Radical Rabies:
An Investigation on the Diagnosis, Signs, and Symptoms of Classical Rabies Virus
Abstract Word Count: 97
Page Count: 6
Andrew Zheng
Biomedical Sciences: Cluster 7
Dr. L and Master Dockter
July 27, 2015
Abstract:
Viruses are cunning. They manage to infiltrate every living thing and are able
manipulate the cells within to duplicate. There are all sort of viruses but one
extremely shrewd and calculating one is rabies. It travels up to the brain and
completely annihilates the nervous system. There are still no tests to diagnosis
rabies in humans before the onset of clinical disease. There are still no reliable
cures to rabies. Yet, the symptoms of rabies are obvious and flagrant. Rabies can
be horrifying to perceive but there must be more awareness to end the sequence of
infection.
Investigation:
The realization of viruses occurred in the late 1880s, a reasonably short time ago, but
viral diseases have morphed the past and evolution of life on this planet as long as they have
existed. As far as we know, all living organisms can potentially become infected by viruses (J.
Strauss and E. Strauss 1). Viruses infringe healthy cells and use them as hosts to replicate, so
they can definitely be serious threats to animal and human health (Mandal). Even though
progress in controlling infectious diseases has improved through upgraded sanitation, safer water
supplies, the development of vaccines and antibiotics, and better medical care, viruses still roam
everywhere (J. Strauss and E. Strauss 1). One virus that is in focus is rabies. The symptoms of
rabies are threatening and lethal, and the diagnosis of the virus before it reaches the brain is
crucial (J. Strauss and E. Strauss 144).
Rabies is a uniformly fatal disease in mammals and humans, and has been known since
the twenty-third century B.C. (J. Strauss and E. Strauss 144). It is a zoonotic disease, as it is
present in the saliva of a rabid animal and is transmitted to humans through its bite. Infection
begins by the tissues around the bite (“Rabies”). Without any response or treatment, the virus
may travel up to the brain. Replication of the virus there leads to rabies (J. Strauss and E. Strauss
144).
The probability that rabies will develop following a rabid animal’s bite depends on the
location of the bite, the animal’s species, and the virus strain. For example, bites on the face and
head resulted in rabies in 40-80% of human cases, whereas bites on the legs caused only 0-10%
of people to become infected. The incubation period of symptomatic rabies can vary from less
than a week to several years. In humans, rabies can be paralytic or may result in nonspecific
neurological symptoms such as anxiety, agitation, and delirium. Biting others is not a
consequence of human rabies and human-to-human transmission does not occur (J. Strauss and
E. Strauss 144).
The diagnosis of rabies in animals can be made after the detection of rabies from any area
of an affected brain. However, in order to rule out rabies, the test must include tissues from two
areas of the brain, preferably the brain stem and cerebellum. The test also requires the animal to
be euthanized. The test takes around two hours but the time to ship the brain samples to a state
public health or veterinary diagnostic laboratory for diagnosis may take several days
(“Diagnosis”).
On the other hand, diagnosing rabies in humans requires a plethora of tests; no single test
is sufficient enough. “Tests are preformed from samples of saliva, serum, spinal fluid, and skin
biopsies of hair follicles at the nape of the neck. 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 rabies virus. Skin biopsy specimens are examined for rabies antigen in the
cutaneous nerves at the base of hair follicles” (“Diagnosis”).
More diagnosis techniques incorporate direct fluorescent antibody tests, histologic
examinations, immunohistochemistry, electron microscopy, and amplification methods. The
direct fluorescent antibody test (dFA) is based on the observation of rabies virus proteins
(antigens) present in the tissues of a rabid animal. The ideal tissue for the test would be from the
brain, since rabies is present in nervous tissues and not the blood like most viruses. The test
works by incubating fluorescently-labeled anti-rabies antibodies with rabies-suspected brain
tissue. The two would then bind together. Unbound antibodies could be washed away whereas
bound ones would be visualized as fluorescent-apple-green areas. If the rabies virus is absent,
then there would be no staining (e.g. see fig. 1) (“Diagnosis”).
Fig. 1
Positive dFA
Negative dFA
http://www.cdc.gov/rabies/diagnosis/direct_fluorescent_antibody.html
Histologic examination of biopsy or autopsy (post-mortem) tissues is sporadically useful
in diagnosing rabies in unsuspected animals that have not been tested by routine methods. When
brain tissue from rabies virus infected animals are stained with histologic stains such as
hematoxylin and eosin, evidence of encephalomyelitis may be documented by a trained
microscopist. Immunohistochemistry methods for the detection of rabies provide sensitive and
specific means to discover rabies in formalin-fixed tissues. These methods are essentially more
sensitive than histologic staining methods (“Diagnosis”).
Electron microscopy can study the ultrastructure of viruses. Using this method, detailed
observation of the structural components of viruses and their inclusions is possible. Rabies virus
is in the family of Rhabdoviruses. Rhabdoviruses seem like bullet-shaped particles underneath an
electron microscope (e.g. see fig. 2) (“Diagnosis”).
“Negatively stained Rhabdovirus as seen through
an electron microscope. Notice the bullet shape of
the virus (A). See the ‘beehive’ like striations of the
RNP (B). Notice the glycoprotein spikes in the
outer member bilayer (C).”
Fig. 2
http://www.cdc.gov/rabies/diagnosis/electron_microscopy.html
Samples that contain very small amounts of rabies virus may be problematic to confirm
as rabies-positive by customary approaches. Virus isolation in cell cultures increases the
concentration of the virus. This is due to replication. Mouse neuroblastoma cells (MNA) and
baby hamster kidney cells (BHK) provide an excellent and ideal environment for the
amplification of rabies virus (“Diagnosis”).
The development of clinical rabies in humans is divided into three general stages: the
prodromal period, an acute neurologic phase, and coma preceding death. The prodromal period
lasts from two to ten days and during that time, symptoms are usually mild and nonspecific.
Some symptoms consist of general malaise, chills, fever, headache, photophobia (light
sensitivity), anorexia, nausea, vomiting, diarrhea, sore throat, cough, and musculoskeletal pain.
One peculiar early symptom though is abnormal sensation around the bite wound. The site might
itch, burn, be numb, or have some sort of paresthesia (1: 914).
During the acute neurologic phase, patients will exhibit signs of nervous system
dysfunction. Anxiety, agitation, dysphagia (difficulty or discomfort swallowing), hypersalivation
(the excess production of saliva), paralysis, and delirium are just some signs that would ensue.
Occasionally, priapism, persistent and painful erections of the penis, or increased libido (sex
drive) may be observed. Cases in which hyperactivity is predominant are categorized as furious
rabies cases. When paralysis is prevalent, it is classified as paralytic or dumb rabies (1: 914).
The percent of patients exhibiting hydrophobia, the fear of water, range from 17% to
80%. Hydrophobia is a pathognomonic sign of rabies believed to be caused by an amplified
respiratory tract protective reflex. Hydrophobic episodes can actually last from one to five
minutes and are triggered by attempts to drink. “In furious rabies, the neurologic period ends
after 2 to 7 days with coma or sudden death from respiratory or cardiac arrest” (1: 914).
Paralytic rabies occurs in about 20% of patients. This type of rabies may be more
frequent in persons exposed to certain strains. One example is the vampire bat RABV. Again,
patients will initially develop paresthesia and weakness, and finally flaccid paralysis. Paralysis
then proceeds to paraplegia (impairment of motor skills in the lower body) and quadriplegia
(disability in all the limbs). In paralytic rabies, the course to death is not exceedingly progressive.
Some patients live up to thirty days with intensive care. Lastly, the final stage of this disease is
coma, which lasts three to seven days and results in death. Patients that received respiratory
assistance had their lives prolonged for several weeks (1: 914-915).
To date, six cases of human recovery from clinical rabies have actually been documented.
Five of the cases had exposures to animal bites while the other case was due to suspected
inhalation of rabies virus in the laboratory. Only one of the patients had never been vaccinated
and was set up in an experimental treatment. The trial included induction of ketamine coma in
conjunction with antiviral compounds and demanding care. “Nevertheless, more than 10
attempts to repeat such experimental treatment (although with deviations and modifications)
failed. However, in one vaccination failure case (immunoglobulin was not administered,
although all five doses of vaccine were administered on time), the experimental treatment was
implanted successfully. In addition, this was the only survival case where the virus variant was
identified (vampire bat RABV)” (1: 915).
Clinical disease in animals is very similar to that of humans, excluding the absence of
hydrophobia. Signs can vary but can comprise of altered phonation (creating certain sounds
through the vocal cords by quasi-periodic vibration), pica (tendency to crave abnormal foods),
cranial nerve deficits, distorted activity patterns, and the loss of fear toward humans (1: 915).
Conclusion:
Rabies is appalling. The diagnosis process is insufficient and delayed. The symptoms are
remarkably detrimental and disheartening. There is no remedy to cure rabies (although there are
injections that need to be administered instantaneously after infection to prevent the virus from
reaching the central nervous system). Rabies cannot be found clearly before it enters the brain,
and cannot be extinguished after it enters the brain, so it is clear that it is perilous on all levels.
Infection causes tens of thousands of deaths per year, especially in Asia and Africa. “40% of
people who are bitten by suspect rabid animals are children under 15 years of age” (“Rabies”).
Rabies cases must be eliminated around the world. Numerous people are at risk and vaccines can
avert the towering figures. Rabies can and will be stopped with awareness and understanding.
Works Cited
"Diagnosis." Centers for Disease Control and Prevention. Centers for Disease Control and
Prevention, 20 Sept. 2011. Web. 26 July 2015.
"Diseases and Conditions: Rabies." Mayo Clinic. Mayo Clinic Staff, n.d. Web. 26 July 2015.
Knipe, David M., PhD, and Peter M. Howley, MD. Fields Virology. 6th ed. Vol. 1. Philadelphia:
Lippincott Williams & Wilkins, 2013. Print.
Mandal, Ananya, MD. "What Is a Virus?" News Medical. News Medical, 09 Jan. 2010. Web. 26
July 2015.
"Rabies." World Health Organization. WHO, 2015. Web. 25 July 2015.
Strauss, James H., and Ellen G. Strauss. Viruses and Human Disease. 2nd ed. N.p.: Academic,
2008. Print.