Case of the Month

June 2012

Lee Baker and Albie de Frey - SASTM

A health care worker on a remote mine site in Guinea, West Africa contacts the supervising medical officer for advice on 31 January, concerning the following case:

A 34-year old British female environmentalist was bitten on the finger by a bat whilst doing a survey in a mountain cave on 30 January 2012. She had been seen at the site clinic that day.

She had her “last vaccinations in October 2011 and all other vaccinations were updated”

On examination there was no puncture wound and no bleeding. The area was cleaned with a disinfectant, not scrubbed. A single dose of rabies vaccine was given. The patient was not unwell and will present for her next vaccine on 2 February 2012.

The health care worker was merely informing his supervising medical officer as a matter of course, but because rabies is almost always 100% fatal it is important to ensure that the case has been managed correctly.

The most frequent causes of failure of post-exposure prophylaxis are delays in administering the first vaccine dose or immunoglobulin, failure to complete the vaccine course and failure of correct wound management.

Question 1: What questions need to be asked?

Answer to Q1

  1. What were the circumstances of the bite - was it ‘provoked’ (She tried to hug or strangle the bat… the former because she is an environmentalist and the latter of course purely for science!) Was the bat ill looking/ aggressive? However it is important to note that bats need not look/act ill /abnormal to transmit rabies.
  2. In most instances of a potential rabies wound, it is important to confirm whether there was a puncture wound and/or bleeding as no broken skin or bleeding vs broken skin and bleeding has bearing on the correct treatment. (category I vs category III exposure) but this is irrelevant in this case as rabies has been transmitted by bats without a visible bite or scratch wound and for this reason any contact with bats is a category lll exposure.
  3. How was the ‘wound’ treated? - wounds with a rabies risk must be thoroughly washed with soap under running water but NOT scrubbed and an iodine-containing ointment applied as it has antiviral properties. Wounds should not be sutured for a couple of days, unless required to stop uncontrollable bleeding or manage gross disfigurement.
  4. Exactly what is meant by “She had her “last vaccinations in October 2011 and all other vaccinations were updated”:
    1. Which vaccines?
    2. Rabies vaccine? (See detail below)
    3. Tetanus toxoid? If no booster in the last 5 years can be confirmed she should receive one. She had had a booster in October 2011
    4. Yellow fever vaccine? This can have a practical implication as she may have to be referred cross-border for urgent management/vaccination in which case, proof of yellow fever vaccination may be a public health requirement of the destination country. A yellow fever vaccination certificate AND passport must be available but may not be for various reasons. This could influence the decision-making - fly the patient out vs fly vaccine/rabies Immunoglobulin (RIG) to the patient. She does have a valid yellow fever certificate.
  5. If it is stated that she did have rabies vaccine pre-exposure it should be ascertained:
    1. That the rabies vaccine was provided in a reliable clinic and made by a reliable manufacturer.
    2. If the pre-exposure vaccine is from an acknowledged manufacturer it is still important to know that the vaccine was treated correctly pre-administration - that the cold chain was maintained and the vaccine was administered prior to the expiry date. This is likely to be the case if the vaccines were given in a clinic in a developed country and less likely to be the case in many other clinics in the world. She had pre-exposure rabies vaccines at a well-known reputable clinic in London.
    3. Was the correct dosing schedule followed - D0, 7 and 21 or 28? Any deviation from a published and widely acknowledged protocol may be questioned should the patient develop rabies in spite of apparently appropriate post-exposure management at a later date. Did she receive THREE pre-exposure vaccines and how long ago? If a number of years ago, had she had a booster recently? She had received all three in the correct schedule in October.

If three pre-exposure vaccines had been reliably received she need only be given TWO post-exposure vaccines on D0 and 3. However, if in doubt as to what she actually had, there are no evidence-based guidelines on what to do.

  1. There are very little data on what to do if she received anything less than the 3 doses. If in doubt, she should receive four or five post-exposure vaccines on days D0, 3, 7, 14 (and 28) (Essen Regimen)
  2. As this was a Category III exposure she would also need RIG (which may be impossible to obtain in West Africa) if she had not had pre-exposure prophylaxis. If she had not had a complete course, what then? The problem is that RIG should not be administered if a pre-exposure vaccine course has been given, as the anamnestic response from the vaccine is excellent and RIG would hinder its efficacy, but there is a paucity of information on what to do, if the course is incomplete.

RIG directions for use:

RIG is indicated for all category lll bites (and category ll for patients who are immunocompromised) in patients who have not previously had the rabies vaccine. It has to be administered in and around a bite (the wound should be infiltrated with as much RIG as possible in order to neutralize the virus) and any excess immunoglobulin given in the deltoid area of the opposite arm to the vaccine.

The dose is 20 IU/kg and the product available in South Africa (Rabigam®) is a 2 ml amp containing 150 IU/ml. This is only sufficient for a child weighing 15kg. It is therefore important for hospitals/clinics that stock the RIG to make sure that they have sufficient amps for use in an adult.

RIG should be administered as soon as possible, but may be given for up to 7 days after the first vaccine.

The administration of RIG complements rabies vaccination in situations where viral transmission may have occurred, as production of vaccine–induced neutralizing antibodies take seven to 10 days after vaccination. RIG is safe and provides rapid passive immunity that persists with a half-life of approximately three weeks.

Booster doses of rabies vaccines are no longer routinely recommended for those who have had a complete primary series of pre-exposure or post-exposure prophylaxis with a Cell culture vaccine. For those that are at continual or frequent risk of exposure, boosters may be advised, but If available, antibody monitoring of personnel at risk is preferred to the administration of routine boosters. Because vaccine-induced immunity persists in most cases for years, a booster would be recommended only if rabies-virus neutralizing antibody titres fall to < 0.5 iu />ml.

Question 2: What tests should be done?

Answer to Q2

There are no tests that can be done to determine whether the patient is incubating rabies. The virus does not enter the blood. Confirmatory tests can only be done once the patient has symptoms and then it is too late for any effective treatment.

To determine whether a person who has previously been vaccinated, has sufficient immunity, serological testing can be done, and if the neutralising antibody level is >0.5 IU/ml he or she would only require the 2 doses of vaccine (day 0 and 3). In the setting of this case, however, it is not feasible to do this test, as is the case in most of Africa and South East Asia.

Question 3: Are there any concerns regarding the rabies vaccine he is administering?

Answer to Q3

  1. What is the trade name of the vaccine being given post-exposure in the clinic in West Africa?
    1. By inference who is the manufacturer and
    2. Where was it sourced - was the cold chain maintained and
    3. what is the expiry date?

Rabies vaccines in developed countries are the new improved cell culture vaccines (CCVs) and are derived from the following sources: Human diploid cells; purified chick embryo cells; purified duck embryo cells; vero cells; and there is a chromatography purified rabies vaccine.

In developing countries neural tissue derived vaccines may still be in use with less immunogenicity and more reactogenicity.

She had Verorab® from Sanofi Pasteur, which is a vaccine grown in monkey kidney (vero) cells.

Both the vaccine and RIG (if required and too much to infiltrate in the wound) should be given in the deltoid muscle in adults and NEVER in the buttocks as this may lead to a poor response. She received her vaccines in the deltoid muscle.

Depending on the actual rabies virus strain involved, bat-associated rabies may have a higher risk of leading to clinical disease and death than incorrectly treated rabies exposure from other animals (Dogs, cats, mongoose and other mammals). The clinician therefore has to be absolutely certain that the patient received the best possible care that will stand up to academic and legal scrutiny at any time in the future. Clinical records must be meticulously kept for the same reason. Post-exposure incubation periods of up to six years have been documented.

Question 4: How effective is rabies vaccine in preventing rabies?

Answer to Q4

This question has to be viewed on the background of the following facts supplied by the WHO and others: Rabies may be contracted in several ways:

  1. Dogs are the main host and transmitter of rabies. They are the source of infection in all of the estimated 55 000 human rabies deaths annually in Asia and Africa where 3.3 billion people are at risk.
  2. Bats are the source of most human rabies deaths in the United States of America and Canada. Bat rabies has also recently emerged as a public health threat in Australia, Latin America and Western Europe. A number of bat rabies deaths have been documented on the African continent.
  3. Human deaths following exposure to foxes, raccoons, skunks, jackals, mongooses and other wild carnivore host species are very rare.
  4. Transmission can also occur when infectious material – usually saliva – comes into direct contact with human mucosa or fresh skin wounds. Human-to-human transmission by bite is theoretically possible but has never been confirmed.
  5. Rarely, rabies may be contracted by inhalation of virus-containing aerosol or via transplantation of an infected organ. Ingestion of raw meat or other tissues from animals infected with rabies is not a source of human infection.

Poor people are at higher risk of dying of rabies - the disease is more common in boys under the age of 15 years.

Mortality related to untreated bites by rabid dogs ranges between 38% and 57%

Post-exposure prophylaxis may be discontinued if the suspect animal is proved by appropriate laboratory examination to be free of rabies or in the case of domestic dogs, cats or ferrets, the animal remains healthy throughout a10-day observation period starting from the date of the bite.

Rabies was considered universally fatal until recently with seven survivors on the “Milwaukee protocol” now documented, all but one in the United States of America. Ketamine, an anaesthetic agent best known for it’s use in military settings in war zones forms part of the protocol and may have anti-rabies virus properties.

Because of the variable incubation period of rabies, it is possible to administer the vaccine after exposure, and antibodies are produced about 10 days after the vaccine, which will neutralise the virus before it enters the central nervous system.

Rabies vaccine is 100% effective in preventing clinical rabies if given correctly and timeously - within days of initial exposure.

Among persons who had been bitten by an animal that was proven to be rabid and who received both RIG and a full course of one of these modern rabies vaccines, there have been no cases of rabies. Previously immunised people still must receive two additional doses of the vaccine if exposed to the virus, and the vaccine is almost 100% effective in these cases as well.

Key facts

  • Rabies occurs in more than 150 countries and territories.
  • Worldwide, more than 55 000 people die of rabies every year.
  • 40% of people who are bitten by suspect rabid animals are children under 15 years of age.
  • Dogs are the source of 99% of human rabies deaths.
  • Wound cleansing and immunization within a few hours after contact with a suspect rabid animal can prevent the onset of rabies and death.
  • Every year, more than 15 million people worldwide receive a post-exposure preventive regimen to avert the disease – this is estimated to prevent 327 000 rabies deaths annually.

Reference http://www.who.int/mediacentre/factsheets/fs099/en/


  1. Keates L. Rabies vaccines: WHO position paper: Recommendations. Vaccine (2010), doi:10.1016/j.vaccine.2010.08.082
  2. WHO Expert Consultation on Rabies 2004: first report. Technical report series; 931. Geneva Switzerland
  3. L. Blumberg, J. Weyer, H. Pienaar, W. Markotter and Rabies Advisory Group 2008.Rabies. Guide for the Medical, Veterinary and Allied Professions. Department of Agriculture, Forestry and Fisheries. 2nd edition 2010. ISBN: 1–86871–119–6
  4. Oxford Handbook of Tropical Medicine – M Eddleston, S Pierini. 1999. ISBN 0 19 262772 4
  5. Manual of Travel Medicine and Health - Third Edition. Steffen, DuPont, Wilder-Smith. 2007. ISBN 1-55009-227-8
  6. Both L, Banyard AC, van Dolleweerd C et al. Passive immunity in the prevention of rabies. Lancet Infect Dis 2012;12:397-407
  7. The National Network for Immunization Information. http://www.immunizationinfo.org/vaccines/rabies
  8. World Rabies Day is 28 September.
Outcome of the case

The management of this environmentalist appears to have been optimal and at the time of publication, she is well.

Lessons learnt

Fortunately this case has been managed well, but it has highlighted problems that could occur, especially when managing a potential rabies case in Africa. Because it is difficult to get rabies immunoglobulin in most African countries, especially in the rural areas, it is advisable to recommend a pre-exposure course of vaccine (day 0, 7 and 21 or 28).

As there is a paucity of evidence-based information on what to do if less than the 3 vaccines are given, travellers should be encouraged to come to the travel clinic timeously so that they can complete the course prior to travelling.

Provided the patient has no symptoms of rabies, it is not too late to start post-exposure prophylaxis. This is possible because of the generally prolonged incubation period.

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