A Predictive Model for Thiamine Responsive Disorders Among Infants and Young Children: Results from a Prospective Cohort Study in Lao People's Democratic Republic.

OBJECTIVE: To develop a predictive model for thiamine responsive disorders (TRDs) among infants and young children hospitalized with signs or symptoms suggestive of thiamine deficiency disorders (TDDs) based on response to therapeutic thiamine in a high-risk setting. STUDY DESIGN: Children aged 21 days to <18 months hospitalized with signs or symptoms suggestive of TDD in northern Lao People's Democratic Republic were treated with parenteral thiamine (100 mg daily) for ≥3 days in addition to routine care. Physical examinations and recovery assessments were conducted frequently for 72 hours after thiamine was initiated. Individual case reports were independently reviewed by three pediatricians who assigned a TRD status (TRD or non-TRD), which served as the dependent variable in logistic regression models to identify predictors of TRD. Model performance was quantified by empirical area under the receiver operating characteristic curve. RESULTS: A total of 449 children (median [Q1, Q3] 2.9 [1.7, 5.7] months old; 70.3% exclusively/predominantly breastfed) were enrolled; 60.8% had a TRD. Among 52 candidate variables, those most predictive of TRD were exclusive/predominant breastfeeding, hoarse voice/loss of voice, cyanosis, no eye contact, and no diarrhea in the previous 2 weeks. The area under the receiver operating characteristic curve (95% CI) was 0.82 (0.78, 0.86). CONCLUSIONS: In this study, the majority of children with signs or symptoms of TDD responded favorably to thiamine. While five specific features were predictive of TRD, the high prevalence of TRD suggests that thiamine should be administered to all infants and children presenting with any signs or symptoms consistent with TDD in similar high-risk settings. The usefulness of the predictive model in other contexts warrants further exploration and refinement. TRIAL REGISTRATION: Clinicaltrials.gov NCT03626337.

Community-based management of acute malnutrition for infants under 6 months of age is safe and effective: analysis of operational data.

OBJECTIVE: To assess the effectiveness of outpatient management with ready-to-use and supplementary foods for infants under 6 months (u6m) of age who were unable to be treated as inpatients due to social and economic barriers. DESIGN: Review of operational acute malnutrition treatment records. SETTING: Twenty-one outpatient therapeutic feeding clinics in rural Malawi. PARTICIPANTS: Infants u6m with acute malnutrition treated as outpatients because of barriers to inpatient treatment. The comparison group consisted of acutely malnourished children 6-9 months of age who were being treated at the same time in the same location in the context of two different randomised clinical trials. RESULTS: A total of 323 infants u6m were treated for acute malnutrition (130 severe and 193 moderate). A total of 357 infants 6-9 months old with acute malnutrition (seventy-four severe and 283 moderate) were included as contemporaneous controls. Among infants u6m with severe acute malnutrition, 98 (75·4 %) achieved nutritional recovery; in comparison, 56 (75·7 %) of those with severe acute malnutrition 6-9 months old recovered. Among infants u6m with moderate acute malnutrition, 157 (81·3 %) recovered; in comparison, 241 (85·2 %) of those aged 6-9 months recovered. CONCLUSIONS: In a rural Malawian population of infants u6m who had generally already stopped exclusive breast-feeding and were now acutely malnourished, treatment with therapeutic or supplementary foods under the community management of acute malnutrition model was safe and effective. In settings where social and financial factors make hospital admission challenging, consideration should be given to lowering the recommended age of ready-to-use therapeutic and supplementary foods to infants u6m.

How do children with severe underweight and wasting respond to treatment? A pooled secondary data analysis to inform future intervention studies.

Children with weight-for-age z-score (WAZ) <-3 have a high risk of death, yet this indicator is not widely used in nutrition treatment programming. This pooled secondary data analysis of children aged 6-59 months aimed to examine the prevalence, treatment outcomes, and growth trajectories of children with WAZ <-3 versus children with WAZ ≥-3 receiving outpatient treatment for wasting and/or nutritional oedema, to inform future protocols. Binary treatment outcomes between WAZ <-3 and WAZ ≥-3 admissions were compared using logistic regression. Recovery was defined as attaining mid-upper-arm circumference ≥12.5 cm and weight-for-height z-score ≥-2, without oedema, within a period of 17 weeks of admission. Data from 24,829 children from 9 countries drawn from 13 datasets were included. 55% of wasted children had WAZ <-3. Children admitted with WAZ <-3 compared to those with WAZ ≥-3 had lower recovery rates (28.3% vs. 48.7%), higher risk of death (1.8% vs. 0.7%), and higher risk of transfer to inpatient care (6.2% vs. 3.8%). Growth trajectories showed that children with WAZ <-3 had markedly lower anthropometry at the start and end of care, however, their patterns of anthropometric gains were very similar to those with WAZ ≥-3. If moderately wasted children with WAZ <-3 were treated in therapeutic programmes alongside severely wasted children, we estimate caseloads would increase by 32%. Our findings suggest that wasted children with WAZ <-3 are an especially vulnerable group and those with moderate wasting and WAZ <-3 likely require a higher intensity of nutritional support than is currently recommended. Longer or improved treatment may be necessary, and the timeline and definition of recovery likely need review.

Croup during the Coronavirus Disease 2019 Omicron Variant Surge.

We conducted a retrospective review of medical records of patients with croup seen during the coronavirus disease 2019 pandemic. Approximately 50% underwent testing for severe acute respiratory syndrome coronavirus 2. During the Delta wave, 2.8% of those tested were positive for severe acute respiratory syndrome coronavirus 2; this increased to 48.2% during the Omicron wave, demonstrating a strong correlation between the Omicron variant and croup.

Cotrimoxazole Prophylaxis Increases Resistance Gene Prevalence and α-Diversity but Decreases ß-Diversity in the Gut Microbiome of Human Immunodeficiency Virus-Exposed, Uninfected Infants.

BACKGROUND: Prophylactic cotrimoxazole treatment is recommended in human immunodeficiency virus (HIV)-exposed, uninfected (HEU) infants, but the effects of this treatment on developing HEU infant gut microbiotas and resistomes are largely undefined. METHODS: We analyzed whole-metagenome sequencing data from 163 longitudinally collected stool samples from 63 HEU infants randomized to receive (n = 34; CTX-T) or to not receive (n = 29; CTX-N) prophylactic cotrimoxazole treatment. We generated taxonomic, functional pathway, and resistance gene profiles for each sample and compared microbiome signatures between the CTX-T and CTX-N infants. RESULTS: Metagenomic analysis did not reveal significant differences in taxonomic or functional pathway α-diversity between CTX-T and CTX-N infants. In contrast, resistance gene prevalence (P = .00719) and α-diversity (P = .0045) increased in CTX-T infants. These differences increased over time for both resistance gene prevalence measured by log-normalized abundance (4-month mean, 0.71 [95% confidence interval {CI}, .2-1.2] and 6-month mean, 0.85 [95% CI, .1-1.7]) and α-diversity (P = .0045). Unlike α-diversity, interindividual gut microbiome taxonomic (mean, -0.11 [95% CI, -.15 to -.077]), functional taxonomic (mean, -0.050 [95% CI, -.084 to -.017]), and resistance gene (mean, -0.13 [95% CI, -.17 to -.099]) ß-diversity decreased in CTX-T infants compared with CTX-N infants. These results are consistent with persistent antibiotic selection pressure. CONCLUSIONS: Cotrimoxazole prophylaxis in HEU infants decreased gut microbiome ß-diversity and increased antibiotic resistance gene α-diversity and prevalence. Antibiotic resistance is a growing threat, especially in low- and middle-income countries where the higher perinatal HIV exposure rates result in cotrimoxazole prophylaxis. Understanding effects from current HEU infant antibiotic prophylaxis guidelines will inform guideline revisions and efforts to reduce increasing antibiotic resistance.

Supplementation With Lactoferrin and Lysozyme Ameliorates Environmental Enteric Dysfunction: A Double-Blind, Randomized, Placebo-Controlled Trial.

INTRODUCTION: Environmental enteric dysfunction (EED) predisposes children throughout the developing world to high rates of systemic exposure to enteric pathogens and stunting. Effective interventions that treat or prevent EED may help children achieve their full physical and cognitive potential. The objective of this study is to test whether 2 components of breast milk would improve a biomarker of EED and linear growth during the second year of life. METHODS: A prospective, randomized, double-blind, placebo-controlled clinical trial among children aged 12-23 months was conducted in rural Malawi. The experimental group received a daily supplement of 1.5 g of lactoferrin and 0.2 g of lysozyme for 16 weeks. The primary outcome was an improvement in EED, as measured by the change in the percentage of ingested lactulose excreted into the urine (Δ%L). RESULTS: Among 214 children who completed the study, there was a significant difference in Δ%L between the control and experimental groups over 8 weeks (an increase of 0.23% vs 0.14%, respectively; P = 0.04). However, this relative improvement was not as strongly sustained over the full 16 weeks of the study (an increase of 0.16% vs 0.11%, respectively; P = 0.17). No difference in linear growth over this short period was observed. The experimental intervention group had significantly lower rates of hospitalization and the development of acute malnutrition during the course of the study (2.5% vs 10.3%, relative risk 0.25; P < 0.02). DISCUSSION: Supplementation with lactoferrin and lysozyme in a population of agrarian children during the second year of life has a beneficial effect on gut health. This intervention also protected against hospitalization and the development of acute malnutrition, a finding with a significant clinical and public health importance. This finding should be pursued in larger studies with longer follow-up and optimized dosing.

Comparison of breath sampling methods: a post hoc analysis from observational cohort studies.

In this report, we present a post hoc analysis from two observational cohorts, comparing the global breath volatile profile captured when using polymer sampling bags (mixed breath) versus Bio-VOC™ (alveolar breath). The cohorts were originally designed to characterize the breath volatile profiles of Malawian children with and without uncomplicated falciparum malaria. Children aged 3-15 years were recruited from ambulatory pediatric centers in Lilongwe, Malawi. Breath sampling was carried out two months apart (one study using a Bio-VOC™ and the second using sampling bags), and all samples were analyzed by gas chromatography/mass spectrometry. The efficacy of breath collection was assessed by quantifying levels of two high prevalence breath compounds, acetone and isoprene, as well as determining the overall number of breath compounds collected and their abundance. We found that the mean number of volatiles detected using sampling bags was substantially higher than when using the Bio-VOC™ (137 vs. 47). Breath collection by Bio-VOC™ also yielded reduced levels of endogenous breath volatiles, isoprene and acetone, even after breath volume correction. This suggests that the Bio-VOC™ dilutes the volatiles and introduces dead air or ambient air. Our results suggest that sampling bags are better suited for biomarker discovery and untargeted search of volatiles in pediatric populations, as evidenced by superior breath volatile detection.

Development of Acute Malnutrition Despite Nutritional Supplementation in Malawi.

Malnutrition in children is most often attributed to inadequate nutrient intake. Utilizing data from 2 prospective, randomized controlled trials of complimentary feeding with supplemental legumes (n = 693, ages 6-24 months) in 2 Malawian villages, Masenjere, and Limera, we document a high rate 70/693 (10.1%) of acute malnutrition (AM). Risks for AM in this setting, as determined by Cox regression analysis, include study village (hazard ratio [HR] 3.0), prior malnutrition (HR 4.12), stunting (HR 2.87), and a marker of food insecurity (HR 1.89). Comparison of Masenjere to Limera demonstrate adequate and similar nutritional intake yet an increased rate of AM in Masenjere, 56 of 400 (14.0%) versus 14 of 293 (4.8%), and stunting, 140 of 400 (35%) versus 80 of 293 (27%), environmental enteric dysfunction 246 of 400 (71%) versus 181/293 (67%), and infectious symptoms (cough and diarrhea). Masenjere did have cleaner water and less food insecurity 200 of 399 (50.5%) versus 204 of 293 (69.6%). These findings suggest adequate complementary nutrient intake does not protect young children against AM.

Bystander Assistance for Trauma Victims in Low- and Middle-Income Countries: A Systematic Review of Prevalence and Training Interventions.

OBJECTIVE: Lack of organized prehospital care may contribute to the disproportionate burden of trauma-related deaths in low- and middle-income countries (LMICs). The World Health Organization (WHO) recommends bystander training in basic principles of first aid and victim transport; however, prevalence of bystander or layperson assistance to trauma victims in LMICs has not been well-described, and organized reviews of existing evidence for bystander training are lacking. This systematic review aims to 1) describe the prevalence of bystander or layperson aid or transport for trauma victims in the prehospital setting in LMICs and 2) ascertain impacts of bystander training interventions in these settings. METHODS: A systematic search of OVID Medline, Cochrane Library, and relevant gray literature was conducted. We included 1) all studies detailing prevalence of bystander-administered aid or transport for trauma victims in LMICs and 2) all randomized controlled trials and observational studies evaluating bystander training interventions. We extracted study characteristics, interventions, and outcomes data. Study quality was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. RESULTS: Sixty-two studies detailed prevalence of bystander transport and aid. Family members, police, and bus or taxi drivers commonly transported patients; a majority of patients, up to >94%, received aid from bystanders. Twenty-four studies examined impacts of training interventions. Only one study looked at transport interventions; the remainder addressed first aid training. Interventions varied in content, duration, and target learners. Evidence was generally of low quality, but all studies demonstrated improvements in layperson knowledge and skills. Five studies reported a mortality reduction. CONCLUSIONS: Heterogeneity in data reporting and outcomes limited formal meta-analysis. However, this review shows high rates of bystander involvement in prehospital trauma care and transport in LMICs and highlights the need for bystander training. Bystander training in these settings is feasible and may have an important impact on meaningful outcomes such as mortality. Categories of involved bystanders varied by region and training interventions should be targeted at relevant groups. "Train the trainer" models appear promising in securing community engagement and maximizing participation. Further research is needed to examine the value of bystander transport networks in trauma.

Down boy! A case of acute abdomen following a dog bite to the scrotum.

BACKGROUND: Dog bite injuries are an ongoing concern in pediatrics. The majority of these occur in low- and middle-income countries where resources, especially subspecialty support services, are limited. Scrotal bites are relatively rare, and even fewer cases of abdominal viscus involvement have been described. No case has previously been reported of a dog bite to the scrotum leading to abdominal viscus perforation. CASE PRESENTATION: A 2-year old boy presented with an acute abdomen as the result of a dog bite to his scrotum in the presence of an unrepaired inguinal hernia. Without revisiting a detailed trauma history and exam, this would have been missed, as the dog bite occurred several days prior to presentation and was nearly completely healed. The patient initially had an emergent laparotomy, small bowel resection, and hernia repair. He then suffered from a delayed anastomotic leak requiring repeat laparotomy with creation of an ileostomy. Following a prolonged post-operative course, the patient was discharged home with his ileostomy in place. He returned 3 months later to have his ileostomy reversed and was discharged after an uncomplicated operation in good condition. CONCLUSIONS: This case demonstrates the primacy of an accurate history and physical, specifically with regards to recent trauma, in the presentation of a pediatric patient with an acute abdomen. Acquiring this may involve multiple re-interviews with the family as new facts may come to light. This is especially important in resource limited areas where advanced imaging and laboratory services are not available.

Breathprinting Reveals Malaria-Associated Biomarkers and Mosquito Attractants.

Current evidence suggests that malarial infection could alter metabolites in the breath of patients, a phenomenon that could be exploited to create a breath-based diagnostic test. However, no study has explored this in a clinical setting. To investigate whether natural human malarial infection leads to a characteristic breath profile, we performed a field study in Malawi. Breath volatiles from children with and those without uncomplicated falciparum malaria were analyzed by thermal desorption-gas chromatography/mass spectrometry. Using an unbiased, correlation-based analysis, we found that children with malaria have a distinct shift in overall breath composition. Highly accurate classification of infection status was achieved with a suite of 6 compounds. In addition, we found that infection correlates with significantly higher breath levels of 2 mosquito-attractant terpenes, α-pinene and 3-carene. These findings attest to the viability of breath analysis for malaria diagnosis, identify candidate biomarkers, and identify plausible chemical mediators for increased mosquito attraction to patients infected with malaria parasites.

Children with Poor Linear Growth Are at Risk for Repeated Relapse to Wasting after Recovery from Moderate Acute Malnutrition.

Background: Nutrition programs frequently approach wasting and stunting as 2 separate conditions with distinct causes and effects. Although several cross-sectional studies have identified an association between the 2 conditions, longitudinal studies are useful to quantify the risk of acute malnutrition based on the trajectory of linear growth. Objective: We analyzed data from a longitudinal study to explore associations between linear growth and relapse to acute malnutrition in high-risk children during the year after recovery from moderate acute malnutrition (MAM). Methods: This was a secondary data analysis from a cluster randomized trial involving 1487 Malawian children 6-62 mo old treated for MAM and enrolled upon recovery. Children were followed for 1 y, during which data were collected on anthropometric progress, symptoms of illness, and household food security. Multivariate fixed-effects logistic regression was used to identify associations between linear growth and relapse to acute malnutrition. Results: Children who have recovered from MAM proved to be a high-risk population, with nearly half experiencing a decrease in height-for-age z score (HAZ) for 12 mo. Children whose HAZ was declining were more likely to relapse to MAM or SAM than were those whose linear growth rate maintained or increased their HAZ (P < 0.001). Mean changes of +0.15, -0.03, -0.17, and -0.53 in HAZ were observed for those who sustained recovery, relapsed to MAM once, relapsed to MAM multiple times, and developed SAM, respectively. Conclusion: Our results add to the body of evidence suggesting that acute wasting is a harbinger of subsequent stunting. Children who experience poor linear growth after MAM are more likely to experience relapse. Given this bidirectional relation between wasting and stunting, supplementary feeding programs should consider both when designing protocols, aiming to optimize linear growth and achieve acute weight gain, as a means of reducing relapse. This trial was registered at clinicaltrials.gov as NCT02351687.

Additional Common Bean in the Diet of Malawian Children Does Not Affect Linear Growth, but Reduces Intestinal Permeability.

Background: Chronic malnutrition, as manifested by linear growth faltering, is pervasive among rural African children. Improvements in complementary feeding may decrease the burden of environmental enteric dysfunction (EED) and thus improve growth in children during the critical first 1000 d of development. Objective: We tested the hypothesis that systematically including common bean or cowpea into complementary feeding would reduce EED and growth faltering among children in rural Malawi. Methods: This was a double-blind clinical trial in which children 12-23 mo of age were randomly assigned to receive complementary feeding with 1 of 3 foods: roasted cowpea or common bean flour, or an isoenergetic amount of corn-soy blend as a control food for 48 wk. Children aged 12-23 mo received 155 kcal/d and thereafter until 35 mo received 200 kcal/d. The primary outcomes were change in length-for-age z score (LAZ) and improvements in a biomarker of EED, the percentage of lactulose (%L) excreted as part of the lactulose:mannitol dual-sugar absorption test. Anthropometric measurements and urinary %L excretion were compared between the 2 intervention groups and the control group separately with the use of linear mixed model analyses for repeated measures. Results: A total of 331 children completed the clinical trial. Compliance with the study interventions was excellent, with >90% of the intervention flour consumed as intended. No significant effects on LAZ, change in LAZ, or weight-for-length z score were observed due to either intervention legume, compared to the control. %L was reduced with common bean consumption (effect estimate was -0.07 percentage points of lactulose, P = 0.0007). The lactulose:mannitol test was not affected by the legume intervention. Conclusion: The addition of common bean to complementary feeding of rural Malawian children during the second year of life led to an improvement in a biomarker of gut health, although this did not directly translate into improved linear growth. This trial was registered at clinicaltrials.gov as NCT02472301.

Household-level factors associated with relapse following discharge from treatment for moderate acute malnutrition.

Factors associated with relapse among children who are discharged after reaching a threshold denoted 'recovered' from moderate acute malnutrition (MAM) are not well understood. The aim of this study was to identify factors associated with sustained recovery, defined as maintaining a mid-upper-arm circumference≥12·5 cm for 1 year after release from treatment. On the basis of an observational study design, we analysed data from an in-depth household (HH) survey on a sub-sample of participants within a larger cluster randomised controlled trial (cRCT) that followed up children for 1 year after recovery from MAM. Out of 1497 children participating in the cRCT, a subset of 315 children participated in this sub-study. Accounting for other factors, HH with fitted lids on water storage containers (P=0·004) was a significant predictor of sustained recovery. In addition, sustained recovery was better among children whose caregivers were observed to have clean hands (P=0·053) and in HH using an improved sanitation facility (P=0·083). By contrast, socio-economic status and infant and young child feeding practices at the time of discharge and HH food security throughout the follow-up period were not significant. Given these results, we hypothesise that improved water, sanitation and hygiene conditions in tandem with management of MAM through supplemental feeding programmes have the possibility to decrease relapse following recovery from MAM. Furthermore, the absence of associations between relapse and nearly all HH-level factors indicates that the causal factors of relapse may be related mostly to the child's individual, underlying health and nutrition status.

Human gut microbiome viewed across age and geography.

Gut microbial communities represent one source of human genetic and metabolic diversity. To examine how gut microbiomes differ among human populations, here we characterize bacterial species in fecal samples from 531 individuals, plus the gene content of 110 of them. The cohort encompassed healthy children and adults from the Amazonas of Venezuela, rural Malawi and US metropolitan areas and included mono- and dizygotic twins. Shared features of the functional maturation of the gut microbiome were identified during the first three years of life in all three populations, including age-associated changes in the genes involved in vitamin biosynthesis and metabolism. Pronounced differences in bacterial assemblages and functional gene repertoires were noted between US residents and those in the other two countries. These distinctive features are evident in early infancy as well as adulthood. Our findings underscore the need to consider the microbiome when evaluating human development, nutritional needs, physiological variations and the impact of westernization.

Gut DNA viromes of Malawian twins discordant for severe acute malnutrition.

The bacterial component of the human gut microbiota undergoes a definable program of postnatal development. Evidence is accumulating that this program is disrupted in children with severe acute malnutrition (SAM) and that their persistent gut microbiota immaturity, which is not durably repaired with current ready-to-use therapeutic food (RUTF) interventions, is causally related to disease pathogenesis. To further characterize gut microbial community development in healthy versus malnourished infants/children, we performed a time-series metagenomic study of DNA isolated from virus-like particles (VLPs) recovered from fecal samples collected during the first 30 mo of postnatal life from eight pairs of mono- and dizygotic Malawian twins concordant for healthy growth and 12 twin pairs discordant for SAM. Both members of discordant pairs were sampled just before, during, and after treatment with a peanut-based RUTF. Using Random Forests and a dataset of 17,676 viral contigs assembled from shotgun sequencing reads of VLP DNAs, we identified viruses that distinguish different stages in the assembly of the gut microbiota in the concordant healthy twin pairs. This developmental program is impaired in both members of SAM discordant pairs and not repaired with RUTF. Phage plus members of the Anelloviridae and Circoviridae families of eukaryotic viruses discriminate discordant from concordant healthy pairs. These results disclose that apparently healthy cotwins in discordant pairs have viromes associated with, although not necessarily mediators, of SAM; as such, they provide a human model for delineating normal versus perturbed postnatal acquisition and retention of the gut microbiota's viral component in populations at risk for malnutrition.

A Combined Intervention of Zinc, Multiple Micronutrients, and Albendazole Does Not Ameliorate Environmental Enteric Dysfunction or Stunting in Rural Malawian Children in a Double-Blind Randomized Controlled Trial.

BACKGROUND: Environmental enteric dysfunction (EED) and linear growth stunting affect many rural agrarian children in the developing world and contribute to the persistently high rates of stunting that are observed worldwide. Effective interventions to consistently ameliorate EED are lacking. OBJECTIVE: We tested whether a bundle of safe and affordable interventions would decrease EED and stunting over 12-24 wk in a cohort of rural Malawian children 12-35 mo old. METHODS: This was a randomized, double-blind, placebo-controlled clinical trial in which the intervention group received a single dose of albendazole and 14 d of zinc at enrollment and after 20 wk. The intervention group also received a daily multiple micronutrient powder throughout the 24 wk of study. The primary outcomes were improvements in EED, as measured by the urinary lactulose-to-mannitol ratio (L:M ratio) from dual-sugar absorption testing, and linear growth. Urinary L:M ratios and anthropometric measurements were evaluated after 12 and 24 wk of intervention and compared with a placebo group that did not receive any of these interventions. RESULTS: A total of 254 children were enrolled at a mean age of 24 mo; 55% were female. Their mean weight-for-age z score was -1.5, and their mean length-for-age z score was -0.9. After 12 and 24 wk of study, increases in the L:M ratio did not differ between the intervention group (0.071 and 0.088 units, respectively) and the placebo group (0.073 and 0.080 units, respectively) (P = 0.87 and 0.19, respectively). Relative changes in length and weight also did not differ significantly between groups at any time point. CONCLUSION: The combined usage of albendazole, zinc, and a daily multiple micronutrient powder did not decrease EED or stunting in this population of agrarian children 12-35 mo old in rural Malawi. Alternative interventions to improve these diseases should be investigated. This trial was registered at clinicaltrials.gov as NCT02253095.

Environmental Enteric Dysfunction Is Associated With Altered Bile Acid Metabolism.

OBJECTIVES: Environmental enteric dysfunction (EED), a clinically asymptomatic condition characterized by inflammation of the small bowel mucosa, villous atrophy, and increased gut permeability, is common among children in developing countries. Because of abnormal gut mucosa and altered gut microbiome, EED could potentially affect the metabolism and enterohepatic circulation of bile acids. METHODS: In 313 children, aged 12 to 59 months, EED was assessed by the dual sugar absorption test. Serum bile acids were measured using stable-isotope liquid chromatography-tandem mass spectrometry. RESULTS: In the overall study population, serum cholic acid and chenodeoxycholic acid were lower, whereas glycocholic acid, taurodeoxycholic acid, glycodeoxycholic acid, glycolithocholic acid, and glycoursodeoxycholic acid were significantly higher at older ages. Independent of age, serum taurochenodeoxycholic acid, tauromuricholic acid, and glycoursodeoxycholic acid were significantly different between 244 children with EED and 69 children without EED. Total serum bile acids (median, interquartile range) were 4.51 (2.45, 7.51) and 5.10 (3.32, 9.01) µmol/L in children with and without EED, respectively (age-adjusted, P = 0.0009). The proportion of bile acids conjugated with taurine instead of glycine was higher in children with EED (P < 0.0001). CONCLUSIONS: EED is associated with altered bile acid metabolism in young children in rural Malawi. Further work is needed to determine the generalizability of these findings in other study populations.

Antibiotics as part of the management of severe acute malnutrition.

BACKGROUND: Severe acute malnutrition contributes to 1 million deaths among children annually. Adding routine antibiotic agents to nutritional therapy may increase recovery rates and decrease mortality among children with severe acute malnutrition treated in the community. METHODS: In this randomized, double-blind, placebo-controlled trial, we randomly assigned Malawian children, 6 to 59 months of age, with severe acute malnutrition to receive amoxicillin, cefdinir, or placebo for 7 days in addition to ready-to-use therapeutic food for the outpatient treatment of uncomplicated severe acute malnutrition. The primary outcomes were the rate of nutritional recovery and the mortality rate. RESULTS: A total of 2767 children with severe acute malnutrition were enrolled. In the amoxicillin, cefdinir, and placebo groups, 88.7%, 90.9%, and 85.1% of the children recovered, respectively (relative risk of treatment failure with placebo vs. amoxicillin, 1.32; 95% confidence interval [CI], 1.04 to 1.68; relative risk with placebo vs. cefdinir, 1.64; 95% CI, 1.27 to 2.11). The mortality rates for the three groups were 4.8%, 4.1%, and 7.4%, respectively (relative risk of death with placebo vs. amoxicillin, 1.55; 95% CI, 1.07 to 2.24; relative risk with placebo vs. cefdinir, 1.80; 95% CI, 1.22 to 2.64). Among children who recovered, the rate of weight gain was increased among those who received antibiotics. No interaction between type of severe acute malnutrition and intervention group was observed for either the rate of nutritional recovery or the mortality rate. CONCLUSIONS: The addition of antibiotics to therapeutic regimens for uncomplicated severe acute malnutrition was associated with a significant improvement in recovery and mortality rates. (Funded by the Hickey Family Foundation and others; ClinicalTrials.gov number, NCT01000298.).