Concordia University
Human Rabies in Public Health
Roxanne Evans
Class - MPH 500
Dr. Rebecca Toland
September 28, 2014
Running head: HUMAN RABIES RISKS, TREATMENT & PREVENTION
Rabies disease has been well intertwined with the human race as one of the first
described zoonotic diseases. Aristotle described rabies as early as the 4th century, he wrote
"Dogs suffer from madness that puts them in a state of fury, and all animals which they bite
when in this condition, become also attacked by madness (Lackenbach, 1912)." Rabies is an
ancient disease which attacks animal and humans alike. It can infect all mammals on earth
(Gomme, Wirblich, Addya, Rall, & Schnell, 2012).
It was stated by the Centers for Disease Control and Prevention (CDC) that “Rabies is
not, a disease of humans.” (Rabies around the World, 2011) Humans are typically an incidental
hosts of the virus. However, because of the high mortality rates caused by rabies when infected
and no cure of disease, there is a huge public health concern to try to prevent exposure and,
therefore, disease. Rabies is greater than 99% fatal with only few survivors known to date
(Kupferschidt, 2012).
Rabies is a Lyssavirus from the Rhadoviridae family. Other viruses of that family can
also cause diseases that are indistinguishable from rabies. (Institute for International Cooperation
in Animal Biologies, 2008) The rabies virus takes on a bullet appearance under an electron
microscope (Quinn, Markey, Cater, Donnelly,, & Leonard, 2002). This is a fitting shape for the
virus, since it needs to be pushes into tissue to be infectious to the host, much like the penetration
of a bullet from a gun.
All mammals on this planet are at risk of rabies infection. There is no animal that can
escape this disease. Rabies can be seen in at least one species of mammal on every continent of
the world (Rabies, 2014). It is typically spread by infected animals biting others, which
introduces the virus to the new host through saliva latent with bullet shaped virus. Here the virus
will locally reproduce in tissue for 1 to 4 days prior to making its way up the nervous system to
2
Running head: HUMAN RABIES RISKS, TREATMENT & PREVENTION
the brain. From bite to development of clinical symptoms can vary dramatically from 13 days to
2 years, with an average of 20 to 60 days. This is due to the location of the bite. The further from
the head, the longer the incubation period, conversely the closer to the head, like a bite on the
face, the quicker symptoms set in (Black, 2002).
Approximately 2.5 billion people across 100 different countries are at risk for contracting
rabies with the majority, 99%, of rabies infections occurring in tropical developing countries
(Haupt, 1999). India, for example, has an estimated 20,000 human fatalities from rabies, this
makes India one of the highest contributors to the global rabies mortality rate. The high
incidence of rabies in India is likely due to the high incidence of dog bites, roughly 17.4 million
annually. In India, the incidence rate of contracting rabies is roughly 2.74 per 100,000 people
annually (Baxter, 2012).
In countries that have a poorly developed public health systems, poorly funded health
departments, or poor individuals, the incidence of rabies seen in people increases dramatically
compared to the incidence of rabies seen in people of well-developed countries. For example, the
annual number of people that die from rabies annually is about 60,000 worldwide (Rabies around
the World, 2011). They are typically people who live in Asia and Africa (Rabies, 2014). This is
compared to only 4 deaths on average from rabies in the United Stated every year (Human
Rabies, 2012).
In developing countries, there are large populations of unvaccinated dogs or rabies naïve
dogs. This allows for dogs to be the primary source of rabies infections with approximately 90
percent of all human cases of rabies are caused by dog bites. In the U.S., for example,
transmission of rabies is most likely to occur from exposure to bats (Rabies Overview, 2014).
3
Running head: HUMAN RABIES RISKS, TREATMENT & PREVENTION
This can be largely due to the fact that there are state laws requiring rabies vaccination for dog
and cats and this will prevent spread of disease to humans (Southwell, 2014).
Children under the age of 15 years old are also a large majority of the victims bitten by
supected rabid animals. It is postulated that children have no fear of affected animal or don’t
know not to interact with them (McGrath, 2014).
Compared to other locations, like the United States which has an incidence rate of rabies
mortality approximately 0.001 per 100,000 people (Haupt, 1999). The country with the highest
incidence rate, from data in 1999, was Ethiopia, 18 per 100,000 people (Haupt, 1999). These
high incidence rates of rabies can be contributed to the lack of available vaccine for people,
either physical or financial, and the high populations of stray dogs in these poor countries. Lack
of education also plays a role, as well as poor hygiene, in the spread of the rabies virus (Rabies
Overview, 2014).
Travelers to endemic rabies countries also have a higher incidence of contracting the
disease than those traveling to rabies free countries. Countries like New Zealand, have never had
rabies in their country. It is also very possible for travelers to contract the virus in an endemic
area and not show symptoms until they are back in their home country, which may be rabies
free, as Carrara et al described in their 2013 review of imported rabies cases. They collected 60
cases of rabies where the individual likely contracted the disease in a different country. For
example, an individual in 2008 contracted rabies in India, but was diagnosed with the disease in
Ireland, which is a rabies free country (Carrara, Parola, Brouqui, & Gautret, 2013).
Rabies exposure is also higher among certain groups of individuals. For example, those
who have more exposure to wild or unvaccinated animals like veterinarians, lab workers,
4
Running head: HUMAN RABIES RISKS, TREATMENT & PREVENTION
travelers to underdeveloped or poor countries, and cavers (Rabies, 2014). In these populations
and other at risk populations of individuals, rabies virus vaccinations are suggested. However,
due to cost of vaccine, most people in poor countries, and even in the US, are unable to afford it
(Rabies around the World, 2011).
The first symptoms humans generally experience once infected with rabies are headache,
nausea, fever, and partial paralysis near the bite site. This can rapidly progress over the next 2
to 10 days to uncoordinated steps, hydrophobia, aerophobia, complete paralysis, coma and death.
Hydrophobia typically develops because of spasms of the throat which cause pain upon
swallowing. Aerophobia, or fear of moving air, is due to increased hypersensitivity caused by the
virus and pain felt by the skin (Black, 2002).
Due to the variable incubation period, of less than 1 week to greater than 1 year, travelers
are able to return home before knowing they might be sick (Rabies, 2014). In addition, rabies
clinical symptoms can be difficult to recognize if an indivual is not educated about the syptoms.
Though finding the exact number of misdiagnosed cases of rabies is impossible, the fact remains
they exsist. A recent example would be of a Maryland man who received a kidney trasplant from
a 20 year old man who died of an unknown encepalitis in 2011. The Maryland man contracted
rabies from his new kidney and also died of the disease. Suspected exposure is not listed for the
donor (Cohen & Bonifield, 2013).
Rabies virus can show two forms seen in infected humans, the furious form and the
paralytic form. The furious form of rabies typically causes hypersensitivity, agitation,
hydrophobia and aerophobia, and cause of death is usually cardio-respiratory arrest (Rabies,
2014). The paralytic form of rabies is described as a slow progressive muscle paralysis leading to
coma and death.
5
Running head: HUMAN RABIES RISKS, TREATMENT & PREVENTION
According to the WHO, approximately 30% of all human rabies case are the paralytic
form. This is form of rabies is also the most likely to be missed diagnosed for an unknown
encephalitis in absence of a known animal bite (Rabies, 2014). It's also been documented that
rabies has been transmitted through organ donation of individual who have died of unknown
encephalopathy (Carrara, Parola, Brouqui, & Gautret, 2013).
Diagnosis of rabies can be very difficult, especially if there is no record of an animal
bite. Currently, there is no test to confirm rabies infection prior to the individual displaying
clinical symptoms (Rabies, 2014). In animals, anti-mortem diagnostics are rarely done. Instead
they are typically place in quarantine and monitored for continuing clinical symptoms. If rabies
is strongly suspected, the animal may be euthanized for further testing rather than waiting for
animal death (Institute for International Cooperation in Animal Biologies, 2008).
In the US, quarantining pets, like cats and dogs, for rabies is often mandated by law. Each
state have individual timelines and protocols to follow if there has been an animal bite from a cat
or dog to a human or other animal, or if the pet has an animal bite or wound of unknown origin
(Administration of Rabies Vaccination State Laws, 2014). In some situations, these quarantines
can be done at home rather than at a veterinary or state facility. If an animal dies while in
quarantine, then it is to be immediately sent for rabies testing in order to aid in the prevention of
disease in the humans that have come in contact with the suspected rabid animal (Administration
of Rabies Vaccination State Laws, 2014).
Once deceased, the animals brain is submitted for further testing. This is done by direct
fluorescent antibody test (FAT) on brain tissue, which yields rapid and specific results (Quinn,
Markey, Cater, Donnelly,, & Leonard, 2002). However, it can have false negatives if the tissue
has started to undergo normal post-mortem changes like autolysis, which is a break down and
6
Running head: HUMAN RABIES RISKS, TREATMENT & PREVENTION
death of individual cells. Therefore, proper handling of deceased animals who will be tested for
rabies is essential for making a correct diagnosis (Gomme, Wirblich, Addya, Rall, & Schnell,
2012). In warm climates, where animals are unlike to be stored in refrigeration it is necessary to
have animals tested quickly after death to provide appropriate treatment to the humans exposed
(Quinn, Markey, Cater, Donnelly,, & Leonard, 2002).
Unfortunately, only once clinical signs are present in people or animals can diagnosis of
rabies can be confirmed using spinal fluid, brain tissue or saliva (Rabies, 2014). Sadly, at this
stage of disease there is no effective treatment established (Human Rabies, 2012).
Treatment of rabies virus, prior to the onset of clinical symptoms, is post-exposure
prophylaxis (PEP) with the current rabies vaccine. The World Health Organization (WHO)
details circumstances in which this method of treatment should be initiated. These situations are
broken up into three categories of contact with rabid animals. Category I involves touching or
feeding animals, where saliva gets on intact skin. In this situation there is no need to place the
animal under quarantine or initiate PEP. Just provide good hygiene and washing with soap to the
area contaminated with saliva (Rabies, 2014).
Category II is described as saliva being present on broken skin or obtaining minor
scratches or abrasions that don’t bleed, and the nibbling of uncovered skin. Category III is where
rabid animal inflicts a single or multiple transdermal bite or scratch to an individual, or if there is
any saliva contamination with a mucous membrane. IN addition to category III is any exposure
to bats' bite or scratches. In these situations of category II and III PEP should be instituted
immediately, along with proper hygiene and washing. PEP consists of intramuscular injections
with rabies vaccinations given in 4 to 5 doses over four weeks. If the victim has received proper
pre-exposure vaccination or previously had a full post-exposure protocol, then the current
7
Running head: HUMAN RABIES RISKS, TREATMENT & PREVENTION
recommendations are for them to have two intramuscular vaccines given over a three day period
(Rabies, 2014).
There are two current protocols to follow for PEP. The 28 day vaccine schedule for postexposure of an rabies naive individual is that they receive an intramuscular vaccine in their
deltoid muscle on days 0, 3, 7, 14, and 30 according to WHO protocol. The abbreviated multisite
schedule of rabies naïve individuals are that they receive vaccines in both, left and right, deltoid
muscles on day 0. Then one dose is given on days 7 and 21. This protocol induces early antibody
response and is thought to be more effective if there is no rabies immunoglobulin administration
give (Rabies, 2014).
Post-exposure prophylaxis has the highest rate of use in children between the ages of 5
and 14 years old, approximately 40 % worldwide (Rabies, 2014). The WHO also reports that the
majority of these children are male. Children are likely at higher risk due to lack of fear and
increased curiosity (Rabies, 2014).
Once clinical symptoms set in, it is recommended not to start PEP. Thus all that can
typically be done is supportive care during the encephalitis stage of diseases. Rabies is
approximately 100% fatal once clinical symptoms set it (Jackson, et al., 2003).
Since children make oup the largest portion of vicitms of rabies, education of children
and adults in all countries regarding how rabies is spread and what can be done to avoid
exposure would drastically reduce the number of individuals exposed to the rabies virus.
Additionally, eduacation on wound care after a bite of scratch from an animal, would also
dramatically reduce the the likelihood of disease in people not able to reviece post-exposure
vaccination (Rabies, 2014).
8
Running head: HUMAN RABIES RISKS, TREATMENT & PREVENTION
The Global Alliance for Rabies Control is tying to improve rabies education in poor
countries, where post exposure vaccination is financially unavailable. In these areas dogs are the
most likely source of infections to humans. There are also programs trying to vaccinate dogs for
the rabies virus in hopes of preventing disease in humans as has been done in the United States.
(Rabies' Victims, 2014).
In the United States, rabies exposure is most commonlly from wild animals, such as
foxes, skunks, raccoons, and, predominantly, bats (Rabies around the World, 2011). This has
changed from dogs and cats because of state laws requiring rabies vaccinations of all dogs and
cats (Administration of Rabies Vaccination State Laws, 2014). This creates protection to the
greater population of humans across the country since pets are more likely to interact with wild
animals and be exposed to rabies. In this sense, people of the US are relying on herd immunity
created from our pets (Schneider, 2014).
For those individuals who are at higher risk of contracting rabies, veterinarians, cavers,
and travelers to poor countries with high stray dog populations, pre-exposure vaccinations are
strongly recommended (Gibbons, Holman, Mosberg, & Rupprecht, 2002). However, even in the
United States cost of human rabies vaccination is expensive and often not covered by insurance
which limits the number of at-risk people who are protected (Trevejo, 2000).
Pre-exposure vaccination is also a series of vaccinations that are given on days 0, 7, and
21 or 28. The vaccines are intramuscular, in the deltoid muscle, with either the human diploid
cell vaccine or the purified chick embryo cell vaccine. Once vaccinated, high risk individuals
should be evaluated for antibody production and antibody presence to rabies every 6 months
9
Running head: HUMAN RABIES RISKS, TREATMENT & PREVENTION
according to the CDC. Titers that fall below complete neutralization in serum of 1:5 then
revaccination or boostering should be done (Rabies around the World, 2011).
If pre-exposure vaccination were more affordable, more individual who were at high risk
for contracting the virus would choose to be vaccinated. This may then reduce the number of
post-exposure prophylaxis required and lower the financial burden on insurance companies
(Vaidya, et al., 2010). In addition, even without the accessability of PEP to preveiously
vaccinated individuals, it may drastically reduce the number of human fatalities to rabies around
the world. Annually, approximately 29 million people receive the post-exposure prophylaxsis
treatment for rabies exposure, which costs an estimated 2.1 billion US dollars (Rabies, 2014).
Currently, the CDC rabies program raises money and helps organize vaccination
programs for dogs in rabies endemic areas. They also use funds to help pay for post-exposure
prophylaxis when people are exsposed and unable to afford treatment. Lastly, they eduate
children about the risk of rabies and how to protect themselves from contracting the virus
(Rabies Prevention in Developing Countries, 2014).
Education should also include the communities in rural or poor countries regarding ways
to protect dogs from contracting the virus. This would include preventing stray animals from
being on their property and keeping their own animals and children supravised when outside
(Haupt, 1999).
Another preventative program that could be initiated in poor or underdeveloped countries
could be oral rabies vaccine bait. This technique has been done in several places in the United
States where raccoons and coyotes pose a huge threat to the spread of rabies. It would be
possible to develop oral rabies vaccine bait suitible for dogs that could be air dropped in poor
10
Running head: HUMAN RABIES RISKS, TREATMENT & PREVENTION
regions that are endemic with disease. This process of vaccination is not as labor intensive as
injectable vaccines and do not require special refrigeration (Raboral V-RG, 2014).
Eradication efforts for the rabies virus have been successful in some countries like Japan.
This was effective due to the governement organizing mass vaccination for dogs of the country
(Watanabe, et al., 2013). This would likely not work in many remote regions of Africa for two
main reasons. One, there are extensively remote areas of the contries population preventing
accessability to receive the vaccine for their pets. And two, the coutry is unlikely to spend
resources on vaccination for rabies while famine are sweaping their nation (Food Crisis, 2014).
Rabies is 100% preventable (Rabies around the World, 2011). It is important for
governments to involved in dissemination of information and vaccination to those at risk. If other
contries were able to disseminate dog vaccination, which is drastically cheaper than human
vaccination, creating herd immunity in rurual and poor areas, there could be a striking drop in the
number of human deaths from rabies around the world. It might even mirror the US where there
are, on average, a couple of deaths from rabies annually (Rabies, 2014).
11
Running head: HUMAN RABIES RISKS, TREATMENT & PREVENTION
References
Administration of Rabies Vaccination State Laws. (2014, August). Retrieved from American Veterinary
Medical Association: https://www.avma.org/Advocacy/StateAndLocal/Pages/rabiesvaccination.aspx
Baxter, J. M. (2012, June). One in a million, or one in thousand: What is the morbidity of rabies in India?
Journal of Global Health, 2(1), 010303. doi:10.7189/jogh.02.010303
Black, J. G. (2002). Microbiology; Principles and Explorations (5th ed.). New York, New York: John Wiley
& Sons.
Carrara, P., Parola, P., Brouqui, P., & Gautret, P. (2013, May 2). Imported Human Rabies Cases
Worldwide, 1990-2012. PLOS Medicine Journal. doi:10.1371/journal.pntd.0002209
Cohen, E., & Bonifield, J. (2013, March 15). CDC: Man died of rabies from kidney transplant. Retrieved
from CNN.com: http://www.cnn.com/2013/03/15/health/organ-transplant-rabies-death/
Food Crisis. (2014). Retrieved from Unicef - United States Fund:
http://www.unicefusa.org/mission/emergencies/food-crises/horn-africa-famine
Gibbons, R. V., Holman, R. C., Mosberg, S. R., & Rupprecht, C. E. (2002, May). Knowledge of Bat Rabies
and Human Exposure Among United States Cavers. Emerging Infectious Disease, 8(5), 532-534.
doi:10.3201/eid0805.010290
Gomme, E. A., Wirblich, C., Addya, S., Rall, G. F., & Schnell, M. J. (2012, October 11). Immune Clearance
of Attenuated Rabies Virus Results in Neuronal Survival with Altered Gene Expression. PLOS
Pathogens, 8(10), e1002971. doi:0.1371/journal.ppat.1002971
Haupt, W. (1999, March 26). Rabies - risk of exposure and current trends in prevention of human cases.
Vaccine, 17(13-14), 1742-9. doi:10.1016/s0264-410x(98)00447-2
Human Rabies. (2012, May 3). Retrieved from Centers for Disease Control and Prevention:
http://www.cdc.gov/rabies/location/usa/surveillance/human_rabies.html
Institute for International Cooperation in Animal Biologies. (2008). Emerging and Exotic Diseases of
Animals (3rd ed.). (A. R. Sprickler, & J. A. Roth, Eds.) Ames, Iowa: Institute for International
Cooperation in Animal Biologies.
Jackson, A. C., Warrell, M. J., Rupprecht, C. E., Ertl, H. C., Dietzschold, B., O'Reilly, M., . . . Wilde, H. (2003,
January 1). Management of Rabies in Humans. Clinical Infectious Disease, 36(1), 60-63.
Retrieved from http://cid.oxfordjournals.org/content/36/1.toc
Kupferschidt, K. (2012, August 1). Some Rabies Patients Live to Tell the Tale. Retrieved from Science
News Magazine: http://news.sciencemag.org/2012/08/some-rabies-patients-live-tell-tale
12
Running head: HUMAN RABIES RISKS, TREATMENT & PREVENTION
Lackenbach, F. I. (1912, March). Rabies and the Pasteur Treatment. California State Journal of Medicine,
10(3), 123-124. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1893649/
McGrath, M. (2014, May 26). Experts' anger over 'invisible' rabies death toll. Retrieved from BBC News:
http://www.bbc.com/news/science-environment-27538721
Quinn, P., Markey, B., Cater, M., D. W., & Leonard, F. (2002). Veterinary Microbiology and Microbial
Disease. Ames, Iowa: Blackwell.
Rabies. (2014). Retrieved from World Health Organization:
http://www.who.int/mediacentre/factsheets/fs099/en/
Rabies around the World. (2011, April 22). Retrieved from Centers for Disease Control and Prevention:
http://www.cdc.gov/rabies/location/world/index.html?s_cid=cs_521
Rabies Overview. (2014, September 9). Retrieved from UpToDate:
http://www.uptodate.com/contents/rabies-beyond-the-basics
Rabies Prevention in Developing Countries. (2014). Retrieved from CDC Foundation:
http://www.cdcfoundation.org/rabies
Rabies' Victims. (2014). Retrieved from Global Alliance for Rabies Control:
http://rabiesalliance.org/rabies/rabies-and-children/
Raboral V-RG. (2014). Retrieved from Raboral: http://www.raboral.com/Pages/index.aspx
Schneider, M.-J. (2014). Introduction to Public Health (4th ed.). Burlington, Massachusetts: Jones &
Bartlett Learning.
Southwell, T. (2014, August). Administration of Rabies Vaccination State Laws. Retrieved from American
Veterinary Medical Association: https://www.avma.org/Advocacy/StateAndLocal/Pages/rabiesvaccination.aspx
Trevejo, R. (2000, December 1). Rabies preexposure vaccination among veterinarians and at-risk staff.
Journal of American Veterinary Medical Association, 217(11), 1647-1650. Retrieved from
https://www.avma.org/News/Journals/Collections/Documents/javma_217_11_1647.pdf
Vaidya, S. A., Manning, S. E., Dhankhar, P., Meltzer, M. I., Rupprecht, C., Hull, H. F., & Fishbein, D. B.
(2010). Estimating the risk of rabies transmission to humans in the U.S.: dephi analysis. BMC
Public Health, 10(278). doi:10.1186/1471-2458-10-278
Watanabe, I., Yamada, K., Aso, A., Suda, O., Matsumoto, T., Yahiro, T., . . . Nishizono, A. (2013).
Relationship between Virus-Neutralizing Antibody Levels and the Number of Rabies
Vaccinations: a Prospective Study of Dogs in Japan. Japan Journal of Infectious Disease, 66, 1721.
13