Rabies
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RABIES Viral infection of animals Excreted in saliva of an infected animal Almost always fatal once symptoms appear ORDER: Mononegavirales Non-segmented, negative stranded RNA genomes Classified in Rhabdoviridae family (bullet shaped) Lyssavirus – includes rabies virus Ephemo virus Vesiculovirus STRUCTURE Approximately 180nm long & 75nm wide Genome encodes 5 proteins: a. Nucleoproteins (N) b. Phosphoprotein (P) c. Matrix Protein (P): associated with RNP & envelope d. Glycoprotein (G) e. Polymerase (L) 2 major structural components 1. helical ribonucleoprotein core (RNP) 2. envelope EPIDEMIOLOGY Asia >3.1 B people potentially exposed to dog bites >35000 human rabies deaths 98% from rabid dog bites >10 M PET annually >40% < 15 years old Philippines 400 cases or 6/M population annually Dogbites >98% of cases Almost 3000 lab confirmed (+) in almost all islands of the country Region V (Central Luzon) II National rabies Control and Eradication Program, 1994 Annual consultation of 400000 cases >80% require PET Only 15% receive PET DOG 98% responsible for all human rabies cases CAT 1.3% Others : <1% RITM (2001) Dog bites # 1 consultation 1500 new cases: >3000 ff-up/ mo 27% : < 5 years 65.5% : <19 yrs Exposures Category III – 83% Category II – 16% Category I – 1% TRANSMISSION Bites of rabid animals Licking of mucosa or open wounds
Rabies
Microbiology (dra De Castro)
VARIATION Severity bite 13ofDecember 07 Site of bite in relation to nerve supply and distance from CNS Size of inoculum, protection offered by clothing Age and immune status of the host CLINICAL MANIFESTATION Animal Rabies Sudden change in behavior Characteristic hoarse howl Watchful, apprehensive expression of eyes, staring, blank gaze Drooling of saliva Paralysis of lower jaw and tongue, inability to drink Pralysis or uncoordinated gait In some cases, lies quiescent, biting when provoked Marked excitability and restlessness pacing in cage If restrained, attacks objects within range, bites cage If at large, runs aimlessly, biting anything in its way Depraved appetite, self-mutilation Snaps at imaginary objects Sudden death without associated s/sx Prodromal Symptom Lasts from 2 to 10 days Non specific (malaise, fatigue, headache, anorexia, nausea and vomiting, restlessness, ill defined anxiety, sore throat, fever, pain or paresthesia close to the site of exposure) 2 Clinical Forms Encephalitic (Furious) rabies : 80% Paralytic (Dumb) rabies : 20% A.
B.
Encephalitic or Neurologic Phase Excessive restlessness Increasing or uncontrollable excitement Agitation, confusion, hallucination, combativeness Seizures, meningismus, opisthotonus, focal paralysis Hydrophobia, foaming at the mouth Aerophobia Dumb or Paralytic Flaccid ascending, symmetric paralysis Sensory abnormalities Decreased tendon reflexes Coma
Respiratory paralysis death Circulatory collapse death
DIAGNOSIS High index of suspicion History of animal exposure Clinical symptoms Fluorescent antibody staining : most rapid skin biopsy Early Intervention Holds The Key
PERIOD OF COMMUNICABILITY Dogs and cats: o 3-5 days before the onset of symptoms until the entire course of the illness
Once inoculated ( dog bite) Virus starts growing at the site of wound
INCUBATION PERIOD 1 day to 5 years (8 weeks) Average IP : 10-90 days N = 707 71% cases < 1 month 87% cases < 3months
Once fixed to peripheral nerves Virus begins to spread to the nervous system
Once symptoms appear
Microbiology – Rabies by Dra De Castro
Page 2 of 3
Death in virtually 100% cases
o
WHO Recommendations on Rabies PET Category Tx I
II
III
Type of Contact Touching or feeding of animals – licks on intact skin Nibbling of uncovered skin Minor scratches or abrasions w/o bleeding, licks on broken skin
Recommended None, if reliable history is available Administer vaccine immediately
Single or multiple transdermal bites or scratches, contamination of mucous membrane w/ saliva
Rabies Ig + vaccine immediately
BITE MANAGEMENT : RITM If dog is > 1 yr old and vaccination certificate shows that it has received at least 2 doses of a potent vaccine, the patient may not need treatment. Observe dog for 10 to 14 days Indications of Admission Only patients requiring parenteral antibiotics for secondarily infected bites Laboratory Work-up
None, unless bite wound is frankly infected Gm stain, C/S of wound discharge
OBSERVE DOG for 14 days from time of bite POST EXPOSURE TREATMENT (PET) General Principles: To minimize the amount of virus at the site of inoculation To develop a high titer of neutralizing antibody early and monitor it for as long as possible Passive Immunization Human rabies Immune Globulin (HRIG) 20 U/kg on day 0 Or Equine Rabies Immune Globulin (ERIG) 40 U/kg on day 0 ANST If total computed dose is inadequate to infiltrate all wounds, it may be diluted 2-3 fold using sterile saline solution
If RIG was omitted on day 0, it may still be given anytime within the 1st 7 days after the initial dose of the vaccine Active Immunization Given : deltoid muscle in adults anterolateral thigh in young infants Recommended Regimen o 2-site ID regimen (2-2-2-0-1-1) o Purified Vero Cell Rabies Vaccine (PVRV) or o Purified Duck Embryo Vaccine (PDEV) 0.2 ml ID @ 2 sites on days 0, 3, 7 and 1 site on days 30 and 90 Alternative Regimen o Full IM regimen (Essen) PVRV 0.5ml/ PDEV 1.0 ml on the deltoid on days 0,3,7,14,28
o
*no training for ID injections 8 site ID regimen (8-0-4-0-1-1) PVRV/ PDEV (0.1ml) ID at 8 sites on day 0 4 sites on day 7 1 site on days 30,90 *useful when RIG is unavailable or cannot given *deltoid, lateral thigh, suprascapular area and lower quadrant of the abdomen D0. deltoid and thigh D7 2-1-1 regimen (zaagreb) PVRV (0.5ml) / PDEV (1.0ml) IM at 2 sites on day 0 1 site on days 7 and 21 * (+) potential suppression of antibody levels if used with RIG
Active Immunization Against Rabies Regimen
Dose PVRV
2 site ID
0.1ml
Standard IM
0.5ml
8 site ID
0.1ml
2-1-1 IM
0.5ml
PDEV 0.2m l 1.0m l 0.2m l 1.0m l
No. of doses on specified days Day Day Day Day 28/3 7 14 21 0
Day 0
Day 3
Day 90
2
2
2
0
0
1
1
1
1
1
1
0
1
0
8
0
4
0
0
1
1
2
0
1
0
1
0
0
Supportive Management Local Wound Care Immediate vigorous washing and flushing with soap and water, detergent or water Apply alcohol, tincture or aqueous solution of iodine or povidone iodine Avoid or delay suturing of wounds. If unavoidable, do so loosely Instill RIG deep into wound before suturing Anti-tetanus prophylaxis should be initiated Antibiotic Prophylaxis Administer prophylactic antibiotics to.. all category III cat bites category III dog bites that are either deep, penetrating, multiple or extensive category III dog bites on the hand Amoxicillin For frankly infected wounds Cloxacillin or Co-Amoxyclav Other exposures (category I and II) may be given antibiotics only IF the wound is infected GUIDELINES Pregnancy is NOT a contraindication for treatment with PVRV, however, nerve tissue vaccine is not recommended
Persons consulting even after months of the bite should be treated as 1st time consultation. If animal was healthy after 14 days, no PET needed. Vaccine should never be given in the gluteal area Avoid chloroquine, anti-epileptic drugs, systemic steroids, heavy alcohol consumption during vaccination interference If cannot be avoided, use standard IM regimen Treat cat bites as dog bites Bites by rats, rabbits, rodents and bats rarely warrant vaccination
POST EXPOSURE PROPHYLAXIS
Microbiology – Rabies by Dra De Castro WHY? To protect To simplify To avoid
Page 3 of 3
even in case of inapparent Exposure or in case of delayed PET PET the need for RIG administration
WHO? Subjects at permanent risk working with rabies virus dx’tic, research, production lab staff Subjects at frequent risk contact with sensitive animals In enzootic areas due to profession (veterinarians) Pastime or travel Children, more likely To be exposed HOW? Regimens: PVRV (0.5ml) or PDEV (1.0ml) IM Or PVRV (0.1ml) or PDEV (0.2ml) ID Booster dose q 1-3 years
MUST be vaccinated SHOULD be vaccinated
SHOULD be particularly considered
1 site on days 0, 7, 28
HOW To Prepare and Transport the Animal’s Head 1. Place the head in leak proof container bigger container with liberal amounts of ice/dry ice 2. Label with owner’s name, date of preparation and words “ CAUTION: RABIES SUSPECT ” 3. Freeze if transit time will be >48 i. If kept in room T not > 12 hours from death of animal ii. If kept in ref for a period not > 2 days iii. If kept in frozen condition 4. DO NOT put head in any chemical disinfectant or preservative “If your patient with rabies survives, it only means the diagnosis was wrong”
Rabies
Microbiology (dra De Castro)
VARIATION Severity bite 13ofDecember 07 Site of bite in relation to nerve supply and distance from CNS Size of inoculum, protection offered by clothing Age and immune status of the host CLINICAL MANIFESTATION Animal Rabies Sudden change in behavior Characteristic hoarse howl Watchful, apprehensive expression of eyes, staring, blank gaze Drooling of saliva Paralysis of lower jaw and tongue, inability to drink Pralysis or uncoordinated gait In some cases, lies quiescent, biting when provoked Marked excitability and restlessness pacing in cage If restrained, attacks objects within range, bites cage If at large, runs aimlessly, biting anything in its way Depraved appetite, self-mutilation Snaps at imaginary objects Sudden death without associated s/sx Prodromal Symptom Lasts from 2 to 10 days Non specific (malaise, fatigue, headache, anorexia, nausea and vomiting, restlessness, ill defined anxiety, sore throat, fever, pain or paresthesia close to the site of exposure) 2 Clinical Forms Encephalitic (Furious) rabies : 80% Paralytic (Dumb) rabies : 20% A.
B.
Encephalitic or Neurologic Phase Excessive restlessness Increasing or uncontrollable excitement Agitation, confusion, hallucination, combativeness Seizures, meningismus, opisthotonus, focal paralysis Hydrophobia, foaming at the mouth Aerophobia Dumb or Paralytic Flaccid ascending, symmetric paralysis Sensory abnormalities Decreased tendon reflexes Coma
Respiratory paralysis death Circulatory collapse death
DIAGNOSIS High index of suspicion History of animal exposure Clinical symptoms Fluorescent antibody staining : most rapid skin biopsy Early Intervention Holds The Key
PERIOD OF COMMUNICABILITY Dogs and cats: o 3-5 days before the onset of symptoms until the entire course of the illness
Once inoculated ( dog bite) Virus starts growing at the site of wound
INCUBATION PERIOD 1 day to 5 years (8 weeks) Average IP : 10-90 days N = 707 71% cases < 1 month 87% cases < 3months
Once fixed to peripheral nerves Virus begins to spread to the nervous system
Once symptoms appear
Microbiology – Rabies by Dra De Castro
Page 2 of 3
Death in virtually 100% cases
o
WHO Recommendations on Rabies PET Category Tx I
II
III
Type of Contact Touching or feeding of animals – licks on intact skin Nibbling of uncovered skin Minor scratches or abrasions w/o bleeding, licks on broken skin
Recommended None, if reliable history is available Administer vaccine immediately
Single or multiple transdermal bites or scratches, contamination of mucous membrane w/ saliva
Rabies Ig + vaccine immediately
BITE MANAGEMENT : RITM If dog is > 1 yr old and vaccination certificate shows that it has received at least 2 doses of a potent vaccine, the patient may not need treatment. Observe dog for 10 to 14 days Indications of Admission Only patients requiring parenteral antibiotics for secondarily infected bites Laboratory Work-up
None, unless bite wound is frankly infected Gm stain, C/S of wound discharge
OBSERVE DOG for 14 days from time of bite POST EXPOSURE TREATMENT (PET) General Principles: To minimize the amount of virus at the site of inoculation To develop a high titer of neutralizing antibody early and monitor it for as long as possible Passive Immunization Human rabies Immune Globulin (HRIG) 20 U/kg on day 0 Or Equine Rabies Immune Globulin (ERIG) 40 U/kg on day 0 ANST If total computed dose is inadequate to infiltrate all wounds, it may be diluted 2-3 fold using sterile saline solution
If RIG was omitted on day 0, it may still be given anytime within the 1st 7 days after the initial dose of the vaccine Active Immunization Given : deltoid muscle in adults anterolateral thigh in young infants Recommended Regimen o 2-site ID regimen (2-2-2-0-1-1) o Purified Vero Cell Rabies Vaccine (PVRV) or o Purified Duck Embryo Vaccine (PDEV) 0.2 ml ID @ 2 sites on days 0, 3, 7 and 1 site on days 30 and 90 Alternative Regimen o Full IM regimen (Essen) PVRV 0.5ml/ PDEV 1.0 ml on the deltoid on days 0,3,7,14,28
o
*no training for ID injections 8 site ID regimen (8-0-4-0-1-1) PVRV/ PDEV (0.1ml) ID at 8 sites on day 0 4 sites on day 7 1 site on days 30,90 *useful when RIG is unavailable or cannot given *deltoid, lateral thigh, suprascapular area and lower quadrant of the abdomen D0. deltoid and thigh D7 2-1-1 regimen (zaagreb) PVRV (0.5ml) / PDEV (1.0ml) IM at 2 sites on day 0 1 site on days 7 and 21 * (+) potential suppression of antibody levels if used with RIG
Active Immunization Against Rabies Regimen
Dose PVRV
2 site ID
0.1ml
Standard IM
0.5ml
8 site ID
0.1ml
2-1-1 IM
0.5ml
PDEV 0.2m l 1.0m l 0.2m l 1.0m l
No. of doses on specified days Day Day Day Day 28/3 7 14 21 0
Day 0
Day 3
Day 90
2
2
2
0
0
1
1
1
1
1
1
0
1
0
8
0
4
0
0
1
1
2
0
1
0
1
0
0
Supportive Management Local Wound Care Immediate vigorous washing and flushing with soap and water, detergent or water Apply alcohol, tincture or aqueous solution of iodine or povidone iodine Avoid or delay suturing of wounds. If unavoidable, do so loosely Instill RIG deep into wound before suturing Anti-tetanus prophylaxis should be initiated Antibiotic Prophylaxis Administer prophylactic antibiotics to.. all category III cat bites category III dog bites that are either deep, penetrating, multiple or extensive category III dog bites on the hand Amoxicillin For frankly infected wounds Cloxacillin or Co-Amoxyclav Other exposures (category I and II) may be given antibiotics only IF the wound is infected GUIDELINES Pregnancy is NOT a contraindication for treatment with PVRV, however, nerve tissue vaccine is not recommended
Persons consulting even after months of the bite should be treated as 1st time consultation. If animal was healthy after 14 days, no PET needed. Vaccine should never be given in the gluteal area Avoid chloroquine, anti-epileptic drugs, systemic steroids, heavy alcohol consumption during vaccination interference If cannot be avoided, use standard IM regimen Treat cat bites as dog bites Bites by rats, rabbits, rodents and bats rarely warrant vaccination
POST EXPOSURE PROPHYLAXIS
Microbiology – Rabies by Dra De Castro WHY? To protect To simplify To avoid
Page 3 of 3
even in case of inapparent Exposure or in case of delayed PET PET the need for RIG administration
WHO? Subjects at permanent risk working with rabies virus dx’tic, research, production lab staff Subjects at frequent risk contact with sensitive animals In enzootic areas due to profession (veterinarians) Pastime or travel Children, more likely To be exposed HOW? Regimens: PVRV (0.5ml) or PDEV (1.0ml) IM Or PVRV (0.1ml) or PDEV (0.2ml) ID Booster dose q 1-3 years
MUST be vaccinated SHOULD be vaccinated
SHOULD be particularly considered
1 site on days 0, 7, 28
HOW To Prepare and Transport the Animal’s Head 1. Place the head in leak proof container bigger container with liberal amounts of ice/dry ice 2. Label with owner’s name, date of preparation and words “ CAUTION: RABIES SUSPECT ” 3. Freeze if transit time will be >48 i. If kept in room T not > 12 hours from death of animal ii. If kept in ref for a period not > 2 days iii. If kept in frozen condition 4. DO NOT put head in any chemical disinfectant or preservative “If your patient with rabies survives, it only means the diagnosis was wrong”
