Exposicion ocupacional al virus de hepatitis c / Occupational exposure to hepatitis C virus

La transmisión ocupacional de virus de hepatitis C (VHC) es un área de creciente preocupacióndada la falta de profilaxis y la poca información de su prevalencia en el medio hospitalario. Sobre128 exposiciones ocupacionales ocurridas en el Hospital Diego Paroissien entre1999 y 2003 hubieron 8 casosde exposición a VHC (6.3%) y un caso de seroconversión posterior a la exposición (0.8%). No existiendo en laactualidad terapia preventiva para VHC resulta de gran interés la posibilidad de tratamiento de la infección aguda.La mayor parte de los autores coincide en recomendar el tratamiento del episodio agudo de hepatitis porVHC basado en la evidencia actual, aunque aún no está bien definida la mejor estrategia diagnóstica y terapéutica.El acatamiento de las Normas de Precauciones Universales sigue siendo en la actualidad la más importantemedida preventiva para evitar la infección ocupacional por VHC en el personal de salud y la de mejor equilibriocosto-beneficio. (AU)

Occupational exposure to Hepatitis C virus is an areaof growing concern due to a lack of prophylaxis and limited knowledge regarding prevalence in hospitalenvironment. Between 1999 and 2003, a total of 128 occupational exposures to this virus were registeredin Diego Paroissien Hospital, eight of which led to hepatitis (6.3%) and one case to serum conversion (0.8%).Currently there is no preventive therapy and great interest is focused on acute infection therapy the effectivenessof which is still controversial. This study reinforces the fact that adherence to the Universal Precautions is stillthe most important preventive measure for health care workers, and the most cost beneficial. (AU)

Exposicion ocupacional al virus de hepatitis c / Occupational exposure to hepatitis C virus

La transmisión ocupacional de virus de hepatitis C (VHC) es un área de creciente preocupacióndada la falta de profilaxis y la poca información de su prevalencia en el medio hospitalario. Sobre128 exposiciones ocupacionales ocurridas en el Hospital Diego Paroissien entre1999 y 2003 hubieron 8 casosde exposición a VHC (6.3%) y un caso de seroconversión posterior a la exposición (0.8%). No existiendo en laactualidad terapia preventiva para VHC resulta de gran interés la posibilidad de tratamiento de la infección aguda.La mayor parte de los autores coincide en recomendar el tratamiento del episodio agudo de hepatitis porVHC basado en la evidencia actual, aunque aún no está bien definida la mejor estrategia diagnóstica y terapéutica.El acatamiento de las Normas de Precauciones Universales sigue siendo en la actualidad la más importantemedida preventiva para evitar la infección ocupacional por VHC en el personal de salud y la de mejor equilibriocosto-beneficio. (AU)

Occupational exposure to Hepatitis C virus is an areaof growing concern due to a lack of prophylaxis and limited knowledge regarding prevalence in hospitalenvironment. Between 1999 and 2003, a total of 128 occupational exposures to this virus were registeredin Diego Paroissien Hospital, eight of which led to hepatitis (6.3%) and one case to serum conversion (0.8%).Currently there is no preventive therapy and great interest is focused on acute infection therapy the effectivenessof which is still controversial. This study reinforces the fact that adherence to the Universal Precautions is stillthe most important preventive measure for health care workers, and the most cost beneficial. (AU)

ErbB2 receptor tyrosine kinase signaling mediates early demyelination induced by leprosy bacilli

Demyelination is a common pathologic feature in many neurodegenerative diseases including infection with leprosy-causing Mycobacterium leprae. Because of the long incubation time and highly complex disease pathogenesis, the management of nerve damage in leprosy, as in other demyelinating diseases, is extremely difficult. Therefore, an important challenge in therapeutic interventions is to identify the molecular events that occur in the early phase before the progression of the disease. Here we provide evidence that M. leprae-induced demyelination is a result of direct bacterial ligation to and activation of ErbB2 receptor tyrosine kinase (RTK) signaling without ErbB2-ErbB3 heterodimerization, a previously unknown mechanism that bypasses the neuregulin-ErbB3-mediated ErbB2 phosphorylation. MEK-dependent Erk1 and Erk2 (hereafter referred to as Erk1/2) signaling is identified as a downstream target of M. leprae-induced ErbB2 activation that mediates demyelination. Herceptin (trastuzumab), a therapeutic humanized ErbB2-specific antibody, inhibits M. leprae binding to and activation of ErbB2 and Erk1/2 in human primary Schwann cells, and the blockade of ErbB2 activity by the small molecule dual ErbB1-ErbB2 kinase inhibitor PKI-166 (ref. 11) effectively abrogates M. leprae-induced myelin damage in in vitro and in vivo models. These results may have implications for the design of ErbB2 RTK-based therapies for both leprosy nerve damage and other demyelinating neurodegenerative diseases.

The continuing challenges of leprosy

Leprosy is best understood as two conjoined diseases. The first is a chronic mycobacterial infection that elicits an extraordinary range of cellular immune responses in humans. The second is a peripheral neuropathy that is initiated by the infection and the accompanying immunological events. The infection is curable but not preventable, and leprosy remains a major global health problem, especially in the developing world, publicity to the contrary notwithstanding. Mycobacterium leprae remains noncultivable, and for over a century leprosy has presented major challenges in the fields of microbiology, pathology, immunology, and genetics; it continues to do so today. This review focuses on recent advances in our understanding of M. leprae and the host response to it, especially concerning molecular identification of M. leprae, knowledge of its genome, transcriptome, and proteome, its mechanisms of microbial resistance, and recognition of strains by variable-number tandem repeat analysis. Advances in experimental models include studies in gene knockout mice and the development of molecular techniques to explore the armadillo model. In clinical studies, notable progress has been made concerning the immunology and immunopathology of leprosy, the genetics of human resistance, mechanisms of nerve injury, and chemotherapy. In nearly all of these areas, however, leprosy remains poorly understood compared to other major bacterial diseases.