Epidemias bacterianas emergentes do século XXI

As doenças infeciosas distantes de serem um problema do passado têm aumentado drasticamente nestes últimos anos, causando epidemias emergentes, quer de origem bacteriana ou vírica ou de outros tipos de microrganismos. Esta dissertação tem como objetivo uma pesquisa atual bibliográfica sobre o estudo de algumas epidemias bacterianas emergentes do século XXI, como a Tuberculose, Cólera, Staphylococcus aureus resistente à meticilina (MRSA) e Meningite Meningocócica, bem como os seus dados epidemiológicos. A Tuberculose é uma das doenças mais antigas, que apresenta uma elevada taxa de mortalidade e com o passar do tempo tem vindo a aumentar a nível mundial. A TB é causada por uma bactéria denominada Mycobacterium tuberculosis que normalmente afeta os pulmões e outros órgãos. O tratamento, a prevenção e o diagnóstico precoce são pontos essenciais, para ter um bom desfecho para o doente. A Cólera tem-se propagado pelo mundo desde o século XX. Esta doença caracteriza-se por uma diarreia aguda grave que é causada pela bactéria Vibrio cholerae. O seu tratamento se for realizado precocemente é tratado facilmente, com apenas hidratação com sais orais. A prevenção é uma medida essencial para ter um bom prognóstico, e evitar surtos emergentes desta infeção. Devido à sua virulência, Staphylococcus aureus é responsável por infeções graves adquiridas em hospital e na comunidade. Na maioria das vezes esta infeção é assintomática, mas pode causar infeções graves até mesmo fatais. Devido às resistências aos antibióticos β-lactâmicos e de outros tipos de antibióticos, e também devido ao aumento do número crescente de quadros infeciosos de MRSA, houve necessidade de novos antibióticos como o linezolide, as cefasloporinas de 5ª geração no combate a estas infeções. As medidas de prevenção são essenciais, visto que se não forem realizadas pode haver progressão da doença. Além de um estudo científico constante dos mecanismos de resistências desta bactéria, ser essencial. A meningite bacteriana é um grave problema de Saúde Pública devido à alta incidência em crianças. A meningite meningocócica é causada pela bactéria Neisseria meningitidis que origina um processo inflamatório das meninges. Há algum tempo atrás a mortalidade era elevada, mas com o advento da antibioterapia reduziu significativamente. As vacinas fizeram com que ocorresse uma mudança bastante significativa na epidemiologia desta patologia, e mais uma vez a prevenção é essencial.

Emergency emicolectomy for intestinal primary Aspergillosis in acute myeloid leukemia

ntestinal aspergillosis is an infection with a very high death rate especially in leukemic patients. Here we describe a case of a 46 years old woman with acute myeloid leukemia (LAM M5) who developed intestinal primary aspergillosis. This patient was diagnosed with LAM M5 through bone marrow aspiration and bone biopsy in March 2004. Symptoms of the disease were slight persistent fever, weight loss, asthenia, anemia, thrombocytopenia,and leukocytosis with high number of blasts in peripheral blood. After induction chemotherapy with ICE (Ifosfamide, Carboplatin, Etoposide), she developed neutropenia and high fever without apparent infective foci. She was treated with empiric antibiotic therapy, nevertheless she developed an intense diarrhea and ileo-cecal distention. Diagnostic exams didn’t show signs of a focal lesion. Despite the change in antibiotic treatment and the transfusions of granulocytes and blood cells, the patient developed extremely critical conditions with persistence of neutropenia and abdominal distention. A surgical treatment was decided at the time. We treated the patient with a two steps surgical procedure. The first step was a right abdominal ileostomy followed by improvement of general conditions and then the second step a right colectomy. The histological morphology confirmed necrotizing colitis with Aspergillus ife. At that time , treatment with voriconazole was started. The general conditions of the patient improved rapidly and we were able to treat the patient with other medical anti-leukemic therapies. The patient is now cured and in healthy state. We obtained a good clinical result as only in other few cases described in literature.

Histopathology findings in common marmosets (Callithrix jacchus Linnaeus, 1758) with chronic weight loss associated with bile tract obstruction by infestation with Platynosomum (Loos, 1907)

Chronic weight loss in marmosets is often associated with wasting marmoset syndrome (WMS), an important disease that occurs in callitrichid colonies around the world. Even though its etiology is very difficult to determine, particular variables, such as weight loss, diarrhea and alopecia, associated or not with infestation in the pancreatic ducts with Trichospirura leptossoma (Nematoda: Thelazioidea), seem to be linked with the syndrome. This study investigated the histopathology of the lungs, duodenum, liver, gallbladder, extrahepatic bile ducts and pancreatic ducts of six common marmosets (Callithrix jacchus) suffering from severe non-diarrheic weight loss. Three individuals died naturally and the other three were euthanized. Microscopic findings showed the presence of adult flukes (Platynosomum) in the liver. These flukes, which provoke common infection in cats, were also observed inside the gallbladder as well as in the intra and extrahepatic bile ducts in common marmosets. Portal fibrosis was observed in two animals, which developed chronic fibrosing hepatopathy (biliary pattern, grade 3). The disease progresses without diarrhea and without pancreatic lesions or infestation. With the rogression, the animals presented with ascending cholangitis, cholestasis and portal fibrosis, sometimes culminating in secondary biliary cirrhosis. Therefore, this nfirmity, associated with chronic weight loss in common marmosets, could be another tiological factor linked with WMS

The effectiveness of community-based interventions to improve maternal and infant health in the Northeast of Brazil

EMOND, Alan et al. The effectiveness of community-based interventions to improve maternal and infant health in the Northeast of Brazil. Revista Panamericana de Salud Pública/ Pan American Journal of Public Health , v.12, n.2, p.101-110, 2002

Whipple’s disease infection surgical treatment: presentation of a rare case and literature review

The Whipple’ Disease (W.D.) is a very rare disease with an incidence of 1 per 1.000.000 inhabitants; it is a systemic infection that may mimic a wide spectrum of clinical disorders, which may have a fatal outcome and affects mainly male 40-50 years old. The infective agent is an actinomycete, Tropheryma Whipplei (T.W.) that was isolated 100 years after first description by Wipple, and identified in macrophages of mucosa of the small intestine by biopsy which is characterized by periodic acid-Schiff-positive, products of the inner membrane of his polysaccharide bacterial cell wall. The multisystemic clinical manifestations evolve rapidly towards an organic decay characterized by weight loss, malabsorption, diarrhea, polyathralgia, opthalmoplegia, neuro-psychiatric disorders and sometimes associated to endocarditis. Early antibiotic treatment with trimethoprim and sulfometathaxazole reduces the fatal evolution of the disease. The authors present a rare experience about a female subject in which the clinical gastrointestinal signs were preceded by neuro-psychiatric disorders, and evolved into obstruction and intestinal perforation which required an emergency surgery with temporary ileostomy, recanalized only after adequate medical treatment with a full dose of antibiotic and resolution of clinical disease for the high risks of fistulae for the edema and lymphadenopathy of mucosa. The diagnosis was histologically examined by intestinal biopsy performed during surgery, which showed PAS-positive histiocytes, while PRC polymerase RNA was negative, which confirms the high sensibility of PAS positive and low specificity of RNA polymerase for T.W.

3531: Neoadjuvant radiotherapy (RT) combined with capecitabine (Cape) and sorafenib (Sor) in patients (pts) with locally advanced, k-ras-mutated rectal cancer (LARC): A phase I/II trial SAKK 41/08

Background: K-ras mutation is found in up to 40% of LARC. Sor is a multitarget tyrosine kinase inhibitor including raf and VEGFR and has demonstrated radiosensitizing effects. Sor might improve outcome of standard preoperative radio-chemotherapy in patients with k-ras mutated LARC. Methods: Pts with k-ras mutated T3-4 and/or N+, M0 disease by MRI were included. Recommended doses from phase I part consisted of RT 1.8 Gy/day x25 with Cape 825mg/m2bid x 33 in combination with Sor 400mg/d. The primary endpoint for the phase II part was pathological complete response (pCR) prospectively defined as grade 3 (near complete regression) or 4 (complete regression) in the histological grading system according to Dworak (DC). A pCR rate of 8% or lower was considered uninteresting and of 22% or higher was promising. Secondary endpoints included sphincter preservation, R0 resection, downstaging and safety. Results: 54 pts were treated in 18 centers in Switzerland und Hungary, 40 pts were included into the single arm phase II part. Median dose intensity per day was 100.0% for RT, 98.6% for Cape and 100.0% for Sor respectively. pCR rate was 60.0% (95%CI: 43.3%, 75.1%) by central independent pathological review (15.0% DC grade 4; 45.0% DC grade 3). Sphincter preservation was achieved in 89.5%, R0 resection in 94.7% and downstaging in 81.6% of the pts. The most common grade 3 toxicities included diarrhea (15.0%), skin toxicity outside of the RT field (12.5%), pain (7.5%), skin toxicity in RT field, proctitis, fatigue and cardiac ischemia (each 5.0%). Laboratory AEs grade 3/4 were neutropenia (1 pt grade 4; 1 grade 3), creatinine elevation (1 pt grade 3). Conclusions: The combination of Sor to standard RCT with Cape in k-ras mutated LARC tumors is highly active with acceptable toxicity and deserves further investigation.

Novel pharmacogenomic markers of irinotecan-induced severe toxicity in metastatic colorectal cancer patients

L’irinotécan est un agent de chimiothérapie largement utilisé pour le traitement de tumeurs solides, particulièrement pour le cancer colorectal métastatique (mCRC). Fréquemment, le traitement par l’irinotécan conduit à la neutropénie et la diarrhée, des effets secondaires sévères qui peuvent limiter la poursuite du traitement et la qualité de vie des patients. Plusieurs études pharmacogénomiques ont évalué les risques associés à la chimiothérapie à base d’irinotécan, en particulier en lien avec le gène UGT1A, alors que peu d’études ont examiné l’impact des gènes codant pour des transporteurs. Par exemple, le marqueur UGT1A1*28 a été associé à une augmentation de 2 fois du risque de neutropénie, mais ce marqueur ne permet pas de prédire la toxicité gastrointestinale ou l’issue clinique. L’objectif de cette étude était de découvrir de nouveaux marqueurs génétiques associés au risque de toxicité induite par l’irinotécan, en utilisant une stratégie d’haplotype/SNP-étiquette permettant de maximiser la couverture des loci génétiques ciblés. Nous avons analysé les associations génétiques des loci UGT1 et sept gènes codants pour des transporteurs ABC impliqués dans la pharmacocinétique de l’irinotécan, soient ABCB1, ABCC1, ABCC2, ABCC5, ABCG1, ABCG2 ainsi que SLCO1B1. Les profils de 167 patients canadiens atteints de mCRC sous traitement FOLFIRI (à base d’irinotécan) ont été examinés et les marqueurs significatifs ont par la suite été validés dans une cohorte indépendante de 250 patients italiens. Nous avons découvert dans la région intergénique en aval du gène UGT1, un nouveau marqueur (rs11563250G) associé à un moindre risque de neutropénie sévère (rapport des cotes (RC)=0.21; p=0.043 chez les canadiens, RC=0.27; p=0.036 chez les italiens, et RC=0.31 p=0.001 pour les deux cohortes combinées). De plus, le RC est demeuré significatif après correction pour multiples comparaisons (p=0.041). Par ailleurs, pour l’haplotype défini par les marqueurs rs11563250G et UGT1A1*1 (rs8175347 TA6), le RC était de 0.17 (p=0.0004). Un test génétique évaluant ces marqueurs permettrait d’identifier les patients susceptibles de bénéficier d’une augmentation de dose d’irinotécan. En revanche, une autre combinaison de marqueurs, ABCC5 rs3749438 et rs10937158 (T–C), a prédit un risque plus faible de diarrhée sévère dans les deux cohortes (RC = 0.43; p=0.001). La coexistence des marqueurs ABCG1 rs225440T et ABCC5 rs2292997A a prédit un risque accru de neutropénie (RC=5.93; p=0.0002), alors qu’une prédiction encore plus significative a été obtenue lorsque ces marqueurs sont combinés au marqueur de risque bien établi UGT1A1*28 rs8175347 (RC=7.68; p<0.0001). Enfin, les porteurs de l’allèle de protection UGT1 rs11563250G en absence d’allèles de risque, ont montré une incidence réduite de neutropénie sévère (8.2% vs. 34.0%; p<0.0001). Nous concluons que ces nouveaux marqueurs génétiques prédictifs pourraient permettre d’améliorer l’évaluation du risque de toxicité et personnaliser le traitement à base d’irinotécan pour les patients atteints du cancer colorectal métastatique.

Vandetanib for the Treatment of Advanced Medullary Thyroid Cancer Outside a Clinical Trial: Results from a French Cohort

International audience

Celiac Crisis in an Adult: Raising Awareness to a Life-Threatening Condition

Objectives: The Authors report the case of a 56-year-old man with celiac disease, who after ingesting a food containing gluten and experiencing a flu-like syndrome, developed severe diarrhea, vomiting, weight loss (15 kg), hypotension, renal dysfunction, hypokalemia and metabolic acidosis. Materials and methods: Admission to the Intensive Care Unit and exclusion of an infectious cause was determined. Results: After receiving noradrenaline, methylprednisolone and correction of ionic disturbances, the patient recovered rapidly and had no further complication. Conclusion: The Authors intend to increase awareness of celiac crisis, because despite being extremely rare in adults, it is potentially fatal and an quick diagnosis and treatment are crucial.

La construction de relations de confiance au sein des équipes-écoles d’établissements en milieu autochtone du Québec selon les perceptions de leur direction

Résumé : La gestion des ressources humaines dans les écoles situées au sein de communautés autochtones est marquée par différents enjeux d’ordres social, culturel, ethnoculturel, économique et administratif qui impactent les pratiques de leurs directions. Ceux-ci touchent à tous les aspects de la gestion des écoles et peuvent être révélateurs d’un malaise dans l’encadrement des actrices et des acteurs à travers des structures administratives, juridiques, éducatives ou de gouvernance qui comportent des défis relationnels et interactionnels majeurs. Ce type de malaise peut moduler les actions des actrices et des acteurs des établissements et peut entrainer des impacts dans leurs relations, notamment au niveau de leurs relations de confiance, essentielles à la qualité de leurs actions communes. L’approfondissement de cette problématique porte essentiellement sur les conditions associées à la construction de la confiance qui sont de différents ordres, c’est-à-dire contextuel, institutionnel, organisationnel, relationnel ou individuel. Utilisant une approche qualitative, cette recherche repose sur vingt-trois entrevues semi-dirigées avec des directions d’établissement provenant de dix-sept communautés et de trois nations autochtones différentes. L’analyse est menée à partir d’une approche exploratoire constructiviste et interprétativiste. Les conclusions permettent de dégager que la construction de relations de confiance entre des actrices et des acteurs sont tributaires de conditions dans lesquelles s’inscrivent des dynamiques interactionnelles particulières. Influencées par le contexte autochtone singulier, ces conditions sont préalables aux actrices et aux acteurs ou associées à leurs comportements, attitudes, actions ou pratiques. Il apparait que ces dynamiques s’inscrivent dans une configuration des équipes-écoles se caractérisant par six catégories-types d’individus qui se déclinent selon leur origine et leur appartenance ou leur identité ethnique, à savoir les voyageurs autochtones et allochtones, les étrangers autochtones et allochtones et les natifs autochtones et allochtones. La meilleure compréhension de cette organisation conduit à une conception large de la configuration des dynamiques interactionnelles entre des individus et des groupes et entre des communautés d’individus. Ces individus s’affilient spécifiquement selon des identités ou des appartenances individuelles ou de groupe qui peuvent être de différents ordres soit particulièrement, mais non exclusivement, ethnique, linguistique, familial ou se rapportant à des croyances particulières.

Intestinal ameliorative effects of traditional Ogi-tutu, Vernonia amygdalina and Psidium guajava in mice infected with Vibrio cholera.

Background: Cholera, a severe acute watery diarrhea caused by Vibrio cholerae is endemic in Nigeria with most cases occurring in the rural areas. In South West Nigeria, some individuals resort to alternative treatments such as Ogi-tutu, Psidium guajava and Vernonia amygdalina during infections. The effectiveness of these alternatives in the prevention and treatment of V. cholerae infection requires experimental investigation. Objective: This study was designed to investigate the ameliorative effects of Ogi-tutu, Vernonia amygdalina and Psidium guajava on intestinal histopathology of experimental mice infected with V. cholerae. Methods: Preliminary investigation of in vitro vibriocidal activities of these alternatives were carried out using agar cup diffusion assay. For ameliorative effects, adult mice were inoculated with 100 μl (106 cells) of Vibrio cholerae and dosed at 0 h (immediate prevention) and 4 h (treatment of infection) and their intestines were histopathologically evaluated. Results: The histopathological changes were the same irrespective of the treated groups, but the lesions varied in extent and severity. The ameliorative effects in decreasing order were V. amygdalina > P. guajava > Ogi-tutu. Conclusion: V. amygdalina gave the best ameliorative effects in the prevention and treatment of V. cholerae infection.

Deficiencias minerales en bovinos para carne: diagnóstico, caracterización y control

La demanda de una producción de alimentos cada vez mayor a nivel mundial sumado a la tecnificación y al ritmo acelerado del progreso de las explotaciones agropecuarias actuales hacen que el ganado deba soportar elevadas presiones de producción aumentando los requerimientos de nutrientes. Este es el caso de los minerales considerados actualmente elementos esenciales para los animales, aunque tradicionalmente fueron definidos como los nutrientes pobres de la nutrición y alimentación animal. Actualmente se ha demostrado con evidencia clínica y productiva, el importante rol metabólico de los minerales en el animal sano y productivo, como también se ha definido qué elemento mineral y porcentaje del mismo es requerido para el normal funcionamiento del organismo. Los macro-minerales (calcio, magnesio, fósforo, sodio, potasio, cloro y azufre) y los oligo-minerales (cobre, zinc, hierro, selenio, cobalto, iodo, manganeso, molibdeno y cromo) son elementos esenciales y necesarios para transformar la proteína y la energía de los alimentos en componentes del organismo o en productos animales como leche, carne, crías, piel, lana. Además, ayudan al organismo a combatir las enfermedades, manteniendo al animal en buen estado de salud. Se ha considerado a los minerales como el tercer grupo limitante en la nutrición animal, siendo a su vez, el que mayor potencial y menor costo tiene para incrementar la producción del ganado. Los minerales desempeñan funciones tan importantes como ser constituyentes de la estructura ósea y dental, de tejidos blandos y líquidos corporales. Están involucrados en el funcionamiento celular, siendo activadores de más de trescientas enzimas, constituyentes esenciales de vitaminas, hormonas y pigmentos respiratorios y facilitando la actividad de los microorganismos del rumen. Cuando el aporte de minerales en la ración no es el adecuado en calidad y/o cantidad se originan las deficiencias minerales, encuadradas dentro de las enfermedades metabólicas o enfermedades de la producción. Estas han sido informadas en casi todo el mundo y son responsables de importantes pérdidas económicas en los rodeos de bovinos para carne. Las deficiencias y/o desequilibrios minerales pueden causar los siguientes trastornos en los animales: bajo porcentaje de parición, mayor número de servicios por concepción, abortos, retenciones placentarias, incremento del intervalo entre partos, baja producción de leche, menor peso al nacimiento y al destete, menor porcentaje de destete, menor ganancia de peso, mayor incidencia de enfermedades infecciosas, fracturas espontáneas, diarrea, deformación de huesos y mortandad. Así cobra importancia el diagnóstico mediante el análisis de la sangre de los animales, del pasto y el agua que consumen y la caracterización de estas deficiencias en primarias o secundarias con el objetivo de poder realizar un control de las mismas mediante un adecuado plan de suplementación mineral acorde a las necesidades de los distintos establecimientos agropecuarios.

Persistent infectious and tropical diseases in immigrant correctional populations

A number of infectious diseases amongst travelers and the immigrant populations are a major public health concern. Some have a long incubation period or remain asymptomatic or paucisymptomatic for many years before leading to significant clinical manifestations and/or complications. HIV, hepatitis B and C, tuberculosis or latent syphilis are among the most significant persistent diseases in migrants. Schistosomiasis and strongyloidiasis, for instance, are persistent helminthic infections that may cause significant morbidity, particularly in patients co-infected with HIV, hepatitis B and C. Chagas disease, which was initially confined to Latin America, must also now be considered in immigrants from endemic countries. Visceral leishmaniasis and malaria are other examples of parasitic diseases that must be taken into account by physicians treating incarcerated migrants. The focus of this review article is on the risk of neglected tropical diseases in particularly vulnerable correctional populations and on the risk of infectious diseases that commonly affect migrants but which are often underestimated.

Role of phospholipase A(2) and tyrosine kinase in Clostridium difficile toxin A-induced disruption of epithelial integrity, histologic inflammatory damage and intestinal secretion

Clostridium difficile-associated disease causes diarrhea to fulminant colitis and death. We investigated the role of phospholipase A(2) (PLA(2)) inhibitors, aristolochic acid (AA), bromophenacyl bromide BPB and quinacrine (QUIN) on the C. difficile toxin A-induced disruption of epithelial integrity, histologic inflammatory damage and intestinal secretion. Toxin A caused severe hemorrhagic and inflammatory fluid secretion at 6-8 h in rabbit ileal segments, an effect that was significantly inhibited by QUIN (71%, P < 0.01), AA (87%, P < 0.0001) or by BPB (51%, P < 0.01). The secretory effect of toxin A was also inhibited in segments adjacent to those with AA (89%, P < 0.01). Furthermore, QUIN or AA substantially reduced the histologic damage seen after 6-8 h in rabbit ileal segments. The cyclooxygenase inhibitor, indomethacin, also significantly inhibited (96%; n = 6) the secretory effects of toxin A in ligated rabbit intestinal segments. The destruction by toxin A of F-actin at the light junctions of T-84 cell monolayers was not inhibited by AA or BPB. AA or QUIN had no effect on the T-84 cell tissue resistance reduction over 8-24 h after toxin A exposure. All the inhibitors were shown to be effective in the doses administered direct in ileal loops to inhibit PLA(2) activity. The data suggest that PLA(2) is involved in the major pathway of toxin A-induced histologic inflammatory damage and hemorrhagic fluid secretion. Cop. right (C) 2008 John Wiley & Sons, Ltd.