Evaluation of Antibody Detection Tests for Visceral Leishmaniasis Diagnosis in Eastern Africa (VL-DX-EAFR)

According to recent estimates by the World Health Organization (WHO) on eastern Africa, not all visceral leishmaniasis (VL) cases reported are confirmed by a laboratory test, probably due to limited access to accurate diagnostic tests and poor reporting. The main approach for VL diagnosis involves antibody detection using the rK39 rapid diagnostic test (RDT) and alternatively the direct agglutination test (DAT) to confirm clinically suspected cases. Suspected cases with negative rK39 RDT and/or DAT results are referred to facilities where examination of tissue aspirate (spleen, bone marrow, lymph node) by microscopy is available. Unfortunately, the diagnostic performance of rK39 in eastern Africa is suboptimal, particularly in settings with a high VL/HIV co-infection rate. A recently developed RDT, based on the recombinant antigen rK28, may overcome this problem, with studies reporting better performance than the rK39. However, data are not definitive, as studies comparing rK28 RDTs with rK39 RDT are limited. Another recently developed RDT detects immunoglobulin G1 (IgG1) specific to Leishmania and has shown promising results in the Indian subcontinent. This study aims to undertake a multi-country assessment of the performance of rK28 and IgG1 RDTs, as compared to the currently used rK39 RDT.

Study Overview

• Status: Completed
• Conditions: Leishmaniasis, Visceral
• Intervention / Treatment: Device: Leishmania Ab Rapid Test (CTK, Biotech)

Detailed Description

Primary objective and endpoint: To evaluate the performance of different diagnostic tests in detecting anti-Leishmania antibodies to improve early diagnosis of VL in eastern Africa, in particular Ethiopia, and Kenya. Evaluation of the diagnostic performance of the RDTs for primary VL diagnosis based on estimates of sensitivity, specificity, positive and negative predictive values, as well as the degree of agreement between tests.

Design: Prospective single arm diagnostic accuracy study. Multicountry. With participants being suspected cases of VL

• Study Type: Observational
• Enrollment (Actual): 704

Contacts and Locations

Study Locations

• Ethiopia
  • Gondar, Ethiopia, PO BOX 196
    • Leishmaniasis Research and Treatment Centre, Gondar University Hospital
• Kenya
  • West Pokot
    • Kacheliba, West Pokot, Kenya, P.O Box 50 Kacheliba 30601
      • Kacheliba District Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 100 years (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Any patient reporting to the participating VL treatment centres in Ethiopia, Kenya, Sudan and Uganda and suspected with primary VL is eligible for inclusion in the study.

Description

Inclusion Criteria:

• Patient with clinical signs compatible with VL.
• Is a first VL episode suspected.
• Patient ≥ 5 years old (≥ 4 years old in Kenya).
• Patient from whom written informed consent can be obtained or signed by parent or legal guardian if patient is under 18 years of age. In the case of minors, assent from the children (12-17 years old in Ethiopia, Uganda and Sudan, and 13-17 years old in Kenya) will be obtained, as per country legal requirements.
• Clinical samples required VL diagnosis (peripheral blood, lymph node or bone marrow or spleen aspirate) can be obtained from the patient and patient shows willingness.

Exclusion Criteria:

• Patient already on treatment for VL.
• Patient is a suspected VL relapse case.
• Patient has had previous VL episodes.
• Patients < 5 years old (< 4 years old in Kenya).
• Pregnant woman.
• Patient has post/para-kala-azar dermal leishmaniasis (PKDL).

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
RDT performance	Evaluation of the diagnostic performance of the RDTs for primary VL diagnosis based on estimates of sensitivity, specificity, positive and negative predictive values, as well as the degree of agreement between tests	an average of 1.5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to diagnosis	Time taken to perform each diagnostic test, measured from the time the patient reports at the health facility to the time diagnosis is made is established.	an average of 1.5 years
New diagnostic algorithm	The data generated will be analysed to assess whether the evaluated RDTs can be combined in a new algorithm to improve and accelerate VL diagnosis	an average of 1.5 years

Collaborators and Investigators

• Sponsor: Foundation for Innovative New Diagnostics, Switzerland
• Collaborators: London School of Hygiene and Tropical Medicine; Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA); Drugs for Neglected Diseases; Kenya Medical Research Institute; University of Gondar
• Investigators: Principal Investigator: Israel Cruz, PhD, Find

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 1, 2019
• Primary Completion (ACTUAL): October 30, 2021
• Study Completion (ACTUAL): December 1, 2021

Study Registration Dates

• First Submitted: August 7, 2018
• First Submitted That Met QC Criteria: August 23, 2018
• First Posted (ACTUAL): August 24, 2018

Study Record Updates

• Last Update Posted (ACTUAL): June 6, 2022
• Last Update Submitted That Met QC Criteria: June 1, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: visceral leishmaniasis; diagnostics; RDT; Eastern Africa
• Additional Relevant MeSH Terms: Skin Diseases; Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Skin Diseases, Parasitic; Skin Diseases, Infectious; Euglenozoa Infections; Leishmaniasis; Leishmaniasis, Visceral
• Other Study ID Numbers: P08002-VL-DX-EAFR

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Data sharing procedures (including data confidentiality) will be carried out in accordance with the regulations defined by IDDO and H2020 Open Research Data Pilot

Drug and device information, study documents

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