Therapeutic responses to different anti-Trypanosoma cruzi drugs in experimental infection by benznidazole-resistant parasite stock

This study describes the role of parasite clearance time induced by benznidazole, fexinidazole and posaconazole treatments upon mice infection with a benznidazole-resistant Trypanosoma cruzi strain in the pathological outcomes. Trypanosoma cruzi-infected mice were treated with different drugs and parasite clearance time was detected by blood and tissue qPCR, to determine the dynamic relationship between the efficacy of the treatments and the intensity of heart lesion/serum inflammatory mediators. Our results indicate that anti-T. cruzi treatments were able to reduce parasite replication and consequently induce immunomodulatory effects, where the degree of the immunopathology prevention was related to the time of parasite clearance induced by different treatments. Nevertheless, in benznidazole and posaconazole treatments, parasite rebounding was detected with parasitism reaching levels similar to infected and non-treated mice; the time for parasitic rebound being earlier among benznidazole-treated mice. In parallel, an increase of cardiac lesions and plasma chemokine levels was also detected and was more accentuated in benznidazole-treated animals. Interestingly, in the presence of parasitological cure (fexinidazole treatment), basal levels of these inflammatory mediators were evidenced as well as an absence of cardiac inflammation or fibrosis. Overall, our data indicate that all treatments have positive effects on the clinical evolution of T. cruzi infection, with success in preventing cardiac alterations being drug-dependen

Dengue Virus 3 Genotype 1 Associated with Dengue Fever and Dengue Hemorrhagic Fever, Brazil

Dengue serotype 3 viruses were isolated from patients in Brazil from 2002 through 2004. On the basis of phylogenetic analyses, these isolates were assigned genotype 1. This genotype had never been reported in South America before. Its appearance indicates a major risk factor for dengue epidemics and severe disease

Perspectives of the regulation in the health insurance face the model assistance

This study discusses the advances and limits of governmental regulation in the health insurance and intends to serve as a map of the integrality of the assistance provided by following the continuum care. The user would be monitored according to a established course of therapeutic plan, led by a process of service provision and not by a logic bent on frivolous consumption (of service). This mechanism allows the state to employ regulating parameters and criteria for the control the quality of the care provided.O atual trabalho discute os avanços e limites da regulação pública da saúde suplementar e propõe mapear a integralidade da assistência pelo acompanhamento da linha do cuidado. Discute um modelo no qual o usuário deveria ser acompanhado segundo determinado projeto terapêutico instituído, comandado por um processo de trabalho cuidador, e não por uma lógica indutora de consumo. Esse mecanismo visaria assegurar a qualidade da assistência prestada.43344

Dengue-2 virus artificial infection of brazilian colonized Aedes aegypti

Submitted by Nuzia Santos ([email protected]) on 2013-06-19T13:23:44Z No. of bitstreams: 1 25.CAMPANELLI, E. S..pdf: 419329 bytes, checksum: 92c70330e3c5da863d1bc51810975893 (MD5)Made available in DSpace on 2013-06-19T13:23:44Z (GMT). No. of bitstreams: 1 25.CAMPANELLI, E. S..pdf: 419329 bytes, checksum: 92c70330e3c5da863d1bc51810975893 (MD5) Previous issue date: 2007CNPq, Capes, FIOCRUZ and FUNEDFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratory of Medical Entomology. Belo Horizonte, MG, Brazil.Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratory of Medical Entomology. Belo Horizonte, MG, BrazilFundação Ezequiel Dias. Laboratory of Molecular Virology. Belo Horizonte, MG, BrazilFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratory of Medical Entomology. Belo Horizonte, MG, Brazil.Fundação Ezequiel Dias. Laboratory of Molecular Virology. Belo Horizonte, MG, Brazil.Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratory of Medical Entomology. Belo Horizonte, MG, Brazil.Dengue is a viral disease transmitted by mosquitoes and caused by four viral serotypes (DENV 1-4). This mosquito-borne disease is a major public health problem and a threat to more than 2.5 billion people, who live in endemic areas. Aedes aegypti is the primary vector of dengue in the Americas. The present study shows the susceptibility of a colony strain of A. aegypti to Dengue 2 virus (DENV-2). A. aegypti females from a laboratory colony were infected with DENV-2 using a membrane feeding technique. The engorged females were dissected on different days (3, 6, 9, 12 and 15). The midguts, ovaries, carcasses and heads were separated. The samples were fixed and immunolabeled with anti-DENV-2 antibody to be analyzed by laser confocal microscopy (LCM). Infected mosquitoes from the 15 th day had their heads and bodies dissected, separated and analyzed by RT-PCR with specific primers. Immunolabeling of the midguts and ovaries showed the presence of DENV-2 in the mosquitoes dissected from the third day until the last day of the experiment. The RT-PCR reactions of the heads and the bodies confirmed the mosquito infection with DENV-2. These results showed that the methodology used for the artificial infection with dengue virus was successful and demonstrated that our colonized A. aegypti mosquitoes were susceptible to artificial dengue infection. Future studies are in progress to better understand the processof invasion by dengue vírus in Aedes mosquito

Therapeutic responses to different anti-Trypanosoma cruzi drugs in experimental infection by benznidazole-resistant parasite stock.

upon mice infection with a benznidazole-resistant Trypanosoma cruzi strain in the pathological outcomes. Trypanosoma cruzi-infected mice were treated with different drugs and parasite clearance time was detected by blood and tissue qPCR, to determine the dynamic relationship between the efficacy of the treatments and the intensity of heart lesion/serum inflammatory mediators. Our results indicate that anti-T. cruzi treatments were able to reduce parasite replication and consequently induce immunomodulatory effects, where the degree of the immunopathology prevention was related to the time of parasite clearance induced by different treatments. Nevertheless, in benznidazole and posaconazole treatments, parasite rebounding was detected with parasitism reaching levels similar to infected and non-treated mice; the time for parasitic rebound being earlier among benznidazole-treated mice. In parallel, an increase of cardiac lesions and plasma chemokine levels was also detected and was more accentuated in benznidazole-treated animals. Interestingly, in the presence of parasitological cure (fexinidazole treatment), basal levels of these inflammatory mediators were evidenced as well as an absence of cardiac inflammation or fibrosis. Overall, our data indicate that all treatments have positive effects on the clinical evolution of T. cruzi infection, with success in preventing cardiac alterations being drug-dependent

Real-time PCR strategy for parasite quantification in blood and tissue samples of experimental Trypanosoma cruzi infection.

The lack of an accurate diagnosis has been a serious obstacle to the advancement of the anti-Trypanosoma cruzi chemotherapy and long-term infection can result in different health risks to human. PCRs are alternative methods, more sensitive than conventional parasitological techniques, which due to their low sensitivities are considered unsuitable for these purposes. The aim of this study was to investigate a sensitive diagnostic strategy to quantify blood and cardiac tissues parasites based on real-time PCR tools during acute and chronic phases of murine Chagas disease, as well as to monitor the evolution of infection in those mice under specific treatment. In parallel, fresh blood examination, immunological analysis and quantification of cardiac inflammation were also performed to confront and improve real-time PCR data. Similar profiles of parasitemia curves were observed in both quantification techniques during the acute phase of the infection. In contrast, parasites could be quantified only by real-time PCR at 60 and 120 days of infection. In cardiac tissue, real-time PCR detected T. cruzi DNA in 100% of infected mice, and using this tool a significant Pearson correlation between parasite load in peripheral blood and in cardiac tissue during acute and chronic phases was observed. Levels of serum CCL2, CCL5 and nitric oxide were coincident with parasite load but focal and diffuse mononuclear infiltrates was observed, even with significant (p < 0.05) reduction of parasitism after 60 days of infection. Later, this methodology was used to monitor the evolution of infection in animals treated with itraconazole (Itz). Itz-treatment induced a reduction of parasite load in both blood and cardiac muscle at the treatment period, but after the end of chemotherapy an increase of parasitism was detected. Interestingly, inflammatory mediators levels and heart inflammation intensity had similar evolution to the parasite load, in the group of animals treated. Taken together, our data show that real-time PCR strategy used was suitable for studies of murine T. cruzi infection and may prove useful in investigations involving experimental chemotherapy of the disease and the benefits of treatment in relation to parasitism and inflammatory respon