Animal Bite Centers FAQ | The Filipino Doctor
Frequently Asked Questions about Rabies

Table of Contents

SECTION 2: FOR HEALTH PROVIDERS

Q1. How does one treat an animal bite?

Q2. What should not be done with an animal bite wound?

Q3. What are the indications for post-exposure rabies prophylaxis (PEP)?

Q4. How should anti-rabies vaccines be stored to maintain safety and potency before administration?

Q5. Can the rabies vaccine and immuno-globulin be given to a pregnant woman or a lactating mother?

Q6. What type of rabies vaccines are used in rabies-endemiccountries of the South-East Asia Region?

Q7. What are the comparative advantages of using the modern rabies vaccines?

Q8. What are the rabies vaccines recommended by WHO?

Q9. What is the standard vaccination schedule for rabies prophylaxis?

Q10. Are there any shorter intradermal (ID) PEP regimens?

Q11. What are the important points to be considered while administering modern rabies vaccines?

Q12. Do we need to consider specific vaccine potency for ID vaccination?

Q13. How does ID rabies vaccination work when the dose is so small? Does it fully protect against rabies exposure?

Q14. What is rabies immunoglobulin (RIG) and how it is used?

Q15. Is it necessary to perform a skin sensitivity test while using ERIG?

Q16. What precautions should be taken while administering RIGs?

Q17. Is it necessary to perform an antibody test on the patient following anti-rabies vaccination?

Q18. Are there any adverse effects of rabies vaccination?

Q19. Are there any contraindicated drugs or dietary restrictions during anti-rabies vaccination?

Q20. If one rabies vaccine has been used for PEP and it is not available for the last two doses, is it possible to interchange rabies vaccine or vaccination route (IM versus ID)?

Q21. Is there any possibility of failure after PEP?

Q22. If a previously immunized person is bitten by arabid dog again, what is the re-exposure vaccination schedule?

 

SECTION 2. FOR HEALTH PROVIDER

Q1. How does one treat an animal bite?

If a person is bitten by an animal:

  • Wounds should be washed and flushed immediately with soap and water for 10–15 minutes. If soap is not available, flush with water alone. This is the most effective first-aid treatment against rabies.
  • Wounds should be cleaned thoroughly at the health care facility with 70% alcohol or povidoneiodine.
  • Assess the vaccination status: e.g. whether diphtheria, pertussis, tetanus (DPT) or tetanustoxoid vaccination has been given in the past.Tetanus toxoid should be inoculated whennecessary.
  • Antimicrobials should be prescribed to prevent possible bacterial infection.

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Q2. What should not be done with an animal bite wound?

Avoid:

  • Covering the wound with dressings or bandages.
  • Suturing which facilitates further inoculation ofrabies virus.
    • If necessary for closing large wounds, suturing should be done after infiltration of wound with rabies immunoglobulin (RIG). Rabies immunoglobulin of human origin (HRIG) is expensive and only limited amounts are available. Rabies immunoglobulin of equineorigin (ERIG) is available in many countries and is considerably cheaper than HRIG.
    • The sutures should be loose and not interfere with free bleeding and drainage. It is well established that secondary suture of bite wounds results in better cosmetic outcomes.

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Q3. What are the indications for post-exposure rabies prophylaxis PEP)?

The WHO Expert Consultation on Rabies (2013) has categorized rabies risk based on category of exposure and made recommendations for PEP, as shown in Table 1.

Table 1: Categorization of exposure and indications for post-exposure rabies prophylaxis

Category of exposureType of exposure to a domestic or wild animal suspected or confirmed to be rabid, or animal unavailable for testingRecommended post-exposure Prophylaxis
I

Touching or feeding animals Licks on intact skin Contact of intact skin with secretions or excretions of a rabid animal or human case

None, if reliable case history is available

II

Nibbling of uncovered skin Minor scratches or abrasions without bleeding

Administer vaccine immediately. Stop treatment if animal remains healthy throughout an observation period of 10 days or is proven to be negative for rabies by a reliable laboratory using appropriate diagnostic techniques.

III

Single or multiple transdermal bites or scratches, licks on broken skin Contamination of mucous membrane with saliva (i.e.licks) Exposure to bats

Administer rabies vaccine immediately and rabies immunoglobulin, preferably as soon as possible after initiation of post-exposure prophylaxis. Rabies immunoglobulin can be injected up to 7 days after first vaccine dose administration. Stop treatment if animal remains healthy throughout an observation period of 10 days or is proven to be negative for rabies by a reliable laboratory using appropriate diagnostic techniques.

  1. World Health Organization (2013). WHO Expert Consultation on Rabies. WHO Technical Report Series 982. Second Report. Geneva.
    1. Exposure to rodents, rabbits or hares does not routinely require rabies post-exposure prophylaxis.
    2. If a n apparently healthy dog or cat in or from a low-risk area is placed underobservation, treatment may be delayed.
    3. This observation period applies only to dogs and cats. Except for threatened or endangered species, other domestic and wild animals suspected of being rabid should be euthanized and their tissues examined for the presence of rabies antigen by appropriate laboratory techniques.
    4. Bites especially on the head, neck, face, hands and genitals are category III exposures because of the rich innervation of these areas.
    5. Post-exposure prophylaxis should be considered when contact between a humanand a bat.

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Q4. How should anti-rabies vaccines be stored to maintain safety and potency before administration?

Modern rabies vaccines are freeze-dried, giving them a longer shelf-life and stability. The vaccine vial should be kept cool and stored in a refrigerator at 2°C to 8°C. The reconstituted vaccine should be used as soon as possible as it is single-dose vaccine. If it is used for intradermal rabies vaccination, there constituted vaccine must be used within 6 hoursand kept at 2°C to 8°C.

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Q5. Can the rabies vaccine and immunoglobulin be given to a pregnant woman or a lactating mother?

Yes. All modern rabies vaccines are inactivated, safe and potent and can be given to pregnant women or lactating mothers. It has no effect on fetal development during pregnancy or breastfed infants during lactation. The rabies virus is not known to cross the placental barrier in women and healthy babies have been born via caesarean section.

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Q6. What type of rabies vaccines are used inrabies-endemic countries of the South East Asia Region?

Rabies vaccines in use can be categorized on the basis of their origin, as follows:

  • tissue culture origin
  • embryonated egg origin.

Modern rabies vaccines are commercially available as human diploid cell vaccine (HDCV), purified Verocell rabies vaccine (PVRV), purified chick-embryo cellvaccine (PCECV) and purified duck embryo vaccine(PDEV).

WHO is encouraging countries to promote the cost-effective intradermal (ID) rabies vaccination schedule – which is safe and efficacious – to improve accessibility, availability and affordability of modern rabies vaccines.

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Q7. What are the comparative advantages of using the modern rabies vaccines?

Modern rabies vaccines are highly potent, safer touse and provide immunity for a longer period of time which is important, considering the long incubation period of rabies infection.

  • These vaccines are available in freeze-dried form so that they have a longer shelf-life and remain very stable.
  • The vaccines are produced in vials with a disposable syringe and diluents for single intramuscular (IM) use.
  • They can be given to high-risk groups such as children and animal handlers for pre-exposure vaccination.
  • They are also given after animal bites, and are known as post-exposure rabies prophylaxis (PEP).
  • A person is either given anti-rabies vaccination for pre-exposure or PEP. This leads to added protection by inducing memory cells to cause an accelerated immune response when a booster dose of vaccine is administered.

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Q8. What are the rabies vaccines recommended by WHO?

WHO maintains a list of WHO-prequalified rabies vaccines which are commercially available on the international market, which concerns only vaccines administered by the IM route.

WHO also maintains another list of vaccines proven to be safe and efficacious by the ID route,using the WHO-recommended ID regimen.

WHO encourages pharmaceutical companies to undergo the WHO pre qualification procedure to ensure good manufacturing practices and quality assurance.

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Q9. What is the standard vaccination schedule for rabies prophylaxis?

Modern rabies vaccines are administered for pre-exposure and post-exposure prophylaxis and the vaccination schedule is determined accordingly.

Pre-exposure prophylaxis

Intramuscular administration: One dose of vaccineis administered intramuscularly on each of days 0,7 and 21 or 28.

Intradermal administration: One intradermal injectionof 0.1 ml is given on each of days 0, 7 and 21 or 28.

To maximize savings, sessions of intradermal pre-exposure prophylaxis should involve enough individuals to use all opened vials within 6 hours.

Three doses/three visitsIM or ID one dose each on day 0, day 7, and day21 or 28.

Day 0 means day of first vaccination, not necessarily day of bite.

Post-exposure prophylaxis(PEP)

There are three vaccination schedules for this purpose:

Five- versus four-doses IM regimen (“Essen”regimen)

One dose of vaccine is administered intramuscularly on days 0, 3, 7, 14 and 28. Injections must be given in the upper arm (deltoid region) or, in small children, into the anterolateral thigh muscle. Vaccines should never be administered into the gluteal region or the buttocks, where absorption is unpredictable.

The reduction in doses (four doses IM regimen) for PEP recommended by the Centers for Disease Control and Prevention (CDC) in Atlanta, USA, was based in part on studies that indicated that four vaccine doses in combination with rabies immuneglobulin (RIG) elicited adequate immune responses,and that a fifth dose of vaccine did not contribute to more favourable outcomes.

(https://www.cdc.gov/mmwr/)

Full Essen regimen (five visits/with or without RIG) IM one dose each on day 0, day 3, day 7, day 14and day 28.

IM one dose each on day 0, day 3, day 7 and day 14.

Shortened Essen regimen (four visits/four doses with or without RIG) IM one dose each on day 0, day 3, day 7 and day 14.

Rabies PEP should be administered using a five dose IM regimen for persons with immuno suppression.

The first dose should be administered as soon as possible after exposure (day 0).Day 0 means day of first vaccination, not necessarily day of bite.

Abbreviated multisite IM regimen (Zagrebregimen), four doses/three visits (2-1-1) regimen

One dose of vaccine is administered intramuscularly into the left and one into the right upper arm (deltoidregion) on day 0 followed by one dose into the upper arm (deltoid region) on days 7 and 21. This schedule saves two clinic visits and one vaccine dose.

Multisite intradermal (ID) vaccination schedule Updated Thai Red Cross (TRC) regimen/two site ID schedule (2-2-2-0-2)

One dose each (0.1 ml) is given at two sites, on both arms (over deltoids) on day 0, day 3, day 7and day 28.

The standard schedule is recommended indesignated health-care facilities by trained health professionals under the supervision of a medical officer.

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Q10. Are there any shorter intradermal (ID)PEP regimens?

There are clinical trials to shorten PEP in order to improve patient compliance for the full course ofvaccination. A four-site one-week PEP regimen (4-4-4) has been proposed to replace the Thai Red Cross(TRC) regimen, given by four-site ID injections on days 0, 3 and 7. The immunogenicity study results are promising. WHO has recommended further assessment of this regimen through a well-designed study.

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Q11. What are the important points to be considered while administering modern rabies vaccines?

All rabies vaccines are available as single-dose vials for IM use and must be given in the deltoid region(i.e. upper arm, near the shoulder) or, in small children, into the anterolateral area of the thigh muscle (on the upper thigh). As with other injections,the rabies vaccine should not be given in the gluteal region (buttocks) because of low absorption due to the presence of adipose (fat) issue.

  • The IM or ID dose is same for all age groups.
  • It is desirable to use the same type of modern rabies vaccine for the full course of vaccination, such as HDCV, PVRV, PCECV or PDEV.
  • All the rabies vaccines can be used for IM regimen, but only PVRV and PCECV are approved for ID.
  • Antibody response to ID regimen has been unsatisfactory in some groups receiving chloroquine for anti-malarial chemoprophylaxis, therefore an IM regimen should be used in such cases.

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Q12. Do we need to consider specific vaccine potency for ID vaccination?

No. There has been concern as single IM doses are reconstituted in different volumes depending on manufacturers. TheWHO-recommended minimum potency is 2.5 IU per IM dose and the WHO recommended volume of a single dose of rabies vaccine administered per ID site is 0.1 ml.

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Q13. How does ID rabies vaccination work when the dose is so small? Does it fully protect against rabies exposure?

It is a multisite (upper arms, lateral thighs,suprascapular or upper trunk region, and lowerquadrant of abdomen) vaccination technique which elicits a prompt and highly protective immune response with a small dose. Initially eight-site and four-site ID inoculation were conducted but clinicaltrials and immunological studies clearly demonstrated that two-site ID inoculation is sufficient and is also user-friendly and cost-effective. The immune response induced by ID rabies vaccination is the same as with the IM regimens. Rabies antigen is inoculated into the dermis of the skin which helps trigger a high immune response. It has been shown that the antigen presenting cells in the skin are more effective than the ones in muscle.

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Q14. What is rabies immunoglobulin (RIG) and how it is used?

RIG is a biological product which is used to provide immediate ready made antibodies until the patient’sown immune system responds to immunization. RIG may be of human or animal origin.

  • Equine rabies immunoglobulin (ERIG)
  • Human rabies immunoglobulin (HRIG).
  • The dose calculation is done as follows:
  • ERIG – 40 IU/kg body weight with a maximumof 3000 units
  • HRIG – 20 IU/kg body weight with a maximumof 1500 units.

For all category III bites, RIG should be given immediately after the incident. RIG should be infiltrated as much as possible in and around all wounds. After infiltration of the wounds, if there is any remaining RIG, it should be given intramuscularly on the anterolateral region or deltoid region.
Anti-rabies vaccines should then be administered, preferably on the same day, but at a different site(right arm for vaccine and left arm for serum, or vice versa).

  • RIGs remain in short supply throughout theworld, but new technology capable of producing monoclonal antibodies (MAbs) against rabies might help increase the supply of RIGs globally.

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Q15. Is it necessary to perform a skin sensitivity test while using ERIG?

Most ERIG products currently being manufacture dare highly purified and the occurrence of adverse events has been significantly reduced. There are no scientific grounds for performing a skin test prior to administering ERIG because testing does not predict reactions, and it should still be given whatever the result of the test.

The treating physician should be prepared to manage anaphylaxis which, although rare, couldoccur during any stage of administration. However,some manufacturers of ERIG still recommend performing a skin test. It should be kept in mind that a negative skin test does not guarantee that anaphylaxis would not occur.

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Q16. What precautions should be taken while administering RIGs?

All emergency drugs and facilities for managing any adverse reactions must be available.

  • The RIG vial(s) taken out from refrigerator should be kept outside for a few minutes before administration to the patient (to warm to room/body temperature).
  • RIG should preferably be administered before administering the anti-rabies vaccination. Itshould, however, never be administered later than 7 days after start of vaccination as it then will suppress native antibody production.
  • RIG should not be administered in the same syringe as the vaccine, or at the same site as the vaccine.
  • While infiltrating RIG into bite wounds, care must be taken to avoid injecting into blood vessels and nerves. Anatomical feasibility must always be keptin mind while injecting RIG.
  • While injecting into finger tips, care must be taken to avoid compartment syndrome.
  • In small children with multiple bites, if the volume is insufficient for infiltration in and around allwounds, RIG should be diluted with sterile normal saline to double or three times the volume.
  • Keep the patient under observation for at least1 hour after ERIG administration before sending him or her home.
  • The patient should not be given RIG on an empty stomach.
  • Pregnancy is not a contraindication for RIG and anti-rabies vaccination.

If an injection is administered into a region that is compartmentalized (fingersetc.) and the volume is more it will cause pressure effects which will include pain, pallor and parasthesia.

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Q17. Is it necessary to perform an anti-bodytest on the patient following anti-rabies vaccination?

It is not necessary on a routine basis when human rabies vaccines are properly stored and given according to the approved schedule in a healthy individual. It is recommended only under special medical conditions, such as for immune-compromised patients, or in cases of delayed vaccination, or cases of frequent exposure to the rabies virus. Such patients require special wound care and careful immunoglobulin infiltration into the wounds.

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Q18. Are there any adverse effects of rabies vaccination?

Mild symptoms such as pain, redness, irritation or swelling at the site of injection may occur. Generalized symptoms such as headache, fever and influenza-like illness might be observed in some patients.

All these adverse effects are temporary and self-limitingand rarely need medication. All patients should be told about the possible adverse effects, but they must be advised that it is essential to continue vaccination – even if there are local or mild systemic adverse reactions.

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Q19. Are there any contraindicated drugs ordietary restrictions during anti-rabies vaccination?

All immuno suppressive drugs are contraindicated during vaccination such as steroids, chloroquine(anti-malarial drug) and anti-cancer drugs. If these drugs cannot be avoided and the patient is in animmune-compromised state, the IM regimen mustbe followed by infiltration of site of bite wound with RIG. Monitoring of antibody titration is recommended in such patients where possible.

There are no dietary restrictions during the course of vaccination.

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Q20. If one rabies vaccine has been used for PEP and it is not available for the last two doses, is it possible to interchange rabies vaccine or vaccination route (IM versus ID)?

If completion of PEP with the same modern rabies vaccine is not possible, the switch can be made. This practice should be the exception.

No study has been done yet on vaccine immunogenicity and change of the route of vaccine administration from IM to ID during PEP.

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Q21. Is there any possibility of failure after PEP?

There are occasional human rabies cases reported despite PEP, due to various factors related to negligence and individual health status. Most cases have been reported due to delayed vaccination, or non-use of rabies immunoglobulin in category III exposure, or incomplete course of vaccination. Some cases are related to immune-compromised status such as HIV/AIDS, cirrhosis or use of chloroquine, steroids or anti-cancer drugs. Unexplained failure in cases where everything was apparently done correctly have also been documented.

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Q22. If a previously immunized person is bitten by a rabid dog again, what is the re-exposure vaccination schedule?

If a person has been previously fully vaccinated against rabies using a modern rabies vaccine, either for pre-exposure or post-exposure vaccination by IM or ID route, only two doses of vaccines are given on days 0 and 3. (However, a full vaccination course is recommended for those previously vaccinated with nerve tissue vaccine.)

Persons previously immunized against rabies have two distinct comparative advantages.

  • It is not necessary to administer RIG, even in acategory III exposure.
  • Pre-vaccination leads to added protection by inducing memory cells causing an accelerated immune response when a booster dose of vaccine is administered. This is the reason why parents are encouraged to vaccinate their children against rabies, because they are most vulnerable to dogbites and category III exposure.

Rabies is one of the oldest diseases known to humans, and is a serious public threat in many countries in South-East Asia. There is still no treatment available once a patient develops the symptoms of rabies.

These FAQs are an attempt to provide accepted and evidence-based answers to common questions about the disease.

If a person is bitten by an animal:

  • Wounds should be washed and flushed immediately with soap andwater for 10–15 minutes. If soap is not available, flush with water alone. This is the most effective first-aid treatment against rabies.
  • Wounds should be cleaned thoroughly with 70% alcohol/ethanol or povidone-iodine, if available.
  • As soon as possible, take the person to a health-care facility for further treatment.

To download this booklet and other FAQs about infectious diseases, please visit:

http://www.searo.who.int/about

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