scholarly journals Faculty Opinions recommendation of Usefulness of real-time PCR during follow-up of patients treated with Benznidazole for chronic Chagas disease: Experience in two referral centers in Barcelona.

Author(s):  
Pedro Legua Leiva
2020 ◽  
Vol 14 (2) ◽  
pp. e0008067 ◽  
Author(s):  
Elena Sulleiro ◽  
Aroa Silgado ◽  
Núria Serre-Delcor ◽  
Fernando Salvador ◽  
Maykon Tavares de Oliveira ◽  
...  

Author(s):  
Marina Simón ◽  
M. Asunción Iborra ◽  
Bartolomé Carrilero ◽  
Manuel Segovia

2020 ◽  
Vol 38 (8) ◽  
pp. 353-355
Author(s):  
Marina Simón ◽  
M. Asunción Iborra ◽  
Bartolomé Carrilero ◽  
Manuel Segovia

2015 ◽  
Vol 8 (1) ◽  
pp. 154 ◽  
Author(s):  
Myllena F Melo ◽  
Otacilio C Moreira ◽  
Priscila Tenório ◽  
Virginia Lorena ◽  
Izaura Lorena-Rezende ◽  
...  

PLoS ONE ◽  
2018 ◽  
Vol 13 (11) ◽  
pp. e0208133 ◽  
Author(s):  
Daniella Alchaar D’Ávila ◽  
Lúcia Maria C. Galvão ◽  
Giovane R. Sousa ◽  
Constança Britto ◽  
Otacilio C. Moreira ◽  
...  

2018 ◽  
Author(s):  
Rudy Parrado ◽  
Juan Carlos Ramirez ◽  
Anabelle de la Barra ◽  
Cristina Alonso-Vega ◽  
Natalia Juiz ◽  
...  

AbstractThis work evaluated a serial blood sampling procedure to enhance the sensitivity of duplex real time PCR (qPCR) for baseline detection and quantification of parasitic loads and post-treatment identification of failure in the context of clinical trials for treatment of chronic Chagas disease, namely DNDi-CH-E1224-001 (NCT01489228) and MSF-DNDi PCR sampling optimization study (NCT01678599). Patients from Cochabamba (N= 294), Tarija (N = 257), and Aiquile (N= 220) were enrolled. Three serial blood samples were collected at each time-point, and qPCR triplicates were tested per sample. The first two samples were collected during the same day and the third one seven days later.A patient was considered PCR positive if at least one qPCR replicate was detectable. Cumulative results of multiple samples and qPCR replicates enhanced the proportion of pre-treatment sample positivity from 54.8 to 76.2%, 59.5 to 77.8%, and 73.5 to 90.2% in Cochabamba, Tarija, and Aiquile cohorts, respectively and increased cumulative detection of treatment failure from 72.9 to 91.7%, 77.8 to 88.9%, and 42.9 to 69.1% for E1224 low, short, and high dosage regimes, respectively; and from 4.6 to 15.9% and 9.5 to 32.1% for the benznidazole (BZN) arm in the DNDi-CH-E1224-001 and MSF-DNDi studies, respectively. The monitoring of patients treated with placebo in the DNDi-CH-E1224-001 trial revealed fluctuations in parasitic loads and occasional non-detectable results. This serial sampling strategy enhanced PCR sensitivity to detecting treatment failure during follow-up and has the potential for improving recruitment capacity in Chagas disease trials which require an initial positive qPCR result for patient admission.


EBioMedicine ◽  
2021 ◽  
Vol 69 ◽  
pp. 103450
Author(s):  
Alejandro Francisco Benatar ◽  
Emmaría Danesi ◽  
Susana Alicia Besuschio ◽  
Santiago Bortolotti ◽  
María Luisa Cafferata ◽  
...  

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4225-4225
Author(s):  
Gareth Gerrard ◽  
Caroline Cloke ◽  
Ian H Gabriel ◽  
Katayoun Rezvani ◽  
Jane F. Apperley ◽  
...  

Abstract Introduction. Chronic myeloid leukaemia (CML) is a malignant clonal myeloproliferative disorder characterised by the presence of the Philadelphia chromosome (Ph) and expression of the BCR-ABL fusion protein with constitutive tyrosine kinase activity and multi-target dysregulation. Standard therapy employs the use of tyrosine kinase inhibitors, such as Imatinib mesylate, with a high level of success. However, in a proportion of patients this approach is sub-optimal necessitating the use other treatment modalities. Allogeneic stem cell transplantation (allo-SCT) is established and potentially curative via the immunologically mediated graft-versus-leukaemia (GvL) effect, but it is associated with significant morbidity, long term effects and high mortality rate (30%). An alternative approach is to employ peptide vaccines directed against leukaemia associated antigens (LAA) in order to evoke a curative anti-leukaemia immune response without the risk of graft versus host disease. Prevalent among these LAAs are WT1 (Wilms Tumour 1) and PRAME (preferentially expressed antigen in melanoma). WT1 encodes a transcription factor of the zinc-finger family, and is known to be over-expressed in many types of leukaemia. PRAME (PRA) is a cancer testis antigens over-expressed in haematological malignancies including CML, making it an attractive target for immunotherapy. HLA-A2 and A-24 restricted epitopes derived from PRA have been shown to be immunogenic by a number of groups. Here, we studied the value of PRA and WT1 measurement in assessing minimal residual disease (MRD) in CML compared to BCR-ABL. Materials & Methods. cDNA from PB samples from 76 diagnostic samples and 127 follow-up samples from 114 patients were tested. The follow-up samples were subdivided into 3 groups according to BCR-ABL expression: MRD1 >10%, MRD2: 1%-10%, MRD3 <1%. All samples were analysed for WT1 and PRA, except for the diagnostic samples, where only 6 were available for PRA analysis due to a lack of material. All expression data was obtained by quantitative real-time PCR (Q-PCR) on the ABI 7500 platform. The BCR-ABL was expressed as a percentage ratio against ABL, using absolute quantification. WT1 and PRA expression was derived using the relative expression dCt method, normalised against a house keeping gene (GUS), after ensuring equivalent Q-PCR efficiencies. Results. WT1 and PRA expression was detectable in all samples analysed. A non-parametric correlation, performed on all data points, found a positive correlation between expression of BCR-ABL and expression of WT1 (r= 0.6710, P<0.0001) and PRA (r= 0.4194, P<0.0001) (Figure 1). The median WT1 and PRA expression of the remission samples was calculated and used as a cut-off to define over-expression (2.89E-05 and 7.04E-05, respectively). This was then used to assess the proportion of samples from the diagnostic and follow-up groups that over-expressed WT1 (Diag= 96.1%, MRD1= 90.0%, MRD2= 66.7%, MRD3= 33.3%) and PRA (Diag= 100%, MRD1= 82.5%, MRD2= 41.7%, MRD3= 60.0%). The differences in over-expression between the groups were found to be highly significant by 2×4 contingency Chi square test (P<0.0001 for both WT1 and PRA). Discussion. This analysis shows that both WT1 and PRA expression positively correlate with BCR-ABL level in CML patients, and can be reliably quantitated using Q-PCR. This technique can therefore provide useful information for treatment monitoring of immunotherapy directed against such antigens. The median expression of the remission samples can be used as a useful cut-off for assessing over-expression for WT1, but maybe of less value in respect to PRA, due to a lack of discrimination at low BCR-ABL levels shown by the discordantly high value of positivity in the MRD3 group. Figure 1. Expression of A: WT1 and B: PRAME in CML, subdivided by BCR-AEL expression (vertical lines) and over-expression thresold (horizontal line). Figure 1. Expression of A: WT1 and B: PRAME in CML, subdivided by BCR-AEL expression (vertical lines) and over-expression thresold (horizontal line).


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