scholarly journals The Trypanosoma cruzi kinetoplast DNA minicircle sequences transfer biomarker of the multidrug treatment of Chagas disease

2021 ◽  
Author(s):  
Antonio R. L. Teixeira ◽  
Alessandro O Sousa ◽  
Clever C Gomes ◽  
Adriana A Sá ◽  
Rubens J Nascimento ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Nuclear Dna ◽  
Germ Line ◽  
Pcr Amplification ◽  
Dna Transfer ◽  
Heart Cells ◽  
Kinetoplast Dna ◽  
Chagas Cardiomyopathy ◽  
Primer Sets

Background: The Trypanosoma cruzi infection renders the transfer of the mitochondrion kinetoplast DNA minicircle sequences into the host’s genome. The Aves are refractory to the infection, but chicks hatched from the T. cruzi inoculated eggs integrate the DNA minicircle sequences into the germ line cells. Rabbits, mice and chickens with the minicircle sequences mutations develop the Chagas cardiomyopathy and the DNA transfer underpins the heart disease. Methodology: The PCR with the specific primer sets revealed the Protist nuclear DNA and the kinetoplast DNA in the agarose gels bands probed with the radiolabel specific sequences from tissues of the T. cruzi-infected rabbits and of the mice. A targetprimer TAIL-PCR amplification employing primer sets from the chickens, rabbits and mice, in combination with primer sets from the the T. cruzi kinetoplast minicircle sequences was used. This approach led us to disclose the integration sites of the kinetoplast DNA biomarker, then, used to monitor the effect of multidrug treatment of the T. cruzi infected mice. Principal findings: The Southern hybridization, clone and sequence of the amplification products revealed the DNA minicircle sequences integrations sites in the LINE transposable elements. An array of inhibitors of eukaryote cells division was used to arrest the DNA transfer. It was shown that nine out of 12 inhibitors prevented the kinetoplast DNA integration into the macrophage genome. The multidrug treatment of the acutely T. cruzi-infected mice with Benznidazole, Azidothymidine and Ofloxacin lessened circa 2.5-fold the rate of the minicircle sequences integrations in the mouse genome and inhibited the rejection of the target heart cells. Conclusion and significance: The T. cruzi mitochondrion kinetoplast minicircle sequences transfer driven pathogenesis of Chagas disease is an ancient Cross-Kingdom DNA phenomenon of evolution and, therefore, paradigm research with effective purposing inhibitors is needed.

scholarly journals Persistent infections in chronic Chagas' disease patients treated with anti-Trypanosoma cruzi nitroderivatives

2000 ◽  
Vol 42 (3) ◽  
pp. 157-161 ◽  
Author(s):  
M. Socorro BRAGA ◽  
Liana LAURIA-PIRES ◽  
Enrique R. ARGAÑARAZ ◽  
Rubens J. NASCIMENTO ◽  
Antonio R. L. TEIXEIRA
Keyword(s):  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Nuclear Dna ◽  
Pcr Amplification ◽  
Study Groups ◽  
Persistent Infections ◽  
The Difference ◽  
Definition Of ◽  
Dna Primers ◽  
Chronic Chagas Disease

We used a molecular method and demonstrated that treatment of the chronic human Trypanosoma cruzi infections with nitroderivatives did not lead to parasitological cure. Seventeen treated and 17 untreated chronic Chagas' disease patients, with at least two out of three positive serologic assays for the infection, and 17 control subjects formed the study groups. PCR assays with nested sets of T. cruzi DNA primers monitored the efficacy of treatment. The amplification products were hybridized to their complementary internal sequences. Untreated and treated Chagas' disease patients yielded PCR amplification products with T. cruzi nuclear DNA primers. Competitive PCR was conducted to determine the quantity of parasites in the blood and revealed < 1 to 75 T. cruzi/ml in untreated (means 25.83 ± 26.32) and < 1 to 36 T. cruzi/ml in treated (means 6.45 ± 9.28) Chagas' disease patients. The difference between the means was not statistically significant. These findings reveal a need for precise definition of the role of treatment of chronic Chagas' disease patients with nitrofuran and nitroimidazole compounds.

scholarly journals Blood-sucking lice may disseminate Trypanosoma cruzi infection in baboons

2001 ◽  
Vol 43 (5) ◽  
pp. 271-276 ◽  
Author(s):  
Enrique R. ARGAÑARAZ ◽  
Gene B. HUBBARD ◽  
Larissa A. RAMOS ◽  
Allen L. FORD ◽  
Nadjar NITZ ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Nuclear Dna ◽  
San Antonio ◽  
Pcr Amplification ◽  
Kinetoplast Dna ◽  
Competitive Pcr ◽  
Blood Sucking ◽  
Sucking Lice ◽  
Nested Sets ◽  
Cruzi Infection

Trypanosoma cruzi (Schyzotrypanum, Chagas, 1909), and Chagas disease are endemic in captive-reared baboons at the Southwest Foundation for Biomedical Research, San Antonio, Texas. We obtained PCR amplification products from DNA extracted from sucking lice collected from the hair and skin of T. cruzi-infected baboons, with specific nested sets of primers for the protozoan kinetoplast DNA, and nuclear DNA. These products were hybridized to their complementary internal sequences. Selected sequences were cloned and sequencing established the presence of T. cruzi nuclear DNA, and minicircle kDNA. Competitive PCR with a kDNA set of primers determined the quantity of approximately 23.9 ± 18.2 T. cruzi per louse. This finding suggests that the louse may be a vector incidentally contributing to the dissemination of T. cruzi infection in the baboon colony.

scholarly journals Molecular characterization of Trypanosoma cruzi Mexican strains and their behavior in the mouse experimental model

2011 ◽  
Vol 44 (6) ◽  
pp. 684-690 ◽  
Author(s):  
César Gómez-Hernández ◽  
Karine Rezende-Oliveira ◽  
Gabriel Antônio Nogueira Nascentes ◽  
Lara Rocha Batista ◽  
Henrique Borges Kappel ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Random Amplified Polymorphic Dna ◽  
Geographic Origin ◽  
Pcr Amplification ◽  
Biological Characterization ◽  
Long Time ◽  
Intergenic Regions ◽  
Mexican Strains

INTRODUCTION: For a long time, the importance of Chagas disease in Mexico, where many regarded it as an exotic malady, was questioned. Considering the great genetic diversity among isolates of Trypanosoma cruzi, the importance of this biological characterization, and the paucity of information on the clinical and biological aspects of Chagas disease in Mexico, this study aimed to identify the molecular and biological characterization of Trypanosoma cruzi isolates from different endemic areas of this country, especially of the State of Jalisco. METHODS: Eight Mexican Trypanosoma cruzi strains were biologically and genetically characterized (PCR specific for Trypanosoma cruzi, multiplex-PCR, amplification of space no transcript of the genes of the mini-exon, amplification of polymorphic regions of the mini-exon, classification by amplification of intergenic regions of the spliced leader genes, RAPD - (random amplified polymorphic DNA). RESULTS: Two profiles of parasitaemia were observed, patent (peak parasitaemia of 4.6×10(6) to 10(7) parasites/mL) and subpatent. In addition, all isolates were able to infect 100% of the animals. The isolates mainly displayed tropism for striated (cardiac and skeletal) muscle. PCR amplification of the mini-exon gene classified the eight strains as TcI. The RAPD technique revealed intraspecies variation among isolates, distinguishing strains isolated from humans and triatomines and according to geographic origin. CONCLUSIONS: The Mexican T. cruzi strains are myotrophic and belong to group TcI.

scholarly journals Treatment of Chagas Cardiomyopathy

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Fernando A. Botoni ◽  
Antonio Luiz P. Ribeiro ◽  
Carolina Coimbra Marinho ◽  
Marcia Maria Oliveira Lima ◽  
Maria do Carmo Pereira Nunes ◽  
...  
Keyword(s):  
North America ◽  
South America ◽  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Therapeutic Approach ◽  
Original Description ◽  
Tropical Disease ◽  
Neglected Tropical Disease ◽  
Underdeveloped Countries ◽  
Chagas Cardiomyopathy

Chagas' disease (ChD), caused by the protozoaTrypanosoma cruzi(T. cruzi), was discovered and described by the Brazilian physician Carlos Chagas in 1909. After a century of original description, trypanosomiasis still brings much misery to humanity and is classified as a neglected tropical disease prevalent in underdeveloped countries, particularly in South America. It is an increasing worldwide problem due to the number of cases in endemic areas and the migration of infected subjects to more developed regions, mainly North America and Europe. Despite its importance, chronic chagas cardiomyopathy (CCC) pathophysiology is yet poorly understood, and independently of its social, clinical, and epidemiological importance, the therapeutic approach of CCC is still transposed from the knowledge acquired from other cardiomyopathies. Therefore, the objective of this review is to describe the treatment of Chagas cardiomyopathy with emphasis on its peculiarities.

scholarly journals The Trypanosoma cruzi Satellite DNA OligoC-TesT and Trypanosoma cruzi Kinetoplast DNA OligoC-TesT for Diagnosis of Chagas Disease: A Multi-cohort Comparative Evaluation Study

2014 ◽  
Vol 8 (1) ◽  
pp. e2633 ◽  
Author(s):  
Koen De Winne ◽  
Philippe Büscher ◽  
Alejandro O. Luquetti ◽  
Suelene B. N. Tavares ◽  
Rodrigo A. Oliveira ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Satellite Dna ◽  
Comparative Evaluation ◽  
Evaluation Study ◽  
Kinetoplast Dna

Incidence and Predictors of Progression to Chagas Cardiomyopathy: Long-Term Follow-Up of Trypanosoma Cruzi Seropositive Individuals

Circulation ◽  
2021 ◽  
Author(s):  
Maria Carmo P. Nunes ◽  
Lewis F. Buss ◽  
Jose Luiz P. da Silva ◽  
Larissa Natany Almeida Martins ◽  
Claudia Di Lorenzo Oliveira ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Clinical Epidemiology ◽  
Outpatient Service ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Blood Collection ◽  
Ventricular Ejection Fraction ◽  
Chagas Cardiomyopathy

Background: There are few contemporary cohorts of Trypanosoma cruzi -seropositive individuals, and the basic clinical epidemiology of Chagas disease is poorly understood. Herein, we report the incidence of cardiomyopathy and death associated with T. cruzi seropositivity. Methods: Participants were selected in blood banks at 2 Brazilian centers. Cases were defined as T. cruzi -seropositive blood donors. T. cruzi -seronegative controls were matched for age, sex, and period of donation. Patients with established Chagas cardiomyopathy were recruited from a tertiary outpatient service. Participants underwent medical examination, blood collection, electrocardiogram, and echocardiogram at enrollment (2008 to 2010) and at follow-up (2018 to 2019). The primary outcomes were all-cause mortality and development of cardiomyopathy, defined as the presence of a left ventricular ejection fraction <50% and/or QRS complex duration ≥ 120 ms. To handle loss to follow-up, a sensitivity analysis was performed using inverse probability weights for selection. Results: We enrolled 499 T. cruzi -seropositive donors (age 48 ± 10 years, 52% male), 488 T. cruzi -seronegative donors (age 49 ± 10 years, 49% male), and 101 patients with established Chagas cardiomyopathy (age 48 ± 8 years, 59% male). The mortality in patients with established cardiomyopathy was 80.9 deaths/1000 person-years (py) (54/101, 53%) and 15.1 deaths/1000py (17/114, 15%) in T. cruzi -seropositives with cardiomyopathy at baseline. Among T. cruzi -seropositive donors without cardiomyopathy at baseline mortality was 3.7 events/1000py (15/385, 4%), which was no different from T. cruzi -seronegative donors with 3.6 deaths/1000py (17/488, 3%). The incidence of cardiomyopathy in T. cruzi -seropositive donors was 13.8 (95% CI 9.5-19.6) events/1000py (32/262, 12%) compared with 4.6 (95% CI 2.3-8.3) events/1000 py (11/277, 4%) in seronegative controls, with an absolute incidence difference associated with T. cruzi seropositivity of 9.2 (95% CI 3.6 - 15.0) events/1000py. T. cruzi antibody level at baseline was associated with development of cardiomyopathy (adjusted OR of 1.4, 95% CI 1.1-1.8). Conclusions: We present a comprehensive description of the natural history of T. cruzi seropositivity in a contemporary patient population. The results highlight the central importance of anti- T. cruzi antibody titer as a marker of Chagas disease activity and risk of progression.

Wnt Signalling Orchestrates the Immune Response and Cardiac Damage During Trypanosoma cruzi Infection

2020 ◽  
Author(s):  
Ximena Volpini ◽  
Laura Fernanda Ambrosio ◽  
Agustina Brajín ◽  
María Belen Brugo ◽  
María Pilar Aoki ◽  
...  
Keyword(s):  
Immune Response ◽  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Acute Phase ◽  
Wnt Signalling ◽  
Signalling Pathways ◽  
Chagas Cardiomyopathy ◽  
Cardiac Lesions ◽  
Parasite Replication ◽  
Chronic Chagas Disease

AbstractChagas’ cardiomyopathy is the consequence of a compromised electrical and mechanical cardiac function, with parasite persistence, unbalanced inflammation and pathological tissue remodelling, being intricately related to the myocardial aggression and the impaired function. Recent studies have shown that Wnt signalling pathways, which are important for developmental processes, play a critical role in the pathogenesis of cardiac and vascular diseases. In addition, we have reported that Trypanosoma cruzi infection activates Wnt signalling pathways in macrophages to promote their intracellular replication, with treatment of mice with IWP-L6 (an inhibitor of the O-acyl-transferase, PORCN, responsible for the post-translational modifications necessary for Wnt proteins secretion) being able to diminish parasitaemia and tissue parasitism. Therefore, Wnt signalling may contribute to the development of Chagas’ cardiomyopathy. In this work we have evaluated the effectiveness of Wnt secretion inhibition to control the parasite replication, modulate the adaptive immune response, and prevent the development of cardiac lesions in an experimental model of chronic Chagas disease. The IWP-L6 treatment, administered to T. cruzi infected BALB/c mice in a time window during the acute phase of the infection, was able to control the parasitaemia and heart parasitism together with the amelioration of the electrical, mechanical and histopathological cardiac alterations observed in chronically infected mice. Moreover, we demonstrated that during the acute phase of the infection Wnt signalling activation contributes to promote specific Th2-type immune response and to maintain the suppressive activity of Treg cells. Our data provide evidence that inhibition of Wnt signalling during the acute phase of T. cruzi infection controls the parasite replication, inhibits the development of parasite-prone and fibrosis-prone Th2-type immune response and prevents the development of cardiac lesions characteristics of chronic Chagas disease. Our study suggests that Wnt signalling pathway might be a potential target to prevent the development of T. cruzi-induced cardiomyopathy.

scholarly journals Possible oral transmission of acute Chagas' disease in Brazil

1991 ◽  
Vol 33 (5) ◽  
pp. 351-357 ◽  
Author(s):  
M.A. Shikanai-Yasuda ◽  
C. Brisola Marcondes ◽  
L. A. Guedes ◽  
G.S. Siqueira ◽  
A.A. Barone ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Fatal Case ◽  
Febrile Illness ◽  
Epidemiological Survey ◽  
High Rate ◽  
Oral Transmission ◽  
Chagas Cardiomyopathy ◽  
Limb Edema ◽  
Acute Chagas Disease

In October, 1986, 7 to 22 days after a meeting at a farm in Paraíba state, 26 individuals presented with a febrile illness associated with bilateral eyelid and lower limb edema, mild hepatosplenomegaly, lymphadenopathy and, occasionally a skin rash. A 11-year-old boy exhibited atrial premature complexes and a 74-year-old patient developed acute heart failure. In two patients hospitalized in São Paulo city, acute Chagas' disease was diagnosed by the demonstration of circulating Trypanosoma cruzi. At autopsy in a fatal case, acute Chagas' cardiomyopathy was demonstrated. Xenodiagnosis were positive in 9 out of 14 tested patients. A specific IgG immune response was found in all patients and specific IgM antibodies were identified in 20 out of 22 tested patients. A epidemiological survey showed the existence of Triatoma brasiliensis in the outbuildings of this farm, but none in the house where most of the guests stayed. A high rate of infection with Trypanosoma cruzi was found in opossums. These observations together with those related to the food consumed by the patients, lead the authors to suggest that the human infections resulted from oral contamination probably originating from naturally infected marsupials in the area or crushed infected bugs.

scholarly journals Variability of Kinetoplast DNA Gene Signatures of Trypanosoma cruzi II Strains from Patients with Different Clinical Forms of Chagas' Disease in Brazil

2006 ◽  
Vol 44 (6) ◽  
pp. 2167-2171 ◽  
Author(s):  
E. Lages-Silva ◽  
L. E. Ramirez ◽  
A. L. Pedrosa ◽  
E. Crema ◽  
L. M. da Cunha Galvao ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Kinetoplast Dna ◽  
Gene Signatures ◽  
Clinical Forms
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