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Rabies and Intradermal Rabies Vaccination

Rabies and Intradermal Rabies Vaccination. Alan C. Jackson, MD Professor of Medicine (Neurology) and of Medical Microbiology Head, Section of Neurology University of Manitoba Winnipeg, Manitoba, Canada. Rabies virus structure. Matrix protein. Glycoprotein. Envelope.

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Rabies and Intradermal Rabies Vaccination

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  1. Rabies and Intradermal Rabies Vaccination Alan C. Jackson, MD Professor of Medicine (Neurology) and of Medical Microbiology Head, Section of Neurology University of Manitoba Winnipeg, Manitoba, Canada

  2. Rabies virus structure Matrix protein Glycoprotein Envelope Nucleocapsid protein Source: http://www.cdc.gov

  3. Human rabies Photo courtesy of David Warrell, UK

  4. Clinical forms of rabies • encephalitic = furious • ~ 80% • paralytic = dumb • ~ 20%

  5. Encephalitic rabies • prodromal symptoms • paresthesias/pain/pruritus at site of bite • episodes of generalized arousal or hyperexcitability separated by lucid periods • autonomic dysfunction • hydrophobia

  6. Paralytic rabies • paresthesias/pain/pruritus at site of bite • early flaccid muscle weakness • often begins in bitten extremity • progresses to produce quadriparesis • bilateral facial weakness • sensory examination is usually normal • sphincter involvement • fatal outcome • often misdiagnosed as Guillain - Barré syndrome

  7. Geographic distribution of rabies - 2000 No information: DRC, Benin ,Burkina, Sierra Leone, Liberia, Gambia, Mauritania, Somalia, Yemen, Malaysia, Laos, Myanmar, Vietnam Cambodia, North Korea

  8. DALY (disability-adjusted life year) scores =years of life lost + years of life with a disability Disease Total DALYs lost (X 1000) Malaria 42,280 Tuberculosis 36,040 Lymphatic filariasis 5,644 Leishmaniosis 2.357 Schistosomiasis 1,760 Trypanosomiasis 1,598 Rabies 1,160 Onchocerciasis 987 Dengue 653 Chagas 649 Leprosy 177 Emerg Inf Dis 10, 2004

  9. Human rabies preventionUnited States Recommendations of the CDC’sAdvisory Committee on Immunization PracticesMMWR Recommendations and ReportsJanuary 8, 1999 http://www.cdc.gov/mmwr

  10. Rabies postexposure guide: exposure to dogs, cats, and ferrets Evaluation of Animal Recommendation No treatment unless animal develops clinical signs of rabies Healthy and available for 10 days observation Rabid or suspected rabid Immediate treatment* Consult local public health department Unknown (e.g., escaped) *Discontinue treatment if tests on animal prove negative.

  11. Recommended prophylaxis in exposed individuals not previously vaccinated against rabies Wound site(s) Immediate thorough cleansing of all wounds with soap and water. Tetanus prophylaxis; antibiotics Human Rabies Immune Globulin (RIG) 20 IU/kg body weight • As much of the RIG as possible should be infiltrated in wound(s) • The remainder should be given IM at a site distant from vaccine Rabies Vaccine IM (1 mL) in the deltoid area on days 0, 3, 7, 14, and 28 MMWR 48: RR-1, 1999

  12. Rabies Vaccines Available in Canada RabAvert®Imovax ® Manufacturer Cell culture Common designation Novartis (Merck Frosst) primary chick embryo fibroblasts PCECV Sanofi Pasteur MRC-5 human lung cell line HDCV MMWR;48:RR-1, January 8, 1999 Product package inserts, 2006

  13. Adverse Reactions to Rabies Vaccines Most common side-effects of rabies vaccines: • Systemic reactions such as headache, myalgia, malaise (5-40%) • Mild to moderate local reactions at injection site (30-74%)

  14. Populations at increased risk of exposure to rabies • Rabies research laboratory workers • Veterinarians, staff, veterinary students • Animal control and wildlife workers • Bat handlers • Spelunkers • Travellers to certain rabies-endemic areas MMWR 48: (RR-1), 1999

  15. Assessing the Rabies Risk for Travellers • Destination • Duration of travel • Anticipated activities • Access to medical care and • appropriate PEP biologics

  16. Preexposure rabies prophylaxis • 3 doses of rabies vaccine (days 0, 7, and 21 or 28) • May check rabies antibody titre periodically – want >0.5 IU/mL • after a rabies exposure: • 2 doses of IM rabies vaccine (days 0 and 3) • no HRIG

  17. Pre-exposure rabies prophylaxis Tissue culture vaccine: 1 dose IM or 0.1 ml ID Day 0 7 21 28 • If CHLOROQUINE malaria prophylaxis, give IM only • If immunosuppressed check neut. Antibody titre ≥0.5 IU/ml • HIV positive patients - CD4 counts <300 may be unresponsive Modified from MJ Warrell, University of Oxford

  18. Photo courtesy of Claudius Malerczyk (Novartis)

  19. Can Comm Dis Rep 31:1, 2005

  20. Intradermal use of rabies vaccine • Gold standard is IM administration of rabies vaccine • ID regimen is an acceptable alternative • Uses one-tenth the dose • Comparable degree of protection • Economical and widely accepted Can Comm Dis Rep 31:1, 2005

  21. Intradermal use of rabies vaccine • Pre-exposure = three 0.1 mL doses on days 0, 7, and 21 or 28 intradermally on upper arm • After reconstitution of 1.0 mL dose, may store at 4 – 8 degrees C for up to 8 hours with proper aseptic precautions • PCECV shown to be immunogenic 7 days after reconstitution with storage in a clinic refrigerator (Khawplod et al. CID 2002) Can Comm Dis Rep 31:1, 2005

  22. Intradermal use of rabies vaccine • Neutralization titres after ID vaccination are lower than after IM, but adequate protective levels • Briggs found that after 2-2.5 years: • 79% of IM vs. 51% of ID had satisfactory titres • ACIP, at 2 years: • 93-98% for IM vs. 83-95% for ID Can Comm Dis Rep 31:1, 2005

  23. Intradermal use of rabies vaccine Manitoba n=488 in 2005 • 6-12 mo after 3rd dose: • 95% >0.5 IU/mL • Median 2.7 IU/mL Ontario and Alberta • favourable, but smaller experience Can Comm Dis Rep 31:1, 2005

  24. Intradermal use of rabies vaccine Manitoba n=1000 as of 2008 • 1 year after 3rd dose: 92% >0.5 IU/mL • 2 years after 3rd dose: 87% >0.5 IU/mL • 3 years after 3rd dose: 80% >0.5 IU/mL • 5 years after 3rd dose: 75% >0.5 IU/mL Preliminary data from Drs. O. Larios and F. Aoki

  25. Importance of maintaining the antibody level is unknown • The response to booster doses is predictable and rapid. • In ‘low responders’ the antibody response may not be so high (significance unknown). • Detectable antibodies may not be necessary for protection if booster doses are given promptly after exposure. Modified from MJ Warrell, University of Oxford

  26. Approach to immunization of travellers 3 dose pre-exposure course If risk of exposure continues, then booster dose at 1 – 2 years Travellers with access to vaccine: If exposed to rabies need no further boosters Travellers to remote areas with no access to vaccine: Should repeat booster dose before departure if last dose was > 3 - 5 years previously (if antibody < 0.5 IU/ml) Ensure booster doses if rabies exposure ASAP Modified from MJ Warrell, University of Oxford

  27. Efficacy of prophylaxis • Pre-exposure vaccine followed by post-exposure boosters – no deaths reported • If no previous vaccine: optimal post-exposure treatment highly effective, but deaths occur with delay or incomplete treatment Modified from MJ Warrell, University of Oxford

  28. Rabies prevention - Summary • Rabies is a preventable disease. • Failure to recognize a risk of infection results in human deaths. • Increased awareness of sources and routes of virus transmission could save lives. • Pre-exposure vaccination should be used widely. • Post-exposure treatment is urgent. • For previously vaccinated people post -exposure treatment is simpler, cheaper and more effective. Modified from MJ Warrell, University of Oxford

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