Fecal biomarkers to characterize intestinal inflammation among children with medically attended diarrhea across six low-resource settings: Findings from the Enterics for Global Health (EFGH) Shigella surveillance study

@article{horne2026fecal,
  title = {{Fecal biomarkers to characterize intestinal inflammation among children with medically attended diarrhea across six low-resource settings: Findings from the Enterics for Global Health (EFGH) Shigella surveillance study}},
  author = {Bri’Anna Horne and Brian Otieno Onyando and Henry Badji and Wardah Mujahid and Taufiqur Rahman Bhuiyan and Mutsai Bakali and Junaid Iqbal and Maribel Paredes Olortegui and Patricia Pavlinac and Bubacar E. Ceesay and Olivia Schultes and Sharon M. Tennant and Billy Ogwel and Desiree Witte and Hannah Atlas and Naveed Ahmed and John Benjamin Ochieng and Khandra Sears and Sadia Islam and Queen Saidi and Samba Juma Jallow and Zarfishan Hussain and Paul Garcia Bardales and James A. Platts-Mills and Richard Omore and Farhana Khanam and Md. Parvel Mosharraf and Ousman Secka and Vitumbiko Munthali and Margaret N. Kosek and Maureen Ndalama and Jen Cornick and Md. Tahir Yousafzai and Md. Jahangir Hossain and Catherine Sonye and Firdausi Qadri and Elizabeth T. Rogawski McQuade and Stephanie A. Brennhofer},
  journal = {PLOS Neglected Tropical Diseases},
  year = {2026},
  month = sep,
  doi = {10.1371/journal.pntd.0014320},
  url = {https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0014320},
  note = {CC BY 4.0},
}

TY  - JOUR
TI  - Fecal biomarkers to characterize intestinal inflammation among children with medically attended diarrhea across six low-resource settings: Findings from the Enterics for Global Health (EFGH) Shigella surveillance study
AU  - Bri’Anna Horne
AU  - Brian Otieno Onyando
AU  - Henry Badji
AU  - Wardah Mujahid
AU  - Taufiqur Rahman Bhuiyan
AU  - Mutsai Bakali
AU  - Junaid Iqbal
AU  - Maribel Paredes Olortegui
AU  - Patricia Pavlinac
AU  - Bubacar E. Ceesay
AU  - Olivia Schultes
AU  - Sharon M. Tennant
AU  - Billy Ogwel
AU  - Desiree Witte
AU  - Hannah Atlas
AU  - Naveed Ahmed
AU  - John Benjamin Ochieng
AU  - Khandra Sears
AU  - Sadia Islam
AU  - Queen Saidi
AU  - Samba Juma Jallow
AU  - Zarfishan Hussain
AU  - Paul Garcia Bardales
AU  - James A. Platts-Mills
AU  - Richard Omore
AU  - Farhana Khanam
AU  - Md. Parvel Mosharraf
AU  - Ousman Secka
AU  - Vitumbiko Munthali
AU  - Margaret N. Kosek
AU  - Maureen Ndalama
AU  - Jen Cornick
AU  - Md. Tahir Yousafzai
AU  - Md. Jahangir Hossain
AU  - Catherine Sonye
AU  - Firdausi Qadri
AU  - Elizabeth T. Rogawski McQuade
AU  - Stephanie A. Brennhofer
PY  - 2026
DA  - 2026/09/15
JO  - PLOS Neglected Tropical Diseases
DO  - 10.1371/journal.pntd.0014320
UR  - https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0014320
AB  - Background: Frequent enteric infections can damage the small intestine causing inflammation and malabsorption, leading to environmental enteric dysfunction. We aimed to characterize the association between intestinal inflammation and enteric pathogens among children in low- and middle-income countries (LMICs) who presented to care with diarrhea. Methodology/principle findings: We conducted a cross-sectional analysis within the Enterics for Global Health - Shigella surveillance study at six LMIC sites: Bangladesh, Kenya, Malawi, Pakistan, Peru, and The Gambia. From August 2022 to July 2024, rectal swabs and whole stool samples were collected from 4,903 children with medically attended diarrhea aged 6–35 months (44.4% females, n = 2178/4903; mean age: 15.4 months ± 7.4 months) and were analyzed for Shigella and four fecal inflammatory biomarkers: hemoglobin, lipocalin-2, myeloperoxidase, and calprotectin via Enzyme Linked Immunosorbent Assays. Caregivers and clinicians demonstrated moderate accuracy in identifying blood in stool compared to fecal hemoglobin (area under the curve (AUC)=0.70). Among 10 pathogens evaluated, Shigella-attributable diarrhea had the highest concentrations of calprotectin, hemoglobin, and myeloperoxidase. Shigella culture-/PCR+ episodes had intermediate levels of inflammation between culture-/PCR- and culture+ episodes. In multivariable models restricted to Shigella episodes, dysentery was positively associated and vomiting was negatively associated with biomarker concentrations, with the strongest associations observed for hemoglobin (dysentery geometric mean ratio: 12.82 (95% CI: 7.21, 22.77) and vomiting geometric mean ratio: 0.45 (95% CI: 0.23, 0.86)). Age, sex, and both acute and chronic malnutrition were not associated with inflammatory biomarker concentrations. Conclusions/significance: Hemoglobin appeared to be a more sensitive marker of blood in stool than visual observation. While Shigella was associated with heightened levels of all inflammatory biomarkers, hemoglobin was most strongly associated with Shigella, especially among attributable and culture positive episodes. The distinct clinical characteristics of Shigella were most closely associated with elevated hemoglobin concentrations. Author summary: Diarrhea is common among children under five years of age in low- and middle-income countries (LMICs). Repeated diarrheal illnesses can damage the gut, leading to issues with growth and brain development. We examined fecal samples collected from 4,903 children with diarrhea who were enrolled in the Enterics for Global Health - Shigella surveillance study. We tested samples for diarrheal pathogens and measured four inflammatory biomarkers. We found that hemoglobin better identified blood in stool than visual observation of blood. Additionally, certain biomarkers (calprotectin, myeloperoxidase, and most notably hemoglobin) were higher when diarrhea was caused by bacteria such as Shigella than when diarrhea was caused by viruses. Also, we discovered that Shigella episodes identified using molecular diagnostics caused a similar illness as those identified by culture. These results support that Shigella diarrhea episodes identified by molecular diagnostics or culture are more inflammatory than other episodes of diarrhea and may require appropriate antibiotic treatment.
SN  - 1935-2735
ER  -