Commercial Typhoid Tests Validation Trial

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

Commercial Typhoid Tests Validation Trial

Official Title

Comparative Study of Commercially Available Typhoid Point of Care Tests to Benchmark Current and Emerging Tools

Brief Summary

      Typhoid fever (typhoid) is an enteric bacterial infection caused by Salmonella enterica
      serovar Typhi (Salmonella Typhi; S. Typhi). It is one of the most common bacterial causes of
      acute febrile illness in the developing world, with an estimated 10.9 million new cases
      worldwide and 116.8 thousand deaths in 2017. Like many febrile illnesses, typhoid presents
      with non-specific symptoms and signs, especially in its early stages. In routine healthcare
      settings in low- and middle-income countries (LMIC), typhoid fever is commonly suspected and
      treated empirically with antibiotics. This overuse of antibiotics creates a selective
      pressure for the development of antimicrobial resistance (AMR), that has resulted in the
      emergence and spread of typhoid strains that are resistant to all first-line antibiotics.
      Similarly, the low specificity of current rapid diagnostic tests (RDTs) can lead to an over
      diagnosis of typhoid fever that may result in the overuse of antibiotics and delay the proper
      treatment for underlying conditions. FIND in collaboration with international typhoid experts
      developed a target product profile outlining the ideal characteristics of point of care
      tests. As part of this activity it became apparent that no quality data are available that
      systematically compare all available commercially point of care tests against the same set of
      reference standards used in multiple populations (e.g. Africa vs Asia). This lack of
      benchmarking data significantly impedes health provider's ability to decide on the utility of
      commercial tests in different settings, ultimately restricting use and access. Further the
      lack of well characterized samples reduces the ability for targeted innovation in the typhoid
      space.

      The current study aims to benchmark different commercial typhoid tests against a defined
      reference standard applied in multiple population and simultaneously develop a sample set
      that can be used in future evaluations of emerging technologies and/or to support innovative
      test development.
    

Detailed Description

      Typhoid is an enteric disease caused by the bacterium Salmonella Typhi; it is estimated that
      11 to 20 million people contract typhoid each year and 128 000 to 161 000 die from the
      disease; children under 5 are at higher risk of contracting the disease.

      Typhoid endemic areas are located mainly in South Asia and Sub-Saharan Africa and is
      transmitted through contaminated water and food. The disease is treatable with a specific
      antibiotics regimen, however antimicrobial resistance has been reported in several countries,
      particularly in Pakistan.Several vaccines have been developed but their uptake has been low,
      partly due to limited information on the exact burden of the disease in endemic countries.

      The symptoms of typhoid are similar to other undifferentiated febrile illnesses and typhoid
      can be mistaken with vector borne febrile illnesses such as scrub typhus.

      Blood and bone marrow cultures are considered the gold standard for the diagnosis of typhoid.
      Those methods require specific infrastructure and skilled staff that are not always available
      in LMICs and are not adequate for rapid patient management. In addition, although very
      specific, blood culture sensitivity is impacted by misuse of antibiotics that lower the
      bacterial load to undetectable levels in patients' blood.

      As a consequence, alternatives to blood culture have been used in LMIC. The Widal test is the
      most used test despite a low performance (sensitivity range: 57-34%; specificity range:
      43-83%;reported in several studies. Other options in typhoid diagnosis are rapid diagnostic
      tests; among them, three tests (Typhidot, Tubex and Test-it™ Typhoid IgM) have been evaluated
      in several studies. It has been reported a variability of tests performance in different
      studies and according to the geographical regions. Variability in the test performance
      reported so far in the literature has hampered WHO to recommend any of these rapid tests in
      the EDL. FIND in collaboration with international typhoid experts developed a target product
      profile outlining the ideal characteristics of point of care tests. As part of this activity
      it became apparent that no quality data are available that systematically compare all
      available commercially point of care tests against the same set of reference standards used
      in multiple populations (e.g. Africa vs Asia). These lack of benchmarking data significantly
      impedes health providers' ability to decide on the utility of commercial tests in different
      settings, ultimately restricting use and access. Further the lack of well characterized
      samples reduces the ability for targeted innovation in the typhoid space. A second gap that
      was identified was the lack of a simple well-performing gold standard suggesting Latent class
      modelling as a solution used for other pathogens with an imperfect gold standard.

      The current study aims to benchmark different commercial typhoid tests against a defined
      reference standard applied in multiple population and simultaneously develop a sample set
      that can be used in future evaluations of emerging technologies and/or to support innovative
      test development.
    


Study Type

Observational


Primary Outcome

To evaluate different RDTs that are commercially available internationally for detecting antigens or antibodies to Salmonella Typhi and use blood culture as standard for comparison.

Secondary Outcome

 Establish a biorepository of well characterized specimen collection that can be used to evaluate emerging tests.

Condition

Typhoid Fever

Intervention

Rapid diagnostic tests


Publications

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

Recruitment Information


Recruitment Status

Diagnostic Test

Estimated Enrollment

4900

Start Date

October 25, 2020

Completion Date

September 25, 2021

Primary Completion Date

July 25, 2021

Eligibility Criteria

        Inclusion Criteria:

          -  - Individuals aged 8 years of age to 65 years of age

          -  Body weight equals to or more than 8kgs

          -  History of fever or axillary temperature of >37.50C for at least 3 consecutive days
             within the last 7 days prior to enrolment

          -  Clinical suspicion of enteric fever

          -  One of the following scenarios:

               -  Presents to outpatient department or Emergency Department

               -  Admitted to hospital within last 12 hours

          -  Able and willing to provide informed consent (and assent when required)

        Exclusion Criteria:

          -  Unwillingness to participate in the study

               -  Inability to provide the required volume of blood

               -  Unwillingness to provide blood

               -  Known non-infectious / Non typhoid Infectious causes of fever or other alternate
                  diagnosis of fever

               -  Taking anticoagulant drugs

               -  Unconscious
      

Gender

All

Ages

2 Years - 65 Years

Accepts Healthy Volunteers

No

Contacts

, 9779851182704, [email protected]

Location Countries

Kenya

Location Countries

Kenya

Administrative Informations


NCT ID

NCT04801602

Organization ID

FE006


Responsible Party

Sponsor

Study Sponsor

Foundation for Innovative New Diagnostics, Switzerland

Collaborators

 Department for International Development, United Kingdom

Study Sponsor

, , 


Verification Date

March 2021