Psychosocial and environmental determinants of child cognitive development in rural south africa and tanzania: findings from the mal-ed cohort

Background Approximately 66% of children under the age of 5 in Sub-Saharan African countries do not reach their full cognitive potential, the highest percentage in the world. Because the majority of studies investigating child cognitive development have been conducted in high-income countries (HICs), there is limited knowledge regarding the determinants of child development in low- and middle-income countries (LMICs). Methods This analysis includes 401 mother-child dyads from the South Africa and Tanzania sites of the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) longitudinal birth cohort study. We investigated the effect of psychosocial and environmental determinants on child cognitive development measured by the Wechsler Preschool Primary Scales of Intelligence (WPPSI) at 5 years of age using multivariable linear regression. Results Socioeconomic status was most strongly associated with child cognitive development (WPSSI Score Difference (SD):14.27, 95% CI:1.96, 26.59). Modest associations between the organization of the home environment and its opportunities for cognitive stimulation and child cognitive development were also found (SD: 3.08, 95% CI: 0.65, 5.52 and SD: 3.18, 95% CI: 0.59, 5.76, respectively). Conclusion This study shows a stronger association with child cognitive development at 5 years of age for socioeconomic status compared to more proximal measures of psychosocial and environmental determinants. A better understanding of the role of these factors is needed to inform interventions aiming to alleviate the burden of compromised cognitive development for children in LMICs.publishedVersio

Brief Report: Estimating Differences and Ratios in Median Times to Event

Time differences and time ratios are often more interpretable estimates of effect than hazard ratios for time-to-event data, especially for common outcomes. We developed a SAS macro for estimating time differences and time ratios between baseline-fixed binary exposure groups based on inverse probability weighted Kaplan-Meier curves. The macro uses pooled logistic regression to calculate inverse probability of censoring and exposure weights, draws Kaplan-Meier curves based on the weighted data, and estimates the time difference and time ratio at a user-defined survival proportion. The macro also calculates the risk difference and risk ratio at a user-specified time. Confidence intervals are constructed by bootstrap. We provide an example assessing the effect of exclusive breastfeeding during diarrhea on the incidence of subsequent diarrhea in children followed from birth to 3 years in Vellore, India. The SAS macro provided here should facilitate the wider reporting of time differences and time ratios

Early Life Antibiotic Exposure Is Not Associated with Growth in Young Children of Vellore, India

To estimate the effects of antibiotic exposures in the first 6 months of life on short- and long-term growth

Acute encephalitis syndrome surveillance, Kushinagar district, Uttar Pradesh, India, 2011-2012

In India, quality surveillance for acute encephalitis syndrome (AES), including laboratory testing, is necessary for understanding the epidemiology and etiology of AES, planning interventions, and developing policy. We reviewed AES surveillance data for January 2011-June 2012 from Kushinagar District, Uttar Pradesh, India. Data were cleaned, incidence was determined, and demographic characteristics of cases and data quality were analyzed. A total of 812 AES case records were identified, of which 23\% had illogical entries. AES incidence was highest among boys<6 years of age, and cases peaked during monsoon season. Records for laboratory results (available for Japanese encephalitis but not AES) and vaccination history were largely incomplete, so inferences about the epidemiology and etiology of AES could not be made. The low-quality AES/Japanese encephalitis surveillance data in this area provide little evidence to support development of prevention and control measures, estimate the effect of interventions, and avoid the waste of public health resources

Determinants and impact of giardia infection in the first 2 years of life in the MAL-ED birth cohort

Background: Giardia are among the most common enteropathogens detected in children in low-resource settings. We describe here the epidemiology of infection with Giardia in the first 2 years of life in the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development Project (MAL-ED), a multisite birth-cohort study.Methods: From 2089 children, 34916 stool samples collected during monthly surveillance and episodes of diarrhea were tested for Giardia using an enzyme immunoassay. We quantified the risk of Giardia detection, identified risk factors, and assessed the associations with micronutrients, markers of gut inflammation and permeability, diarrhea, and growth using multivariable linear regression.Results: The incidence of at least 1 Giardia detection varied according to site (range, 37.7%-96.4%) and was higher in the second year of life. Exclusive breastfeeding (HR for first Giardia detection in a monthly surveillance stool sample, 0.46 [95% confidence interval (CI), 0.28-0.75]), higher socioeconomic status (HR, 0.74 [95% CI, 0.56-0.97]), and recent metronidazole treatment (risk ratio for any surveillance stool detection, 0.69 [95% CI, 0.56-0.84]) were protective. Persistence of Giardia (consecutive detections) in the first 6 months of life was associated with reduced subsequent diarrheal rates in Naushahro Feroze, Pakistan but not at any other site. Giardia detection was also associated with an increased lactulose/mannitol ratio. Persistence of Giardia before 6 months of age was associated with a -0.29 (95% CI, -0.53 to -0.05) deficit in weight-for-age z score and -0.29 (95% CI, -0.64 to 0.07) deficit in length-for-age z score at 2 years.Conclusion: Infection with Giardia occurred across epidemiological contexts, and repeated detections in 40% of the children suggest that persistent infections were common. Early persistent infection with Giardia, independent of diarrhea, might contribute to intestina

Use of quantitative molecular diagnostic methods to assess the aetiology, burden, and clinical characteristics of diarrhoea in children in low-resource settings: A reanalysis of the MAL-ED cohort study

Background: Optimum management of childhood diarrhoea in low-resource settings has been hampered by insufficient data on aetiology, burden, and associated clinical characteristics. We used quantitative diagnostic methods to reassess and refine estimates of diarrhoea aetiology from the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) cohort study.Methods: We re-analysed stool specimens from the multisite MAL-ED cohort study of children aged 0–2 years done at eight locations (Dhaka, Bangladesh; Vellore, India; Bhaktapur, Nepal; Naushero Feroze, Pakistan; Venda, South Africa; Haydom, Tanzania; Fortaleza, Brazil; and Loreto, Peru), which included active surveillance for diarrhoea and routine non-diarrhoeal stool collection. We used quantitative PCR to test for 29 enteropathogens, calculated population-level pathogen-specific attributable burdens, derived stringent quantitative cutoffs to identify aetiology for individual episodes, and created aetiology prediction scores using clinical characteristics.Findings: We analysed 6625 diarrhoeal and 30 968 non-diarrhoeal surveillance stools from 1715 children. Overall, 64·9% of diarrhoea episodes (95% CI 62·6–71·2) could be attributed to an aetiology by quantitative PCR compared with 32·8% (30·8–38·7) using the original study microbiology. Viral diarrhoea (36·4% of overall incidence, 95% CI 33·6–39·5) was more common than bacterial (25·0%, 23·4–28·4) and parasitic diarrhoea (3·5%, 3·0–5·2). Ten pathogens accounted for 95·7% of attributable diarrhoea: Shigella (26·1 attributable episodes per 100 child-years, 95% CI 23·8–29·9), sapovirus (22·8, 18·9–27·5), rotavirus (20·7, 18·8–23·0), adenovirus 40/41 (19·0, 16·8–23·0), enterotoxigenic Escherichia coli (18·8, 16·5–23·8), norovirus (15·4, 13·5–20·1), astrovirus (15·0, 12·0–19·5), Campylobacter jejuni or C coli (12·1, 8·5–17·2), Cryptosporidium (5·8, 4·3–8·3), and typical enteropathogenic E coli (5·4, 2·8–9·3). 86·2% of the attributable incidence for Shigella was non-dysenteric. A prediction score for shigellosis was more accurate (sensitivity 50·4% [95% CI 46·7–54·1], specificity 84·0% [83·0–84·9]) than current guidelines, which recommend treatment only of bloody diarrhoea to cover Shigella (sensitivity 14·5% [95% CI 12·1–17·3], specificity 96·5% [96·0–97·0]).Interpretation: Quantitative molecular diagnostics improved estimates of pathogen-specific burdens of childhood diarrhoea in the community setting. Viral causes predominated, including a substantial burden of sapovirus; however, Shigella had the highest overall burden with a high incidence in the second year of life. These data could improve the management of diarrhoea in these low-resource settings

Costs analysis of a population level rabies control programme in Tamil Nadu, India

The study aimed to determine costs to the state government of implementing different interventions for controlling rabies among the entire human and animal populations of Tamil Nadu. This built upon an earlier assessment of Tamil Nadu’s efforts to control rabies. Anti-rabies vaccines were made available at all health facilities. Costs were estimated for five different combinations of animal and human interventions using an activity-based costing approach from the provider perspective. Disease and population data were sourced from the state surveillance data, human census and livestock census. Program costs were extrapolated from official documents. All capital costs were depreciated to estimate annualized costs. All costs were inflated to 2012 Rupees. Sensitivity analysis was conducted across all major cost centres to assess their relative impact on program costs. It was found that the annual costs of providing Anti-rabies vaccine alone and in combination with Immunoglobulins was \$0.7 million (Rs 36 million) and \$2.2 million (Rs 119 million), respectively. For animal sector interventions, the annualised costs of rolling out surgical sterilisation-immunization, injectable immunization and oral immunizations were estimated to be \$ 44 million (Rs 2,350 million), \$23 million (Rs 1,230 million) and \$ 11 million (Rs 590 million), respectively. Dog bite incidence, health systems coverage and cost of rabies biologicals were found to be important drivers of costs for human interventions. For the animal sector interventions, the size of dog catching team, dog population and vaccine costs were found to be driving the costs. Rabies control in Tamil Nadu seems a costly proposition the way it is currently structured. Policy makers in Tamil Nadu and other similar settings should consider the long-term financial sustainability before embarking upon a state or nation-wide rabies control programme

Relationships among common illness symptoms and the protective effect of breastfeeding in early childhood in MAL-ED: An eight-country cohort study

Children in low-income countries experience multiple illness symptoms in early childhood. Breastfeeding is protective against diarrhea and respiratory infections, and these illnesses are thought to be risk factors of one another, but these relationships have not been explored simultaneously. In the eight-site MAL-ED study, 1,731 infants were enrolled near birth and followed for 2 years. We collected symptoms and diet information through twice-weekly household visits. Poisson regression was used to determine if recent illness history was associated with incidence of diarrhea or acute lower respiratory infections (ALRI), accounting for exclusive breastfeeding. Recent diarrhea was associated with higher risk of incident diarrhea after the first 6 months of life (relative risk [RR] 1.10, 95% confidence interval [CI] 1.04, 1.16) and with higher risk of incident ALRI in the 3- to 5-month period (RR 1.23, 95% CI 1.03, 1.47). Fever was a consistent risk factor for both diarrhea and ALRI. Exclusive breastfeeding 0-6 months was protective against diarrhea (0-2 months: RR 0.39, 95% CI 0.32, 0.49; 3-5 months: RR 0.83, 95% CI 0.75, 0.93) and ALRI (3-5 months: RR 0.81, 95% CI 0.68, 0.98). Children with recent illness who were exclusively breastfed were half as likely as those not exclusively breastfed to experience diarrhea in the first 3 months of life. Recent illness was associated with greater risk of new illness, causing illnesses to cluster within children, indicating that specific illness-prevention programs may have benefits for preventing other childhood illnesses. The results also underscore the importance of exclusive breastfeeding in the first 6 months of life for disease prevention

Reduction in diarrhoeal rates through interventions that prevent unnecessary antibiotic exposure early in life in an observational birth cohort

Antibiotic treatment early in life is often not needed and has been associated with increased rates of subsequent diarrhea. We estimated the impact of realistic interventions, which would prevent unnecessary antibiotic exposures before 6 months of age, on reducing childhood diarrheal rates

Use of antibiotics in children younger than two years in eight countries: A prospective cohort study

Objective: To describe the frequency and factors associated with antibiotic use in early childhood, and estimate the proportion of diarrhoea and respiratory illnesses episodes treated with antibiotics.Methods: Between 2009 and 2014, we followed 2134 children from eight sites in Bangladesh, Brazil, India, Nepal, Pakistan, Peru, South Africa and the United Republic of Tanzania, enrolled in the MAL-ED birth cohort study. We documented all antibiotic use from mothers’ reports at twice-weekly visits over the children’s first two years of life. We estimated the incidence of antibiotic use and the associations of antibiotic use with child and household characteristics. We described treatment patterns for diarrhoea and respiratory illnesses, and identified factors associated with treatment and antibiotic class.Findings: Over 1 346 388 total days of observation, 16 913 courses of antibiotics were recorded (an incidence of 4.9 courses per child per year), with the highest use in South Asia. Antibiotic treatment was given for 375/499 (75.2%) episodes of bloody diarrhoea and for 4274/9661 (44.2%) episodes of diarrhoea without bloody stools. Antibiotics were used in 2384/3943 (60.5%) episodes of fieldworker-confirmed acute lower respiratory tract illness as well as in 6608/16742 (39.5%) episodes of upper respiratory illness. Penicillins were used most frequently for respiratory illness, while antibiotic classes for diarrhoea treatment varied within and between sites.Conclusion: Repeated antibiotic exposure was common early in life, and treatment of non-bloody diarrhoea and non-specific respiratory illnesses was not consistent with international recommendations. Rational antibiotic use programmes may have the most impact in South Asia, where antibiotic use was highest