Rabies (ra’bez) n. from Latin rabere – to rage

 

by Camilla Heum

 

Introduction:

Rabies is a highly infectious viral disease that can easy ruin and eventually end the lives of both humans and animals. There are essentially two different forms of rabies in animals which are the paralytic, and the furious rabies. The paralytic rabies puts you in the paralysis right away, completely skipping the symptoms of agitation and excitability. The furious rabies differs in the way that it makes the victim restless, vicious and agitated. Rabies belongs to the genus Lyssavirus, family Rhabdoviridae of the order Mononegavirales. [4] The disease that have an effect on the brain and spinal cord. It is a preventable viral disease that affects all mammals, mostly transmitted through a bite of a rabid animal. “The vast majority of rabies cases reported to the Centers for Disease Control and Prevention (CDC) each year occur in wild animals like raccoons, skunks, bats, and foxes.” [1] The early most common symptoms are unfortunately similar to that of many other illnesses, including fever, headache, and general weakness or discomfort.  “Rabies is present on all continents with the exception of Antarctica, but more than 95% of human deaths occur in Asia and Africa.” [11] Once symptoms of the disease develop, rabies is nearly always fatal.

 

Transmission & Reservoirs:

The meaning of a zoonotic viral disease is that it transmits with the aid of animals. “All mammals alive are susceptible to the Rabies virus, however, only few are significant as reservoirs for the disease.” [1] Humans are exposed to rabies by bites from rabid wildlife such as raccoons, skunks, bats, foxes, or coyotes which are the most prone reservoirs. There is also probable infection from a dog that has previously been exposed. [2] “The rabies virus cannot pass through intact skin, but can only enter skin that is punctured or open.” [3] The most common source of the rabies virus in the United States originate from bats, but thanks to the vaccines we have today, the number of infected dogs have significantly decreased.

 

http://www.who-rabies-bulletin.org/about_rabies/Images/Virion.jpghttp://aeneary.myweb.uga.edu/rabies_files/image011.gif

Figure 1. Rabies Reservoirs in the United States.

 

General characteristics:

“Rabies virus is a rod- or bullet-shaped, single-stranded, negative-sense, unsegmented, enveloped RNA virus.” [5] The genomic RNA is tightly wrapped by the nucleoprotein, and contains phospoprotein and polymerase which are viral proteins. “Glycoprotein (G) forms approximately 400 trimeric spikes on the envelope which are tightly arranged on the surface of the virus and point outward. The M protein is associated both with the envelope and the RNP and may be the central protein of the assembly.” [1] The virus has a bullet-like shape with one end being rounded while the other is planar, “. . . the core of the virion consists of helically arranged ribonucleoprotein.” [1] The lipid bi layer from the host cell builds the outer envelope, and is covered with spike like projections “corresponding to G-Protein trimers, which recognise and bind cell receptors.”[5]

 

http://www.cdc.gov/rabies/images/genome.gif

Figure 3. The rabies virus genome is single-stranded, antisense, nonsegmented, RNA of approximately 12 kb.

Key tests for identification:

The test that is most frequently used to diagnose rabies in animals is the direct fluorescent antibody test (dFA), which requires brain tissue from the suspected rabid animal. [6]

When it comes to the diagnosing rabies in humans before death, there are several key tests that can be performed on samples of saliva, serum, spinal fluid, and skin. “Saliva can be tested by virus isolation or reverse transcription followed by polymerase chain reaction (RT-PCR). Serum and spinal fluid are tested for antibodies to the rabies virus. Skin specimens are examined for the rabies antigen in the nerves at the base of most hair follicles.” [1]

 

Signs and symptoms of disease:

The symptoms following an infection of the rabies virus in humans start out with simple headaches, fever and later progresses to terrible things such as becoming hydrophobic because of painful throat spasm and paralysis. The first symptoms of rabies may be nonspecific and include lethargy, fever, vomiting, anorexia, and can easily be mistaken for other less lethal illnesses. “Signs progress within days to cerebral dysfunction, cranial nerve dysfunction, ataxia, weakness, paralysis, seizures, difficulty breathing, difficulty swallowing, excessive salivation, abnormal behavior, aggression, and/or self-mutilation.” The incubation period vary from 10 days to rarely over a year, with the average incubation period at 31 to 90 days. “Pain and paresthesia are common at the wound site. Non-specific complaints such as general malaise, chills, fever, headache, sore throat and fever are commonly reported, as are behavioral changes such as apprehension, anxiety, agitation, irritability, insomnia and depression.” [7]

Rabies infected animals, causes acute encephalitis in all warm-blooded hosts and the outcome is almost always fatal. “Initial symptoms in animals include behavior changes, agitation and reflex excitability.” With the furious form, animals become dangerously aggressive, biting objects, other animals and humans. There can be paralysis of a limb beginning at the site of exposure. “Dogs show either the furious or dumb form of rabies, with the symptoms described above. Cats generally show the furious type, followed by paralysis 2-4 days later.” [7]

 

http://4.bp.blogspot.com/_vHPTP1DEyzs/TKnsjbAnglI/AAAAAAAAA80/blaBpUiB2aI/s1600/rabies+illustration.jpg

 

Historical information:

Extending way back to about 2300 B.C, people in ancient Babylon have acknowledged the presence of this terrifying disease. Rabies literally means “furious” in Latin, and is commonly known for its ability to degrade the human brain and spinal cord resulting in many fatalities through the ages. The disease is fatal and a great amount of people has dedicated their lives to finding ways to control and prevent it from spreading. Pasteur is the first scientists to acquire a vaccine for rabies in the 1800’s. “When a 9-year-old boy was bitten by a rabid dog in 1885, Louis Pasteur treated him with a rabid spinal cord vaccine, becoming the first human being successfully immunized, as the boy did not develop rabies. Rabies is a virus that ranks 10th in causes of mortality in the world. There are approximately 55,000 deaths annually. The vast majority of these are clearly in Third World countries.” [8]

 

Virulence factors:

The virulence factors for the rabies virus include the G protein, glycoprotein, and cytopathic effects associated with the disease. [9]

 

Diagram of the rabies virion

Figure 4. Rabies virons are bullet-shaped with 10-nm spike-like glycoprotein peplomers covering the surface. The ribonucleoprotein is composed of RNA ecnased in nucleoprotein, phosphorylated or phosphoprotein.

 

Whenever the virus has successfully entered the human or animal, the virus proceeds to replicate at the injection site. Aided by the G protein, the viral envelope attaches and fuses with the host cell membrane (Figure 5, part 2). “Invagination of the plasma membrane with clathrin-coated pits allows cytoplasmic absorption via pinocytosis. The virions aggregate with the large endosomes, and after fusion with their membranes, they initiate the uncoating and release of the viral RNP into the cytoplasm (Figure 5, part 3).  Since the rabies virus has a linear –ssRNA genome, messenger RNAs are produced to permit virus replication using the host cell machinery.  In particular, translation of the genome occurs on the free ribosomes in the cytoplasm, and some posttranslational processing occurs in the endoplasmic reticulum and Golgi apparatus.” [9]

 

http://aeneary.myweb.uga.edu/rabies_files/image009.jpg

Figure 5. Rabies virus cycle of infection and replication.

 

Control/Treatment:

One unfortunate affect of the rabies is that once you have been exposed, there is no treatment. However, a vaccine can be injected after an exposure to grant immunity. It is also evident that people, who are more prone to potential exposure, are more likely to survive if the antibodies are already present. “This method of prevention in monitored every few months for antibodies in the blood, and ultimately simplifies therapy by decreasing the number of vaccines doses needed and eliminating the use of human rabies immune globulin. If a person becomes infected with rabies, he or she would receive a course of rabies immune globulin and five doses of vaccines.” [3] The state of Texas requires that dogs and cats be vaccinated against rabies by 4 months of age and on a 1-year or 3-year basis thereafter depending on the vaccine used.

 

Prevention:

Eliminating rabies in dogs through proper vaccination is the most cost-effective solution to prevent rabies in humans and other animals. The vaccination of dogs had reduced the number of rabies cases in many dog infested countries. “However, recent increases in human rabies deaths in parts of Africa, Asia and Latin America suggest that rabies is re-emerging as a serious public health issue.” [11]

You should always avoid being bitten by animals, especially wild ones. Signs of rabies in wild animals can be hard to detect, but their behavior is typically abnormal, as in the following:

 

·         Wild animals may not appear vicious, shy, or afraid when people approach them.

·         Nocturnal animals (such as bats, skunks, raccoons, and foxes) are out during the day.

·         Bats make unusual noises or have difficulty flying.

·         Animals bite without being provoked.

·         Animals are weak or agitated and vicious. [3]

There are three vaccines approved by the FDA currently in use to prevent rabies:

·         Human diploid cell vaccine (HDCV) or Imovax-most widely used

·         Michigan Biologic Products Institute (monkey cell cultures)

·         Inactivated diploid cell origin (DCO) [1]

 

Outbreaks/cases locally:

The number of animal rabies cases in Texas is higher than normal this year, warns the Texas Department of State Health Services. “As with many diseases of public health significance, control of rabies consists of legislation; education; surveillance; quarantine and isolation; and direct medical intervention, such as vaccination.” [12]

 

The most recent outbreak of rabies in the United States: [10]

 

Case #

Year

Age

Sex

Race

Location

Exposure

Animal

RV Ecotype

Incubation

Comments

211

2011

71

F

B

New Jersey

Haiti

Dog

dog/mongoose

60 - 70 days

Bitten in April

 

all_positives.jpg

 

Outbreaks/cases globally:

Rabies is present on all continents with the exception of Antarctica, but more than 95% of human deaths occur in Asia and Africa. “Dog rabies potentially threatens over 3.3 billion people in Asia and Africa. People most at risk live in rural areas where human vaccines and immunoglobulin are not readily available or accessible.” [11]

 

·         Rabies occurs in more than 150 countries and territories.

·         Worldwide, more than 55 000 people die of rabies every year.

·         40% of people who are bitten by suspect rabid animals are children under 15 years of age.

·         Dogs are the source of 99% of human rabies deaths.

·         Wound cleansing and immunization within a few hours after contact with a suspect rabid animal can prevent the onset of rabies and death.

·         Every year, more than 15 million people worldwide receive a post-exposure preventive regimen to avert the disease – this is estimated to prevent 327 000 rabies deaths annually. [11]

 

 

Work Cited:

 

1.       "CDC - Rabies." Centers for Disease Control and Prevention. 7 July 2007. Web. 01 Dec. 2011. <http://www.cdc.gov/rabies/>.

 

2.       Health Canada. “Animals and Your Health.” April 14, 2009. Web. 11/28/2011. <http://www.hc-sc.gc.ca/fniah-spnia/promotion/public-publique/anima_health-sante-eng.php#a3>.

 

3.       Jacewicz, Michael. The Merck Manuals Online Medical Library: Rabies. May 2008. Web. 11/28/2011. <http://www.merck.com/mmhe/sec06/ch089/ch089e.html>.

 

4.       "About Rabies." Rabies - Bulletin - Europe. World Health Organization, Geneva, 2006. Web. 29 Nov. 2011. <http://www.who-rabies-bulletin.org/about_rabies/classification.aspx>.

 

5.       Rupprecht, Charles E. "Rhabdoviruses: Rabies Virus - Medical Microbiology - NCBI Bookshelf." National Institute of Health. University of Texas Medical Branch at Galveston, 1996. Web. 01 Dec. 2011. <http://www.ncbi.nlm.nih.gov/books/NBK8618/>.

 

6.       "Rabies - Oklahoma State Department of Health." Welcome to Oklahoma's Official Web Site. Oklahoma State Department of Health, 2011. Web. 01 Dec. 2011. <http://www.ok.gov/health/Disease,_Prevention,_Preparedness/Public_Health_Laboratory/Services/Rabies/>

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7.       "Rabies." Ohio Department of Health Fact Sheet. Ohio Department of Health, July 2011. Web. 1 Dec. 2011. <http://www.odh.ohio.gov/pdf/idcm/rabies.pdf>.

 

8.       Williams, Dan. "Rabies Virus, Symptoms, Vaccine, Treatment." Survive Outdoors. 2008. Web. 04 Dec. 2011. <http://www.surviveoutdoors.com/reference/rabies.asp>.

 

9.       Fletcher, Erica, Cory Gresham, Ashley Neary, and Katie Price. "Rabies." Zoonosis. Dr. Peterson, 2001. Web. 04 Dec. 2011. <http://aeneary.myweb.uga.edu/rabies.htm>.

 

10.   "Texas Department of State Health Services, Infectious Disease Control Unit Cases." Texas Department of State Health Services Mobile. 11 Aug. 2011. Web. 04 Dec. 2011. <http://www.dshs.state.tx.us/idcu/disease/rabies/cases/>

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11.   "WHO | Rabies." World Health Organization, WHO.com. 2011. Web. 04 Dec. 2011. <http://www.who.int/mediacentre/factsheets/fs099/en/>

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12.   "Rabies in Texas; a Historical Perspective." Www.dshs.state.tx.us. 2004. Web. 2 Dec. 2011. <www.dshs.state.tx.us/idcu/disease/rabies/history/historyInTexas.pdf>.