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

Abstract

Background Little 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. Methods Clinical 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. Results Over 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). Conclusion Identification 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 registration ClinicalTrials.gov ClinicalTrials.gov, ID NCT03356665

Monitoring the elimination of gambiense human African trypanosomiasis in the historical focus of Batié, South–West Burkina Faso

“…As expected, the laboratory tests on DBS showed high specificity. The specificity of the ELISA/ T. b. gambiense was similar to the specificity in Côte d’Ivoire [ 29 ], and in several studies carried out in the Democratic Republic of Congo [ 20 , 22 , 33 ]. The 100% specificity for trypanolysis confirms previous observations in the historical Gaoua HAT focus [ 12 ].…”

“…As no HAT cases were detected, the diagnostic sensitivity could not be assessed. For all tested RDTs, the specificities were lower than those reported for passive case detection in Côte d’Ivoire [ 29 ]. This lower specificity seems to be the most pronounced with HAT-Sero- K -Set, which was previously reported to be 97.8% specific (95% CI: 97.2–98.2%), while in the present study, specificity was only 89.1% (95% CI: 88.3–89.8%).…”

“…Furthermore, trypanolysis performance has been linked to prevalence levels [ 12 ]. It is therefore not surprising that the specificity of trypanolysis in Bonon in Côte d’Ivoire was lower (94.4%), as HAT cases in this focus are still observed [ 29 ].…”

Two-Year Follow-Up of Trypanosoma brucei gambiense Serology after Successful Treatment of Human African Trypanosomiasis: Results of Four Different Sero-Diagnostic Tests

“…To minimize the number of missed cases, but also to avoid massive overtreatment, near-perfect sensitivity and specificity are essential requirements for these HAT serological tests. The existing serological tests mainly use the native form of variant surface glycoprotein (VSG) antigens LiTat 1.3 and/or LiTat 1.5, although in the last years, new serological tests that use recombinant antigens have been developed [ 10 , 11 ]. The CATT and RDTs using native antigens are the most commonly used serological screening tests at the moment.…”

The elimination of human African trypanosomiasis: Achievements in relation to WHO road map targets for 2020

“…New, easier-to-use and more effective tools currently in the pipeline are expected to help the integration process. These new tools include a single-dose oral treatment for both stages of the disease (acoziborole [ 54 , 55 ]), performant and easier-to-produce second generation rapid diagnostic tests [ 56 , 57 ], and high throughput referral tests performed in dry blood spots not requiring sophisticated transport conditions (ELISA [ 58 ] and other molecular tests [ 59 , 60 ]). The adaptation of control strategies to the evolving patterns of disease transmission was one of the keys to success in past years, and it should continue in the future.…”