Dataset Information

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

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.

SUBMITTER: Santos FLN

PROVIDER: S-EPMC6221211 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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

Santos Fred Luciano Neves FLN Campos Ana Clara Paixão ACP Amorim Leila Denise Alves Ferreira LDAF Silva Edimilson Domingos ED Zanchin Nilson Ivo Tonin NIT Celedon Paola Alejandra Fiorani PAF Del-Rei Rodrigo Pimenta RP Krieger Marco Aurélio MA Gomes Yara Miranda YM

The American journal of tropical medicine and hygiene 20181101 5

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 <i>Trypanosoma cruzi</i>-chimeric proteins (Molecular Biology Institute of Paraná [IBMP]-8.1, -8. ...[more]

PMID: 30226130

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Project description:BackgroundDogs are considered sentinels in areas of Trypanosoma cruzi transmission risk to humans. ELISA is generally the method of choice for diagnosing T. cruzi exposure in dogs, but its performance substantially depends on the antigenic matrix employed. In previous studies, our group has developed four chimeric antigens (IBMP-8.1, 8.2, 8.3, and 8.4) and evaluated their potential for diagnosing T. cruzi exposure in humans. For human sera, these chimeric antigens presented superior diagnostic performances as compared to commercial tests available in Brazil, Spain, and Argentina. Therefore, in this study we have evaluated the potential of these antigenic proteins for detection of anti-T. cruzi IgG antibodies in dog sera.Methodology/principal findingsThe IBMP-ELISA assays were optimized by checkerboard titration. Subsequently, the diagnostic potential was validated through analysis of ROC curves and the performance of the tests was determined using double entry tables. Cross-reactivity was also evaluated for babesiosis, ehrlichiosis, dirofilariosis, anaplasmosis, and visceral leishmaniasis. Best performance was shown by IBMP-8.3 and IBMP-8.4, although all four antigens demonstrated a high diagnostic performance with 46 positive and 149 negative samples tested. IBMP-8.3 demonstrated 100% sensitivity, followed by IBMP-8.4 (96.7-100%), IBMP-8.2 (73.3-87.5%), and IBMP-8.1 (50-100%). The highest specificities were achieved with IBMP-8.2 (100%) and IBMP-8.4 (100%), followed by IBMP-8.3 (96.7-97.5%) and IBMP 8.1 (89.1-100%).Conclusions/significanceThe use of chimeric antigenic matrices in immunoassays for anti-T. cruzi IgG antibody detection in sera of infected dogs was shown to be a promising tool for veterinary diagnosis and epidemiological studies. The chimeric antigens used in this work allowed also to overcome the common hurdles related to serodiagnosis of T. cruzi infection, especially regarding variation of efficiency parameters according to different strains and cross-reactivity with other infectious diseases.

Project description:AimsThe main focus of this study is to illustrate the importance of the statistical analysis in the evaluation of the accuracy of malaria diagnostic tests, without admitting a reference test, exploring a dataset (n=3317) collected in São Tomé and Príncipe.MethodsBayesian Latent Class Models (without and with constraints) are used to estimate the malaria infection prevalence, together with sensitivities, specificities, and predictive values of three diagnostic tests (RDT, Microscopy and PCR), in four subpopulations simultaneously based on a stratified analysis by age groups (< 5, ? 5 years old) and fever status (febrile, afebrile).ResultsIn the afebrile individuals with at least five years old, the posterior mean of the malaria infection prevalence is 3.2% with a highest posterior density interval of [2.3-4.1]. The other three subpopulations (febrile ? 5 years, afebrile or febrile children less than 5 years) present a higher prevalence around 10.3% [8.8-11.7]. In afebrile children under-five years old, the sensitivity of microscopy is 50.5% [37.7-63.2]. In children under-five, the estimated sensitivities/specificities of RDT are 95.4% [90.3-99.5]/93.8% [91.6-96.0]--afebrile--and 94.1% [87.5-99.4]/97.5% [95.5-99.3]--febrile. In individuals with at least five years old are 96.0% [91.5-99.7]/98.7% [98.1-99.2]--afebrile--and 97.9% [95.3-99.8]/97.7% [96.6-98.6]--febrile. The PCR yields the most reliable results in four subpopulations.ConclusionsThe utility of this RDT in the field seems to be relevant. However, in all subpopulations, data provide enough evidence to suggest caution with the positive predictive values of the RDT. Microscopy has poor sensitivity compared to the other tests, particularly, in the afebrile children less than 5 years. This type of findings reveals the danger of statistical analysis based on microscopy as a reference test. Bayesian Latent Class Models provide a powerful tool to evaluate malaria diagnostic tests, taking into account different groups of interest.

Project description:BackgroundChagas disease is a public health challenge in Colombia, where only an estimated 1.2% of people at risk have accessed diagnosis, while less than 0.5% of affected people have obtained treatment. The development of simplified diagnostic algorithms would enable progress in access to diagnosis; however, the current diagnostic algorithm relies on at least two laboratory-based tests that require qualified personnel, processing equipment, and infrastructure, which are still generally lacking at the primary care level. Rapid diagnostic tests (RDTs) for Chagas disease could simplify diagnosis, but their performance in the epidemiological context of Colombia is not well known.MethodologyA retrospective analytical observational study of RDTs was performed to estimate the operational characteristics of 11 commercially available RDTs designed for in vitro detection of anti-T. cruzi IgG antibodies. The study was performed under controlled laboratory conditions using human serum samples.Principal findingsEleven RDTs were assessed, ten using 585 serum samples and one using 551 serum samples. Employing the current national diagnostic algorithm as a reference standard for serological diagnosis of chronic infection, the sensitivity of the assessed RDTs ranged from 75.5% to 99.0% (95% CI 70.5-100), while specificity ranged from 70.9% to 100% (95% CI 65.3-100). Most tests (7/11, 63.6%) had sensitivity above 90%, and almost all (10/11, 90.9%) had specificity above 90%. Five RDTs had both sensitivity and specificity above 90%.Conclusions/significanceThe evaluation of these 11 commercially available RDTs under controlled laboratory conditions is a first step in the assessment of the diagnostic performance of RDTs in Colombia. As a next step, field studies will be conducted on available RDTs with sensitivity and specificity greater than 90% in this study, to evaluate performance in real world conditions, with the final goal to allow simplified diagnostic algorithms.

Dataset Information

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

Publications

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

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