Usefulness of FC-TRIPLEX Chagas/Leish IgG1 as confirmatory assay for non-negative results in blood bank screening of Chagas disease

Campos, Fernanda Magalhães Freire; Repolês, Laura Cotta; Araújo, Fernanda Fortes de; Peruhype-Magalhães, Vanessa; Xavier, Marcelo Antônio Pascoal; Sabino, Éster Cerdeira; Proietti, Anna Bárbara de Freitas Carneiro; Andrade, Mariléia Cháves; Teixeira-Carvalho, Andréa; Martins‐Filho, Olindo Assis; Gontijo, Célia Maria Ferreira

doi:10.1016/j.jim.2018.01.006

Cited by 7 publications

(3 citation statements)

References 28 publications

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“…In human VL, several studies have shown issues related to cross-reactivity with Chagas disease, owing to the sharing of antigens associated with phylogenetic proximity [47,48]. However, we demonstrated that the mixture of peptides increased the specificity and accuracy compared to that shown by isolated peptides, as confirmed by the higher performance values and lower crossreactivity in T. cruzi, E. canis, and B. canis pathogens [49], and have previously reported that the association of antigens can lead to better performance because of the use of a single platform for the simultaneous serological measurement of antibodies against different antigens of L. infantum. This fact can be associated with the binding of antibodies with higher avidity to the antigens, and the peptide mix could select these antibodies more effectively, favoring a more specific interaction.…”

Section: Discussionsupporting

confidence: 57%

Synthetic Peptides Selected by Immunoinformatics as Potential Tools for the Specific Diagnosis of Canine Visceral Leishmaniasis

Moreira,

Maia,

Soares

et al. 2024

Microorganisms

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Diagnosing canine visceral leishmaniasis (CVL) in Brazil faces challenges due to the limitations regarding the sensitivity and specificity of the current diagnostic protocol. Therefore, it is urgent to map new antigens or enhance the existing ones for future diagnostic techniques. Immunoinformatic tools are promising in the identification of new potential epitopes or antigen candidates. In this study, we evaluated peptides selected by epitope prediction for CVL serodiagnosis in ELISA assays. Ten B-cell epitopes were immunogenic in silico, but two peptides (peptides No. 45 and No. 48) showed the best performance in vitro. The selected peptides, both individually and in combination, were highly diagnostically accurate, with sensitivities ranging from 86.4% to 100% and with a specificity of approximately 90%. We observed that the combination of peptides showed better performance when compared to peptide alone, by detecting all asymptomatic dogs, showing lower cross-reactivity in sera from dogs with other canine infections, and did not detect vaccinated animals. Moreover, our data indicate the potential use of immunoinformatic tools associated with ELISA assays for the selection and evaluation of potential new targets, such as peptides, applied to the diagnosis of CVL.

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Section: Discussionsupporting

confidence: 57%

Synthetic Peptides Selected by Immunoinformatics as Potential Tools for the Specific Diagnosis of Canine Visceral Leishmaniasis

Moreira,

Maia,

Soares

et al. 2024

Microorganisms

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“…In a previous report of anti- T. cruzi IgG1 levels following accidental infection with T. cruzi , the anti- T. cruzi IgG1, IgG3 and IgG4 returned to pre-infection levels 55 days post-chemotherapy and 80 days after infection, whereas the IgG2 titres remained high at 300 days after infection [ 59 ]. Anti- T. cruzi IgG1 serology has been shown to be highly sensitive and specific for screening blood donors when conventional serological methods (ELISA and IIF) previously gave inconclusive results [ 60 ]. Similarly, anti-epimastigote IgG1 has been able to distinguish between T. cruzi -infected and non-infected individuals [ 61 ].…”

Section: Discussionmentioning

confidence: 99%

Assessing antibody decline after chemotherapy of early chronic Chagas disease patients

et al. 2021

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Background Chagas disease remains a significant public health problem in Latin America. There are only two chemotherapy drugs, nifurtimox and benznidazole, and both may have severe side effects. After complete chemotherapy of acute cases, seropositive diagnosis may revert to negative. However, there are no definitive parasitological or serological biomarkers of cure. Methods Following a pilot study with seven Bolivian migrants to Spain, we tested 71 serum samples from chronic patients (mean age 12.6 years) inhabiting the Argentine Chaco region. Benznidazole chemotherapy (5–8 mg/kg day, twice daily for 60 days) was administered during 2011–2016. Subsequently, pre-and post-chemotherapy serum samples were analysed in pairs by IgG1 and IgG ELISA using two different antigens and Chagas Sero K-SeT rapid diagnostic tests (RDT). Molecular diagnosis by kDNA-PCR was applied to post-treatment samples. Results Pilot data demonstrated IgG1 antibody decline in three of seven patients from Bolivia 1 year post-treatment. All Argentine patients in 2017 (averaging 5 years post-treatment), except one, were positive by conventional serology. All were kDNA-PCR-negative. Most (91.5%) pre-treatment samples were positive by the Chagas Sero K-SeT RDT, confirming the predominance of TcII/V/VI. IgG1 and IgG of Argentine patients showed significant decline in antibody titres post-chemotherapy, with either lysate (IgG, P = 0.0001, IgG1, P = 0.0001) or TcII/V/VI peptide antigen (IgG, P = 0.0001, IgG1, P = 0.0001). IgG1 decline was more discriminative than IgG. Antibody decline after treatment was also detected by the RDT. Incomplete treatment was associated with high IgG1 post-treatment titres against lysate (P = 0.013), as were IgG post-treatment titres to TcII/V/VI peptide (P = 0.0001). High pre-treatment IgG1 with lysate was associated with Qom ethnicity (P = 0.045). No associations were found between gender, age, body mass index and pre- or post-treatment antibody titres. Conclusions We show that following chemotherapy of early chronic Chagas disease, significant decline in IgG1 antibody suggests cure, whereas sustained or increased IgG1 is a potential indicator of treatment failure. Due to restricted sensitivity, IgG1 should not be used as a diagnostic marker but has promise, with further development, as a biomarker of cure. Graphical abstract We show that following chemotherapy of early chronic Chagas disease, a significant decline in IgG1 antibody suggests cure, whereas sustained or increased IgG1 is a potential indicator of treatment failure. Due to restricted sensitivity, IgG1 should not be used as a diagnostic marker but has promise, with further development, as a biomarker of cure.

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“…Serological tests cannot discriminate between treated individuals and those with CD and have shown inconsistent results in adult studies [ 9 ]. Blood bank evaluations rely on serological testing, and confirmation assays must be performed to elucidate the status of non-negative results [ 10 , 11 ]. In addition, seroreversion, the gold standard, can take decades in adults.…”

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confidence: 99%

Validation of Apolipoprotein A-1 and Fibronectin Fragments as Markers of Parasitological Cure for Congenital Chagas Disease in Children Treated With Benznidazole

Ruiz-Lancheros

Rasoolizadeh

Chatelain

et al. 2018

Open Forum Infectious Diseases

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BackgroundNo reliable tests or validated biomarkers exist to ensure parasitological cure following treatment of Chagas disease (CD) patients chronically infected with Trypanosoma cruzi. As seroreversion, the only marker of cure, happens more quickly in children, we investigated the correlation between previously identified biomarkers and seroreversion in children.MethodsThirty CD children (age 1 month to 10 years) diagnosed as T. cruzi positive (time point S0) were treated with benznidazole (BZ) 5–8 mg/kg/d for 60 days. At least 2 serological tests were used to evaluate treatment efficacy from the end of treatment (S1) until seroreversion (S2). Thirty children (age 1 month to 10 years) and 15 adults were used as healthy controls (HCs). Immunoblot and a proteomic-based assay were used to validate previously identified fragments of apolipoprotein A-1 (ApoA1) and fibronectin (FBN) as CD biomarkers.ResultsCorrelation between seroreversion and absence of ApoA1 and FBN fragments by immunoblot was observed in 30/30 (100%) and 29/30 (96.6%) CD children, respectively. ApoA1 and FBN fragments were absent at the end of BZ treatment in 20/30 (66.6%) and 16/30 (53.3%) children, respectively. Absence of fragments in serum profiles was confirmed by mass spectrometry. Using intact protein analysis, a 28 109-Da protein identified as full-length ApoA1 by tandem mass spectrometry was detected in HC serum samples.ConclusionsThese data confirm that ApoA1 and FBN fragments can discriminate between healthy and T. cruzi–infected samples. Correlation with seroreversion was shown for the first time; results suggest predictive capacity potentially superior to serology, making them potentially useful as surrogate biomarkers.

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Usefulness of FC-TRIPLEX Chagas/Leish IgG1 as confirmatory assay for non-negative results in blood bank screening of Chagas disease

Cited by 7 publications

References 28 publications

Synthetic Peptides Selected by Immunoinformatics as Potential Tools for the Specific Diagnosis of Canine Visceral Leishmaniasis

Synthetic Peptides Selected by Immunoinformatics as Potential Tools for the Specific Diagnosis of Canine Visceral Leishmaniasis

Assessing antibody decline after chemotherapy of early chronic Chagas disease patients

Validation of Apolipoprotein A-1 and Fibronectin Fragments as Markers of Parasitological Cure for Congenital Chagas Disease in Children Treated With Benznidazole

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