Passive surveillance of human African trypanosomiasis in Côte d'Ivoire: Understanding prevalence, clinical symptoms and signs, and diagnostic test characteristics.

Minayégninrin Koné,Mathurin Koffi,Philippe Solano,Cyrille Mambo Kouamé,Dramane Kaba,Bernardin Ahouty,Laura Cristina Falzon,Vincent Jamonneau,Philippe Büscher,Jacques Kaboré,Emmanuel Kouassi N’Gouan,Charlie Franck Alfred Compaoré,Eric Fèvre,Veerle Lejon,Lian Francesca Thomas,Grace Adira Murilla

doi:10.1371/journal.pntd.0009656

Abstract

BackgroundLittle is known about the diagnostic performance of rapid diagnostic tests (RDTs) for passive screening of human African trypanosomiasis (HAT) in Côte d’Ivoire. We determined HAT prevalence among clinical suspects, identified clinical symptoms and signs associated with HAT RDT positivity, and assessed the diagnostic tests’ specificity, positive predictive value and agreement.MethodsClinical suspects were screened with SD Bioline HAT, HAT Sero-K-Set and rHAT Sero-Strip. Seropositives were parasitologically examined, and their dried blood spots tested in trypanolysis, ELISA/Tbg, m18S-qPCR and LAMP. The HAT prevalence in the study population was calculated based on RDT positivity followed by parasitological confirmation. The association between clinical symptoms and signs and RDT positivity was determined using multivariable logistic regression. The tests’ Positive Predictive Value (PPV), specificity and agreement were determined.ResultsOver 29 months, 3433 clinical suspects were tested. The RDT positivity rate was 2.83%, HAT prevalence 0.06%. Individuals with sleep disturbances (p<0.001), motor disorders (p = 0.002), convulsions (p = 0.02), severe weight loss (p = 0.02) or psychiatric problems (p = 0.04) had an increased odds (odds ratios 1.7–4.6) of being HAT RDT seropositive. Specificities ranged between 97.8%-99.6% for individual RDTs, and 93.3–98.9% for subsequent tests on dried blood spots. The PPV of the individual RDTs was below 14.3% (CI 2–43), increased to 33.3% (CI 4–78) for serial RDT combinations, and reached 67% for LAMP and ELISA/Tbg on RDT positives. Agreement between diagnostic tests was poor to moderate (Kappa ≤ 0.60), except for LAMP and ELISA/Tbg (Kappa = 0.66).ConclusionIdentification of five key clinical symptoms and signs may simplify referral for HAT RDT screening. The results confirm the appropriateness of the diagnostic algorithm presently applied, with screening by SD Bioline HAT or HAT Sero-K-Set, supplemented with trypanolysis. ELISA/Tbg could replace trypanolysis and is simpler to perform.Trial registrationClinicalTrials.gov NCT03356665.

Highlights

Sleeping sickness, or human African trypanosomiasis (HAT), is a parasitic disease that is fatal if left untreated
Specificities ranged between 97.8%-99.6% for individual rapid diagnostic tests (RDTs), and 93.3–98.9% for subsequent tests on dried blood spots
The Positive Predictive Value (PPV) of the individual RDTs was below 14.3% (CI 2–43), increased to 33.3% (CI 4–78) for serial RDT combinations, and reached 67% for Loopamp Trypanosoma brucei Detection Kit (LAMP) and ELISA/Tb gambiense (Tbg) on RDT positives

Summary

Introduction

Human African trypanosomiasis (HAT), is a parasitic disease that is fatal if left untreated. This disease is caused by an extracellular protozoan of the Trypanosoma brucei (Tb) species, which is transmitted by the tsetse fly. HAT form, responsible for 98% of cases and endemic across Central and West Africa, is caused by Tbg [1,2]. Thanks to a very effective response, the number of cases decreased gradually, and HAT was included in the 2012 WHO roadmap on Neglected Tropical Diseases (NTDs), with the goal of elimination as a public health problem by 2020 [4]. In the new WHO NTD roadmap, Tbg HAT is targeted for interruption of transmission by 2030 [6]. We determined HAT prevalence among clinical suspects, identified clinical symptoms and signs associated with HAT RDT positivity, and assessed the diagnostic tests’ specificity, positive predictive value and agreement

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