Performance Assessment of a Trypanosoma cruzi Chimeric Antigen in Multiplex Liquid Microarray Assays

Santos, Fred Luciano Neves; Celedón, Paola Alejandra Fiorani; Zanchin, Nilson Ivo Tonin; Leitolis, Amanda; Crestani, Sandra; Foti, Leonardo; Souza, Wayner Vieira de; Gomes, Yara de Miranda; Krieger, Marco Aurélio

doi:10.1128/jcm.00851-17

Cited by 23 publications

(46 citation statements)

References 30 publications

(37 reference statements)

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“…This level of accuracy improves the detection limit by LMA assays [48,49]. Despite the advantages offered by LMA-based technology, the need for a more complex laboratory infrastructure, well-trained workforce, and substantial financial investment [50] did not allow the study to be conducted using this diagnostic methodology alone.…”

Section: Discussionmentioning

confidence: 99%

Performance of Treponema pallidum recombinant proteins in the serological diagnosis of syphilis

et al. 2020

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Syphilis serodiagnosis is challenging because distinct clinical forms of the infection may influence serological performance and discordant results between tests make clinical decisions difficult. Several recombinant Treponema pallidum-proteins have already been tested for syphilis diagnosis and they are critical to achieve high accuracy in serological testing. Our aim was to assess the varied from performance of T. pallidum-recombinant proteins TmpA, TpN17 and TpN47 for syphilis serodiagnosis. The proteins were evaluated using sera of 338 T. pallidum-negative, 173 T. pallidum-positive individuals and 209 sera from individuals infected with unrelated diseases. The diagnostic potential was validated by analysis of ROC curves. In the liquid microarray analyses, the ROC curve varied from 99.0% for TmpA and TpN17 to 100% for TpN47. The sensitivity score yielded values of up to 90% for TpN17, 100% for TpN47 and 80.0% for TmpA. The lowest and highest specificity values were presented by TpN47 (91.9%) and TmpA antigens (100%), respectively. TpN47 showed the highest accuracy score (95.5%) among all the recombinant proteins assayed. For the ELISA, the ROC curve was 97.2%, 91.8% and 81.6% for TpN17, TmpA and TpN47, respectively. TpN17 and TmpA yielded a sensitivity of 69.9%, while TpN47 obtained a value of 53.8%. Specificity was almost 100% for all three proteins. No cross-reaction was observed for TpN17 in the serum samples from non-bacterial infections. Regarding leptospirosis-positive samples, cross-reactivity score was varied from 8.6 to 34.6%. This is most probably due to conservation of the epitopes in these proteins across bacteria. The use of recombinant proteins in immunoassays for syphilis diagnosis was showed provide greater reliability to results of the treponemal assays. Despite the low sensitivity, the proteins showed high diagnostic capacity due to the AUC values found. However, an improvement in sensitivity could be achieved when antigenic mixtures are evaluated.

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Section: Discussionmentioning

confidence: 99%

Performance of Treponema pallidum recombinant proteins in the serological diagnosis of syphilis

et al. 2020

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“…These results are in agreement with previous reports using commercial tests as a gold standard, in which the performance of these proteins was previously assessed by both ELISA and liquid microarray (LMA). 20 , 22 With respect to ELISA, these values ranged from 94.3% to 99.3% and 99.4% to 100%, respectively, 20 whereas under LMA, these values ranged from 96.9% to 99.1% and 99.1% to 100%, 22 respectively. Regarding accuracy, IBMP-8.4 was found to be nearly 100% accurate (99.6%), which suggests that this antigen is the best of the four chimeras for chronic CD laboratory diagnostic purposes.…”

Section: Discussionmentioning

confidence: 91%

Highly Accurate Chimeric Proteins for the Serological Diagnosis of Chronic Chagas Disease: A Latent Class Analysis

Santos

Campos

Amorim

et al. 2018

The American Journal of Tropical Medicine and Hygiene

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Abstract.The existence of an imperfect reference standard presents complications when evaluating the unbiased performance of novel diagnostic techniques. This is especially true in the absence of a gold standard, as is the case in chronic Chagas disease (CD) diagnosis. To circumvent this constraint, we elected to use latent class analysis (LCA). Previously, our group demonstrated the high performance of four Trypanosoma cruzi–chimeric proteins (Molecular Biology Institute of Paraná [IBMP]-8.1, -8.2, -8.3, and -8.4) for CD diagnosis using several distinct immunoassays. Although commercial tests had previously been established as a reference standard, the diagnostic performance of these chimeric antigens could present bias because these tests fail to produce 100% accurate results. Thus, we used LCA to assess the performance of these IBMP chimeric antigens in chronic CD diagnosis. Using the LCA model as a gold standard, sensitivity and specificity values ranged from 93.5% to 99.4% and 99.6% to 100%, respectively. The accuracy values were 96.2% for IBMP-8.2, approximately 98% for IBMP-8.1 and IBMP-8.3, and nearly 100% for IBMP-8.4. For IBMP-8.1 and IBMP-8.2, higher positive predictive values were associated with increases in hypothetical prevalence. Similarly, higher hypothetical prevalence resulted in lower negative predictive values for IBMP-8.1, IBMP-8.2, and IBMP-8.3. In addition, samples with serodiscordant results from commercial serological tests were analyzed using LCA. Molecular Biology Institute of Paraná -8.1 demonstrated potential for use in confirmatory testing with regard to samples with inconsistent results. Moreover, our findings further confirmed the remarkable performance of the IBMP-8.4 antigen to diagnose chronic CD in both endemic and non-endemic areas.

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“…Taking in consideration the lack of agreeability between tests' performance in different areas, our group previously assessed the performance of four T. cruzi chimeric antigens in various platforms, such as ELISA and liquid microarray BioMed Research International (LUMINEX) [15,[16][17][18]. To expand our studies, we tested in 32 clinical samples from people of distinct geographical regions in this investigation.…”

Section: Discussionmentioning

confidence: 99%

“…Considering the predicaments herein set forth, our group recently expressed and purified four T. cruzi-chimeric proteins (IBMP-8.1, -8.2, -8.3, and -8.4) and assessed their diagnostic performance in the serologic diagnostic of CD under ELISA or liquid microarray format assays [15][16][17][18] in different endemic settings in several Latin American countries [19] and in their immigrants living in Barcelona/Spain [20]. Additionally, these chimeric proteins have shown a negligible cross-reactivity with both American cutaneous and visceral leishmaniasis, demonstrating their utility in regions where T. cruzi and Leishmania spp.…”

Section: Introductionmentioning

confidence: 99%

Development of a New Lateral Flow Assay Based on IBMP-8.1 and IBMP-8.4 Chimeric Antigens to Diagnose Chagas Disease

Silva

Santos

et al. 2020

BioMed Research International

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Despite several available methodologies for Chagas disease (CD) serological screening, the main limitation of chronic CD diagnosis is the lack of effective tools for large-scale screening and point-of-care diagnosis to be used in different CD epidemiological scenarios. Taking into account that developing such a diagnostic tool will significantly improve the ability to identify CD carriers, we aimed at performing a proof-of-concept study (phase I study) to assess the use of these proteins in a point-of-care platform using serum samples from different geographical settings of Brazil and distinct clinical presentations. The diagnostic accuracy study was conducted on a panel of two WHO International Standards (IS) and 14 sera from T. cruzi-positive and 16 from T. cruzi-negative individuals. The results obtained with the test strips were converted to digital images, allowing quantitative comparison expressed as a relative band intensity ratio (RBI). The diagnostic potential and performance were also determined. Regardless of the geographical origin or clinical presentation, all sera with T. cruzi antibodies returned positive both for IBMP-8.1 and IBMP-8.4 chimeric antigens. The area under the ROC curve (AUC) values was 100% for both antigens, demonstrating an outstanding overall diagnostic accuracy (100%). Based on the data, we believe that the lateral flow assays based on these antigens are promising methodologies for screening CD.

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Performance Assessment of a Trypanosoma cruzi Chimeric Antigen in Multiplex Liquid Microarray Assays

Cited by 23 publications

References 30 publications

Performance of Treponema pallidum recombinant proteins in the serological diagnosis of syphilis

Performance of Treponema pallidum recombinant proteins in the serological diagnosis of syphilis

Highly Accurate Chimeric Proteins for the Serological Diagnosis of Chronic Chagas Disease: A Latent Class Analysis

Development of a New Lateral Flow Assay Based on IBMP-8.1 and IBMP-8.4 Chimeric Antigens to Diagnose Chagas Disease

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