The impact of non-dysentery Shigella-associated diarrhea in children

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PROJECT SUMMARY / ABSTRACT 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. Such a rapid test is currently unavailable. 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 under 5 years of age seeking care in the Kumudini hospital in rural Mirzapur, Bangladesh with diarrhea (both dysentery and NDSD), that is positive for Shigella will be enrolled and prospectively followed. A third group with Shigella negative watery diarrhea will also be enrolled to compare. 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 our novel, simple and rapid test S-RLDT capable of identifying NDSD cases. 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.