Usefulness of PCR-based assays to assess drug efficacy in Chagas disease chemotherapy: value and limitations

Britto, Constança

doi:10.1590/s0074-02762009000900018

Cited by 99 publications

(76 citation statements)

References 112 publications

(138 reference statements)

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“…Studies in different endemic areas have shown that genetic differences between parasite strains can influence parasitemia and PCR positivity 54 . This positivity may still be related to several factors, such as the number of transient trypomastigotes in the peripheral circulation at the time of blood collection, appropriate storage conditions of the samples, DNA extraction procedures, amplification targets, the use of the same thermal cycler, and the ability to detect minimal quantities of parasite DNA 7,22,28 .…”

Section: Discussionmentioning

confidence: 99%

Combined parasitological and molecular-based diagnostic tools improve the detection of Trypanosoma cruzi in single peripheral blood samples from patients with Chagas disease

Volpato

Sousa

D’Ávila

et al. 2017

Rev. Soc. Bras. Med. Trop.

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Introduction:In order to detect Trypanosoma cruzi and determine the genetic profiles of the parasite during the chronic phase of Chagas disease (ChD), parasitological and molecular diagnostic methods were used to assess the blood of 91 patients without specific prior treatment. Methods: Blood samples were collected from 68 patients with cardiac ChD and 23 patients with an indeterminate form of ChD, followed by evaluation using blood culture and polymerase chain reaction. T. cruzi isolates were genotyped using three different genetic markers. Results: Blood culture was positive in 54.9% of all patients, among which 60.3% had the cardiac form of ChD, and 39.1% the indeterminate form of ChD. There were no significant differences in blood culture positivity among patients with cardiac and indeterminate forms. Additionally, patient age and clinical forms did not influence blood culture results. Polymerase chain reaction (PCR) was positive in 98.9% of patients, although comparisons between blood culture and PCR results showed that the two techniques did not agree. Forty-two T. cruzi stocks were isolated, and TcII was detected in 95.2% of isolates. Additionally, one isolate corresponded to TcIII or TcIV, and another corresponded to TcV or TcVI. Conclusions: Blood culture and PCR were both effective for identifying T. cruzi using a single blood sample, and their association did not improve parasite detection. However, we were not able to establish an association between the clinical form of ChD and the genetic profile of the parasite.

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Section: Discussionmentioning

confidence: 99%

Combined parasitological and molecular-based diagnostic tools improve the detection of Trypanosoma cruzi in single peripheral blood samples from patients with Chagas disease

Volpato

Sousa

D’Ávila

et al. 2017

Rev. Soc. Bras. Med. Trop.

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“…Regrettably, serological markers may take up to 10 years to disappear and parasitological tests by haemoculture or xenodiagnosis have limited sensitivity (Gontijo et al 1999). An upcoming polymerase chain reaction (PCR)-based assay is a promising tool in the evaluation of parasitological cure, but it still presents limitations (Britto 2009). Therefore, the lack of a better marker for indicating parasitological cure is a major impediment to advances in the treatment and development of more effective drugs for Chagas disease.…”

Section: ± 1 µM Comparison Of Bz Susceptibility Of the Pre-treatmentmentioning

confidence: 99%

Trypanosoma cruzi benznidazole susceptibility in vitro does not predict the therapeutic outcome of human Chagas disease

Moreno

D’Ávila²,

Silva

et al. 2010

Mem. Inst. Oswaldo Cruz

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“…These tests have sensitivity and specificity rates higher than 90%. Chagas disease can be diagnosed with greater sensitivity by the detection of T. cruzi specific sequences of DNA by PCR reaction (Britto, 2009;Sousa et al, 2009). …”

Section: Clinical Aspects Of Chagas Diseasementioning

confidence: 99%

“…This can be done through sensitive methods such as immunohistochemistry, polymerase chain reaction (PCR), and in situ hybridization (Britto, 2009;Deborggraeve et al, 2009;Duffy et al, 2009;Rassi et al, 2009a;Rassi and Rassi, 2009;Rassi et al, 2009c). Experimentally, this is demonstrated by attenuation of cardiomyopathy with parasite load reduction by trypanocidal treatment (Britto, 2009;Bustamante et al, 2008;Coura, 2009;Marin-Neto et al, 2009;Perez-Molina et al, 2009;Urbina, 2009b;Viotti et al, 2009). However, myocardial inflammatory infiltrates and lesions are not uniformly reduced in mice infected with different T. cruzi strains and treated with benznidazole (Bz) (Caldas et al, 2008;MarinNeto et al, 2009;Rassi and Rassi, 2009).…”

Section: Myocardial Damage Directly Related To Parasite Persistencementioning

confidence: 99%

Chagas disease: Present status of pathogenic mechanisms and chemotherapy

et al. 2010

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There are approximately 7.8 million people in Latin America, including Chile, who suffer from Chagas disease and another 28 million who are at risk of contracting it. Chagas is caused by the flagellate protozoan Trypanosoma cruzi. It is a chronic disease, where 20%-30% of infected individuals develop severe cardiopathy, with heart failure and potentially fatal arrhythmias. Currently, Chagas disease treatment is more effective in the acute phase, but does not always produce complete parasite eradication during indeterminate and chronic phases. At present, only nifurtimox or benznidazole have been proven to be superior to new drugs being tested. Therefore, it is necessary to find alternative approaches to treatment of chronic Chagas. The current treatment may be rendered more effective by increasing the activity of anti-Chagasic drugs or by modifying the host's immune response. We have previously shown that glutathione synthesis inhibition increases nifurtimox and benznidazole activity. In addition, there is increasing evidence that cyclooxygenase inhibitors present an important effect on T. cruzi infection. Therefore, we found that aspirin reduced the intracellular infection in RAW 264.7 cells and, decreased myocarditis extension and mortality rates in mice. However, the long-term benefit of prostaglandin inhibition for Chagasic patients is still unknown.

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Usefulness of PCR-based assays to assess drug efficacy in Chagas disease chemotherapy: value and limitations

Cited by 99 publications

References 112 publications

Combined parasitological and molecular-based diagnostic tools improve the detection of Trypanosoma cruzi in single peripheral blood samples from patients with Chagas disease

Combined parasitological and molecular-based diagnostic tools improve the detection of Trypanosoma cruzi in single peripheral blood samples from patients with Chagas disease

Trypanosoma cruzi benznidazole susceptibility in vitro does not predict the therapeutic outcome of human Chagas disease

Chagas disease: Present status of pathogenic mechanisms and chemotherapy

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