Anti-Interleukin-23 Treatment Linked to Improved Infection Survival.

is a leading cause of healthcare associated infection and an unacceptably high proportion of patients with infection die despite conventional antibiotic treatment. Host-directed immunotherapy has been proposed as an ideal treatment modality for infection to mitigate the underlying toxin-mediated pathogenic immune response while sparing protective gut microbes. Interleukin-23 monoclonal antibody inhibitors are used extensively to control pro-inflammatory Th17 immune pathways in psoriasis and inflammatory bowel disease that are similarly important during infection.

The IL-33/ST2 signaling axis drives pathogenesis in acute SARS-CoV-2 infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), remains a significant threat to global public health. Immunopathological damage plays a role in driving pneumonia, acute respiratory distress syndrome (ARDS), and multiorgan failure in severe COVID-19. Therefore, dissecting the pulmonary immune response to SARS-CoV-2 infection is critical to understand disease pathogenesis and identify immune pathways targetable by therapeutic intervention.

Enhanced immunogenicity of a TcdB vaccine adjuvanted with a synthetic dual-TLR ligand adjuvant.

We report a comprehensive evaluation of the toxin B (TcdB) vaccine adjuvanted with a dual Toll-like receptor ligand liposome adjuvant for infection (CDI). The vaccine completely protected mice from a lethal infection. Compared to alum adjuvanted TcdB, it generated functionally superior systemic antibodies and supported strong memory B cell and gut IgA responses.

FMT Restores Colonic Protein Biosynthesis and Cell Proliferation in Patients with Recurrent Disease.

Recurrent infection (CDI) is a major health threat with significant mortality and financial costs. Fecal Microbiota Transplantation (FMT) is an effective therapy, however the mechanisms by which it acts, particularly on the host, are poorly understood. Here we enrolled a prospective cohort of human patients with recurrent CDI (n=16) undergoing FMT therapy.

Antibiotic use in infants in the 6 weeks after delivery in seven low- and middle-income countries: findings from the A-PLUS trial.

Objectives: Antibiotic use is increasing in low- and middle-income countries (LMIC); however, few studies have examined the rates of use in a population. The use of antibiotics for liveborn infants in LMIC was examined.

Design: The study, a planned prospective, observational secondary analysis of the A-PLUS randomised controlled trial of azithromycin, was conducted in Global Network sites in seven countries: Bangladesh, Pakistan, India (two sites), Kenya, Zambia, the Democratic Republic of Congo and Guatemala.

Anthropometry relationship with duodenal histologic features of children with environmental enteric dysfunction: a multicenter cross-sectional study.

Background: Environmental enteric dysfunction (EED) is a precursor of growth faltering in children living in impoverished conditions who are frequently exposed to environmental toxins and enteropathogens, leading to small bowel inflammatory, malabsorptive, and permeability derangements and low-grade chronic systemic inflammation.

Objectives: We explored the association between anthropometrics and duodenal histologic features of EED among children from 3 lower middle-income country centers.

Methods: In this cross-sectional study, Pakistani children (n = 63) with wasting, Bangladesh children (n = 116) with stunting or at risk for stunting (height-for-age Z score [HAZ] <-1 but ≥-2), and Zambian children (n = 108) with wasting or stunting received nutritional intervention.

Duodenal transcriptomics demonstrates signatures of tissue inflammation and immune cell infiltration in children with environmental enteric dysfunction across global centers.

Background: Environmental enteric dysfunction (EED) is an inflammatory condition of the small intestine that is prevalent in children residing in low- and middle-income countries. EED is accompanied by profound histopathologic changes in the small bowel, loss of absorptive capacity, increased intestinal permeability, increased microbial translocation, and nutrient loss.

Objectives: We sought to identify dysregulated genes and pathways that might underlie pediatric EED.

Multiplexed immunohistochemical evaluation of small bowel inflammatory and epithelial parameters in environmental enteric dysfunction.

Background: Environmental enteric dysfunction (EED) is characterized by reduced absorptive capacity and barrier function of the small intestine, leading to poor ponderal and linear childhood growth.

Objectives: To further define gene expression patterns that are associated with EED to uncover new pathophysiology of this disorder.

Methods: Duodenal biopsies from cohorts of children with EED from Bangladesh, Pakistan and Zambia were analyzed by immunohistochemistry (IHC) to interrogate gene products that distinguished differentiation and various biochemical pathways in immune and epithelial cells, some identified by prior bulk RNA sequence analyses.

Exploration of auditory statistical learning, socioeconomic status, and language outcomes in Bangladeshi children: A functional near-infrared spectroscopy study.

Auditory statistical learning, or the ability to detect statistical regularities in continuously presented stimuli, is thought to be one element that underlies language acquisition. Prior studies have uncovered behavioral and neural correlates of statistical learning, yet additional work is needed from low- and middle-income countries to explore whether statistical learning varies across cultures or underlies associations often found between socioeconomic status (SES) and language outcomes. In the present study, we explored the feasibility of using functional near-infrared spectroscopy (fNIRS) to explore auditory statistical learning in Bangladesh, a lower-middle-income country.

Intrapartum and postpartum antibiotic use in seven low- and middle-income countries: Findings from the A-PLUS trial.

Objective: To describe the intrapartum and postpartum use of non-study antibiotics in low- and middle-income countries (LMICs) during the double-blinded NICHD Global Network Azithromycin in Labor (A-PLUS) trial.

Design: The antibiotic use sub-study was a planned prospective, observational sub-study of the A-PLUS trial.

Settings: The study was carried out in hospitals or health centres affiliated with eight sites of the Global Network for Women's and Children's Health Research (Global Network) in seven countries: Bangladesh, Pakistan, India (two sites), Kenya, Zambia, The Democratic Republic of the Congo (DRC) and Guatemala.

Immunogenicity and safety of an adjuvanted protein vaccine candidate (LecA+GLA-3M-052 liposomes) in rhesus macaques.

, the causative agent of amebiasis, is one of the top three parasitic causes of mortality worldwide. However, no vaccine exists against amebiasis. Using a lead candidate vaccine containing the LecA fragment of Gal-lectin and GLA-3M-052 liposome adjuvant, we immunized rhesus macaques via intranasal or intramuscular routes.

Differences in Rotavirus Shedding and Duration by Infant Oral Rotavirus Vaccination Status in Dhaka, Bangladesh, 2011-2014.

To evaluate how breakthrough rotavirus disease contributes to transmission, we examined the impact of rotavirus vaccination on fecal shedding and duration of illness. We used multivariable linear regression to analyze rotavirus quantity by RT-qPCR and duration among 184 episodes of rotavirus diarrhea positive by ELISA in the PROVIDE study. Vaccinated children had less fecal viral shedding compared to unvaccinated children (mean difference = -0.

Predicting Clostridioides difficile infection outcomes with explainable machine learning.

Background: Clostridioides difficile infection results in life-threatening short-term outcomes and the potential for subsequent recurrent infection. Predicting these outcomes at diagnosis, when important clinical decisions need to be made, has proven to be a difficult task.

Methods: 52 clinical features from existing models or the literature were collected retrospectively within ±48 h of diagnosis among 1660 inpatient infections.

Malnutrition: From Mother to Child.

Malnutrition in children, defined as a child who is more than 2 standard deviations below the norm for height- or weight-for-age, is a pervasive, population-wide problem in low- and middle-income countries. Malnutrition is associated with increased infant mortality and delayed neurocognitive development. A recent pooled analysis of more than 30 longitudinal cohort studies demonstrated that the conditions mothers lived in during pregnancy, and their access to adequate nutrition, was a major factor in the subsequent growth and health of their children.

Persistent dysbiosis of duodenal microbiota in patients with controlled pediatric Crohn's disease after resolution of inflammation.

Crohn's disease is an inflammatory condition of the intestine characterized by largely unknown etiology and a relapse remission cycle of disease control. While possible triggers have been identified, research is inconsistent on the precise cause of these relapses, especially in the under-researched pediatric population. We hypothesized that patients in remission would have persistent microbial and inflammatory changes in small intestinal tissue that might trigger relapse.

Validation of clinical risk tools for recurrent infection.

Objective: We sought to validate available tools for predicting recurrent infection (CDI) including recurrence risk scores (by Larrainzar-Coghen, Reveles, D'Agostino, Cobo, and Eyre ) alongside consensus guidelines risk criteria, the leading severity score (ATLAS), and PCR cycle threshold (as marker of fecal organism burden) using electronic medical records.

Design: Retrospective cohort study validating previously described tools.

Setting: Tertiary care academic hospital.

IL-13 protects from Clostridioides difficile colitis.

Objectives: Clostridioides difficile infection (CDI) is the leading hospital-acquired infection in North America. We have previously discovered that antibiotic disruption of the gut microbiota decreases intestinal IL-33 and IL-25 and increases susceptibility to CDI. We further found that IL-33 promotes protection through type 2 Innate Lymphoid Cells (ILC2s), which produce IL-13.

The impact of existing total anti-toxin B IgG immunity in outcomes of recurrent Clostridioides difficile infection.

Late anti-toxin-B humoral immunity acquired after treatment is important for preventing recurrent Clostridioides difficile infection. We prospectively-measured anti-toxin-B IgG and neutralization titers at diagnosis as potential early predictors of recurrence. High anti-toxin-B-IgG/neutralizing antibodies were associated with short-lasting protection within 6-weeks, however, no difference in recurrence risk was observed by 90-days post-infection.

Small Intestine Bacterial Overgrowth is associated with increased Campylobacter and epithelial injury in duodenal biopsies of Bangladeshi children.

Small intestine bacterial overgrowth (SIBO) has been associated with enteric inflammation, linear growth stunting, and neurodevelopmental delays in children from low-income countries. Little is known about the histologic changes or epithelial adherent microbiota associated with SIBO. We sought to describe these relationships in a cohort of impoverished Bangladeshi children.