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HUMAN RABIES AFTER LATE ADMINISTRATION OF HUMAN DIPLOID CELL VACCINE WITHOUT HYPERIMMUNE SERUM
870 vaccine
Letters
to
the Editor
ACYCLOVIR FOR HERPES SIMPLEX ENCEPHALITIS: THE PRICE OF SURVIVAL?
SIR,-Intravenous acyclovir has been used with promising results herpes simplex virus infections in immunocompromised patients.’ We have treated a case of herpes simplex encephalitis with acyclovir. The patient survived with almost no physical deficit, for
but she was left with a severe limbic dementia syndrome,2,3 and now needs 24 h nursing care. A 29-year-old woman was admitted to the Royal Perth Hospital on June 9, 1982, with a 4 day history of fever, headache, and general malaise. She was mildly confused and had mild neck stiffness. A lumbar puncture showed raised protein (0-48 g/1), with normal sugar, but 75 lymphocytes/1. She then deteriorated and became dysphasic and drowsy. An electroencephalogram was abnormal with slow background activity and left fronto-temporal delta activity, suggestive of herpes simplex encephalitis. A computerised tomographic (CT) scan revealed left temporal lobe low density lesion. Brain scan confirmed the left temporal lobe lesion. She was then started on a high dose of dexamethasone with intravenous acyclovir 1800 mg daily. However, she continued to deteriorate: bilateral papilloedema developed and she became stuporose. Repeat CT scan revealed bilateral temporal lobe lesion with cerebral oedema. A Richmond screw was then inserted for intracranial pressure monitoring. The high intracranial pressure was controlled with artificial hyperventilation and mannitol. The pressure was stable for 3 days and she then gradually recovered. However, clinically she now exhibited limbic dementia syndrome due to bilateral temporal lobe damage with Wernicke’s aphasia, visual agnosia, hyperbulimia, memory loss with confabulation, and change of personality. She has eaten soap, paper, paint, and various objects. The herpes simplex virus titre has risen from less than 10 to greater than 320 within 7 days, confirming a diagnosis of herpes
simplex encephalitis. This patient with herpes simplex encephalitis survived after a 10 day course of acyclovir but she has been left with a severe disability requiring constant supervision. Although the case fatality was reduced in a series of herpes simplex encephalitis cases treated with vidarabine, the morbidity was still worrying, twenty-six out of fifty-six patients being either moderately or severely debilitated.We have reviewed a series of thirteen cases of herpes simplex encephalitis seen in Royal Adelaide Hospital from 1967 to 1980 and treated with either vidarabine or cytarabine. Only five patients survived and they were severely debilitated and had to be admitted to a long-stay hospital. Are we lowering the mortality from this disease at the price of prolonging a miserable life? This question can only be answered in a controlled study-in the meantime the decision to treat herpes encephalitis with acyclovir will depend on the clinician’s interpretation of the results
so
far available.
Neurology Department, Royal Perth Hospital, Perth, Western Australia
6000
DAVID CHIN R. EDIS
HUMAN RABIES AFTER LATE ADMINISTRATION OF HUMAN DIPLOID CELL VACCINE WITHOUT HYPERIMMUNE SERUM
SIR,-Rabies is almost always fatal unless immediate local wound is done and post-exposure prophylaxis is administered. Semple type nervous tissue vaccine has been used in Thailand since 1930. Neurological complication and vaccine failure rates have been reported to be 1 in 2000 and 1 in 400, respectively.Duck embryo treatment
1.
2
was
also used up
to
1980
to a
limited extent, but data
on
complications are not available in Thailand. Human diploid cell vaccine (HDCV) from a French manufacturer
Crumpacker CS, Schnipper LE, Marlowe SI, Kowalsky PN, Hershey BJ, Levin MJ. Resistance to anti-viral drugs of herpes simplex virus isolated from a patient treated with acyclovir. N Engl J Med 1982, 306: 343-46. Gascon G, Gillies, F. Limbic dementia. J Neurol Neurosurg Psychiatry 1973; 36: 421-30
WB, Mancall EL, Thomas JJ. Complete Kluver-Bucy syndrome in man. Cortex 1975, 11: 53-59. 4. Whitley RJ, et al. Herpes simplex encephalitis N Engl J Med 1981; 304: 313-18. 5 Phong-Aksara S Antirabies work ofthe science division of the Thai Red Cross Society. Roy Thai Army Med J 1971; 24: 303-28.
has been licensed and distributed in Thailand since 1978. It is probably the most potent rabies vaccine available today. Only one reported case of vaccine failure, due to administration of HDCV without serum for post-exposure treatment, has been published. Having used this type of vaccine in Thailand for three years, we have encountered another case of human rabies in a patient given four doses of HDCV vaccine. A Chinese woman aged 35, living in Chachoengsao Province, 60 km south-east of Bangkok, was bitten by a stray dog on Nov. 6,1980. The dog caused multiple severe wounds on both her wrists, left knee, and calf and scratches on her left eye-brow. The dog had previously bitten several other people and it was killed on Nov. 7. No laboratory tests were done. The patient visited the district hospital on Nov. 6 for local wound treatment. She went to her private physician the following day (Nov. 7) for consultation and was referred to another local hospital where she received her first dose of HDCV vaccine on Nov. 8. Subsequent dosages were given on Nov. 10, 15, and 21. No hyperimmune antirabies globulin was administered. She was well until Nov. 27 when she began complaining ofadeep pain in her right hand associated with anorexia. Her consciousness was normal and she could swallow water freely. On Nov. 28 there was motor weakness and hypersensation of the right arm. She was referred to Paolo Memorial Hospital in Bangkok on Nov. 29. At the outpatient department she had cyanosis and difficulty in swallowing. An endotracheal tube was inserted and the patient was connected to a respirator. Laboratory tests and lumbar puncture
hyperimmune
were
unhelpful.
When rabies was diagnosed she was transferred to Bamrasnaradur Infectious Diseases Hospital. Her symptoms became progressively worse. She died on Nov. 30, 10 h after admission to the infectious diseases hospital and 24 days after the dog bites. Permission for necropsy was refused, so the diagnosis of rabies was based on clinical grounds only. Another patient bitten by the same dog and treated at the local health centre where sixteen injections of Semple vaccine were given, also died of clinical rabies 22 days later. W.H.O. recommends that everyone bitten by a rabid animal should receive hyperimmune serum of the equine or human type.7 Prophylaxis should be started as soon as possible, especially for severe bites. Our patient was not given hyperimmune serum and the first dose of vaccine was given on the third day after the bite. Inadequate post-exposure treatment was probably the main reason for failure in this case, as in the 1981 case in Rwanda.Immediate administration of hyperimmune serum is strongly recommended, even when a potent vaccine is used. Department of Microbiology, Faculty of Medicine, Siriraj Hospital, Bangkok 10700, Thailand; and Division of Epidemiology and Bamrasnaradur Infectious
Hospital,
Ministry of Public Health, Bangkok
SOMSAK WATTANASRI PRAKORB BOONTHAI PRASERT THONGCHAROEN
DANGER TO ASTHMATICS OF A BETA BLOCKER IN A THREE-COMPONENT TABLET
SIR,-Products combining two or more drugs have become fashionable, especially in cardiovascular pharmacology. There may, however, be an inherent danger, as the following case illustrates, if the prescriber does not bear in mind the individual components. A 60-year-old woman had had asthma for 25 years. This was well controlled on prednisolone 5 mg twice daily and a twice daily tablet of ’Franol Plus’ (ephedrine, phenobarbitone, theophylline, thenyldiamine), with isoprenaline by ’Medihaler’ as needed, and she had never needed hospital care for her asthma. On the day of admission she had a nose bleed and saw her general practitioner who
3. Marlow
6. Devriendt J, Staroukine M. Human rabies-Rwanda. Morbid Mortal Wkly Rep 1982; 31: 135. 7. Report of consultation on rabies prevention and control (Lyon, France, March 10-12,
1980). WHO/Rab. Res/80.8.
Letters
to
the Editor
ACYCLOVIR FOR HERPES SIMPLEX ENCEPHALITIS: THE PRICE OF SURVIVAL?
SIR,-Intravenous acyclovir has been used with promising results herpes simplex virus infections in immunocompromised patients.’ We have treated a case of herpes simplex encephalitis with acyclovir. The patient survived with almost no physical deficit, for
but she was left with a severe limbic dementia syndrome,2,3 and now needs 24 h nursing care. A 29-year-old woman was admitted to the Royal Perth Hospital on June 9, 1982, with a 4 day history of fever, headache, and general malaise. She was mildly confused and had mild neck stiffness. A lumbar puncture showed raised protein (0-48 g/1), with normal sugar, but 75 lymphocytes/1. She then deteriorated and became dysphasic and drowsy. An electroencephalogram was abnormal with slow background activity and left fronto-temporal delta activity, suggestive of herpes simplex encephalitis. A computerised tomographic (CT) scan revealed left temporal lobe low density lesion. Brain scan confirmed the left temporal lobe lesion. She was then started on a high dose of dexamethasone with intravenous acyclovir 1800 mg daily. However, she continued to deteriorate: bilateral papilloedema developed and she became stuporose. Repeat CT scan revealed bilateral temporal lobe lesion with cerebral oedema. A Richmond screw was then inserted for intracranial pressure monitoring. The high intracranial pressure was controlled with artificial hyperventilation and mannitol. The pressure was stable for 3 days and she then gradually recovered. However, clinically she now exhibited limbic dementia syndrome due to bilateral temporal lobe damage with Wernicke’s aphasia, visual agnosia, hyperbulimia, memory loss with confabulation, and change of personality. She has eaten soap, paper, paint, and various objects. The herpes simplex virus titre has risen from less than 10 to greater than 320 within 7 days, confirming a diagnosis of herpes
simplex encephalitis. This patient with herpes simplex encephalitis survived after a 10 day course of acyclovir but she has been left with a severe disability requiring constant supervision. Although the case fatality was reduced in a series of herpes simplex encephalitis cases treated with vidarabine, the morbidity was still worrying, twenty-six out of fifty-six patients being either moderately or severely debilitated.We have reviewed a series of thirteen cases of herpes simplex encephalitis seen in Royal Adelaide Hospital from 1967 to 1980 and treated with either vidarabine or cytarabine. Only five patients survived and they were severely debilitated and had to be admitted to a long-stay hospital. Are we lowering the mortality from this disease at the price of prolonging a miserable life? This question can only be answered in a controlled study-in the meantime the decision to treat herpes encephalitis with acyclovir will depend on the clinician’s interpretation of the results
so
far available.
Neurology Department, Royal Perth Hospital, Perth, Western Australia
6000
DAVID CHIN R. EDIS
HUMAN RABIES AFTER LATE ADMINISTRATION OF HUMAN DIPLOID CELL VACCINE WITHOUT HYPERIMMUNE SERUM
SIR,-Rabies is almost always fatal unless immediate local wound is done and post-exposure prophylaxis is administered. Semple type nervous tissue vaccine has been used in Thailand since 1930. Neurological complication and vaccine failure rates have been reported to be 1 in 2000 and 1 in 400, respectively.Duck embryo treatment
1.
2
was
also used up
to
1980
to a
limited extent, but data
on
complications are not available in Thailand. Human diploid cell vaccine (HDCV) from a French manufacturer
Crumpacker CS, Schnipper LE, Marlowe SI, Kowalsky PN, Hershey BJ, Levin MJ. Resistance to anti-viral drugs of herpes simplex virus isolated from a patient treated with acyclovir. N Engl J Med 1982, 306: 343-46. Gascon G, Gillies, F. Limbic dementia. J Neurol Neurosurg Psychiatry 1973; 36: 421-30
WB, Mancall EL, Thomas JJ. Complete Kluver-Bucy syndrome in man. Cortex 1975, 11: 53-59. 4. Whitley RJ, et al. Herpes simplex encephalitis N Engl J Med 1981; 304: 313-18. 5 Phong-Aksara S Antirabies work ofthe science division of the Thai Red Cross Society. Roy Thai Army Med J 1971; 24: 303-28.
has been licensed and distributed in Thailand since 1978. It is probably the most potent rabies vaccine available today. Only one reported case of vaccine failure, due to administration of HDCV without serum for post-exposure treatment, has been published. Having used this type of vaccine in Thailand for three years, we have encountered another case of human rabies in a patient given four doses of HDCV vaccine. A Chinese woman aged 35, living in Chachoengsao Province, 60 km south-east of Bangkok, was bitten by a stray dog on Nov. 6,1980. The dog caused multiple severe wounds on both her wrists, left knee, and calf and scratches on her left eye-brow. The dog had previously bitten several other people and it was killed on Nov. 7. No laboratory tests were done. The patient visited the district hospital on Nov. 6 for local wound treatment. She went to her private physician the following day (Nov. 7) for consultation and was referred to another local hospital where she received her first dose of HDCV vaccine on Nov. 8. Subsequent dosages were given on Nov. 10, 15, and 21. No hyperimmune antirabies globulin was administered. She was well until Nov. 27 when she began complaining ofadeep pain in her right hand associated with anorexia. Her consciousness was normal and she could swallow water freely. On Nov. 28 there was motor weakness and hypersensation of the right arm. She was referred to Paolo Memorial Hospital in Bangkok on Nov. 29. At the outpatient department she had cyanosis and difficulty in swallowing. An endotracheal tube was inserted and the patient was connected to a respirator. Laboratory tests and lumbar puncture
hyperimmune
were
unhelpful.
When rabies was diagnosed she was transferred to Bamrasnaradur Infectious Diseases Hospital. Her symptoms became progressively worse. She died on Nov. 30, 10 h after admission to the infectious diseases hospital and 24 days after the dog bites. Permission for necropsy was refused, so the diagnosis of rabies was based on clinical grounds only. Another patient bitten by the same dog and treated at the local health centre where sixteen injections of Semple vaccine were given, also died of clinical rabies 22 days later. W.H.O. recommends that everyone bitten by a rabid animal should receive hyperimmune serum of the equine or human type.7 Prophylaxis should be started as soon as possible, especially for severe bites. Our patient was not given hyperimmune serum and the first dose of vaccine was given on the third day after the bite. Inadequate post-exposure treatment was probably the main reason for failure in this case, as in the 1981 case in Rwanda.Immediate administration of hyperimmune serum is strongly recommended, even when a potent vaccine is used. Department of Microbiology, Faculty of Medicine, Siriraj Hospital, Bangkok 10700, Thailand; and Division of Epidemiology and Bamrasnaradur Infectious
Hospital,
Ministry of Public Health, Bangkok
SOMSAK WATTANASRI PRAKORB BOONTHAI PRASERT THONGCHAROEN
DANGER TO ASTHMATICS OF A BETA BLOCKER IN A THREE-COMPONENT TABLET
SIR,-Products combining two or more drugs have become fashionable, especially in cardiovascular pharmacology. There may, however, be an inherent danger, as the following case illustrates, if the prescriber does not bear in mind the individual components. A 60-year-old woman had had asthma for 25 years. This was well controlled on prednisolone 5 mg twice daily and a twice daily tablet of ’Franol Plus’ (ephedrine, phenobarbitone, theophylline, thenyldiamine), with isoprenaline by ’Medihaler’ as needed, and she had never needed hospital care for her asthma. On the day of admission she had a nose bleed and saw her general practitioner who
3. Marlow
6. Devriendt J, Staroukine M. Human rabies-Rwanda. Morbid Mortal Wkly Rep 1982; 31: 135. 7. Report of consultation on rabies prevention and control (Lyon, France, March 10-12,
1980). WHO/Rab. Res/80.8.