Clinical Trial: Global Genomic and Proteomic Profiling of African Children With Typhoid Fever

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational

Official Title: Global Genomic and Proteomic Profiling of African Children With Typhoid Fever

Brief Summary: To develop a rapid, sensitive, and inexpensive diagnostic method, as well as more efficacious vaccine, for countries where typhoid fever remains a major public health burden.

Detailed Summary:

Typhoid fever is caused by Salmonella enteric serovar Typhi (S. typhi), a human specific pathogen. The World Health Organization (WHO) recognizes typhoid fever as a global health problem, with an estimated 21 million cases and 200,000-600,000 deaths annually. In Africa and South Asia, young children represent a subgroup with the highest disease burden. The onset of the illness is insidious and clinical diagnosis is often unreliable. Definitive diagnosis through blood or bone-marrow culture is labor-intensive, expensive, and invasive, with a sensitivity of 40 to 70%. WHO recommends routine typhoid fever vaccination but currently licensed vaccines provide only 55-75% protection against the disease. Therefore, there is an urgent need to develop rapid, sensitive, and inexpensive diagnostic methods, as well as more efficacious vaccines for countries where typhoid fever remains a major public health burden. Our long term goals are 1) to develop innovative molecular diagnostic assays for rapid and inexpensive detection of typhoid fever and, 2) to better understand the molecular mechanisms of host response to facilitate the development of next-generation typhoid fever vaccines. Our immediate objective is to obtain global gene expression and proteomic profiles of S. Typhi infected African children, identify and validate the classifier genes and proteins as potential diagnostic biomarkers and vaccine targets. We have already established a bacteremia surveillance system in central Nigeria since 2008. A pilot study was initiated from a small cohort of Nigerian children with typhoid fever. Our preliminary data showed unique gene expression profiles of host response in peripheral blood of children with typhoid fever compared with other bacteremic infections, as well as patients in acute vs. convalescent phase. Here, we hypothesize that distinct classifier genes and proteins based on host response in the peripheral blood and serum can
Sponsor: University of Nebraska

Current Primary Outcome:

  • Define typhoid fever-specific host response classifier genes using gene expression (GE) micro-arrays. [ Time Frame: 10 years ]
  • Discover specific serum anti-typhoid fever proteins using newly established S. Typhi proteome micro-arrays and develop prototype serologic assay for acute typhoid (ELISA) [ Time Frame: 10 years ]
  • Validate classifier genes and field-test prototype ELISAs using new, independent cohorts. [ Time Frame: 10 years ]


Original Primary Outcome: Same as current

Current Secondary Outcome:

Original Secondary Outcome:

Information By: University of Nebraska

Dates:
Date Received: December 1, 2014
Date Started: September 2012
Date Completion: September 2018
Last Updated: October 25, 2016
Last Verified: October 2016