Poor growth in early childhood has been associated with increased risk of mortality and morbidity, as well as long-term deficits in cognitive development and economic productivity.
Data from the ...MAL-ED cohort study were used to identify factors in the first 2 y of life that are associated with height-for-age, weight-for-age, and body mass index z-scores (HAZ, WAZ, BMIZ) at 5 y of age.
A total of 1017 children were followed from near birth until 5 y of age at sites in Bangladesh, Brazil, India, Nepal, Peru, South Africa, and Tanzania. Data were collected on their growth, environmental enteric dysfunction (EED), micronutrient status, enteric pathogen burden, illness prevalence, dietary intake, and various other socio-economic and environmental factors.
EED biomarkers were related to size at 5 y. Mean lactulose:mannitol z-scores during the first 2 y of life were negatively associated with all of the growth measures (HAZ: −0.11 95% CI: −0.19, −0.03; WAZ: −0.16 95% CI: −0.26, −0.06; BMIZ: −0.11 95% CI: −0.23, 0.0). Myeloperoxidase was negatively associated with weight (WAZ: −0.52 95% CI: −0.78, −0.26 and BMIZ: −0.56 95% CI: −0.86, −0.26); whereas α-1-antitrypsin had a negative association with HAZ (−0.28 95% CI: −0.52, −0.04). Transferrin receptor was positively related to HAZ (0.18 95% CI: 0.06, 0.30) and WAZ (0.21 95% CI: 0.07, 0.35). Hemoglobin was positively related to HAZ (0.06 95% CI: 0.00, 0.12), and ferritin was negatively related to HAZ (−0.08 95% CI: −0.12, −0.04). Bacterial density in stool was negatively associated with HAZ (−0.04 95% CI: −0.08, 0.00), but illness symptoms did not have any effect on size at 5 y.
EED markers, bacterial density, and iron markers are associated with growth at 5 y of age. Interventions to reduce bacterial burden and EED may improve long-term growth in low-income settings.
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.
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.
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.
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.
Diarrhea is a common cause of morbidity and mortality among children younger than 5 years in developing countries. Children from 3 to 60 months of age were recruited from two hospitals in Nepal- ...Bharatpur Hospital, Bharatpur, and Kanti Children's Hospital, Kathmandu-in 2006 to 2009. Stool specimens collected from 1,200 children with acute diarrhea (cases) and 1,200 children without diarrhea (control subjects) were examined for a broad range of enteropathogens by standard microbiology, including microscopy, enzyme immunoassay for viral pathogens (adenovirus, astrovirus, and rotavirus) and protozoa (Giardia, Cryptosporidium, and Entamoeba histolytica), as well as by using reverse transcription real-time polymerase for norovirus. Antimicrobial susceptibility testing was performed using the disk diffusion method. Overall, rotavirus (22% versus 2%), norovirus (13% versus 7%), adenovirus (3% versus 0%), Shigella (6% versus 1%), enterotoxigenic Escherichia coli (8% versus 4%), Vibrio (7% versus 0%), and Aeromonas (9% versus 3%) were identified significantly more frequently in cases than control subjects. Campylobacter, Plesiomonas, Salmonella, and diarrheagenic E. coli (enteropathogenic, enteroinvasive, enteroaggregative) were identified in similar proportions in diarrheal and non-diarrheal stools. Campylobacter was resistant to second-generation quinolone drugs (ciprofloxacin and norfloxacin), whereas Vibrio and Shigella were resistant to nalidixic acid and trimethoprim/sulfamethoxazole. This study documents the important role of rotavirus and norovirus in acute diarrhea in children younger than 5 years, followed by the bacteria Shigella, enterotoxigenic E. coli, Vibrio cholera, and Aeromonas. Data on the prevalence and epidemiology of enteropathogens identify potential pathogens for public health interventions, whereas pathogen antibiotic resistance pattern data may provide guidance on choice of therapy in clinical settings.
Abstract Eight serotypes of human astroviruses (the classic human astroviruses) are causative agents of diarrhea. Recently, five additional astroviruses belonging to two distinct clades have been ...described in human stool, including astroviruses MLB1, MLB2, VA1, VA2 and VA3. We report the discovery in human stool of two novel astroviruses, astroviruses MLB3 and VA4. The complete genomes of these two viruses and the previously described astroviruses VA2 and VA3 were sequenced, affording seven complete genomes from the MLB and VA clades for comparative analysis to the classic human astroviruses. Comparison of the genetic distance, number of synonymous mutations per synonymous site (dS), number of non-synonymous mutations per non-synonymous site (dN) and the dN/dS ratio in the protease, polymerase and capsid of the classic human, MLB and VA clades suggests that the protease and polymerase of the classic human astroviruses are under distinct selective pressure.
Objective:
The objectives of this study were to describe the incidence and genetic diversity of Rotavirus (RV) infection among children up to 3 years of age in a community in Nepal.
Methods:
We ...investigated community-acquired cases of asymptomatic and symptomatic RV infections in children from birth to 36 months of age in a community-based birth cohort in Bhaktapur, Nepal. Monthly surveillance and diarrheal stool samples were collected from 240 children enrolled at birth, of which 238 completed the 3 years of follow-up. Samples were screened for rotavirus by Enzyme Immuno Assay (EIA). All RV screened positives were further genotyped by reverse transcription-polymerase chain reaction for the capsid genes VP7 and VP4.
Results:
In total, 5,224 stool samples were collected from 238 children, followed from birth to 36 months of age. Diarrhea occurred in 92.4% (230/238) of all children in the cohort. During the 3 years study period, RV was more frequently seen in children with symptoms (7.6%) than in non-symptomatic children (0.8%). The highest RV detection rate was found in younger children between 3 and 21 months of age. Although rotavirus is known as winter diarrhea, it was detected throughout the year except in August. The highest positivity rate was observed in the months between December and March, with a peak in January. Four common G types were seen: G2 (30%), G1 (29%), G12 (19%), and G9 (16%). The most predominant genotypes seen were G2P4 (30%), followed by G1P8 (27.0%), G12P6 (14.0%), G9P8 (10%), and remaining were mixed, partial, and untyped.
Conclusion:
Our study confirms that rotavirus is a common cause of gastroenteritis in young children in the community. The prevalence and pathogenicity of rotavirus infection differed by age. There was substantial variability in circulating strains in the community samples compared to samples collected from hospitals. This shows the importance of including community-based surveillance systems to monitor the diversity of circulating rotavirus strains in Nepal.
Objective To estimate the abilities of weight and length velocities vs attained growth measures to predict stunting, wasting, and underweight at age 2 years. Study design We analyzed data from a ...community-based cohort study (The Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development study MAL-ED study) in Bhaktapur, Nepal. A total of 240 randomly selected children were enrolled at birth and followed up monthly up to age 24 months. Linear and logistic regression models were used to predict malnutrition at 2 years of age with growth velocity z scores at 0-3, 0-6, 3-6, 6-9, 6-12, and 9-12 months (using the World Health Organization Growth Standards) or attained growth at 0, 3, 6, and 12 months as predictors. Results At age 2 years, 4% of the children were wasted, 13% underweight, and 21% stunted. Children who were malnourished at age 2 years had lower mean growth z scores already at birth and throughout the study period. Anthropometric indicators in infancy were significant predictors for growth at the age of 2 years during most periods and at most ages in infancy. Weight-for-age z score, length-for-age z score, and weight-for-length z score at age 12 months had excellent areas under the curve (91-95) to predict the value of the same indicator at age 24 months. Maximum area under the curve values for weight and length velocity were somewhat lower (70-84). Conclusions Growth measured at one time point in infancy was better correlated with undernutrition at age 2 years than growth velocity.
To measure the role of water, sanitation and hygiene (WASH) practices on recovery from stunting and assess the role of timing of stunting on the reversal of this phenomenon.
Data from the MAL-ED ...multi-country birth cohort study was used for the current analysis. Generalised linear mixed-effects models were used to estimate the probability of reversal of stunting with WASH practice and timing of stunting as the exposures of interest.
Seven different countries across three continents.
A total of 612 children <2 years of age.
We found that not WASH practice but timing of stunting had statistically significant association with recovery from stunting. In comparison with the children who were stunted at 6 months, children who were stunted at 12 months had 1·9 times (β = 0·63, P = 0·03) more chance of recovery at 24 months of age. And, children who were stunted at 18 months of age even had higher odds (adjusted OR = 3·01, β = 1·10, P < 0·001) of recovery than children who were stunted at 6 months. Additionally, mother's height (β = 0·59, P = 0·04) and household income (β = 0·02, P < 0·05) showed statistically significant associations with the outcome.
The study provided evidence for the role of timing of stunting on the recovery from the phenomenon. This novel finding indicates that the programmes to promote linear growth should be directed at the earliest possible timepoints in the course of life.
Globally, rotavirus A (RV) is a leading cause of acute gastroenteritis (AGE) in young children under 5 years. The main aim of this study was to describe the prevalence of RV in children with and ...without diarrhea whose age ranged from 3 months to 5 years from two different hospitals of Nepal. We also described the diversity of rotavirus circulating during the pre-vaccination period in Nepal between 2006–2009.
A total of 2400 stool samples collected from children's years with diarrhea (cases, N = 1200) and without diarrhea (controls, N = 1200) were tested for the presence of RV by both enzyme-linked immunosorbent assay and real-time reverse transcription polymerase chain reaction (RT-PCR). All samples positive for RT PCR and/or ELISA were further characterized for G and P genotypes by conventional RT-PCR.
In total, 500 of the 2398 (20.8 %) samples (424 cases and 76 controls), were positive for RV. The most frequently detected G-types were G12, G1, and G9 and P-types were P8 and P6. The predominant genotypes G12P6, G12P8, G1P8 and G9P8 were identified in 27.8 %, 24.2 %, 11.8 % and 10.8 % of the samples, respectively.
This study observed high prevalence of G12P6 rotavirus circulating in Nepal before vaccine introduction and they may pose an emerging challenge to current and future vaccine. Therefore, continuous molecular surveillance of circulating genotypes and emerging rotavirus strain should be carried out to better understand the effectiveness of vaccination program.
Growth and development shortfalls that are disproportionately prevalent in children living in poor environmental conditions are postulated to result, at least in part, from abnormal gut function. ...Using data from The Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) longitudinal cohort study, we examine biomarkers of gut inflammation and permeability in relation to environmental exposures and feeding practices. Trends in the concentrations of three biomarkers, myeloperoxidase (MPO), neopterin (NEO), and α-1-antitrypsin (AAT), are described from fecal samples collected during the first 2 years of each child's life. A total of 22,846 stool samples were processed during the longitudinal sampling of 2,076 children 0-24 months of age. Linear mixed models were constructed to examine the relationship between biomarker concentrations and recent food intake, symptoms of illness, concurrent enteropathogen infection, and socioeconomic status. Average concentrations of MPO, NEO, and AAT were considerably higher than published references for healthy adults. The concentration of each biomarker tended to decrease over the first 2 years of life and was highly variable between samples from each individual child. Both MPO and AAT were significantly elevated by recent breast milk intake. All three biomarkers were associated with pathogen presence, although the strength and direction varied by pathogen. The interpretation of biomarker concentrations is subject to the context of their collection. Herein, we identify that common factors (age, breast milk, and enteric infection) influence the concentration of these biomarkers. Within the context of low- and middle-income communities, we observe concentrations that indicate gut abnormalities, but more appropriate reference standards are needed.
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