Global Genomic and Proteomic Profiling of African Children With Typhoid Fever

Typhoid Fever Clinical Trial

Official title:

Global Genomic and Proteomic Profiling of African Children With Typhoid Fever

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02947295
• Other study ID #: 0445-12 EP
• Status: Completed
• Start date: September 13, 2012
• Est. completion date: March 1, 2017

Study information

• Verified date: September 2023
• Source: University of Nebraska
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 969
• Est. completion date: March 1, 2017
• Est. primary completion date: March 1, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Minute to 14 Years

Eligibility

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.

Related Conditions & MeSH terms

• Fever
• Typhoid Fever

Locations

Country	Name	City	State
Nigeria	National Hospital of Nigeria	Abuja

Sponsors (1)

Lead Sponsor	Collaborator
University of Nebraska

Country where clinical trial is conducted

Nigeria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Typhoid fever-specific host response classifier genes	Define typhoid fever-specific host response classifier genes using gene expression (GE) micro-arrays.	10 years
Primary	Serum anti-typhoid fever proteins	Discover specific serum anti-typhoid fever proteins using newly established S. Typhi proteome micro-arrays and develop prototype serologic assay for acute typhoid (ELISA)	10 years
Primary	Validate classifier genes and field-test prototype ELISAs	Validate classifier genes and field-test prototype ELISAs using new, independent cohorts.	10 years