Passive surveillance of human African trypanosomiasis in the Democratic Republic of the Congo: clinical presentation and prospective evaluation of rapid diagnostic and reference laboratory test accuracy
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Background
Passive screening of gambiense human African trypanosomiasis (HAT) is based on rapid diagnostic tests (RDT), but sensitivity of the currently commercialised RDTs has hardly been assessed prospectively. In view of the increasing importance of remote testing for HAT, the diagnostic performance of reference laboratory tests also needs further documentation.
Methodology/Principal Findings
The study is registered in ClinicalTrials.Gov under identifier NCT03356665 . Clinical suspects in 29 health facilities in DR Congo were screened consecutively between October 2017 and December 2020 with 3 HAT RDTs, including HAT Sero K -SeT, an RDT that is nowadays still commercialised. HAT RDT positives were examined parasitologically and their dried blood spots tested in trypanolysis, indirect ELISA/ T.b. gambiense , LAMP Trypanosoma brucei Detection Kit and m18S and TgsGp qPCR. Association of clinical signs with HAT, and sensitivity, specificity, and predictive values of the screening and reference laboratory tests were estimated using parasitology as the gold standard. Trypanosomes were detected in 42/3113 study participants. Logistic regression revealed that sleep disruption, enlarged lymph nodes, psychiatric problems, recurrent fever not responding to anti-malarials and motor disorders were significantly associated with HAT ( p <0.05, odds 3.0-10.6). Together, the RDTs detected 253/3113 seropositives. Sensitivity and specificity of HAT Sero K -SeT were respectively 100% (42/42; 95% CI 91.6-100%) and 93.9% (2882/3071; 95% CI 92.9-94.6%). Specificities of the reference laboratory tests were ≥ 91.6%, except for LAMP. Sensitivity of ELISA/ T.b. gambiense and trypanolysis were 93.9% (31/33; 95% CI 80.4-98.9) and 84.9% (28/33; 95% CI 69.1-93.4), and were ≤ 63.6% for LAMP, m18S and TgsGp qPCR.
Conclusions/Significance
Compared to the WHO’s target product profiles for gambiense HAT RDTs, the HAT Sero K -SeT RDT had ideal sensitivity but its specificity was on the borderline of minimally acceptable. Sub-optimal sensitivities of trypanolysis and to a lesser extent, indirect ELISA/ T.b. gambiense when applied on DBS, were confirmed. Molecular tests for remote testing need to be improved and evaluated further.
Author summary
While gambiense human African trypanosomiasis (HAT) approaches elimination, its diagnosis increasingly relies on fixed health structures screening clinical suspects with rapid diagnostic tests (RDT). For confirmation of infection and for epidemiological purposes, remote testing of blood specimens from RDT seropositives also gains importance. The low HAT prevalence hampers assessment of the sensitivity of HAT RDTs and remote tests. All available results should therefore be published. We prospectively evaluated HAT RDTs and remote reference laboratory tests diagnostic performances in passive screening in 3 countries, and report the results of the Democratic Republic of the Congo here. The sensitivity of the HAT Sero K -SeT, one of the 2 HAT RDTs that are actually commercialised, complied with the ideal >99% sensitivity of the target product profile established by WHO, but its specificity was on the limit of minimally acceptable, set by WHO at >95%. Antibody detection with trypanolysis and/or indirect ELISA/ T.b. gambiense is already routinely implemented, but the use of dried blood spots seems to reduce the tests’ sensitivity. LAMP Trypanosoma brucei Detection Kit, m18S and TgsGp qPCR were not reliable. These results confirm other study data from Guinea and Côte d’Ivoire. The diagnostic performance of newly emerging molecular tests, should be further evaluated.
