EM@3AM: Rabies

Author: Rachel Bridwell, MD (EM Attending Physician; Tacoma, WA) // Reviewed by: Sophia Görgens, MD (EM Resident Physician, Zucker-Northwell NS/LIJ, NY); Cassandra Mackey, MD (Assistant Professor of Emergency Medicine, UMass Chan Medical School); Brit Long, MD (@long_brit)

Welcome to EM@3AM, an emDOCs series designed to foster your working knowledge by providing an expedited review of clinical basics. We’ll keep it short, while you keep that EM brain sharp.

A 13-year-old male presents to the ED for aggressive behavior which progressed to confusion and decreased level of consciousness. He initially was very agitated and aggressive and refused to drink any water. He then became disoriented and is now difficult to rouse. The parents note that he had recently had a fever, sore throat, and general malaise prior to this behavior but those symptoms resolved, although they note excessive salivation. Review of systems is remarkable for a bat bite for which he never sought care.

Triage vital signs (VS): BP 96/41, HR 126, T 102.4 temporal, RR 24 though erratic, SpO2 90% on room air.

Pertinent physical examination findings:
General: Toxic, difficulty to arouse,
Neuro: Pupils 6mm and sluggish, negative Kernig and Brudzinski
Head and neck: Supple, no trauma
Skin: Poorly healing bite to R lower extremity

What’s the most likely diagnosis?

Answer: Rabies1-14


  • Extremely rare in the U.S., with 1-3 cases reported annually
    • 25 total cases in the U.S. reported between 2009-2018
  • Globally, greater impacts with approximately 61,000 deaths per year
    • 20,000 of those fatalities are in India
  • Transmission occurs through exposure to mammals carrying rabies, most commonly bats, raccoons, foxes, and skunks, though pets and livestock can also transmit rabies
    • Cannot be carried by reptiles, amphibians, rabbits, or insects
    • 70% of most recent cases are via bat
  • 60,000 Americans annually receive post exposure prophylaxis (PEP)
  • Nearly fatal once symptoms appear
    • 20 reported cases of survival worldwide


Microbiology and Pathophysiology:

  • Rabies is a neurotropic Lyssavirus, a vaccine preventable disease
  • Transmitted via saliva of infected animals
  • Enters the peripheral nervous system via neuromuscular junctions and then moves proximally to central nervous system where it replicates
    • Moves centrifugally thereafter to salivary glands as well as other organs
  • Incubation is typically 2-3 weeks but may range from 1 week to 1 year


Clinical Presentation:

  • Progressive encephalitis
    • Prodrome with fever, pharyngitis, malaise, anorexia, dysphagia, gastrointestinal symptoms
    • Aggressive behavior, hydrophobia, priapism, increased libido, insomnia, nightmares, potential aerophobia
    • Furious rabies accounts for 80% and is characterized by hyperactivity and hydrophobia
      • Onset to death is approximately 5.7 days
    • Paralytic (dumb) rabies accounts for 20% and is characterized by a paralytic state
      • Onset to death is approximately 11 days
    • Both forms may have high fever, paresthesias, focal or generalization convulsions, hyperventilation, hypersalivation
    • This state is then followed by irregular and rapid breathing patterns and then respiratory arrest and coma



  • Assess ABCs
  • Vital signs may reveal high fever, tachycardia, hypotension, and altered mental status
    • ENT: Hypersalivation, facial muscle fasciculations
    • Neuro: altered mental status ranging from agitation to coma, fasciculations, nuchal rigidity, paresthesias at the site of viral entry
    • Skin: evaluate for potential bite for inciting transmission
  • Laboratory evaluation hinges on detection of the virus
    • Most rapid antemortem method of diagnosis of rabies is direct immunofluorescence test on skin biopsy from the nape of the neck
    • Other methods include cerebral spinal fluid, saliva, serum, RT-PCR
  • Lumbar puncture: rule out other etiologies of encephalitis and acquire CSF for rabies antibodies testing
  • Imaging: Consider MRI
    • Abnormal hypersignaling in the brainstem, hippocampus, or hypothalamus



  • Manage ABCs
    • Depending on location in clinical course, may require intubation
  • Milwaukee protocol:
    • Supportive care: antipyretics, fluid resuscitation, enteral nutrition to support increased metabolic demands, consideration of venous thromboembolism prophylaxis or treatment, enteral nutrition and vitamins
    • Therapeutic coma: benzodiazepine and ketamine
      • Decreases cerebral metabolic demands and autonomic hyperactivity
    • Antivirals: amantadine to decrease viral load (VL)
      • Ketamine decreases VL as well
    • Avoid barbiturates if possible due to their T cell inhibition
    • Diagnosis would be challenging to confirm in ED, likely will treat for encephalitis
    • Rabies Immunoglobulin (RIG) IM—20 IU/kg
      • Ideally inject as much as allowable into the rabies transmission site
    • Post exposure prophylaxis:
      • RIG 20 IU/kg IM
      • Rabies vaccination schedule
        • Immunocompetent: day 0, 3, 7, 14
        • Immunosuppressed: day 0, 3, 7, 14, 28
        • If can observe or capture/autopsy animal, can delay vaccination



  • Admission to ICU
  • Consult ID



  • Incredibly rare in the US, but in the cases in which it does occur, bats are usually involved
  • Consider rabies in any meningitis or encephalitis differential diagnosis
  • While likely fatal, consider Milwaukee protocol with airway management, supportive care, induced coma, and amantadine
  • Avoid barbiturates if possible
  • PEP: 20/kg IU IM with rabies vaccination on days 0,3,7,14 with an additional dose on day 28 if immunosuppressed

A 10-year-old girl presents to the emergency department with agitation. She emigrated from an isolated region of Africa 2 weeks ago, and her immunization status is unclear. Over the last 4 days, she had a sore throat, fever up to 38.5°C, malaise, myalgias, and chills, which her family attributed to a typical childhood illness. This morning, they noticed her disoriented and salivating more than usual. She also developed a new overwhelming fear of water, and she begins choking and coughing at even the sight of water. On exam, her vital signs are within normal limits for her age, but she has periods of profound encephalopathy with intermittent lucidity. Her exam is remarkable for dilated pupils, increased tearing, sweating, and increased salivation. Which of the following illnesses most likely explains this patient’s symptoms?

A) Anticholinergic syndrome

B) Bacterial meningitis

C) Epiglottitis

D) Rabies



Answer: D

Rabies is a single-stranded RNA virus that is almost universally fatal. Worldwide, it is most commonly transmitted from dogs and most commonly occurs in isolated regions of Africa and Asia. In the United States, most rabies is transmitted from bats and only occurs in one to three people yearly. Other animals that can transmit rabies are wild carnivores, including raccoons, skunks, foxes, and coyotes. Rabies is transmitted through the saliva via bite wounds or mucous membranes and does not transmit via fomites or skin exposure to secretions. The incubation period for rabies is between 1 and 3 months. Symptoms start with a prodromal illness lasting a few days to a week with nonspecific symptoms of malaise, low-grade fevers, myalgias, weakness, anorexia, sore throat, nausea, vomiting, and headache. These symptoms usually accompany paresthesia or itching near the site of the bite. The excitement stage of the illness progresses to fluctuating profound encephalitis and agitation with intermittent periods of lucidity. Two of the nonuniversal but cardinal signs of rabies are hydrophobia and aerophobia, with patients developing spasms of the pharynx, neck, and diaphragm at the sight or suggestion of water or by fanning air in their face. The illness worsens to include complete cerebral and brainstem dysfunction and results in death in the vast majority of patients. Given the near-universal fatality of rabies, treatment is largely prevention, but there are a handful of survivors and experimental treatments. Postexposure vaccination with both the rabies vaccine and rabies immune globulin is effective at preventing the progression of the disease when given within a short time of exposure.

Anticholinergic syndrome (A) can present with fever, flushed skin, mydriasis, and delirium but results in a dry mouth, dry eyes, and decreased sweating and does not have a prodromal phase. Patients with fever and encephalitis should be tested and treated for bacterial meningitis (B), but meningitis is not associated with profound waxing and waning of mental status and fear of water. Epiglottitis (C) typically presents with sudden onset of high fever, drooling, and change in voice, but not with encephalitis.

Rosh Review Website Link

Further Reading

Further Reading:

Other FOAMed:

  1. CORE EM: https://coreem.net/podcast/episode-94-0/
  2. https://litfl.com/rabies-vaccine/



  1. World Health Organization, 2013. WHO Expert Consultation on Rabies: Second Report. World Health Organization Technical Report Series 982. Geneva, Switzerland: WHO.
  2. Sudarshan MK, Madhusudana SN, Mahendra BJ, Rao NS, Ashwath Narayana DH, Abdul Rahman S, Meslin FX, Lobo D, Ravikumar K, Gangaboraiah, 2007. Assessing the burden of human rabies in India: results of a national multi-center epidemiological survey. Int J Infect Dis11: 29–35.
  3. CDC. Rabies. https://www.cdc.gov/rabies/about.html. Accessed 21 Aug 2022
  4. Amoako, Y.A., El-Duah, P., Sylverken, A.A. et al.Rabies is still a fatal but neglected disease: a case report. J Med Case Reports15, 575 (2021).
  5. McDermid RC, Saxinger L, Lee B, Johnstone J, Gibney RT, Johnson M, Bagshaw SM. Human rabies encephalitis following bat exposure: failure of therapeutic coma. CMAJ. 2008 Feb 26;178(5):557-61. doi: 10.1503/cmaj.071326. Erratum in: CMAJ. 2008 May 6;178(10):1324.
  6.  Fooks AR, et al. 2017. Rabies. Nat Rev Dis Primers3: 17091.
  7. Centers for Disease Control: Compendium of animal rabies control, 1995. MMWR 44 (RR-2): 1, 1995
  8. Audu SW, Mshelbwala PP, Jahun BM, Bouaddi K, Weese JS. Two fatal cases of rabies in humans who did not receive rabies postexposure prophylaxis in Nigeria. Clin Case Rep. 2019;7(4):749-752.
  9. Nigg AJ, Walker PL. Overview, prevention, and treatment of rabies. Pharmacotherapy. 2009;29(10):1182-1195.
  10. Hemachudha T, Laothamatas J, Rupprecht CE. Human rabies: a disease of complex neuropathogenetic mechanisms and diagnostic challenges. Lancet Neurol 2002;1:101–9
  11. Medical College of Wisconsin. The Milwaukee protocol, 2007. Available from http://www.chw.org/display/PPF/DocID/33223/ router.asp. Accessed December 22, 2008.
  12. Meslin FX. Rabies as a traveler’s risk, especially in high endemicity areas. J Travel Med 2005;12 (suppl 1):S30–40.
  13. Madhusudana SN, Sukumaran SM, 2008. Antemortem diagnosis and prevention of human rabies. Ann Indian Acad Neurol11: 3–12.
  14. Willoughby RE, Jr., Tieves KS, Hoffman GM, Ghanayem NS, Amlie-Lefond CM, Schwabe MJ, Chusid MJ, Rupprecht CE, 2005. Survival after treatment of rabies with induction of coma. N Engl J Med352: 2508–2514.

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