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 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.
|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|
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