Commercial Typhoid Tests Validation

Typhoid Fever Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04673487
• Other study ID #: SERU 4076
• Status: Not yet recruiting
• Start date: January 2021
• Est. completion date: December 2021

Study information

• Verified date: December 2020
• Source: Kenya Medical Research Institute
• Contact: Robert S Onsare, PhD
• Phone: +254722337004
• Email: robert.s.onsare[@]gmail.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 2000
• Est. completion date: December 2021
• Est. primary completion date: June 2021
• Gender: All
• Age group: 8 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Typhoid Fever

Intervention

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

Locations

Country	Name	City	State
Kenya	Kenya Medical Research Institute	Nairobi

Sponsors (2)

Lead Sponsor	Collaborator
Kenya Medical Research Institute	Foundation for Innovative New Diagnostics (FIND)

Country where clinical trial is conducted

Kenya, 

References & Publications (14)

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. 2 — View Citation

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. Review. — View Citation

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. Review. — View Citation

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

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. Review. — View Citation

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

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 Ac — View Citation

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. — View Citation

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.00 — View Citation

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. — View Citation

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, Chittagon — View Citation

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 Cambod — View Citation

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 — View Citation

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

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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