0Case Report
Rabies in Oman: Failed Postexposure Vaccination in a Lactating Woman Bitten by a Fox
Euan Macgregor Scrimgeour, MD, FRACP, DTM&H;* and Firdosi Rustom Mehta, MDf
Rabies was first detected in the Sultanate of Oman in 1990, when a child from Buraimi, northern Oman, on the border with the United Arab Emirates (U.A.E), died after being bitten by a fox.1 Subsequently, animal-bite surveillance revealed evidence of a country-wide epizootic of rabies in the common fox (Vulpes vulpes), which spread from the border of the U.A.E. to involve the whole of Oman, excepting Musandem Province in the northeast.23 Shortly after the first case, postexposure prophylactic immunization for rabies (passive immunization with human rabies immune globulin [HRIG] and active immunization with human diploid cell vaccine [HDCV]), was made available in all Omani hospitals. Nevertheless, despite adequate postexposure prophylaxis, two more cases of rabies occurred in 1991 and 1992, following bites by a wolf and a fox, respectively.4 This report presents another case of rabies that developed despite postexposure immunization in a lactating woman who was bitten by a fox.
On April 20,1997, while sleeping in the desert, a 17-year-old Bedouin woman was bitten on the upper lip by a fox. Her husband immediately drove her to the district hospital, where two deep lacerations on her upper lip were cleaned and dressed, but not stitched. Two 1-mL doses of inactivated Merieux rabies HDCV were administered by intramuscular injection into each deltoid, according to the Ministry of Health protocol. Antitetanus toxoid was given. At the time, HRIG was unavailable in the hospital, but the woman was ordered to go immediately to the regional hospital, a distance of several hours' drive on a surfaced road, where HRIG was available. Unfortunately, she delayed attending the regional hospital until April 22, when, according to official guidelines for patients presenting more than 48 hours after injury,
*Senior Lecturer in Infectious and Tropical Diseases, Department of Medicine, Sultan Qaboos University; and f Director, Department of Surveillance and Disease Control, Ministry of Health, Sultanate of Oman.
Address correspondence to Dr. Euan Scrimgeour, Associate Professor in Infectious and Tropical Diseases, Department of Medicine, PO. Box 35, Al Khod 123, Oman. E-mail scrim@squ.edu.om.
she was given 800 international units (20 IU/kg body weight) of Merieux HRIG intramuscularly into the gluteal region only (with no infiltration of the wound). Since Oman followed the 2-1-1 regimen (two 1.0-mL doses of HDCV on day 0, and one dose on days 7 and 21, respectively) for vaccine administration,5 on April 26, she was given the third 1-mL dose of HDCV into the deltoid muscle.
On May 3, the patient developed fever, headache, and vomiting, and on May 7, presented to the district hospital with fever, delirium, hyperesthesia, and aerophobia. She was referred at once to the Sultan Qaboos University Hospital as a case of suspected rabies. She brought her 7-month-old infant boy with her; she had continued to breastfeed the child despite being bitten by the fox. On admission, the patient was febrile, agitated, confused, and had hydrophobia. There were two healed lacerations on her upper lip (Figure 1). She had signs of brain stem dysfunction, including a right sixth cranial nerve palsy, but no signs of meningitis. The clinical diagnosis of rabies was confirmed, and she was transferred to the Intensive Care Unit, where she was sedated, paralyzed, and given assisted ventilation. The patient died May 9,1997. Prior to decease, a skin biopsy was taken from the back of the neck, and corneal impressions and washings were obtained. A positive fluorescent antibody test for rabies virus was obtained only from the corneal washings. Serum was obtained for rabies antibody measurement, but unfortunately, the specimen was not processed and was discarded. The infant received HRIG on admission, and a full course of HDCV was administered. He remained well.
DISCUSSION
Although the patient received immunization with HDCV within a few hours of being bitten, the delay of over 48 hours before she received HRIG may have contributed to the development of rabies. In addition, the two lacerations on her upper lip were very deep, and presumably virus was injected close to, or directly into facial nerve tissue.
In two previous cases of failed postexposure immunization in Oman, which occurred in 1991 and 1992,4
Rabies in Oman / Scrimgeour and Mehta 161
Figure 1. Patient with rabies. Arrows indicate site of bite.
multiple, deep penetrating injuries of the face and scalp were sustained. The first patient, a 45-year-old woman, was severely bitten on the face (with severance of the left facial nerve), scalp, neck, and arm, by a wolf (Canis lupus arabs). Within 5 hours, she received two 1-mL doses of inactivated Merieux rabies HDCV intramuscularly into each deltoid, 600 IU (20 Ill/kg) of Merieux HRIG into the wounds, and 600 IU into the gluteal muscles. On day 7, she received 1 mL HDCV by intramuscular injection into the deltoid. Rabies developed on day 13, and she died in a coma on day 18. Rabies virus was detected in corneal impressions, using the fluorescent antibody test. Serum obtained 2 days before decease, revealed rabies antibodies at a titer of 1:810 in the neutralizing cell-culture test. Three other patients bitten on the same day by the same wolf, including two who had multiple, severe bites on the face and head, were similarly immunized and remained well.
The second patient, a 5-month-old female child, was severely bitten by a fox on the face and scalp, exposing the pericranium. No suturing was performed. She received two 1-mL doses of inactivated Merieux rabies HDCV injected into the deltoids, 60 IU of Merieux HRIG infiltrated into the wounds, and 60 IU injected into the gluteal region. She received the second 1-mL dose of HDCV on day 7, but developed rabies on day 14, and she died 2 days later. Rabies virus was identified in corneal impressions by a positive fluorescent antibody test.
Failure of prophylaxis in these two cases was attributed to the presumed injection of a large inoculum of virus into nervous tissue in the face and scalp, and the impossibility of infiltrating the extensive, deep lacerations adequately.
In Oman, the 2-1-1 regimen, which is recommended by the World Health Organization (WHO) for developing countries, has until now proved to be dependable. Many hundreds of patients have received postexposure prophylaxis over the past decade, and the only failures have been those described here. Failures have been
reported from several countries using the 2-1-1 procedure, including Thailand,6 Burkino Faso,7 and India,8 and in all of these, the recommended guidelines were not followed exactly. Failed postexposure immunization has also been reported recently from France.9 In the United States, as well as initial HRIG and HDCV four further doses of HDCV are given. Failed postexposure prophylaxis has not been reported in humans, but it has in animals (in which only three doses of vaccine are given).10 It is clear that whichever protocol is used for postexposure immunization, meticulous adherence to the recommended guidelines is imperative, including appropriate dosage and timely administration of HDCV and HRIG.
Continuation of lactation in the patient reported here may have exposed the child to the risk of rabies. Transient viremia occurs in rabies, and if there were micro-abrasions around the nipple, exposure to infection might occur. Rabies has been transmitted by breast milk in animals, but confirmed cases have not been reported in humans.11 Virus is also present in mucous membranes and cornea, and could be transferred if the mother touched her child's eyes after rubbing her own; however, person-to-person transmission of rabies has never been reported. Early immunization of the infant with HRIG and HDCV in this case, may have played a part in preventing infection.
There has been one further case of rabies in Oman since this case. In 1999, a 13-year-old girl, was scratched below the right lower eyelid at night while sleeping in her house, by an unidentified animal, suspected to be a feral cat. No medical attention was sought, and 1 week later she developed rabies, confirmed by immunofluorescence of corneal impressions and washings.12 Cats have rarely been identified as being rabid during the past 10 years of animal-bite surveillance in Oman; foxes and dogs have usually been affected. Although a rat or a mouse was suspected to be the source of rabies (Lassa virus gentoype I) in a soldier in Israel,13 rodents are not regarded as a risk in Oman, and prophylactic immunization is not recommended.
REFERENCES
1. Novelli VM, Marquex B, Malankar P Rabies in Oman. Med Newsletter Oman 1990; 7:19-21.
2. Novelli VM, Malankar P Epizootic of fox rabies in the Sultanate of Oman. Trans R Soc Trop Med Hyg 1991; 85:543.
3- Anonymous. Wildlife rabies in Oman and the United Arab Emirates. Wkly Epidemiol Rec 1992; 67:65-68.
4. Ata FA, Tageldin MH, Al-Sumry HS, Al-Ismaily SI. Rabies in the Sultanate of Oman. Vet Rec 1993; 132:68-69.
5. Vodopija I, Sueau P, Smderdel S, et al. Interaction of rabies vaccine with human rabies immunoglobulin and reliability of a 2-1-1 schedule application for post-exposure treatment. Vaccine 1988; 6:283-286.
6. Anonymous. Human rabies despite treatment with rabies immunoglobulin and human dipoid cell rabies vaccine in Thailand. MMWR Morb Mortal Wkly Rep 1987; 36:759-760.
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7. Ki-Zerbo GA, Kyelem N, Ouattara Y, Ouedraogo JP, Thiom-biano R, Kabore J. Apropos of a case of rabies occurring despite vaccination after exposure. Med Trop (Mars) 2000; 60:67-698. Deshmaukh RA,Yemul VI. Fatal rabies encephalitis despite post-exposure vaccination in a diabetic patient: a need for use of rabies immunoglobulin in all post-exposure cases. J Assoc Physicians India 1999; 47:546-547. 9. Gacouin A, Bourhy H, Renaud JC, Camus C, Suprin E, Thomas R. Human rabies despite post-exposure vaccination. Eur J Clin Microbiol Infect Dis 1999; 18:233-235.
10. Wilson PJ, Clark KA. Post-exposure rabies prophylaxis protocol for domestic animals and epidemiological character of rabies vaccination failure in Texas 1995-1999. J Am Vet Med Assoc 2001; 15:522-525.
11. Warrell DA. Rabies in man. In: Kaplan C, Turner GS, Warrell DA, eds. Rabies the facts. 2nd ed. Oxford: Oxford University Press, 1986:21-48.
12. Abraham AK. Human rabies. Oman Med J 2001; 17:45-47.
13. Gdalevich M, Mimouni D, Ashkenazi I, Shemer J. Rabies in Israel: decades of prevention and a human case. Public Health 2000; 114:484-487.
