Dr. Amlan Goswami, Consultant Physician, Kolkata
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Physicians managing cases of animal bites or exposures to animals usually follow some guidelines. Those Physicians who are most concerned about providing the most authentic and state of the art treatment to their patients, usually follow the WHO TRS 931, which is most commonly called, the WHO guidelines. The WHO TRS 931 is a very useful document, which helps the Physicians in most cases. However, there are certain situations where it is found to be deficient. In those situations the Physician is left to his or her sense of judgment and clinical acumen for managing the critical situations faced by them. In the preface of the TRS 931, it is mentioned that "the responsibility for the interpretation and use of the material lies with the reader. In no event shall the World Health Organization be liable for damages arising from its use".1 In the actual scenario of treating animal bites and exposures, a good sense of judgment and good clinical acumen is essential for managing the critical cases. WHO TECHNICAL REPORT SERIES 931 also mentions about the fact, that modifications of the recommendations may be warranted in certain situations, but not limited to them only. A careful risk assessment should be conducted by a qualified medical professional on every patient exposed to a potentially Rabid Animal. Local wound treatment is of very great importance in the management of each and every case of animal bite or exposures to animals. Since the rabies virus enters the human body through a bite or scratch of a rabies infected animal, it is important to remove saliva containing the rabies virus at the site of bite by chemical or physical means. This can be done by prompt, gentle and thorough washing with soap or detergent and flushing the wound with running tap water for at least 15 minutes or washing the wound for about 2-3 times. After washing with water and soap, disinfectants like Povidone iodine (which is Viricidal)/surgical spirit / household antiseptics must be applied. Washing of the would must be done irrespective of the time since bite, as the rabies virus can persist and even multiply at the site of bite for a long time. However, care must be taken not to disturb scabs if formed. In addition, tetanus prophylaxis, analgesics & anti bacterial treatment/antibiotics may be given. By mere washing of wounds & application of antiseptics, the risk of rabies will reduce by about 50%. Suturing of the wound(s) should be avoided. Suturing of lacerated wounds with severe bleeding can be done as a life saving measure by putting minimum number of loose stay sutures under the cover of Rabies Immunoglobulin. If RIG is not available & suturing is needed, it can be done only after 2 weeks, after administering 3 doses of anti rabies vaccine. Post Exposure Prophylaxis [PEP] of previously vaccinated persons. consists of proper and adequate Local wound treatment. In the case of patients who had received pre-exposure or post exposure vaccination with a vaccine of unproven potency, or in whom the presence of immunological memory is no longer assured (immunocompromised patients, etc) should receive full Post-exposure Vaccination series + RIG. Individuals who are not immunocompromised and who have been previously vaccinated with a potent and effective rabies vaccine that meets WHO criteria for vaccine production and have adequate documentation should receive a TWO Booster series consisting of one I.M. or I.D. dose on Day 0 and Day 3 and No RIG. In many incidents of animal bites or exposure to potentially rabid animals the sense of judgment of the clinician and his experience are both very essential for a satisfactory outcome and not merely following the guidelines. Highlighted here is a case of a Lady of 63 years in age. She was bitten by Stray Dogs on 20/ 09/2006, again on 14/10/2006, and again on 01/01/ 2007. The biting dogs (of the incidents on 20/09/2006 and 01/01/2007) were suspected to be rabid (killed by mob on same day because of unprovoked biting). The biting dog of the incident on 14/10/2006 was not known. The Bites were over her legs and feet, hands and the forearms, and all were transdermal. All the exposures were of Category III. She received PCEC vaccine 1M over deltoid on 22/09/2006, 25/09/2006, 29/09/2006, 06/10/2006, 20/10/2006, & 21/12/2006. She received ERIG by local infiltration on 23/09/2006. For the bite on 14110/2006, no TCV or RIG was advised. Proper and adequate Local Wound treatment was done. For the bite on 01/01/2007, no TCV or RIG was advised. Only proper and adequate Local Wound treatment was done. Patient is alive and normal for more than a year after her last exposure. In the case of the exposure on 14/10/2006, as the vaccination process was continuing and more than 14 days had passed since the start of vaccination, and she had received RIG on 23/09/2006, so she was supposed to have Rabies Virus Neutralising Antibodies in adequate titre in her circulation at that time, so she was not advised Fresh PEP (for the exposure on 14/10/2006) or a Fresh 2 booster protocol (for the exposure on 01/01/2007) as per the Guidelines. The WHO TRS 931 and the National Guidelines for Rabies Prophylaxis is silent about the problem posed in this case. Another case where the clinical judgment and experience of the clinician was the basis of correct management is the case of a gentleman aged about 36 years. He had received for a previous exposure 6 doses of PCEC vaccine in ESSEN schedule from 11.9.04 to 10.12.04. For a 2nd exposure on 20.2.05, he received 2 doses of PCEC vaccine on 24.2.05 and 27.2.05. He came for consultation on 10.4.05, for his third exposure, six weeks after getting two boosters for his second exposure. A dog ran over the Right foot with no definite injury on 10.04.05. Patient was very much worried. However, he had washed the site of contact (right foot), thoroughly with soap and water, immediately after the incident. He did not feel any burning sensation on application of soap and water soon after the exposure. He did not feel any burning sensation on application of rectified spirit in the clinic, at the time of the consultation. Rabies Virus Neutralising Antibody Titre on 11.4.05 was found to be 2 iu. / m.l. of serum, so no boosters were advised. The WHO Guidelines for re-exposure cases are [In cases where the patient completed the previous course of PEP properly] 2 booster doses, one on 0 0 and the other on D3. There are different guidelines for re-exposure cases in different countries in Asia.4 In Thailand the guidelines are [In cases where the patient completed the previous course of PEP properly] as follows: For cases Reporting at < 6 months: 1 booster. For cases Reporting at >= 6 months: 2 boosters, one on D0 and the other on D3. The guidelines for re-exposure cases in Sri Lanka [In cases where the patient completed the previous course of PEP properly] are as follows: For cases, reporting at <= 8 months from last date of vaccination: No booster. For cases, reporting from 8 months to 1 year: from last PEP, and in the case of very high risk exposures up to 1 year: 1 booster. For cases, reporting at 1 to 5 years: 2 boosters, day 0 and 3. For cases reporting at >5 yrs: full PEP with RIG in category III exposures. Ideally rabies antibody titres should be determined by RFFIT before recommending boosters. The guidelines for re-exposure in the Philippines [In cases where the patient completed the previous course of PEP properly] are as follows: For cases, reporting Up to 1 month after the last PEP: no booster. For cases reporting from 1 to 6 months after the last PEP: 1 booster. For cases, reporting from 6 months to 3 years after the last PEP: 2 boosters. One on 0 0, and one on 03. For cases, reporting after 3 years: full PEP without RIG. The Basis for the Different Guidelines is many. A three injection protocol [HOCV or PVRV on DO, 07,028], followed by 0365 booster [B1], maintained seroconversion up to 10 years in the majority of subjects. An important decrease was observed during the first year after B1. At the end of 10 years a booster re-established the GMT to its level on 0379. A return to seronegative status may develop in some subjects within the first 3 years after the I-year booster. A titer of >= 30 IV/roL on D379 corresponded, with a nearlylOO% probability of being still seroconverted at the end of lO years, called "Good Responders". A titre of <30 IU/mL correlated with an 18% probability of having a titer <0.5 IU/mL in the 3 years following the B1. This group of seronegative subjects is called poor responders because their response to B1 is significantly lower than that of the other subjects. After the titers fell to <0.5 IU/mL, a booster injection seroconverted these subjects, but with a significantly lower amplitude than that observed after the initial B1. One year later, the titers were again low, and after 2 years, certain subjects became seronegative again. Some subjects who had seroreverted at 3 years are confirmed "poor responders" and should justify the use of a booster dose every 3 years They tend to serorevert once again, in an average time span of 3 years, as shown by their follow-up in the study cohort. Those subjects who were seroconverted at 3 years will remain so at 10 years and only require a booster dose every 10 years are termed "good responders". In absence of the possibility of serological testing at D379 and/or Y3, this strategy proposes that a booster dose may be injected every 5 years. Some times the Second exposure is more serious than the first. It is very risky for a doctor to depend on the theory of Amanmesis alone. In long duration Pre-exposure Vaccination studies, there are evidences of Good and Poor immune responders. There are not many well documented long term studies in Re-exposure cases, in actual patients. Reviewing scientific literature, I could gather the fact that in previously vaccinated patients who have Rabies VNA of less than 0.5 i.u. / ml, and in immunocompromised patients, including those on steroid therapy, should receive the complete immunization schedule including RlG. I would like to highlight the case of a gentleman aged 32 years. He was bitten by stray dog on 8.12.2004. The said. Dog suspected to be suffering from rabies [based on the clinical features described by the patient and persons accompanying him]. The bite was over his left hand. There were multiple marks, and all were transdermal. This was category III exposure. He had a history of receiving 6 doses of PCEC Vaccine I.M. in ESSEN schedule from 27.08.2002 to 25.11.2002 (about 2 years back). The patient and his relatives did not want any short cut treatment. They did not want to take any risks. He was advised to get the Rabies Virus Neutralising Antibody level checked at the only establishment providing such tests commercially in India. The Rabies VNA titre with a sample drawn on 8.12.2004 was <0.3 i.u. / m.l. of serum. He again received 5 doses of PCEC vaccine in ESSEN schedule from 9.12.2004 to 6.1.2005. He received ERIG on 12.12.2004 by local infiltration. The Rabies Virus Neutralising Antibody Titre of a sample of his blood drawn on 09.02.2005 was> 10 i.u./ m.l. of serum. Patient is Normal & Healthy for more than three years after the incident. A lady aged 53 years was bitten by a stray cat on 09.5.2005. The cat was showing symptoms of rabies, and it died on 10.5.2005. The lady was bitten in many parts of her left hand. For a previous exposure in October 2004 (about 6 months ago), she received 5 doses of PCEC vaccine in ESSEN schedule, and the biting animal a known pet dog was normal and healthy for more than six months after the incident. She also gave a history of suffering from Diabetes Mellitus (NIDDM) for many years. As the second exposure was more serious than the first one, and as the patient and her relatives were insisting on not taking any chances, a sample of blood was drawn and sent for Rabies Virus Neutralising Antibody estimation at the only commercial establishment conducting such tests in India. The Rabies Virus Neutralising Antibody Titre on 09.5.2005 was <0.3 i.u. / m.l. of serum. As a result she received 5 doses of PCEC vaccine again from 9.5.05 to 6.6.05. She also received ERiG by local infiltration on 12.5.05. Again, the Rabies VNA level was checked at the same establishment as before. The Rabies Virus Neutralising Antibody Titre on 21.6.05 was> 10 i.u. / m.l. of serum. The patient is keeping fine till two years after the incident. The basis for the current WHO recommendations on management of re-exposure cases relies on certain facts obtained from some scientific observations. These are as follows : The anamnestic antibody response to a booster dose of TCV seems to be independent of the pre existing antibody titre. A single booster dose [on Day 0] in previously vaccinated persons produces adequate Antibody Response within 7 days, a second dose on Day 3 would nevertheless provide more protection. A prospective study followed the immune response in 118 patients who were given a two-dose 0.1 ml ID booster of PVRV on D0 and D3 after having been given either pre-(n=38) or post-exposure (n=80) rabies vaccine 5 to 20 years previously. Of these subjects, 109 had received PVRV and 9 had received HDCV as primary vaccination. Anti-rabies GMTs on days 5, 7 and 14 after boosting showed a good anamnestic response. All volunteers had detectable (>= 0.03 IU/mL) neutralizing antibodies on day O. Only one had an antibody titer < 0.5 IU/mL on day 7 (0.48 IU/ mL). That was a 75 year old female who had received an ID post-exposure series of PVRV 10 years previously, but her titer was 6.25 IU/ mL by day 14. This study supports current recommendations that immunity is long lasting and that boosters without immunoglobulin are sufficient even when prior vaccination was more than 5 years previously. Points to note from the Study are as follows: All the volunteers had detectable (>= 0.03 IU/ mL) neutralizing antibodies on day 0. The baseline antibody titres on day 0 were higher in female volunteers. Only one volunteer had an antibody titer < 0.5 IU/mL on day 7 (0.48 IU/mL), after getting boosters on day 0 and day 3, and she was a 75 year old female. Please Note, the study was done on volunteers only and not on actual patients. This was simulated re-exposure and not actual re-exposure. Taking the case of the lady in that study, who had an antibody titre < 0.5 IU/mL on day 7. If the re- exposure was by a confirmed rabid animal, then she could have succumbed to rabies, because she had circulating antibodies in the protective range only after 7 to 14 days after the re-exposure. This interval of time would have been sufficient for the rabies virus to get entry into the nervous system. Conclusion Fortunately most animals are not rabid and this is the reason why we have not heard of treatment failures in re-exposure cases. There are two factors involved for a treatment failure to occur in a re-exposure case. The patient should be a poor immune responder and the animal causing the exposure should be rabid. Combination of both is very rare.
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