Sistema de Gestión del Conocimiento ANLIS MALBRÁN
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Major Kinds of Drug Targets in Chagas Disease or American Trypanosomiasis
No full textFil: Duschak, Vilma G. ANLIS Dr. C. G. Malbrán. Instituto Nacional de Parasitología Dr. Mario Fatala Chaben; Argentina.American Trypanosomiasis, a parasitic infection commonly named Chagas disease, affects millions of people all over Latin American countries. Presently, the World Health Organization (WHO) predicts that the number of international infected individuals extends to 7 to 8 million, assuming that more than 10,000 deaths occur annually. The transmission of the etiologic agent, Trypanosoma cruzi, through people migrating to non-endemic world nations makes it an emergent disease. The best promising targets for trypanocidal drugs may be classified into three main groups: Group I includes the main molecular targets that are considered among specific enzymes involved in the essential processes for parasite survival, principally Cruzipain, the major antigenic parasite cysteine proteinase. Group II involves biological pathways and their key specific enzymes, such as Sterol biosynthesis pathway, among others, specific antioxidant defense mechanisms, and bioenergetics ones. Group III includes the atypical organelles /structures present in the parasite relevant clinical forms, which are absent or considerably different from those present in mammals and biological processes related to them. These can be considered potential targets to develop drugs with extra effectiveness and fewer secondary effects than the currently used therapeutics. An improved distinction between the host and the parasite targets will help fight against this neglected disease
Major Kinds of Drug Targets in Chagas Disease or American Trypanosomiasis
No full textFil: Duschak, Vilma G. ANLIS Dr. C. G. Malbrán. Instituto Nacional de Parasitología Dr. Mario Fatala Chaben; Argentina.American Trypanosomiasis, a parasitic infection commonly named Chagas disease, affects millions of people all over Latin American countries. Presently, the World Health Organization (WHO) predicts that the number of international infected individuals extends to 7 to 8 million, assuming that more than 10,000 deaths occur annually. The transmission of the etiologic agent, Trypanosoma cruzi, through people migrating to non-endemic world nations makes it an emergent disease. The best promising targets for trypanocidal drugs may be classified into three main groups: Group I includes the main molecular targets that are considered among specific enzymes involved in the essential processes for parasite survival, principally Cruzipain, the major antigenic parasite cysteine proteinase. Group II involves biological pathways and their key specific enzymes, such as Sterol biosynthesis pathway, among others, specific antioxidant defense mechanisms, and bioenergetics ones. Group III includes the atypical organelles /structures present in the parasite relevant clinical forms, which are absent or considerably different from those present in mammals and biological processes related to them. These can be considered potential targets to develop drugs with extra effectiveness and fewer secondary effects than the currently used therapeutics. An improved distinction between the host and the parasite targets will help fight against this neglected disease
Study on the obtaining of Tityus trivittatus venom in Argentina
No full textFil: de Roodt, Adolfo Rafael. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Producción de Biológicos. Servicio antígenos y antisueros; Argentina.Fil: Lanari, Laura Cecilia. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Producción de Biológicos. Servicio antígenos y antisueros; Argentina.Fil: Laskowicz, Rodrigo Daniel. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Producción de Biológicos. Servicio antígenos y antisueros; Argentina.Fil: Costa de Oliveira, Vanessa. Primera Cátedra de Toxicología, Facultad de Medicina, Universidad de Buenos Aires, Argentina; Laboratorio de Toxinopatología, Centro de Patología Experimental y Aplicada, Facultad de Medicina, Universidad de Buenos Aires; Argentina.Fil: Litwin, Silvana. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Producción de Biológicos; Argentina.Fil: Calderon, Leandro. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Producción de Biológicos; Argentina.Fil: Damin, Carlos Fabián. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Producción de Biológicos; Argentina.Fil: Dokmetjian, Christian. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Producción de Biológicos; Argentina.Fil: Dolab, Jorge A. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Producción de Biológicos; Argentina.Fil: Lago, Néstor Rubén. Laboratorio de Toxinopatología, Centro de Patología Experimental y Aplicada, Facultad de Medicina, Universidad de Buenos Aires; Argentina.Fil: Lértora, Emiliano. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Producción de Biológicos; Argentina.Envenomation by scorpions of the genus Tityus is an important public health problem in Argentina, involving near 8000 stings and 2 deaths each year. Treatment for envenomation is the use of specific antivenom and intensive hospital care. Antivenom is produced by the Ministry of Health and freely distributed throughout the country. For antivenom production it is necessary to collect scorpion venom, which is a difficult task because although scorpions can be found in Argentina, they are less abundant than in warmer latitudes. For this reason venom collection constitutes a bottleneck for antivenom production. Although in Argentina several species of Tityus can be found, most of the accidents are caused by Tityus trivittatus, and the venom of this scorpion has historically been the venom used for antivenom production. We analyzed retrospectively 26 pools of telson homogenates (6964 telsons) and 37 pools of milked venom obtained by electrical stimulation (equivalent to 6841 milkings). Lethal potencies of samples from different provinces were very similar, although venom from scorpions of Buenos Aires city showed the lowest potency. The venom obtained by milking (median LD50 12.3 μg), provided batches containing LD50s more potent when compared with the venom obtained from telson homogenates (p < 0.0001). Many batches of telson homogenates (30%) showed lower potencies than acceptable for antivenom production and control. In addition to the study of the venom yield, the records of immunization of horses, the potency of the batches and the protein content of each batch of anti-scorpion antivenom produced were analyzed, comparing those produced using milked venom with those using telson homogenates as immunogens. Batches produced using milked venom required a shorter period of immunization (p < 0.0001), rendered higher neutralizing titers (p 0.0350) and possessed lower protein content (p 0.0092). Results clearly showed that the milking of scorpions is a more efficient tool to obtain venom for antivenom production in comparison to the use of telson homogenates
Klebsiella pneumoniae ST258 Negatively Regulates the Oxidative Burst in Human Neutrophils
No full textFil: Castillo, Luis A. Consejo Nacional de investigaciones Científicas y Tecnológicas (CONICET). Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental (IMEX). Laboratorio de Fisiología de los Procesos Inflamatorios; Argentina.Fil: Birnberg-Weiss, Federico. Consejo Nacional de investigaciones Científicas y Tecnológicas (CONICET). Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental (IMEX). Laboratorio de Fisiología de los Procesos Inflamatorios; Argentina.Fil: Rodriguez-Rodrigues, Nahuel. Consejo Nacional de investigaciones Científicas y Tecnológicas (CONICET). Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental (IMEX). Laboratorio de Fisiología de los Procesos Inflamatorios; Argentina.Fil: Martire-Greco, Daiana. Consejo Nacional de investigaciones Científicas y Tecnológicas (CONICET). Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental (IMEX). Laboratorio de Fisiología de los Procesos Inflamatorios; Argentina.Fil: Bigi, Fabiana. Consejo Nacional de investigaciones Científicas y Tecnológicas (CONICET). Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular (IABIMO); Argentina.Fil: Landoni, Veronica I. Consejo Nacional de investigaciones Científicas y Tecnológicas (CONICET). Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental (IMEX). Laboratorio de Fisiología de los Procesos Inflamatorios; Argentina.Fil: Gomez, Sonia A. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Bacteriología. Servicio Antimicrobianos; Argentina.Fil: Fernandez, Gabriela C. Consejo Nacional de investigaciones Científicas y Tecnológicas (CONICET). Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental (IMEX). Laboratorio de Fisiología de los Procesos Inflamatorios; Argentina.The epidemic clone of Klebsiella pneumoniae (Kpn), sequence type 258 (ST258), carbapenamase producer (KPC), commonly infects hospitalized patients that are left with scarce therapeutic option since carbapenems are last resort antibiotics for life-threatening bacterial infections. To improve prevention and treatment, we should better understand the biology of Kpn KPC ST258 infections. Our hypothesis was that Kpn KPC ST258 evade the first line of defense of innate immunity, the polymorphonuclear neutrophil (PMN), by decreasing its functional response. Therefore, our aim was to evaluate how the ST258 Kpn clone affects PMN responses, focusing on the respiratory burst, compared to another opportunistic pathogen, Escherichia coli (Eco). We found that Kpn KPC ST258 was unable to trigger bactericidal responses as reactive oxygen species (ROS) generation and NETosis, compared to the high induction observed with Eco, but both bacterial strains were similarly phagocytized and cause increases in cell size and CD11b expression. The absence of ROS induction was also observed with other Kpn ST258 strains negative for KPC. These results reflect certain selectivity in terms of the functions that are triggered in PMN by Kpn, which seems to evade specifically those responses critical for bacterial survival. In this sense, bactericidal mechanisms evasion was associated with a higher survival of Kpn KPC ST258 compared to Eco. To investigate the mechanisms and molecules involved in ROS inhibition, we used bacterial extracts (BE) and found that BE were able to inhibit ROS generation triggered by the well-known ROS inducer, fMLP. A sequence of experiments led us to elucidate that the polysaccharide part of LPS was responsible for this inhibition, whereas lipid A mediated the other responses that were not affected by bacteria, such as cell size increase and CD11b up-regulation. In conclusion, we unraveled a mechanism of immune evasion of Kpn KPC ST258, which may contribute to design more effective strategies for the treatment of these multi-resistant bacterial infections
PCR-Based Method for Shigella flexneri Serotyping: International Multicenter Validation
Get PDFFil: Brengi, Silvina P. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Bacteriología. Servicio Enterobacterias; Argentina.Fil: Sun, Qiangzheng. Chinese Center for Disease Control and Prevention. National Institute for Communicable Diseases Control and Prevention. State Key Laboratory for Infectious Disease Prevention and Control, Changping, Beijing; China.Fil: Bolaños, Hilda. Centro Nacional de Referencia de Bacteriología, Inciensa, Cartago; Costa Rica.Fil: Duarte, Francisco. Centro Nacional de Referencia de Bacteriología, Inciensa, Cartago; Costa Rica.Fil: Jenkins, Claire. Public Health England. Gastrointestinal Bacteria Reference Unit, Londres, Inglaterra.Fil: Pichel, Mariana. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Bacteriología. Servicio Enterobacterias; Argentina.Fil: Shahnaij, Mohammad. International Center for Diarrheal Disease Research. Laboratory Sciences and Services Division. Enteric and Food Microbiology Laboratory Dhaka; Bangladés.Fil: Sowers, Evangeline G. Centers for Disease Control and Prevention. National Institute for Escherichia and Shigella Reference Unit, Atlanta, Georgia, Estados Unidos.Fil: Strockbine, Nancy. Centers for Disease Control and Prevention. National Institute for Escherichia and Shigella Reference Unit, Atlanta, Georgia, Estados Unidos.Fil: Talukder, Kaisar A. International Center for Diarrheal Disease Research. Laboratory Sciences and Services Division. Enteric and Food Microbiology Laboratory Dhaka; Bangladés.Fil: Derado, Gordana. Centers for Disease Control and Prevention. Biostatistics and Information Management Office. Waterborne and Environmental Diseases. Division of Foodborne, Atlanta, Georgia, Estados Unidos.Fil: Viñas, María R. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Bacteriología. Servicio Enterobacterias; Argentina.Fil: Kam, Kai Man. The Chinese University of Hong Kong. Faculty of Medicine. School of Public Health and Primary Care. Stanley Ho Centre for Emerging Infectious Diseases, Hong Kong; China.Fil: Xu, Jianguo. Chinese Center for Disease Control and Prevention. National Institute for Communicable Diseases Control and Prevention. State Key Laboratory for Infectious Disease Prevention and Control, Changping, Beijing; China.Shigella spp. are a leading cause of human diarrheal disease worldwide, with Shigella flexneri being the most frequently isolated species in developing countries. This serogroup is presently classified into 19 serotypes worldwide. We report here a multicenter validation of a multiplex-PCR-based strategy previously developed by Q. Sun, R. Lan, Y. Wang, A. Zhao, et al. (J Clin Microbiol 49:3766-3770, 2011) for molecular serotyping of S. flexneri This study was performed by seven international laboratories, with a panel of 71 strains (researchers were blind to their identity) as well as 279 strains collected from each laboratory's own local culture collections. This collaborative work found a high extent of agreement among laboratories, calculated through interrater reliability (IRR) measures for the PCR test that proved its robustness. Agreement with the traditional method (serology) was also observed in all laboratories for 14 serotypes studied, while specific genetic events could be responsible for the discrepancies among methodologies in the other 5 serotypes, as determined by PCR product sequencing in most of the cases. This work provided an empirical framework that allowed the use of this molecular method to serotype S. flexneri and showed several advantages over the traditional method of serological typing. These advantages included overcoming the problem of availability of suitable antisera in testing laboratories as well as facilitating the analysis of multiple samples at the same time. The method is also less time-consuming for completion and easier to implement in routine laboratories. We recommend that this PCR be adopted, as it is a reliable diagnostic and characterization methodology that can be used globally for laboratory-based shigella surveillance
Estudio Nacional de Diagnóstico Institucional y Prevalencia de Infecciones Asociadas al Cuidado de la Salud de Hospitales de Argentina
No full textEste informe presenta los resultados del Estudio Nacional de Diagnóstico Institucional y Prevalencia de Infecciones Asociadas al Cuidado de la Salud de Hospitales de Argentina - Edición 2018 (ENPIHA-ARG 2018), realizado por el Programa Nacional de Vigilancia de Infecciones Hospitalarias de Argentina (VIHDA) del Instituto Nacional de Epidemiología de la Administración Nacional de Laboratorios e Institutos de Salud Dr. Carlos G. Malbrán
Putative virulence factors and clonal relationship of O174 Shiga toxin-producing Escherichia coli isolated from human, food and animal sources
No full textFil: Cundon, Cecilia. Universidad de Buenos Aires, Facultad de Ciencias Veterinarias, Cátedra de Microbiología; Argentina.Fil: Carbonari, Claudia C. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Bacteriología. Servicio Fisiopatogenia; Argentina.Fil: Zolezzi, Gisela. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Bacteriología. Servicio Fisiopatogenia; Argentina.Fil: Rivas, Marta. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Bacteriología. Servicio Fisiopatogenia; Argentina.Fil: Bentancor, A. Universidad de Buenos Aires, Facultad de Ciencias Veterinarias, Cátedra de Microbiología; Argentina.Shiga toxin-producing Escherichia coli (STEC) is th etiological agent of gastrointestinal diseases as haemorrhagic colitis and haemolytic-uraemic syndrome (HUS). Shiga toxin (Stx) is the main virulence factor. There are two types, Stx1 and Stx2, and several subtypes. Other virulence factors are involved in pathogenesis. While O157:H7 is the predominant serotype, at present non-O157 STEC strains are increasingly recognized as foodborne pathogens worldwide. In Argentina, STEC O174 stands out as an emerging pathogen and is one of the four most prevalent non-O157 STEC serogroups. The aim of this study was to characterize 41 O174:[H21, H28] STEC strains isolated from animals, food, and humans. Isolates were characterized by stx genotyping, adhesion factors (afaC, eae, iha, lpfO113, saa, and toxB), additional toxins (cdtV, ehxA, subA) and clonal relationship by pulsed-field gel electrophoresis (PFGE). Among 30 O174:H21 strains, the most prevalent stx subtype was stx2c (56.7%), and among 11 O174:H28 strains, the most prevalent was stx2a (90.9%). Regarding virulence factors, all strains were positive for afaC gene and negative for eae and toxB genes. In O174:H21, the frequency of additional factors was lpfO113 (96.6%), iha (83.3%), ehxA and saa (10%), and subA (3.3%), meanwhile in O174:H28 strains the frequency was iha and subA (100%), lpfO113 (90.9%), ehxA and saa (90.9%), and cdtV (9.09%). By Xbal-PFGE, 29 patterns were established with 64.01% similarity and three clusters were detected. Given the fact that the O174 serogroup is a local emergent, it is important to study the virulence profiles to understand its potential pathogenicity
Chagas cardiomyopathy associated with serological cure after trypanocidal treatment during childhood
No full textFil: Fernández, Marisa Liliana. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología. Departamento de Clínica, Patología y Tratamiento; Argentina.Fil: Hernández, Yolanda. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología. Departamento de Clínica, Patología y Tratamiento; Argentina.Fil: Scollo, Karenina. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología. Departamento de Diagnóstico; Argentina.Fil: Esteva, Mónica Ines. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología. Departamento de Investigación; Argentina.Fil: Riarte, Adelina Rosa. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología. Departamento de Clínica, Patología y Tratamiento; Argentina.Fil: Prado, Graciela Nilda. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología. Departamento de Clínica, Patología y Tratamiento; Argentina.Chagas disease is a chronic parasitological disease, which could cause cardiac manifestations in approximately one-third of affected individuals. Benznidazole and nifurtimox are used to treat this parasitological infection caused by Trypanosoma cruzi. Conventionally, the criterion for cure is consistently negative serological tests after treatment. We report a case of a patient who was treated when she was 13 years old and achieved T. cruzi negative seroconversion but developed Chagas disease cardiomyopathy as an adult
Trypanosoma cruzi-specific IFN-γ-producing cells in chronic Chagas disease associate with a functional IL-7/IL-7R axis
No full textFil: Natale, María A. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina.Fil: Cesar, Gonzalo. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina.Fil: Alvarez, María G. Hospital Interzonal General de Agudos Eva Perón, Buenos Aires; Argentina.Fil: Castro Eiro, Melisa D. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina.Fil: Lococo, Bruno. Hospital Interzonal General de Agudos Eva Perón, Buenos Aires; Argentina.Fil: Bertocchi, Graciela. Hospital Interzonal General de Agudos Eva Perón, Buenos Aires; Argentina.Fil: Albareda, María Cecilia. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina.Fil: Laucella, Susana A. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina.The severity of cardiac disease in chronic Chagas disease patients is associated with different features of T-cell exhaustion. Here, we assessed whether the ability of T cells to secrete IFN-γ in response to T. cruzi was linked to disruption in immune homeostasis and inflammation in patients with chronic Chagas disease
Genomic analysis of the first isolate of KPC-2-producing Klebsiella pneumoniae from Uruguay
No full textSince KPC-2-producing Klebsiella pneumoniae are associated with successful dissemination of a major clone, defined as sequence type 258 (ST258), the aim of this study was to perform whole-genome sequencing (WGS) of the first colistin-resistant K. pneumoniae strain (Kpn666) carrying blaKPC-2 identified in Uruguay in 2011 in order to identify genomic and phylogenetic traits