scholarly journals Sequential combined treatment with allopurinol and benznidazole in the chronic phase of Trypanosoma cruzi infection: a pilot study

2012 ◽  
Vol 68 (2) ◽  
pp. 424-437 ◽  
Author(s):  
D. E. Perez-Mazliah ◽  
M. G. Alvarez ◽  
G. Cooley ◽  
B. E. Lococo ◽  
G. Bertocchi ◽  
...  
Keyword(s):  
Pilot Study ◽  
Trypanosoma Cruzi ◽  
Combined Treatment ◽  
Chronic Phase ◽  
Cruzi Infection

Dynamics of T Cells Repertoire During Trypanosoma cruzi Infection and its Post-Treatment Modulation

2019 ◽  
Vol 26 (36) ◽  
pp. 6519-6543 ◽  
Author(s):  
Adriana Egui ◽  
Paola Lasso ◽  
Elena Pérez-Antón ◽  
M. Carmen Thomas ◽  
Manuel Carlos López
Keyword(s):  
Immune Response ◽  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Cardiac Tissue ◽  
Acute Infection ◽  
Clinical Status ◽  
Chronic Phase ◽  
Parasite Load ◽  
Chronic Patients ◽  
Cruzi Infection

Chagas disease courses with different clinical phases and has a variable clinical presentation and progression. The acute infection phase mostly exhibits a non-specific symptomatology. In the absence of treatment, the acute phase is followed by a chronic phase, which is initially asymptomatic. This chronic asymptomatic phase of the disease is characterized by a fragile balance between the host’s immune response and the parasite replication. The loss of this balance is crucial for the progression of the sickness. The virulence and tropism of the T. cruzi infecting strain together to the inflammation processes in the cardiac tissue are the main factors for the establishment and severity of the cardiomyopathy. The efficacy of treatment in chronic Chagas disease patients is controversial. However, several studies carried out in chronic patients demonstrated that antiparasitic treatment reduces parasite load in the bloodstream and leads to an improvement in the immune response against the Trypanosoma cruzi parasite. The present review is mainly focused on the cellular patterns associated to the clinical status and the evolution of the disease in chronic patients, as well as the effectiveness of the treatment related to T. cruzi infection control. Therefore, an emphasis is placed on the dynamics of specific-antigens T cell subpopulations, their memory and activation phenotypes, their functionality and their contribution to pathogenesis or disease control, as well as their association with risk of congenital transmission of the parasite.

Combined treatment with benznidazole and allopurinol in mice infected with a virulentTrypanosoma cruziisolate from Nicaragua

Parasitology ◽  
2013 ◽  
Vol 140 (10) ◽  
pp. 1225-1233 ◽  
Author(s):  
NOELIA L. GROSSO ◽  
MICAELA LOPEZ ALARCON ◽  
JAQUELINE BUA ◽  
SUSANA A. LAUCELLA ◽  
ADELINA RIARTE ◽  
...  
Keyword(s):  
Survival Rate ◽  
Trypanosoma Cruzi ◽  
Endemic Area ◽  
Low Dose ◽  
Combined Treatment ◽  
Chronic Phase ◽  
Experimental Models ◽  
Specific Antibodies ◽  
Histopathological Studies ◽  
Virulent Parasite

SUMMARYWe evaluated the effect of chemotherapy with a sequential combined treatment of a low dose of benznidazole and allopurinol, in different schedules of administration, in experimental models of acute and chronicTrypanosoma cruziinfection. Mice were infected with NicaraguaT. cruziisolate, a virulent parasite from an endemic area of Nicaragua, genotyped asTcI (Grossoet al. 2010). We assessed survival rate, IgG levels, histopathological studies and quantified parasitaemia. A 15% survival rate was recorded in untreated mice during the acute phase ofT. cruziinfection. Allopurinol administered immediately after benznidazole treatment was able to reduce parasitaemia and attenuate tissue damage by reducing inflammation.Trypanosoma cruzi-specific antibodies also decreased in 40–50% of the treated mice. The addition of allopurinol during the chronic phase showed the highest beneficial effect, not only by reducing parasitaemia but also by lowering the degree of inflammation and fibrosis.

scholarly journals Evolution of subpatent parasitaemia in Trypanosoma cruzi chronically infected mice with the help of a cyclophosphamide amplification transfer assay

1991 ◽  
Vol 33 (6) ◽  
pp. 509-514 ◽  
Author(s):  
José M. Alvarez ◽  
Ayumi Oshima ◽  
Veronica Mozer ◽  
Liliane Guimarães ◽  
Hércules Menezes
Keyword(s):  
Trypanosoma Cruzi ◽  
Acute Phase ◽  
Chronic Phase ◽  
Detection Tool ◽  
Highly Sensitive ◽  
Parasite Detection ◽  
Cyclophosphamide Treatment ◽  
One Year ◽  
Cruzi Infection

We have evaluated the sensitivity of the classical blood subinoculation method, modified through cyclophosphamide treatment of transferred mice, for the detection of occult parasitaemias in Trypanosoma cruzi chronically infected mice. Besides its simplicity, the method was shown to be highly sensitive for both the "chronic" phase parasites (99% of chronic cases were shown to harbour occult parasitaemias) and for the acute phase parasites (T. cruzi could be detected in 53.8% of animals transferred with one Y strain parasite and in 20% of animals transferred with one CL strain parasite). Using acute phase bloodforms, the assay proved to be more sensitive than conventional subinoculation when dealing with the CL, but not the Y strain of the parasite. With the help of this parasite detection tool, we have studied during a one year period, the evolution of subpatent parasitaemias in a group of mice which survived through chemotherapy from lethal acute phase of T. cruzi infection. Cyclophosphamide transfer assay revealed occult parasitaemias in 100% of the chronic animals, nevertheless, continuous and discontinuous patterns of positivity were observed.

scholarly journals Disagreement between PCR and serological diagnosis of Trypanosoma cruzi infection in blood donors from a Colombian endemic region

Biomédica ◽  
2021 ◽  
Vol 41 (Supl. 1) ◽  
pp. 47-59
Author(s):  
Liliana Torcoroma García Sánchez ◽  
Jhancy Rocío Aguilar Jiménez ◽  
Marly Yojhana Bueno ◽  
Erika Marcela Moreno Moreno ◽  
Herminia Ramírez ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Blood Donors ◽  
False Negative ◽  
Chronic Phase ◽  
Antibody Detection ◽  
Low Grade ◽  
Endemic Region ◽  
Infected People ◽  
Cruzi Infection

Introduction: Chagas’ disease is the leading cause of infectious myocarditis worldwide. This infection caused by Trypanosoma cruzi is usually life-long and asymptomatic; however, the third part of infected people can develop severe or even fatal cardiomyopathy. As the parasitemia in the chronic phase is both low-grade and intermittent, T. cruzi infection is principally detected by serology, although this method has sensitivity and specificity limitations.Objective: To determine the level of agreement between serologic and molecular tests in 658 voluntary blood donors from six provinces in the Colombian department of Santander.Materials and methods: We evaluated an array of diagnostic technologies by cross-section sampling performing a serological double diagnostic test for T. cruzi antibody detection (Chagas III ELISA™, BiosChile Group, and ARCHITECT Chagas CMIA™, Abbott), and DNA detection by polymerase chain reaction (PCR). We collected the demographic, clinical, and epidemiological information of participants. The sample size was calculated using Epidat™ and the statistical analysis was done with Stata 12.1™.Results: PCR was six times more sensitive in detecting T. cruzi infection than ELISA/CMIA with prevalence values of 1.8% (12/658) and 0.3% (2/658), respectively, and kappa=0.28 (95%CI: -0.03 - 0.59). In contrast, serology showed a sensitivity of 16.7% (95%CI: 2.09 - 48.4) and a specificity of 100% (95%CI: 99.4 - 100). All seropositive samples were found to be positive by PCR.Conclusions: The implementation of PCR as a complementary method for screening donors could reduce the probability of false negative and the consequent risk of transfusional-transmission of Chagas’ disease, especially in endemic regions.

scholarly journals Detection of parasite-derived transrenal DNA for the diagnosis of chronic Trypanosoma cruzi infection

2019 ◽  
Author(s):  
Ana G. Madrigal ◽  
Rachel Marcus ◽  
Robert Gilman ◽  
Alan L. Scott ◽  
Clive Shiff
Keyword(s):  
Trypanosoma Cruzi ◽  
Chronic Phase ◽  
Protozoan Parasite ◽  
Public Health Issue ◽  
Global Public Health ◽  
Detection Approach ◽  
Life Threatening ◽  
No Gold Standard ◽  
Antibody Tests ◽  
Cruzi Infection

AbstractChagas disease, caused by the protozoan parasite Trypanosoma cruzi, is a potentially life-threatening infection endemic to Latin America that has emerged as a global public health issue due to globalization and emigration patterns. Diagnosis of T. cruzi infection is complex, especially for the chronic phase of the disease that is characterized by a low to moderate burden of the difficult to detect, tissue-dwelling, intracellular form of the parasite. Diagnosis relies on a multistep indirect serological detection approach that requires positive results in at least two independent anti-T. cruzi antibody tests. With no gold standard diagnostic method for chronic T. cruzi, new approaches are needed that can more directly test for the presence of the parasite. Here, we report on of the potential utility of a noninvasive diagnostic approach that specifically detects T. cruzi-derived cell-free repeat DNA in the urine of patients who are both serologically positive and negative.

scholarly journals The Effect of the GH/IGF-1 Axis During Trypanosoma Cruzi Infection

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A492-A493
Author(s):  
Patricia Mora-Criollo ◽  
Reetobrata Basu ◽  
Yanrong Qian ◽  
Jaime A Costales ◽  
Jaime Guevara-Aguirre ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Cell Lines ◽  
Chronic Phase ◽  
Mouse Fibroblast ◽  
Host Cells ◽  
Cervical Cancer Cell Line ◽  
Cell Line Hela ◽  
Vitro Effect ◽  
Cruzi Infection

Abstract Trypanosoma cruzi is the parasite responsible for Chagas disease (CD), that affects 6-8 million people worldwide. CD treatment is limited to two drugs (benznidazole and nifurtimox). Treatment is mostly effective during the acute phase of the disease (initial two months post-infection), while their efficacy during the chronic phase is controversial. In the absence of treatment, 30% of infected individuals suffer irreversible chronic cardiac and digestive damages, which lead to inability and, in some instances, death. Patients with Laron Syndrome (LS, a form of congenital GH insensitivity) are short in stature with low levels of IGF-1, elevated levels of GH and, surprisingly, are resistant to cancer and diabetes. A cohort of LS patients living in southern Ecuador, where CD is endemic, has been studied by Dr. Jaime Guevara for over 25 years (1). Few, if any, cases of CD have been reported among these patients (Dr. Guevara, personal communications). T. cruzi infection has been shown to directly modulate pituitary hormones such as GH, PRL and glucocorticoids (stress related hormones), leading to immunosuppression and thymic atrophy by depletion of CD4+ CD8+ cells. Previously, rats infected with T. cruzi and treated with GH showed reduced parasitism and less tissue damage compared to controls (2). The purpose of this research is to investigate the in vitro effect of GH during T. cruzi infection, simulating conditions of GH insensitivity. First, we separately treated T. cruzi and the host cells [human cervical cancer cell line (HeLa) and male mouse fibroblast (L-cells)] with relatively low or high levels of GH, IGF-1, PRL, and EGF. Next, we treated the parasite and host cells simultaneously with these hormones. When the parasites were treated alone, T. cruzi responded to exogenous GH (5ng/ml-50ng/ml) by significantly increasing the percentage of amastigotes (less infective form of the parasite). Also, when GH (50ng/ml) were administered to the host cells, T. cruzi infectivity was significantly reduced by 12% (percentage of infection) compared to 20% from untreated conditions. Similarly, both parasite and host cells treated with GH significantly reduced T. cruzi infectivity (10%) compared to untreated conditions (18%). We further treated both cell lines with a combination of GH/IGF-1. Conditions used were as follows: control (no-treatment), moderate levels (5ng/ml GH+150 ng/ml IGF-1), relatively high levels (50ng/ml GH+600ng/ml IGF-1), or levels that would simulate those found in patients with LS(50ng/ml GH+20 ng/ml IGF-1). Of these, the LS concentrations significantly reduced infection in both cell lines (11%) compared to control (16%). Together these results indicate that GH can influence T. cruzi infectivity and that GH, not IGF-1, is mediating the decreased infectivity. Finally, the results suggest that high concentrations of GH, as seen in LS patients, could be protective during T. cruzi infection. 1)Guevara-Aguirre et al., 2011 2) Frare et al., 2010

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