Conducting active screening for human African trypanosomiasis with rapid diagnostic tests: The Guinean experience (2016-2021)

Abstract

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.

Fig 1. Usage of the different HAT-RDTs for door-to-door active medical surveys from 2016 to 2021 in Guinea.

The evolution of the total annual number of HAT cases detected by both passive and active surveillance is shown on the upper graph. Different strategies have been successively implemented according to the availability and cost of the different RDTs. From 2016 to 2018, SD Bioline HAT was applied (details in Table 1). From 2019 to mid-2021, HAT Sero-K-SeT was used either alone, or in combination with SD Bioline HAT then with Abbott Bioline HAT 2.0 (details Table 2). From mid-2021 to date, Abbott Bioline HAT 2.0 was applied alone, then with HAT Sero-K-SeT used as secondary test (details in Table 3). The positivity rates (number of positive RDTs / number of screened individuals) were only calculated for RDTs used as first line tests. The Positive Predictive Values (PPVs) were calculated by combining results from primary and secondary RDTs.

Fig 2. Map of the HAT foci in Guinea.

Endemic transmission foci in red, old foci with last cases reported before 2004 in orange, zones at risk in yellow, Atlantic Ocean in blue. This map was elaborated in-house with QGIS 3.28.12 from an OSM standard layer (www.openstreetmap.org).

Fig 3. Current algorithm used by the HAT-NCP to detect HAT cases by active screening in Guinea.

mAECT: mini-anion exchange centrifugation test.