The Childhood Acute Illness and Nutrition Network

Bifidobacterium longum and B. infantis are pioneer colonizers of the neonatal gut and are widely used as probiotics to support infant growth, development, and disease resistance. However, commercial strains derived largely from high-income countries (HICs) may be suboptimal for infants in low- and middle-income countries (LMICs). We assembled a global genomic atlas of more than 4,000 genomes from 48 countries, increasing representation from LMICs by 12- to 17-fold. High-resolution phylogenomic and functional analyses support delineating B. longum and B. infantis as distinct species with divergent functions and epidemiological patterns. B. infantis dominates early-life microbiota in LMICs but is rarely detected in HICs. Natural B. infantis strains show extreme biogeographic stratification and predicted adaptations to local plant-glycan-rich diets and breast-milk-derived substrates, including urea and B vitamins. This genomic resource enables genome-guided selection of geographically matched strains to inform more effective probiotics and precision microbiome therapeutics for diverse infant populations.

Background: Undernutrition among infants and young children in South Asia remains a major public health concern, contributing to high rates of morbidity and mortality. While quantitative systematic reviews have identified various risk factors for undernutrition, no review has focused on qualitative studies. This study aims to review published literature on family member and healthcare provider perceptions about influences on undernutrition among infants and young children in South Asia. Methods: We searched for qualitative research articles published from 2000 to 2026 in the PubMed, Scopus and CINAHL databases, and used the Critical Appraisal Skills Program (CASP) tool to assess the quality of selected articles. Selected articles were analyzed thematically. The PROSPERO registration number is CRD42022385382. Results: After screening 201 research articles, 19 articles were selected for inclusion in this review. Perceived influences of undernutrition among children were categorized into individual, socio-cultural, economic, environmental and system factors. Interconnected influences included maternal illness, single motherhood, mothers' knowledge and awareness, convenience of providing low-quality ready-made and junk food, spiritual beliefs and superstition, violence against women, financial constraints in a context of rising food prices and seasonal impacts on food production, and physical accessibility of healthcare services. Conclusions: This review emphasizes the complex interplay of influences on undernutrition among young children in South Asia. Potential interventions must be culturally tailored and gender-sensitive, with key strategies including nutrition education, community-based support, maternal health improvements, and policies addressing food insecurity and healthcare accessibility.

The co-occurrence of mental illness and substance use disorders (SUDs) presents a significant public health challenge with affected individuals facing compounded stigma that leads to poor health outcomes, social exclusion, and systemic neglect. Despite growing recognition of stigma as a social determinant of health in people with comorbid mental illness and SUDs, current responses remain largely confined to clinical and academic settings. This article argues that civil society, particularly groups led by individuals with lived experience, represents an underutilized yet powerful force in combating stigma. Drawing from historical movements such as HIV/AIDS activism and contemporary examples from peer-led movements, we highlight how civil society organizations (CSOs) have reshaped public discourse, influenced policy, and fostered inclusive research. We examine emerging efforts in low resource settings and explore the transformative potential of digital civil society spaces. We advocate for a shift in stigma reduction paradigms to those that center lived experience, supports cross-sectoral collaboration, and recognizes both physical and digital civil society as essential to inclusive and sustainable change. To addressing the complex and intersecting stigmas associated with comorbid mental illness and SUDs, we recommend investing in CSOs, especially those grounded in participatory, culturally relevant approaches, particularly in low- and middle-income settings.

We use machine learning to identify innovative strategies to target azithromycin to the children with watery diarrhea who are most likely to benefit. Using data from a randomized trial of azithromycin for watery diarrhea (NCT03130114), we develop personalized treatment rules given sets of diagnostic, child, and clinical characteristics, employing a robust ensemble machine learning-based procedure. This procedure estimates the child-level expected benefit for a given set of covariates by combining predictions from a library of statistical models. For each rule, we estimate the proportion treated under the rule and the average benefits of treatment. Among 6692 children, treatment under the most comprehensive rule is recommended on average for one third of children. The risk of diarrhea on day 3 is 10.1% lower (95% CI: 5.4, 14.9) with azithromycin compared to placebo among children recommended for treatment (NNT: 10). For day 90 re-hospitalization and death, risk is 2.4% lower (95% CI: 0.6, 4.1; NNT: 42). While pathogen diagnostics are strong determinants of azithromycin effects on diarrhea duration, host characteristics may better predict benefits for re-hospitalization or death. This suggests that targeting antibiotic treatment for severe outcomes among children with watery diarrhea may be possible without access to pathogen diagnostics.

We report on carbapenem-resistant Escherichia coli ST46 and 167 strains isolated from fecal samples of 4- and 8-month-old infants, respectively, in Kenya, collected at discharge after more than 4 days of hospitalization. The isolates carried blaNDM-5 carbapenemase and a PBP3 (333YRIN/K334) insertion. This finding has implications for patient management.

Abstract Infant gut microbiome assembly influences childhood growth and development. However, current understanding is based almost exclusively on infants from highly industrialised, high-income countries. Here, we present a high-resolution map of gut microbiome assembly in 596 infants from six non-industrialised countries across sub-Saharan Africa and South Asia. Microbiome assembly followed a unified trajectory comprising three distinct stages, characterised by the ordered acquisition and loss of bacterial species and functions. Progression through these stages is governed by breastfeeding and the timing of weaning, revealing an ancestral pattern of microbiome succession conserved across diverse non-industrialised populations. Core microbiome functions are rapidly established by a defined consortium of pioneer species, followed by age-dependent expansions in functional capacity, including pathways implicated in metabolism, immune regulation, and neurodevelopment. Comparison with infant microbiomes from highly industrialised populations reveals that key bacteria underpinning the ancestral assembly trajectory—Bifidobacterium, Lactobacillus and Prevotella—are depleted with industrialisation. Our microbiome assembly map provides a reference for optimising infant microbiome development and supporting child growth through rational design of next-generation infant probiotics, and highlights commensal microbes that should be prioritised for preservation amid global lifestyle transitions.

BackgroundMulti-pathogen molecular diagnostics enhance our understanding of the pathogen-specific burden of diarrhea. However, attributing etiology remains challenging in high-burden settings where coinfections are common. The Antibiotics for Children with severe Diarrhea (ABCD) trial provides a unique opportunity to leverage azithromycin treatment response to identify bacterial diarrhea.MethodsWe analyzed data from 6,692 children with watery diarrhea enrolled in ABCD (2017 to 2019) who were randomized to receive azithromycin or placebo. We modelled the heterogeneity in the azithromycin treatment response by the enteric pathogen quantity detected by quantitative PCR using log-binomial regression.ResultsAzithromycin treatment response varied by pathogen quantity, with the strongest effect observed for Shigella. Each log₁₀ increase in Shigella quantity was associated with a 13% reduction (95% CI: 3–23%) in diarrhea risk at day 3 in the azithromycin group compared to placebo. We observed similar, though non-significant, trends for Vibrio cholerae, ST-ETEC, and tEPEC. In contrast, no association was found between pathogen quantity and azithromycin response for Campylobacter, LT-ETEC, or EAEC. These patterns remained consistent when evaluating hospitalization or death risk within 90 days.ConclusionThe observed associations between azithromycin treatment response and pathogen quantity for Shigella, Vibrio cholerae, ST-ETEC, and tEPEC support prior evidence that these pathogens are likely causes of diarrhea when present in high quantities. Conversely, the absence of a similar response pattern for Campylobacter, LT-ETEC, and EAEC is consistent with large-scale studies showing a limited association between their quantities and diarrhea.

The participation of non-state actors in global health law has undergone tremendous change over the years, with non-state actors playing an increasingly important role in the formation of global health law - in terms of engagement in international health governance forums and health policy decision processes. Global health movements and advocacy groups dedicated to specific diseases (for instance HIV/AIDS, tuberculosis and malaria) and health rights have been increasingly pivotal in ensuring that global health policies are rights-based. This article interrogates the role that nongovernmental organizations (NGOs) have played in shaping global health law. Looking at how the historical and traditional roles of NGOs have evolved over time, this article analyzes the contribution that NGOs have made in advancing and defining a rights-based approach to health.

BackgroundAlthough mortality risk associated with HIV is well described, HIV-exposed uninfected (HEU) young children are also at increased risk of hospitalization and death as compared to HIV-unexposed uninfected (HUU) children. The drivers of poor outcomes among HEU children remain unknown, limiting the development of interventions to support this vulnerable population.MethodsWe performed a secondary analysis of data from a large multi-country prospective cohort [Childhood Acute Illness and Nutrition (CHAIN) Network] study. Data from 5 sites in Uganda, Kenya, and Malawi were included. Hospitalized children aged 2–23 months were followed from an index admission for 6 months after discharge to determine acute and long-term outcomes. Using perinatal HIV exposure (HEU and HUU) as the primary exposure and adjusting for child, caregiver, and household characteristics, we compared inpatient and 30-day survival outcomes, nutritional status, hospital length of stay, illness severity, and utilization of inpatient resources.ResultsWe included 1486 children: 217 HEU and 1269 HUU. HEU children had an increased risk of mortality both during hospitalization [adjusted OR 1.96, 95% CI (1.14–3.37)] and in the 30 days following hospital admission [adjusted hazard ratio 2.20, 95% CI (1.10–4.42)]. Wasting and stunting were more frequent in HEU than HUU children, with adjusted OR 1.41, 95% CI (1.03–1.95) and adjusted OR 1.91, 95% CI (1.34–2.70), respectively. HEU children were also more likely to have a prolonged hospital stay compared to HUU children [adjusted OR 1.58, 95% CI (1.08–2.29)], although admission diagnoses, illness severity at admission, and use of inpatient resources (supplemental oxygen, nasogastric tube, and second-line antibiotics) did not differ significantly between groups.ConclusionsHEU children are more likely to die during hospitalization and within 30 days of admission, to be wasted and stunted upon hospital admission, and to require a prolonged hospital stay, as compared to HUU children. Hospitals in settings with a high prevalence of women-living-with-HIV should ensure that maternal HIV status is established among children requiring admission and build capacity to provide additional hospital monitoring and early post-discharge support for HEU children.

Reducing systemic inequities in testing, access to care, social protection - and in the scientific process - is essential to end TB. Incorporating social science methods and expertise on inequity into the mainstream TB response would help ensure that political commitments to equity move beyond symbolic gestures. We convened a meeting between TB social scientists, people with lived experience, civil society and community members to discuss equity within the global TB response. Here, we propose five means by which a social science lens can strengthen equitable, person-centred responses and reconcile the public health significance of TB with the principles of social justice.