous hydration, who had dysentery, or who were hospitalised were eligible for inclusion as MSD. The remaining new and acute diarrhoea episodes among children who sought care at the same health centres were considered LSD. We aimed to enrol the first eight or nine eligible children with MSD and LSD at each site during each fortnight in three age strata: infants (aged 0-11 months), toddlers (aged 12-23 months), and young children (aged 24-59 months). For each included case of MSD or LSD, we enrolled one to three community control children without diarrhoea during the previous 7 days. From patients and controls we collected clinical and epidemiological data, anthropometric measurements, and faecal samples to identify enteropathogens at enrolment, and we performed a follow-up home visit about 60 days later to ascertain vital status, clinical outcome, and interval growth. Primary outcomes were to characterise, for MSD and LSD, the pathogen-specific attributable risk and population-based incidence values, and to assess the frequency of adverse clinical consequences associated with these two diarrhoeal syndromes. FINDINGS: From Oct 31, 2011, to Nov 14, 2012, we recruited 2368 children with MSD, 3174 with LSD, and one to three randomly selected community control children without diarrhoea matched to cases with MSD (n=3597) or LSD (n=4236). Weighted adjusted population attributable fractions showed that most attributable cases of MSD and LSD were due to rotavirus, Cryptosporidium spp, enterotoxigenic Escherichia coli encoding heat-stable toxin (with or without genes encoding heat-labile enterotoxin), and Shigella spp. The attributable incidence per 100 child-years for LSD versus MSD, by age stratum, for rotavirus was 22·3 versus 5·5 (0-11 months), 9·8 versus 2·9 (12-23 months), and 0·5 versus 0·2 (24-59 months); for Cryptosporidium spp was 3·6 versus 2·3 (0-11 months), 4·3 versus 0·6 (12-23 months), and 0·3 versus 0·1 (24-59 months); for enterotoxigenic E coli encoding heat-stable toxin was 4·2 versus 0·1 (0-11 months), 5·2 versus 0·0 (12-23 months), and 1·1 versus 0·2 (24-59 months); and for Shigella spp was 1·0 versus 1·3 (0-11 months), 3·1 versus 2·4 (12-23 months), and 0·8 versus 0·7 (24-59 months). Participants with both MSD and LSD had significantly more linear growth faltering than controls at follow-up. INTERPRETATION: Inclusion of participants with LSD markedly expands the population of children who experience adverse clinical and nutritional outcomes from acute diarrhoeal diseases. Since MSD and LSD have similar aetiologies, interventions targeting rotavirus, Shigella spp, enterotoxigenic E coli producing heat-stable toxin, and Cryptosporidium spp might substantially reduce the diarrhoeal disease burden and its associated nutritional faltering. FUNDING: Bill & Melinda Gates Foundation.

Colonization factors among enterotoxigenic Escherichia coli isolates from children with moderate-to-severe diarrhea and from matched controls in the Global Enteric Multicenter Study (GEMS).

BACKGROUND: Enterotoxigenic Escherichia coli (ETEC) encoding heat-stable enterotoxin (ST) alone or with heat-labile enterotoxin (LT) cause moderate-to-severe diarrhea (MSD) in developing country children. The Global Enteric Multicenter Study (GEMS) identified ETEC encoding ST among the top four enteropathogens. Since the GEMS objective was to provide evidence to guide development and implementation of enteric vaccines and other interventions to diminish diarrheal disease morbidity and mortality, we examined colonization factor (CF) prevalence among ETEC isolates from children age <5 years with MSD and from matched controls in four African and three Asian sites. We also assessed strength of association of specific CFs with MSD. METHODOLOGY/PRINCIPAL FINDINGS: MSD cases enrolled at healthcare facilities over three years and matched controls were tested in a standardized manner for many enteropathogens. To identify ETEC, three E. coli colonies per child were tested by polymerase chain reaction (PCR) to detect genes encoding LT, ST; confirmed ETEC were examined by PCR for major CFs (Colonization Factor Antigen I [CFA/I] or Coli Surface [CS] antigens CS1-CS6) and minor CFs (CS7, CS12, CS13, CS14, CS17, CS18, CS19, CS20, CS21, CS30). ETEC from 806 cases had a single toxin/CF profile in three tested strains per child. Major CFs, components of multiple ETEC vaccine candidates, were detected in 66.0% of LT/ST and ST-only cases and were associated with MSD versus matched controls by conditional logistic regression (p≤0.006); major CFs detected in only 25.0% of LT-only cases weren't associated with MSD. ETEC encoding exclusively CS14, identified among 19.9% of 291 ST-only and 1.5% of 259 LT/ST strains, were associated with MSD (p = 0.0011). No other minor CF exhibited prevalence ≥5% and significant association with MSD. CONCLUSIONS/SIGNIFICANCE: Major CF-based efficacious ETEC vaccines could potentially prevent up to 66% of pediatric MSD cases due to ST-encoding ETEC in developing countries; adding CS14 extends coverage to ~77%.

An early life course association of pulse pressure with adulthood estimated glomerular filtration rate: evidence from a large community-based birth cohort study.

BACKGROUND: Little is known about pulse pressure (PP) during early life and its association with renal function at young adulthood. This study describes an early life course association of PP with adult renal function at 30 years from a large community-based birth cohort study in Australia. METHOD: Sample comprises 1169 young adults aged 30 years from the Mater-University of Queensland Study of Pregnancy, whose blood pressure was recorded in at least three follow-ups (5, 14, 21, and 30 years) and renal function was assessed at 30 years. Estimated glomerular filtration rate was estimated to determine the stages of chronic kidney disease (CKD). A group-based trajectory modelling was developed to identify patterns of PP from childhood to adulthood. Multiple logistic regression was used to determine whether PP trajectories predict adult CKD. RESULTS: In total, 7% of participants (91) had mild CKD. Three PP trajectories were identified: 16% were in the high PP trajectory group characterized by substantial increase in PP over time; 58% were in the middle group who had lower PP at 5 years, which increased at 14 years and then gradually declined at 21 and 30 years, and the remaining 26% were in a lower group which remained static. In the adjusted model, significantly higher odds were found for the high [odds ratio: 2.42 (95% confidence interval: 1.02-5.74)] and middle [2.23 (1.19-4.19)] PP trajectory groups for development of mild CKD at 30 years compared with the low (static) group. CONCLUSION: Early life high and middle PP trajectories predict the risk of subclinical renal insufficiency by age 30 years.

Socioeconomic Determinants of Cipro-floxacin-Resistant Shigella Infections in Bangladeshi Children.

BACKGROUND: Shigella species (spp.) are a leading cause of moderate to severe diarrhea in children worldwide. The recent emergence of quinolone-resistant Shigella spp. gives cause for concern, and South Asia has been identified as a reservoir for global spread. The influence of socioeconomic status on antimicrobial resistance in developing countries, such as those in South Asia, remains unknown. METHODS: We used data collected from 2009 to 2014 from a hospital specializing in the treatment of diarrhea in Dhaka, Bangladesh, to determine the relationship between Ciprofloxacin-resistant Shigella spp. isolates and measures of socioeconomic status in Bangladeshi children less than 5 years of age. RESULTS: We found 2.7% (230/8,672) of children who presented with diarrhea had Shigella spp. isolated from their stool, and 50% (115/230) had resistance to Ciprofloxacin. Using multivariable logistic regression analysis, we found that children from families where the father's income was in the highest quintile had significantly higher odds of having Ciprofloxacin-resistant Shigella spp. compared to children in the lowest quintile (OR = 6.1, CI 1.9-19). Factors protective against the development of resistance included access to improved sanitation (OR = 0.27, CI 0.11-0.7), and improved water sources (OR = 0.48, CI 0.25-0.92). We did not find a relationship between Ciprofloxacin resistance and other proxies for socioeconomic status, including the presence of animals in the home, nutritional status, paternal education level, and the number of family members in the home. CONCLUSIONS: Although the associations between wealth and antimicrobial resistance are not fully understood, possible explanations include increased access and use of antibiotics, greater access to healthcare facilities and thus resistant pathogens, or greater consumption of commercially produced foods prepared with antibiotics.

Impact of fortified biscuits on micronutrient deficiencies among primary school children in Bangladesh.

BACKGROUND: Micronutrient deficiencies can compromise the development potential of school-aged children, and their later health and productivity as adults. School feeding and school-based fortification approaches have been utilized globally to redress nutritional deficiencies in this age group. OBJECTIVE: We explored the acceptability and micronutrient impact of a Bangladesh Government supported school-based micronutrient fortification program for children attending rural primary schools in 10 disadvantaged sub-districts. METHODS: We applied a mixed methods approach. The quantitative component assessed the impact of micronutrient fortification on 351 children aged 6-11 years using a cohort pre-post research design with a control group. The qualitative component explored the acceptability of the intervention using focus group discussions, body mapping and semi-structured interviews with teachers, school-going children and school authorities. RESULTS: Daily consumption of fortified biscuits by primary school children had a significant positive impact on mean levels of iron, folic acid, vitamin B12, retinol and vitamin D controlling for sex, baseline deficiency status, CRP, and H. pylori. Levels of anemia and vitamin D deficiency were also significantly reduced. Qualitative findings indicated the widespread acceptability of the daily biscuit. Teachers perceived students to be more attentive in class, less tired, and some attributed better school performance to biscuit consumption. Children reported similar improvements in concentration and energy levels. CONCLUSIONS: This study is among the first in Bangladesh to comprehensively assess a school-based fortification program in terms of its acceptability and impact on micronutrient status of children aged 6-11 years of age. While results strongly support this modality of school feeding, research on the cognitive impacts of micronutrient fortified biscuits will help clarify the case for scaled-up investments in school- based feeding program in Bangladesh and other low and middle income countries.

Minimum Acceptable Diet at 9 Months but Not Exclusive Breastfeeding at 3 Months or Timely Complementary Feeding Initiation Is Predictive of Infant Growth in Rural Bangladesh.

The association between suboptimal infant feeding practices and growth faltering is well-established. However, most of this evidence comes from cross-sectional studies. To prospectively assess the association between suboptimal infant feeding practices and growth faltering, we interviewed pregnant women at 28-32 weeks' gestation and followed-up their offspring at postnatal months 3, 9, 16 and 24 months in rural Bangladesh. Using maternal recall over the past 24 hours, exclusive breastfeeding (EBF) status at 3 months, age at complementary feeding (CF) initiation, and receipt of minimum acceptable diet (MAD; as defined by WHO) at 9 months were assessed. Infant length and weight measurements were used to produce length-for-age (LAZ) and weight-for-length (WLZ) z-scores at each follow-up. Generalized estimating equations were used to estimate associations of LAZ and WLZ with infant feeding practices. All models were adjusted for baseline SES, infant sex, maternal height, age, literacy and parity. Follow-up was completed by 2189, 2074, 1969 and 1885 mother-child dyads at 3, 9, 16 and 24 months, respectively. Stunting prevalence increased from 28% to 57% between infant age 3 and 24 months. EBF at 3 months and age at CF initiation were not associated with linear infant growth, but receipt of MAD at 9 months was. By age 24 months, infants receiving MAD had attained a higher LAZ compared to infants who did not receive MAD (adjusted ß = 0.25, 95% CI: 0.13-0.37). Although prevalence of stunting was already high at age 3 months, ensuring infants receive a diverse, high quality diet from 6 months onwards may reduce rates of stunting in the second year of life.

Aeromonas-Associated Diarrhea in Children Under 5 Years: The GEMS Experience.

We report the clinical findings, epidemiology, and risk factors for moderate-to-severe diarrhea (MSD) associated with Aeromonas species in children 0-59 months of age, from the Global Enteric Multicenter Study, conducted at three sites in south Asia and four sites in sub-Saharan Africa. Children with MSD were enrolled along with controls matched for age, gender, and neighborhood. Pooled, age-stratified conditional logistic regression models were applied to evaluate the association of Aeromonas infection controlling for coinfecting pathogens and sociodemographic variables. A pooled, age-stratified, multivariate logistic regression analysis was done to identify risk factors associated with Aeromonas positivity in MSD cases. A total of 12,110 cases and 17,291 matched controls were enrolled over a period of 48 months. Aeromonas was identified as a significant pathogen in 736 cases of MSD in Pakistan and Bangladesh (22.2%). Aeromonas remained a significant pathogen even after adjustment for the presence of other pathogens and sociodemographic factors. Odds ratio (OR) for Aeromonas were higher in the presence of Shigella (matched OR: 6.2, 95% confidence interval [CI]: 1.9-20.2). Cases of Aeromonas were likely to present with dysentery, particularly in the 0-11 months (OR: 1.4, 95% CI 1.0-2.0) and 12-23 months (OR: 1.8, 95% CI: 1.3-2.5) age group. The odds of Aeromonas increased with increasing degree of stunting, being highest for severe stunting (OR: 10.1, 95% CI: 3.6-28.9). Aeromonas is a significant pathogen for MSD in Pakistan and Bangladesh. Presence of dysentery and co-occurrence with other pathogens, notably Shigella spp. are significant features of Aeromonas-associated diarrhea.