RABIES

INFECTIOUS AND TROPICAL DISEASE DIVISION DEPARTMENT OF PEDIATRICS FACULTY OF MEDICINE UNIVERSITY OF NORTH SUMATERA

Conclusions
Chocolate consumption enhances cognitive function, which is a sine qua non for winning the Nobel Prize, and it is closely correlated with the number of Nobel laureates in each country.

RABIES VIRUS
Rabies virus is a member of the genus Lyssavirus in the family Rhabdoviridae. The viruses are bullet shape with 10-nm spike like glycoprotein peplomers covering the surface.

Rabies is spread to people through close contact with infected saliva via bites or scratches.

Though transmission has been rarely documented via other routes such as contamination of mucous membranes (i.e. eyes, nose, mouth), aerosol transmission, and corneal and organ transplantations.

RABIES
Rabies is a zoonotic disease (a disease that is transmitted from animals to humans) that is caused by a virus. All species of mammals are susceptible to rabies virus infection, but only a few species are important as reservoirs of the disease. Domestic dogs, cats, cattle, foxes, raccoons, bats, ferrets, skunks.

INCUBATION PERIOD
The incubation period is typically 1 3 months, but may vary from < 1 week to > 1 year. Incubation period is shorter in children, and the nearer the bite is to the head the shorter the incubation period. It also depends on the severity of wound.

RESPONSE TO INFECTION
Following a rabid bite, no immune response is detectable in unvaccinated subjects before encephalitis has developed. Rabies antibody is found in serum, then in CSF at least a week after the onset.

Pleocytosis is observed in only 60% of patients.

SYMPTOMS
Prodromal Symptoms
Itching or paraesthesiae at the site of the healed bite wound in 40% of patients
Nonspecific symptoms including fever, headache, myalgia, fatigue, sore throat, gastrointestinal symptoms, irritability, anxiety and insomnia. The disease progresses within 1 week.

Common Symptoms
1. 2. 3. 4. 5. 6. Itching at the healed bite wound Hydrophobic spasms Aerophobia Feeling of terror Aggression Hypersalivation

FURIOUS

VS

PARALYTIC
Furious (Encephalitic) Rabies

Occurred in 80% of cases. Fever, confusion, hallucinations, combativeness, muscle spasms, hyperactivity and seizures.

Autonomic dysfunction including hypersalivation, excessive perspiration, gooseflesh, pupillary dilation and/or priapism.
Hydrophobia and aerophobia: involuntary, painful contraction of the diaphragm and accessory respiratory, laryngeal and pharyngeal muscles in response to swallowing liquids (hydrophobia) or a draft of air (aerophobia).

Hypersalivation and pharyngeal dysfunction resulted in appearance of foaming at the mouth Episodes of excitation, aggression, anxiety or hallucinations interspersed with periods of calm lucidity.

Cranial nerve lesions (III, VII and IX)

Coma followed withing days by death.

FURIOUS
Less common.

VS

PARALYTIC
Paralytic (Dumb) Rabies

Prodromal symptoms are followed by paraesthesiae or hypotonic weakness.

Started near the site of the bite and spreading cranially.

Ascending paralysis results in constipation, urinary retention, respiratory failure and inability to swallow.

Hydrophobic spasms may occur in terminal phase and death after 1-3 weeks.

DIFFERENTIAL DIAGNOSIS
Tetanus Intoxication GuillainBarre syndrome Other viral encephalomyelitides

DIAGNOSIS
Laboratory is usually normal initially. Complete blood counts are usually normal. CSF may reveals mild mononuclear cell pleocytosis, with a mildly elevated protein level. Diagnostic useful specimens: serum, CSF, fresh saliva, brain tissue, skin biopsy from the neck (must include at least 10 hair follicles)

Rabies virus-specific antibodies

RT-PCR DFA

BITE AND SCRATCH WOUND

LOCAL TREATMENT
Prompt local treatment of all bite wounds and scratches. Immediate and thorough flushing and washing of the wound for a minimum of 15 minutes with soap and water, or detergent. Followed by application of 70% ethanol or povidone-iodine solution. The wound closure, if possible, should not be sutured. Tetanus toxoid and antibiotics for other infection (if needed).

CATEGORIES OF CONTACT AND RECOMMENDED PEP

Categories of contact with suspected rabid animal Category I Touching or feeding animals, licks of intact skin Category II Nibbling of uncovered skin, minor scratches or abrasions without bleeding Category III Single or multiple transdermal bites or scratches, licks on broken skin; contamination of mucous membrane with saliva from licks, contacts with bats Post-exposure prophylaxis measures

None

Immediate vaccination and local treatment of the wound

Immediate vaccination and administration of rabies immunoglobulin; local treatment of the wound

History of animal bite (dog, cat, monkey) Animal is missing or death High risk wound Give Rabies vaccine & Rabies IG Low risk wound Give Rabies vaccine Animal can be observed for 10-14 days

Check the specimen of animal brain Positive Continue vaccine Negative Stop vaccine

If brain specimen is not checked, continue vaccine

History of animal bite (dog, cat, monkey) Animal is missing or death Animal can be observed for 10-14 days High risk wound Give Rabies vaccine & Rabies IG Animal is healthy Animal died Animal died Low risk wound Wait for the observatio n outcome

Animal is healthy
No vaccine

Stop vaccine

Continue vaccine Check the specimen of animal brain

Positive

Negative

Continue vaccine

Stop vaccine

RABIES VACCINE & IMMUNOGLOBULIN

WHO (Essen) Regimen
Day 0
3 7 14 28

Rabies Vaccine 1 dose IM

1 dose IM 1 dose IM 1 dose IM 1 dose IM

Rabies Immunoglobulin +
-

Zagreb Regimen
Day 0 7 21 Rabies Vaccine 2 dose IM 1 dose IM 1 dose IM Rabies Immunoglobulin + -

RABIES VACCINE & IMMUNOGLOBULIN

Rabies vaccine
Purified vero cell vaccine (available in Indonesia as Verorab) Dose 0,5 mL IM on deltoideus muscle in adult or lateral thigh in children Human diploid cell vaccine Purified chick embryo cell vaccine Dose 0.5 mL IM on deltoideus muscle in adult or lateral thigh in children

Rabies Immunoglobulin
Human rabies immunoglobulin; dose 20 IU/kg Equine rabies immunoglobulin; dose 40 IU/kg Half of the dose is given around the wound, and the other half is intramuscularly injected in different part from the vaccine. Should be given within 7 days after vaccination.

PROGNOSIS
Wound cleansing and vaccination within a few hours after contact with a suspect rabid animal can prevent the onset of rabies and death.

PROGNOSIS
Once a person exhibit signs of the disease, the person most likely will die. Less than 10 documented cases worldwide survive from clinical rabies have been reported, and only 2 have not had a history of pre- or postexposure prophylaxis.

15-year-old girl in whom clinical rabies developed one month after she was bitten at her left index finger by a bat. Rabies vaccine was not administered. Treatment including induction of coma with ketamine and midazolam was done, while a native immune response matured. Ribavirin and amantadine were also added. Lumbal puncture after 8 days showed increased level of rabies antibody, and sedation was tapered. Patient was removed from isolation after 31 days, and discharged after 76 days. After 5 months, she was alert and communicative, but with choreoathetosis, dysarthria, and unsteady gait.

RECOMMENDED READINGS
Rabies fact sheets. World Health Organization. http://www.who.int/mediacentre/factsheets/fs099/en/ Rabies. Centers for Disease Control and Prevention. http://www.cdc.gov/rabies/index.html Warrell MJ. Rabies. In: Cook GC, Zumla A, eds. Mansons Tropical Diseases, 22nd ed. Wiloughby Jr RE, Tieves KS, Hoffman GM, Ghanayem NS, AmlieLefond CM, Schwabe MJ, et al. Survival after treatment of rabies with induction of coma. NEJM. 2005; 352:2508-14

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