Survival after Treatment of Rabies
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《新英格兰医药杂志》
To the Editor: Willoughby et al. (June 16 issue)1 reported success in treating a patient with rabies related to a bite from a bat. The approach taken by these clinicians was devised on the basis of evidence that functional derangements and apoptosis are the primary causes of death from rabies and that treatment with immune globulin and vaccine might be counterproductive.2,3 This case is unique in that the rabies virus was not detected in several procedures, there were normal results from magnetic resonance imaging (MRI) of the brain, and the presence of rabies-neutralizing antibodies in the serum and cerebrospinal fluid was not detected until the sixth day after the onset of symptoms. In other studies, rabies-virus RNA could be demonstrated in 21 of 23 patients on the first day of hospitalization.4 In another study, MRI revealed abnormalities in a patient with rabies who had local pain but as yet no brain symptoms.5 In only one third of bat-related cases of rabies were antibodies present in the cerebrospinal fluid after the ninth day.6 We suggest that this therapy should be reserved for only those patients who have confirmed cases of rabies, who remain conscious, and who already have rabies-neutralizing antibodies in serum and cerebrospinal fluid. In the case reported by Willoughby and colleagues, the native immune response must have superseded the neuronal death induced by rabies infection.
Thiravat Hemachudha, M.D.
Chulalongkorn University Hospital
Bangkok 10330, Thailand
th-cu@usa.net
Henry Wilde, M.D.
Queen Saovabha Memorial Institute
Bangkok 10330, Thailand
References
Willoughby RE Jr, Tieves KS, Hoffman GM, et al. Survival after treatment of rabies with induction of coma. N Engl J Med 2005;352:2508-2514.
Hemachudha T. Human rabies: clinical aspects, pathogenesis, and potential therapy. Curr Top Microbiol Immunol 1994;187:121-143.
Hemachudha T, Sunsaneewitayakul B, Mitrabhakdi E, et al. Paralytic complications following intravenous rabies immune globulin treatment in a patient with furious rabies. Int J Infect Dis 2003;7:76-77.
Hemachudha T, Wacharapluesadee S. Antemortem diagnosis of human rabies. Clin Infect Dis 2004;39:1085-1086.
Laothamatas J, Hemachudha T, Mitrabhakdi E, Wannakrairot P, Tulayadaechanont S. MR imaging in human rabies. AJNR Am J Neuroradiol 2003;24:1102-1109.
Hemachudha T, Laothamatas J, Rupprecht CE. Human rabies: a disease of complex neuropathogenetic mechanisms and diagnostic challenges. Lancet Neurol 2002;1:101-109.
The authors reply: We agree that there are features that are unique to all six known survivors of rabies — all cases were confirmed serologically without detection of the rabies virus. In our patient, abnormalities detectable on MRI later developed that were consistent with "nonenhancing, ill-defined, mild hyperintensity changes" and the observation that brain destruction and inflammation were minimal.1 We never entertained the hypothesis that apoptosis was a primary cause of death, and that hypothesis is not strongly supported by laboratory experiments.2
We are perplexed by the recommendation that therapy be reserved for selected patients. Some patients with rabies are so profoundly injured as a result of complications or aggressive modulation of the immune system that further medical care is futile.3 Given little direct viral cytolytic effect or inflammation and poor evidence for apoptosis, it is not clear why restricting treatment to the earliest of cases makes biologic sense. Whereas we are uncertain whether our results can be replicated, the alternative is palliation. Our therapy also provides sedation and anesthesia. As Jackson notes in his editorial on our report, we need to elucidate which component of our protocol worked.4 We have established a registry (www.mcw.edu/rabies) to record outcomes of rabies cases treated similarly and to address his question as well as to discover which patients might benefit.
Rodney E. Willoughby, Jr., M.D.
Medical College of Wisconsin
Milwaukee, WI 53226
rewillou@mail.mcw.edu
Charles E. Rupprecht, V.M.D., Ph.D.
Centers for Disease Control and Prevention
Atlanta, GA 30333
References
Laothamatas J, Hemachudha T, Mitrabhakdi E, Wannakrairot P, Tulayadaechanont S. MR imaging in human rabies. AJNR Am J Neuroradiol 2003;24:1102-1109.
Jackson AC. Rabies virus infection: an update. J Neurovirol 2003;9:253-258.
Dolman CL, Charlton KM. Massive necrosis of the brain in rabies. Can J Neurol Sci 1987;14:162-165.
Jackson AC. Recovery from rabies. N Engl J Med 2005;352:2549-2550.
Thiravat Hemachudha, M.D.
Chulalongkorn University Hospital
Bangkok 10330, Thailand
th-cu@usa.net
Henry Wilde, M.D.
Queen Saovabha Memorial Institute
Bangkok 10330, Thailand
References
Willoughby RE Jr, Tieves KS, Hoffman GM, et al. Survival after treatment of rabies with induction of coma. N Engl J Med 2005;352:2508-2514.
Hemachudha T. Human rabies: clinical aspects, pathogenesis, and potential therapy. Curr Top Microbiol Immunol 1994;187:121-143.
Hemachudha T, Sunsaneewitayakul B, Mitrabhakdi E, et al. Paralytic complications following intravenous rabies immune globulin treatment in a patient with furious rabies. Int J Infect Dis 2003;7:76-77.
Hemachudha T, Wacharapluesadee S. Antemortem diagnosis of human rabies. Clin Infect Dis 2004;39:1085-1086.
Laothamatas J, Hemachudha T, Mitrabhakdi E, Wannakrairot P, Tulayadaechanont S. MR imaging in human rabies. AJNR Am J Neuroradiol 2003;24:1102-1109.
Hemachudha T, Laothamatas J, Rupprecht CE. Human rabies: a disease of complex neuropathogenetic mechanisms and diagnostic challenges. Lancet Neurol 2002;1:101-109.
The authors reply: We agree that there are features that are unique to all six known survivors of rabies — all cases were confirmed serologically without detection of the rabies virus. In our patient, abnormalities detectable on MRI later developed that were consistent with "nonenhancing, ill-defined, mild hyperintensity changes" and the observation that brain destruction and inflammation were minimal.1 We never entertained the hypothesis that apoptosis was a primary cause of death, and that hypothesis is not strongly supported by laboratory experiments.2
We are perplexed by the recommendation that therapy be reserved for selected patients. Some patients with rabies are so profoundly injured as a result of complications or aggressive modulation of the immune system that further medical care is futile.3 Given little direct viral cytolytic effect or inflammation and poor evidence for apoptosis, it is not clear why restricting treatment to the earliest of cases makes biologic sense. Whereas we are uncertain whether our results can be replicated, the alternative is palliation. Our therapy also provides sedation and anesthesia. As Jackson notes in his editorial on our report, we need to elucidate which component of our protocol worked.4 We have established a registry (www.mcw.edu/rabies) to record outcomes of rabies cases treated similarly and to address his question as well as to discover which patients might benefit.
Rodney E. Willoughby, Jr., M.D.
Medical College of Wisconsin
Milwaukee, WI 53226
rewillou@mail.mcw.edu
Charles E. Rupprecht, V.M.D., Ph.D.
Centers for Disease Control and Prevention
Atlanta, GA 30333
References
Laothamatas J, Hemachudha T, Mitrabhakdi E, Wannakrairot P, Tulayadaechanont S. MR imaging in human rabies. AJNR Am J Neuroradiol 2003;24:1102-1109.
Jackson AC. Rabies virus infection: an update. J Neurovirol 2003;9:253-258.
Dolman CL, Charlton KM. Massive necrosis of the brain in rabies. Can J Neurol Sci 1987;14:162-165.
Jackson AC. Recovery from rabies. N Engl J Med 2005;352:2549-2550.