Rabies prevention

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comprehensive presentation on Rabies Prevention
Concepts on pathogenesis, Active and Passive Immunisation

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  • References
    1. AS Benenson. Control of communicable disease manual. 1995
  • References
    World Health Organization (WHO). Who expert consultation on rabies, 5-8 October 2004. Technical Report Series 931 – First Report. Switzerland: WHO Press; 2004
    Nadin-Davis SA. Molecular epidemiology. In: Jackson AC, Wunner WH, eds. Rabies. 2nd edn. London: Elsevier Academic Press; 2007:69-122
    3. Bleck TP, Rupprecht CE. Rhabdoviruses. In: Mandell GL, Bennett JE, Dolin R, eds. Principles and Practice of Infectious Diseases. 6th edn. Philadelphia: Churchill Livingstone Inc.; 2005:2047-56
    4. Centers for Disease Control and Prevention (CDC). Rabies. http://www.cdc.gov/rabies/bats.html. Accessed March 2, 2009
  • References
    1. Centers for Disease Control and Prevention (CDC). Rabies. The Rabies Virus. http://www.cdc.gov/rabies/virus.html. Accessed March 2, 2009
    2. Bleck TP, Rupprecht CE. Rhabdoviruses. In: Mandell GL, Bennett JE, Dolin R, eds. Principles and Practice of Infectious Diseases. 6th edn. Philadelphia: Churchill Livingstone Inc.; 2005:2047-56
    3. Plotkin SA, Koprowski H, Rupprecht CE. Rabies vaccines. In: Plotkin SA, Orenstein WA, Offit PA, eds. Vaccines. 5th edn. Philadelphia: Saunders; 2008:687-714
  • References
    1. Bleck TP, Rupprecht CE. Rhabdoviruses. In: Mandell GL, Bennett JE, Dolin R, eds. Principles and Practice of Infectious Diseases. 6th edn. Philadelphia: Churchill Livingstone Inc.; 2005:2047-56
    2. Plotkin SA, Koprowski H, Rupprecht CE. Rabies vaccines. In: Plotkin SA, Orenstein WA, Offit PA, eds. Vaccines. 5th edn. Philadelphia: Saunders; 2008:687-714
  • Reference
    Jackson AC. Human disease. In: Jackson AC, Wunner WH, eds. Rabies. 2nd edn. London: Elsevier Academic Press; 2007:309-40
    2. Hemachudha T, Laothamatas J, Rupprecht CE. Human rabies: a disease of complex neuropathogenic mechanisms and diagnostic challenges. Lancet Neurol 2002;1:101-09
  • References
    1. Jackson AC. Human disease. In: Jackson AC, Wunner WH, eds. Rabies. 2nd edn. London: Elsevier Academic Press; 2007:309-40
  • Reference
    1. World Health Organization (WHO). Rabies. Fact sheet No. 99. December 2008. http://www.who.int/mediacentre/factsheets/fs099/en/. Accessed March 2, 2009
  • References
    World Health Organization (WHO). RABNET. Rabies, countries or areas at risk. 23 Feb 2009. http://gamapserver.who.int/mapLibrary/Files/Maps/Global_Rabies_ITHRiskMap.png. Accessed March 2, 2009
  • References
    1. Cliquet F, Gurbuxani JP, Pradhan HK, et al. The safety and efficacy of the oral rabies vaccine SAG2 in Indian stray dogs. Vaccine 2007;25:3409-18
    2. Sudarshan MK, Madhusudana SN, Mahendra BJ, et al. Assessing the burden of human rabies in India: results of a national multi-center epidemiological survey. Int J Infect Dis 2007;11:29-35
  • References
    1. Plotkin SA, Koprowski H, Rupprecht CE. Rabies vaccines. In: Plotkin SA, Orenstein WA, Offit PA, eds. Vaccines. 5th edn. Philadelphia: Saunders; 2008:687-714
  • References
    1. Plotkin SA, Koprowski H, Rupprecht CE. Rabies vaccines. In: Plotkin SA, Orenstein WA, Offit PA, eds. Vaccines. 5th edn. Philadelphia: Saunders; 2008:687-714
    2. Centers for Disease Control and Prevention (CDC). Current trends rabies vaccine, adsorbed: A new rabies vaccine for use in humans. MMWR Morb Mortal Wkly Rep 1988:37;217-18, 223
  • References
    1. Plotkin SA, Koprowski H, Rupprecht CE. Rabies vaccines. In: Plotkin SA, Orenstein WA, Offit PA, eds. Vaccines. 5th edn. Philadelphia: Saunders; 2008:687-714
  • References
    1. World Health Organization (WHO). Who expert consultation on rabies, 5-8 October 2004. Technical Report Series 931 – First Report. Switzerland: WHO Press; 2004
    2. Centers for Disease Control and Prevention (CDC). Advisory Committee on Immunization Practices (ACIP) 2008. http://www.cdc.gov/vaccines/recs/acip/default.htm. Accessed 2 March, 2009
  • References
    1. World Health Organization (WHO). Who expert consultation on rabies, 5-8 October 2004. Technical Report Series 931 – First Report. Switzerland: WHO Press; 2004
    2. World Health Organization (WHO). Rabies vaccines. WHO position paper. Wkly Epidemiol Rec 2007;82:425–35
    Photos from Program 44: Dog Bites and Rabies Prevention; Prof David C. Anderson, Medi-Vision film. (http://www.medivisionfilms.com/index.php?vid=176&type=ZHZk)and Dr. Beatriz Quiambao, RITM, Manila, Philippines
  • References
    1. World Health Organization (WHO). Who expert consultation on rabies, 5-8 October 2004. Technical Report Series 931 – First Report. Switzerland: WHO Press; 2004
    2. World Health Organization (WHO). Rabies vaccines. WHO position paper. Wkly Epidemiol Rec 2007;82:425–35
  • References
    1. World Health Organization (WHO). Who expert consultation on rabies, 5-8 October 2004. Technical Report Series 931 – First Report. Switzerland: WHO Press; 2004
    2. World Health Organization (WHO). Rabies vaccines. WHO position paper. Wkly Epidemiol Rec 2007;82:425–35
  • References
    1. World Health Organization (WHO). Who expert consultation on rabies, 5-8 October 2004. Technical Report Series 931 – First Report. Switzerland: WHO Press; 2004
    2. World Health Organization (WHO). Rabies vaccines. WHO position paper. Wkly Epidemiol Rec 2007;82:425–35
  • References
    1. National Guidelines for Rabies Prophylaxis and Intra-dermal Administration of Cell Culture Rabies Vaccines, 2007
  • References
    1. World Health Organization (WHO). Who expert consultation on rabies, 5-8 October 2004. Technical Report Series 931 – First Report. Switzerland: WHO Press; 2004
    2. World Health Organization (WHO). Rabies vaccines. WHO position paper. Wkly Epidemiol Rec 2007;82:425–35
  • More information
    Novartis Vaccines. Rabipur® Summary of Product Characteristics, 2007
  • References
    1. Ljubicic M, Vodopija I, Smerdel S, et al. Efficacy of PCEC vaccine in post-exposure rabies prophylaxis. In: Vodopija I, et al. eds. Improvements in rabies post exposure treatment. Zagreb. Zagreb Institute of Public Health; 1985:95-101
    2. Wasi C, Chaiprasithikul P, Puthavathana P, et al. Immunogenicity and reactogenicity of the new tissue culture rabies vaccine for human use (purified chick embryo cell-culture). In: Vodopija I, et al. eds. Improvements in rabies post exposure treatment. Zagreb. Zagreb Institute of Public Health: 1985:85-94
    3. Tanphaichitra D and Siristonpun Y. Study of the efficacy of a purified chick embryo cell vaccine in patients bitten by rabid animals. Intern Med 1987:163-165
    4. Sehgal S, Bhardwaj M, Bhatia R. Clinical evaluation of purified chick embryo cell antirabies vaccine for post-exposure treatment. J Commun Dis 1988;20:293-300
    5. Sehgal S, Bhattacharya D, Bhardwaj M. Ten year longitudinal study of efficacy and safety of purified chick embryo cell vaccine for pre- and post-exposure prophylaxis of rabies in Indian population. J Commun Dis 1995;27:36-43
  • References
    1. Briggs DJ, Dreesen DW, Nicolay U, et al. Purified Chick Embryo Cell Culture Rabies Vaccine: interchangeability with Human Diploid Cell Culture Rabies Vaccine and comparison of one versus two-dose post-exposure booster regimen for previously immunized persons. Vaccine 2000;19:1055-60
  • References
    Kamoltham T, Singhsa J, Promsaranee U, et al. Elimination of human rabies in a canine endemic province in Thailand: five-year programme. Bull World Health Organ 2003;81:375-81
    Quiambo BP, Dimaanob EN, Ambasa C. Reducing the cost of post-exposure rabies prophylaxis: efficacy of 0.1 ml. PCEC rabies vaccine administered intradermally using the Thai Red Cross post-exposure regimen in patients severely exposed to laboratory-confirmed rabid animals. Vaccine 2005;23:1709–1714
    3. Madhusudana SN, Anand NP, Shamsundar R. Economical multi-site intradermal regimen with purified chick embryo cell vaccine (Rabipur) prevents rabies in people bitten by confirmed rabid animals. Int J Infect Dis 2002;6:210-14
  • References
    1. Sehgal S, Bhattacharya D, Bhardwaj M. Ten year longitudinal study of efficacy and safety of purified chick embryo cell vaccine for pre- and post-exposure prophylaxis of rabies in Indian population. J Commun Dis 1995;27:36-43
  • Rabies prevention

    1. 1. Understanding Rabies Disease and Prevention Dr (Lt Col) Ashutosh Ojha 151 Army Base Hospital,India ashutosh8116@gmail.com 1
    2. 2. Section 1 Rabies disease background
    3. 3. 3 Benenson 1995 M al a ria ox ru s al lp ta vi gu e er le ra No treatment Sm Ha n D en e tis fe v Ch o gi ag u en in Pl ax ie s an th r Ra b lo w .m ic Ye l M on at io n um ha l Pn e In Case fatality rate Rabies is virtually 100% fatal Treatment 100 90 80 70 60 50 40 30 20 10 0
    4. 4. Rabies Rabies is an ancient disease Painting of a rabid dog biting a man Arabic A.D. 1224 Baghdad school, by Abdallah ibn al-Fadl 4 Picture courtesy of Smithonian Institution, Washington D.C.
    5. 5. The rabies virus Taxonomy: Family: Rhabdoviridae Genus: Lyssavirus Species: Rabies virus bullet-shaped, ~180 nm long and ~75 nm wide single-strand, negative sense RNA 5 CDC 2007; Bleck 2005
    6. 6. Pathogenesis: Exposure Bite transmission Human infection by rabies virus usually occurs as a result of a transdermal bite from an infected wild or domestic animal Non-bite transmission Scratches from a rabid animal Saliva from a rabid animal comes into contact with a victim’s mucous membranes or fresh skin lesions Rare cases have been reported via: Inhalation of virus-containing aerosols Human-to-human transmission through transplantation 6 1. Bleck 2005; 2. WHO 2004
    7. 7. How does the Rabies virus travel from wound to brain
    8. 8. Human rabies: Clinical stages Exposure First clinical signs First neurologic signs Onset of coma Death Incubation period Prodrome phase Acute neurologic phase Coma Usual duration 20-90 days 2-10 days 2-7 days 0-14 days Clinical stage Onset of rabies symptoms may start rather late, ie, onset of symptoms documented months, even years, after exposure Death usually occurs within a few days after the appearance of clinical symptoms 8 1. Jackson 2007; 2. Hemachudha 2002
    9. 9. Clinical rabies in humans Two forms of rabies are distinguished: Furious (75-80%) (encephalitic; three-forth of all cases): – Rabies transmitted from dogs is usually furious Paralytic (20-25%) (dumb; one-fourth of all cases) Clinical Presentation: First clinical symptoms: non-specific, i.e., malaise, fever, and headache Paresthesia: pain and abnormal feelings at the wound site are common Acute neurologic phase: including throat spasms with an inability to swallow, and anxiety, confusion, and hallucinations: – Hydrophobia (only documented in humans), respiratory spasms with aerophobia, hyperactivity only exhibited with furious rabies – Ascending paralysis or a symmetric quadriparesis only exhibited with paralytic rabies Coma and death 9 Jackson 2002
    10. 10. Rabies in children Due to their short stature, children are susceptible to bites on face, scalp, and upper part of the body Children are more susceptible to animal bites by playing in open grounds or in streets Children cannot ward off animals easily Children are more likely to provoke animals Children might not report a bite or scratch 40-60% of all animal bite cases are reported to occur in children <15 years of age 10 WHO 2008
    11. 11. Section 2 Epidemiology of rabies
    12. 12. Worldwide risk of rabies (2008) No risk 12 WHO 2009 Low risk Medium risk High risk
    13. 13. India carries highest Rabies disease burden Estimated 20,000 human rabies deaths per year Principal reservoir of the disease is dogs No surveillance system of rabies cases – lack of reliable data Estimated 27 million dogs – although the number of stray dogs is unknown 17.4 million dog bites annually 1. Cliquet 2007; 2. Sudarshan 2007 13
    14. 14. Rabies vaccines
    15. 15. Historical development of rabies vaccines 1885: Louis Pasteur developed the first rabies vaccine Infected rabbit spinal cord partially inactivated by desiccation 1911: Semple vaccine; Sir David Semple improved Pasteur treatment Inactivated virus using formalin and phenol Infected adult rabbit, sheep, or goat brain tissue Reactogenic, poorly immunogenic, up to 23 daily injections 1955: Fuenzalida vaccine; Drs Fuenzalida and Palacios Suckling mouse brain (SMB) vaccine Decreased reactogenicity with improved immunogenicity; 10-15 doses required 1956: Duck embryo vaccine; first effective cell-culture vaccine Duck embryo vaccine (DEV) Poorly immunogenic, high rate of allergic reactions. STOPPED 1980s 1970s: Modern cell-culture vaccines Highly immunogenic with good safety profile 15 Plotkin 2008
    16. 16. Currently produced rabies vaccines I Human diploid cell vaccines (HDCV): First-generation cell-culture rabies vaccine Virus grown on human diploid cells, Pitman-Moore strain Good immunogenicity and tolerability (hypersensitivity reactions are however reported with the unpurified HDCV)2 Suitable for pre-exposure vaccination and post-exposure prophylaxis † Purified Vero cell rabies vaccines (PVRV): Second-generation cell-culture rabies vaccine Continuous cell line produced on Vero cells (vervet monkey origin), virus grown in microcarrier system Good immunogenicity and tolerability Clinical trials not permitted in the US; no FDA approval due to risk of residual DNA associated with continuous cell line Intradermal administration is currently licensed in India, the Philippines, Sri Lanka, Thailand, and Vietnam; regulatory approval will continue to be adapted for other countries 16 1. Plotkin 2008; 2. CDC 1988
    17. 17. Currently produced rabies vaccines II Purified chick embryo cell-culture vaccine (PCECV): Second-generation cell-culture rabies vaccine Prepared in primary chick embryo cells using Flury LEP strain of fixed rabies virus Good immunogenicity and tolerability High purity and potency Approved by the US FDA (intramuscular regimen only) Recommended for each and every established WHO vaccination schedule where intradermal administration is licensed† Intradermal administration is currently licensed in India, Myanmar the Philippines, Sri Lanka, Thailand, and Vietnam; regulatory approval will continue to be adapted for other countries † 17 Plotkin 2008
    18. 18. WHO categories (I-III): Schedules for post-exposure prophylaxis Type of contact with a suspect or confirmed rabid domestic or wilda animal, or animal unavailable for testing Type of exposure Recommended post-exposure prophylaxis I Touching or feeding animals, licks on intact skin (ie, no exposure) None No prophylaxis is required II Nibbling of uncovered skin, minor scratches or abrasions without bleeding Minor Administer vaccine immediately III Single or multiple transdermal bites or scratches, licks on broken skin, contamination of mucous membrane with saliva from licks, exposures to bats Severe Administer rabies immunoglobulin and vaccine immediately. Category 18 1. WHO 2004; 2. CDC/ACIP 2008
    19. 19. Post-exposure prophylaxis Wound treatment (all WHO categories) Vaccine administration (WHO category II and III) – Active immunization with highly immunogenic rabies vaccine RIG administration, if appropriate (WHO category III) – Passive immunization followed by administration of specific antibodies 19
    20. 20. Prevention of human rabies The 5 Important Things Magico-Religious Practices (e.g. witchcraft, turmeric powder etc.) DO NOT HELP Do not cover or Suture the wound Wash the wound thoroughly with plenty of water and soap Apply an antiseptic (povidone iodine) or even alcohol Vaccinate Immediately e.g. Raibipur 1 mL IM
    21. 21. Rabies immunoglobulin (RIG) RIG needs to be administered to all Category III wounds along with complete course of ARV, 5 doses (0,3,7,14,&,28 days) for 1st exposure Subsequent exposure will require only 2 doses of ARV (0 & 3 days) and no RIG’s RIG infiltrated in and around wounds Two types of RIG – – Human RIG, dose 20 IU/kg of body weight Equine RIG, dose 40 IU/kg of body weight RIG provides passive immunity – – 21 Immediate access to rabies virus-neutralizing antibodies (RVNA) Provides protection until active immunity begins (7-10 days post-vaccination) Courtesy Medi-Vision and B. Quiambao, RITM, Manila
    22. 22. Prevention of human rabies Vaccine administration Post-exposure prophylaxis IM regimens: – Essen regimen: 5 doses, 5 patient visits (DCGI approved regimen) – Zagreb regimen: 4 doses, 3 patient visits Post-exposure prophylaxis ID regimens: – Updated Thai Red Cross: 8 doses, 4 patient visits (DCGI approved regimen) – Thai Red Cross: 8 doses, 5 patient visits – Oxford 8-site: 14 doses, 4 patient visits 22 1. WHO 2004; 2. WHO 2007 National Guidelines for Rabies Prophylaxis and Intra-dermal Administration of Cell Culture Rabies Vaccines, 2007
    23. 23. Post-exposure prophylaxis IM administration: Essen regimen One IM dose of vaccine on Days 0, 3, 7, 14, and 28 1 mL (IM) into deltoid (adults) or into anterolateral area of thigh (children) 5 doses – 5 visits RIG is always recommended for transdermal wounds 23 1. WHO 2004; 2. WHO 2007
    24. 24. Post-exposure prophylaxis IM administration: Updated Thai Red Cross (2-2-2-0-2) Days 0, 3, 7, and 28 – two 0.1 mL doses 0.1 mL per site Administered in right and left deltoid 8 doses – 4 visits RIG is always recommended for transdermal wounds 24 1. WHO 2004; 2. WHO 2007
    25. 25. DCGI recommended post-exposure IM and ID regimens: Summary Regimen Day 0 Day 3 Day 7 Day 14 Day 21 Day 28 Day 90 Vials Visits Essen 1.0 mL 1.0 mL 1.0 mL 1.0 mL – 1.0 mL – 5 5 Day 0 Day 3 Day 7 Day 14 Day 21 Day 28 Day 90 mL Visits Thai Red 2x 2x Cross 0.1 mL 0.1 mL (updated) 2x 0.1 mL – – 2x 0.1 mL – <1 4 Regimen National Guidelines for Rabies Prophylaxis and Intra-dermal Administration of Cell Culture Rabies Vaccines, 2007 25
    26. 26. Post-exposure prophylaxis in patients previously vaccinated with a cell-culture rabies vaccine Day 0 3 x1 x1 Two doses administered IM or ID Administered into (IM) or above (ID) deltoid No RIG is required 26 1. WHO 2004; 2. WHO 2007
    27. 27. National Guidelines for Rabies Prophylaxis and Intra-dermal Administration of Cell Culture Rabies Vaccines Intra-muscular (IM) Regimen The currently available vaccines and regimen in India for post exposure IM administration are described below. Vaccines 1. Cell Culture Vaccines  Human Diploid Cell Vaccine (HDCV)  Purified Chick Embryo Cell Vaccine (PCEC)  Purified Vero Cell Rabies Vaccine (PVRV) 2. Purified Duck Embryo Vaccine Regimen Essen Schedule: Five dose intramuscular regimen on days 0, 3, 7, 14 and 28. National Guidelines for Rabies Prophylaxis and Intra-dermal Administration of Cell Culture Rabies Vaccines, 2007
    28. 28. National Guidelines for Rabies Prophylaxis and Intradermal Administration of Cell Culture Rabies Vaccines Intra-dermal (ID) Regimens General guidelines for use of IDRV  Vaccines to be applied by intra-dermal route of administration should be approved by DCGI.  The vaccine package leaflet should include a statement indicating that the potency as well as immunogenicity and safety allow safe use of vaccine by ID pre- and post-exposure.  Post Marketing Surveillance (PMS) data should be maintained for minimum of two years by vaccine manufacturers on a pre-designed and approved protocol.  Intra-dermal injections must be administered by staff trained in this technique.  Vaccine vials must be stored at 2º to 8ºC after reconstitution.  The total content of reconstitute vial should be used as soon as possible, within 8 hours.  Rabies vaccines formulated with an adjuvant should not be administered intra-dermally.  Vaccine when given intra-dermally should raise a visible and palpable bleb in the skin.  In the event that the dose is inadvertently given subcutaneously or intra-muscularly or in the event of spillage, a new dose should be given intradermally in near by site.  Animal bite victims on chloroquine therapy (anti-malarial therapy) should be given ARV by intramuscular route. National Guidelines for Rabies Prophylaxis and Intra-dermal Administration of Cell Culture Rabies Vaccines, 2007
    29. 29. National Guidelines for Rabies Prophylaxis and Intradermal Administration of Cell Culture Rabies Vaccines DCGI approved ARV for use by intra-dermal route. • • • • PVRV – Verorab, Aventis Pasteur (Sanofi Pasteur) India Pvt. Ltd. PCECV – Rabipur, Chiron Behring Vaccines Pvt. Ltd. PVRV – Pasteur Institute of India, Coonoor PVRV – Abhayrab, Human Biologicals Institute. Regimen Updated Thai Red Cross Schedule (2-2-2-0-2). This involves injection of 0.1ml of reconstituted vaccine per ID site and on two such ID sites per visit (one on each deltoid area, an inch above the insertion of deltoid muscle) on days 0, 3, 7 and 28 (Note: A DCGI order dated 9th August 2006, has revised the eligibility criteria for intradermal administration of tissue culture rabies vaccines at anti- rabies clinics (ARC) in India from those with a minimum attendance of 50 patients per day to those with a minimum of 10 patients per day) National Guidelines for Rabies Prophylaxis and Intra-dermal Administration of Cell Culture Rabies Vaccines, 2007
    30. 30. Composition Composition: one vial of powder and diluent for solution, for one immunization dose (1 mL) contains: Active ingredient: – Rabies virus† (inactivated, Flury LEP strain ) potency ≥2.5 IU Other ingredients‡ – Powder: ◦ TRIS-(hydroxymethyl)-aminomethane ◦ Sodium chloride ◦ Disodium edetate (Titriplex III) ◦ Potassium-L-glutamate ◦ Polygeline † ◦ Sucrose Produced on purified chick embryo cells; ‡May contain traces of neomycin, – Diluent: chlortetracycline, amphotericin B, and chicken proteins ◦ Water for injection 30 Rabipur SmPC 2007 LEP: Low egg passage
    31. 31. Clinical database since 1981 More than 90 completed clinical trials – More than 30 pre-exposure trials – More than 50 post-exposure trials – 7 booster trials – 8 efficacy trials Total: ~6000 subjects vaccinated 31 Rabipur Product Monograph 2008
    32. 32. PCECV Immunogenicity (Essen regimen) 100 GMC (IU/mL) Adults administered IM rabies vaccine on Days 0, 3, 7, 14, 30, and 90† – Rabipur 1.0 mL (n=15) PCECV demonstrated consistent and high antibody concentrations using the standard WHO IM regimen Adverse reactions were mainly mild (31.2% systemic reactions, 56.5% local reactions) 10 1 ‡ 0.1 0 7 Scheiermann 1987 30 90 Time following immunization (days) Current Essen regimen administration is Days 0, 3, 7, 14, and 28 ‡ 0.5 IU/mL † 33 14
    33. 33. Efficacy studies (IM) No. of Study subjects (total) No. of subjects bitten by proven rabid animals Schedule/ vaccination day No. of subjects Follow-up who received period RIG (months) Survival rate after bite by proven rabid animal (%) 1 45 45 IM (Essen)† 6 dose 45 (HRIG) >12 100 2 28 28 IM (Essen)† 6 dose 28 (HRIG) >6 100 3 21 21 IM (Essen)† 6 dose 4 (HRIG) 4 56 56 IM (Essen)† 6 dose 41 (ERIG) 19-34 100 5 1252 145 IM 2-6 dose no RIG >12 100 15 100 100% survival rate of subjects after exposure to laboratory-confirmed rabid animals Current Essen regimen administration is Days 0, 3, 7, 14, and 28 † 34 References on note page
    34. 34. Immunogenicity following the Thai Red Cross ID regimen 36 Briggs 2000 100 GMC (IU/mL) Adults who had received WHO Category II and III wounds administered ID rabies vaccine on Days 0, 3, and 7 (two sites) and Days 30 and 90 (one site) – PCECV 0.1 mL – PVRV 0.1 mL Rabipur is welltolerated and immunogenic when following the Thai Red Cross ID regimen PCECV PVRV 10 1 † 0.1 0 7 14 30 90 Time following immunization (days) † 0.5 IU/mL
    35. 35. Efficacy studies (ID) No. of subjects Category No. of Vaccination No. of Followexposed to of Study subjects schedule subjects who up period proven contact (total) received RIG (months) rabid animals Survival rate (%) 1 148 148 I, II, or III ID 2-site (TRC) <3% (ERIG) ≥12 100 2 113 113 III ID 2-site (TRC) 113 (HRIG/ERIG) ≥12 100 3 32 32 III ID 8-site 12 (HRIG) 10 (ERIG) 36 100 100% survival rate of subjects after exposure to laboratory-confirmed rabid animals 37 References on note page † All subjects received PCECV
    36. 36. Post-marketing Surveillance Study 38 Sehgal 1995 10 Subjects reporting adverse events (%) In a post-marketing surveillance study (n=1252) with PCECV – 4.0% reported adverse events, all were mild-tomoderate Occurred mainly after Dose 1 or 2 but resolved spontaneously within 48 hours Mild fever was the most common systemic adverse event, reported by 0.5% of individuals 8 6 4 2.1% 1.1% 2 0 Injection-site pain Injection-site induration
    37. 37. Section 6 Summary
    38. 38. Summary - I Rabies is a viral zoonosis that is transmitted from animals to humans – Human infection usually occurs as a result of a transdermal bite or scratch from an infected animal Dogs are the principal vector causing transmission of rabies to humans in Africa, Asia, and parts of Latin America There are no immediate clinical symptoms following exposure to rabies virus Rabies is almost invariably fatal following the onset of clinical symptoms Rabies is present throughout the world and >3 billion people are at risk of infection in >100 countries – The WHO estimates that the annual number of human rabies deaths worldwide is ~55,000, and most occur in Asia and Africa 40
    39. 39. Summary - II There are two active immunization strategies available to prevent rabies in humans: – Pre-exposure vaccination protects against potential exposure to rabies particularly vulnerable children, individuals who live in or travel to high-risk areas or work in high-risk occupations – Post-exposure prophylaxis (PEP) is administered following contact with a suspected or confirmed rabid animal. The WHO and CDC provide guidelines for both strategies PCECV is a purified chick embryo cell-culture rabies vaccine which provides active immunization and protection Approved by the US FDA (intramuscular regimen only) Recommended for each and every established WHO vaccination schedule where intradermal vaccination licensed† Intradermal administration is currently licensed in India, Myanmar, the Philippines, Sri Lanka, Thailand, and Vietnam; regulatory approval will continue to be adapted for other countries † 41
    40. 40. Summary - III PCECV has been available for post-exposure and preexposure prophylaxis since 1984 The immunogenicity, efficacy, and safety profiles of PCECV are well established and have been evaluated in >90 clinical trials worldwide 42

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