Bacilos gramnegativos de crecimiento lento: grupo HACEK, Capnocytophaga y Pasteurella / Fastidious gram-negative rods: HACEK group, Capnocytophaga and Pasteurella

Las bacterias del grupo HACEK (Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, Kingella), Pasteurella y Capnocytophaga son las bacterias gramnegativas de crecimiento lento que con mayor frecuencia causan infecciones en el ser humano. Forman parte de la microbiota del tracto respiratorio superior y genitourinario del ser humano y de animales, y pueden causar infecciones en cualquier localización, pero fundamentalmente de piel y tejidos blandos, así como bacteriemia y endocarditis. Su clasificación taxonó- mica es compleja y está en constante revisión. Son bacterias nutricionalmente exigentes, y para el desarrollo de colonias visibles requieren agar sangre y agar chocolate, una atmósfera aerobia, generalmente enriquecida en CO2 y una incubación de 48 h. La identificación fenotípica de especie es complicada y no siempre es posible, ya que requiere múltiples sustratos que normalmente no están disponibles en los laboratorios de rutina, ni en los sistemas automatizados. La aplicación de las técnicas moleculares y proteómicas ha permitido una mejor identificación de estas bacterias. El tratamiento de estas infecciones se encuentra con el problema de que los datos de sensibilidad a los agentes antimicrobianos son limitados; no obstante, de los datos disponibles se conoce que amoxicilina-ácido clavulánico, cefalosporinas de segunda y tercera generaciones y fluoroquinolonas son generalmente activas frente a ellas (AU)

Bacteria from the HACEK group (Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, Kingella), Pasteurella and Capnocytophaga are slow-growing gram-negative bacteria that most frequently cause infections in humans. They are part of the microbiota of the upper respiratory and genitourinary tracts of humans and animals, and can cause infections in any location, although mainly skin and soft tissue infections, as well as bacteraemia and endocarditis. Taxonomic classification is complex and under constant review. These are nutritionally demanding bacteria that require blood and chocolate agar, an aerobic atmosphere, generally CO2-enriched, and 48 h incubation for the development of visible colonies. Phenotypic identification at the species level is complicated and not always possible because it requires multiple substrates that are not normally available in routine laboratories or in automated systems. Application of molecular and proteomic techniques has enabled better identification of these bacteria. Treatment of related infections is hindered by a lack of data on susceptibility to antimicrobial agents. However, evidence suggests that amoxicillin-clavulanic acid, second- and third-generation cephalosporins and fluoroquinolones are generally active against these bacteria (AU)

[HPV-associated carcinomas of the female genital tract. Molecular mechanisms of development]. / HPV-assoziiertes Karzinom des weiblichen Genitaltrakts. Molekulare Mechanismen der Entstehung.

Infections with human papillomaviruses (HPV) are a common occurrence in both men and women. In contrast HPV-associated neoplasias are relatively rare and occur only in certain areas of the body. The virus has obviously developed efficient mechanisms for its persistence without inducing too much damage to the host. The formation of neoplasia seems to be more an exception. Epigenetic mechanisms play an important role in the regulation of viral gene expression. Investigations have indicated that exactly the transition from the permissive infection stage to a transformation stage, where neoplastic alterations can occur due to expression of the viral oncogenes, is associated with certain methylation patterns of the viral genome which promote the expression of the oncogenes E6 and E7. The transforming stage is seen as the actual carcinogenic event and can be immunohistochemically detected by the biomarker p16(INK4a).

Imaging of slow viruses.

The symptoms associated with slow viral or prion diseases of the central nervous system tend to have multiple neurologic symptoms, and different patients may present with different symptoms. This review discusses the most common slow virus infections and their imaging findings.

[Multiple sclerosis and Epstein-Barr virus : new developments and perspectives]. / Multiple Sklerose und Epstein-Barr-Virus : Neue Entwicklungen und Perspektiven.

Data from studies of twins and migrants with multiple sclerosis (MS) imply environmental factors in the development of MS. In this respect, increasing evidence indicates that Epstein-Barr virus (EBV) plays a unique role as an infectious risk factor for MS. A nearly 100% seroprevalence of antibodies to EBV in patients with MS, elevated EBV antibody titers years before clinical onset of the disease, and an increased risk for MS after symptomatic primary EBV infection (infectious mononucleosis) suggest an association of MS with a previous infection with EBV. However, the precise mechanisms through which EBV may contribute to MS are still unclear. Currently discussed potential mechanisms are outlined. The notion of a persisting (possibly immunological) change caused during the acute phase of primary EBV infection and subsequently leading to permanently elevated MS risk appears compatible with several aspects of the association found between MS and EBV.

[Disease concept of the slow virus infection].

This article gives a brief history of the terminology of slow virus infection, the conceptual change that occurred in it, the features common to slow infection and the current concept of slow virus infection. Björn Sigurdsson from the field of veterinary medicine proposed slow virus infection as unique mode of infection in 1954. Its initial concept was remodeled along with the general acceptance of prion theory of sheep scrapie that was proposed in 1982. The features common to slow infection include very long latency, unanimous poor prognosis, central nervous system involvement, etc. Currently the slow infection comprises those caused by slow conventional viruses that is the slow virus infection (for example subacute sclerosing panencephalitis and progressive multifocal encephalopathy in human and visna-maedi in sheep) and prion diseases (for example kuru, Creutzfeldt-Jakob disease, Gerstmann-Sträussler-Scheinker syndrome in human, scrapie and bovine spongiform encephalopathy).

[Establishment of the concept of prion diseases].

The history of prion diseases is derived from descriptions of scrapie of sheep and goats in the eighteenth century. In 1920, Creutzfeldt-Jakob disease was reported as the first case of human prion diseases, which was recognized as subacute spongiform encephalopathy, one of neurodegenerative diseases. Afterwards, many transmission experiments were performed, which lead to the establishment of the fundamental concept, transmissible spongiform encephalopathy(TSE). The infectious agent was supposed to be a novel virus, so TSE was classified into slow virus infection. In 1982, Prusiner investigated the infectious fraction of scrapie-infected brain homogenate, defined the infectious agent as proteinaceous infectious particles that resist inactivation by procedures that modify nucleic acid and newly designated as prion after virion in viral infection.

Utility of positive bronchoalveolar lavage in predicting respiratory failure after hematopoietic stem cell transplantation: a retrospective analysis.

Pulmonary complications occur frequently after hematopoietic stem cell transplantation (HSCT) and account for considerable mortality when associated with respiratory failure. Bronchoalveolar lavage (BAL) is commonly used in the diagnostic evaluation of pulmonary infiltrates in HSCT patients. Although the yield of BAL is well established in this setting, the impact on outcome is controversial. In addition, respiratory failure in HSCT patients is associated with high mortality. To determine if positive BAL predicted less respiratory failure and better survival, a retrospective review (between 1992 and 1998) of all HSCT patients who had bronchoscopy with BAL as part of their diagnostic evaluation for new pulmonary infiltrates was performed. Twenty-one patients met the inclusion criteria. Eleven patients (52%) had a positive BAL, defined as the isolation of infectious microorganisms or pulmonary hemorrhage in the lavage specimen. Most of the positive findings were pathogenic organisms (bacterial, fungal, and viral). Respiratory failure (defined as need for both intubation and mechanical ventilation) occurred in 11 of 21 patients (52%)-8 of 11 (73%) who had positive BAL compared with 3 of 10 (30%) who had negative BAL (P = .09). The overall mortality rate was 11 of 21 patients (52%). All deaths except one occurred as a direct result of respiratory failure. Although this study confirmed the high mortality rate in HSCT patients with respiratory failure, the BAL results were not predictive of outcome.

Helminths as vectors of pathogens in vertebrate hosts: a theoretical approach.

Pathogens frequently use vectors to facilitate transmission between hosts and, for vertebrate hosts, the vectors are typically ectoparasitic arthropods. However, other parasites that are intimately associated with their hosts may also be ideal candidate vectors; namely the parasitic helminths. Here, we present empirical evidence that helminth vectoring of pathogens occurs in a range of vertebrate systems by a variety of helminth taxa. Using a novel theoretical framework we explore the dynamics of helminth vectoring and determine which host-helminth-pathogen characteristics may favour the evolution of helminth vectoring. We use two theoretical models: the first is a population dynamic model amalgamated from standard macro- and microparasite models, which serves as a framework for investigation of within-host interactions between co-infecting pathogens and helminths. The second is an evolutionary model, which we use to predict the ecological conditions under which we would expect helminth vectoring to evolve. We show that, like arthropod vectors, helminth vectors increase pathogen fitness. However, unlike arthropod vectors, helminth vectoring increases the pathogenic impact on the host and may allow the evolution of high pathogen virulence. We show that concomitant infection of a host with a helminth and pathogen are not necessarily independent of one another, due to helminth vectoring of microparasites, with profound consequences for pathogen persistence and the impact of disease on the host population.

Prognostic impact of EBV-related LMP-1, histologic type, and environmental factors in nasopharyngeal carcinoma in a German population.

INTRODUCTION: This retrospective study addressed the possible involvement of latent Epstein-Barr virus (EBV) infection, in particular LMP-1 expression, and further exogenous factors, i.e. tobacco, alcohol and occupational hazardous substances, in nasopharyngeal carcinoma (NPC) in a German population. PATIENTS AND METHODS: From 1980 to 2000, 44 patients suffering from histologically confirmed NPC were entered into the study. 33 specimens were available for immunostaining (IHC) to analyze LMP-1 expression. Information about environmental exposures were obtained employing a detailed standardized questionnaire. RESULTS: Outcome of patients with squamous cell NPC (SC-NPC) was significant worse than that of those with non-keratinizing NPC (NK-NPC). Age and tumor size correlated with response to therapy. The group with negative conventional LMP-1 staining showed better overall survival after 5 years compared to the group with positive or marginally positive LMP-1 detection (not significant). Nevertheless, after staining by tyramid-augmented IHC (TSA-IHC), nearly all specimens with negative LMP-1-staining in conventional IHC were found to be clearly positive. All patients with SC-NPC were smokers. The distribution of smokers and non-smokers in the group of NK-NPC was balanced. Comparable to the tobacco observation, there was also a correlation between high alcohol consumption and SC-NPC. CONCLUSION: Prognosis of NPC is mainly dependent on histologic type. Prognostic impact of LMP-1 is still unclear since LMP-1 was detected in all specimens using TSA-IHC. Therefore, TSA-IHC-LMP-1 detection might be interesting for diagnostic specification and development of new therapeutic strategies in NPC.

Enfermedades por virus lentos del sistema nervioso central: ¿un nexo fisiopatogénico común? Vías hacia nuevos enfoques terapéuticos / Slow virus diseases of the central nervous system: a common physiopathogenic nexus? Paths towards new therapeutic approaches

Las enfermedades por virus lentos del sistema nervioso central (SNC) son aquellas en las que el periodo de incubación previo a las manifestaciones clínicas es muy prolongado y se mide en meses e incluso en años. Nos proponemos revisar la concepción actual existente sobre la fisiopatogénesis de estas enfermedades, con el fin de abrir el debate sobre nuevos enfoques terapéuticos, dado el oscuro pronóstico y el escaso éxito de los tratamientos actuales para ellas. El enfoque clásico ante cualquier enfermedad infecciosa es el de actuar frente al patógeno. En este artículo expondremos el importante papel que puede desempeñar el sistema inmune en estas afecciones y, por tanto, la posibilidad de un enfoque terapéutico desde el punto de vista de la inmunomodulación. Nuestra opinión es que los pacientes quizá se beneficien de combinar la estrategia clásica antiviral (inosiplex, ribavirina, IFN-alfa) con el uso de inmunomoduladores del tipo de la pentoxifilina, o de los nuevos que se describen (hormona estimulante de los melanocitos alfa [MSH-alfa], dexanabinol). Mientras, no existan fármacos antivirales específicos de cada uno de estos patógenos, los inmunomoduladores podrían aportar un beneficio clínico como fármacos adyuvantes o paliativos. Esto supondría, no sólo una innovación en el tratamiento de estas enfermedades, sino también un cambio en la concepción del enfoque terapéutico, poniendo al sistema inmune en el mismo plano de importancia que el propio virus (AU)

[Malignant atrophic papulosis (Köhlmeier-Degos disease). Failure to respond to interferon alpha-2a, pentoxifylline and aspirin]. / Maligne atrophische Papulose (Morbus Köhlmeier-Degos) Kein Ansprechen auf Interferon alpha-2a, Pentoxifyllin und Azetylsalizylsäure.

A 45 year old female patient presented with the cutaneous manifestations of malignant atrophic papulosis (Köhlmeier-Degos disease) for two years. The typical papules with central porcelain-white atrophy correspond histologically to wedge-shaped necrosis of the connective tissue due to thrombotic occlusion of small vessels in the corium. The pathogenesis of malignant atrophic papulosis and effective treatment modalities are unknown. A slow virus infection has been suggested by some authors. Therefore, we attempted an immune therapy with interferon alpha-2a over a period of 11 months, but failed to cause a significant effect on the appearance and progression of the skin lesions. Furthermore, we could not confirm the effectiveness of a recently reported treatment modality with pentoxifylline and aspirin administered to our patient over a period of 5 months.

[Prions, infections and confusions in the "transmissible" spongiform encephalopathies. The other evidence-based science. III. Review]. / Priones, infecciones y confusiones en las encefalopatías espongiformes "trasmisibles". Ciencia basada en la otra evidencia III. Revisión.

There are some neurological disorders with a pathological hallmark called spongiosis which include Creutzfeld-Jakob disease and its new variant, the Gertsmann-Straussler-Scheinker Syndrome and the Fatal Familial Insomnia in humans; and Scrapie and Bovine Spongiform Encephalopathy, among others, in animals. The etiological agent has been considered either transmissible or hereditary or both. Curiously, this agent has no nucleic acids, is impossible to filter, is resistant to inactivation by chemical means, has not been cultured and is unobservable at electron microscopy. All of these facts have led to some researches to claim that these agents are similar to viruses appearing in computers. However, after almost fifty years of research, is still not possible to explain why and how such elements produce the diseases commented about. On the contrary, during these years have been possible to know that these entities called slow viral infections, transmissible amyloidosis, transmissible dementia, transmissible spongiform encephalopathies or prion diseases appear in individuals with genetical predispositions exposed to several worldwide immunological stressors. The possibility that prions are the consequence and not the cause of these diseases in animals and man is day by day more reliable, and supports the suggestion that a systematic intoxication due to pesticides as well as mycotoxin ingestion, produced mainly by different molds such as Aspergillus, Penicillium or Fusarium, seem to be the true etiology of these neurodegenerative disorders.

Doxycycline control of prion protein transgene expression modulates prion disease in mice.

Conversion of the cellular prion protein (PrPC) into the pathogenic isoform (PrPSc) is the fundamental event underlying transmission and pathogenesis of prion diseases. To control the expression of PrPC in transgenic (Tg) mice, we used a tetracycline controlled transactivator (tTA) driven by the PrP gene control elements and a tTA-responsive promoter linked to a PrP gene [Gossen, M. and Bujard, H. (1992) Proc. Natl. Acad. Sci. USA 89, 5547-5551]. Adult Tg mice showed no deleterious effects upon repression of PrPC expression (>90%) by oral doxycycline, but the mice developed progressive ataxia at approximately 50 days after inoculation with prions unless maintained on doxycycline. Although Tg mice on doxycycline accumulated low levels of PrPSc, they showed no neurologic dysfunction, indicating that low levels of PrPSc can be tolerated. Use of the tTA system to control PrP expression allowed production of Tg mice with high levels of PrP that otherwise cause many embryonic and neonatal deaths. Measurement of PrPSc clearance in Tg mice should be possible, facilitating the development of pharmacotherapeutics.

[Neurotropic viruses--classification, structure and characteristics].

Classification, structure and characteristics of neurotropic viruses are briefly summarized. Neurotropic viruses causing acute infection include Japanese, Venezuelan equine, and California encephalitis viruses, polio, coxsackie, echo, mumps, measles, influenza, and rabies viruses as well as members of the family Herpesviridae such as herpes simplex, varicella-zoster, cytomegalo and Epstein-Barr viruses. Those causing latent infection include herpes simplex and varicella-zoster viruses. Those causing slow virus infection include measles, rubella and JC viruses, and retroviruses such as human T-lymphotropic virus 1 and human immunodeficiency virus. Prion, which is not a virus but a host-derived non-physiological protein, causes transmissible spongiform encephalopathy such as kuru and Creutzfeldt-Jakob disease that resemble slow virus infection.

[The Epstein-Barr virus in patients with infectious endocarditis]. / Virus Epshteina--Barr u bol'nykh infektsionnym éndokarditom.

Serological markers of Epstein-Barr virus (EBV) infection has been investigated in 28 patients with infectious endocarditis. In 75% of patients IgM antibodies to "early" antigen of the virus which are the marker of active viral infection occurred vs 6.2% among healthy blood donors. Specific for infectious endocarditis reaction profile (anti-EBV combination in one person) indicates reactivation of latent viral infection. The conclusion is made on the necessity of further investigation of both the role of EBV in pathogenesis of pyoseptic diseases and immunologic mechanisms for reactivation of latent viral infections.

[Creutzfeldt-Jakob disease]. / A Creutzfeldt-Jakob-betegségröl.

A most common form of human prion disease, also known as non-conventional slow virus diseases; Creutzfeldt-Jakob's disease is described in detail. The available data on the pathogenesis of the illness have recently changed and constitute a most exciting article of contemporary medicine. 109 cases are introduced that have been verified neuropathologically in Hungary until now; their summed up clinical data, the pathological findings and their epidemiological characteristics are discussed. It must be emphasized that the diagnosis of the illness cannot be inevitably confirmed clinically. Transplantation of organs or tissues of all deceased, who suffered of an illness with dementia, should be strictly avoided accordingly.