Commercial Typhoid Tests Validation Trial

NCT04801602 | Completed

• 1 other identifier: FE006
• Study Type: observational
• Target: 3,091
• Locations: 2 countries
• Sites: 2

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.

Conditions

Typhoid Fever

Keywords

Typhoid; Enteric Fever; RDTs; Widal test

Outcome Measures

Primary Outcomes (1)

• 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.

  Estimates of sensitivity and specificity will be calculated based on the definitions; 95% confidence intervals will be calculated using Wilson's score method.

  6-10 months

Secondary Outcomes (2)

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

  5 years

• Evaluation of operational characteristics of different RDTs including invalid and indeterminate rates

  6-10 months

Interventions

Rapid diagnostic tests DIAGNOSTIC_TEST

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.

Eligibility Criteria

• Age: 2 Years - 65 Years
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

The trial population will be composed of adults and children suspected of typhoid between 2-65 years of age. Participants will be recruited when they present to Aga Khan University or its collection site and 3 different hospitals at Nairobi, Kenya

You may qualify if:

• \- 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Foundation for Innovative New Diagnostics, Switzerland: lead
• Department for International Development, United Kingdom: collaborator

Study Sites (2)

KEMRI

Nairobi, Kenya

Location

Aga Khan University

Karachi, Sindh, Pakistan

Location

Related Publications (1)

• Sapkota J, Hasan R, Onsare R, Arafah S, Kariuki S, Shakoor S, Qamar F, Mundalo S, Njeru F, Too R, Ndegwa E, Andrews JR, Dittrich S. Comparative Analysis of Commercially Available Typhoid Point-of-Care Tests: Results of a Prospective and Hybrid Retrospective Multicenter Diagnostic Accuracy Study in Kenya and Pakistan. J Clin Microbiol. 2022 Dec 21;60(12):e0100022. doi: 10.1128/jcm.01000-22. Epub 2022 Nov 30.

  PMID: 36448816 DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

Serum samples are stored

MeSH Terms

Conditions

Typhoid Fever

Interventions

Rapid Diagnostic Tests

Condition Hierarchy (Ancestors)

Salmonella Infections; Enterobacteriaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Point-of-Care Testing; Point-of-Care Systems; Patient Care Management; Health Services Administration

Study Officials

• Rumina Hasan, M.D

  AKU

  PRINCIPAL INVESTIGATOR

• Robert S Onsare, PhD

  Kenya Medical Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 12, 2021
• First Posted: March 17, 2021
• Study Start: October 25, 2020
• Primary Completion: September 30, 2021
• Study Completion: December 31, 2021
• Last Updated: May 24, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

KE (1); PA (1)