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)

[The infectiousness of 18- to 20-kd proteins isolated from the brain of people who have died from amyotrophic leukospongiosis]. / Infektsionnost' belkov 18--20 kd, vydelennykh iz mozga liudei, umershikh ot amiotroficheskogo leikospongioza.

Specific globular structures, 10-12 nm in diameter, having a high resistance to various physicochemical factors and infectivity have been isolated for the first time from the brain of 2 patients, who died of amyotrophic leukospongiosis (AL). It has been shown that these globules contain infectious major protease-resistant protein with a molecular weight of about 18-20 kD. The findings indicate the unique nature of a disease and they open new aspects of AL etiopathogenesis.

Spongiform encephalopathy in a captive puma (Felis concolor).

A captive adult puma developed ataxia, a hypermetric gait and whole body tremor. The signs progressed over a period of six weeks. Histopathological examination following euthanasia demonstrated spongiform encephalopathy, gliosis and mild non-suppurative meningoencephalitis. Immunostaining with a polyclonal antiserum revealed prion protein (PrP) associated with these changes in sections of cervical spinal cord and medulla. This is the first confirmed case of a scrapie-like spongiform encephalopathy described in a non-domestic cat in the United Kingdom.

Molecular studies of viral pathogenesis in the central nervous system. The Linacre Lecture 1991.

What is the molecular biological basis of viral pathogenesis in the central nervous system (CNS), ie by what molecular mechanisms do different viruses produce particular patterns of neurological disease in man and animal models, and can one use molecular techniques to ascertain the viral aetiology of certain neurological conditions? This complex subject can be approached in three different but interrelated ways. First, one may relate molecular techniques to specific biological properties such as viral spread to the CNS, to neurotropism, ie the affinity of the virus for particular neural regions and cells, and to neurovirulence, which refers to the actual ability to cause neurological disease. Second, the reverse approach can be adopted by considering these different aspects of virus-host relationships and then how the techniques have contributed to their understanding. Third, one can select specific neurotropic viruses, such as polio or herpes viruses, and then relate these to both particular techniques and pathogenetic mechanisms [1]. The second component of this paper will deal with the immunopathological mechanisms seen in three specific CNS viral infections, all of which have been the focus of study in the author's laboratory over the past six years.

[Latent cervical virus infection as a possible cause of early abortion]. / Latente zervikale Virusinfektion als mögliche Ursache des Frühaborts.

Cervical smears of 50 women who had an abortion were examined by dot-blot hybridization for human papillomavirus (HPV), herpes simplex virus (HSV) types 1 and 2, and cytomegalovirus (CMV) DNA. HPV DNA type 16 or 18 positivity was shown in 17.6% of the cases; in the aborted material, however, it amounted to 30.8%. IgM-positive titres were present in a few cases. In cervical smears of intact pregnancies, positivity for HPV DNA types 6 and 11 was detected in 9.5% and for the HSV DNA types 1 and 2 and CMV DNA in 48.0% of the cases. In this group of patients mostly positive IgM and IgG titers were present.

From slow virus to prion: a review of transmissible spongiform encephalopathies.

Spongiform encephalopathies include seven neurodegenerative diseases: three in man (Creutzfeldt-Jakob disease, Gerstmann-Sträussler-Scheinker disease and kuru) and four in animals (scrapie, mink encephalopathy, bovine spongiform encephalopathy and chronic wasting disease in deer and elks). They are all transmissible to a variety of species, and man-to-man propagation of the diseases in the form of iatrogenic transmission has been well-documented. The infectious agent is highly unusual and the pathogenesis of infection remains controversial. The term prion was introduced to describe the proteinaceous infectious agent. Purification of this agent yielded a unique sialoglycoprotein, associated with the neuronal cell membrane, which is all or part of the infectious agent. Molecular genetics revealed variations in the prion protein; these are linked to or associated with the inherited forms of spongiform encephalopathies: familial Creutzfeldt-Jakob disease and Gerstmann-Sträussler-Scheinker disease. The histological triad of spongiform change, neuronal loss and astrocytosis dominate the histological picture of spongiform encephalopathies. A recent case which did not develop any of the histological hallmarks of disease, but did have genetic abnormalities typical of the disease, indicates that the true incidence of Creutzfeldt-Jakob disease may be considerably higher than previously accepted, and a combination of molecular screening and immunohistochemistry for prion protein should complement traditional neuropathology to establish the diagnosis. The descriptive term of spongiform encephalopathy may now have to be abandoned in favour of prion disease.

[Mechanism of accumulation of prion amyloid in the CNS in experimental amyotrophic leukospongiosis]. / K mekhanizmu nakopleniia prionovogo amiloida v TsNS pri éksperimental'nom amiotroficheskom leikospongioze.

The mechanism of accumulation of prion amyloid in guinea pig CNS in experimental slow virus disease--amyotrophic leuco-spongiosis (AL) was studied. The complex histochemical, immuno-cytochemical and ultrastructural studies revealed specific amyloid deposits in a few brain capillaries and in most of pia matter vessels. Taking into account the high AL agent titer in spleen throughout the disease period, conclusion was drawn of entering AL agent in CNS through blood-liquor barrier and blood-brain barrier. It was supposed that primary immune system damaging took place in AL pathogenesis.

Epidemiological and experimental studies on a new incident of transmissible mink encephalopathy.

Epidemiological investigation of a new incident of transmissible mink encephalopathy (TME) in Stetsonville, Wisconsin, U.S.A. in 1985 revealed that the mink rancher had never fed sheep products to his mink but did feed them large amounts of products from fallen or sick dairy cattle. To investigate the possibility that this occurrence of TME may have resulted from exposure to infected cattle, two Holstein bull calves were injected intracerebrally with mink brain from the Stetsonville ranch. Each bull developed a fatal spongiform encephalopathy 18 and 19 months after inoculation, respectively, and both bovine brains passaged back into mink were highly pathogenic by either intracerebral or oral inoculation. These results suggest the presence of a previously unrecognized scrapie-like infection in cattle in the United States.

Molecular biology and transgenetics of prion diseases.

Considerable progress has been made deciphering the role of an abnormal isoform of the prion protein (PrP) in scrapie of animals and Gerstmann-Sträussler syndrome (GSS) of humans. Some transgenic (Tg) mouse (Mo) lines that carry and express a Syrian hamster (Ha) PrP gene developed scrapie 75 d after inoculation with Ha prions; non-Tg mice failed to show symptoms after greater than 500 d. Brains of these infected Tg(HaPrP) mice featured protease-resistant HaPrPSc, amyloid plaques characteristic for Ha scrapie, and 10(9) ID50 units of Ha-specific prions upon bioassay. Studies on Syrian, Armenian, and Chinese hamsters suggest that the domain of the PrP molecule between codons 100 and 120 controls both the length of the incubation time and the deposition of PrP in amyloid plaques. Ataxic GSS in families shows genetic linkage to a mutation in the PrP gene, leading to the substitution of Leu for Pro at codon 102. Discovery of a point mutation in the Prp gene from humans with GSS established that GSS is unique among human diseases--it is both genetic and infectious. These results have revised thinking about sporadic Creutzfeldt-Jakob disease, suggesting it may arise from a somatic mutation. These findings combined with those from many other studies assert that PrPSc is a component of the transmissible particle, and the PrP amino acid sequence controls the neuropathology and species specificity of prion infectivity. The precise mechanism of PrPSc formation remains to be established. Attempts to demonstrate a scrapie-specific nucleic acid within highly purified preparations of prions have been unrewarding to date. Whether transmissible prions are composed only of PrPSc molecules or do they also contain a second component such as small polynucleotide remains uncertain.