Rabies Clinical Presentation

  • Author: Sandra G Gompf, MD, FACP, FIDSA; Chief Editor: Burke A Cunha, MD   more...
 
Updated: Dec 12, 2011
 

History

Identify the following in any suspected case of rabies virus exposure:

  • The nature of the interaction with the animal (Recall that "provocation" is not an indication of rabies risk, since humans may not understand what is provocative to a wild animal.)
  • Strange animal behavior (eg, nocturnal animal out during the daytime)
  • Vaccination status of the animal for rabies[7]
  • Availability of the animal for testing

Incubation period

The infected individual remains asymptomatic during this period. The average duration of incubation is 20-90 days. Rarely, incubation has been reported up to 7-19 years. In more than 90% of cases, incubation is less than 1 year. Patients may not recall exposure because of the prolonged incubation period.

The incubation period is less than 50 days if the patient is bitten on the head or neck or if a heavy inoculum is transferred through multiple bites, deep wounds, or large wounds. A person with a scratch on the hand may take longer to develop symptoms of rabies than a person who receives a bite to the head.

The rabies virus is segregated from the immune system during this period, and no antibody response is observed.

Prodromal period

The virus enters the CNS. The duration of this period is 2-10 days. Nonspecific symptoms and signs develop. Paresthesia, pain, or intense itching at the inoculation site is pathognomonic for rabies and occurs in 50% of cases during this phase; this may be the individual’s only presenting sign. Symptoms may include the following:

  • Malaise
  • Anorexia
  • Headaches
  • Fever
  • Chills
  • Pharyngitis
  • Nausea
  • Emesis
  • Diarrhea
  • Anxiety
  • Agitation
  • Insomnia
  • Depression

Acute neurologic period

This period is associated with objective signs of developing CNS disease. The duration is 2-7 days. Symptoms include muscle fasciculations, priapism, and focal or generalized convulsions. Patients may die immediately or may progress to paralysis, which may be present only in the bitten limb at first but usually becomes diffuse.

The form of rabies known as furious rabies may develop during this period. Patients develop agitation, hyperactivity, restlessness, thrashing, biting, confusion, or hallucinations. After several hours to days, this becomes episodic and interspersed with calm, cooperative, lucid periods. Furious episodes last less than 5 minutes. Episodes may be triggered by visual, auditory, or tactile stimuli or may be spontaneous. Seizures may occur. This phase may end in cardiorespiratory arrest or may progress to paralysis.

Another form of rabies, paralytic rabies, is also known as dumb rabies or apathetic rabies, because the patient is relatively quiet compared with a person with the furious form. Twenty percent of patients do not develop the furious form. Paralysis occurs from the outset, and fever and headache are prominent.

Coma

This begins within 10 days of onset, and the duration varies. Without intensive supportive care, respiratory depression, arrest, and death occur shortly after coma.

Next

Physical Examination

Neurologic period

With furious rabies, patients present with episodic delirium, psychosis, restlessness, thrashing, muscular fasciculations, seizures, and aphasia. Hydrophobia and aerophobia are pathognomonic for rabies and occur in 50% of patients. Attempting to drink or having air blown in the face produces severe laryngeal or diaphragmatic spasms and a sensation of asphyxia. This may be related to a violent response of the airway irritant mechanisms. Even the suggestion of drinking may induce hydrophobic spasm.

Autonomic instability is observed with furious rabies, with symptoms that include the following:

  • Fever
  • Tachycardia
  • Hypertension
  • Hyperventilation
  • Anisocoria, fixed pupillary dilation (“blown pupil”), optic neuritis (may falsely suggest brain death)
  • Facial palsy
  • Mydriasis
  • Lacrimation
  • Excessive salivation
  • Perspiration
  • Postural hypotension

In patients with paralytic rabies, fever and nuchal rigidity may occur. Paralysis is symmetrical and may be either generalized or ascending and may be mistaken for Guillain-Barré syndrome. The sensory system is usually spared. Calm clarity gradually progresses to delirium, stupor, and then coma.

Coma

Respiratory failure occurs within 1 week of neurologic symptoms. Hypoventilation and metabolic acidosis predominate. Acute respiratory distress syndrome is common. Wide variations in blood pressure, cardiac arrhythmias, and hypothermia ensue. Bradycardia and cardiac arrest occur. With intensive support, life may be extended for 3 or 4 months; however, death is usually the outcome.

Death

It is important to determine brain death by brain biopsy or absence of cerebral arterial flow, because some of the neurologic signs may falsely suggest brain death (see above).

Previous
Proceed to Differential Diagnoses
 
 
Contributor Information and Disclosures
Author

Sandra G Gompf, MD, FACP, FIDSA  Associate Professor of Infectious Diseases and International Medicine, University of South Florida College of Medicine; Chief, Infectious Diseases Section, Director, Occupational Health and Infection Control Programs, James A Haley Veterans Hospital

Sandra G Gompf, MD, FACP, FIDSA is a member of the following medical societies: American College of Physicians and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Coauthor(s)

Tri M Pham, MD  Consulting Physician, Division of Infectious Diseases, Watson Clinic, Lakeland

Tri M Pham, MD is a member of the following medical societies: American College of Physicians and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Charurut Somboonwit, MD, FACP  Assistant Professor of Medicine, Division of Infectious Disease and International Medicine, University of South Florida College of Medicine; Director of Communicable Diseases and Clinical Research, Hillsborough County Health Department

Charurut Somboonwit, MD, FACP is a member of the following medical societies: American College of Physicians, American Medical Association, and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Albert L Vincent, PhD  Associate Professor, Division of Infectious Diseases and International Health, Department of Internal Medicine, University of South Florida College of Medicine; Scientific and Research Advisor to the Division of Epidemiology, Hillsborough County Health Department

Disclosure: none None None

Chief Editor

Burke A Cunha, MD  Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital

Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Additional Contributors

Leslie L Barton, MD Professor Emerita of Pediatrics, University of Arizona College of Medicine

Leslie L Barton, MD is a member of the following medical societies: American Academy of Pediatrics, Association of Pediatric Program Directors, Infectious Diseases Society of America, and Pediatric Infectious Diseases Society

Disclosure: Nothing to disclose.

Richard B Brown, MD, FACP Chief, Division of Infectious Diseases, Baystate Medical Center; Professor, Department of Internal Medicine, Tufts University School of Medicine

Richard B Brown, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Chest Physicians, American College of Physicians, American Medical Association, American Society for Microbiology, Infectious Diseases Society of America, and Massachusetts Medical Society

Disclosure: Nothing to disclose.

Wendy Carter, DO, Division of Infectious and Tropical Medicine, University of South Florida College of Medicine

Wendy Carter, DO is a member of the following medical societies: American College of Physicians, American Medical Association, American Osteopathic Association, and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Lucinda Elko, MD, Division of Infectious and Tropical Medicine, University of South Florida College of Medicine

Lucinda Elko, MD is a member of the following medical societies: Alpha Omega Alpha

Disclosure: Nothing to disclose.

Donna J Fisher, MD Assistant Professor of Pediatrics, Tufts University School of Medicine; Interim Chief, Division of Pediatric Infectious Diseases, Baystate Children's Hospital

Donna J Fisher, MD is a member of the following medical societies: American Academy of Pediatrics, American Society for Microbiology, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, and Society for Healthcare Epidemiology of America

Disclosure: Nothing to disclose.

Anibal Jose Maldonado, MD, Fellow, Division of Infectious Diseases and International Medicine, University of South Florida

Anibal Jose Maldonado, MD is a member of the following medical societies: American College of Physicians, American Medical Association, and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Russell W Steele, MD Head, Division of Pediatric Infectious Diseases, Ochsner Children's Health Center; Clinical Professor, Department of Pediatrics, Tulane University School of Medicine

Russell W Steele, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Immunologists, American Pediatric Society, American Society for Microbiology, Infectious Diseases Society of America, Louisiana State Medical Society, Pediatric Infectious Diseases Society, Society for Pediatric Research, and Southern Medical Association

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Additional Contributors

Leslie L Barton, MD Professor Emerita of Pediatrics, University of Arizona College of Medicine

Leslie L Barton, MD is a member of the following medical societies: American Academy of Pediatrics, Association of Pediatric Program Directors, Infectious Diseases Society of America, and Pediatric Infectious Diseases Society

Disclosure: Nothing to disclose.

Richard B Brown, MD, FACP Chief, Division of Infectious Diseases, Baystate Medical Center; Professor, Department of Internal Medicine, Tufts University School of Medicine

Richard B Brown, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Chest Physicians, American College of Physicians, American Medical Association, American Society for Microbiology, Infectious Diseases Society of America, and Massachusetts Medical Society

Disclosure: Nothing to disclose.

Wendy Carter, DO, Division of Infectious and Tropical Medicine, University of South Florida College of Medicine

Wendy Carter, DO is a member of the following medical societies: American College of Physicians, American Medical Association, American Osteopathic Association, and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Lucinda Elko, MD, Division of Infectious and Tropical Medicine, University of South Florida College of Medicine

Lucinda Elko, MD is a member of the following medical societies: Alpha Omega Alpha

Disclosure: Nothing to disclose.

Donna J Fisher, MD Assistant Professor of Pediatrics, Tufts University School of Medicine; Interim Chief, Division of Pediatric Infectious Diseases, Baystate Children's Hospital

Donna J Fisher, MD is a member of the following medical societies: American Academy of Pediatrics, American Society for Microbiology, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, and Society for Healthcare Epidemiology of America

Disclosure: Nothing to disclose.

Anibal Jose Maldonado, MD, Fellow, Division of Infectious Diseases and International Medicine, University of South Florida

Anibal Jose Maldonado, MD is a member of the following medical societies: American College of Physicians, American Medical Association, and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Russell W Steele, MD Head, Division of Pediatric Infectious Diseases, Ochsner Children's Health Center; Clinical Professor, Department of Pediatrics, Tulane University School of Medicine

Russell W Steele, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Immunologists, American Pediatric Society, American Society for Microbiology, Infectious Diseases Society of America, Louisiana State Medical Society, Pediatric Infectious Diseases Society, Society for Pediatric Research, and Southern Medical Association

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

References

  1. Centers for Disease Control and Prevention. Investigation of rabies infections in organ donor and transplant recipients--Alabama, Arkansas, Oklahoma, and Texas, 2004. MMWR Morb Mortal Wkly Rep. Jul 9 2004;53(26):586-9. [Medline].

  2. Srinivasan A, Burton EC, Kuehnert MJ, et al. Transmission of rabies virus from an organ donor to four transplant recipients. N Engl J Med. Mar 17 2005;352(11):1103-11. [Medline].

  3. Blanton JD, Palmer D, Christian KA, Rupprecht CE. Rabies surveillance in the United States during 2007. J Am Vet Med Assoc. Sep 15 2008;233(6):884-97. [Medline].

  4. Messenger SL, Smith JS, Rupprecht CE. Emerging epidemiology of bat-associated cryptic cases of rabies in humans in the United States. Clin Infect Dis. Sep 15 2002;35(6):738-47. [Medline].

  5. Willoughby RE Jr, Hammarin AL. Prophylaxis against rabies in children exposed to bats. Pediatr Infect Dis J. Dec 2005;24(12):1109-10. [Medline].

  6. McLean RG. Rabies in raccoons in the Southeastern United States. J Infect Dis. Jun 1971;123(6):680-1. [Medline].

  7. National Association of State Public Health Veterinarians. Compendium of animal rabies prevention and control, 2004: National Association of State Public Health Veterinarians, Inc. (NASPHV). MMWR Recomm Rep. Jun 25 2004;53:1-8. [Medline].

  8. Moore DA, Sischo WM, Hunter A, Miles T. Animal bite epidemiology and surveillance for rabies postexposure prophylaxis. J Am Vet Med Assoc. Jul 15 2000;217(2):190-4. [Medline].

  9. Doyle TJ, Bryan RT. Infectious disease morbidity in the US region bordering Mexico, 1990-1998. J Infect Dis. Nov 2000;182(5):1503-10. [Medline].

  10. Rupprecht CE, Blass L, Smith K, et al. Human infection due to recombinant vaccinia-rabies glycoprotein virus. N Engl J Med. Aug 23 2001;345(8):582-6. [Medline].

  11. Jackson AC. Screening of organ and tissue donors for rabies. Lancet. Dec 11-17 2004;364(9451):2094-5. [Medline].

  12. WHO. WHO expert consultation on rabies. First Report. WHO technical report series. 2004;931:1-121.

  13. WHO. WHO Guide for Rabies Pre- and Post-exposure Prophylaxis in Humans. World Health Organization. Available at http://www.who.int/rabies/PEP_prophylaxis_guidelines_June10.pdf. Accessed October 18, 2010.

  14. Manning SE, Rupprecht CE, Fishbein D, et al. Human rabies prevention--United States, 2008: recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep. May 23 2008;57:1-28. [Medline].

  15. Willoughby RE Jr, Tieves KS, Hoffman GM, et al. Survival after treatment of rabies with induction of coma. N Engl J Med. Jun 16 2005;352(24):2508-14. [Medline]. [Full Text].

  16. McDermid RC, Saxinger L, Lee B, et al. Human rabies encephalitis following bat exposure: failure of therapeutic coma. CMAJ. Feb 26 2008;178(5):557-61. [Medline]. [Full Text].

  17. Hu WT, Willoughby RE Jr, Dhonau H, Mack KJ. Long-term follow-up after treatment of rabies by induction of coma. N Engl J Med. Aug 30 2007;357(9):945-6. [Medline].

  18. Goldstein EJ. Current concepts on animal bites: bacteriology and therapy. Curr Clin Top Infect Dis. 1999;19:99-111. [Medline].

  19. Baer GM. The Natural History of Rabies. Boston, MA: CRC Press; 1991.

  20. Hantson P, Guérit JM, de Tourtchaninoff M, et al. Rabies encephalitis mimicking the electrophysiological pattern of brain death. A case report. Eur Neurol. 1993;33(3):212-7. [Medline].

  21. Hemachudha T. Human rabies: clinical aspects, pathogenesis, and potential therapy. Curr Top Microbiol Immunol. 1994;187:121-43. [Medline].

  22. Willoughby RE, Roy-Burman A, Martin KW, et al. Generalised cranial artery spasm in human rabies. Dev Biol (Basel). 2008;131:367-75. [Medline].

  23. University of Wisconsin. Care of rabies. Version 3.1. Available at http://www.mcw.edu/FileLibrary/Groups/Pediatrics/InfectiousDiseases/Milwaukee_rabies_protocol_V3_1.pdf. Accessed September 2011.

  24. Wacharapluesadee S, Hemachudha T. Nucleic-acid sequence based amplification in the rapid diagnosis of rabies. Lancet. Sep 15 2001;358(9285):892-3. [Medline].

  25. Wacharapluesadee S, Hemachudha T. Urine samples for rabies RNA detection in the diagnosis of rabies in humans. Clin Infect Dis. Mar 15 2002;34(6):874-5. [Medline].

  26. WHO. Guide for post-exposure prophylaxis. World Health Organization. Available at http://www.who.int/rabies/human/postexp/en/. Accessed October 18, 2010.

  27. World Health Organization. Rabnet Database. Department of Communicable Diseases Surveillance and Response. Animal and Food related Public Health Risks. Geneva, Switzerland: World Health Organization; 2001:[Full Text].

  28. Rupprecht CE, Gibbons RV. Clinical practice. Prophylaxis against rabies. N Engl J Med. Dec 16 2004;351(25):2626-35. [Medline].

  29. Fisher DJ. Resurgence of rabies. A historical perspective on rabies in children. Arch Pediatr Adolesc Med. Mar 1995;149(3):306-12. [Medline].

  30. Committee on Infectious Diseases, American Academy of Pediatrics. 2006 Red Book - Report of the Committee on Infectious Diseases. 27. Elk Grove, IL: American Academy of Pediatrics; 2006:552-9.

  31. Arya SC, Agarwal N. Assessing the safety of post-exposure rabies immunization in pregnancy. Hum Vaccin. Sep-Oct 2007;3(5):155; author reply 155. [Medline].

  32. Abazeed ME, Cinti S. Rabies prophylaxis for pregnant women. Emerg Infect Dis. Dec 2007;13(12):1966-7. [Medline]. [Full Text].

  33. Complete List of Vaccines Licensed for Immunization and Distribution in the U.S. Food and Drug Administration. Available at http://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm093833.htm.

  34. Willoughby RE Jr. "Early death" and the contraindication of vaccine during treatment of rabies. Vaccine. Nov 27 2009;27(51):7173-7. [Medline].

  35. Centers for Disease Control and Prevention. Recovery of a patient from clinical rabies--Wisconsin, 2004. MMWR Morb Mortal Wkly Rep. Dec 24 2004;53(50):1171-3. [Medline]. [Full Text].

  36. Dandoy S, Scanlon F. Teaching kids about rabies. Am J Public Health. Mar 1999;89(3):413-4. [Medline].

  37. Murray KO, Arguin PM. Decision-based evaluation of recommendations for preexposure rabies vaccination. J Am Vet Med Assoc. Jan 15 2000;216(2):188-91. [Medline].

  38. Moran GJ, Talan DA, Mower W, et al. Appropriateness of rabies postexposure prophylaxis treatment for animal exposures. Emergency ID Net Study Group. JAMA. Aug 23-30 2000;284(8):1001-7. [Medline].

  39. Prosniak M, Faber M, Hanlon CA, et al. Development of a cocktail of recombinant-expressed human rabies virus-neutralizing monoclonal antibodies for postexposure prophylaxis of rabies. J Infect Dis. Jul 1 2003;188(1):53-6. [Medline].

  40. Wilson JM, Hettiarachchi J, Wijesuriya LM. Presenting features and diagnosis of rabies. Lancet. Dec 6 1975;2(7945):1139-40. [Medline].

  41. A Human Monoclonal Antibody to Rabies Virus Provides Protective Neutralizing Activity: Results of a Phase 1 Study, 50th Annual Meeting, Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). Boston, MA, 2010.

  42. World Health Organization. Rabies. 2006;Fact Sheet #99:[Full Text].

 
Previous
Next
 
Hematoxylin and eosin stain of Negri body in a rabies-infected neuron. Courtesy of the US Centers for Disease Control and Prevention.
Distribution of the 5 strains of rabies virus and the associated wildlife in the United States.
Table 1. Risk Categories for Active Preexposure Immunization and Rabies Titer Monitoring
CategoryTarget PopulationImmunization RegimenSerologic Testing
ContinuousRabies research laboratory or biologics production workersPrimary course; booster when serum antibody is less than 1:5 dilution based on RFFIT resultsEvery 6 months
FrequentRabies diagnostic laboratory workers, spelunkers, veterinarians and staff, animal control and wildlife workers in rabies-enzootic areas, travelers to areas of enzootic rabies for more than 30 days Primary course; booster every 2 years or when serum antibody is less than 1:5 dilution based on RFFIT resultsEvery 2 years if not regularly boosted
InfrequentVeterinarians and staff/students, animal control and wildlife workers in areas of low rabies riskPrimary course; no boosterNone
RareUS population at largeNoneNone
Previous
Next
 
 
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.