- Email: [email protected]
TWO RABIES DEATHS AFTER CORNEAL GRAFTS FROM ONE DONOR
791
at onset of ipecacuanha-induced vomiting in 62-year-old man. A: sinus bradycardia, complete atrioventricular block, and ventricular asystole developed and patient required pacing. B: vomiting after
Electrocardiograms
pretreatment with intravenous atropine
bradycardia or heart block.
p = p waves; V
not associated with sinus ventricular pacing.
was =
examination were normal. However, balloon inflation in the middle third (one patient) and lower third (two patients) of the oesophagus induced some sinus bradycardia and transient complete atrioventricular block. Pretreatment with atropine (600 ltg)
.
;
prevented the response to both vomiting (figure) and balloon inflation. Swallowing a large bolus of food was not associated with atrioventricular block in any patient. Limited electrophysiological investigations in two patients showed that conduction times were normal. Echocardiographic studies in all three patients were normal. Cardiovascular responses to vagal manoeuvres including Valsalva, carotid sinus massage, and face immersion (diving reflex) were also normal. We postulate that vomiting syncope results from a hypersensitive parasympathetic (vago-vagal) reflex. Responses of the heart to vagal manoeuvres indicated normal function of the vagal efferents to the heart. The abnormality appears to be in the afferent limb where pressure sensors in the oesophageal wall produce an excessive discharge on sudden distension (as occurs in vomiting). Although the responses of the cardiac rhythm to vagal manoeuvres were normal, the effect of stimulation of the vagal efferents to the heart in the case described by Lewis and colleagues and our cases was predominantly on the atrioventricular node rather than on the sinus node. Why this should be is not clear, but the distribution of vagal fibres to the atrioventricular node and sinoatrial node may be differentiated in the central nervous system.’ Furthermore the effect of simple vagal manoeuvres on atrioventricular node function is normally masked by simultaneous sinoatrial node slowing.’ The long history in our patients may reflect a developmental abnormality: one of the patients had a family history of unexplained sudden death. We suggest a careful and detailed evaluation of all patients with vomiting-related dizziness or syncope, because this life-threatening condition can be easily treated by cardiac pacing. St George’s Hospital Medical School, Cranmer Terrace, London SW17 0RE; and St Peter’s Hospital,
Chertsey, Surrey
D. MEHTA T. G. FARRELL
M. JOY D. WARD A. J. CAMM
1. Martin P. The influence of the
parasympathetic nervous system on atnoventricular conduction. Circ Res 1977; 41: 593-601. 2. James TJ, Urthaler FN, Hageman GR. Reflex heart block. Am Heart J 1980; 45: 1182-88.
TWO RABIES DEATHS AFTER CORNEAL GRAFTS FROM ONE DONOR
SiR,—On Sept 17, 1987, two patients received comeal grafts from a single donor. 9 days later one recipient, a 62-year-old physician, had redness, swelling, and intense pain in the operated eye. After 2 days, be became very restless and apprehensive of impending death and manifested hydrophobia; he denied a history of an animal bite. His thinking was clear enough to prepare his last will and testament with the help of an attomey. He died on Oct 1, 1987. The second recipient, a 48-year-old man, lived about 80 miles away. He was promptly advised by a doctor, who was a friend to both men, to take a full course of purified chick embryo cell vaccine. He had two vaccine injections during the second week of October but refused the remaining four because his transplant was
functioning satisfactorily. On June 1, 1988, he experienced difficulty in swallowing with pain, redness, and swelling of the operated eye. After 2 days hydrophobia developed and rabies was diagnosed, even though a history of animal bite was absent. He was referred to a specialist centre where the diagnosis was confirmed. He died on June 6. Necropsy was not done and the bodies of both men were promptly cremated. On June 8, 1988, a close friend of the second recipient consulted us in a panic over the risk that he might have got "rabies contamination" from his now dead friend; this prompted the inquiry that disclosed the facts reported here. The eye surgeon, who works about 200 miles away, had operated upon both patients without wearing gloves-a common practice to achieve greater digital precision and skill. He is now being given prophylaxis. Pain, redness, and swelling of the operated eye just at the explosive onset of clinical rabies were observed in these two patients. Pain, itching, or paraesthesia at or around the operated eye were complained of in two of the other four reported cases of death from rabies after corneal transplantation.1-3 Probably this is the equivalent of the itching and paraesthesia at and around the site of the bite which is often reported at the onset of clinical rabies acquired through the usual route. It seems likely that both these patients acquired rabies from the corneas of the donor who had died of unsuspected rabies. Of the first previously reported cases of corneal transplant recipients who contracted the disease from donors who had died of unsuspected rabies, only one was detected promptly and disaster prevented by intensive immunotherapy; the other four died, unsuspected and untreated, 22-50 days after the corneal graft. 1-3 Two previous cases, like ours, had a common rabies-infected donor.2 Our first patient died 14 days after the operation, an interval compatible with the incubation period of rabies. The second man survived for over 8 months, perhaps because he had had two injections of vaccine. Had he taken the remaining four he might have lived. Corneal transplantation is becoming more widely used in countries in which rabies is endemic. In India some 1,1million patients need a corneal transplant but every year only about 2000 operations are done.’ Successful grafting depends upon the speed with which eyes can be obtained, and these two deaths emphasise the need for a good clinical history from the donor and for facilities for the rapid diagnosis of rabies infection in donor eyes in the 131 eye collection centres in India. The value of briefly immersing corneas in human antirabies immunoglobulin should be explored experimentally. Ophthalmic surgeons who insist on not using gloves should be immunised. Department of Anaesthesiology, All-India Institute of Medical Sciences, New Delhi-110029, India
G. R. GODE N. K. BHIDE
RC, Wilson RW, et al. Human-to-human transmission of rabies transplant. N Engl J Med 1979; 300: 603-04. 2 Thongcharoen P, Wasi C, Sinkavin S, et al. Human-to-human transmission of rabies via comeal transplant-Thailand MMWR 1981; 30: 473-74. 3. Kaplan C, Turner GS, Warrell DA. Rabies: the facts 2nd ed. Oxford: Oxford University Press, 1986: 24-25. 4. Eye donation volunteer manual. New Delhi: Times of India Eye Research Foundation, 1. Houff SA, Burton
virus by corneal
1988 1-2.
MALARIA CHEMOPROPHYLAXIS AND TRAVELLER’S WEIGHT
SiR,—A survey at Barcelona airport’ revealed that 117 of 910 passengers flying to the tropics had been advised to take chloroquine prophylaxis at doses that we thought insufficient. A weekly dose of at least 5 mg/kg body weight was our criterion for correct prophylaxis, based on the minimum recommended dose for prophylaxis in children2,3 and the World Health Organisation advice of 300 mg weekly for people weighing from 50-70 kg.4 The main sources of health information for travellers are travel agencies1 and general practitioners.’,5 Travel agents use the Travel Information Manual,6 the latest edition of which advises travellers to consult a doctor for information on which prophylaxis to take and at what dose. However, European medical students are not usually given any special training in advising travellers. A general
at onset of ipecacuanha-induced vomiting in 62-year-old man. A: sinus bradycardia, complete atrioventricular block, and ventricular asystole developed and patient required pacing. B: vomiting after
Electrocardiograms
pretreatment with intravenous atropine
bradycardia or heart block.
p = p waves; V
not associated with sinus ventricular pacing.
was =
examination were normal. However, balloon inflation in the middle third (one patient) and lower third (two patients) of the oesophagus induced some sinus bradycardia and transient complete atrioventricular block. Pretreatment with atropine (600 ltg)
.
;
prevented the response to both vomiting (figure) and balloon inflation. Swallowing a large bolus of food was not associated with atrioventricular block in any patient. Limited electrophysiological investigations in two patients showed that conduction times were normal. Echocardiographic studies in all three patients were normal. Cardiovascular responses to vagal manoeuvres including Valsalva, carotid sinus massage, and face immersion (diving reflex) were also normal. We postulate that vomiting syncope results from a hypersensitive parasympathetic (vago-vagal) reflex. Responses of the heart to vagal manoeuvres indicated normal function of the vagal efferents to the heart. The abnormality appears to be in the afferent limb where pressure sensors in the oesophageal wall produce an excessive discharge on sudden distension (as occurs in vomiting). Although the responses of the cardiac rhythm to vagal manoeuvres were normal, the effect of stimulation of the vagal efferents to the heart in the case described by Lewis and colleagues and our cases was predominantly on the atrioventricular node rather than on the sinus node. Why this should be is not clear, but the distribution of vagal fibres to the atrioventricular node and sinoatrial node may be differentiated in the central nervous system.’ Furthermore the effect of simple vagal manoeuvres on atrioventricular node function is normally masked by simultaneous sinoatrial node slowing.’ The long history in our patients may reflect a developmental abnormality: one of the patients had a family history of unexplained sudden death. We suggest a careful and detailed evaluation of all patients with vomiting-related dizziness or syncope, because this life-threatening condition can be easily treated by cardiac pacing. St George’s Hospital Medical School, Cranmer Terrace, London SW17 0RE; and St Peter’s Hospital,
Chertsey, Surrey
D. MEHTA T. G. FARRELL
M. JOY D. WARD A. J. CAMM
1. Martin P. The influence of the
parasympathetic nervous system on atnoventricular conduction. Circ Res 1977; 41: 593-601. 2. James TJ, Urthaler FN, Hageman GR. Reflex heart block. Am Heart J 1980; 45: 1182-88.
TWO RABIES DEATHS AFTER CORNEAL GRAFTS FROM ONE DONOR
SiR,—On Sept 17, 1987, two patients received comeal grafts from a single donor. 9 days later one recipient, a 62-year-old physician, had redness, swelling, and intense pain in the operated eye. After 2 days, be became very restless and apprehensive of impending death and manifested hydrophobia; he denied a history of an animal bite. His thinking was clear enough to prepare his last will and testament with the help of an attomey. He died on Oct 1, 1987. The second recipient, a 48-year-old man, lived about 80 miles away. He was promptly advised by a doctor, who was a friend to both men, to take a full course of purified chick embryo cell vaccine. He had two vaccine injections during the second week of October but refused the remaining four because his transplant was
functioning satisfactorily. On June 1, 1988, he experienced difficulty in swallowing with pain, redness, and swelling of the operated eye. After 2 days hydrophobia developed and rabies was diagnosed, even though a history of animal bite was absent. He was referred to a specialist centre where the diagnosis was confirmed. He died on June 6. Necropsy was not done and the bodies of both men were promptly cremated. On June 8, 1988, a close friend of the second recipient consulted us in a panic over the risk that he might have got "rabies contamination" from his now dead friend; this prompted the inquiry that disclosed the facts reported here. The eye surgeon, who works about 200 miles away, had operated upon both patients without wearing gloves-a common practice to achieve greater digital precision and skill. He is now being given prophylaxis. Pain, redness, and swelling of the operated eye just at the explosive onset of clinical rabies were observed in these two patients. Pain, itching, or paraesthesia at or around the operated eye were complained of in two of the other four reported cases of death from rabies after corneal transplantation.1-3 Probably this is the equivalent of the itching and paraesthesia at and around the site of the bite which is often reported at the onset of clinical rabies acquired through the usual route. It seems likely that both these patients acquired rabies from the corneas of the donor who had died of unsuspected rabies. Of the first previously reported cases of corneal transplant recipients who contracted the disease from donors who had died of unsuspected rabies, only one was detected promptly and disaster prevented by intensive immunotherapy; the other four died, unsuspected and untreated, 22-50 days after the corneal graft. 1-3 Two previous cases, like ours, had a common rabies-infected donor.2 Our first patient died 14 days after the operation, an interval compatible with the incubation period of rabies. The second man survived for over 8 months, perhaps because he had had two injections of vaccine. Had he taken the remaining four he might have lived. Corneal transplantation is becoming more widely used in countries in which rabies is endemic. In India some 1,1million patients need a corneal transplant but every year only about 2000 operations are done.’ Successful grafting depends upon the speed with which eyes can be obtained, and these two deaths emphasise the need for a good clinical history from the donor and for facilities for the rapid diagnosis of rabies infection in donor eyes in the 131 eye collection centres in India. The value of briefly immersing corneas in human antirabies immunoglobulin should be explored experimentally. Ophthalmic surgeons who insist on not using gloves should be immunised. Department of Anaesthesiology, All-India Institute of Medical Sciences, New Delhi-110029, India
G. R. GODE N. K. BHIDE
RC, Wilson RW, et al. Human-to-human transmission of rabies transplant. N Engl J Med 1979; 300: 603-04. 2 Thongcharoen P, Wasi C, Sinkavin S, et al. Human-to-human transmission of rabies via comeal transplant-Thailand MMWR 1981; 30: 473-74. 3. Kaplan C, Turner GS, Warrell DA. Rabies: the facts 2nd ed. Oxford: Oxford University Press, 1986: 24-25. 4. Eye donation volunteer manual. New Delhi: Times of India Eye Research Foundation, 1. Houff SA, Burton
virus by corneal
1988 1-2.
MALARIA CHEMOPROPHYLAXIS AND TRAVELLER’S WEIGHT
SiR,—A survey at Barcelona airport’ revealed that 117 of 910 passengers flying to the tropics had been advised to take chloroquine prophylaxis at doses that we thought insufficient. A weekly dose of at least 5 mg/kg body weight was our criterion for correct prophylaxis, based on the minimum recommended dose for prophylaxis in children2,3 and the World Health Organisation advice of 300 mg weekly for people weighing from 50-70 kg.4 The main sources of health information for travellers are travel agencies1 and general practitioners.’,5 Travel agents use the Travel Information Manual,6 the latest edition of which advises travellers to consult a doctor for information on which prophylaxis to take and at what dose. However, European medical students are not usually given any special training in advising travellers. A general