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Trial record 7 of 249 for:    Recruiting, Not yet recruiting, Available Studies | "Fever"

Global Genomic and Proteomic Profiling of African Children With Typhoid Fever

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ClinicalTrials.gov Identifier: NCT02947295
Recruitment Status : Recruiting
First Posted : October 27, 2016
Last Update Posted : September 28, 2017
Sponsor:
Information provided by (Responsible Party):
Stephen Obaro, MD, University of Nebraska

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.

Condition or disease
Typhoid Fever

Detailed 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 Type : Observational
Estimated Enrollment : 192 participants
Observational Model: Ecologic or Community
Time Perspective: Prospective
Official Title: Global Genomic and Proteomic Profiling of African Children With Typhoid Fever
Study Start Date : September 2012
Estimated Primary Completion Date : September 2018
Estimated Study Completion Date : September 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Fever




Primary Outcome Measures :
  1. Define typhoid fever-specific host response classifier genes using gene expression (GE) micro-arrays. [ Time Frame: 10 years ]
  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) [ Time Frame: 10 years ]
  3. Validate classifier genes and field-test prototype ELISAs using new, independent cohorts. [ Time Frame: 10 years ]

Biospecimen Retention:   Samples With DNA
Blood, urine, stool, nasopharyngeal swab/aspirate as well as cerebrospinal fluid (CSF), pleural fluid, induced sputum, gastric aspirates or synovial fluid with clinical indication.


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Ages Eligible for Study:   up to 14 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Children 1-14 years old who present with an acute febrile illness that is clinically suggestive of bacteremia.
Criteria

Inclusion Criteria:

  • Children ages 1-14 years who present with an acute febrile illness that is clinically suggestive of bacteremia.

Exclusion Criteria:

  • Children who have underlying conditions that are recognized to increase susceptibility to invasive salmonellosis. Other conditions that are associated with frequent opportunistic infections that may cause aberrations of immune function will also be excluded, such as human immunodeficiency virus (HIV) infection and malnutrition. Clinical conditions that are known to be associated with increased risk of salmonella carriage will also be excluded, such as schistosomiasis.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02947295


Contacts
Contact: Stephen Obaro, MD 517-706-9001 stephen.obaro@unmc.edu

Locations
Nigeria
National Hospital of Nigeria Recruiting
Abuja, Nigeria
Contact: Stephen Obaro, MD    517-706-9001    stephen.obaro@unmc.edu   
Sponsors and Collaborators
University of Nebraska
Investigators
Principal Investigator: Stephen Obaro, MD Univeristy of Nebraska Medical Center

Responsible Party: Stephen Obaro, MD, Professor, Pediatric International Research Director, University of Nebraska
ClinicalTrials.gov Identifier: NCT02947295     History of Changes
Other Study ID Numbers: 445-12 EP
First Posted: October 27, 2016    Key Record Dates
Last Update Posted: September 28, 2017
Last Verified: September 2017

Additional relevant MeSH terms:
Fever
Typhoid Fever
Body Temperature Changes
Signs and Symptoms
Salmonella Infections
Enterobacteriaceae Infections
Gram-Negative Bacterial Infections
Bacterial Infections