Evaluation of Antigens for Development of a Serological Test for Human African Trypanosomiasis

Biéler, Sylvain; Waltenberger, Harald; Barrett, Michael P.; McCulloch, Richard; Mottram, Jeremy C.; Carrington, Mark; Schwaeble, Wilhelm; McKerrow, James H.; Phillips, Margaret A.; Michels, Paul A.M.; Büscher, Philippe; Sanchez, Jean‐Charles; Bishop, Richard P.; Robinson, Derrick R.; Bangs, James D.; Ferguson, Michael A. J.; Nerima, Barbara; Albertini, Audrey; Michel, Gerd; Radwandska, Magdalena; Ndung’u, Joseph Mathu

doi:10.1371/journal.pone.0168074

Cited by 14 publications

(9 citation statements)

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“…In fact, sera from animals infected with either T. congolense , T. b. brucei or T. evansi have been shown to cross-react with antigens used in the RDT and the card agglutination test for gambiense human African trypanosomiasis [ 18 , 43 , 61 ]. Moreover, sera from both T. b. gambiense and T. b. rhodesiense patients have induced cross-reactions with a large number of trypanosome antigens including VSG LiTat 1.3 and VSG LiTat 1.5 [ 1 ]. The identification of T. congolense and T. vivax in equines of the same HAT foci [ 58 ] and the fact that three animals found with trypanosome infections by CTC, but in which trypanosomes of the subgenus Trypanozoon was not detected by PCR, suggest the presence of other trypanosome species in the study area.…”

Section: Discussionmentioning

confidence: 99%

Molecular identification of Trypanosoma brucei gambiense in naturally infected pigs, dogs and small ruminants confirms domestic animals as potential reservoirs for sleeping sickness in Chad

et al. 2020

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Human African trypanosomiasis (HAT) has been targeted for zero transmission to humans by 2030. Animal reservoirs of gambiense-HAT could jeopardize these elimination goals. This study was undertaken to identify potential host reservoirs for Trypanosoma brucei gambiense by detecting its natural infections in domestic animals of Chadian HAT foci. Blood samples were collected from 267 goats, 181 sheep, 154 dogs, and 67 pigs. Rapid diagnostic test (RDT) and capillary tube centrifugation (CTC) were performed to search for trypanosomes. DNA was extracted from the buffy coat, and trypanosomes of the subgenus Trypanozoon as well as T. b. gambiense were identified by PCR. Of 669 blood samples, 19.4% were positive by RDT and 9.0% by CTC. PCR revealed 150 animals (22.4%) with trypanosomes belonging to Trypanozoon, including 18 (12%) T. b. gambiense. This trypanosome was found in all investigated animal species and all HAT foci. Between animal species or villages, no significant differences were observed in the number of animals harboring T. b. gambiense DNA. Pigs, dogs, sheep and goats appeared to be potential reservoir hosts for T. b. gambiense in Chad. The identification of T. b. gambiense in all animal species of all HAT foci suggests that these animals should be considered when designing new control strategies for sustainable elimination of HAT. Investigations aiming to decrypt their specific role in each epidemiological setting are important to achieve zero transmission of HAT.

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Section: Discussionmentioning

confidence: 99%

Molecular identification of Trypanosoma brucei gambiense in naturally infected pigs, dogs and small ruminants confirms domestic animals as potential reservoirs for sleeping sickness in Chad

et al. 2020

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“…Alternatively, investing in the development of a new screening test that would be more sensitive than the tests that were evaluated here, and which would include multiple antigens, could be considered. Such a test might be developed by combining three or more antigens, which could include those in the RDT2, as well as other promising candidates identified in previous studies [ 23 – 28 ]. Other RDTs being developed using recombinant antigens will also need to be considered once they are available and their performance has been evaluated [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

Prospective evaluation of a rapid diagnostic test for Trypanosoma brucei gambiense infection developed using recombinant antigens

et al. 2018

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BackgroundDiagnosis and treatment are central elements of strategies to control Trypanosoma brucei gambiense human African trypanosomiasis (HAT). Serological screening is a key entry point in diagnostic algorithms. The Card Agglutination Test for Trypanosomiasis (CATT) has been the most widely used screening test for decades, despite a number of practical limitations that were partially addressed by the introduction of rapid diagnostic tests (RDTs). However, current RDTs are manufactured using native antigens, which are challenging to produce.Methodology/Principal findingsThe objective of this study was to evaluate the accuracy of a new RDT developed using recombinant antigens (SD BIOLINE HAT 2.0), in comparison with an RDT produced using native antigens (SD BIOLINE HAT) and CATT. A total of 57,632 individuals were screened in the Democratic Republic of the Congo, either passively at 10 health centres, or actively by 5 mobile teams, and 260 HAT cases were confirmed by parasitology. The highest sensitivity was achieved with the SD BIOLINE HAT 2.0 (71.2%), followed by CATT (62.5%) and the SD BIOLINE HAT (59.0%). The most specific test was CATT (99.2%), while the specificity of the SD BIOLINE HAT and SD BIOLINE HAT 2.0 were 98.9% and 98.1%, respectively. Sensitivity of the tests was lower than previously reported, as they identified cases from partially overlapping sub-populations. All three tests were significantly more sensitive in passive than in active screening. Combining two or three tests resulted in a markedly increased sensitivity: When the SD BIOLINE HAT was combined with the SD BIOLINE HAT 2.0, sensitivity reached 98.4% in passive and 83.0% in active screening.Conclusions/SignificanceThe recombinant antigen-based RDT was more sensitive than, and as specific as, the SD BIOLINE HAT. It was as sensitive as, but slightly less specific than CATT. While the practicality and cost-effectiveness of algorithms including several screening tests would need to be investigated, using two or more tests appears to enhance sensitivity of diagnostic algorithms, although some decrease in specificity is observed as well.

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“…In other studies, the CATT test, which has the VSG LiTat 1.3 antigen, was also positive in animals infected with either T. congolense, T. b. brucei or T. evansi [ 46 – 48 ]. In another study, a large number of trypanosome antigens, including VSG LiTat 1.3 and VSG LiTat 1.5, reacted to sera from both T. b. gambiense and T. b. rhodesiense patients [ 49 ]. Another candidate, rISG65-2 had a sensitivity of 92% and a specificity of 85% for T. b. rhodesiense [ 50 , 51 ], indicating that, while the antigens in these studies had good sensitivity for both T. b. gambiense and T. b. rhodesiense , their sensitivity was not restricted to the two sub-species of trypanosomes.…”

Section: Discussionmentioning

confidence: 99%

Serological tests for gambiense human African trypanosomiasis detect antibodies in cattle

et al. 2017

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BackgroundSerological tests for gambiense human African trypanosomiasis (gHAT) detect antibodies to antigens on the cell surface of bloodstream trypanosomes. As trypanosomes that cause animal African trypanosomiasis (AAT) also express related antigens, we have evaluated two rapid diagnostic tests (RDTs) on cattle in trypanosomiasis endemic and non-endemic regions, to determine whether gHAT serological tests could also be used to screen for AAT.MethodsTwo RDTs, 1G RDT, made with native antigens, and p2G RDT, made with recombinant antigens, were tested on 121 cattle in a trypanosomiasis-free region, and on 312 cattle from a rhodesiense HAT and AAT endemic region. A subset of samples from the endemic region were also tested with two immune trypanolysis (TL) tests. The sensitivity of the tests was estimated by evaluating the result of the RDT on samples that were positive by both microscopy and internal transcribed spacer (ITS) PCR, whilst specificity was the result of the RDT on samples that were negative by ITS PCR and microscopy, and others from the non-endemic region.ResultsThe specificity of the p2G RDT on cattle from the non-endemic region was 97.5% (95% CI: 93.0–99.2%), compared to only 57.9% (95% CI: 48.9–66.3%) for 1G RDT. The specificities of 1G RDT, p2G RDT and TL on endemic control cattle were 14.6% (95% CI: 9.7–21.5%), 22.6% (95% CI: 16.4–30.3%) and 68.3% (95% CI: 59.6–75.9%), respectively. The sensitivities of the tests on trypanosome positive samples were 85.1% (95% CI: 79.1–89.7%), 89.1% (95% CI: 83.7–93.0%) and 59.3% (95% CI: 51.8–66.4%), respectively. Among the same samples, 51.7% were positive by both TL and the 1G RDT.ConclusionsThese serological tests detect cross-reacting antibodies in cattle. The p2G RDT based on recombinant antigens had a high specificity in a non-endemic region, while the 1G RDT had a lower specificity, suggesting cross-reactivity with other pathogens.Electronic supplementary materialThe online version of this article (10.1186/s13071-017-2487-8) contains supplementary material, which is available to authorized users.

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Evaluation of Antigens for Development of a Serological Test for Human African Trypanosomiasis

Cited by 14 publications

References 65 publications

Molecular identification of Trypanosoma brucei gambiense in naturally infected pigs, dogs and small ruminants confirms domestic animals as potential reservoirs for sleeping sickness in Chad

Molecular identification of Trypanosoma brucei gambiense in naturally infected pigs, dogs and small ruminants confirms domestic animals as potential reservoirs for sleeping sickness in Chad

Prospective evaluation of a rapid diagnostic test for Trypanosoma brucei gambiense infection developed using recombinant antigens

Serological tests for gambiense human African trypanosomiasis detect antibodies in cattle

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