Clinical Trials Logo

Clinical Trial 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.


Clinical Trial Description

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. The 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. The 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. A bacteremia surveillance system was established in central Nigeria in 2008; a pilot study was initiated from a small cohort from this system composed of children with typhoid fever. 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, it is hypothesized that distinct classifier genes and proteins based on host response in the peripheral blood and serum can be obtained to discriminate typhoid fever from other bacteremic infections and healthy controls. Specific aims: 1. Define typhoid fever-specific host response classifier genes using gene expression (GE) micro-arrays, 2. Discover specific serum anti-typhoid fever proteins using newly established S. Typhi proteome micro-arrays and develop prototype serologic assay for acute typhoid (ELISA) 3. Validate classifier genes and field-test prototype ELISAs using new, independent cohorts. To accomplish these objectives, a multidisciplinary team with expertise in infectious disease, immunology, molecular genomics/proteomics, micro-arrays, and bioinformatics has been assembled to ensure success of this project. These studies will identify distinct classifier genes and proteins of typhoid fever infection based on immunological responses. Classifiers that discriminate S. Typhi from other bacteremia are possible to develop and offer rapid, inexpensive, non-invasive, and sensitive molecular diagnostic assays specific for typhoid fever. Classifier proteins obtained from the new, custom whole-proteome typhoid fever micro-arrays will provide new insights of targeted proteins and antibodies for next-generation vaccine development. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT02947295
Study type Observational
Source University of Nebraska
Contact
Status Completed
Phase
Start date September 13, 2012
Completion date March 1, 2017

See also
  Status Clinical Trial Phase
Completed NCT04830371 - Non-inferiority and Safety Study of EuTCV Compared to Typbar-TCV in Healthy 6 Months-45 Years Aged Participants Phase 2/Phase 3
Recruiting NCT04543877 - WHNRC (Western Human Nutrition Research Center) Fiber Intervention Study Early Phase 1
Completed NCT02324751 - Vaccines Against Salmonella Typhi Phase 2
Completed NCT01421693 - Gatifloxacin Versus Ceftriaxone in the Treatment of Enteric Fever Phase 4
Completed NCT05579821 - Evaluation Study of DPP® Typhoid Assay
Completed NCT01405521 - Understanding Typhoid Disease After Vaccination Phase 2
Completed NCT00386789 - Long Term Protection by and Persistence of Vi Antibodies Induced by Vi-rEPA Conjugate Vaccines in Vietnamese Children Injected at 2-5 Years or at 5-8 Years of Age N/A
Completed NCT04801602 - Commercial Typhoid Tests Validation Trial
Recruiting NCT06104345 - Immune Response Elicited by Concomitant Administration of Oral Typhoid Fever (Vivotif®) and Cholera (Dukoral®) Vaccines Phase 4
Completed NCT01438996 - Extension Study of H01_04TP to Evaluate the Booster Response Induced by Vi-CRM197 in Adults Phase 2
Completed NCT01437267 - Safety and Immunogenicity of Vi-CRM197 Vaccine Against S. Typhi in Children, Older Infants and Infants Phase 2
Completed NCT01193907 - Safety and Immunogenicity of Three Formulations of Vi-CRM197 Vaccine Against S. Typhi in Adults (18-40 Years Old) Phase 2
Recruiting NCT04349826 - The Azithromycin and Cefixime Treatment of Typhoid in South Asia Trial (ACT-South Asia Trial) Phase 4
Completed NCT01608815 - Study of a Single Dose of SP093 Typhoid Vi Polysaccharide Vaccine in Japanese Subjects Phase 3
Completed NCT01123941 - Safety and Immunogenicity of Vi-CRM197 Vaccine Against S. Typhi in Adult (18-40 Years Old) Phase 1
Recruiting NCT05500482 - Vellore Typhoid Vaccine Impact Trial Phase 4
Completed NCT03926455 - Safety and Immunogenicity of Typhax, a Typhoid Vaccine Phase 1
Completed NCT01229176 - Safety and Immunogenicity of Vi-CRM197 Vaccine Against S. Typhi in Adults, Children, Older Infants and Infants Phase 2
Completed NCT03956524 - Safety and Tolerability of Typhoid Conjugate Vaccine (EuTCV) in Healthy Adults Phase 1
Completed NCT04154722 - Comparison of Two Drugs Regimen in Treatment of Complicated Typhoid Fever in Children Phase 4