Clinical trial NCT04673487: Commercial Typhoid Tests Validation
Official title: Comparative Study of Commercially Available Typhoid Point of Care Tests to Benchmark Current and Emerging Tools
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Typhoid Fever
Lead sponsor: Kenya Medical Research Institute
Sponsor class: OTHER
Collaborators: name: Foundation for Innovative New Diagnostics (FIND)
First posted: 2020-12-17
Enrollment: 2000
Sex: ALL
Minimum age (years): 8
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The trial population will be composed of adults and children suspected of typhoid between 8-65 years of age. Participants will be recruited in 3 hospitals in Nairobi, Kenya.The three hospitals are in Nairobi County and include Mbagathi County Hospital, Mbagathi Road; Medical Missionaries of Mary, Reuben Centre Hospital in Mukuru Slum, Embakasi and City Council Clinic in Mukuru Slum, Embakasi.

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Point estimates of sensitivity and specificity for each test, with 95% confidence interval, using blood culture as reference standard.
timeFrame: At the end of the 6-month sampling period
Secondary outcomes:
measure: Establishment of a bio repository of well characterized specimen collection at the site available for future assessments of emerging technologies
timeFrame: At the end of the 6-month sampling period
measure: Estimates of operational characteristics of different RDTs based on quantitative assessment including invalid and indeterminate rates
timeFrame: At the end of the 6-month sampling period
Other outcomes:
Locations:
city: Nairobi
country: Kenya
facility: Kenya Medical Research Institute
Study officials:
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