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Detection of Trypanosoma cruzi DNA in blood by PCR is associated with Chagas cardiomyopathy and disease severity.

ABSTRACT: The significance of detection of Trypanosoma cruzi DNA in blood of antibody-positive patients for risk of development of Chagas heart disease is not well established. The objective of this study was to compare detection of T. cruzi DNA with known clinical and laboratory markers of Chagas cardiomyopathy (CC) severity.This is a case-control study nested within a retrospective cohort developed in Brazil to understand the natural history of Chagas disease. The study enrolled 499 T. cruzi seropositive blood donors (SP-BD) and 488 frequency matched seronegative control donors (SN-BD) who had donated between 1996 and 2002, and 101 patients with clinically diagnosed CC. In 2008-2010 all enrolled subjects underwent a health questionnaire, medical examination, electrocardiograms and echocardiograms and polymerase chain reaction (PCR) analyses. A blinded panel of three cardiologists adjudicated the outcome of CC. Trypanosoma cruzi kinetoplast minicircle sequences were amplified by real-time PCR using an assay with a sensitivity of one parasite per 20?mL of blood. All testing was performed on coded samples.Rates of PCR detection of T. cruzi DNA were significantly (P?=?0.003) higher in CC patients and SP-BD diagnosed with CC (79/105 [75.2 %]) compared with SP-BD without CC (143/279 [51.3%]). The presence of parasitaemia was significantly associated with known markers of disease progression such as QRS and QT interval duration, lower left ventricular ejection fraction, higher left ventricular index mass, and elevated troponin and NTpro-BNP levels.Trypanosoma cruzi PCR positivity is associated with presence and severity of cardiomyopathy, suggesting a direct role of parasite persistence in disease pathogenesis.

SUBMITTER: Sabino EC

PROVIDER: S-EPMC5665686 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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Detection of Trypanosoma cruzi DNA in blood by PCR is associated with Chagas cardiomyopathy and disease severity.

Sabino E C EC Ribeiro A L AL Lee T H TH Oliveira C L CL Carneiro-Proietti A B AB Antunes A P AP Menezes M M MM Ianni B M BM Salemi V M VM Nastari L L Fernandes F F Sachdev V V Carrick D M DM Deng X X Wright D D Gonçalez T T TT Murphy E L EL Custer B B Busch M P MP

European journal of heart failure 20150210 4

<h4>Background</h4>The significance of detection of Trypanosoma cruzi DNA in blood of antibody-positive patients for risk of development of Chagas heart disease is not well established. The objective of this study was to compare detection of T. cruzi DNA with known clinical and laboratory markers of Chagas cardiomyopathy (CC) severity.<h4>Methods</h4>This is a case-control study nested within a retrospective cohort developed in Brazil to understand the natural history of Chagas disease. The stud ...[more]

PMID: 25678239

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Project description:BackgroundFamilial aggregation of Chagas cardiac disease in T. cruzi-infected persons suggests that human genetic variation may be an important determinant of disease progression.ObjectiveTo perform a GWAS using a well-characterized cohort to detect single nucleotide polymorphisms (SNPs) and genes associated with cardiac outcomes.MethodsA retrospective cohort study was developed by the NHLBI REDS-II program in Brazil. Samples were collected from 499 T. cruzi seropositive blood donors who had donated between 1996 and 2002, and 101 patients with clinically diagnosed Chagas cardiomyopathy. In 2008-2010, all subjects underwent a complete medical examination. After genotype calling, quality control filtering with exclusion of 20 cases, and imputation of 1,000 genomes variants; association analysis was performed for 7 cardiac and parasite related traits, adjusting for population stratification.ResultsThe cohort showed a wide range of African, European, and modest Native American admixture proportions, consistent with the recent history of Brazil. No SNPs were found to be highly (P<10(-8)) associated with cardiomyopathy. The two mostly highly associated SNPs for cardiomyopathy (rs4149018 and rs12582717; P-values <10(-6)) are located on Chromosome 12p12.2 in the SLCO1B1 gene, a solute carrier family member. We identified 44 additional genic SNPs associated with six traits at P-value <10(-6): Ejection Fraction, PR, QRS, QT intervals, antibody levels by EIA, and parasitemia by PCR.ConclusionThis GWAS identified suggestive SNPs that may impact the risk of progression to cardiomyopathy. Although this Chagas cohort is the largest examined by GWAS to date, (580 subjects), moderate sample size may explain in part the limited number of significant SNP variants. Enlarging the current sample through expanded cohorts and meta-analyses, and targeted studies of candidate genes, will be required to confirm and extend the results reported here. Future studies should also include exposed seronegative controls to investigate genetic associations with susceptibility or resistance to T. cruzi infection and non-Chagas cardiomyopathy.

Dataset Information

Detection of Trypanosoma cruzi DNA in blood by PCR is associated with Chagas cardiomyopathy and disease severity.

Publications

Detection of Trypanosoma cruzi DNA in blood by PCR is associated with Chagas cardiomyopathy and disease severity.

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