Typhoid FeverNCT04801602
Commercial Typhoid Tests Validation Trial
An observational study of Typhoid Fever, run by Foundation for Innovative New Diagnostics, Switzerland at 2 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 2 to 65 years
- Conditions the study is for
- Typhoid Fever
- What is being tested?
- Rapid diagnostic tests
- How many people
- 3,091 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 25 Oct 2020to 31 Dec 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
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
Who may be able to join
- - 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)
Who cannot join
- 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
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
Official title: Comparative Study of Commercially Available Typhoid Point of Care Tests to Benchmark Current and Emerging Tools
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.
Read the 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.
- Conditions
- Typhoid Fever
- Being tested
- Rapid diagnostic tests
- Keywords
- Typhoid, Enteric Fever, RDTs, Widal test
- Medical subject headings
- Typhoid Fever
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rapid diagnostic testsDiagnostic 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.
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6-10 months
Secondary outcomes (2)
Establish a biorepository of well characterized specimen collection that can be used to evaluate emerging tests.
does not require any statistical analysis
Measured: 5 years
Evaluation of operational characteristics of different RDTs including invalid and indeterminate rates
The number of indeterminate and invalid test results will be reported for each RDT, together with the relative percentage over the total number of tests performed.
Measured: 6-10 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Mar 2021
- Study start25 Oct 2020
- Primary completion30 Sep 2021
- Study completion31 Dec 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Typhoid FeverStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 3,091 participants (actual)
Sponsor and investigators
- Lead sponsor
- Foundation for Innovative New Diagnostics, Switzerland
- Sponsor type
- University, hospital or other
- Collaborators
- Department for International Development, United Kingdom
- Responsible party
- Sponsor
- Investigators
- Rumina Hasan, M.D, Principal investigator, AKURobert S Onsare, PhD, Principal investigator, Kenya Medical Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04801602
- Sponsor's protocol ID
- FE006
- Status last verified
- May 2022
- First submitted
- 12 Mar 2021
- Last updated
- 24 May 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Hasan R, Azizullah Z, Shams H, Dittrich S, Andrews JR, Charles RC, Esfandiari J, Gunasekera D, Tetteh KK, Sapkota J. Evaluation of a point-of-care multiplex immunochromatographic assay for the diagnosis of typhoid: results from a retrospective diagnostic accuracy study. J Clin Microbiol. 2024 Oct 16;62(10):e0042824. doi: 10.1128/jcm.00428-24. Epub 2024 Sep 20.
PubMed 39302169Sapkota 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.
PubMed 36448816
Study at a glance
From the registry record, last updated by the sponsor on 24 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparative Study of Commercially Available Typhoid Point of Care Tests to Benchmark Current and Emerging Tools
- ClinicalTrials.gov ID
- NCT04801602
- Acronym / sponsor ID
- FE006
- Conditions
- Typhoid Fever
- Keywords
- Typhoid, Enteric Fever, RDTs, Widal test
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 3,091 participants (actual)
- Lead sponsor
- Foundation for Innovative New Diagnostics, SwitzerlandUniversity, hospital or other
- Collaborators
- Department for International Development, United Kingdom
- Study start
- 25 Oct 2020 (actual)
- Primary completion
- 30 Sep 2021 (actual)
- Study completion
- 31 Dec 2021 (actual)
- First posted
- 17 Mar 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 2 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- 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
Key inclusion criteria (8 listed)
- - 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:
Key exclusion criteria (6 listed)
- Unwillingness to participate in the study
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Rapid diagnostic testsTo evaluate different RDTs that are commercially available internationally for detecting antigens or antibodies to Salmonella Typhi and use blood culture as standard for comparison. | Diagnostic test | – |
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.
Time frame: 6-10 months
Estimates of sensitivity and specificity will be calculated based on the definitions; 95% confidence intervals will be calculated using Wilson's score method.
2 secondary outcomes
Establish a biorepository of well characterized specimen collection that can be used to evaluate emerging tests.
Time frame: 5 years
Evaluation of operational characteristics of different RDTs including invalid and indeterminate rates
Time frame: 6-10 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 May 2022.
- Derived from this study: PubMed 39302169Hasan R, Azizullah Z, Shams H, Dittrich S, Andrews JR, Charles RC, Esfandiari J, Gunasekera D, Tetteh KK, Sapkota J. Evaluation of a point-of-care multiplex immunochromatographic assay for the diagnosis of typhoid: results from a retrospective diagnostic accuracy study. J Clin Microbiol. 2024 Oct 16;62(10):e0042824. doi: 10.1128/jcm.00428-24. Epub 2024 Sep 20.
- Derived from this study: PubMed 36448816Sapkota 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rumina Hasan, M.D principal investigator
AKU
Robert S Onsare, PhD principal investigator
Kenya Medical Research Institute
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Typhoid Fever, run by Foundation for Innovative New Diagnostics, Switzerland at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 May 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Kenya, Pakistan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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. (time frame: 6-10 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04801602, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 May 2022.