Sensitivity and Specificity of a Prototype Rapid Diagnostic Test for the Detection of Trypanosoma brucei gambiense Infection: A Multi-centric Prospective Study.

Alvaro Acosta-Serrano,Victor Kande,Paul R Bessell,Gedeao Vatunga,Marleen Boelaert,Crispin Lumbala,Laurence Flevaud,Sylvain Biéler,Joseph M Ndung’U,Etienne Nguertoum,Theophile Josenando,Sylvie Bisser,Philippe Büscher

doi:10.1371/journal.pntd.0004608

Abstract

BackgroundA major challenge in the control of human African trypanosomiasis (HAT) is lack of reliable diagnostic tests that are rapid and easy to use in remote areas where the disease occurs. In Trypanosoma brucei gambiense HAT, the Card Agglutination Test for Trypanosomiasis (CATT) has been the reference screening test since 1978, usually on whole blood, but also in a 1/8 dilution (CATT 1/8) to enhance specificity. However, the CATT is not available in a single format, requires a cold chain for storage, and uses equipment that requires electricity. A solution to these challenges has been provided by rapid diagnostic tests (RDT), which have recently become available. A prototype immunochromatographic test, the SD BIOLINE HAT, based on two native trypanosomal antigens (VSG LiTat 1.3 and VSG LiTat 1.5) has been developed. We carried out a non-inferiority study comparing this prototype to the CATT 1/8 in field settings.Methodology/Principal FindingsThe prototype SD BIOLINE HAT, the CATT Whole Blood and CATT 1/8 were systematically applied on fresh blood samples obtained from 14,818 subjects, who were prospectively enrolled through active and passive screening in clinical studies in three endemic countries of central Africa: Angola, the Democratic Republic of the Congo and the Central African Republic. One hundred and forty nine HAT cases were confirmed by parasitology. The sensitivity and specificity of the prototype SD BIOLINE HAT was 89.26% (95% confidence interval (CI) = 83.27–93.28) and 94.58% (95% CI = 94.20–94.94) respectively. The sensitivity and specificity of the CATT on whole blood were 93.96% (95% CI = 88.92–96.79) and 95.91% (95% CI = 95.58–96.22), and of the CATT 1/8 were 89.26% (95% CI = 83.27–93.28) and 98.88% (95% CI = 98.70–99.04) respectively.Conclusion/SignificanceAfter further optimization, the prototype SD BIOLINE HAT could become an alternative to current screening methods in primary healthcare settings in remote, resource-limited regions where HAT typically occurs.

Highlights

Human African trypanosomiasis (HAT) or sleeping sickness is a neglected tropical disease that is endemic in remote, resource-limited regions of sub-Saharan African countries [1]
Availability of simple, easy to use, instrument-free rapid diagnostic tests would improve screening and coverage of the population at risk and contribute to elimination of the disease. It would enable technicians with limited training and clinicians in emergency or medical wards to make rapid differential diagnosis for neurological syndromes or malaria-like illnesses. Introduction of such tests in all healthcare facilities in endemic regions would enable early detection of cases, reducing the time lost by patients before they get adequate and safe treatment
We evaluated a prototype rapid diagnostic test for human African trypanosomiasis (HAT), the SD BIOLINE HAT in Angola, the Democratic Republic of the Congo and the Central African Republic

Summary

Introduction

Human African trypanosomiasis (HAT) or sleeping sickness is a neglected tropical disease that is endemic in remote, resource-limited regions of sub-Saharan African countries [1]. Gambiense which is the focus of this study Both forms of HAT evolve in two disease phases: an early or haemo-lymphatic phase or stage one, and a late meningo-encephalitic phase or stage two. Due to the chronic nature of the disease and a lack of specific symptoms during stage one, identification of cases relies on passive and active screening of patients and populations in endemic areas. A major challenge in the control of human African trypanosomiasis (HAT) is lack of reliable diagnostic tests that are rapid and easy to use in remote areas where the disease occurs. In Trypanosoma brucei gambiense HAT, the Card Agglutination Test for Trypanosomiasis (CATT) has been the reference screening test since 1978, usually on whole blood, and in a 1/8 dilution (CATT 1/8) to enhance specificity. We carried out a non-inferiority study comparing this prototype to the CATT 1/8 in field settings

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