RABIES PROPHYLAXIS

Rabies is an acute viral disease that causes fatal encephalomyelitis in most of the warm blooded animals including man. The virus is found in wild and some domestic animals and is transmitted to other animals and humans through their saliva (following bites, scratches, licks on broken skin and mucus membrane). In India, dogs are responsible for about 95% of human rabies, followed by cats (2%), jackals, mongoose and others (1%). Therefore, the disease is mainly transmitted by the bite of a rabid dog. 

Rabies is caused by a RNA virus that is present in saliva of rabid animal, which is being neurotropic (high affinity for nerves). The virus enters the peripheral nerve through a free nerve ending via the neuromuscular junction and moves internally through axoplasm slowly at a speed of 3mm per hour to reach the spinal cord and brain. 

The incubation period for rabies is typically 2-3 months but may vary form 1 week to 1 year, depending upon factors such as the location of virus entry and viral load. Initial symptoms of rabies include a fever with pain and unusual tingling, pricking, or burning sensation at the wound site. As the virus spreads to the central nervous system, progressive and fatal inflammation of the brain and spinal cord develops.

There are two forms of disease;

1. Furious rabies: results in signs of hyperactivity, excitable behavior, hydrophobia (fear of water) and sometimes aerophobia. Death occurs after a few days due to cardiorespiratory arrest.
2. Paralytic rabies: accounts for 20% cases, less dramatic and usually longer course than the furious form. Muscles gradually become paralyzed, starting at the site of bite or scratch. A comma slowly develops and eventually death occurs.    

POST EXPOSURE PROPHYLAXIS (PEP)

When to seek medical care ?

In countries like India, the disease is endemic with sustained dog to dog transmission, every animal bite is suspected and treatment should be started immediately after exposure. Post exposure prophylaxis should be considered in the following conditions.

• Bites by all warm blooded animals
• Exposure to wild animals
• Rodent bites (especially in forest areas)
• Exposure to bats
• Human to human transmission: Risk is minimal and there are no well documented cases. 

Observation of biting dog/cat:

The PEP should be administered immediately after the exposure. The observation period of 10 days is valid for dogs and cats only. The treatment may be modified if the suspected animal is healthy after a 10 day observation period and PEP can be converted to Pre-exposure prophylaxis.

Vaccination status of biting animal:

Animals vaccinated against rabies do not suffer and transmit the disease. However, animal vaccine failures may occur because of improper administration, inadequate doses, poor quality of vaccines or poor health status of the animal. Hence, irrespective of the vaccination status of the biting animal, the PEP should be given. 

The following World Health Organization (WHO) classification is used for grading the exposure to rabies and guide to provide rabies prophylaxis.

Categories of contact with suspect rabid animal	Post-exposure prophylaxis measures
Category I - touching or feeding animals, animal licks on intact skin (no exposure)	Washing of exposed skin surfaces, no PEP
Category II - nibbling of uncovered skin, minor scratches or abrasions without bleeding (exposure)	Wound washing and immediate vaccination
Category III - single or multiple transdermal bites or scratches, contamination of mucous membrane or broken skin with saliva from animal licks, exposures due to direct contact with bats (severe exposure)	Wound washing, immediate vaccination and administration of rabies immunoglobulin

Post exposure prophylaxis include;

1. Management of animal bite wound
2. Passive immunization with Rabies Immunoglobulin (RIG)
3. Active immunization with Anti-Rabies vaccines (Rabies vaccines)

1. Management of animal bite wound

Prompt local treatment of all bite wounds and scratches is important. The recommended first aid procedures include immediate, thorough flushing and washing of all wounds with soap and water and application of Povidone iodine or Antiseptic having virucidal activity. Washing of wounds is desirable up to 15 minutes and should be carried out as soon as possible with soap and water. If soap or a virucidal agent is not available, the wounds should be thoroughly and extensively rinsed with water.

A bleeding wound at any site indicates severe exposure and should be infiltrated with RIG. Severe bite wounds are best treated by daily dressing, followed by secondary suturing when necessary. 

Tetanus prophylaxis should be given to prevent sepsis in the wounds. 

2. Rabies Immunoglobulin (RIG)

The anti-rabies serum/RIG provides passive immunity in the form of readymade neutralizing antibodies at the site of exposure before the patient to produce his/her own antibodies following anti-rabies vaccination. RIG should be administered to all patients with category III exposure.

There are two types of RIG- Equine RIG (ERIG) and Human RIG (HRIG)

• Equine RIG (ERIG): ERIG is produced by hyper immunization of horses. It carries a small risk of anaphylaxis due to heterogenous origin. (Dosage : 40 IU per kg body weight)
• Human RIG (HRIG): Is of homologous origin and relatively free form the side effects encountered in ERIG. (Dosage : 20 IU per kg body weight).

RIG is administered only once, preferably at or as soon as possible after initiation of post exposure vaccination. It is not recommended beyond the seventh day after the first dose of rabies vaccine. The entire immunoglobulin dose or as much as possible should be infiltrated carefully into or as close as possible to the wounds or exposure sites. RIG must never be given intravenously.

3. Rabies vaccines

Active immunization is achieved by administration of potent cell culture vaccines (CCVs). Currently available CCVs should be administered by IM regimen and CCVs approved for ID use shall be administered by ID regimen.

All animal bite victims of Category II and III exposures, irrespective of their age and body weight require, the same number of injections and dose per injection. 

Rabies vaccines can be administered by intradermal or intramuscular route. 

• Intradermal route: Regimen for PEP (Updated Thai Red Cross Schedule 2-2-2-0-2): This involves the injection of 0.1 ml of reconstituted vaccine per ID site and on two sites per visit (one on each deltoid area, an inch above the insertion of deltoid muscle) on days 0,3,7, and 28.
• Intra muscular route: Regimen for PEP (Essen regimen 1-1-1-1-1) : Intramuscular administration at deltoid region of five injections, one dose each given on days 0,3,7,14 and 28.

Management of Re-exposure in in previously vaccinated individuals

• Proper wound management should be done
• No need for administration of RIG
• One-site intradermal vaccine administration on days 0 and 3 or
• One-site intramuscular administration of an entire vaccine vial on days 0 and 3.

PRE-EXPOSURE PROPHYLAXIS

Pre-exposure vaccination may be offered to High Risk groups such as

• Laboratory staff handling the virus and infected material, clinicians and individuals attending to human rabies case
• Veterinarians, animal handlers and dog catchers
• Wildlife wardens, quarantine officers, etc
• Travelers from rabies free areas to rabies endemic areas

Vaccination: Total three doses are recommended for pre-exposure prophylaxis.

• IM route: 1 full vial to be given on days 0,7 and booster on either day 21 or 28
• ID route: 0.1 ml on one site to be given on days 0,7 and booster dose on either day 21 or 28

High risk groups should check their antibody titers on every 6 months during the initial two year period after the primary vaccination. If it is less than 0.5 IU.ml, a booster dose of vaccine should be given.

Hand, Foot and Mouth Disease (HFMD)

Hand, foot and mouth disease (HFMD) is a viral infection caused by agents of Enterovirus family. Common causes of HFMD are Coxsackievirus A16, Coxsackievirus A6, and Enterovirus 71 (EV-A71). It is a common viral illness of infants and children and uncommon in adults.

Transmission

HFMD is moderately contagious. Infection is spread from person to person by direct contact with nose and throat discharges, saliva, fluid from blisters, or the stool of infected persons. Rarely, infection by swallowing recreational water, such as water in swimming pools. This can happen if the water is not properly treated with chlorine and becomes contaminated with feces from a person who has HFMD.

Clinical features

HFMD is mucocutaneous manifestation that usually affects persons in their preteen and teenage years. Serotypes CVA16 and EV71 are responsible for most epidemic cases of HFMD, but occasionally may be associated with CVA4-CVA7, CV9, CVA10, CVB1-CVB3, CVB5, and echovirus 4. 

After an incubation period of 3-6 days, a prodrome characterized by low fever, malaise, and abdominal or respiratory symptoms precedes the mucosal lesions by 12-24 hours. Adult cases have been associated with severe symptoms and occasional onychomadesis.

Oral lesions typically appear first and are most common on the hard palate, tongue, and  buccal mucosa. The lesions can vary in number from 1 to 10 and typically begin as macules that rapidly progress to 2 to 3 mm vesicles and then to shallow, yellow-grey painful ulcers with an erythematous halo.

Cutaneous vesicles appear concomitantly with or soon after the oral lesions and are most prevalent on the hands and feet, including the palms and soles, but can appear on the face, legs, and buttocks. The lesions can vary in number from a few to over 100. Cutaneous lesions also begin as erythematous macules, but are larger (3-7mm) and develop into cloudy, white oval vesicles with a red halo. Both oral and cutaneous lesions are usually tender or painful and resolve in 5-10 days without treatment or scarring.

HFMD can cause neurologic manifestations that range from aseptic meningitis to acute flaccid paralysis and brainstem encephalitis, which can be associated with systemic features such as severe pulmonary edema and shock. 

Laboratory diagnosis

In mild cases of HFMD, particularly in patients with a high probability of having the disease based on their clinical characteristics and sick contacts, laboratory testing is not necessary. Testing is usually reserved for severe cases and epidemiological studies.

Samples collected : Throat and vesicle specimens are considered to be the most useful sources for diagnostic purpose. Other samples collected include blood, rectal swabs, stool. 

Laboratory tests include: Viral culture, Polymerase chain reaction and ELISA.

Prevention

• Frequent washing of hands with soap and water after changing diapers, after using toilets, after using blowing nose, coughing or sneezing , and before and after caring for someone who is sick.
• Clean and disinfect frequently touched surfaces and shred items including toys and doorknobs.
• Avoid touching eyes, nose and mouth with unwashed hands
• Avoid close contact with sick people

Treatment

No proven antiviral treatment exists for HFMD. Thus, the goal of treatment are typically supportive, as for any self limited viral syndrome.