Failure of the Milwaukee Protocol in a Child With Rabies

Division of Critical Care Medicine, Children's Hospital & Research Center Oakland, California 94609, USA.
Clinical Infectious Diseases (Impact Factor: 8.89). 09/2011; 53(6):572-4. DOI: 10.1093/cid/cir483
Source: PubMed


Rabies has the highest case-fatality rate of all infectious diseases, with 50,000 cases occurring annually worldwide. In 2004 an unvaccinated adolescent survived after novel therapy. We report the management of a child with rabies. Although the implementation of this same therapeutic protocol was successful, the child died after 1 month of hospitalization.

25 Reads
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Preventive therapy for rabies, including wound cleansing and active and passive immunization after a recognized exposure, is highly efficacious. Unfortunately, there is no established therapy that is effective for patients who develop rabies encephalomyelitis. There have been several survivors from rabies and all but one received rabies vaccine prior to the onset of clinical illness. Aggressive approaches to therapy of human rabies may be appropriate in certain situations. There is no scientific rationale for the use of therapeutic coma, and there are many reports of failures using this approach. Therapeutic coma should be abandoned for the therapy of rabies. New approaches such as therapeutic hypothermia should be evaluated, in combination with other therapeutic agents. More basic research is needed on the mechanisms involved in rabies pathogenesis, which will hopefully facilitate the development of new therapeutic approaches in the future for this ancient disease.
    Advances in Virus Research 01/2011; 79:365-75. DOI:10.1016/B978-0-12-387040-7.00017-2 · 4.57 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Rabies has the highest case fatality of any infectious disease. Pathobiological and clinical insights have questioned the assertion that death is inevitable after onset of acute encephalomyelitis. Relying upon national laboratory-based surveillance, we reviewed records of human rabies acquired in the United States during 1960-2009. Changes in the epidemiology of human rabies were notable, due to improved animal management, safer and more efficacious biologics, and revisions in prevention guidelines. Historically, domestic animals were the most important source of infection. Since the 1990s, more human cases were associated with rabid bats. Prior to 1980, postexposure prophylaxis failures were reported. After development of modern rabies immune globulin and vaccines, none occurred. Of 75 human cases identified, only four patients survived. Rabies remains an extremely high consequence zoonosis, but the disease is not uniformly fatal, per se. Rabies is essentially preventable when primary exposures are averted, or appropriate prophylaxis occurs before illness.
    Current Infectious Disease Reports 06/2012; 14(4):408-22. DOI:10.1007/s11908-012-0268-2 · 1.68 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Minocyline is a tetracycline derivative with anti-inflammatory, anti-apoptotic, and anti-oxidant properties. Therapy has proved useful in some experimental models of both noninfectious and infectious neurological diseases and also in clinical trials in humans, including acute traumatic cervical spinal cord injury. In models of viral encephalitis, treatment has shown both beneficial and deleterious effects. In reovirus infection in mice, minocycline delayed the disease, but did not improve either the morbidity or mortality of the disease. In neuroadapted Sindbis virus infection of mice, minocycline prevented disease, but therapy needed to be given before clinical signs were present in most of the animals. In experimental rabies in neonatal mice minocycline aggravated the disease, likely related to anti-inflammatory effects. Minocycline has also been shown to aggravate disease in a mouse model of Huntington disease, in a monkey model of Parkinson disease, and in a mouse model of hypoxic-ischemic brain injury. Hence, there is experimental evidence of benefit of minocycline in both infectious and noninfectious neurological diseases, but there is a lack of benefit and harmful effects in other diseases. This may reflect multiple mechanisms of actions that cannot be predicted in a new disease or in an infection caused by a specific viral agent. Minocycline therapy is a double-edged sword and this drug should not be given empirically to patients with acute viral encephalitis for anticipated neuroprotective effects. Much more work needs to be done in experimental models in animals as well as in clinical trials. Because patient enrollment in clinical trials on acute viral encephalitis has proven to be difficult, funding will be a challenge.
    Antiviral research 06/2012; 95(3):242-4. DOI:10.1016/j.antiviral.2012.06.005 · 3.94 Impact Factor
Show more

Similar Publications


25 Reads