Rabies pathophysiology and disease management includes therapies and adverse effects and drug interactions. Content taken from published articles and books valid and accurate content.

1. Rabies
Presented By: Waqas Siddiqe
Reg No: 06332013059
Presented By: Waqas Siddiqe
Reg No: 06332013059
RABIES
Presented By: Waqas Siddiqe
Reg No: 06332013059
RABIES
Presented By: Waqas Siddiqe
Reg No: 06332013059

2. Content:
Content of Discussion!!
1.
Introduction,
Clinical
Symptoms and
Diagnosis of
Rabies
2.
Disease
Management
(PREP, PEP,
Antiviral and other
protocols)
4.
Recent
Advancements
and Case Studies
3.
Contra
Indications and
Adverse Effects of
Treatment

3. Introduction to Rabies:
• Rabies is a viral zoonotic disease that causes progressive and
fatal inflammation of the brain and spinal cord in humans and
other mammals. It was historically referred to
as hydrophobia ("fear of water")
• All warm-blooded animals, including humans, are susceptible to
rabies infection. The virus, a rhabdovirus, is often present in
the salivary glands of rabid animals and is excreted in
the saliva; thus, the bite of the infected animal introduces the
virus into a fresh wound.
• Rabies is one of the neglected tropical diseases (NTD) that
predominantly affects already marginalized, poor and vulnerable
populations.
Introduction to Rabies:
 Hydrophobia
 Rabies is a viral zoonotic disease
 Progressive and fatal inflammation of
the brain and spinal cord in humans
and other mammals
 Rhabdovirus, is often present in
the salivary glands
 Rabies is one of the neglected tropical
diseases (NTD)

4. Content:
How Does Rabies Affect Your Body?
Rabies moves from an infected wound to brain over time.
1. Incubation:
Rabies virus can spend
days to weeks in your
body before it gets into
your nervous system
(incubation).
2. Prodromal phase:
RABV travels through your nerve
cells into your brain and spinal
cord, causing nerve damage as it
goes. Immune system tries to fight
back, causing flu-like symptoms.
Nerve damage might cause
tingling, pain or numbness.
4. Coma.
Many people enter a coma
in the final stages of a rabies
infection. Rabies eventually
leads to death.
3. Acute neurologic
phase:
In this phase, the rabies virus
starts damaging brain and
spinal cord. About two-thirds
of people have furious rabies,
and others having paralytic
rabies.

5. Clinical Symptoms:
The first are flu-like symptoms
• Fever
• Headache and anxiety
• Sore throat and cough
Then follows a neurologic period
• Aggression
• Convulsions
• Hyper salivation and hydrophobia
• Hallucinations
• Paralysis
• Hyperventilation
• The final stage is coma which leads to
death.
The first are flu-like symptoms
 Fever
 Headache and anxiety
 Sore throat and cough
Then follows a neurologic period
 Aggression
 Convulsions
 Hyper salivation and hydrophobia
 Hallucinations
 Paralysis
 Hyperventilation
 The final stage is coma which leads to death.
Clinical Symptoms:

6. Clinical Diagnosis:
Rabies can be difficult to diagnose because, in the early stages, it is easily confused with other diseases or
even with a simple aggressive temperament. The reference method for diagnosing rabies is the fluorescent
antibody test (FAT).
Clinical Diagnosis:
Rabies can be difficult to diagnose because, in the early stages, it is easily confused with other diseases or even
with a simple aggressive temperament. The reference method for diagnosing rabies is the fluorescent
antibody test (FAT).
Saliva test.
Saliva spit into a tube. Saliva
can be tested by virus isolation
or reverse transcription followed
by polymerase chain reaction
(RT-PCR).
Skin biopsy.
a small sample of skin from the back
of your neck. Skin biopsy specimens
are examined for rabies antigen in the
cutaneous nerves at the base of hair
follicles.
Cerebrospinal fluid test
(lumbar puncture).
a needle to take a cerebrospinal
fluid (CSF) from your lower
back. Blood tests. Serum and
spinal fluid are tested for
antibodies to rabies virus.
MRI.
You’ll lie in a machine that
takes pictures of your brain.
Your provider will use the
pictures to help determine
what’s causing your symptoms

7. Pre-exposure prophylaxis (PREP)
 Vaccination before exposure based on the
recommendations of your local health
authority.
 It’s a series of two shots. Frequently need
boosters depends on how high your risk
of exposure is.
 Once certain symptoms of a rabies
infection develop, it’s almost always fatal.
To date, there have been fewer than 20
cases of humans surviving a symptomatic
rabies infection.
Management of Rabies:

8. Dose:
Single dose vial of vaccine should be
reconstituted with accompanying
sterile diluent to final volume of 1mL
before administration.
Administration Route:
Intramuscular in the deltoid area for
adults, in the deltoid area or the
anterolateral aspect of the thigh for
children. Do NOT use the gluteal
area for HDCV or PCECV.
Indications:
Pre-exposure AND post-
exposure prophylaxis.

9. Post exposure prophylaxis (PEP)
 It consists of a dose of human rabies
immune globulin (HRIG) and rabies
vaccine given on the day of the rabies
exposure, and then a dose of vaccine
given again on days 3, 7, and 14.
 For people who have never been
vaccinated against rabies previously, post
exposure prophylaxis (PEP) should
always include administration of both
HRIG and rabies vaccine.
Management of Rabies:

10. Treatment of Rabies:
• Wound Care:
• If you're bitten by an animal, the first
step is to clean the wound immediately
and thoroughly with soap and water.
• Regardless of rabies risk, animal bites
can cause serious damage when the
wound is severe. For example, bites may
lead to local and/or systemic infection
and can damage nerves or tendons.
• For post-bite first aid, the World Health
Organization recommends flushing and
washing the wound for a minimum of 15
minutes. This cleaning should include the
use of soap and water, and a povidone-
iodine solution if it is available.
Wound Care:
 Clean the wound immediately and thoroughly with soap and
water.
 Regardless of rabies risk, animal bites can cause serious
damage when the wound is severe.
 For example, bites may lead to local and/or systemic infection
and can damage nerves or tendons.
 For post-bite first aid, the World Health Organization
recommends flushing and washing the wound for a minimum
of 15 minutes.
 This cleaning should include the use of soap and water, and a
povidone-iodine solution if it is available.
Management of Rabies:

11. Administration Route:
Local infiltration around wound, with
remaining immunoglobulin administered
intramuscularly in an anatomical site
distant from where vaccine was placed.
Indications:
Post-exposure prophylaxis with human rabies
immunoglobulins is indicated for ONLY those persons who
1) did not receive appropriate pre-exposure prophylaxis and
2) 2) have not previously received post-exposure
prophylaxis for rabies in accordance with ACIP
recommendations.

12. Antiviral Agents for Rabies:
Ribavirin:
Ribavirin has in vitro activity against rabies virus
infection.
Favipiravir:
It sold under the brand name Avigan among others, is
an antiviral medication used to treat influenza in Japan. It
is also being studied to treat a number of other viral
infections
Bufotenine:
Bufotenine is able to inhibit the rabies virus infection in
in vitro and in vivo models, increasing the survival rate of
infected animals. It can also delay the onset of
symptoms. Bufotenine inhibits the penetration of rabies
virus in mammalian cells through an apparent competitive
mechanism by the nicotinic acetylcholine receptor.
Side Effects:
 There is evidence that use during
pregnancy may result in harm to
the baby. Teratogenic and embryo
toxic effects were shown on four
animal species.
 The risk or severity of CNS
depression can be increased when
Bufotenine administrated
Antiviral Agents for Rabies:
Ribavirin:
Ribavirin has in vitro activity against rabies virus
infection.
Favipiravir:
It sold under the brand name Avigan among
others, is an antiviral medication used to
treat influenza in Japan. It is also being studied to
treat a number of other viral infections
Bufotenine:
 Bufotenine is able to inhibit the rabies virus
infection in in vitro and in vivo models,
increasing the survival rate
 It can also delay the onset of symptoms.
 inhibits the penetration of rabies virus in
mammalian cells through an apparent
competitive mechanism by the nicotinic
acetylcholine receptor.
Side Effects:
 There is evidence that use during
pregnancy may result in harm to the
baby Teratogenic and embryo toxic
effects were shown on four animal
species.
 The risk or severity of CNS depression
can be increased when Bufotenine
administrated
3

13. Management of Rabies:
Milwaukee Protocol
Jeanna Giese, in 2004, survived rabies using the experimental
Milwaukee Protocol
 The Milwaukee Protocol, an experimental rabies
treatment, involves inducing a coma and administering
antiviral drugs to buy time for the immune system.
 Introduced in 2004, its efficacy is unproven, and it's not
widely adopted. Rabies prevention through vaccination
and post-exposure prophylaxis remains the standard
approach.
4

14. Management of Rabies:
Aggressive or Palliative Approach to Therapy:
• Neurological symptoms and medical complications may be alleviated by the use of sedatives,
narcotic analgesics, antiepileptic medications, and neuromuscular blockers. Barrier nursing
techniques should always be used to prevent exposures of health care workers or family
members during management of a patient with rabies. However, transmission of rabies virus to a
health care worker has not been documented to date.
• In unusual circumstances, the attending physicians and the patients (or, more commonly, their
relatives) may wish to use an aggressive approach to therapy with the aim of curing the disease.
However, it must be clearly understood that even if such an approach were successful, the patient
likely would be left with permanent disabling neurological deficits.
• Patients considered for aggressive care must be admitted to a hospital where there is access to a
critical care unit with sophisticated modern medical technology and skilled medical and nursing
personnel, in anticipation of the development of multiple medical complications, including
multiple-organ failure
Management of Rabies:
Management of Rabies:
Management of Rabies:
Aggressive or Palliative Approach to
Therapy:
Neurological symptoms and medical complications may be
alleviated by the use of sedatives, narcotic analgesics,
antiepileptic medications, and neuromuscular blockers.
 Barrier nursing techniques should always be used to
prevent exposures of health care workers or family
members during management of a patient with rabies
 In unusual circumstances, the attending physicians and
the patients (or, more commonly, their relatives) may
wish to use an aggressive approach to therapy with the
aim of curing the disease.
 Patients considered for aggressive care must be admitted
to a hospital where there is access to a critical care unit
with sophisticated modern medical technology and
skilled medical and nursing personnel.
5

15. Management of Rabies:
Combination Therapy
• It is possible that a combination of specific therapies may be more effective. This
approach with the use of, for example, vidarabine and IFN has been tried for patients
with a late stage of disease. Combinations of therapies are also being used for the
treatment of other viral diseases. Ribavirin and IFN-α provide a clinically synergistic
effect in the treatment. For example, combination therapy for a patient with rabies might
include administration of rabies vaccine (multiple-site intradermal route), HRIG
(intramuscular), ribavirin (intravenous and intraventricular), IFN-α (intravenous and
intraventricular), and ketamine (intravenous infusion).
Management of Rabies:
Combination Therapy
It is possible that a combination of specific therapies may be
more effective.
 vidarabine and IFN has been tried for patients with a late
stage of disease.
 Ribavirin and IFN-α provide a clinically synergistic effect in
the treatment.
For example, combination therapy for a patient with rabies might include
administration of rabies vaccine (multiple-site intradermal route), HRIG
(intramuscular), ribavirin (intravenous and intraventricular), IFN-α (intravenous and
intraventricular), and ketamine (intravenous infusion).
6

16. Contraindications:
Immunosuppression:
• Immunosuppressive agents should not be administered during post
exposure therapy unless essential for the treatment of other conditions.
When post exposure prophylaxis is administered to an immunosuppressed
person, they should receive the current 4 dose vaccines schedule with an
additional dose of vaccine on day 28 (1mL IM in deltoid on days 0, 3, 7,
14, and 28) in addition to HRIG on day 0.
• Corticosteroids, other immunosuppressive agents, anti-malarials, and
immunosuppressive illnesses can interfere with the development of active
immunity after vaccination. For persons with immunosuppression, pre
exposure prophylaxis should be administered with the awareness that the
immune response might be inadequate.
Immunosuppression:
Immunosuppressive agents should not be administered during
post exposure therapy unless essential for the treatment of other
conditions.
Corticosteroids, other immunosuppressive agents, anti-
malarials , and immunosuppressive illnesses can interfere with
the development of active immunity after vaccination. For
persons with immunosuppression, pre exposure prophylaxis
should be administered with the awareness that the immune
response might be inadequate.
In mouse models, administration of corticosteroids increased
the mortality rate and shortened the incubation period.
Corticosteroid therapy generally is not considered for the
management of brain edema in rabies. Severe edema associated
with a risk of brain herniation is rare in patients with rabies.
Contraindications:
Immunosuppression:
Immunosuppressive agents should not be
administered during post exposure therapy
unless essential for the treatment of other
conditions.
Corticosteroids, other immunosuppressive
agents, anti- Malaria interfere with the
development of active immunity after
vaccination.
In mouse models, administration of
corticosteroids increased the mortality
rate and shortened the incubation period.
Allergies:
People who have a history of serious
hypersensitivity to components of rabies
vaccine should be revaccinated with caution.
History of serious hypersensitivity to rabies
vaccine must be revaccinated, antihistamines
can be administered. Epinephrine should be
readily available to counteract anaphylactic
reactions.

17. Adverse Reactions:
• Once initiated, rabies prophylaxis should not be interrupted or discontinued
because of local or mild systemic adverse reactions to rabies vaccine. Usually,
such reactions can be successfully managed with anti-inflammatory and
antipyretic agents, such as ibuprofen or acetaminophen.
• Although serious systemic, anaphylactic, or neuro paralytic reactions are rare
during and after the administration of rabies vaccines, such reactions pose a
serious dilemma for the patient and the attending physician. A patient’s risk of
acquiring rabies must be carefully considered before deciding to discontinue
vaccination.
Human Diploid Cell Vaccine (HDCV)
• Studies of HDCV recipients reported local reactions (e.g., pain at the injection
site, redness, swelling, induration) among 60-89.5% of recipients. Most local
reactions were mild and resolved spontaneously within a few days. Mild
systemic reactions (e.g., fever, headache, dizziness, gastrointestinal symptoms)
were reported.
 Once initiated, rabies prophylaxis should not be interrupted or discontinued because
of local or mild systemic adverse reactions to rabies vaccine. Usually, such reactions
can be successfully managed with anti-inflammatory and antipyretic agents, such as
ibuprofen or acetaminophen.
 Although serious systemic, anaphylactic, or neuro paralytic reactions are rare during
and after the administration of rabies vaccines, such reactions pose a serious dilemma
for the patient and the attending physician. A patient’s risk of acquiring rabies must be
carefully considered before deciding to discontinue vaccination.
Human Diploid Cell Vaccine (HDCV)
Studies of HDCV recipients reported local reactions (e.g., pain at the injection site,
redness, swelling, induration) among 60-89.5% of recipients. Most local reactions were
mild and resolved spontaneously within a few days. Mild systemic reactions (e.g., fever,
headache, dizziness, gastrointestinal symptoms) were reported.
Adverse Reactions:

18. Adverse Reactions:
Purified Chick Embryo Cell Vaccine
(PCEC)
• In studies of PCEC use, local reactions
(e.g., pain at the injection site,
redness, swelling, induration)
reported. In one study, 7% of children
administered PCEC experienced mild
to moderate clinical reactions. It could
be due to administration of PCEC
alone, or post exposure prophylaxis
(PCEC co-administered with HRIG) or
PCEC administered concomitantly with
another vaccine.
Purified Chick Embryo Cell Vaccine (PCEC)
In studies of PCEC use, local reactions (e.g.,
pain at the injection site, redness, swelling,
induration) reported.
 In one study, 7% of children administered
PCEC experienced mild to moderate clinical
reactions.
 It could be due to administration of PCEC
alone, or post exposure prophylaxis (PCEC
co-administered with HRIG) or PCEC
administered concomitantly with another
vaccine.
Adverse Reactions:

19. Adverse Reactions:
Human Rabies Immune Globulin (HRIG)
• In a clinical trial involving 16 volunteers,
participants receiving HRIG alone (no vaccine)
commonly reported local reactions including
pain/tenderness , erythema and induration.
• Systemic reactions were reported in 75% of
participants in conventional HRIG group and 81%
in heat-treated group. Headache was the most
commonly reported systemic
Neurological Adverse Events
• Rare, individual case reports of neurologic adverse
events following rabies vaccination have been
reported, but in none of the cases has causality been
established. Five cases of neurologic illness
resembling Guillain-Barre syndrome occurring after
treatment with HDCV or PCEC have been
identified. One case of acute neurologic syndrome
involving seizure activity was reported following the
administration of HDCV and human RIG. Other
central and peripheral nervous system disorders
have been temporally associated with HDCV
vaccine.
Human Rabies Immune Globulin
(HRIG):
 In a clinical trial involving 16
volunteers, participants receiving HRIG
alone reported local reactions including
pain/tenderness , erythema and
induration.
 Systemic reactions were reported in 75%
of participants. Headache was the most
commonly reported systemic
Adverse Reactions:
Neurological Adverse Events:
Rare, individual case reports of neurologic adverse events
following rabies vaccination have been reported, but in
none of the cases has causality been established. Five
cases of neurologic illness resembling Guillain-Barre
syndrome occurring after treatment with HDCV or
PCEC have been identified.
One case of acute neurologic syndrome involving seizure
activity was reported following the administration of
HDCV and human RIG. Other central and peripheral
nervous system disorders have been temporally
associated with HDCV vaccine.

20. 1. Monoclonal antibody cocktails
a type of new anti-rabies
treatment. Monoclonal antibodies
are biologic medications that act
as artificial antibodies.
2. Other recent research found a
combination of two monoclonal
antibodies could cure rabies in
preliminary animal studies, even
after they showed symptoms of
rabies in their brains.
These treatments are meant to replace HRIG in PEP, which is sometimes
in short supply and carries risk for transmitting blood-borne pathogens

21. Case Studies:
1) Ahmad a 25-year-old wildlife biologist, was conducting fieldwork in an area known for its bat population. One
evening, he was bitten on the hand by a bat while handling it for research purposes. Concerned about the risk of
rabies transmission, he sought medical attention promptly.
Clinical Presentation:
• Patient presented with a bat bite on the right hand, experiencing pain and mild swelling. The patient reported the
incident occurred within the last 24 hours.
Medical Decision Making:
• The healthcare team took immediate action, cleaning the wound thoroughly and administering rabies post-
exposure prophylaxis (PEP). The treatment involved a series of rabies vaccinations over a 28-day period and a
dose of rabies immune globulin.
2) A 40-year-old individual from a rural area, presented to a healthcare facility with advanced symptoms of rabies.
The patient reported a history of an unexplained fever, anxiety, and hydrophobia over the past week.
Clinical Presentation:
Upon examination, Patient Z exhibited severe neurological symptoms, including paralysis, difficulty swallowing,
and hyperactivity. The patient's clinical history revealed a dog bite.
Medical Management:
Given the advanced stage of the disease, the medical team focused on providing palliative care to manage
symptoms. Antiviral therapies were considered, but their efficacy in advanced cases is limited. Supportive measures
included pain management, sedation for agitation, and nutritional support