LCMV Transmission by Organ Transplantation
http://www.100md.com
《新英格兰医药杂志》
To the Editor: In the report by Fischer et al.1 and the accompanying Perspective article by Peters2 (May 25 issue) on two outbreaks of lymphocytic choriomeningitis virus (LCMV) infection in organ-transplant recipients, the authors focus long overdue attention on a neglected teratogenic zoonosis. My colleagues and I have collected clinical, laboratory, and epidemiologic information on 60 neonates with LCMV infection and their 58 mothers from many geographic locales in the United States and Europe.3,4,5 Symptomatic maternal infection was documented in two thirds of the patients, and exposure to wild or pet rodents was recorded in approximately half the mothers. More than 90% of surviving infants have had chorioretinitis and hydrocephalus, with consequent neurodevelopmental retardation, seizures, and blindness. We would suggest that physicians caution their patients to defer the acquisition of rodents when contemplating pregnancy and to relegate the care of such existing pets to other household members. A significant fraction of cases of neonatal mental retardation and blindness remain unexplained. Congenital LCMV infection represents an understudied potential cause of a portion of these cases.
Leslie L. Barton, M.D.
University of Arizona School of Medicine
Tucson, AZ 85724
llb@peds.arizona.edu
References
Fischer SA, Graham MB, Kuehnert MJ, et al. Transmission of lymphocytic choriomeningitis virus by organ transplantation. N Engl J Med 2006;354:2235-2249.
Peters CJ. Lymphocytic choriomeningitis virus -- an old enemy up to new tricks. N Engl J Med 2006;354:2208-2211.
Barton LL, Mets MB. Congenital lymphocytic choriomeningitis virus infection: decade of rediscovery. Clin Infect Dis 2001;33:370-374.
Barton LL, Mets MB, Beauchamp CL. Lymphocytic choriomeningitis virus: emerging fetal teratogen. Am J Obstet Gynecol 2002;187:1715-1716.
Greenhow TL, Weintrub PS. Your diagnosis please: neonate with hydrocephalus. Pediatr Infect Dis J 2003;22:1099, 1111-2.
To the Editor: The mortality associated with LCMV infection among patients with immunosuppression is very high. Fischer et al. report that seven of eight transplant recipients with LCMV infection died 9 to 76 days after transplantation. Peters describes the experimental induction of LCMV infection in two subjects — a healthy volunteer and a patient with Hodgkin's disease — through inoculation. The patient with Hodgkin's disease later died, possibly from bacterial pneumonia and LCMV infection. Such an outcome is not surprising, since Hodgkin's disease is characterized by functional deficits in cellular immunity and T-cell–mediated immune responses. How would an ethics committee explain its decision to allow the induction of LCMV infection in a patient with Hodgkin's disease, an experiment with a predictably high risk of death that is not supported by the literature?
Christian Sauter, M.D.
University of Zurich
CH-8057 Zurich, Switzerland
cesauter@bluewin.ch
Bernhard V. Sauter, M.D.
Hirslanden Clinic
CH-8032 Zurich, Switzerland
Dr. Peters replies: I agree with Sauter and Sauter that the intentional inoculation with LCMV of immunosuppressed patients who have lymphoma would not be justified today. Indeed, I would not initiate the other experiment — intentional infection of an immunocompetent host — that was illustrated in my article. However, they miss two critical points. First, a limitation on the number of references prevented me from citing the original articles — published in 19421 (citing an earlier thesis2) and 19713 — in which these experiments were reported. Instead, I cited a chapter of a book that was published in 19954; the chapter leads to the original literature, covers copyright issues, and reviews other biologic aspects of LCMV for the interested reader. Second, the risks to the recipients of the LCMV inoculation were not clearly understood in 1971. T cells had been identified, but their role in arenavirus infection was not well understood. Lassa virus was unknown, and the arenaviral hemorrhagic fever syndrome was not well described in the English-language literature. Also, there were experiments in mice indicating that LCMV infection could lead to the regression of lymphoid tumors, thus providing an experimental basis for undertaking this experiment in humans.3
C.J. Peters, M.D.
University of Texas Medical Branch
Galveston, TX 77551
References
Farmer TW, Janeway CA. Infections with the virus of lymphocytic choriomeningitis. Medicine (Baltimore) 1942;21:1-64.
Kreis B. La maladie d'Armstrong, choromeningite lymphocytaire: une nouvelle entite morbide? Paris: J.B. Bailliere, 1937.
Horton J, Hotchin JE, Olson KB, Davies JN. The effects of MP virus infection in lymphoma. Cancer Res 1971;31:1066-1068.
Peters CJ. Arenavirus diseases. In: Porterfield JS, ed. Kass handbook of infectious diseases: exotic viral infections. London: Chapman & Hall Medical, 1995:227-46.
Leslie L. Barton, M.D.
University of Arizona School of Medicine
Tucson, AZ 85724
llb@peds.arizona.edu
References
Fischer SA, Graham MB, Kuehnert MJ, et al. Transmission of lymphocytic choriomeningitis virus by organ transplantation. N Engl J Med 2006;354:2235-2249.
Peters CJ. Lymphocytic choriomeningitis virus -- an old enemy up to new tricks. N Engl J Med 2006;354:2208-2211.
Barton LL, Mets MB. Congenital lymphocytic choriomeningitis virus infection: decade of rediscovery. Clin Infect Dis 2001;33:370-374.
Barton LL, Mets MB, Beauchamp CL. Lymphocytic choriomeningitis virus: emerging fetal teratogen. Am J Obstet Gynecol 2002;187:1715-1716.
Greenhow TL, Weintrub PS. Your diagnosis please: neonate with hydrocephalus. Pediatr Infect Dis J 2003;22:1099, 1111-2.
To the Editor: The mortality associated with LCMV infection among patients with immunosuppression is very high. Fischer et al. report that seven of eight transplant recipients with LCMV infection died 9 to 76 days after transplantation. Peters describes the experimental induction of LCMV infection in two subjects — a healthy volunteer and a patient with Hodgkin's disease — through inoculation. The patient with Hodgkin's disease later died, possibly from bacterial pneumonia and LCMV infection. Such an outcome is not surprising, since Hodgkin's disease is characterized by functional deficits in cellular immunity and T-cell–mediated immune responses. How would an ethics committee explain its decision to allow the induction of LCMV infection in a patient with Hodgkin's disease, an experiment with a predictably high risk of death that is not supported by the literature?
Christian Sauter, M.D.
University of Zurich
CH-8057 Zurich, Switzerland
cesauter@bluewin.ch
Bernhard V. Sauter, M.D.
Hirslanden Clinic
CH-8032 Zurich, Switzerland
Dr. Peters replies: I agree with Sauter and Sauter that the intentional inoculation with LCMV of immunosuppressed patients who have lymphoma would not be justified today. Indeed, I would not initiate the other experiment — intentional infection of an immunocompetent host — that was illustrated in my article. However, they miss two critical points. First, a limitation on the number of references prevented me from citing the original articles — published in 19421 (citing an earlier thesis2) and 19713 — in which these experiments were reported. Instead, I cited a chapter of a book that was published in 19954; the chapter leads to the original literature, covers copyright issues, and reviews other biologic aspects of LCMV for the interested reader. Second, the risks to the recipients of the LCMV inoculation were not clearly understood in 1971. T cells had been identified, but their role in arenavirus infection was not well understood. Lassa virus was unknown, and the arenaviral hemorrhagic fever syndrome was not well described in the English-language literature. Also, there were experiments in mice indicating that LCMV infection could lead to the regression of lymphoid tumors, thus providing an experimental basis for undertaking this experiment in humans.3
C.J. Peters, M.D.
University of Texas Medical Branch
Galveston, TX 77551
References
Farmer TW, Janeway CA. Infections with the virus of lymphocytic choriomeningitis. Medicine (Baltimore) 1942;21:1-64.
Kreis B. La maladie d'Armstrong, choromeningite lymphocytaire: une nouvelle entite morbide? Paris: J.B. Bailliere, 1937.
Horton J, Hotchin JE, Olson KB, Davies JN. The effects of MP virus infection in lymphoma. Cancer Res 1971;31:1066-1068.
Peters CJ. Arenavirus diseases. In: Porterfield JS, ed. Kass handbook of infectious diseases: exotic viral infections. London: Chapman & Hall Medical, 1995:227-46.