Commercial Typhoid Tests Validation

Study Overview
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Brief Summary
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The study aims to perform a head to head comparison of 11 typhoid tests currently in the market and simultaneously develop a sample set that can be used in future evaluations of emerging technologies. The central objective is to evaluate different Typhoid Rapid Diagnostic Tests (RDTs) that are commercially available internationally for detecting antigens or antibodies to Salmonella Typhi and use Blood culture as standard for comparison. The end point will be to determine estimates of sensitivity and specificity for each test, with 95% confidence interval, using blood culture as reference.

Detailed Description
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Typhoid fever is an enteric bacterial infection caused by Salmonella enterica serovar Typhi (Salmonella Typhi; S. Typhi). It is an important infectious disease in low- and middle-income countries with over 10.9 million new cases worldwide and 116.8 thousand death in 2017. South Asia and Sub Saharan Africa are the most affected areas of the world. Typhoid fever is common in areas with inadequate sanitation and hygiene. In routine practice, diagnosis of typhoid fever is rarely confirmed as diagnostic tests are unavailable or have limited diagnostic accuracy. Blood culture is the commonest reference standard test but has a lower sensitivity. Alternatives to those methods exist but their performance is poor. The Widal test is still used but as it is based on cross-reactive antigens, it lacks sensitivity and specificity. Clinician often use rapid diagnostic tests to diagnose typhoid. A number of typhoid fever RDTs are commercially available but performance data are not available or not consistent from a study to another. This prospective, multicentre, cross-sectional study will be carried out in 3 hospitals of Nairobi, Kenya. 2000 clinically suspected typhoid cases will be enrolled in this study, blood culture as well as serum for RDT will be received. All typhoid positive and equal typhoid negative serum will be tested for investigational RDTs. This collaborative study between Kenya Medical Research Institute (KEMRI) and Foundation for Innovative New Diagnostics (FIND) will systematically compare different point of care typhoid tests currently available in the market against the same set of reference standard. The knowledge gained from this trial may benefit health providers' by providing information on diagnostic accuracy of current typhoid test and to decide on utility of these commercial tests. The result obtained from this trial will also be made available to help inform Ministry of Health in Kenya and the World Health Organization (WHO) Essential Diagnostic list (EDL) and stakeholder decision making more broadly.

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

Conditions
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Typhoid Fever

Intervention / Treatment
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* Diagnostic Test: 1. SD Bioline Salmonella Typhi IgG/IgM Fast test, 2. Typhidot Rapid IgG/IgM combo test, 3. TUBEX TF test, 4.Typhoid IgG/IgM Combo Rapid Test CE, 5. Enterocheck WB test, 6. Test-itTM Typhoid IgM test


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Individuals aged 8 years of age to 65 years of age History of fever or axillary temperature of >37.5 °C for at least 3 consecutive days within the last 7 days prior to enrollment 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

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Diagnostic Test: 1. SD Bioline Salmonella Typhi IgG/IgM Fast test, 2. Typhidot Rapid IgG/IgM combo test, 3. TUBEX TF test, 4.Typhoid IgG/IgM Combo Rapid Test CE, 5. Enterocheck WB test, 6. Test-itTM Typhoid IgM test|Evaluation of 11 different Typhoid Rapid Diagnostic Tests that are commercially available internationally and use Blood culture as standard for comparison|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Point estimates of sensitivity and specificity for each test, with 95% confidence interval, using blood culture as reference standard. | Evaluation of different Rapid Diagnostic Tests (RDTs) that are commercially available internationally for detecting antigens or antibodies to Salmonella Typhi and use Blood culture as standard for comparison. | At the end of the 6-month sampling period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Establishment of a bio repository of well characterized specimen collection at the site available for future assessments of emerging technologies | Establishment of a bio repository of well characterized specimen collection that can be used to evaluate emerging tests. | At the end of the 6-month sampling period | 
| Estimates of operational characteristics of different RDTs based on quantitative assessment including invalid and indeterminate rates | Evaluation of operational characteristics (invalid and indeterminate rates) of Typhoid RDTs | At the end of the 6-month sampling period |