Shigella is a primary cause of moderate-to-severe diarrhea in children living in impoverished areas of the world. Shigella is known for causing dysentery (blood in stool). However, majority of the children infected with Shigella present with watery diarrhea. The current World Health Organization (WHO) guidelines for treatment of shigellosis (in the absence of a rapid, sensitive, simple and inexpensive diagnostic test) recommends treatment with antibiotics when presence of visible blood in stool. Thus, the non-dysentery Shigella associated diarrhea (NDSD) cases would not be treated with antibiotics. Absence of dysentery may not indicate a low risk of death and does not exclude Shigella as a cause of diarrhea. In particularly vulnerable younger children or with malnutrition, identification and treatment of Shigella infection might be life-saving. It may be hypothesized that NDSD cases, if identified quickly, should be treated with antibiotics to improve survival and long-term developmental potential in children. Identification of such cases will require a rapid test to document these infections so that treatment can be initiated promptly, and evidence based. To address these questions, we propose to conduct a prospective longitudinal case control study to understand the pathophysiology of NDSD and the impact of NDSD in children compared to dysentery shigellosis. The children seeking care in the hospital in Bangladesh with diarrhea (both dysentery and NDSD), that is positive for Shigella and a third group with Shigella negative watery diarrhea will be enrolled and prospectively followed. Our study has the following specific aims:
AIM 1. Determine morbidity and risk of hospitalization associated with NDSD cases and its impact on nutritional status and cognitive development of the children.
AIM 2. Understand the impact of NDSD on gut barrier function, systemic and gut inflammation in children.
AIM 3. Evaluate if the simple and rapid test S-RLDT could be applicable for case detection and treatment of shigellosis in the clinical settings of the rural hospitals of the endemic countries. Collectively, our proposed research would broadly impact the field by understanding the pathophysiology of NDSD and the impact of NDSD in child health. This study will help to understand if there is a need to change the current guidelines of shigellosis treatment for better survival and development of the children. This study will also validate a rapid test capable of identifying the patients who will benefit from antibiotics.

Public Health Relevance

Shigella is a primary cause of moderate-to-severe diarrhea including dysentery in children living in impoverished areas of the world. The current World Health Organization (WHO) guidelines for treatment of shigellosis (in the absence of a rapid, simple and inexpensive diagnostic test) recommends treatment with antibiotics when presence of visible blood in stool, although, majority of the Shigella diarrhea are watery diarrhea in nature and thus the non-dysentery Shigella associated diarrhea (NDSD) cases would not be treated, which might result in an appreciable amount of unaddressed Shigella-associated morbidity and mortality. We aim to study the pathophysiology of NDSD and the impact of NDSD in children to understand if there is a need to change the current treatment guidelines for shigellosis to improve survival and long-term developmental potential in children and we also aim to evaluate our novel, simple, rapid and sensitive diagnostic assay, if capable of identifying the patients with shigellosis who will benefit from antibiotics.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI153399-01A1
Application #
10209109
Study Section
Clinical Research and Field Studies of Infectious Diseases Study Section (CRFS)
Program Officer
Mills, Melody
Project Start
2021-03-09
Project End
2026-02-28
Budget Start
2021-03-09
Budget End
2022-02-28
Support Year
1
Fiscal Year
2021
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218