Specificity of serological screening tests and reference laboratory tests to diagnose gambiense human African trypanosomiasis: a prospective clinical performance study.

Autor: N'Djetchi MK; Laboratory of Biodiversity and Ecosystem Management, Jean Lorougnon Guédé University, Daloa, Côte d'Ivoire., Camara O; National Program for Neglected Tropical Disease Control, Patient Management, Ministry of Health, Conakry, Guinea., Koffi M; Laboratory of Biodiversity and Ecosystem Management, Jean Lorougnon Guédé University, Daloa, Côte d'Ivoire., Camara M; National Program for Neglected Tropical Disease Control, Patient Management, Ministry of Health, Conakry, Guinea., Kaba D; Trypanosomosis Research Unit, Pierre Richet Institute, Bouaké, Côte d'Ivoire., Kaboré J; International Research and Development Centre on Livestock in Subhumid Zones, Bobo-Dioulasso, Burkina Faso., Tall A; National Program for Malaria Control, Conakry, Guinea., Rotureau B; Parasitology Unit, Institut Pasteur de Guinée, Conakry, Guinea., Glover L; Trypanosome Molecular Biology Unit, Department of Parasites and Insect Vectors, Pasteur Institute, Paris Cité University, Paris, France., Traoré MB; Laboratory of Biodiversity and Ecosystem Management, Jean Lorougnon Guédé University, Daloa, Côte d'Ivoire., Koné M; Laboratory of Biodiversity and Ecosystem Management, Jean Lorougnon Guédé University, Daloa, Côte d'Ivoire., Coulibaly B; Trypanosomosis Research Unit, Pierre Richet Institute, Bouaké, Côte d'Ivoire., Adingra GP; Trypanosomosis Research Unit, Pierre Richet Institute, Bouaké, Côte d'Ivoire., Soumah A; National Program for Neglected Tropical Disease Control, Patient Management, Ministry of Health, Conakry, Guinea., Gassama M; National Program for Neglected Tropical Disease Control, Patient Management, Ministry of Health, Conakry, Guinea., Camara AD; National Program for Neglected Tropical Disease Control, Patient Management, Ministry of Health, Conakry, Guinea., Compaoré CFA; International Research and Development Centre on Livestock in Subhumid Zones, Bobo-Dioulasso, Burkina Faso., Camara A; Parasitology Unit, Institut Pasteur de Guinée, Conakry, Guinea., Boiro S; Parasitology Unit, Institut Pasteur de Guinée, Conakry, Guinea., Anton EP; Trypanosome Molecular Biology Unit, Department of Parasites and Insect Vectors, Pasteur Institute, Paris Cité University, Paris, France., Bessell P; Independent Consultant, Edinburgh, UK., Van Reet N; Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium., Bucheton B; National Program for Neglected Tropical Disease Control, Patient Management, Ministry of Health, Conakry, Guinea.; Intertryp, IRD-CIRAD-University of Montpellier, Montpellier, France., Jamonneau V; Trypanosomosis Research Unit, Pierre Richet Institute, Bouaké, Côte d'Ivoire.; Intertryp, IRD-CIRAD-University of Montpellier, Montpellier, France., Bart JM; National Program for Neglected Tropical Disease Control, Patient Management, Ministry of Health, Conakry, Guinea.; Intertryp, IRD-CIRAD-University of Montpellier, Montpellier, France., Solano P; Intertryp, IRD-CIRAD-University of Montpellier, Montpellier, France., Biéler S; Foundation for Innovative New Diagnostics, Geneva, Switzerland., Lejon V; Intertryp, IRD-CIRAD-University of Montpellier, Montpellier, France. Veerle.lejon@ird.fr.
Jazyk: angličtina
Zdroj: Infectious diseases of poverty [Infect Dis Poverty] 2024 Jul 08; Vol. 13 (1), pp. 53. Date of Electronic Publication: 2024 Jul 08.
DOI: 10.1186/s40249-024-01220-5
Abstrakt: Background: Serological screening tests play a crucial role to diagnose gambiense human African trypanosomiasis (gHAT). Presently, they preselect individuals for microscopic confirmation, but in future "screen and treat" strategies they will identify individuals for treatment. Variability in reported specificities, the development of new rapid diagnostic tests (RDT) and the hypothesis that malaria infection may decrease RDT specificity led us to evaluate the specificity of 5 gHAT screening tests.
Methods: During active screening, venous blood samples from 1095 individuals from Côte d'Ivoire and Guinea were tested consecutively with commercial (CATT, HAT Sero-K-SeT, Abbott Bioline HAT 2.0) and prototype (DCN HAT RDT, HAT Sero-K-SeT 2.0) gHAT screening tests and with a malaria RDT. Individuals with ≥ 1 positive gHAT screening test underwent microscopy and further immunological (trypanolysis with T.b. gambiense LiTat 1.3, 1.5 and 1.6; indirect ELISA/T.b. gambiense; T.b. gambiense inhibition ELISA with T.b. gambiense LiTat 1.3 and 1.5 VSG) and molecular reference laboratory tests (PCR TBRN3, 18S and TgsGP; SHERLOCK 18S Tids, 7SL Zoon, and TgsGP; Trypanozoon S 2 -RT-qPCR 18S2, 177T, GPI-PLC and TgsGP in multiplex; RT-qPCR DT8, DT9 and TgsGP in multiplex). Microscopic trypanosome detection confirmed gHAT, while other individuals were considered gHAT free. Differences in fractions between groups were assessed by Chi square and differences in specificity between 2 tests on the same individuals by McNemar.
Results: One gHAT case was diagnosed. Overall test specificities (n = 1094) were: CATT 98.9% (95% CI: 98.1-99.4%); HAT Sero-K-SeT 86.7% (95% CI: 84.5-88.5%); Bioline HAT 2.0 82.1% (95% CI: 79.7-84.2%); DCN HAT RDT 78.2% (95% CI: 75.7-80.6%); and HAT Sero-K-SeT 2.0 78.4% (95% CI: 75.9-80.8%). In malaria positives, gHAT screening tests appeared less specific, but the difference was significant only in Guinea for Abbott Bioline HAT 2.0 (P = 0.03) and HAT Sero-K-Set 2.0 (P = 0.0006). The specificities of immunological and molecular laboratory tests in gHAT seropositives were 98.7-100% (n = 399) and 93.0-100% (n = 302), respectively. Among 44 reference laboratory test positives, only the confirmed gHAT patient and one screening test seropositive combined immunological and molecular reference laboratory test positivity.
Conclusions: Although a minor effect of malaria cannot be excluded, gHAT RDT specificities are far below the 95% minimal specificity stipulated by the WHO target product profile for a simple diagnostic tool to identify individuals eligible for treatment. Unless specificity is improved, an RDT-based "screen and treat" strategy would result in massive overtreatment. In view of their inconsistent results, additional comparative evaluations of the diagnostic performance of reference laboratory tests are indicated for better identifying, among screening test positives, those at increased suspicion for gHAT.
Trial Registration: The trial was retrospectively registered under NCT05466630 in clinicaltrials.gov on July 15 2022.
(© 2024. The Author(s).)
Databáze: MEDLINE
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