This proposal is for a five year K08 Mentored Clinical Scientist Research Development Award for Daniel T. Leung, M.D., M.Sc. This candidate completed a clinical fellowship in Infectious Diseases at Beth Israel Deaconess Medical Center, and has entered post-doctoral research training in the laboratory of Dr. Edward T. Ryan in the Division of Infectious Diseases at Massachusetts General Hospital (MGH). The proposed training plan, with Dr. Ryan as primary mentor, will include both didactic and practical training focused on immune responses of Vibrio cholera infection in children. This research builds upon a longstanding collaboration between MGH and the International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B). Dr. Firdausi Qadri, Director of Center for Vaccine Sciences at ICDDR,B, will provide co-mentorship to the applicant. Dr. Stephen B. Calderwood, Professor and Chief of ID at MGH will chair the Training Advisory Group. Cholera is an acute dehydrating diarrheal disease caused by Vibrio cholera, endemic in over 50 countries, and affecting 2 to 3 million people each year, causing more than 100,000 deaths. In endemic areas, children under 5 years of age have a high burden of disease. Despite this, currently available cholera vaccines achieve a lower efficacy and a shorter duration of protection in young children compared to that achieved in adults. Even in adults, immunity after vaccination is short-lived. In comparison, protective immunity after natural infection lasts for several years, and duration of protection in young children is thought to be comparable to that of adults. The mediators and mechanism of protective immune response to cholera in children remain poorly understood. The candidate has spent the last 24 months beginning to address this deficiency, has moved to Bangladesh, and has begun to characterize the acute and convalescent immune- responses to cholera infection and vaccination in children in Dhaka, Bangladesh. In this application, the applicant now proposes a K08 career development program that extends these studies, and builds upon ongoing and fully approved NIAID and SIDA/SAREC supported projects. This career development program would assist the candidate in his development into an independent biomedical investigator, would improve our understanding of host- pathogen events during a human restricted infection of global significance, and could lead to a long acting and protective improved cholera vaccine for children, the population that bears the largest global burden of cholera.

Public Health Relevance

/ Public Health Relevance Cholera is a diarrheal disease affecting millions of people worldwide each year. Compared to natural infection, current oral cholera vaccines provide relatively short-term protection, especially in young children who bear the largest global burden of cholera. We propose a career development program that focuses on advancing our understanding of immune responses to cholera infection and vaccination in children in Bangladesh; such knowledge could lead to an improved cholera vaccine.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Clinical Investigator Award (CIA) (K08)
Project #
Application #
Study Section
Microbiology and Infectious Diseases B Subcommittee (MID)
Program Officer
Hall, Robert H
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Utah
Internal Medicine/Medicine
Schools of Medicine
Salt Lake City
United States
Zip Code
Bliss, Jesse; Bouhenia, Malika; Hale, Peter et al. (2018) High Prevalence of Shigella or Enteroinvasive Escherichia coli Carriage among Residents of an Internally Displaced Persons Camp in South Sudan. Am J Trop Med Hyg 98:595-597
Schlaberg, Robert; Barrett, Amanda; Edes, Kornelia et al. (2018) Fecal Host Transcriptomics for Non-Invasive Human Mucosal Immune Profiling: Proof of Concept in Clostridium Difficile Infection. Pathog Immun 3:164-180
Andrews, Jason R; Leung, Daniel T; Ahmed, Shahnawaz et al. (2017) Determinants of severe dehydration from diarrheal disease at hospital presentation: Evidence from 22 years of admissions in Bangladesh. PLoS Negl Trop Dis 11:e0005512
Bennett, Michael S; Trivedi, Shubhanshi; Iyer, Anita S et al. (2017) Human mucosal-associated invariant T (MAIT) cells possess capacity for B cell help. J Leukoc Biol 102:1261-1269
Azman, Andrew S; Bouhenia, Malika; Iyer, Anita S et al. (2017) High Hepatitis E Seroprevalence Among Displaced Persons in South Sudan. Am J Trop Med Hyg 96:1296-1301
Charles, Richelle C; Nakajima, Rie; Liang, Li et al. (2017) Plasma and Mucosal Immunoglobulin M, Immunoglobulin A, and Immunoglobulin G Responses to the Vibrio cholerae O1 Protein Immunome in Adults With Cholera in Bangladesh. J Infect Dis 216:125-134
Gruninger, Randon J; Johnson, Russell A; Das, Sumon K et al. (2017) Socioeconomic Determinants of Cipro-floxacin-Resistant Shigella Infections in Bangladeshi Children. Pathog Immun 2:89-101
Giddings, Stanley L; Stevens, A Michal; Leung, Daniel T (2016) Traveler's Diarrhea. Med Clin North Am 100:317-30
Leung, Daniel T; Chisti, Mohammod J; Pavia, Andrew T (2016) Prevention and Control of Childhood Pneumonia and Diarrhea. Pediatr Clin North Am 63:67-79
Uddin, Muhammad Ikhtear; Islam, Shahidul; Nishat, Naoshin S et al. (2016) Biomarkers of Environmental Enteropathy are Positively Associated with Immune Responses to an Oral Cholera Vaccine in Bangladeshi Children. PLoS Negl Trop Dis 10:e0005039

Showing the most recent 10 out of 33 publications