Family and Community Medicine

Didactics

Animas, Julie Faith C.

Clinical Clerk
Overview
An acute infection of the central nervous system that is almost always
fatal.
Transmitted to humans from the bite or scratch of a rabid animal.
Caused by Rabies virus (RABV), a member of the Lyssavirus genus
100% fatal once clinical symptoms appear, but 100% preventable through
vaccination
Properties of the Virus
Properties of the Virus
Epidemiology
~59,000 human deaths annually worldwide
Recent data: 1,750 Filipinos have died due to rabies in the past 5 years
95% of cases occur in Asia and Africa
Main vector globally: domestic dogs (99%)
Mostly affects 15 years old male
Epidemiology
Pathophysiology
→
Entry: Virus inoculated through bite/scratch deposited in
muscle/connective tissue.
Local replication: Initial viral multiplication at the site (may be
bypassed).
Neural invasion: Virus enters peripheral nerves at neuromuscular
junctions(specifically nicotinic acetylcholine receptors)
Pathophysiology
Retrograde spread: Ascends along nerves to the central nervous system.
CNS phase: Replicates in neurons, causing progressive encephalitis.
→
Centrifugal spread: From CNS via nerves to salivary glands (highest
titers) and other organs (pancreas, kidney, heart, retina, cornea).
Once in the CNS, the disease is almost universally fatal.
Mode of Transmission
BITE EXPOSURE NON-BITE EXPOSURE
From infected animals Scratches, open wounds or
Dogs mucous membranes licked by
Cats an infected animals
Contamination of intact mucosa
Bats
Inhalation of aerosolized virus
Human - Human
Incubation period
Prodromal phase
Clinical
Acute neurologic phase Manifestations
Coma/Death
Incubation Period
Extremely variable ranging from 4 days to 7 years; generally 20-
90 days
Virus is close to or present at the site of infection
Asymptomatic
Prodromal phase
Lasts for 10 days; generally 2-3 days, sometimes only a few hours
Non-specific manifestations
Fever, sore throat, anorexia, nausea, vomiting, generalized body
malaise, headache, abdominal pain
Paresthesia or pain at site of bite
Due to viral multiplication at spinal ganglion just before it enters brain
Acute neurologic phase
Furious rabies (80% cases)
Paralytic rabies (20% cases)
Furious Type (Encephalitic rabies)
Usually lasts 1-7 days
3 Cardinal Signs:
1. Fluctuating consciousness- normal periods alternating with agitation
depression
irritability
2. Phobic or Inspiratory spasms
Phobic spasms: hydrophobia, aerophobia
Inspiratory spasms: occur without stimulation, are infrequent and less intense.
Furious Type (Encephalitic rabies)
[Link] instability: hypersalivation, hypertension, hyperthermia,
tachycardia, arrhythmia (can be cause of death), piloerection, fixed dilated
or constricted pupils, anisocoria, excessive sweating, priapism, and
spontaneous ejaculations
Paralytic Type (Dumb or Atonic rabies)
Develops 2-10 days after clinical signs; usually last 2-4 days
Weakness, varied forms of paralysis
Localized to bitten extremity
Diffuse, symmetric paralysis
Ascending paralysis, GBS-like
Hyperactivity & agitation usually absent
Aerophobia and hydrophobia in 50 %
Paralytic Type (Dumb or Atonic rabies)
Meningeal signs (headache, neck stiffness) may be prominent
despite a normal sensorium
Persistent fever from the onset of limb weakness
Intact sensory function of all modalities except at the bitten region
Bladder dysfunction
DIAGNOSTIC TESTS
Direct Fluorescent Antibody Testing (FAT)
Direct Rapid Immunohistochemical Test (DRIT)
Realtime Polymerase Chain Reaction (PCR)
Histologic: Negri Bodies
DIAGNOSTIC TESTS
Fluorescent Antibody Testing (FA)-
- gold standard for rabies diagnosis;
- rapid and sensitive;
Specimen: tissue samples from brainstem, thalamus, cerebellum and the hippocampus
(Ammon’s horn)- are recommended for increased sensitivity of the test

Positive DFA test showing

rabies antigens as
fluorescent-apple-green
areas
 DIAGNOSTIC TESTS
Polymerase Chain Reaction (PCR)
- “amplifying” a specific DNA sequence;
- Specimen: CSF, serial saliva specimens
Serology Serum Rapid Fluorescent Focus Inhibition Test (RFFIT)
Histologic findings
- Negri bodies are Cerebral inclusion bodies are round cytoplasmic inclusions of
assembling nucleocapsid are pathognomonic of rabies infection, but are found in only about 80% of
cases.
o The biting animal should be examined for rabies
 Management
and Prevention
Management of Potential
Rabies Exposure
 Management of Potential Rabies
Exposure
[Link] of post-exposure prophylaxis (PEP) shall not be delayed for any
reason.
[Link] washing of the bite wound/ exposed area with soap and water
and application of an antiseptic solution.
[Link] are no absolute contraindications to rabies PEP. Patients allergic to
a specific vaccine/RIG or its components shall be given the alternative
vaccine/RIG.
[Link] owners have the responsibility to keep their dogs for observation
under the Rabies Act of 2007.
Immunization
Active Immunization
Intradermal (ID) regimen:
Dose: 0.1 mL for both Purified Vero Cell Rabies Vaccine (PVRV) and
Purified Chick Embryo Cell Vaccine (PCECV)
One dose should be given on each deltoid (right & left) or anterolateral
thighs in infants on days 0,3,7,28.
Intramuscular (IM) regimen:
Dose: 0.5 mL for PVRV and 1.0 mL for PCECV
Zagreb regimen schedule: Day 0, 7, 21.
CDC shortened schedule: Day 0,3,7,14.
Active Immunization (Vaccine)

Generic Name Preparation Dose

Purified Verocell Rabies ID - 0.1 ml
0.5 ml/vial
Vaccine (PVRV) IM - 0.5 ml

Purified Chick Embryo Cell ID - 0.1 ml

1 ml/vial
Vaccine (PCECV) IM - 1.0 ml
Passive Immunization (Vaccine)

Generic Name Preparation Dose

Human Rabies
Immune Globulin 150 IU/ml at 2 ml/vial 20 IU/kg
(HRIG)
Equine Rabies
Immune Globulin 200 IU/ml at 2 ml/vial 40 IU/kg
(ERIG)
Passive Immunization (Vaccine)
Computation and Dosage of Rabies Immune Globulin
HRIG at 20 IU/kg. body weight (150 IU/ml)
50 kg patient x 20 IU/kg = 1000 IU
1000 IU ÷ 150 IU/ml
= 6.7 ml
ERIG/ F(ab')2 at 40 IU/kg. body weight (200 IU/ml)
50 kg patient x 40 10/kg = 2000 IU
2000 IU ÷ 200 IU/ml
= 10 ml
Post-Exposure Prophylaxis
Local Wound Treatment
Wounds shall be immediately and vigorously washed and flushed with soap
or detergent, and water preferably for 10 minutes.
Apply alcohol, povidone iodine or any antiseptic.
Suturing of wounds shall be avoided at all times since it may inoculate
virus deeper into the wounds.
Any ointment, cream or wound dressing shall not be applied to the bite
site because it will favor the growth of bacteria and will occlude drainage
of the wound, if any.
Anti-tetanus immunization may be given, if indicated.
Tetanus Prophylaxis

Vaccination History
Indication for
Unknown or <3 Doses 3 or More Doses
TT
Immunization
Td TIG/ATS Td TIG/ATS

All Animal Bites YES YES NO NO

Antimicrobials
Recommended antimicrobials for frankly infected wounds
Adults: 500 mg PO TID
Amoxicillin/ Clavulanic Children: 30-40 mg/kg/day in 3 divided
doses
Adults: 500 mg PO QID
Cloxacillin Children: 10-150-100 mg/kg/day in 4 divided
doses
Adults: 500 mg PO BID
Cefuroxime axetil
Children: 10-15 mg/kg/day in 2 divided doses
Antimicrobials

Recommended antimicrobials for frankly infected wounds

For penicillin allergic Adults: Doxycycline
patients Children: Erythromycin

Instances where there are no obvious signs of Infection

Adults: 500 mg PO TID
Amoxicillin
Children: 30-45 mg/kg/day in 3 divided doses
 Management of Previously Vaccinated
Individuals
PEP/PrEP History RIG Management
Patient received complete PrEP (Day 0
and 7) OR Patient received at least No Determine if high or low risk bite
days 0 and 3 doses of PEP ID/IM
Patient received complete PrEP (Day 0
and 7) OR Patient received at least
Yes, if
days 0 and 3 doses of PEP ID/IM AND Give full course PEP
indicated
Patient is immunocompromised OR
bitten by a bat
Patient did not complete PrEP OR Yes, if
Give full course PEP
Patient received only 1 dose of PEP indicated
Criteria for high and low risk exposure
Risk of exposure Criteria Recommendation

ANY ONE OF THE FOLLOWING:

Immediately provide booster
1. Biting animal cannot be observed,
injections to the patient
dies or is sick
Booster doses:
2. Site of bite is in highly innervated
High risk parts of the body - neck, head,
0.1 ml ID at 4 sites on day 0
OR
genital area, hands and toes
0.1 ml ID/IM at 1 site on days 0 and
3. Multiple deep bites
3
4. Patient is coming from GIDA*
Criteria for high and low risk exposure
Risk of exposure Criteria Recommendation

Last dose of vaccine was within the

previous 3 months AND Biting animal is
healthy, owned, kept on a leash or can
be confined and is available for
observation Observe biting animal for 14 days.
Low risk AND ANY ONE OF THE FF: If animal remains health, withhold
1. Biting animal is the same animal booster dose
that bit the patient previously,
2. Biting animal is previously
immunized
3. Bite is on the extremities/trunk
Pre-Exposure Prophylaxis
Benefits
The need for passive immunization product (RIG) is eliminated
PET vaccine regimen is reduced from five to two doses Protection
against rabies is possible if PET is delayed
Protection against inadvertent exposure to rabies is possible
The cost of PEP is reduced
Target Population
Personnel in rabies diagnostic laboratories
Veterinarians and veterinary students
Animal handlers
Health care workers directly involved in care of rabies patients
Individuals directly involved in rabies control
Field workers
It is recommended that children 2-10 yrs old also be immunized because
increased risk and severity of animal bites in this age group
Regimen
Regimen PVRV PCECV
Day 0 - 0.1 ml Day 0 - 0.1 ml
Intradermal (2doses) Day 7- 0.1 ml Day 7- 0.1 ml
Day 21/28** - 0.1 ml Day 21/28** - 0.1 ml

Day 0 - 0.5 ml Day 0 - 0.1 ml

Intramuscular * Day 7- 0.5 ml Day 7- 0.1 ml
Day 21/28** - 0.5 ml Day 21/28** - 0.1 ml
Regimen
Type of Recommended Booster Schedule (Without
Population at Risk
Risk definite exposure)
-1 Booster dose 1 year after primary immunization:
1. Health workers a. One (1 site) 0.1 ml ID dose of
handling rabies cases PVRV or PCEC on DO; OR
2. Workers in rabies b. One (1site) Vial of 0.5 ml PVRV or 1.0 ml PCEC
High Risk
laboratories, intramuscularly on D0
(exposures
3. Veterinarians, given
may not
4. Veterinary students, -Thereafter, 1 booster, if Ab titers fall below 0.5
known)
5. Animal handlers (dog IU/ml
trainers, workers in pet OR
shops, zoos, etc.) - In the absence of serologic testing, 1 booster dose
every 5 years
Regimen
Type of Recommended Booster Schedule
Population at Risk
Risk (Without definite exposure)

Low Risk
(exposures General Population No routine booster after primary immunization
are known)
PREVENTION
NATIONAL RABIES CONTROL PROGRAM
Department of Agriculture and Department of Health
Standardized the treatment and management guidelines of human rabies
Address management of animal rabies particularly; Massive dog vaccination
Health Promotion
Massive health information campaigns
Integration of rabies programs in school curriculums
Establishment of Animal Bite Treatment Centers
NATIONAL RABIES CONTROL PROGRAM
Vision: Rabies Free Philippines by 2030
Goal: To end human deaths from dog-mediated rabies by 2027
NATIONAL RABIES CONTROL PROGRAM
Anti-Rabies Act of 2007 (RA 9482)
Batas Pambansa Bilang 97
Executive Order No. 84
Memorandum of Agreement on Interagency Implementation of the NPRCP
Thank you for your kind
attention!