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Strategies to detect Human African Trypanosomiasis (HAT) cases rely on serological screening of populations exposed to trypanosomes. In Guinea, mass medical screening surveys performed with the Card Agglutination Test for Trypanosomiasis have been progressively replaced by door-to-door approaches using Rapid Diagnostic Tests (RDTs) since 2016. However, RDTs availability represents a major concern and medical teams must often adapt, even in the absence of prior RDT performance evaluation. For the last 5 years, the Guinean HAT National Control Program had to combine three different RDTs according to their availability and price: the SD Bioline HAT (not available anymore), the HAT Sero-K-SeT (most expensive), and recently the Abbott Bioline HAT 2.0 (limited field evaluation). Here, we assess the performance of these RDTs, alone or in different combinations, through the analysis of both prospective and retrospective data. A parallel assessment showed a higher positivity rate of Abbott Bioline HAT 2.0 (6.0%, n = 2,250) as compared to HAT Sero-K-SeT (1.9%), with a combined positive predictive value (PPV) of 20.0%. However, an evaluation of Abbott Bioline HAT 2.0 alone revealed a low PPV of 3.9% (n = 6,930) which was surpassed when using Abbott Bioline HAT 2.0 in first line and HAT Sero-K-SeT as a secondary test before confirmation, with a combined PPV reaching 44.4%. A retrospective evaluation of all 3 RDTs was then conducted on 189 plasma samples from the HAT-NCP biobank, confirming the higher sensitivity (94.0% [85.6–97.7%]) and lower specificity (83.6% [76.0–89.1%]) of Abbott Bioline HAT 2.0 as compared to SD Bioline HAT (Se 64.2% [52.2–74.6%]—Sp 98.4% [94.2–99.5%]) and HAT Sero-K-SeT (Se 88.1% [78.2–93.8%]—Sp 98.4% [94.2–99.5%]). A comparison of Abbott Bioline HAT 2.0 and malaria-RDT positivity rates on 479 subjects living in HAT-free malaria-endemic areas further revealed that a significantly higher proportion of subjects positive in Abbott Bioline HAT 2.0 were also positive in malaria-RDT, suggesting a possible cross-reaction of Abbott Bioline HAT 2.0 with malaria-related biological factors in about 10% of malaria cases. This would explain, at least in part, the limited specificity of Abbott Bioline HAT 2.0. Overall, Abbott Bioline HAT 2.0 seems suitable as first line RDT in combination with a second HAT RDT to prevent confirmatory lab overload and loss of suspects during referral for confirmation. A state-of-the-art prospective comparative study is further required for comparing all current and future HAT RDTs to propose an optimal combination of RDTs for door-to-door active screening.

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. Graphical Abstract

BackgroundSerological tests play a crucial role to diagnose gambiense human African trypanosomiasis (HAT) by preselecting individuals for microscopic examination, and, in the near future, by directly identifying patients for treatment. Variability in reported specificities, the introduction of new rapid diagnostic tests (RDT) and the hypothesis that malaria decreases RDT specificity, led us to evaluate the specificity of 5 HAT screening tests.MethodsVenous blood samples from 1095 individuals from Côte d’Ivoire and Guinea were tested with commercial (Bioline HAT 2.0, HAT Sero-K-SeT, CATT/T.b. gambiense) and experimental (HAT Sero-K-SeT 2.0, DCN) HAT screening tests and with a malaria RDT. Individuals negative with all 5 HAT tests were considered HAT free, while positives underwent microscopy. HAT case definition was based on trypanosome detection by microscopy.ResultsOne HAT case was detected. Test specificities (n=1094) were: CATT/T.b. gambiense [98.9% (98.1–99.4%), p<0.0001] > HAT Sero-K-SeT [86.7% (84.5–88.5%), p<0.002] > Bioline HAT 2.0 [82.1% (79.7–84.2%), p=0.0113] > HAT Sero-K-SeT 2.0 [78.5% (76.0–80.9%)] and DCN [78.2% (75.7–80.6%)]. Bioline HAT 2.0 and DCN include 2 test lines, and specificities of line 1 [respectively 83.7% (81.4–85.8%) and 80.6% (78.2–82.9%)], corresponding to ISG-65, were significantly lower (p 0.0001) than with line 2 [respectively 95.8% (94.4–96.8%) and 94.5% (93.0–95.7%)]. The ISG-65 line therefore significantly decreased overall test specificity. Although all the HAT tests were less specific in malaria positive than in malaria negative individuals, differences (p values >0.08) were not significant.ConclusionCATT/T.b. gambiense is more specific than HAT RDTs. The HAT Sero-K-SeT is more specific than second generation RDTs which all contain ISG-65, either as a separate test line (Bioline HAT 2.0 and DCN) or within a single “mixed antigen” test line (HAT Sero-K-SeT 2.0). To improve specificity, removing ISG-65 from experimental RDTs or ignoring the ISG-65 line should be considered, if test sensitivity is not significantly impacted.

Abstract We conducted 3 successive seroprevalence surveys, 3 months apart, using multistage cluster sampling to measure the extent and dynamics of the severe acute respiratory syndrome coronavirus 2 epidemic in Conakry, the capital city of Guinea. Seroprevalence increased from 17.3% (95% CI, 12.4%–23.8%) in December 2020 during the first survey (S1) to 28.9% (95% CI, 25.6%–32.4%) in March/April 2021 (S2), then to 42.4% (95% CI, 39.5%–45.3%) in June 2021 (S3). This significant overall trend of increasing seroprevalence (P < .0001) was also significant in every age class, illustrating a sustained transmission within the whole community. These data may contribute to defining cost-effective response strategies.

The skin is an anatomical reservoir for African trypanosomes, yet the prevalence of extravascular parasite carriage in the population at risk of gambiense Human African Trypanosomiasis (gHAT) remains unclear. Here, we conducted a prospective observational cohort study in the HAT foci of Forecariah and Boffa, Republic of Guinea. Of the 18,916 subjects serologically screened for gHAT, 96 were enrolled into our study. At enrolment and follow-up visits, participants underwent a dermatological examination and had blood samples and superficial skin snip biopsies taken for examination by molecular and immuno-histological methods. In seropositive individuals, dermatological symptoms were significantly more frequent as compared to seronegative controls. Trypanosoma brucei DNA was detected in the blood of 67% of confirmed cases (22/33) and 9% of unconfirmed seropositive individuals (3/32). However, parasites were detected in the extravascular dermis of up to 71% of confirmed cases (25/35) and 41% of unconfirmed seropositive individuals (13/32) by PCR and/or immuno-histochemistry. Six to twelve months after treatment, trypanosome detection in the skin dropped to 17% of confirmed cases (5/30), whereas up to 25% of unconfirmed, hence untreated, seropositive individuals (4/16) were still found positive. Dermal trypanosomes were observed in subjects from both transmission foci, however, the occurrence of pruritus and the PCR positivity rates were significantly higher in unconfirmed seropositive individuals in Forecariah. The lower sensitivity of superficial skin snip biopsies appeared critical for detecting trypanosomes in the basal dermis. These results are discussed in the context of the planned elimination of gHAT.