Establishing tools for early diagnosis of congenital toxoplasmosis: Flow cytometric IgG avidity assay as a confirmatory test for neonatal screening

Zacche-Tonini, Aline de Castro; Fonseca, Giuliana Schmidt França; Jesus, Laura Néspoli Nassar Pansini de; Barros, Geisa Baptista; Coelho-dos-Reis, Jordana Grazziela Alves; Béla, Samantha Ribeiro; Machado, Anderson Silva; Carneiro, Ana Carolina Aguiar Vasconcelos; Andrade, Gláucia Manzan Queiroz de; Vasconcelos-Santos, Daniel Vítor; Januário, José Nélio; Teixeira-Carvalho, Andréa; Vítor, Ricardo Wagner Almeida; Ferro, Eloísa Amália Vieira; Mineo, José Roberto; Martins‐Filho, Olindo Assis; Lemos, Elenice Moreira

doi:10.1016/j.jim.2017.08.005

Cited by 10 publications

(9 citation statements)

References 20 publications

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“…The role of the IgG subclasses as an early diagnostic tool, indicator of parasite clearance or predictor of disease prognosis has been assessed in other protozoan infections including malaria [ 51 – 54 ] and toxoplasmosis [ 55 , 56 ]. In visceral leishmaniasis, the level of IgG1 response has been shown to be a potential therapeutic marker, principally in India; patients considered to be cured had significantly lower levels of anti- Leishmania IgG1 compared to those with treatment failure or relapse [ 57 , 58 ], possibly due the lack of sustained antigenic stimulus associated with successful chemotherapy.…”

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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Section: Discussionmentioning

confidence: 99%

Assessing antibody decline after chemotherapy of early chronic Chagas disease patients

et al. 2021

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“…Congenital infection with T. gondii can lead to severe neurological and ophthalmological sequelae and therefore the early diagnosis is relevant to support prompt clinical management and therapeutic intervention 15 . The most common methods employed for the diagnosis of congenital toxoplasmosis in newborns and infants are serological-based detection of T. gondii specific IgM, IgG and IgA antibodies 18,19 .…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, the sensitivities for IgM and IgA detection do not exceed 70% and 65% of infected babies, respectively 2 .In general, a definitive serological diagnosis of congenital toxoplasmosis requires subsequent follow-up for at least one year 21,22 . Several analytical methods have been proposed as complementary laboratory biomarkers for early diagnosis of congenital toxoplasmosis with high sensitivity and specificity aiming to improve clinical decision-making 15,17 . In the present work we have evaluated the sensitivity and specificity of a broad spectrum of immunological parameters and characterized their accuracy as complementary biomarkers for early diagnosis and prognosis of congenital toxoplasmosis.…”

Section: Discussionmentioning

confidence: 99%

“…Several analytical methods have been proposed as complementary laboratory biomarkers for early diagnosis of congenital toxoplasmosis with high sensitivity and specificity aiming to improve clinical decision-making 15 , 17 . In the present work we have evaluated the sensitivity and specificity of a broad spectrum of immunological parameters and characterized their accuracy as complementary biomarkers for early diagnosis and prognosis of congenital toxoplasmosis.…”

Section: Discussionmentioning

confidence: 99%

“…Surprisingly, the studies that investigated the potential role of cell immunity in diagnosis of congenital toxoplasmosis or methods with prognostic potential to predict the retinochoroidal lesion status are still scarce. It has been proposed that IgM screening at birth, followed by flow cytometric IgG avidity analysis at 30-45 days after birth, displays high performance for early serological diagnosis of congenital toxoplasmosis 15 . Moreover, the use of flow cytometric serology has been recognized as a potential method for early prognosis of ocular lesions in T. gondii-infected infants 16 .…”

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Putative biomarkers for early diagnosis and prognosis of congenital ocular toxoplasmosis

Araújo

Santos

Gomes

et al. 2020

Sci Rep

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In the present study we have evaluated the performance of several immunological biomarkers for early diagnosis and prognosis of congenital toxoplasmosis. Our results showed that ex vivo serum levels of CXCL9, and the frequencies of circulating CD4+CD25+ T-cells and T. gondii-specific IFN-γ+CD4+ T-cells measured 30–45 days after birth presented high accuracy to distinguish T. gondii-infected infants from healthy age-matched controls (Global Accuracy/AUC = 0.9; 0.9 and 0.8, respectively). Of note was the enhanced performance (Accuracy = 96%) achieved by using a combined stepwise analysis of CD4+CD25+ T-cells and CXCL9. In addition, high global accuracy (AUC = 0.9) with elevated sensitivity (Se = 98%) was also reached by using the total frequency of in vitro IFN-γ-producing T. gondii-specific T-cells (∑ IFN-γ+ CD4+ & CD8+) as a biomarker of congenital toxoplasmosis. Furthermore, the analysis of in vitro T. gondii-specific IL5+CD4+ T-cells and IFN-γ+NK-cells displayed a high accuracy for early prognosis of ocular lesion in infant with congenital toxoplasmosis (Global Accuracy/AUC = 0.8 and 0.9, respectively). Together, these findings support the relevance of employing the elements of the cell-mediated immune response as biomarkers with potential to endorse early diagnosis and prognosis of congenital ocular toxoplasmosis to contribute for a precise clinical management and effective therapeutic intervention.

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Recent advances and new strategies in Leishmaniasis diagnosis

Brito

Aguiar-Soares

Cardoso

et al. 2020

Appl Microbiol Biotechnol

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Establishing tools for early diagnosis of congenital toxoplasmosis: Flow cytometric IgG avidity assay as a confirmatory test for neonatal screening

Cited by 10 publications

References 20 publications

Assessing antibody decline after chemotherapy of early chronic Chagas disease patients

Assessing antibody decline after chemotherapy of early chronic Chagas disease patients

Putative biomarkers for early diagnosis and prognosis of congenital ocular toxoplasmosis

Recent advances and new strategies in Leishmaniasis diagnosis

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