Approach to RABIES

Approach to RABIES

Introduction

Rabies is a zoonotic disease (a disease that is transmitted from animals to humans), caused by the rabies virus, of theLyssavirus genus, within the family Rhabdoviridae. Domestic dogs are the most common reservoir of the virus, with more than 95% of human deaths caused by dog-mediated rabies.

The virus is transmitted in the saliva of rabid animals and generally enters the body via infiltration of virus-laden saliva from a rabid animal into a wound (e.g. scratches), or by direct exposure of mucosal surfaces to saliva from an infected animal (e.g. bites). The virus cannot infiltrate intact skin. Once the virus reaches the brain, it further replicates, resulting in presentation of clinical signs from the patient.

There are two clinical manifestations of rabies :

• furious (classical or encephalitic) or 
• paralytic 

Furious rabies is most common form of human rabies, accounting for approximately 80% of cases.

Rabies is a 100% vaccine-preventable disease. Countries embarking on rabies elimination programmes have successfully experienced marked reductions, often progressing to the elimination of rabies. Elimination programs often revolve around mass dog vaccination campaigns, where at least 70% of the dog population should be covered in order to break the cycle of transmission in dogs, and to humans.

History

Identify the following in any suspected case of rabies virus exposure : 

• The nature of the interaction with the animal (Recall that "provocation" is not an indication of rabies risk, since humans may not understand what is provocative to a wild animal.)
• Strange animal behavior (eg, nocturnal animal out during the daytime)
• Vaccination status of the animal for rabies [8]
• Availability of the animal for testing

Incubation period

The infected individual remains asymptomatic during this period. The average duration of incubation is 20-90 days.In more than 90% of cases, incubation is less than 1 year.

The incubation period is less than 50 days if the patient is bitten on the head or neck or if a heavy inoculum is transferred through multiple bites, deep wounds, or large wounds. A person with a scratch on the hand may take longer to develop symptoms of rabies than a person who receives a bite to the head.

The rabies virus is segregated from the immune system during this period, and no antibody response is observed.

Prodromal period

The virus enters the CNS. The duration of this period is 2-10 days. Nonspecific symptoms and signs develop. Paresthesia, pain, or intense itching at the inoculation site is pathognomonic for rabies and occurs in 50% of cases during this phase; this may be the individual’s only presenting sign. Symptoms may include the following:

• Malaise
• Anorexia
• Headaches
• Fever
• Chills
• Pharyngitis
• Nausea
• Emesis
• Diarrhea
• Anxiety
• Agitation
• Insomnia
• Depression

Acute neurologic period

This period is associated with objective signs of developing CNS disease. The duration is 2-7 days. Symptoms include muscle fasciculations, priapism, and focal or generalized convulsions. Patients may die immediately or may progress to paralysis, which may be present only in the bitten limb at first but usually becomes diffuse.

The form of rabies known as furious rabies may develop during this period. Patients develop agitation, hyperactivity, restlessness, thrashing, biting, confusion, or hallucinations. After several hours to days, this becomes episodic and interspersed with calm, cooperative, lucid periods. Furious episodes last less than 5 minutes. Episodes may be triggered by visual, auditory, or tactile stimuli or may be spontaneous. Seizures may occur. This phase may end in cardiorespiratory arrest or may progress to paralysis.

Another form of rabies, paralytic rabies, is also known as dumb rabies or apathetic rabies, because the patient is relatively quiet compared with a person with the furious form. Twenty percent of patients do not develop the furious form. Paralysis occurs from the outset, and fever and headache are prominent.

Coma

This begins within 10 days of onset, and the duration varies. Without intensive supportive care, respiratory depression, arrest, and death occur shortly after coma.

Decision to treat Rabies infection

It depends on type of contact or exposure which based on WHO recommendations.

Approach to Post-Exposure Prophylaxis (PEP)

The post-exposure prophylaxis is a three pronged approach. All three carry equal importance and should be done simultaneously as per the category of the bite

• Management of animal bite wound : 
• Passive immunisation: Rabies Immunoglobulins (RIG)
• Active immunisation: Anti-Rabies Vaccines (ARV)

1. Management of animal bite wound : 

• Physical 
  Wash with running tap water Wash the wound with soap and water
• Chemical 
  Apply disinfectant Inactivation of the virus
• Biological 
  Infiltrate immunoglobulins in the depth and around the wound in Category III exposures.

Suturing of wound should be avoided as far as possible. If surgically unavoidable, minimum loose sutures should be applied after adequate local treatment along with proper infiltration of rabies immunoglobulins.

Injection tetanus toxoid should be given to the un-immunised individual. To prevent sepsis in the wound, a suitable course of an antibiotic may be recommended.

2. Passive immunization : Rabies Immunoglobulins (RIG)

The anti-rabies serum/rabies immunoglobulin provides passive immunity in the form of ready-made anti-rabies antibody to tide over the initial phase of the infection. Anti-rabies serum or RIG has the property of binding with the rabies virus, thereby resulting in the loss of infectivity of the virus.

Two types of RIGs are available:

Equine Rabies Immunoglobulins (ERIG) : ERIG is of heterologous origin raised by hyper-immunisation of horses. However, currently manufactured ERIGs are highly purified and the occurrence of adverse events has been significantly reduced. Still these should be administered after sensitivity test.

Human Rabies Immunoglobulins (HRIG) : HRIG are free from the side effects encountered in a serum of heterologous origin, and because of their longer half life, are given in half the dose of equine anti-rabies serum. The anti-rabies sera should always be brought to room temperature (20 – 25ºC) before use.

Dose of rabies immunoglobulins : The dose of equine rabies immunoglobulins is 40 IU per kg body weight of patient and is given after testing for sensitivity, upto a maximum of 3000 IU. The dose of the human rabies immunoglobulins (HRIG) is 20 IU per kg body weight (maximum 1500 IU). HRIG does not require any prior sensitivity testing.

Multiple needle injections into the wound should be avoided. Remaining, if any, after all wounds have been infiltrated, should be administered by deep intramuscular injection at an injection site distant from the vaccine injection site. Animal bite wounds inflicted can be severe and multiple, especially in small children. In such cases, the calculated dose of the rabies immunoglobulin may not be sufficient to infiltrate all wounds. In these circumstances, it is advisable to dilute the immunoglobulins in sterile normal saline 2 to 3 fold to be able to permit infiltration of all wounds. 

The total recommended dose of immunoglobulin must not be exceeded as it may suppress the antibody production by the vaccine. If immunoglobulin was not administered when vaccination was begun, it can be administered upto the seventh day after the administration of the first dose of vaccine. Beyond the seventh day, Rabies Immunoglobulin (RIG) is not indicated since an antibody response to anti-rabies vaccine is presumed to have occurred. Immunoglobulin should never be administered in the same syringe or at the same anatomical site as vaccine.

When more than one wound exists, each wound should be locally infiltrated with a portion of the RabIg using a separate needle and syringe. In such instances, the RabIg can be diluted twofold to threefold in a solution of 0.9% sodium chloride in order to provide the full amount of RabIg required for thorough infiltration of all wounds.

Protective antibodies are present immediately after passive vaccination with RabIg, but they have a half-life of only approximately 21 days. Since vaccine-induced antibodies begin to appear within 1 week, if RabIg is not administered as recommended at the initiation of the rabies vaccine series, there is no value in administering RabIg more than 8 days after initiating an approved vaccine course

Sensitivity test before administration of ERIG: With antisera of equine origin, anaphylactic shock may occur and thus sensitivity testing is mandatory before giving ERIG

3. Active immunisation: Anti-Rabies Vaccines (ARV)

Intra-muscular (IM) Regimens

The currently available vaccines and regimen for IM administration are described below.

1. Cell Culture Vaccines : 

• Human Diploid Cell Vaccine (HDCV)
• Purified Chick Embryo Cell Vaccine (PCEC)
• Purified Vero Cell Rabies Vaccine (PVRV)

2. Purified Duck Embryo.

Five dose intramuscular regimen - The course for post-exposure prophylaxis should consist of intramuscular administration of five injections on days 0, 3, 7, 14 and 28. The sixth injection (D90) should be considered as optional and should be given to those individuals who are immunologically deficient, are at the extremes of age and on steroid therapy. Day 0 indicates date of first injection. 

Site of inoculation : The deltoid region is ideal for the inoculation of these vaccines. Gluteal region is not recommended because the fat present in this region retards the absorption of antigen and hence impairs the generation of optimal immune response. In case of infants and young children antero-lateral part of the thigh is the preferred site.

Intra-dermal (ID) Regimens

Intradermal regimens consist of administration of a fraction of intramuscular dose of certain rabies vaccine on multiple sites in the layers of dermis of skin. The vaccines used are same; however route, dose and site of administration differ. Using ID route, small amount (0.1ml) of rabies vaccines/antigen is deposited in the layers of the skin at multiple sites. The antigen is directly presented to the antigen presenting cells (with out circulation/dilution in blood) at multiple sites triggering a stronger immune response. While , single dose (0.5ml/1ml) of rabies vaccine/antigen when given by IM route gets deposited in the muscles. There after the antigen is absorbed by the blood vessels and is presented to antigen presenting cells which triggers immune response.

Other Consideration

1. Post-Exposure Prophylaxis for previously vaccinated persons

Managing re-exposure following post-exposure treatment with TCV: If reexposed, persons who have previously received full post-exposure prophylaxis (either by IM or ID route) with a potent cell-culture vaccine should now be given only two booster doses, intramuscularly (0.5ml/1ml)/intra-dermally (0.1 ml at 1 site) on days 0 and 3. Proper wound toilet should be done. Treatment with RIG is not necessary.

2.Pregnancy

Because of the potential consequences of inadequately treated rabies exposure and because there is no indication that fetal abnormalities have been associated with rabies vaccination, pregnancy is not considered a contraindication to post-exposure prophylaxis. If the risk of exposure to rabies is substantial, pre-exposure prophylaxis might also be indicated during pregnancy. Rabies exposure or the diagnosis of rabies in the mother should not be regarded as reasons to terminate the pregnancy.

3. Contraindications and Precautions

There are no contraindications to the use of rabies vaccine or RabIg after significant exposure to a proven rabid animal; however, care should be taken if PEP is to be administered to persons who are hypersensitive to the products or to any ingredient in the formulation or component of the container. Expert opinion should be sought in the management of these individuals.

Source : www.rcdhu.com

              www.ncdc.gov.in

              www.who.in