Human Rabies Post-Exposure Prophylaxis and Animal Rabies in Ontario,

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Human Rabies Post-Exposure Prophylaxis and Animal Rabies in Ontario, 2001 2012 PHO Grand Rounds Tuesday April 21, 2015 Dean Middleton Enteric, Zoonotic and Vector-Borne Diseases Unit

Outline Introduction Purpose of the Study Methods Results Discussion Conclusions MNRF stock photo 2

Human Rabies Post-Exposure Prophylaxis and Animal Rabies in Ontario, Canada, 2001 2012 D. Middleton 1,2, K.O. Johnson 1, R.C. Rosatte 3, J. L. Hobbs 1, S.R. Moore 1, L. Rosella 1,2, N.S. Crowcroft 1,2 1 Public Health Ontario, 480 University Avenue, Toronto, Ontario, Canada, M5G 1V2 2 Dalla Lana School of Public Health, University of Toronto, 155 College St., Health Sciences Building, 6th Floor, Toronto, Ontario, Canada, M5T 3M7 3 Ontario Ministry of Natural Resources, Trent University, DNA Building, 2140 East Bank Dr., Peterborough, Ontario, K9J 7B8 http://onlinelibrary.wiley.com/doi/10.1111/zph.12155/full Published September, 2014. 3

Introduction Rabies is caused by a group of antigenically related viruses in the genus Lyssavirus. Rabies affects mammals, including humans. Virus infects the neurologic system. Symptoms related to this. Once symptoms of rabies are exhibited in humans, the disease is almost always fatal. Transmission to humans is usually through saliva via the bite of an infected animal. Worldwide, an estimated 55,000 human deaths occur annually (Hemachuda et. al, 2008). 4

Introduction 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 Ontario. 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. In Ontario, bats currently pose the biggest threat of transmitting the virus to humans. 5

Introduction 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. 3. Vaccinating bridge vectors such as dogs, cats, other pets, and farm animals. 4. Human Rabies Post-Exposure Prophylaxis (RPEP). 6

Introduction 2. 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. MNRF stock photos 7

Introduction 4. Human Rabies Post-Exposure Prophylaxis (RPEP) 1. A course of four rabies vaccines as well as rabies immune globulin (RIG). 2. Public health staff have a role that includes assessing human exposures to animals to advise on the need for RPEP. a. Dogs, cats and ferrets may be observed for 10 days post-exposure. b. Other animals assessed by different criteria. 8

Costs Associated with RPEP Administration Vaccine (5-dose series) and rabies immune globulin for a 70 kg person was approximately $2,200 CAD (2011). Public Health staff time. A study in Quebec estimated $1,189 to $1,590 CAD per person for household bat exposures (Huot et al., 2008). These costs included: nurses, physicians and veterinarians time, obtaining the bats for testing, the cost of testing the bats, and excluded biologics. 9

Purpose of the Study To describe the relationship between the number of animal rabies cases and the number of RPEP administered in Ontario from 2001 2012. Further, to describe the relationship between various categories of animal rabies cases and the number of RPEP administered due to each of those animal categories respectively from 2007 2012. 10

Objective To evaluate whether the decrease in the number of animal rabies cases resulted in a decrease in the number of RPEP administered. MNRF stock photo 11

Study Design and Ethical Approval A retrospective, descriptive epidemiological study Ethical approval was not required to publish the findings for this analysis because this was considered a public health investigation under the Ontario Health Protection and Promotion Act (1990, R.S.O. 1990, c.h.7) (HPPA). 12

Methods Animal rabies cases are reportable under the Health of Animals Act (S.C. 1990, c. 21). 2001-2012 Animal Rabies Case Data Source Ontario Ministry of Natural Resources (from the Canadian Food Inspection Agency, Nepean) 13

Methods Exposures to animals that may result in rabies are reportable under the HPPA and in accordance with the Ontario Rabies Prevention and Control Protocol. RPEP Data Source 2001-2006 - Reports manually provided from Ontario health units Domestic vs. travel exposures could not be differentiated Animal type could not be differentiated 2007-2012 iphis (integrated Public Health Information System) exception for one health unit in 2007-2008 when data were provided manually 14

Categories of animals that resulted in RPEP being administered and animals diagnosed with rabies in Ontario Category Rabies Post-Exposure Prophylaxis Administered Due To: Animals Diagnosed with Rabies A. Animals for which the 10-day observation period applies Dogs, cats, ferrets. Dogs, cats. B. Farm Animals Cattle, horses, donkeys, sheep, Livestock. goats and other farm animals Bats Bats. Bats. Terrestrial Animals, excluding A and B Foxes, raccoons, skunks, wild ferrets, pet rabbits, squirrels, chipmunks and other terrestrial animals. Foxes, raccoons, skunks, other wildlife. Unknown Unknown. Not applicable. Missing Missing data. Not applicable. 15

Results MNR stock photo 16

Animal rabies cases, RPEP administered and RPEP rate: Ontario Parameter Mean Median Low High Annual number of animal rabies cases 2001-2012 96 89 26 210 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) 17

Number of RPEP and animal rabies cases RPEP rate per 100,000 persons Animal Rabies Cases and RPEP Data, Ontario, 2001 2012 3000 25.0 2500 20.0 2000 15.0 1500 10.0 1000 500 5.0 0 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 RPEP 1640 1728 1498 1426 1526 1988 2257 2692 1678 1542 1512 1806 Animal Rabies Cases 210 202 124 114 96 82 106 79 50 39 26 28 RPEP Rate/100,000 13.8 14.3 12.2 11.5 12.2 15.7 17.6 20.8 12.8 11.7 11.3 13.3 0.0 18

Number of RPEP and animal rabies cases Animal Rabies Cases and RPEP Data, Ontario, 1958 2012 4500 4000 3500 3000 All RPEP administered using human diploid vaccine Last human rabies case acquired in Ontario MNR wildlife control Includes bat found in room when a person was sleeping unattended 2500 2000 1500 1000 500 0 1958 1959 1961 1963 1965 1967 1969 1971 1973 1975 1977 1980 1982 1984 1986 1988 1990 1992 1994 1996 1998 2000 2002 2004 2006 2008 2010 2012 RPEP Animal Rabies Cases Ref. for 1958-2000 data: Postexposure Treatment and Animal Rabies, Ontario, 1958-2000. Nunan et.al. Emerging Infectious Diseases, 2002. 19

Number of RPEP and animal rabies cases RPEP rate per 100,000 persons RPEP administered for exposures that occurred within Ontario (i.e., domestic) and animal rabies cases, 2007 2012 3000 25.0 2500 20.0 2000 15.0 1500 10.0 1000 500 5.0 0 2007 2008 2009 2010 2011 2012 Domestic RPEP 2062 2544 1547 1412 1352 1629 Animal Rabies Cases 106 79 50 39 26 28 RPEP Rate/100,000 16.1 19.7 11.8 10.7 10.1 12.0 0.0 20

Number of RPEP and rabid animals Annual number of RPEP administered for exposures to animals for which the 10-day observation period applies that occurred within Ontario (domestic), and number of rabid animals for which the 10-day observation period applies 1400 1200 2008 - At least 377 RPEP resulted from exposure to a single rabid puppy and its littermates 1000 800 600 400 200 2007 2008 2009 2010 2011 2012 Domestic RPEP 742 1397 869 810 784 882 Rabid animals for which the 10-day observation period applies 0 2 5 0 0 0 2 21

Number of RPEP and rabid bats Annual number of RPEP administered for exposures to bats that occurred within Ontario (domestic) and annual number of rabid bats, 2007 2012 1200 Aug 7, 2008 - RPEP recommendations changed to 1000 Bat bite, scratch, or direct contact required. 800 600 400 200 0 2007 2008 2009 2010 2011 2012 Domestic RPEP for Bats 1130 880 396 357 316 463 Rabid Bats 62 38 30 29 24 25 22

Number of RPEP and rabid animals Annual number of RPEP administered for exposures to terrestrial animals that occurred within Ontario (domestic) and annual number of rabid terrestrial animals, 2007 2012 300 250 200 150 100 50 0 2007 2008 2009 2010 2011 2012 Domestic RPEP for Terrestrial Animals 233 213 254 225 245 250 Rabid Terrestrial Animals 30 27 11 10 1 1 Note: The category terrestrial animals excludes animals for which the 10-day observation period applies and farm animals, e.g., foxes raccoons, skunks. 23

Number of RPEP and rabid animals Annual number of RPEP administered for exposures to farm animals that occurred within Ontario (domestic) and annual number of rabid farm animals, 2007 2012 50 45 40 2008 1 rabid horse and 3 cattle combined for 29 RPEP 35 30 25 20 15 10 5 0 2007 2008 2009 2010 2011 2012 Domestic RPEP for Farm Animals 14 49 8 1 4 2 Number of Rabid Farm Animals 12 9 9 0 1 0 24

Discussion The annual number of animal rabies cases decreased steadily to unprecedented low numbers. The number of RPEP administered was stable over the study period. The decrease in animal rabies cases did not result in a decrease in the number of RPEP administered. 25

Animal Categories Difference between the number of RPEP administered and corresponding number of rabid animals 1. 10-day Observation group (dogs, cats, ferrets) (>740) 2. Bats (~1000 vs >300) 3. Terrestrial animals (not including 10-day and farm ) (>200) 4. Farm animals (40 max) 26

Wildlife Rabies Control Program 1. Wildlife rabies cases decrease due to vaccination 2. Companion and farm animals (bridge vectors) rabies infections decrease Both result in a decrease in the risk of rabies infections in humans. P.S. - The wildlife rabies control program has no effect on bat rabies. MNRF stock photo 27

Reason for Absence of RPEP Decrease 1980s - the annual number of animal rabies cases was most frequently > 2,000; following the RPEP recommendations verbatim likely served its purpose well in preventing human cases of rabies. 2001-2012 - strictly following the recommendations as they were written would result in RPEP administration that, more often than not, would not prevent a case of rabies. 2012 new Canadian Immunization Guide recommendations provide more flexibility with regard to risk assessment. 28

Canadian Immunization Guide 2012 Factors to Consider How prevalent is rabies in the species of animal involved in the exposure? In North America, rabies occurs mainly in bats, foxes, skunks, raccoons, stray dogs and cats. How prevalent is rabies in the involved species in the geographic area? Presently in Ontario, mainly bats. 29

Canadian Immunization Guide 2012 Factors to Consider Can a bite or saliva exposure into a scratch, wound or mucous membrane be ruled out? Rabies transmission occurs most commonly through a bite. transmission through scratches, wounds, or mucous membranes contaminated from saliva are rare. What were the circumstances of the exposure (e.g., provoked or unprovoked attack)? An unprovoked attack is more likely to indicate that the animal is rabid. 30

Number of RPEP and rabid bats Effect of RPEP Recommendations on RPEP Associated with Bat Exposures 1200 1000 Aug 7, 2008 - RPEP recommendations changed to Bat bite, scratch, or direct contact required. 800 600 400 200 0 2007 2008 2009 2010 2011 2012 Domestic RPEP for Bats 1130 880 396 357 316 463 Rabid Bats 62 38 30 29 24 25 31

Erring on the Side of Safety RPEP is a safe intervention compared with the almost certainty of death in an individual infected with, and exhibiting symptoms of, rabies. Reported positive animals only represent a fraction of the true number of positive animals. Rabid animals are identified in the USA close to the Ontario border. Bat rabies continues to be a threat. 32

Conclusions A decrease in the number of RPEP administered would provide some financial savings for the government. Ideally, an increased use of the risk assessment approach in keeping with recent guidelines, rather than adhering to previous prescriptive recommendations for RPEP administration, coupled with a continuing low incidence of animal rabies cases will result in decreased, and yet appropriate, use of RPEP. MNRF stock photo 33

Data Caveats iphis is a dynamic disease reporting system which allows ongoing updates to data previously entered. As a result, data extracted from iphis represent a snap shot at the time of extraction and may differ from previous or subsequent reports. The data were extracted from iphis on March 17, 2014. The data only represent cases reported to public health and recorded in iphis. As a result, all counts will be subject to varying degrees of underreporting due to a variety of factors, such as disease awareness, medical care seeking behaviours, reporting behaviours, clinical practice, and severity of illness. 34

Acknowledgements Staff in Ontario health units for providing the RPEP data. Bryna Warshawsky for reviewing the manuscript and presentation. Peter Bachmann and Bev Stevenson, Ontario Ministry of Natural Resources, for providing insights regarding animal rabies case data. Kenny Wong for cleaning the iphis RPEP data. Sarah Morgan and Rajitha Liyanage for their work managing references. 35

Human Rabies Post-Exposure Prophylaxis and Animal Rabies in Ontario, 2001 2012 PHO Grand Rounds Tuesday April 21, 2015 Dean Middleton Dean.Middleton@oahpp.ca Enteric, Zoonotic and Vector-Borne Diseases Unit

Number of RPEP and animal rabies cases Animal Rabies Cases and RPEP Data, Ontario, 1958 2012 4500 4000 3500 3000 All RPEP administered using human diploid vaccine Last human rabies case acquired in Ontario MNR wildlife control Includes bat found in room when a person was sleeping unattended 2500 2000 1500 1000 500 0 1958 1959 1961 1963 1965 1967 1969 1971 1973 1975 1977 1980 1982 1984 1986 1988 1990 1992 1994 1996 1998 2000 2002 2004 2006 2008 2010 2012 RPEP Animal Rabies Cases Ref. for 1958-2000 data: Postexposure Treatment and Animal Rabies, Ontario, 1958-2000. Nunan et.al. Emerging Infectious Diseases, 2002. 37