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INFECTIOUS DISEASES

Topic: Rabies
Lecturer: Dr. San Diego

ANIMAL BITES: RABIES

Regions 3, 4-A, 5 and 12


reported the most number
of cases from 2008 to 2018

 95% Rabies death occurs in Asia and Africa


 Rabies is a major public health problem
o Fatal once symptoms appear
o One death every 15 mins. worldwide News report cases of
o 99% human cases result from dog bites rabies every now and
o 4 out of 10 deaths are in children then to keep us aware
 Rabies is 100% vaccine preventable that there a lot of lives
o Vaccinate to save lives taken away by this
o Vaccinate to stop transmission infection
o No bites = No rabies
 Zero by 2030
 September 28 – World Rabies Day SPECIES AFFECTED BY RABIES
 Factors for rabies incidence (WHO, 2013):
o Poverty  Canine (Dog samples):
o Poor sanitation common
o Crowding  Category 2: Predominates
in all cases
 Male patients are common
to be bitten
 Age >15 years old
predominates
 Most are domestically
owned

R.A. No. 9482: ANTI RABIES ACT OF 2007


 Goals:
o Adequate funding for Vaccine production
o Eliminate Rabies and Declare Philippines as Rabies Free
Country by 2030
Lecture Discussion: Rabies, Countries or Areas at Risk  This law penalizes irresponsible dog owners

2 Countries are shaded light green  means there is no risk of rabies


infection at all Fine for Irresponsible Owners:
 Japan  500 – dog became stray
 New Zealand because it was not caged or
leashed
Africa and Asia in general are shaded red  high risk of rabies infection  2,000 – owner refuses to get
 Travelers who want to visit some countries here  WHO their dog vaccinated
recommends that they get pre-exposure immunization (PrEP)  10,000 – unvaccinated dog bit
 Other people whom contact with domestic animals is very likely someone
(e.g. dogs and other vectors of rabies)  get also PrEP  25,000 – unvaccinated dog bit
someone and the owner
refuses to give help/
assistance to the victim

 Although we have this law in the Philippines, the problem right now is
implementation

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INFECTIOUS DISEASES
Topic: Rabies
Lecturer: Dr. San Diego

RABIES Non-bite exposures are less important and are infrequent modes of
 An infectious Viral disease caused by Lyssa Virus transmission:
 Envelope, ssRNA virus under the family Rhabdoviridae  Contamination of intact mucosa (eyes, nose, mouth, genitalia) with the
 This viral infection is mainly spread by infected animals saliva of infected animal
 Mode of transmission: Close contact with infected saliva from rabid  Licks on broken skin
animals  Inhalation of aerosolized virus in closed areas (e.g. caves with rabid
bats, laboratories for rabies diagnosis)
Rhabdovirus:
1. Rabies – meningoencephalitis Lecture Discussion: Non-bite exposures in the Clinical Setting
2. Ebola – hemorrhagic fever Non-bite exposures can happen in the clinical setting  intubating of a
3. Marburg – hemorrhagic fever rabies infected patient
 When this happens, the team involved in intubating will need to be
CASE: given vaccination

Pathology of Rabies Infection

 Case above is a rat bite


 However, bites from rats, rabbits, other rodents, reptiles and birds
do not pose a risk for rabies infection

What if the patient is asking you “Do I need to receive an anti-rabies


vaccination?”
 No, it is not necessary to take PEP in bite cases by house rats
(domesticated rats)
 If the patient is bitten by wild rats/rodents  prudent to take PEP
from an infectious disease physician  Entry of infection  virus is introduced from a rabid dog bite (the virus
is present in saliva)
 Initially, virus will replicate on the muscle where the patient was bitten
 Main objective of the virus is to ascend to the brain, so it will utilize the
nervous system, starting from the peripheral nervous system to the CNS
 Virus ascends spinal cord
 Virus reaches the brain and causes fatal encephalitis
 Once it reaches the brain, it will spread to different organs, one of which
is the salivary glands

 Although rat rabies is extremely rare  if the patient is willing to


JEANNA GIESE:
pay then you can give the vaccine. The difference is that the
regimen you will give is the pre-exposure prophylaxis (PrEP)
wherein you just give 3 doses

How to treat a Rat Bite:

 While she was trekking on a park, she saw a bat lying on the ground.
Due to her curiosity, not knowing it was rabid, she picked it up and
was bitten
 When her symptoms appeared she was rushed to the hospital and
the Milwaukee protocol wherein she was induced to a comatose
state and antiviral medication was given
 She was able to survive the rabies infection  In 2011, she was able
to graduate from college
Trivia about Jeanna Giese:
 Jeanna Giese was only 15 yrs. old when she became the world’s first
known survivor of Rabies without receiving any vaccination
 New method of Rabies treatment was formulated, known as
 Control bleeding Milwaukee protocol developed by Rodney Willoughby Jr. and is a
 Clean the wound with soap and warm water treatment used in rabies-infected human beings
 Apply antibiotic ointment  It involves chemically inducing the patient into a coma, followed by
 Cover with a clean, dry dressing the administration of antiviral drugs combined with ketamine and
 Watch for signs of infection amantadine

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INFECTIOUS DISEASES
Topic: Rabies
Lecturer: Dr. San Diego

INCUBATION PERIOD STAGES OF HUMAN RABIES INFECTION

 Once the virus enters the body, it will initially in an incubation period
 Incubation period  it is the phase where there is presence of the virus
but no signs and symptoms develops
o Length of incubation period depends on:
 Infecting strain
 Size of inoculum
 Prodrome  stage where you develop the classic manifestations
 Degree of innervation
o Typical constitutional signs like fever, headache, malaise,
 Proximity to CNS
irritability, nausea and vomiting
o It can happen within months or even years
o The virus has already arrived at the CNS
 Incubation period  best time to give the 2 types of vaccines
o Duration 2-10 days
o Active vaccine – takes care of the virus that has a slow phase
 Acute neurologic phase  stage where you see the encephalitic or
of ascending infection
paralytic rabies
o Passive vaccine – introducing antibodies to immediately kill
o Symptoms are hyperexcitability, hyperactivity, hallucinations,
any virus (creates an immediate response)
excessive salivation, hydrophobia, and aerophobia
o Duration 1 week
Incubation Period
 Coma  stage where patient becomes calm
 Average: 1-3 months (90-95% of cases)
o Results from the damage to brain stem and hypothalamus
 >1 year (5-10% of cases)
o Virus is spread to other organs  multiorgan failure and
 Duration of incubation period depends on certain factors:
autonomic instability
o The amount of the virus inoculated into the wound or mucosa
o Duration 5-14 days
o Severity of exposure
 Death
 Patients with multiple and/or deep penetrating bite
o Cumulative impact of cardiac, respiratory, and organ failure
wounds may have shorter incubation period
from other stages  increased risk cardiac arrhythmias and
o Location of exposure
respiratory depression
 Patients with bite wounds in highly innervated areas
o Duration is variable
and/or close to the CNS may have shorter incubation
period
Acute Neurologic Stage
 Is the stage when the virus reaches the CNS and replicates most
 In vitro studies show that velocity of axonal transport of the virus exclusively within the gray matter
ranges from 25 to 50 mm per day  Has 2 types: Neurologic or Paralytic
 The spread of the rabies virus in the coulometer and optic nerves
could be as fast as 12 mm/day
 This happens in patients who are bitten on the head or
near the vicinity of the CNS

 Neurologic/Furious Type – accounts for 80-90%


o Classic manifestations are seen here: hydrophobia and
aerophobia
 Paralytic/Dumb Type – accounts for 10-20%
o Silent type
 Incubation period is the 1st stage of human rabies infection o Manifestation: paralysis, muscle fasciculation, and sensory
disturbance

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INFECTIOUS DISEASES
Topic: Rabies
Lecturer: Dr. San Diego

Coma
 Begins within 5-10 days after symptoms start
 Cardiac arrhythmias is common
 Hyperventilation which leads to periodic and ataxic respiration to apnea
 Hematemesis is experienced by 30-60% of patients before death
 Pituitary dysfunction is also present as part of disordered water balance

LABORATORY DIAGNOSIS

 Category 3 examples:
o For letter c)  intubation of rabies infected patients
o For letter e)  Kinilaw/Kilawin na aso, a type of dish wherein
dog meat is prepared raw (uncooked) and is cured in vinegar
 NOTE: If meat is properly cooked (through heat) 
rabies virus will die because they are sensitive to heat

Case What Category Is It?

CATEGORY OF EXPOSURE
Category 3  because although it is a minor or
superficial scratch, since it is located on the face,
Dog owners fall on this category it is automatically elevated to Category 3

Category 3  it is also a minor or superficial


scratch but since it is bleeding spontaneously
then it is Category 3

Category 3  because it is a bite with punctured


wounds

ACTIVE VS. PASSIVE IMMUNITY

Remember this! Even if it is a Category 2 exposure,


if it is in the head and neck  automatically
elevated to Category 3

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INFECTIOUS DISEASES
Topic: Rabies
Lecturer: Dr. San Diego

 Most patients are initially okay to receive the vaccine BUT if they will be
given the idea that they are to receive 2 types of rabies vaccine, they
will now become hesitant. Why is this so?
o Due to the payment
o Another is injecting it on the site of bite (very painful)
 As physicians, we need to be able to explain the importance of them
receiving the 2 types of vaccine to prevent the rabies infection
o Explain to the patient that once symptoms already manifest 
it is already late and nothing can be done to reverse the
condition

ACTIVE RABIES VACCINE  Intramuscular  uses 1.0 mL dose and the syringe is angulated at a 90o
angle for it to hit the muscle

How to Perform the ID and IM PEP regimen

 3 Types of Active Vaccines:


o Verorab
o Rabipur
o Speeda

 Vials are usually prepared as 1.0 mL and route of administration is


either ID or IM Lecture Discussion:
o In private practice, we usually give the whole 1.0 mL vial When doing the intradermal method, this is the dosing  2-2-2-0-2
o An alternative practice is that we can use just 0.1 mL of it so it  Schedule: 0, 3, 7 and 28
can be divided into 10  more will be shared with the vaccine  Initially, the patient will have 1 dose (0.1 mL) given ID at 2 sites (right
 This practice was initially introduced by WHO and left deltoid)
 Each time the patient goes back to you (starting day 0), you give it
at the 2 sites
 Based on the latest guidelines  day 28 can be omitted. This means
that the patient can just receive until day 7 (2-2-2-0)

Lecture Discussion:
When doing the intramuscular method, this is the dosing  1-1-1-1-1
 5 dose IM regimen
 Schedule: 0, 3, 7, 14 and 28
 Give the vaccine on the deltoid region
 If the patient cannot comply with this schedule, then a different
schedule may be utilized  2-1-1 regimen

 Intradermal  uses 0.1 mL dose and you angulate the syringe in a 15o
angle so that it will not penetrate the subcutaneous and muscle.
Vaccine is introduced in between the epidermis and dermis

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INFECTIOUS DISEASES
Topic: Rabies
Lecturer: Dr. San Diego

How to give the Passive Vaccine:


 It is directly injected on the site of bite
o So if a patient is bitten on the face, then you inoculate the
passive vaccine on the face

Lecture Discussion:
Alternative schedule for IM method  2-1-1
 No anesthesia is given because it will just intervene with the vaccine
 2-0-1-0-1
 2 doses are given on day 0 on the right and left deltoid  If the patient has multiple bite sites, then distribute the vaccine to the
 If the patient is a child, inject it on the right and left thigh different areas using the computed dose
 Patient must go back for an additional dose on day 7 and 21  If the computed dose is lesser than what is needed by the patient, you
can dilute the vaccine with sterile water to at least 2x
PASSIVE RABIES VACCINE

 When a patient receives the full vaccination at day 7, at day 14, 90 or


 HRIG  immune globulins are from humans. It is more expensive
after 1 year  there is seroconversion
because you will be needing more vials (as it is only prepared at 2
o Seroconversion is the transition from the point of viral
mL/vial)
infection to when antibodies of the virus become present in
 ERIG  immune globulins are from horses (equine). It is more
the blood
affordable than HRIG (prepared at 5 mL/vial)
 What if the patient did not comeback at day 7?
o Then the seroconversion will be lesser (less production of
antibodies against the rabies virus)

MANAGEMENT OF REACTION
Anaphylaxis
 Give 0.1% adrenaline or epinephrine (1:1,000 or 1 mg/mL) underneath
the skin (subcutaneous) or into the muscle (intramuscular)
o Adult – 0.5 mL
 Comparing the use of HRIG vs. ERIG on a 50 kg patient: o Children – 0.01 mL/kg, maximum of 0.5 mL
o For HRIG, you will be needing 1000 IU  Repeat epinephrine dose every 10-20 minutes for 3 doses
 1000 / 150 (since each vial has 150 IU/mL) = 6.6 mL  Give steroids after epinephrine
 6.6 / 2 (since each vial has 2 mL) = 3.3 vials needed
 You cannot buy a 3.3 vial in the market so you Hypersensitivity Reactions
will be needing a total of 4 vials  Give antihistamines, either as single drug or in combination
 If status quo for 48 hrs. despite combination of antihistamines, may give
o For ERIG, you will needing 2000 IU short course (5-7 days) of combined oral antihistamines plus steroids
 2000 / 200 (since each vial has 200 IU/mL) = 10 mL  If patient worsens and condition requires hospitalization or becomes
 10 / 5 (since each vial has 5 mL) = 2 vials needed life threatening, may give IV steroids in addition to antihistamines
 We can see from the computation that although HRIG requires a lower
IU, since its preparation contains less  it is much more expensive

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INFECTIOUS DISEASES
Topic: Rabies
Lecturer: Dr. San Diego

CRITERIA FOR HIGH AND LOW RISK EXPOSURES ADDITIONAL VACCINE

 If the patient does not know his vaccination history about anti-tetanus
 give tetanus toxoid (Td) and TIG/ATS
o Td  active immunization
o TIG/ATS  passive immunization
 Td is given on the deltoid
 TIG/ATS is directly inoculated on the site of bite
MEDICAL MANAGEMENT OF ANIMAL BITES
Key steps in medical management of bite wounds: CLINICAL MANAGEMENT
 Considering the fatal outcome and absence of cure for human rabies
 Wash with soap and water
once signs and symptoms begin, management should center on
 Liberal irrigation
ensuring comfort for the patient, using sedation, avoiding intubation
 Debridement of devitalized tissue
and life support measures
 If signs of infection are present:
o Swab for culture
o Antibiotic therapy
 Immediate suturing of the wound – not advisable

Antibiotic Use in Wound Management:


 In any classification of any animal bites, these are the medications you
can give
 Recommended antimicrobials for frankly infected wounds include:
o Amoxicillin/clavulanic
 Adults - 500 mg p.o. TID
 Children - 30-45 mg/kg/day in 3 divided doses SUPPORTIVE CARE
o Cloxacillin  Patients should be admitted in a quiet, draft-free, isolation room
 Adults - 500 mg p.o. QID  IV fluids may be given
 Children - 10-150-100 mg/kg/day in 4 divided doses  Invasive and Heroic procedures must be avoided. (Intubation,
o Cefuroximeaxetil Mechanical Ventilation, Cutdown)
 Adults - 500 mg p.o. BID  Provide suitable emotional and physical support
 Children - 10-15 mg/kg/day in 2 divided doses  Discuss and provide important information to relatives concerning
transmission of disease and indication for post-exposure prophylaxis of
contacts.
 Honest gentle communication concerning prognosis should be provided
to the relatives

ISOLATION ROOM
 Isolation rooms are advised to minimize harm on patients and care
givers
 Rooms should be draft-free; with grilled windows and doors that can be
locked from outside

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