Global Genomic and Proteomic Profiling of African Children With Typhoid Fever

Learn more about:
Related Clinical Trial
Transcriptomic Responses for the Identification of Pathogens Evaluation of Typhoid Conjugate Vaccine Effectiveness in Ghana Non-inferiority and Safety Study of EuTCV Compared to Typbar-TCV in Healthy 6 Months-45 Years Aged Participants Commercial Typhoid Tests Validation Trial Commercial Typhoid Tests Validation WHNRC (Western Human Nutrition Research Center) Fiber Intervention Study The Azithromycin and Cefixime Treatment of Typhoid in South Asia Trial (ACT-South Asia Trial) Phase 4 Study To Assess The Safety Of Vivotif At Different Release Titers Among Travelers Extension Study of H01_04TP to Evaluate the Booster Response Induced by Vi-CRM197 in Adults Safety and Immunogenicity of Three Formulations of Vi-CRM197 Vaccine Against S. Typhi in Adults (18-40 Years Old) Safety and Immunogenicity of Vi-CRM197 Vaccine Against S. Typhi in Adult (18-40 Years Old) Effects of Aging on Primary and Secondary Vaccine Responses in a 15-Year Longitudinal Cohort Safety and Immunogenicity of Typhax, a Typhoid Vaccine Safety and Tolerability of Typhoid Conjugate Vaccine (EuTCV) in Healthy Adults Immune Equivalence Between Multi-dose and Single Dose Formulation of Vi-DT and Their Overall Safety (Phase III) Investigating Enteric Fever – Salmonella Typhi and Paratyphi Challenge Study Induction of Gut Permeability by an Oral Vaccine Studies of Immune Responses to Orally Administered Vaccines in Developing Country 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 Salmonella Typhi Vi O-Acetyl Pectin-rEPA Conjugate Vaccine Safety and Immunogenicity of Vi-CRM197 Vaccine Against S. Typhi in Adults, Children, Older Infants and Infants Safety and Immunogenicity of Vi-CRM197 Vaccine Against S. Typhi in Children, Older Infants and Infants Typhoid Fever: Combined vs. Single Antibiotic Therapy Vaccines Against Salmonella Typhi Immune Non-inferiority and Safety of a Vi-DT Typhoid Conjugate Vaccine Dose Ranging Study to Determine the Safety, Reactogenicity and Immunogenicity of Typhoid Fever Vaccine (Ty800) in Healthy Adult Subjects Immunogenicity, Safety and Tolerability of the Typhoid Fever Vaccine Candidate M01ZH09 in Healthy Adults CVD 909 Vi Prime Boost Study Gatifloxacin Versus Ceftriaxone in the Treatment of Enteric Fever Safety, Reactogenicity and Immunogenicity of Vi-DT;Typhoid Conjugate Vaccine Typhoid Conjugate Vaccine Introduction in Navi Mumbai, India Clinical Efficacy of Typhoid Conjugate Vaccine (Vi-TCV) Among Children Age 9 Months Through 12 Years in Blantyre, Malawi Study of a Single Dose of SP093 Typhoid Vi Polysaccharide Vaccine in Japanese Subjects Typhoid Conjugate Vaccine Trial Among Children Younger Than 2 Years in Ouagadougou, Burkina Faso Understanding Typhoid Disease After Vaccination Typhoid Vi Vaccine Effectiveness in Hechi, Guangxi, China Introduction of the Vi Polysaccharide Typhoid Vaccine in Hue City, Central Vietnam Comparison of Two Drugs Regimen in Treatment of Complicated Typhoid Fever in Children Evaluation of the Vi Polysaccharide Vaccine Against Typhoid Fever Safety and Immunogenicity of a Vi-DT Typhoid Conjugate Vaccine Combined Vi Vaccination and Health Education Program on the Burden of Typhoid in Childhood Global Genomic and Proteomic Profiling of African Children With Typhoid Fever

Brief Title

Global Genomic and Proteomic Profiling of African Children With Typhoid Fever

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 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


Primary Outcome

Define typhoid fever-specific host response classifier genes using gene expression (GE) micro-arrays.


Condition

Typhoid Fever



Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information



Estimated Enrollment

192

Start Date

September 2012

Completion Date

September 2018

Primary Completion Date

September 2018

Eligibility 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.
      

Gender

All

Ages

N/A - 14 Years

Accepts Healthy Volunteers

No

Contacts

Stephen Obaro, MD, 517-706-9001, [email protected]

Location Countries

Nigeria

Location Countries

Nigeria

Administrative Informations


NCT ID

NCT02947295

Organization ID

445-12 EP


Responsible Party

Principal Investigator

Study Sponsor

University of Nebraska


Study Sponsor

Stephen Obaro, MD, Principal Investigator, Univeristy of Nebraska Medical Center


Verification Date

September 2017