Early childhood enteric infection with Shigella/EIEC, enteroaggregative E. coli (EAEC), Campylobacter, and Giardia has been associated with reduced child growth, yet a recent randomized trial of ...antimicrobial therapy to reduce these infections did not improve growth outcomes. To interrogate this discrepancy, we measured the enteric infections from this study. We leveraged the Early Life Interventions for Childhood Growth and Development in Tanzania (ELICIT) trial, a randomized double-blind placebo-controlled trial of antimicrobial therapy with azithromycin and nitazoxanide provided quarterly to infants from 6 to 15 months of age. We tested 5,479 stool samples at time points across the study for 34 enteropathogens using quantitative PCR. There was substantial carriage of enteropathogens in stool. Azithromycin administration led to reductions in Campylobacter jejuni/coli, enteroaggregative E. coli, and Shigella/EIEC (absolute risk difference ranged from -0.06 to 0.24) 2 weeks after treatment however there was no effect after 3 months. There was no difference in Giardia after nitazoxanide administration (ARR 0.03 at the 12 month administration). When examining the effect of azithromycin versus placebo on the subset of children infected with specific pathogens at the time of treatment, a small increase in weight-for-age Z score was seen only in those infected with Campylobacter jejuni/coli (0.10 Z score, 95% CI -0.01-0.20; length-for-age Z score 0.07, 95% CI -0.06-0.20). The antimicrobial intervention of quarterly azithromycin plus or minus nitazoxanide led to only transient decreases in enteric infections with Shigella/EIEC, enteroaggregative E. coli (EAEC), Campylobacter, and Giardia. There was a trend towards improved growth in children infected with Campylobacter that received quarterly azithromycin.
We identified the determinants of positive (children who had a birth weight < 2.5 kg and/or maternal height < 145 cm but were nonstunted at 24 months of age) and negative (children who had a birth ...weight ≥ 2.5 kg and maternal height ≥ 145 cm but were stunted at 24 months of age) deviance in childhood linear growth. We found that socioeconomic status (β = 1.54, P < 0.01), serum retinol (β = 0.05, P < 0.01), hemoglobin (β = 0.36, P < 0.01), length-for-age Z-score (LAZ) at birth (β = 0.47, P < 0.01), and tetanus vaccine titer (β = 0.182, P < 0.05) were positively and maternal depressive symptom (β = -0.05, P < 0.01), serum ferritin (β = -0.03, P < 0.01), male sex (β = -1.08, P < 0.01), and α1-antitrypsin (β = -0.81, P < 0.01) were negatively associated with positive deviance. Further, diarrhea episodes (β = 0.02, P < 0.01), male sex (β = 0.72, P < 0.01), and α1-antitrypsin (β = 0.67, P < 0.01) were positively and hemoglobin (β= -0.28, P < 0.01), soluble transferrin receptor level (β = -0.15, P < 0.01), and LAZ score at birth (β = -0.90, P < 0.01) were negatively associated with negative deviance. To summarize, enteric protein loss, micronutrient deficiency, vaccine responses and maternal depressive symptoms were associated with linear growth deviance in early childhood. In such a background, public health approaches aimed at reducing the risk of intestinal inflammation and altered gut permeability could prove fruitful in ensuring desired linear growth in children. In addition, maternal mental health issue should also be considered, especially for promoting better nutritional status in children in the context of linear growth deviance.
In this longitudinal multicenter study, 65% of children experienced Cryptosporidium infection during the first 2 years of life. Cryptosporidium was associated with severe diarrhea and dehydration ...and, in 2 South Asian sites, with stunted growth at age 2 years.
Abstract
Background
Cryptosporidium species are enteric protozoa that cause significant morbidity and mortality in children worldwide. We characterized the epidemiology of Cryptosporidium in children from 8 resource-limited sites in Africa, Asia, and South America.
Methods
Children were enrolled within 17 days of birth and followed twice weekly for 24 months. Diarrheal and monthly surveillance stool samples were tested for Cryptosporidium by enzyme-linked immunosorbent assay. Socioeconomic data were collected by survey, and anthropometry was measured monthly.
Results
Sixty-five percent (962/1486) of children had a Cryptosporidium infection and 54% (802/1486) had at least 1 Cryptosporidium-associated diarrheal episode. Cryptosporidium diarrhea was more likely to be associated with dehydration (16.5% vs 8.3%, P < .01). Rates of Cryptosporidium diarrhea were highest in the Peru (10.9%) and Pakistan (9.2%) sites. In multivariable regression analysis, overcrowding at home was a significant risk factor for infection in the Bangladesh site (odds ratio, 2.3 95% confidence interval {CI}, 1.2-4.6). Multiple linear regression demonstrated a decreased length-for-age z score at 24 months in Cryptosporidium-positive children in the India (β = -.26 95% CI, -.51 to -.01) and Bangladesh (β = -.20 95% CI, -.44 to .05) sites.
Conclusions
This multicountry cohort study confirmed the association of Cryptosporidium infection with stunting in 2 South Asian sites, highlighting the significance of cryptosporidiosis as a risk factor for poor growth. We observed that the rate, age of onset, and number of repeat infections varied per site; future interventions should be targeted per region to maximize success.
Aim
We explored the diagnostic accuracy of the clinical dehydration scale (CDS), the World Health Organization (WHO) scale and the Gorelick scale for assessing dehydration in children admitted to a ...Tanzanian referral hospital.
Methods
This was a prospective, observational study, carried out from April 2015 to January 2017 on children aged one month to five years admitted to the hospital with acute diarrhoea lasting less than five days. Before rehydration therapy, each patient's weight was recorded and the degree of dehydration was assessed based on the three scales. The reference standard was the percentage weight change between admission and discharge. The main outcomes were the sensitivity, specificity and positive and negative likelihood ratios (LRs) of the scales.
Results
Data from 124 eligible patients were available. The CDS showed limited value for ruling in cases with some dehydration (LR 1.9, 95% confidence interval 1.1–2.8), but was of no value in assessing no and moderate to severe dehydration. The WHO and Gorelick scales were of no value in evaluating any degree of dehydration.
Conclusion
The WHO and Gorelick dehydration scales were no use for assessing dehydration in small children, and the CDS was of limited use for predicting cases with some dehydration.
Extreme floods pose multiple direct and indirect health risks. These risks include contamination of water, food, and the environment, often causing outbreaks of diarrheal disease. Evidence regarding ...the effects of flooding on individual diarrhea-causing pathogens is limited, but is urgently needed in order to plan and implement interventions and prioritize resources before climate-related disasters strike. This study applied a causal inference approach to data from a multisite study that deployed broadly inclusive diagnostics for numerous high-burden common enteropathogens. Relative risks (RRs) of infection with each pathogen during a flooding disaster that occurred at one of the sites-Loreto, Peru-were calculated from generalized linear models using a comparative interrupted time series framework with the other sites as a comparison group and adjusting for background seasonality. During the early period of the flood, increased risk of heat-stable enterotoxigenic
(ST-ETEC) was identified (RR = 1.73 1.10, 2.71) along with a decreased risk of enteric adenovirus (RR = 0.36 0.23, 0.58). During the later period of the flood, sharp increases in the risk of rotavirus (RR = 5.30 2.70, 10.40) and sapovirus (RR = 2.47 1.79, 3.41) were observed, in addition to increases in transmission of
spp. (RR = 2.86 1.81, 4.52) and
spp. (RR = 1.41 (1.01, 1.07). Genotype-specific exploratory analysis reveals that the rise in rotavirus transmission during the flood was likely due to the introduction of a locally atypical, non-vaccine (G2P4) strain of the virus. Policy-makers should target interventions towards these pathogens-including vaccines as they become available-in settings where vulnerability to flooding is high as part of disaster preparedness strategies, while investments in radical, transformative, community-wide, and locally-tailored water and sanitation interventions are also needed.
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.
Newborn mortality is a global challenge with around 2.4 million neonatal deaths in 2019. One third of these occur within the first-and-only day of life with labour complications and birth asphyxia ...being the primary causes. Existing guidelines for newborn resuscitation are based on limited scientific evidence, and evidens based research is sought for. To increase our knowledge on resuscitation of newborns, it is crucial to first quantify what is currently being done in terms of therapeutic activities, such as ventilation and stimulation, and how they affect resuscitation outcomes. In the current study, the therapeutic activities during newborn resuscitation are quantified by estimating a timeline describing the start and stop of activities. The proposed approach is combining methods using both video and time series data recorded during resuscitation, where the predictions are based on the available sources. From video the activity recognition is done by a 3D CNN method. For the signal data feature extraction is performed on ECG and accelerometer signals and thereafter machine learning is done to perform stimulation detection. We show that best results are achieved with all signals and video available, for the activity “stimulation” we get an AUC of 0.86, sensitivity of 82.32%, specificity of 82.23%, and precision of 57.59%. If only signals or video is available we still get good results with AUC at 0.80, and 0.84 respectively.
•Improved method for estimating when stimulation occurs during newborn resuscitation.•Combining signal- and video-based methods to improve performance.•An important step in understanding the newborn resuscitation process.
Etiologic studies of diarrhea are limited by uneven diagnostic methods and frequent asymptomatic detection of enteropathogens. Polymerase chain reaction-based stool pathogen quantification may help ...distinguish clinically significant infections. We performed a nested case-control study of diarrhea in infants from a community-based birth cohort in Tanzania. We tested 71 diarrheal samples and pre-diarrheal matched controls with a laboratory-developed TaqMan Array Card for 19 enteropathogens. With qualitative detection, no pathogens were significantly associated with diarrhea. When pathogen quantity was considered, rotavirus (odds ratio OR = 2.70 per log10 increase, P < 0.001), astrovirus (OR = 1.49, P = 0.01), and Shigella/enteroinvasive Escherichia coli (OR = 1.47, P = 0.04) were associated with diarrhea. Enterotoxigenic E. coli (0.15 SD decline in length-for-age z score after 3 months per log10 increase, P < 0.001) and Campylobacter jejuni/C. coli (0.11 SD decline, P = 0.003) in pre-diarrheal stools were associated with poor linear growth. Quantitative analysis can help refine the association between enteropathogens and disease in endemic settings.
Antibiotic-resistant bacterial infections are a major public health problem, and children in low-resource settings represent a particularly high-risk group. Few data are available on the dynamics of ...and risk factors for gastrointestinal carriage of antibiotic-resistant bacteria in these vulnerable populations. In this study, we described the antibiotic susceptibility profiles of
isolated from stool specimens collected from children aged 6 to 60 months enrolled in a birth cohort study in Haydom, Tanzania. We estimated the association between sociodemographic risk factors, child illnesses, and antibiotic exposure and
drug resistance. Carriage of antibiotic-resistant
was common starting early in life and did not clearly increase with age. The majority of isolates were resistant to ampicillin (749/837; 89.5%), cefazolin (742/837; 88.6%), and cotrimoxazole (721/837; 86.1%). Resistance to amoxicillin/clavulanate (361/836; 43.2%), ampicillin/sulbactam (178/819; 21.7%), nalidixic acid (131/831; 15.8%), and azithromycin (115/837; 13.7%) was also seen. Only 1.8% (15/837) of the pooled
isolates met the criteria for extended-spectrum beta-lactamase production. High antibiotic use (0.26 additional resistant antibiotic classes; 95% CI: 0.05, 0.47) and high income (0.28 additional resistant antibiotic classes; 95% CI: 0.06, 0.50) were associated with the carriage of antibiotic-resistant
, whereas hospital birth, crowding in the home, improved drinking water and sanitation, and common childhood illnesses were not. In this setting, the carriage of antibiotic-resistant
was common. Other than recent antibiotic exposure and high income, individual risk factors for the acquisition and carriage of resistance could not be identified, suggesting that population-level interventions are needed.
Background: Growth trajectories are highly variable between children, making epidemiological analyses challenging both to the identification of malnutrition interventions at the population level and ...also risk assessment at individual level. We introduce stochastic differential equation (SDE) models into child growth research. SDEs describe flexible dynamic processes comprising: drift - gradual smooth changes – such as physiology or gut microbiome, and diffusion - sudden perturbations, such as illness or infection. Methods: We present a case study applying SDE models to child growth trajectory data from the Haydom, Tanzania and Venda, South Africa sites within the MAL-ED cohort. These data comprise n=460 children aged 0-24 months. A comparison with classical curve fitting (linear mixed models) is also presented. Results: The SDE models offered a wide range of new flexible shapes and parameterizations compared to classical additive models, with performance as good or better than standard approaches. The predictions from the SDE models suggest distinct longitudinal clusters that form distinct ‘streams’ hidden by the large between-child variability. Conclusions: Using SDE models to predict future growth trajectories revealed new insights in the observed data, where trajectories appear to cluster together in bands, which may have a future risk assessment application. SDEs offer an attractive approach for child growth modelling and potentially offer new insights.
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