Chagas disease in the 21st Century: a public health success or an emerging threat?

Bonney, Kevin M.

doi:10.1051/parasite/2014012

Cited by 151 publications

(150 citation statements)

References 83 publications

(141 reference statements)

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“…In this case, after 60 days of treatment, up to 80% of the patients can expect its remission. 4 However, chemotherapy with BNZ presents some drawbacks including the dosage regimen, long treatments, and often appearance of several side effects such as allergic dermatitis, peripheral neuropathy, and anorexia. BNZ exhibits low water solubility, which may produce low and/or variable bioavailability after oral administration.…”

Section: Introductionmentioning

confidence: 99%

Promising Efficacy of Benznidazole Nanoparticles in Acute Trypanosoma cruzi Murine Model: In-Vitro and In-Vivo Studies

Scalise

Arrúa

Rial

et al. 2016

The American Society of Tropical Medicine and Hygiene

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Abstract. The aim of this study was to evaluate the effectiveness of benznidazole nanoparticles (BNZ-nps) on trypomastigote forms and on intracellular infection in mammalian cells and primary cardiac myocyte cells. Its effectiveness was also evaluated on acute Trypanosoma cruzi Nicaragua mice infection. Trypomastigotes from culture were treated with different concentrations of BNZ-nps to determine the drug concentration that lyses 50% of trypomastigotes (LC 50 ). Infected mammalian cells were incubated with different concentrations of BNZ-nps to determine the percentage of amastigote inhibition. C 3 H/HeN mice with lethal acute infection were treated with 10, 25, and 50 mg/kg/day of BNZnps for 30 and 15 days to control the survival rate of animals. BNZ-nps having a mean particle size of 63.3 nm, a size distribution of 3.35, and a zeta potential of −18.30 were successfully prepared using poloxamer 188 as a stabilizer. BNZ-nps 25 and 50 μg/mL showed no significant differences in the percentage of inhibition of infected mammalian cells. Infected mice treated with BNZ-nps (50, 25, and 10 mg/kg/day) for 30 days and with BNZ-nps (50 and 25 mg/kg/day) for 15 days presented a 100% survival, whereas the animals treated with 10 mg/kg/day for 15 days of BNZ-nps showed a 70% survival rate. The results obtained demonstrate, for the first time, that benznidazole nanoparticles are a useful and attractive approach to treat Chagas disease in infected mice.

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Section: Introductionmentioning

confidence: 99%

Promising Efficacy of Benznidazole Nanoparticles in Acute Trypanosoma cruzi Murine Model: In-Vitro and In-Vivo Studies

Scalise

Arrúa

Rial

et al. 2016

The American Society of Tropical Medicine and Hygiene

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“…Up to 10 million people across Latin America are infected with this protozoan parasite, a distribution range that is expanding driven by migration of infected insects and hosts, with CD now emerging as a public health problem at nonendemic sites (1,2). T. cruzi strains are heterogeneous, exhibiting a high degree of biochemical and genetic variability.…”

mentioning

confidence: 99%

Kinetics, subcellular localization, and contribution to parasite virulence of a Trypanosoma cruzi hybrid type A heme peroxidase ( Tc APx-CcP)

Hugo

Martínez

Trujillo

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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The Trypanosoma cruzi ascorbate peroxidase is, by sequence analysis, a hybrid type A member of class I heme peroxidases [TcAPx-cytochrome c peroxidase (CcP)], suggesting both ascorbate (Asc) and cytochrome c (Cc) peroxidase activity. Here, we show that the enzyme reacts fast with H 2 O 2 (k = 2.9 × 10 7 M −1 ·s −1 ) and catalytically decomposes H 2 O 2 using Cc as the reducing substrate with higher efficiency than Asc (k cat /K m = 2.1 × 10 5 versus 3.5 × 10 4 M −1 ·s −1 , respectively). Visible-absorption spectra of purified recombinant TcAPx-CcP after H 2 O 2 reaction denote the formation of a compound I-like product, characteristic of the generation of a tryptophanyl radical-cation (Trp 233•+ ). Mutation of Trp 233 to phenylalanine (W233F) completely abolishes the Cc-dependent peroxidase activity. In addition to Trp 233•+ , a Cys 222 -derived radical was identified by electron paramagnetic resonance spin trapping, immunospin trapping, and MS analysis after equimolar H 2 O 2 addition, supporting an alternative electron transfer (ET) pathway from the heme. Molecular dynamics studies revealed that ET between Trp 233 and Cys 222 is possible and likely to participate in the catalytic cycle. Recognizing the ability of TcAPx-CcP to use alternative reducing substrates, we searched for its subcellular localization in the infective parasite stages (intracellular amastigotes and extracellular trypomastigotes). TcAPx-CcP was found closely associated with mitochondrial membranes and, most interestingly, with the outer leaflet of the plasma membrane, suggesting a role at the host-parasite interface. TcAPx-CcP overexpressers were significantly more infective to macrophages and cardiomyocytes, as well as in the mouse model of Chagas disease, supporting the involvement of TcAPx-CcP in pathogen virulence as part of the parasite antioxidant armamentarium.Trypanosoma cruzi | heme peroxidase | oxidants | virulence | kinetics

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“…These recommendation are particularly relevant for patients who might obtain greater benefits from treatment, such as women of childbearing age, young patients, transplant recipients, and patients who are immunosuppressed. 15 Additionally, blood, blood products, and organs donated by people from endemic areas should be screened.…”

Section: Screeningmentioning

confidence: 99%

“…However, health policies regarding the control of congenital transmission are also lacking in so many non-endemic European countries. 15 In fact, a multidisciplinary approach is essential to address this health problem that is multifaceted, which includes the coordination of various control programs (vector, vertical, blood banks, transplant), and the attention to affected people (primary care, different specialists). Moreover, the decision makers must decide priorities within their competence in face of other health problems and coordinate with professionals working in the field and with the people affected.…”

Section: Future Perspectivesmentioning

confidence: 99%

Epidemiology of Chagas Disease in Non-Endemic European Countries

Cambronero-Cortinas¹

2016

ICFJ

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<p>Chagas disease results from infection by the protozoan Trypanosoma cruzi and was presviously described as an endemic disease focused in populations living in poor rural areas of Latin American countries. Currently, migrant populations and some modes of transmission such as blood and organ donation or vertical transmission from infected mothers to their children have caused the spread of this disease beyond its natural geographical boundaries. In Europe, Spain, with over half of these migrants, is undoubtedly the most important recipient, followed by Italy, France and United Kingdom. However, in non-endemic countries there is no universal screening systems and also physicians are often poorly trained in recognizing this disease. So far, few countries are aware of the emergence of this disease and only few European countries have established changes in their health system to address this disease. The National European Health authorities should take part to this model-of-care, adapting in this new epidemiological scenario with screening this pathology in blood donors, organ donations or vertically from mother to child at birth. These mechanisms are the main forms of human infestation in nonendemic countries and are, therefore, the major targets for reduction of spread.</p>

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Chagas disease in the 21st Century: a public health success or an emerging threat?

Cited by 151 publications

References 83 publications

Promising Efficacy of Benznidazole Nanoparticles in Acute Trypanosoma cruzi Murine Model: In-Vitro and In-Vivo Studies

Promising Efficacy of Benznidazole Nanoparticles in Acute Trypanosoma cruzi Murine Model: In-Vitro and In-Vivo Studies

Kinetics, subcellular localization, and contribution to parasite virulence of a Trypanosoma cruzi hybrid type A heme peroxidase ( Tc APx-CcP)

Epidemiology of Chagas Disease in Non-Endemic European Countries

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