NAME : Duaa Amer Abed

U.O.A C.O.PHARMACY

RABIES
MICROBIOLOGY

2019-2020
 Overview

Rabies is an acute fatal viral illness of the central nervous system (CNS)
commonly resulting in encephalitis. Rabies virus is a bullet shaped,
enveloped, helical nucleocapsid containing a negative-sense RNA genome
of the rhabdoviridae family. The word rabies is derived from the Latin verb
“to rage,” which suggests the appearance of the rabid patient. It can affect
all mammals and is transmitted between them by infected secretions, most
often by bite.

It was first recognized more than 3000 years ago and has been the most
feared of infectious diseases. It is said that Aristotle recognized that rabies
could be spread by a rabid dog. Rabies involves the development of severe
neurologic symptoms and signs in a patient who was previously bitten by
an animal (a rabid dog or wild animals).

The incubation period is 10 days to 1 year. The virus replicates at the site
of bite followed by entry into the peripheral nervous system at the
neuromuscular junctions and spreads to the CNS, where it replicates
exclusively within the gray matter and then spreads centrifugally to the
autonomic nervous system. The neurologic manifestations are very
characteristic, with a relentlessly progressive excess of motor activity,
agitation, hallucinations, and salivation.

The patient appears to be foaming at the mouth and has severe throat
contractions if swallowing is attempted. Involvement of the respiratory
center produces respiratory paralysis, the major cause of death. Recovery
is rare. The postexposure vaccination is considered treatment for rabies
because the killed rabies vaccine is given to people after exposure at days
0, 3, 7, and 14. In addition, hyper immune globulin serum should be
instilled in the wound to neutralize the virus.
 PATHOGENESIS
The essential first event in human or animal rabies infection is the
inoculation of virus through the epidermis, usually as a result of an animal
bite. Inhalation of heavily contaminated material, such as bat droppings,
can also cause infection. The incubation period is between 10 days and 1
year (average 20-90 days). Rabies virus first replicates in striated muscle
tissue at the site of inoculation. Immunization at this time is presumed to
prevent migration of the virus into neural tissues. In the absence of
immunity, the virus then enters the peripheral nervous system at the
neuromuscular junctions and spreads to the CNS, where it replicates
exclusively within the gray matter.

It then passes centrifugally along

autonomic nerves to reach other
tissues, including the salivary
glands, adrenal medulla, kidneys,
and lungs. Passage into the
salivary glands in animals
facilitates further transmission of
the disease by infected saliva. The
neuropathology of rabies
resembles that of other viral
diseases of the CNS, with
infiltration of lymphocytes and
plasma cells into CNS tissue and
nerve cell destruction. The
pathognomonic lesion is the Negri
body , an eosinophilic cytoplasmic
inclusion distributed throughout
the brain, particularly in the
hippocampus, cerebral cortex,
cerebellum, and dorsal spinal
ganglia.
 symptoms
The first symptoms of rabies may be very similar to those of the flu and
may last for days.

Later signs and symptoms may include:

 Fever  Anxiety
 Headache  Confusion
 Nausea  Hyperactivity
 Vomiting  Difficulty swallowing
 Agitation  Excessive salivation

 Fear brought on by attempts

to drink fluids because of
difficulty swallowing water

 Hallucinations
 Insomnia
 Partial paralysis
 Diagnosis
Several tests are necessary to diagnose rabies ante-mortem (before death)
in humans; no single test is sufficient. Tests are performed on 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.

As diagnosis based on clinical ground alone is difficult and often unreliable;

it is recommended to confirm a clinical case of rabies through the use of
laboratory-based techniques. For post mortem diagnosis, the gold-standard
diagnostic technique is to detect rabies virus antigen in infected tissues,
preferably brain smears or touch impressions collected from a biopsy, by
fluorescent antibody test (FAT). FAT is recommended by WHO and in 95-
99% of cases, gives reliable results on fresh specimens within a few hours.
Other methods for detection of lyssavirus antigens such as direct rapid
immunohistochemistry tests are proven to have sensitivity and specificity
comparable to the FAT. WHO recommends further development of direct
rapid immunohistochemistry tests as an alternative to the FAT for improved
decentralized laboratory-based surveillance in endemic areas.

Ante-mortem diagnosis, or diagnosis of rabies during life (by intra-vitam

techniques) is difficult and dependent on widespread dissemination of virus
through the nervous system. It is strongly discouraged for rabies diagnosis
in animals as sensitivity varies widely according to the stage of the disease,
immunological status, intermittent viral excretion and training of the
technical staff.
 TREATMENT
Prevention is the mainstay of controlling rabies in humans immediately
after exposure by starting the rabies vaccination process. With
symptomatic rabies, intensive supportive care has resulted in four or five
long-term survivals; despite the best modern medical care, however, the
mortality rate still exceeds 90%. In addition, because of the infrequency of
the disease, many patients die without definitive diagnosis. Human
hyperimmune antirabies globulin, interferon, and vaccine do not alter the
disease once the symptoms have developed.

Postexposure prophylaxis is considered as a treatment for rabies exposure

to humans after bites from rabid or wild animals. In a controversial
experimental treatment strategy in 2004, known as the Wisconsin or
Milwaukee protocol, a 15-year old patient with rabies symptoms was placed
in a chemically induced coma to protect her brain from rabies virus and
treated with antivirals (ribavirin and amantadine). The coma was reversed
in the patient after 6 days when her immune system started making rabies
antibodies. The patient became free of rabies virus and survived.
 Prevention
Almost all human cases of rabies were fatal until a vaccine was developed
in 1885 by Louis Pasteur and Émile Roux. Their original vaccine was
harvested from infected rabbits, from which the virus in the nerve tissue
was weakened by allowing it to dry for five to ten days.[58] Similar nerve
tissue-derived vaccines are still used in some countries, as they are much
cheaper than modern cell culture vaccines

The human diploid cell rabies vaccine was started in 1967. Less expensive
purified chicken embryo cell vaccine and purified vero cell rabies vaccine
are now available. A recombinant vaccine called V-RG has been used in
Belgium, France, Germany, and the United States to prevent outbreaks of
rabies in undomesticated animals. Immunization before exposure has been
used in both human and nonhuman populations, where, as in many
jurisdictions, domesticated animals are required to be vaccinated.

The Missouri Department of Health and Senior Services Communicable

Disease Surveillance 2007 Annual Report states the following can help
reduce the risk of contracting rabies:

 Vaccinating dogs, cats, and ferrets against rabies.

 Keeping pets under supervision.
 Not handling wild animals or strays.
 Contacting an animal control officer upon observing a wild animal
or a stray, especially if the animal is acting strangely.
 If bitten by an animal, washing the wound with soap and water for
10 to 15 minutes and contacting a healthcare provider to determine
if post-exposure prophylaxis is required.
References

 Ryan, K., 2018. Sherris Medical Microbiology, 7E. 7th ed. New York, N.Y.:
McGraw-Hill Education LLC.
 Cotran RS, Kumar V, Fausto N (2005). Robbins and Cotran Pathologic Basis
of Disease (7th ed.). Elsevier/Saunders.
 AskMayoExpert. Rabies. Mayo Clinic; 2019.
 Rabies. Centers for Disease Control and Prevention.
http://www.cdc.gov/rabies/. Accessed Sept. 9, 2019.