Commercial Typhoid Tests Validation

NCT ID: NCT04673487

Last Updated: 2020-12-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

2000 participants

Study Classification

OBSERVATIONAL

Study Start Date

2021-01-31

Study Completion Date

2021-12-31

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.

Conditions

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Typhoid Fever

Study Design

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Observational Model Type

OTHER

Study Time Perspective

PROSPECTIVE

Interventions

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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

Intervention Type DIAGNOSTIC_TEST

Other Intervention Names

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7. Typhoid IgG/IgM Rapid Test Cassette 8. S.typhi-S.paratyphi "A" Direct Antigen Detection test 9. DiaquickS.typhi IgG/IgM Ab test 10. Diaquick S. typhi/paratyphi Ag cassette test 11. Widal test.

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
Minimum Eligible Age

8 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Foundation for Innovative New Diagnostics (FIND)

UNKNOWN

Sponsor Role collaborator

Kenya Medical Research Institute

OTHER

Sponsor Role lead

Responsible Party

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Dr. Robert Onsare

Dr

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Kenya Medical Research Institute

Nairobi, , Kenya

Site Status

Countries

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Kenya

Central Contacts

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Robert S Onsare, PhD

Role: CONTACT

Phone: +254722337004

Email: [email protected]

References

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Crump JA. Progress in Typhoid Fever Epidemiology. Clin Infect Dis. 2019 Feb 15;68(Suppl 1):S4-S9. doi: 10.1093/cid/ciy846.

Reference Type RESULT
PMID: 30767000 (View on PubMed)

Amicizia D, Micale RT, Pennati BM, Zangrillo F, Iovine M, Lecini E, Marchini F, Lai PL, Panatto D. Burden of typhoid fever and cholera: similarities and differences. Prevention strategies for European travelers to endemic/epidemic areas. J Prev Med Hyg. 2019 Dec 20;60(4):E271-E285. doi: 10.15167/2421-4248/jpmh2019.60.4.1333. eCollection 2019 Dec.

Reference Type RESULT
PMID: 31967084 (View on PubMed)

Ayukekbong JA, Ntemgwa M, Atabe AN. The threat of antimicrobial resistance in developing countries: causes and control strategies. Antimicrob Resist Infect Control. 2017 May 15;6:47. doi: 10.1186/s13756-017-0208-x. eCollection 2017.

Reference Type RESULT
PMID: 28515903 (View on PubMed)

Hamaguchi S, Cuong NC, Tra DT, Doan YH, Shimizu K, Tuan NQ, Yoshida LM, Mai LQ, Duc-Anh D, Ando S, Arikawa J, Parry CM, Ariyoshi K, Thuy PT. Clinical and Epidemiological Characteristics of Scrub Typhus and Murine Typhus among Hospitalized Patients with Acute Undifferentiated Fever in Northern Vietnam. Am J Trop Med Hyg. 2015 May;92(5):972-978. doi: 10.4269/ajtmh.14-0806. Epub 2015 Mar 16.

Reference Type RESULT
PMID: 25778504 (View on PubMed)

Moore CE, Pan-Ngum W, Wijedoru LPM, Sona S, Nga TVT, Duy PT, Vinh PV, Chheng K, Kumar V, Emary K, Carter M, White L, Baker S, Day NPJ, Parry CM. Evaluation of the diagnostic accuracy of a typhoid IgM flow assay for the diagnosis of typhoid fever in Cambodian children using a Bayesian latent class model assuming an imperfect gold standard. Am J Trop Med Hyg. 2014 Jan;90(1):114-120. doi: 10.4269/ajtmh.13-0384. Epub 2013 Nov 11.

Reference Type RESULT
PMID: 24218407 (View on PubMed)

Baker S, Favorov M, Dougan G. Searching for the elusive typhoid diagnostic. BMC Infect Dis. 2010 Mar 5;10:45. doi: 10.1186/1471-2334-10-45.

Reference Type RESULT
PMID: 20205702 (View on PubMed)

Bhaskaran D, Chadha SS, Sarin S, Sen R, Arafah S, Dittrich S. Diagnostic tools used in the evaluation of acute febrile illness in South India: a scoping review. BMC Infect Dis. 2019 Nov 13;19(1):970. doi: 10.1186/s12879-019-4589-8.

Reference Type RESULT
PMID: 31722678 (View on PubMed)

Wijedoru L, Mallett S, Parry CM. Rapid diagnostic tests for typhoid and paratyphoid (enteric) fever. Cochrane Database Syst Rev. 2017 May 26;5(5):CD008892. doi: 10.1002/14651858.CD008892.pub2.

Reference Type RESULT
PMID: 28545155 (View on PubMed)

Mather RG, Hopkins H, Parry CM, Dittrich S. Redefining typhoid diagnosis: what would an improved test need to look like? BMJ Glob Health. 2019 Oct 31;4(5):e001831. doi: 10.1136/bmjgh-2019-001831. eCollection 2019.

Reference Type RESULT
PMID: 31749999 (View on PubMed)

Lim C, Wannapinij P, White L, Day NP, Cooper BS, Peacock SJ, Limmathurotsakul D. Using a web-based application to define the accuracy of diagnostic tests when the gold standard is imperfect. PLoS One. 2013 Nov 12;8(11):e79489. doi: 10.1371/journal.pone.0079489. eCollection 2013.

Reference Type RESULT
PMID: 24265775 (View on PubMed)

Lalremruata R, Chadha S, Bhalla P. Retrospective audit of the widal test for diagnosis of typhoid Fever in pediatric patients in an endemic region. J Clin Diagn Res. 2014 May;8(5):DC22-5. doi: 10.7860/JCDR/2014/7819.4373. Epub 2014 May 15.

Reference Type RESULT
PMID: 24995178 (View on PubMed)

Begg CB. Statistical methods in medical diagnosis. Crit Rev Med Inform. 1986;1(1):1-22.

Reference Type RESULT
PMID: 3331577 (View on PubMed)

Njuguna HN, Cosmas L, Williamson J, Nyachieo D, Olack B, Ochieng JB, Wamola N, Oundo JO, Feikin DR, Mintz ED, Breiman RF. Use of population-based surveillance to define the high incidence of shigellosis in an urban slum in Nairobi, Kenya. PLoS One. 2013;8(3):e58437. doi: 10.1371/journal.pone.0058437. Epub 2013 Mar 7.

Reference Type RESULT
PMID: 23505506 (View on PubMed)

Maude RR, de Jong HK, Wijedoru L, Fukushima M, Ghose A, Samad R, Hossain MA, Karim MR, Faiz MA, Parry CM; CMCH Typhoid Study Group. The diagnostic accuracy of three rapid diagnostic tests for typhoid fever at Chittagong Medical College Hospital, Chittagong, Bangladesh. Trop Med Int Health. 2015 Oct;20(10):1376-84. doi: 10.1111/tmi.12559. Epub 2015 Jul 15.

Reference Type RESULT
PMID: 26094960 (View on PubMed)

Provided Documents

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Document Type: Study Protocol, Statistical Analysis Plan, and Informed Consent Form

View Document

Other Identifiers

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SERU 4076

Identifier Type: -

Identifier Source: org_study_id