Dual Point-of-care Test for the Diagnosis of Yaws (YARADI)

Evaluation of a Rapid Dual Point-of-care Assay for Targeting Antibiotic Treatment for Yaws Eradication: a Prospective Descriptive Study

A dual POC immunoassay simultaneously detecting non-treponemal and treponemal antibodies was developed for the diagnosis of infections with T. pallidum. The assay is designed for use in resource-limited settings where challenging conditions (such as lack of electricity, running water, or laboratory equipment) commonly exist. We sought to compare performance of the dual-POC assay for diagnosis of yaws infection with that of the RPR and TPHA as reference standards.

Study Overview

• Status: Completed
• Conditions: Yaws

Detailed Description

Yaws is an infectious disease caused by Treponema pallidum subspecies pertenue, a bacterium which closely resembles the causative agent of syphilis, and is spread by skin to skin contact. In the field, yaws is diagnosed on the basis of epidemiological context, evocative symptoms and signs and positive serological tests or dark field microscopy. The darkfield microscopy is not easy to perform , hence the interest in serological tests. The serological tests used to confirm yaws are the same as those used to diagnose syphilis. Yaws serologic diagnosis relies on testing for non-treponemal and treponemal antibodies. These antibodies differ markedly with respect to antigenic reactivities and kinetics during the disease process.

Historically screening for yaws has involved the use of nontreponemal tests, such as rapid plasma reagin or venereal disease research laboratory. Positive results of nontreponemal tests of specimens are then confirmed using a more specific treponemal test, such as Treponema pallidum haemagglutination. However, the equipment and personnel requirements for conducting and interpreting these laboratory-tests are rarely available in low-resource settings in developing countries where yaws occurs.

Rapid treponemal tests which detect antibodies to T. pallidum antigen have become popular for the diagnosis of venereal syphilis due to their many advantages. These tests that can be performed outside a laboratory setting with minimal training and using blood collected by a finger prick, which makes them extremely useful in remote areas where laboratories are not available. However, the rapid treponemal tests for syphilis detect treponemal antibodies, which limits their use for interpretation of the disease status since they cannot distinguish between active and past or treated infection.

A combined point-of-care (POC) test which detects both treponemal and non-treponemal antibodies has recently been evaluated for the diagnosis of syphilis, and appears promising for yaws diagnosis. The use of the dual POC test would result in the ability to both screen and confirm the serological status of patients with suspected yaws within 15 minutes and give a better indication of active disease.

• Study Type: Observational
• Enrollment (Actual): 703

Contacts and Locations

Study Locations

• Papua New Guinea
  • Madang
    • Marup village, Madang, Papua New Guinea
      • Karkar Island
  • New Ireland Province
    • Londolovit, New Ireland Province, Papua New Guinea, 034
      • Lihir Medical Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 15 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients will be recruited from Lihir Island villages in April 2013. This community has been described previously. We will conduct community-based surveys and we invited children aged 1 - 15 years suspected to have yaws by clinical examination to participate in the study. All children for whom a parent or guardian gives written informed consent will be included consecutively

Description

Inclusion Criteria:

• Children from 2 to 15 years with clinical suspicion of active yaws

Exclusion Criteria:

• Persons who are unable to sustain venipuncture; persons who do not provide an informed consent, or withdraw consent

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
DPP/RPR-TPHA comparison; The evaluation of T1 (treponemal line) will be conducted by using the T1 positivity identified by naked eye or automated reader to compare with that of TPHA; while the evaluation of T2 (non-treponemal line) will be conducted by using the T2 positivity identified by naked eye, or automatic reader at cut-off value of 20, to compare with the result of RPR.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To determine the accuracy of the dual-test as compared to recognized standard methods	Sensitivity and Specificity as compared to RPR and TPHA; Proportion of actual TPHA/RPR positives which are correctly identified as such by DPP (dual-test)T1 and T2 respectively; Proportion of TPHA/RPR negatives which are correctly identified as such by DPP (dual-test)T1 and T2 respectively	1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Accuracy of DPP in whole blood and plasma	Specimens will be randomly tested using DPP, either in plasma or blood. Sensitivity and Specificity of DPP in whole blood and DPP in plasma will be compared.	1 month
Accuracy of DPP determined by Naked eye and Reader	Specimens will be tested using DPP, read by naked eye and also using automated reader. Sensitivity and Specificity of DPP result read by naked eye and DPP using automated reader will be compared.	1 month

Collaborators and Investigators

• Sponsor: Oriol Mitja
• Collaborators: Papua New Guinea Institute of Medical Research; Barcelona Centre for International Health Research; Papua New Guinea National Department of Health, Disease Control; Divine Word University

Publications and helpful links

General Publications

• Ayove T, Houniei W, Wangnapi R, Bieb SV, Kazadi W, Luke LN, Manineng C, Moses P, Paru R, Esfandiari J, Alonso PL, de Lazzari E, Bassat Q, Mabey D, Mitja O. Sensitivity and specificity of a rapid point-of-care test for active yaws: a comparative study. Lancet Glob Health. 2014 Jul;2(7):e415-21. doi: 10.1016/S2214-109X(14)70231-1. Epub 2014 May 31.

Study record dates

Study Major Dates

• Study Start: April 1, 2013
• Primary Completion (Actual): November 1, 2013
• Study Completion (Actual): November 1, 2013

Study Registration Dates

• First Submitted: April 19, 2013
• First Submitted That Met QC Criteria: April 23, 2013
• First Posted (Estimate): April 26, 2013

Study Record Updates

• Last Update Posted (Estimate): November 18, 2014
• Last Update Submitted That Met QC Criteria: November 14, 2014
• Last Verified: November 1, 2014

More Information

Terms related to this study

• Keywords: Diagnosis; eradication; Rapid tests; non-treponemal serology
• Additional Relevant MeSH Terms: Skin Diseases; Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Skin Diseases, Infectious; Skin Diseases, Bacterial; Spirochaetales Infections; Treponemal Infections; Yaws
• Other Study ID Numbers: YARADI