Evaluation Study of DPP® Typhoid Assay

Evaluation of DPP® Typhoid Assay (Chembio Diagnostic System, Inc) for the Diagnosis of Typhoid From Well Characterized Serum Sample.

Fever management is a major problem in Low and Middle Income Countries (LMICs) where access to good quality diagnostic test is often unavailable. Fever due to typhoid is similar to other undifferentiated febrile illnesses and typhoid can be mistaken with other vector borne febrile illnesses such as scrub typhus. Currently available diagnostic tests, blood and bone marrow culture, and RDTs have several limitations including a low sensitivity and specificity . Recently, several antigens of Salmonella Typhi useful for serodiagnosis of typhoid has been identified. Salmonella Typhi lipopolysaccharide (LPS) and hemolysin E (HlyE) have been identified as top candidate antigens by several studies to differentiate acute typhoid patients from healthy individuals. DPP® Typhoid Assay is a multiplex rapid test that detects IgA antibodies to LPS and HlyE antigen. It is considered to have high sensitivity and specificity and its results were found to be highly correlated with ELISA results. However, very few studies have been conducted to evaluate this test and limited information about the accuracy of this test is present. Hence, this study will evaluate the sensitivity and specificity of this test in archived serum sample of well characterized blood culture positives and negatives in support of new innovation on typhoid diagnostics.

Study Overview

• Status: Completed
• Conditions: Typhoid Fever
• Intervention / Treatment: Diagnostic test: Typhoid DPP assay

Detailed Description

Typhoid is an acute febrile illness caused by Salmonella enterica serovar Typhi (S. Typhi). Annually, an estimated 11-21 million people become infected with typhoid fever and 128000-161000 people die from the disease . It is commonly transmitted through consumption of contaminated food or water. Low and middle-income countries and areas with poor access to safe water, food and sanitation are at higher risk of infection.

Blood and bone marrow culture is considered as the mainstay for laboratory confirmation of typhoid. However, it is expensive, requires specific laboratory equipment and technical expertise and takes longer time to generate results. Several RDTs and Widal test are available which do not require specialized laboratory and well-trained staff but lack sensitivity and specificity. Several studies have been done for identification of promising antigens that can be used to develop an accurate serodiagnostic assay. S. Typhi lipopolysaccharide (LPS) and hemolysin E (HlyE) have been identified as top candidate antigens by several studies to differentiate acute typhoid patients from healthy individuals. HlyE is a pore-forming toxin that affects bacterial growth within human macrophages and contributes to the cytotoxicity and invasion of epithelial cells.

Dual Path Platform (DPP) Typhoid Assay of Chembio is a point-of-care (POC) immunochromatographic technology which has the capability of measuring IgA response in blood, plasma and serum to both LPS and HlyE. A previous study done on this POC showed promising sensitivity and specificity to diagnose typhoid.Thus, the current study aims to assess the sensitivity and specificity of DPP ® Typhoid Assay using blood culture as the reference point.

• Study Type: Observational
• Enrollment (Actual): 387

Contacts and Locations

• Study Contact: Name: Jyotshna Sapkota, MD; Phone Number: 977-9851182704; Email: Jyotshna.Sapkota@finddx.org

Study Locations

• Pakistan
  • Karachi, Pakistan
    • Aga Khan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 months to 63 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Probability Sample

Study Population

The study will be conducted at AKU research laboratory using well characterized typhoid positive and typhoid negative serum samples, which were archived for further research purposes from previous trial "Comparative study of commercially available typhoid point of care tests to benchmark current and emerging tools" conducted at AKU in 2020-2021. Precisely, the population is represented by children and adults (age 2-65) who presented with fever of 3-7 days duration.

All patients from whom these samples were obtained have consented to store their sample at AKU and to use them for research on diagnostic tool for fever management.

Prospective approval of protocol deviations to recruitment and enrolment criteria, also known as protocol waivers or exemptions, is not permitted.

Description

Inclusion Criteria:

• Inclusion criteria identical to the prior prospective study in AKU (Protocol ref number: FE006)
• Serum stored frozen at AKU as a part of afore mentioned study and cold-chain maintained.

Exclusion Criteria:

• Samples whose reference standard data (Blood culture report) are not available in FIND's OpenClinica database.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Point estimates of sensitivity and specificity with 95% confidence interval of DPP Typhoid assay using blood culture as reference standard	October 2022

Secondary Outcome Measures

Outcome Measure	Time Frame
Estimates of operational characteristics of DPP Typhoid Assay, based on quantitative assessment including invalid rates	Nov 2022

Collaborators and Investigators

• Sponsor: Foundation for Innovative New Diagnostics, Switzerland
• Collaborators: Aga Khan University

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2022
• Primary Completion (Actual): November 30, 2022
• Study Completion (Actual): June 30, 2023

Study Registration Dates

• First Submitted: October 11, 2022
• First Submitted That Met QC Criteria: October 11, 2022
• First Posted (Actual): October 14, 2022

Study Record Updates

• Last Update Posted (Estimated): November 21, 2023
• Last Update Submitted That Met QC Criteria: November 20, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Enterobacteriaceae Infections; Salmonella Infections; Typhoid Fever
• Other Study ID Numbers: FE006C

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No