MICROBIOLOGY

Rhabdoviridae
Dr. Quiles
CHARACTERISTICS OF RHABDOVIRUS Picture on Lower Left: Structure of Rabies Virus
 Single stranded (-) sense non-segmented RNA virus The Rabies virus is bullet-shaped, and inside you will find the single-stranded
 Enveloped RNA. On the outside, is the envelope (light blue), and on the envelope you
 Rod or Bullet-shaped will notice the spikes projecting which is the G protein (Glycoprotein). The
 The only medically important Rhabdovirus inner layer of the envelope is the M protein (Matrix protein), located
between the capsid and the viral envelope
 Has wide host range
It can infect all types of animals
REACTION TO ENVIRONMENTAL CONDITION
 Can survive:
 Only one serotype
o 4 oC for weeks
Supposedly, since Rhabdovirus has only one serotype, it should be
o -70 oC for years
very easy to produce a vaccine against it and at the same time,
 Inactivated by CO2
easier to eradicate the disease. But unfortunately up to the
present, the Rabies disease is still not eradicated and still remains  Killed by:
as one of the problems of WHO o UVL, sunlight, X-ray
o Heat (1 hr. at 50 oC)
 Genera: Lyssavirus  Rabies virus  the only medically important o Lipid solvents (ether, Sodium deoxycholate)
member Vesiculovirus o Trypsin
o Detergents
STRUCTURE o Extremes of pH
 RNA encodes 5 proteins:
1. Nucleoprotein (N) Since the Rabies virus is an enveloped virus, it is easily destroyed
2. Large Proteins (L)
3. Non-Structural Proteins (NS) ANIMAL SUSCEPTIBILITY TO RABIES
4. Matrix Proteins (M) Susceptibility Animal
5. Glycoprotein (G) Very High Foxes, wolves, coyotes, jackals, cotton rats
Skunks, raccoons, cats, bats, hamsters, rabbits,
N Protein High
cattle
 Major structural protein Moderate Dogs, sheep, goats, horse, non-human primates
 Protect RNA from ribonuclease digestion Low Opposums
 Maintains RNA in a configuration for transcription
The configuration of your RNA virus is important to be maintained Lecture discussion of Dr. Quiles:
because if it gets destroyed, transcription would not take place Cotton rats, hamsters, ra bbits, and opposums are questionable to be
susceptible to the Rabies virus because before, Jawetz had a reviewer where
L & NS Protein he listed “rodents and rats do not transmit rabies.”
 Constitutes the RNA-dependent RNA polymerase
Since the virus is a negative stranded virus, therefore the virus SOURCES OF INFECTION
must encode its own RNA-dependent RNA polymerase  Major sources: Saliva in bite of rabid animals
 Minor sources: Aerosols in bat caves containing rabid bats
G protein Bats sleep inside the caves upside down from the trees or ceiling.
 Viral attachment protein Instances when they sleep is that their saliva drips from their mouth
and drops to the floor and then it dries up and gets aerosolized along
 Major factor in the neuro-invasiveness & pathogenicity
with the virus. So people who goes spelunking inside caves, they are
 Generates neutralizing antibodies prone to viral infection through inhalation of the aerosolized saliva
Neutralizing antibodies are antibodies produced by the bodyonce
you get vaccinated by an inactivated Rabies virus. These
antibodies are the ones that destroy the Rabies virus. But still,
Rabies virus is still a problem in the present time

Picture Above: Representation of worldwide distribution of rabies virus

affected area continent wise

Philippines is Endemic to Rabies virus

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Rhabdoviridae
Dr. Quiles

Picture Above: Provinces with Highest Reported Human Rabies, Philippines 2018
Picture Above: Human Rabies Trend (2007-2017)
The Rabies Trend from 2007-2017 shows the plot of the number of cases of RABIES CARRIER IN THE PHILIPPINES
Rabies reported. It also shows how effective the program of DOH. As you can  Endemic
see there is a downward and upward trend but looking at 2017, it i s not as  98.5% of cases  Domestic Dogs
high as that of 2007. The incidence of Rabies infection as opposed to the  1.3%  Cats
program of DOH is continuously going down  0.2%  Other domestic animals
 No reported cases due to bats & other animals

RABIES
 Acute, rapidly progressive fatal encephalitis
 55,000 deaths annually
 Affects all warm-blooded animals
 Worldwide distribution
 Enters the body through breaks in the skin or direct contact with
mucosal surfaces
 Cellular receptors  Nicotinic Acetylcholine Receptor (located in
the muscles)

Mode of Transmission:
1. Bite of Rabid Animals
2. Non-Bites
Picture Above: Animal Bites 2007-2017
o Scratching, licking of open skin, inhalation of aerosolized
Unfortunately there is an increase in the number of animal bites per year.
virus in bat caves, corneal & organ transplantation
This can be attributed to increasing number of people adopting animals. In
2017, there is about 1.2 million animal bites reported
INCUBATION PERIOD
 Incubation Period: 6 days to 6 months (6 years)
According to the Book 6 days to 6 months. But according to DOH,
the longest IP was 6 years recorded in Ilocos Sur

 Factors that determine the length of Incubation Period:

a) Site of the bite
Bite should classified as Major or Minor bite.
Major bite  head & neck. The closer the bite to the
CNS, the shorter would be the I.P. So the farther from
the CNS, the longer would be the I.P.

b) Severity of the bite

c) Condition of the animal prior to the bite
Although this factor is not included in Jawetz, this
should be included. We have to know if the animal was
provoked or not. If an animal is provoked, it will
hypersalivate = more virus in the saliva

d) Condition of the victim

e) Amount of virus in the inoculation

Picture Above: Reported Human Rabies Case by Region, Philippines 2018

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 MICROBIOLOGY
Rhabdoviridae
Dr. Quiles
FORMS OF RABIES VIRUS
2 Forms:
1. Dumb or Paralytic Form
o Extreme bradycardia
o Paresthesia
o Flaccid paralysis
o 30% of cases
o Bat infected

2. Furious or Fulminant Form

o Most common
o Fulminant – will soon lead to death of the patient
o Hydrophobia
o Aerophagia
o CNS lability
Picture Above: Progression of the Rabies Virus
It will start from a bite of a rabid animal. From the bite site, the virus will gain
access to the muscles where the nicotinic acetylcholine receptors are 5 STAGES OF RABIES DISEASE
located. In the muscles, the virus will replicate and then from there, there
would be retrograde axonal transmission travelling from the peripheral
nerves to the spinal cord and then to the brain. In the brain, there will be
another round of replication. From the brain, the virus will go down causing
descending infection going to the salivary glands and other organs. That is
why there is many virus in the sa liva because of the descending infection
after replication in the brain

Picture Above: 5 Stages of Rabies Disease

Rabies Disease is divided into 5 stages, from the incubation period,
prodromal period (0-10 days from the I.P.), acute neurologic period – the
virus is in the CNS already (2-7 days after the prodrome), coma and the later
death. We have to take note of the amount of virus. During the acute
neurologic stage, there is an increase of amount of virus. The same is true
with that of the salivary gland. Why? Because after the virus replicated in the
CNS, it will descend to the salivary glands so there will also increase virus in
the saliva.
Rabies PEP (Post-Exposure Prophylaxis) is only effective when given during
INCUBATION PERIOD which is after the bite of the rabid animal
Picture Above: Another picture of Pathogenesis of Rabies Virus
From the bite site  Muscles  Peripheral Nerves  Spinal Cord  Brain.
Prodromal Phase
In the brain there will be pathologic changes such as formation of the Negri
bodies and Perivascular cuffing  Non-specific symptoms
 Usually lasts for 2-7 days
Pathogenesis:  Malaise, anorexia, headache
Virus multiplies at the site of inoculation in striated muscles, remaining localized  Photophobia, nausea & vomiting
for days to months  Peripheral nerves  Retrograde Neuronal Transport   Fever
Spinal Cord  Brain follows hippocampus, brainstem, ganglionic cells of Pontine  Paresthesia at the bite site
nuclei  Itching at the bite site

Continued next page….

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 MICROBIOLOGY
Rhabdoviridae
Dr. Quiles
Acute Neurologic Phase DIAGNOSIS
 Last for 2-7 days A. Histopathology  Negri Bodies in the brain
 NS dysfunction  nervousness, apprehension, hallucinations & Histopathology is highly specific but has lesser reliability &
bizarre behavior sensitivity because once you see Negri bodies in a specimen then
 General sympathetic overactivity  lacrimation, pupillary dilatation, you are sure that there is Rabies infection, it’s just that there can
increase salivation & perspiration be cases wherein the part of the brain where you got the specimen
 Hydrophobia or Aerophagia could be an area not yet invaded by the Rabies virus, making you
rule out the Rabies infection
Aerophagia  Excessive air swallowing, panic when blown with air
Hydrophobia  They are thirsty but when they see water or hear drops
of water they get enraged. This is due to the painful spasm of the B. Direct Immunofluorescence  highly specific & sensitive
throat muscle. Patients with rabies are not really afraid of water, but C. Culture  hazardous
because of the spasms on the throat caused by the stimulus from D. Serology  late results
water they get enraged

 Painful throat muscle spasms

 Once symptoms develop  rabies encephalitis is almost always fatal
Once the manifestations of Rabies develop, expect that the
patient will go into coma and eventually death. In Rabies, once the
virus reaches the peripheral nerves, they are sequestered from the
cells of the immune system. So even if you vaccinate the patient,
there is nothing can be done about it. Expect that the infection will
go into rapid progression
Negri Bodies are intracytoplasmic eosinphilic inclusion bodies with
perivascular cuffing
Coma & Death
CLINICAL MANAGEMENT
 Convulsive seizure  Coma  Death
 Observe the dog for 10 days
 Cause of Death  Cardio-respiratory arrest
 Exposed persons require administration within 24 hours of
hyperimmune immunoglobulins and vaccine
Clinical Syndrome (from Manual)
 There is no cure once the symptoms have appeared
 Hydrophobia is the most common characteristic symptom of
rabies
 Focal and generalized seizures, disorientation and hallucination RABIES PREVENTION
occurs during neurologic phase 2 Main Strategies
 About 15% exhibits paralysis as the only manifestation of rabies 1. Animal Rabies Control: Rabies Vaccination
 Illness is usually non-specific 2. Human Rabies Control
 Actually produce an encephalitis as well as meningitis o Post-Exposure Prophylaxis (PEP)
 Febrile illness with myalgia occurs more often  Exposed individuals

o Pre-Exposure Prophylaxis (PrEP)

 Before exposure
 High risk individuals – Animal Handlers,
Veterinarian, Breeders

Picture Above: PEP and PrEP

Picture Above: Furious Form vs. Paralytic Rabies PEP makes use of Vaccine + RIG
PrEP makes use of Vaccine only
RIG - Immunoglobulin Ab against rabies. Given immediately after the bite and
around the bite site. Since it is a neutralizing Ab, it will neutralize the virus
around the bite site stopping it from replicating and from reaching the deeper
muscles

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 MICROBIOLOGY
Rhabdoviridae
Dr. Quiles
Active Immunization:
a) Purified Verocell Rabies Vaccine ( PVRV) Category 2
b) Purified Duck Embryo Vaccine (PDEV)  Wash wound with soap & water
c) Purified Chick Embryo Vaccine (PCEV)  Start vaccine immediately
d) Human Diploid Cell Vaccine (HDCV) – safest to use  Complete vaccination regimen until day 7 regardless of the status of
biting animal
Passive Immunization  RIG is not indicated
a) Equine Rabies Immunoglobulin (ERIG)
b) Human Rabies Immunoglobulin (HRIG) Category 3
 Wash wound with soap & water
Components of Pre-Exposure Prophylaxis (PrEP)  Vaccine & RIG
 Local wound care  Complete vaccination regimen until day 7 regardless of status of
 Active immunization biting animal
 Passive immunization
o With RIG when indicated Post Exposure Prophylaxis (PEP)
 Given to high risk individuals
Local Wound Care:  Give the Verocell Vaccine or Duck Embryo Vaccine
a) Allow wound to bleed and wash thoroughly with soap and running  Boosters are given every 3 years while risks persists
water for at least 10-15 minutes
b) Do not suture lacerations CAUSES OF VACCINE FAILURE
c) Do not apply cream or occlusive dressings a) Short IP
d) ATS & antibiotics b) Delay in treatment
c) Incomplete vaccination
If suturing is unavoidable, you have to infiltrate RIG on the wound first before d) No passive immunoglobulin
suturing. You also have to delay the suturing for 2 hours for the RIG infiltration e) Presence of chronic illness
and allow the diffusion of RIG throughout the tissue that are involved

CATEGORIES OF EXPOSURE
Category 1
 Feeding/Touching the animal
 Licking of intact skin
 Exposure to symptomatic patients by sharing of eating & drinking
utensils
 Causal contact to symptomatic patients like talking, visiting and
routine healthcare delivery

Category 2
 Nibbling of uncovered skin with or without bruising
 Minor or superficial abrasion
 Scratches with or without bleeding
o If without bleeding, you have to induce bleeding
 All category 2 involving the head & neck should be classified as
category 3 and manage as such

Category 3
 Licks on broken skin & mucous membranes
Active Immunization (PEP)
 Exposure to rabies patients through bites
 IM, deltoid region
 Contamination of mucous membranes
 1 ml each, over 2-week period (days 0, 3, 7, and 14)
 Mouth to mouth resuscitation
 For persons with immunosuppression (days 0, 3, 7, 14 & 30)
 Unprotected handling of infected carcass
You give 5 doses, but for the sixth dose, it is for additional margin
 Ingestion of raw infected meat
of safety
 Exposure to bats
 All category 2 exposure on head and neck  5 doses of vaccine administered on days 0, 3, 7, 14, & 30

MANAGEMENT OF EACH CATEGORIES REFERENCES

Category I
 PPT
 Wash exposed skin immediately with soap & running water
 Microbiology Manual (2019)
 No vaccine or RIG needed
 Dr. Quiles Recordings
 PrEP may be considered for high risk individuals

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