Performance of clinical signs and symptoms, rapid and laboratory diagnostic tests for diagnosis of human African trypanosomiasis by passive screening in Guinea: a non-interventional, prospective cross-sectional study

Abstract

Background: Passive diagnosis of human African trypanosomiasis (HAT) at the health facility level is a major component of HAT control in Guinea. We examined which clinical signs and symptoms are associated with HAT, and assessed the performance of selected clinical presentations, of rapid diagnostic tests (RDT), and of laboratory tests on dried blood spots (DBS) for diagnosing HAT. Method: The study took place in 11 health facilities in Guinea, where 2345 clinical suspects were tested with RDTs HAT Sero-K-Set, rHAT Sero-Strip, and SD Bioline HAT. Seropositives underwent parasitological examination to confirm HAT and their DBS were tested in indirect ELISA/T.b. gambiense, trypanolysis, LAMP and m18S qPCR. Multivariable regression analysis assessed association of clinical presentation with HAT. Sensitivity, specificity, positive and negative predictive values of key clinical presentations, of the RDTs and of the DBS tests for HAT diagnosis were determined. Results: The HAT prevalence, as confirmed parasitologically, was 2.0% (1.5-2.7%). Odds ratios (OR) for HAT were increased for participants with swollen lymph nodes (OR 96.7), important weight loss (OR 20.4), severe itching (OR 45.9) or motor disorders (OR 4.5). Presence of at least one of these clinical presentations was 75.6% (73.8-77.4%) specific and 97.9% (88.9-99.9%) sensitive for HAT. HAT Sero-K-Set, rHAT Sero-Strip, and SD Bioline HAT were respectively 97.5% (96.8-98.1%), 99.4% (99.0-99.7%) and 97.9% (97.2-98.4%) specific, and 100% (92.5-100.0%), 59.6% (44.3-73.3%) and 93.8% (82.8-98.7%) sensitive for HAT. All DBS tests had specificities ≥ 92.9%. While LAMP and m18S qPCR sensitivities were below 50%, trypanolysis and ELISA/T.b. gambiense had sensitivities of 85.3% (68.9-95.0%) and 67.6% (49.5-82.6%). Conclusions: Presence of swollen lymph nodes, important weight loss, severe itching or motor disorders are simple but accurate clinical criteria for HAT referral in Guinea. Diagnostic performances of HAT Sero-K-Set and SD Bioline HAT are sufficient for referring positives to microscopy. Trypanolysis on DBS may discriminate HAT patients from false RDT positives. Trial registration: The trial was registered under NCT03356665 in clinicaltrials.gov (November 29, 2017, retrospectively registered https://clinicaltrials.gov/ct2/show/NCT03356665).

Low specificity of rapid diagnostic tests and lack of coherence between laboratory tests to diagnose gambiense human African trypanosomiasis, as evidenced by a prospective clinical performance study in Côte d’Ivoire and in Guinea

“…Among the immunological laboratory tests, the speci city values obtained for trypanolysis on DBS are in line with previously reported values of 92.9-100% [13,33,34], although LiTat 1.6 is not often included in the trypanolysis test battery. For indirect ELISA/T.b.…”

“…For indirect ELISA/T.b. gambiense as well, speci city was in the range of the 95.3-99.8% values reported in the literature [13,21,33,34]. The indirect ELISA/T.b.…”

“…This could be due to the use of DBS, which is less sensitive than plasma for trypanolysis, and has moderate sensitivity in ELISA/T.b. gambiense as well [20,33]. Overall, both trypanolysis and indirect ELISA/T.b.…”

“…The rst prospective clinical performance study of the rst generation HAT Sero-K-Set in DRC demonstrated a speci city of 98.6% [9], based on a mix of active and passive recruitment. Next, speci cities of 97.0-97.8% were observed in prospective trials in DRC, Côte d'Ivoire and Guinea, based on passive screening [13,32,33]. More recently, during active screening in Burkina Faso, 89.1% speci city was obtained [34], while in door-to-door screening in Guinea, positivity rates ranged 1.9-9.4% [31].…”