R01AI153399

The impact of non-dysentery Shigella-associated diarrhea in children - 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, the majority of 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) recommend treatment with antibiotics when the 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 those 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 on 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.

The Johns Hopkins University

TO ASSIST PUBLIC AND PRIVATE NONPROFIT INSTITUTIONS AND INDIVIDUALS TO ESTABLISH, EXPAND AND IMPROVE BIOMEDICAL RESEARCH AND RESEARCH TRAINING IN INFECTIOUS DISEASES AND RELATED AREAS, TO CONDUCT DEVELOPMENTAL RESEARCH, TO PRODUCE AND TEST RESEARCH MATERIALS. TO ASSIST PUBLIC, PRIVATE AND COMMERCIAL INSTITUTIONS TO CONDUCT DEVELOPMENTAL RESEARCH, TO PRODUCE AND TEST RESEARCH MATERIALS, TO PROVIDE RESEARCH SERVICES AS REQUIRED BY THE AGENCY FOR PROGRAMS IN INFECTIOUS DISEASES, AND CONTROLLING DISEASE CAUSED BY INFECTIOUS OR PARASITIC AGENTS, ALLERGIC AND IMMUNOLOGIC DISEASES AND RELATED AREAS. PROJECTS RANGE FROM STUDIES OF MICROBIAL PHYSIOLOGY AND ANTIGENIC STRUCTURE TO COLLABORATIVE TRIALS OF EXPERIMENTAL DRUGS AND VACCINES, MECHANISMS OF RESISTANCE TO ANTIBIOTICS AS WELL AS RESEARCH DEALING WITH EPIDEMIOLOGICAL OBSERVATIONS IN HOSPITALIZED PATIENTS OR COMMUNITY POPULATIONS AND PROGRESS IN ALLERGIC AND IMMUNOLOGIC DISEASES. BECAUSE OF THIS DUAL FOCUS, THE PROGRAM ENCOMPASSES BOTH BASIC RESEARCH AND CLINICAL RESEARCH. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM EXPANDS AND IMPROVES PRIVATE SECTOR PARTICIPATION IN BIOMEDICAL RESEARCH. THE SBIR PROGRAM INTENDS TO INCREASE AND FACILITATE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. THE SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM STIMULATES AND FOSTERS SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. RESEARCH CAREER DEVELOPMENT AWARDS SUPPORT THE DEVELOPMENT OF SCIENTISTS DURING THE FORMATIVE STAGES OF THEIR CAREERS. INDIVIDUAL NATIONAL RESEARCH SERVICE AWARDS (NRSAS) ARE MADE DIRECTLY TO APPROVE APPLICANTS FOR RESEARCH TRAINING IN SPECIFIED BIOMEDICAL SHORTAGE AREAS. IN ADDITION, INSTITUTIONAL NATIONAL RESEARCH SERVICE AWARDS ARE MADE TO ENABLE INSTITUTIONS TO SELECT AND MAKE AWARDS TO INDIVIDUALS TO RECEIVE TRAINING UNDER THE AEGIS OF THEIR INSTITUTIONAL PROGRAM.

93.855 - Allergy and Infectious Diseases Research

National Institute of Allergy and Infectious Diseases (NIAID) [HHS - NIH]

Baltimore, Maryland 212052103 United States

Single Zip Code

NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-20-185)

Amendment Since initial award the total obligations have increased 798% from $406,753 to $3,651,470.