Rabies medical therapy: Difference between revisions

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** [[Dizziness]]
** [[Dizziness]]
* [[Pain|Local pain]] and [[low-grade fever]] may follow injection of [[rabies immune globulin]].
* [[Pain|Local pain]] and [[low-grade fever]] may follow injection of [[rabies immune globulin]].
= Human Rabies Immune Globulin =
=== Human Rabies Immune Globulin ===
[[Human rabies virus immune globulin|Human rabies immune globulin (HRIG)]] is administered only once, at the beginning of anti-rabies prophylaxis, to previously unvaccinated persons. This will provide immediate [[antibodies]] until the body can respond to the [[vaccine]] by actively producing [[antibodies]] of its own. If possible, the full dose of [[Human rabies virus immune globulin|HRIG]] should be thoroughly infiltrated in the area around and into the [[wounds]]. Any remaining volume should be [[Intramuscular injection|injected intramuscularly]] at a site distant from [[vaccine]] administration.
[[Human rabies virus immune globulin|Human rabies immune globulin (HRIG)]] is administered only once, at the beginning of anti-rabies prophylaxis, to previously unvaccinated persons. This will provide immediate [[antibodies]] until the body can respond to the [[vaccine]] by actively producing [[antibodies]] of its own. If possible, the full dose of [[Human rabies virus immune globulin|HRIG]] should be thoroughly infiltrated in the area around and into the [[wounds]]. Any remaining volume should be [[Intramuscular injection|injected intramuscularly]] at a site distant from [[vaccine]] administration.



Revision as of 18:59, 27 September 2017

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Medical Therapy

while considering rabies for treatment, 2 different scenarios should be considered:

  • A patient introducing to emergency department due to symptomatic rabies with delay seeking medical care
  • A patient with a suspicious interact with the disease or an early diagnosed rabies patient that is asymptomatic

In the first case the survival rate is very low. The best treatment choice for this group of patients far by now is a protocol known as "Milwaukee protocol" which is still under investigation. The second group can benefit from a combined vaccine and immune globulin, with a good prognosis.

The flowchart of patient treatment behavior is summarized in the algorithm below:

Rabies Treatment Flowchart

Courtesy dedicatetd to CDC

Patient with Symptomatic Rabies

Milwaukee protocol

The Milwaukee protocol, sometimes referred to as the Wisconsin protocol, is an experimental course of treatment of an infection of rabies in a human being. The treatment involves putting the patient into a chemically induced coma and administering antiviral drugs.

Clinical trials

Out of 36 rabies patients treated with the Milwaukee Protocol, 5 have survived. Giese's treatment regimen has undergone revision (the second version omits the use of ribavirin). Two of 25 patients treated under the first protocol survived. A further 10 patients have been treated under the revised protocol, with a further two survivors.[1][2]

In June 2011, another child survived infection with rabies without receiving the vaccine before showing symptoms. Precious Reynolds, an eight-year-old girl from Willow Creek, California, contracted the disease in April 2011 but did not receive medical care until mid-May, after her grandmother took her to the doctor because of influenza-like symptoms that grew so serious, her grandmother said they resembled polio. The hospital said doctors followed the protocol established for Giese. Reynolds was placed in a drug-induced coma and received antiviral medications. She survived after spending two weeks in intensive care undergoing the treatments.[3][2]

Some critics say those survivors are due to the patients having a genetic rabies immunity and that the Milwaukee protocol has nothing to do with the survival rate;[4] however this would imply the five patients all happened to coincidentally survive rabies while receiving the Milwaukee protocol—despite no documented survivors before them. Medical experts disagree about the effectiveness of the Milwaukee treatment, pointing out that a certain antibody type appears in all survivors. This suggests that a genetic or other immunological factor may affect survival.[2]

Ketamine has been shown to have a direct effect against the rabies virus.[5]

Asymptomatic Patient Suspicious of Rabies

Treatment management in these patients start with wound care, postexposure vaccination, and human immune globulin injection:

Wound Care

Regardless of the risk of rabies, bite wounds can cause serious injuries such as:

In the wound treatment procedure, cosmetic issues should be considered.

For many types of bite wounds, immediate gentle irrigation with water or a dilute water povidone-iodine solution has been shown to markedly decrease the risk of bacterial infection. Wound cleansing is especially important in rabies prevention since, in animal studies, thorough wound cleansing alone without other postexposure prophylaxis has been shown to markedly reduce the likelihood of rabies.

Patient should receive a tetanus shot if has not been immunized in the previous ten years. Decisions regarding the use of antibiotics, and primary wound closure should be considered.

Rabies Post-exposure Vaccinations

For people who have never been vaccinated against rabies previously, postexposure anti-rabies vaccination should always include administration of both passive antibody and vaccine. The combination of human rabies immunoglobulin (HRIG) and vaccine is recommended for both bite and non-bite exposures, regardless of the interval between exposure and initiation of treatment. People who have been previously vaccinated or are receiving preexposure vaccination for rabies should receive only vaccine.

Post-exposure prophylaxis recommendations based on contact type

In countries or areas at risk of rabies, the circumstances of an animal bite or other contact with an animal suspected to be rabid may require post-exposure prophylaxis. In such situations, medical advice should be obtained immediately. Strict adherence to the WHO-recommended guidelines for optimal post-exposure rabies prophylaxis virtually guarantees protection from the disease. The administration of vaccine, and of immunoglobulin if required, must be conducted by, or under the direct supervision of, a physician.

Category Type of contact with a suspected or confirmed rabid domestic or wild (a) animal or animal unavailable for testing Type of exposure Recommended post-exposure prophylaxis
I
  • Touching or feeding of animals
  • Licks on intact skin
None
  • None, if reliable case history is available
II
  • Nibbling of uncovered skin
  • Minor scratches or abrasions without bleeding
Minor
  • Administer vaccine immediately (b). Stop treatment if animal remains healthy throughout an observation period of 10 days (c) or is proved to be negative for rabies by a reliable laboratory using appropriate diagnostic techniques.
III
  • Single or multiple transdermal bites or scratches, licks on broken skin
  • Contamination of mucous membrane with saliva (i.e. licks)
  • Exposures to bats(d)
Severe
  • Administer rabies immunoglobulin and vaccine immediately. Stop treatment if animal remains healthy throughout an observation period of 10 days (c) or is proved to be negative for rabies by a reliable laboratory using appropriate diagnostic techniques.

a) Exposure to rodents, rabbits and hares seldom, if ever, requires specific anti-rabies post-exposure prophylaxis.

b) If an apparently healthy dog or cat in or from a low-risk country or area is placed under observation, the situation may warrant delaying initiation of treatment.

c) This observation period applies only to dogs and cats. Except in the case of threatened or endangered species, other domestic and wild animals suspected to be rabid should be humanely killed and their tissues examined for the presence of rabies virus antigen using appropriate laboratory techniques.

d) Post-exposure prophylaxis should be considered for individuals who have been in close contact with bats, particularly following bites or scratches or exposure to mucous membranes.

Rabies Vaccines and Immunoglobulin Available in the United States

Type Name Route Indications
Human Diploid Cell Vaccine (HDCV) Imovax® Rabies Intramuscular Preexposure or Postexposure
Purified Chick Embryo Cell Vaccine (PCEC) RabAvert® Intramuscular Preexposure or Postexposure
Human Rabies Immune Globulin Imogam® Rabies-HT Local infusion at wound site, with additional amount intramuscular at site distant from vaccine Postexposure
Human Rabies Immune Globulin HyperRab TM S/D Local infusion at wound site, with additional amount intramuscular at site distant from vaccine Postexposure

Rabies postexposure prophylaxis (PEP) schedule

These regimens are applicable for persons in all age groups, including children

Vaccination status Intervention Regimen
Not previously vaccinated Wound cleansing All PEP should begin with immediate thorough cleansing of all wounds with soap and water. If available, a virucidal agent (e.g., povidone-iodine solution) should be used to irrigate the wounds.
HRIG Administer 20 IU/kg body weight. If anatomically feasible, the full dose should be infiltrated around and into the wound(s), and any remaining volume should be administered at an anatomical site (intramuscular [IM]) distant from vaccine administration. Also, HRIG should not be administered in the same syringe as vaccine. Because RIG might partially suppress active production of rabies virus antibody, no more than the recommended dose should be administered.
Vaccine Human diploid cell vaccine (HDCV) or purified chick embryo cell vaccine (PCECV) 1.0 mL, IM (deltoid area†), 1 each on days 0, 3, 7 and 14.
Previously vaccinated Wound cleansing All PEP should begin with immediate thorough cleansing of all wounds with soap and water. If available, a virucidal agent such as povidone-iodine solution should be used to irrigate the wounds.
HRIG HRIG should not be administered.
Vaccine HDCV or PCECV 1.0 mL, IM (deltoid area†), 1 each on days 0 and 3.

HRIG= Human rabies immune globulin, PEP= Postexposure prophylaxis, HDCV=Human diploid cell vaccine, PCECV= Purified chick embryo cell vaccine, IM= Intramuscular

Considerations:

Adverse Reactions to Rabies Vaccine and Human Rabies Immune Globulin

Adverse reactions to rabies vaccine and immune globulin are not common. Newer vaccines in use today cause fewer adverse reactions than previously available vaccines. The most common adverse reaction reported with rabies vaccine/immune globulin injection include:

Human Rabies Immune Globulin

Human rabies immune globulin (HRIG) is administered only once, at the beginning of anti-rabies prophylaxis, to previously unvaccinated persons. This will provide immediate antibodies until the body can respond to the vaccine by actively producing antibodies of its own. If possible, the full dose of HRIG should be thoroughly infiltrated in the area around and into the wounds. Any remaining volume should be injected intramuscularly at a site distant from vaccine administration.

HRIG should never be administered in the same syringe or in the same anatomical site as the first vaccine dose. However, subsequent doses of vaccine in the four-dose series can be administered in the same anatomic location where the HRIG dose was administered.

If HRIG was not administered when vaccination was begun, it can be administered up to seven days after the administration of the first dose of vaccine. Beyond the seventh day, HRIG is not recommended since an antibody response to the vaccine is presumed to have occurred.

Dosage:

  • Preferred regimen: Because HRIG can partially suppress active production of antibody, no more than the recommended dose should be administered. The recommended dose of HRIG is 20 IU/kg body weight. This formula is applicable to all age groups, including children.

References

  1. Willoughby RE (2009). "Are we getting closer to the treatment of rabies?: medical benchmarks". Future Virology. MedScape. 4 (6): 563&ndash, 570. doi:10.2217/fvl.09.52.
  2. 2.0 2.1 2.2 "Human Rabies --- Indiana and California, 2006".
  3. "UC Davis Children's Hospital patient becomes third person in U.S. to survive rabies". UC Davis Medical Center. Retrieved 3 May 2012.
  4. "Undead: The Rabies Virus Remains a Medical Mystery". Retrieved May 15, 2015.
  5. Lockhart BP, Tordo N, Tsiang H (1992). "Inhibition of rabies virus transcription in rat cortical neurons with the dissociative anesthetic ketamine". Antimicrob Agents Chemother. 36 (8): 1750–5. doi:10.1128/AAC.36.8.1750. PMC 192041. PMID 1416859.
  6. Rupprecht CE, Briggs D, Brown CM, Franka R, Katz SL, Kerr HD, Lett SM, Levis R, Meltzer MI, Schaffner W, Cieslak PR (2010). "Use of a reduced (4-dose) vaccine schedule for postexposure prophylaxis to prevent human rabies: recommendations of the advisory committee on immunization practices". MMWR Recomm Rep. 59 (RR-2): 1–9. PMID 20300058.

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