1. Charles Gardner, MD, CCFP, MHSc, FRCPC May 8 th, 2015 Orillia Soldiers Memorial Hospital

2. ACKNOWLEDGEMENTS Dr. Dean Middleton Veterinarian and Senior Public Health Epidemiologist, Enteric, Zoonotic and Vector-Borne Diseases Unit, Public Health Ontario Dr. Catherine Filejski Public Health Veterinarian Enteric and Zoonotic Diseases Unit Ontario Ministry of Health and Long Term Care

3. OBJECTIVES By the end of this presentation the participants will have an understanding of:  The nature and the epidemiology of rabies as a zoonotic disease, internationally and in Ontario;  The overall control measures for rabies in Ontario;  The management of patients presenting with an animal exposure of concern – including more recent protocol changes;  The management supports provided by the SMD Health Unit.

4. CLINICAL SCENARIOS Case 1: Facial Bite by Dog in Guatemala  Dog unavailable  Dog known to be vaccinated  Victim previously immunized 5 years ago Case 2: Bat Found in Bedroom  Husband awoke to something touching him, he grabbed bat and threw it across room  Wife reports not being touched by bat  Bat killed… awaiting testing for rabies

5. RABIES VIROLOGY Zoonotic disease of mammalian species – humans are incidental hosts RNA virus  Single strand, negative-sense  Rhabdoviridae family, genus Lyssavirus Most severe acute viral infection of humans, with a case fatality rate of almost 100%. Transmitted by percutaneous or mucous membrane exposure to infected saliva – a bite, scratch, (organ transplants) Migration of virus to CNS via the peripheral nerves - encephalomyelitis

6. RABIES TRANSMISSION CHARACTERISTICS Likelihood of transmission post bite of a rabid animal is 15% (up to 60% with deep wounds) without rabies post exposure prophylaxis Completely prevented with timely vaccination – pre or post exposure  failure rates (with a delay or breach in protocol) range from 1 in 80,000 in developed countries to 1 in 12,000 in developing countries Incubation period 3 to 8 weeks after exposure – can range from a few days to several years  Depends on wound severity, innervation of location, distance from CNS Period of communicability  Only known reliably for dogs, cats, ferrets 3-7 days before onset of clinical signs  Longer in other species (skunks, bats)

7. INTERNATIONAL AND HISTORICAL EPIDEMIOLOGY History of significant burden of illness in humans in western society  100 human cases per year in the USA, early 1900’s Control measures succeeding in Ontario / Canada human cases of canine rabies in Canada and the United States dramatically declined in the 1950s with dog vaccination  bat-variant virus recently has become the dominant cause of rabies in humans Continued heavy disease burden in developing countries  55,000 human cases / year globally  Would be much greater (est. of 327,000 annually) without post- exposure prophylactic vaccination – 15 million prophylaxed annually  WHO reports more deaths than from dengue fever, polio, meningococcal meningitis or Japanese encephalitis.

8. HUMAN CASES IN CANADA / ONTARIO In Canada, 9 human cases occurred between 1960 and 2009 (NACI, 2012). In Ontario, 1 human case occurred in 2012 that was acquired while travelling outside of Canada The last case of human rabies that was acquired in Ontario occurred in 1967. Historically, skunks, foxes and raccoons are the main reservoirs in Ontario. Arrival from northern Ontario in the 1950’s In Ontario, bats currently pose the biggest threat of transmitting the virus to humans. Dog exposures are the greatest risk for returning travelers – other mammalian species also a risk Source: Based on PHO Grand Rounds, Tuesday April 21, 2015

9. HUMAN RABIES INDIGENOUSLY TRANSMITTED IN THE US AND CANADA: TRANSITION BAT SOURCE Source: Bat Rabies in the US and Canada. CID 2008 (46)

10. TRANSITION TO BAT RABIES

11. AGENT AGENT HOST ENVIRONMENT CONTROL STRATEGIES FOR RABIES

12. RABIES CONTROL STRATEGIES In Ontario, four main strategies have been used to prevent rabies cases in humans: 1. Public Health messaging informing people to avoid contact with wild animals. 2. Wildlife rabies control programs targeting skunks, raccoons and foxes. (note: no program for bat rabies) 3. Vaccinating bridge vectors such as dogs, cats, other pets, and farm animals. 4. Human Rabies Post-Exposure Prophylaxis (RPEP), and Pre- Exposure Prophylaxis Source: PHO Grand Rounds, Tuesday April 21, 2015

13. MANY PARTNERS TO CONTROL RABIES CFIA OMAFRA SMDHU Other Health Units Primary Care Providers Animal Control MOHLTC PHO MOHLTC PHO Humane Society Municipalities OAVT Veterinarians Police MNR Hospitals/ ER Rooms

14. WILDLIFE RABIES CONTROL Wildlife rabies control programs targeting skunks, raccoons and foxes. 1. Oral Vaccination via aerial baiting 2. Point Infection Control (PIC)  Different aspects of the program have been implemented annually since 1989. Source: PHO Grand Rounds, Tuesday April 21, 2015

15. HISTORIC MIGRATION OF RACCOON RABIES IN THE USA (SOURCE CDC WEBSITE)

16. RACCOON RABIES WOULD INCREASE HUMAN EXPOSURES Raccoons are very common (including in cities):  greater than 100 raccoons / km 2 in urban areas RPEP increased 20 X in NY State when raccoon rabies arrived after 1990

18. ORAL BAITING PROGRAM IN 2003

19. CURRENT ONTARIO WILDLIFE RABIES VACCINATION PROGRAM Niagara rabies bating St. Lawrence River rabies bating

20. PublicHealthOntario.ca Animal rabies cases, RPEP administered and RPEP rate: Ontario ParameterMeanMedianLowHigh Annual number of animal rabies cases 2001-2012968926210 Annual number of RPEP administered 2001-2012 (only due to exposures in Ontario 2007-2012 data) 1,774 (1,758) 1,659 (1,588) 1,426 (1,352) 2,692 (2,544) Annual rate of RPEP administered per 100,000 persons 2001-2012 (only due to exposures in Ontario 2007-2012 data) 13.9 (13.4) 13.1 (11.9) 11.1 (10.1) 20.8 (19.7)

21. SURVEILLANCE IN SIMCOE MUSKOKA InvestigationsVaccineReleases Positive Animals SMDHU Positive Animals Ontario 2011884530 24 bats 1 bovine 1 striped skunk 2012972410 24 bats 1 dog 1 cat 1 skunk 2013932620 27 bats 1 dog 20141097850 18 bats

22. PublicHealthOntario.ca Animal Rabies Cases and RPEP Data, Ontario, 1958–2012 22 All RPEP administered using human diploid vaccine Includes bat found in room when a person was sleeping unattended Ref. for 1958-2000 data: Postexposure Treatment and Animal Rabies, Ontario, 1958-2000. Nunan et.al. Emerging Infectious Diseases, 2002. Number of RPEP and animal rabies cases Last human rabies case acquired in Ontario MNR wildlife control

23. PublicHealthOntario.ca Annual number of RPEP administered for exposures to bats that occurred within Ontario (domestic) and annual number of rabid bats, 2007–2012 23

24. RABIES POST-EXPOSURE MANAGEMENT APPROACH 1. Wound care – irrigation (15 minutes), tetanus prophylaxis and antibiotics as appropriate, delayed wound closure 2. Report animal bites to local Public Health (requirement of the HPPA).  Public health staff role includes assessing human exposures to animals to advise on the need for RPEP. Dogs, cats and ferrets may be observed for 10 days post- exposure. Testing of animals (wild or ill domestic) 3. A course of four rabies vaccines as well as rabies immune globulin (RIG). Decision based on risk assessment – Canadian Immunization Guidelines, and the Guidance Document for the Management of Suspected Rabies Exposures (Public Health Division, MOHLTC 2013) Source: PHO Grand Rounds, Tuesday April 21, 2015

25. EXPOSURE INDICATIONS FOR VACCINATION Species and local prevalence of rabies (exposing animal and in other species) The type of exposure - bite, non-bite (e.g. salivary contact with open skin or mucous membrane, transplant of infected organs), or direct contact with a bat. Provoked versus unprovoked bite (not helpful for wild animals) The vaccination status and behaviour of a domestic animal. The age of the exposed person (children higher risk) The location and severity of the bite ( hands and face) Source animal for observation (cats, dogs, ferrets) or testing Resources  Table 1: Risk Assessment Related to the Exposure to the Potentially Rabid Animal – Canadian Immunization Guide  Table 1: Summary of Post-Exposure Prophylaxis (PEP) for Persons Potentially Exposed to Rabies - Guidance Document for the Management of Suspected Rabies Exposures, MOHLTC

26. EXPOSURE RISK RECOMMENDATIONS: BATS Current bat exposure recommendation: Post-exposure rabies prophylaxis following bat contact is recommended when:  There has been direct contact with a bat (touching or landing on a person), AND  A bite, scratch, or saliva exposure into a wound or mucous membrane cannot be ruled out. Revision of NACI recommendation from 1998 to 2009, that people who may not be aware of or able to report a bat bite (e.g., sleeping person, young child, cognitively impaired) receive vaccination :  expected to prevent a case in Canada once every 84 years  314,000 people would need to be treated (cost of $2 billion) to prevent 1 case  therefore revised recommendation in 2009

27. HISTORY OF CHANGES IN POST EXPOSURE PROPHYLAXIS Number of doses of rabies vaccine has declined over time with its increase in potency Reduction from a standard of 5 doses to 4 in 2010, bases on NACI and ACIP review, with the following rationale:  Protection is needed rapidly to prevent viral entry to CNS (therefore need RIG at the wound site)  Animal models of serological response and protection from rabies  Human immunogenicity studies with antibodies detected 14 days post vaccine initiation  No human cases attributed to failure to receive a fifth dose Source: MMWR, 19 Mar, 2010

28. POST-EXPOSURE PROPHYLAXIS PROTOCOL: RABIES VACCINE  Rabies vaccines (Rab) Human Diploid Cell Rabies Vaccine). (HDCV) IMOVAX ® Rabies Purified Chick Embryo Cell Rabies Vaccine), (PCECV) RabAvert ®  Not Previously Immunized Immunocompetent –4 doses (Day 0, 3, 7, 14) – 1 ml IM (never gluteal, as risking reduced immune response) Immunocompromised (including corticosteroids, chloroquine) –5 doses (Day 0, 3, 7, 14, 28) – 1 ml IM  Previously immunized 2 doses – 1 ml IM (Day 0, 3)

29. POST-EXPOSURE PROPHYLAXIS PROTOCOL: RABIES IMMUNE GLOBULIN Post Exposure Prophylaxis  Not Previously Immunized To achieve prompt levels of neutralizing antibodies in the wound during the initial phase of management 20 IU/kg - Day 0 (can be up to 7 days post onset of PEP series, if not immediately available) If possible, entire volume to be given at the wound site(s) – remainder IM (away from first dose of rabies vaccine)  Previously Immunized - not indicated

30. PRE-EXPOSURE PROPHYLAXIS E fficacy  Adequate antibody titres for up to 2 years after immunization – may wane after 7 days after a booster dose 100% are adequately protected Indications:  Laboratory workers who handle rabies virus.  Veterinarians, veterinary staff, animal control and wildlife workers. Refer to Workers.  Travelers to high risk locations – WHO (http://www.who.int/rabies/Global_Rabies_ITH_2008.png )http://www.who.int/rabies/Global_Rabies_ITH_2008.png  Hunter and trappers in areas with confirmed rabies.  Spelunkers (cavers). Rabies Vaccine  3 doses – 1 ml IM (days 0, 7 and 21 or 28) Rabies Immune Globulin  Not indicated

31. VACCINATION SAFETY HDCV risk is estimated to be minor;  Pain, erythema, swelling and itching at the injections site in 30% to 74%;  Headache, nausea, abdominal pain and dizziness in 20%.  Immune complex-like allergic reactions in up to 6% of persons receiving booster doses of HDCV. Few hospitalizations and no deaths.  Anaphylaxis in up to 1 in 10,000  In 2012 in Ontario, of the 9812 doses administered, there were 4 adverse events, none with serious outcomes (PHO) RIG  Local pain, erythema and induration are common. Headache and low-grade fever may follow administration.  Made from human plasma – potential risk of undetected infectious agents (CDC)

32. CONTRAINDICATIONS AND PRECAUTIONS No contraindications to the use of rabies vaccine or RIG after significant exposure to a proven rabid animal  Pregnancy not a contraindication for post exposure prophylaxis Caution re compartment syndrome with wound infiltration Seek expert consultation if hypersensitive to any ingredient in the formulation or container:  IMOVAX® Rabies: neomycin, phenol red  RabAvert®: amphotericin B, chick protein, chlortetracycline, neomycin, polygeline  (gelatin)  IMOGAM® Rabies: latex in vial stopper RIG:  Potential anaphylaxis with subsequent serum products for patients with specific IgA deficiency  Postpone live vaccinations 3 months afterward

33. Serologic testing is not routinely indicated with vaccination (pre or post exposure prophylaxis) for healthy persons Indications for serology testing:  Vaccination given by the ID route – check serology at least 2 weeks after completion of series.  Ongoing high risk of exposure to rabies (every 6 / 12 for continuous risk, to every 2 years for frequent risk).  Substantial deviation from the recommended post- exposure schedule – check serology 7 to 14 days after completing the series.  Immunization with a vaccine other than HDCV or PCECV – check serology at least 7 to 14 days after completing the series.  Immunocompromised persons, or if taking chloroquine - check serology 7 to 14 days after completing the series. Revaccination with a second rabies vaccine series if unacceptable response, followed by serologic testing POST VACCINATION SEROLOGIC TESTING

34. CLINICAL PRESENTATION OF HUMAN CASES Initially nonspecific:  fever, headache, and general weakness Progresses over days with specific signs and symptoms:  discomfort or pain at the exposure site  agitated (furious) presentation: insomnia, anxiety, confusion, excitation, hallucinations, agitation, hypersalivation (increase in saliva), difficulty swallowing, and hydrophobia (fear of water)  paralytic presentation: 30% of cases, more prolonged, progressive flaccid paralysis, piloerection and fasciculations, more difficult to diagnose  missed / diagnosed post mortem (11% of human cases in bat rabies between 1950 to 2007 in Canada and the US – organ transplant risk) Death within 1 to 2 weeks of the onset of symptoms

35. TREATMENT OF HUMAN CASES  7 well documented human rabies survival cases internationally  Most received rabies vaccination before onset of symptoms  Bat rabies less virulent  “Milwaukee protocol” N Engl J Med 352;24 June 16, 2005 15 yo female, bat induced laceration to hand, developed symptoms 1 month later ICU, treated with ketamine anesthesia, ribavirin, and amantadine, benzodiazepines and barbiturates, midazolam, aggressive management of hyperthermia Failure to reproduce results since then has resulted in it not being recommended

36. PUBLIC HEALTH MANDATE / SERVICES Animal Bite Investigation  Receive reports of all animal bites (1097 in 2014)  Animal Management Specimen testing (102 in 2013; 13 in 2014) Quarantine animal (dogs, cats, ferrets) –Normal 10 days –Follow up on animal vaccination Companion animal vaccination  Low cost vaccination clinics  Animal vaccination enforcement (HPPA) Vaccine consultation and provision (62 in 2013; 83 in 2014) Public and health care provider communication

37. HEALTH UNIT WEBSITE RESOURCES Main SMDHU website http://www.simcoemuskokahealth.org/ Home.aspx

38. HEALTH UNIT WEBSITE RESOURCES Main SMDHU website http://www.simcoemuskokahealth.org/ Home.aspx Primary Care Portal http://www.simcoemuskokahealth.org/JFY/PCPortal.aspx

39. HEALTH UNIT WEBSITE RESOURCES Environmental Health: Clinical Resources - Rabies Primary Care Portal http://www.simcoemuskokahealth.org/JFY/PCPortal.aspx

40. HEALTH UNIT WEBSITE RESOURCES Environmental Health: Clinical Resources - Rabies Environmental Health: Forms - Rabies

41. HOW TO CONTACT US Website resources – Primary Care Professionals’ Portal (Environmental Health)  http://www.simcoemuskokahealth.org/JFY/PCPortal.aspx http://www.simcoemuskokahealth.org/JFY/PCPortal.aspx Rabies email: rabies.program@smdhu.orgrabies.program@smdhu.org New Rabies Program Phone Line 705-721-7520 ext. 8894  For physician consult and vaccine release Animal exposure reporting  Rabies fax line 705-725-8132  Reporting form: http://www.simcoemuskokahealth.org/Libraries/JFY_Health_Care_Professio nals/150203Rabies_and_Animal_Exposure_Report_Form.sflb.ashx http://www.simcoemuskokahealth.org/Libraries/JFY_Health_Care_Professio nals/150203Rabies_and_Animal_Exposure_Report_Form.sflb.ashx

42. CLINICAL SCENARIOS REVISITED Case 1: Facial Bite by Dog in Guatemala  Dog unavailable  Dog known to be vaccinated  Victim previously immunized 5 years ago Case 2: Bat Found in Bedroom  Husband awoke to something touching him, he grabbed bat and threw it across room  Wife reports not being touched by bat  Bat killed… awaiting testing for rabies

43. FINAL THOUGHTS Rabies is a deadly zoonotic disease  Human rabies from dog and other animal exposures in returning travelers Rabies is presently rare in Ontario in domestic animals and wild species other than bats  Bat rabies remains a threat – changed risk assessment approach in 2008  Patient vaccination post exposure based on risk assessment, in consultation with Public Health In 2010 RPEP changed to 4 doses (with certain exceptions) with RIG SMD Health Unit provides consultation, rabies vaccine & RIG, follow up with animal exposures, and assistance with testing