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Abstract Background Poor growth in early childhood has been considered irreversible after 2–3 years of age and has been associated with morbidity and mortality over the short-term and with poor economic and cognitive outcomes over the long-term. The MAL-ED cohort study was performed in eight low-income settings with the goal of evaluating relationships between the child’s environment and experience (dietary, illness, and pathogen exposure, among others) and their growth and development. The goal of this analysis is to determine whether there are differences in the factors associated with growth from 24 to 60 months using two different metrics. Methods Across six MAL-ED sites, 942 children had anthropometry data at 24 and 60 months, as well as information about socioeconomic status, maternal height, gut permeability (lactulose-mannitol z-score (LMZ)), dietary intake from 9 to 24 months, and micronutrient status. Anthropometric changes were in height- or weight-for-age z-score (HAZ, WAZ), their absolute difference from the growth standard median (HAD (cm), WAD (kg)), as well as recovery from stunting/underweight. Outcomes were modeled using multivariate regression. Results At 24 months, almost half of the cohort was stunted (45%) and 21% were underweight. Among those who were stunted at 24 months (n = 426), 185 (43%) were no longer stunted at 60 months. Most children increased their HAZ from 24 to 60 months (81%), whereas fewer (33%) had positive changes in their HAD. Linear regression models indicate that girls improved less than boys from 24 to 60 months (HAZ: -0.21 (95% CI -0.27, -0.15); HAD: -0.75 (-1.07, -0.43)). Greater intestinal permeability (higher LMZ) at 0–24 months was associated with lower relative and absolute changes from 24 to 60 months (HAZ: -0.10 (-0.16, -0.04); HAD: -0.47 (-0.73, -0.21)). Maternal height (per 10 cm) was positively associated with changes (HAZ: 0.09 (0.03, 0.15); HAD: 0.45 (0.15, 0.75)). Similar relationships were identified for changes in WAZ and WAD. Conclusions The study children demonstrated improved growth from 24 to 60 months of age, but only a subset had positive changes in HAD and WAD. The same environmental factors were associated with growth from 24 to 60 months regardless of metric used (change in HAZ or HAD, or WAZ and WAD).

Abstract Background Multidrug-resistant (MDR) Gram-negative bacterial species are an increasingly dangerous public health threat, and are now endemic in many areas of South Asia. However, there are a lack of comprehensive data from many countries in this region determining historic and current MDR prevalence. Enterotoxigenic Escherichia coli (ETEC) is a leading cause of both acute infant diarrhea and traveler’s diarrhea in Nepal. The MDR prevalence and associated resistance mechanisms of ETEC isolates responsible for enteric infections in Nepal are largely unknown. Methods A total of 265 ETEC isolates were obtained from acute diarrheal samples (263/265) or patient control samples (2/265) at traveler’s clinics or regional hospitals in Nepal from 2001 to 2016. Isolates were screened for antibiotic resistance, to include extended spectrum beta-lactamase (ESBL) production, via the Microscan Automated Microbiology System. ETEC virulence factors, specifically enterotoxins and colonization factors (CFs), were detected using multiplex PCR, and prevalence in the total isolate population was compared to ESBL-positive isolates. ESBL-positive isolates were assessed using multiplex PCR for genetic markers potentially responsible for observed resistance. Results A total of 118/265 (44.5%) ETEC isolates demonstrated resistance to ≥2 antibiotics. ESBL-positive phenotypes were detected in 40/265 isolates, with isolates from 2008, 2013, 2014, and 2016 demonstrating ESBL prevalence rates of 1.5, 34.5, 31.2, and 35.0% respectively. No difference was observed in overall enterotoxin characterization between the total ETEC and ESBL-positive populations. The CFs CS2 (13.6%), CS3 (25.3%), CS6 (30.2%), and CS21 (62.6%) were the most prevalent in the total ETEC population. The ESBL-positive ETEC isolates exhibited a higher association trend with the CFs CS2 (37.5%), CS3 (35%), CS6 (42.5%), and CS21 (67.5%). The primary ESBL gene identified was bla CTX-M-15 (80%), followed by bla SHV-12 (20%) and bla CTX-M-14 (2.5%). The beta-lactamase genes bla TEM-1 (40%) and bla CMY-2 (2.5%) were also identified. It was determined that 42.5% of the ESBL-positive isolates carried multiple resistance genes. Conclusion Over 30% of ETEC isolates collected post-2013 and evaluated in this study demonstrated ESBL resistance. Persistent surveillance and characterization of enteric ETEC isolates are vital for tracking the community presence of MDR bacterial species in order to recommend effective treatment strategies and help mitigate the spread of resistant pathogens.