Evaluation Study of Dengue RDTs

Evaluation Study of Commercially Available Rapid Diagnostic Tests (RDTs) Detecting Antigen and Antibodies Against Dengue Virus

RT-PCR and virus isolation are considered gold standard for diagnosis of Dengue from blood during first few days of infection. Serological methods such as enzyme-linked immunosorbent assays (ELISA), confirms the presence of a recent or past infection with detection of NS1 antigen and anti-dengue antibodies. However, these methods are time-consuming and need significant laboratory infrastructure, including instrumentation, trained personnel and refrigeration for reagents. Hence, in areas where DENV is endemic, have limited resources and inadequate laboratory capacity to perform these tests, rapid diagnostic tests (RDTs) can be used for quick and simple screening. Recently various RDTs which detect Antigen (NS1) and Antibodies (IgM and IgG) in single format are widely available and in use, but the performance data are not available or not consistent from one study to another. Therefore, this study aims to evaluate the sensitivity and specificity of different RDTs that detect antigens and antibodies to Dengue viruses in one cassette during acute febrile stage thereby helping healthcare providers to decide on the best test.

Study Overview

• Status: Completed
• Conditions: Dengue Fever
• Intervention / Treatment: Diagnostic test: Diagnostic test: 5 different Rapid diagnostic test and Reference tests

Detailed Description

Dengue is an emerging infectious disease and is endemic to more than 100 tropical nations. It is a serious public health issue, with an estimated global incidence of > 100 million in 2016, a rise of almost 60% in age-standardized rates since 2006. While rising dengue infection rates affect all major regions of the world, the Asia-Pacific region is disproportionately affected by severe dengue, with rates 18 times higher in Southeast Asia than in the Americas. Climate change and globalization has facilitated the geographic spread of both the mosquito vector and the pathogen to previously unaffected areas, thereby increasing the number of people affected by dengue. Unfortunately, no specific antiviral medication and vaccine exists for Dengue. Hence, an accurate and early diagnosis is essential for proper and timely management and control of the disease in endemic regions. Dengue causes wide spectrum of disease. Primary dengue can range from sub clinical disease to flu-like symptoms. Although less common secondary dengue is associated with increased mortality and morbidity. Accurate, efficient, and rapid diagnosis of dengue in the acute stage is essential as a delay in diagnosis increases the risk of severe dengue and can lead to poor disease outcome. The most commonly used tests to diagnose acute dengue infection are commercial ELISA. Many Dengue RDTs came in rise and flooded the market in the past two decades due to the growing demand for point-of-care diagnostics. RDT is the easiest and most cost-effective method for diagnosis of this virus infection. It is user-friendly, requires no equipment and provide results faster than PCR and ELISA. Different format of Dengue RDTs are available in the market which can detect NS1, IgM and IgG. Detection of NS1, IgM and IgG in single RDT, not only detects primary dengue but also detects past dengue infection and can be helpful in disease prognosis. Many studies have been conducted previously focusing on individual markers of dengue RDTs and not the combined assessment of the test. This has significantly impeded healthcare providers to decide on deciding which overall tests is best to diagnose acute dengue and detects past dengue in a single test format. Hence, this study will aim to perform a head-to-head comparison of Dengue RDTs which detects antigen and antibodies in single test format currently in the market to diagnose acute dengue to help stakeholder decision making more broadly.

• Study Type: Observational
• Enrollment (Actual): 430

Contacts and Locations

Study Locations

• Pakistan
  • Sindh
    • Karachi, Sindh, Pakistan
      • Aga Khan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 65 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 leftover serum samples, which were archived for further research purposes for 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.

Description

Inclusion Criteria:

• Have been obtained from patients presented with fever of < 1 week who have given consent for sample storage for further research purpose.
• Have minimum sample volume of 1 ml.
• Are non-haemolytic
• Have a limited number of freeze-thaw cycles (<3)
• Have been stored at or below -200C

Exclusion Criteria:

• Only samples that meet the inclusion criteria listed above will be selected for the study. Therefore, samples in the study site sample archives which do not meet these criteria will be excluded from the study.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Point estimates of sensitivity and specificity of each RDTs to detect acute dengue with 95% confidence intervals using ELISA as reference standard.	Point estimates of sensitivity and specificity, with 95% confidence intervals based on Wilson's score methods, will be calculated	7 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Estimates of operational characteristics of different RDTs, based on quantitative assessment including invalid rates	Rate of invalid runs: Percent of invalid runs per RDTs	7 months

Collaborators and Investigators

• Sponsor: Foundation for Innovative New Diagnostics, Switzerland
• Collaborators: Aga Khan University
• Investigators: Principal Investigator: Rumina Hasan, Aga Khan University

Study record dates

Study Major Dates

• Study Start (Actual): July 31, 2022
• Primary Completion (Actual): February 24, 2023
• Study Completion (Actual): June 28, 2023

Study Registration Dates

• First Submitted: October 12, 2022
• First Submitted That Met QC Criteria: October 12, 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: RNA Virus Infections; Virus Diseases; Infections; Arbovirus Infections; Vector Borne Diseases; Flavivirus Infections; Flaviviridae Infections; Hemorrhagic Fevers, Viral; Dengue
• Other Study ID Numbers: FE006B

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