Prevention and Control of Chagas Disease – An Overview

Teixeira, Antonio R. L.; Gomes, Clever; Rosa, Adriana Helena; Araujo, Perla F.; Anunciação, Carlos Eduardo; Silveira-Lacerda, Elisângela de Paula; Almeida, Ana Carolina da Veiga Rodarte de; Petrofeza, Silvana

doi:10.9734/isrr/2018/42594

Cited by 5 publications

(15 citation statements)

References 74 publications

(268 reference statements)

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“…It can be contracted nosocomially, orally, by blood transfusion, organ transplant, mother to child, and contaminated water and food consumption. There is an emerging possibility that it is also being transmitted sexually [6–8] . Chagas disease has become largely urbanized as its cases are being reported in countries where the disease is nonindigenous [9,10] …”

Section: Introductionmentioning

confidence: 99%

A Mechanistic Probe into the Dual Inhibition of T. cruzi Glucokinase and Hexokinase in Chagas Disease Treatment – A Stone Killing Two Birds?

Omolabi

Odeniran

2021

Chemistry & Biodiversity

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Glucokinase (GLK) and Hexokinase (HK) have been characterized as essential targets in Trypanosoma cruzi (Tc)‐mediated infection. A recent study reported the propensity of the concomitant inhibition of TcGLK and TcHK by compounds GLK2‐003 and GLK2‐004, thereby presenting an efficient approach in Chagas disease treatment. We investigated this possibility using atomic and molecular scaling methods. Sequence alignment of TcGLK and TcHK revealed that both proteins shared approximately 33.3 % homology in their glucose/inhibitor binding sites. The total binding free energies of GLK2‐003 and GLK2‐004 were favorable in both proteins. PRO92 and THR185 were pivotal to the binding and stabilization of the ligands in TcGLK, likewise their conserved counterparts, PRO163 and THR237 in TcHK. Both compounds also induced a similar pattern of perturbations in both TcGLK and TcHK secondary structure. Findings from this study therefore provide insights into the underlying mechanisms of dual inhibition exhibited by the compounds. These results can pave way to discover and optimize novel dual Tc inhibitors with favorable pharmacokinetics properties eventuating in the mitigation of Chagas disease.

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Section: Introductionmentioning

confidence: 99%

A Mechanistic Probe into the Dual Inhibition of T. cruzi Glucokinase and Hexokinase in Chagas Disease Treatment – A Stone Killing Two Birds?

Omolabi

Odeniran

2021

Chemistry & Biodiversity

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“…The T. cruzi infections transmitted by blood transfusion [21][22][23], by oral route [24], and by accident in hospitals and research laboratories [25,26]. Moreover, the congenital, sexually transmitted T. cruzi infection from males and females to naive mates could play an ongoing pandemic role [6,[27][28][29][30][31][32][33][34][35][36][37][38]39].…”

Section: Introductionmentioning

confidence: 99%

“…The early phase T. cruzi infections in humans are usually asymptomatic and not perceived by the individual with the flagellates in the blood, and thus he or she, and the family, do not seek for health care (2,6,39). However, some oligosymptomatic acute cases refer to fever, headache, malaise, muscle pain, and prostration, and occasional fatal cases with severe acute T. cruzi infection show myocarditis and/or encephalitis.…”

Section: Introductionmentioning

confidence: 99%

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

Teixeira

Sousa

Gomes

et al. 2021

Preprint

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BackgroundThe 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.MethodologyThe 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 target- primer 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 findingsThe 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 significanceThe 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.Authors summaryChagas disease is considered the main cause of human heart failure in the Western Hemisphere. The treatment of the clinically manifested Chagas heart disease is considered unsatisfactory. Perhaps the most important problem in the field of Chagas disease is determination of the pathogenesis of the target heart cells lysis. We showed the transfer of the T. cruzi kDNA minicircle sequences into the genome of rabbits and mice, and to Bird refractory to the infections. The inoculation of a few T. cruzi in the fertile chicken eggs renders the kDNA sequences integration in the stem cells. Interestingly, the chicks that hatched retain the kDNA and develop the Chagas-like cardiomyopathy indistinguishable to that in the rabbits and mice. This result prompted the multidrug treatment of the Chagas heart disease with inhibitors of the eukaryotic cells division. We showed that nine out of 12 inhibitors prevented the transfer of the kDNA mutations into the macrophage genome, and that the treatment of the acutely T. cruzi-infected mice with Benznidazole + Ofloxacin + Azidothymidine lowered circa 2.5-fold the rate of the mutations in the chromosomes. These findings translated to the pathology showing inhibition of the heart lesions in the treated T. cruzi-infected mice. We suggest purposing new inhibitors should be tested to overturning the Chagas heart disease.

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“…In addition, the T. cruzi can be transmitted sexually to naive females and males. [8][9][10] Acute Chagas disease with fever and malaise usually subsides on average of three months. The chronic infection can continue for life without clinical manifestation.…”

Section: Introductionmentioning

confidence: 99%

Blood transfusion and diagnostic accuracy of chagas disease

Gomes¹,

Santos²,

Silveira-Lacerda³

et al. 2019

JBMOA

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Introduction: Disclaim of the Chagas disease case in Blood Center is based on the immunofluorescence and enzyme-linked immunosorbent antibody assays. Methods: The antibody assays were conducted in parallel with the nuclear DNA-PCR test in blood samples of 145 families' members. Result: The specific antibody tests were positive in 26.9% (39/145) subjects. Contrastingly, the Trypanosoma cruzi nuclear DNA-PCR was positive in 72.4% (105/145) of those blood samples. Conclusion: The immune tolerance herein explains the reported discrepancies of results between the specific antibody and the accurate DNA analysis. The warranty of safe blood transfusion is achieved by the PCR technology.

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Prevention and Control of Chagas Disease – An Overview

Cited by 5 publications

References 74 publications

A Mechanistic Probe into the Dual Inhibition of T. cruzi Glucokinase and Hexokinase in Chagas Disease Treatment – A Stone Killing Two Birds?

A Mechanistic Probe into the Dual Inhibition of T. cruzi Glucokinase and Hexokinase in Chagas Disease Treatment – A Stone Killing Two Birds?

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

Blood transfusion and diagnostic accuracy of chagas disease

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