were noted. The concentration of 5FU was then increased to 100 mg in 1000 ml of saline and the bladder of four patients was irrigated, with continuous outflow, for 96 hours, again without adverse effects. A control urine specimen was collected from each patient prior to the beginning of the bladder irrigations. During treatment all bladder washings were collected for each 24hour period. The volume was measured and a sample taken for ultraviolet spectrophotometric analysis in the 5-FU range, with the control urine as a blank. No new medications were administered while the irrigations were being done. We recovered from the bladder washings 5% and 10% of the total dose of 5-FU instilled. There was no evidence of bladder disturbance, either during or after irrigation. No effects on the hematopoietic system and no systemic effects were detected.
We have recently increased the concentration of 5-FU to 150 mg in 1000 ml of saline and have completed three 5-day irrigations in 10 patients, with no side effects being noted. Since we have no data on the optimum dose of 5-FU used in this manner we propose to do a trial with this concentration, using each patient as his or her own control, to see if we can influence the recurrence rate. This study was supported by grant 273 from the Ontario Cancer Treatment and Research Foundation. References 1. GREENE LF, HANASH KA, FARROW
GM: Benign papilloma or papillary carcinoma of the bladder. J Urol 110: 205, 1973 2. BARNES RW, DICK AL, HADLEY HL,
et al: Survival following transurethral resection of bladder carcinoma. Cancer Res 37: 2895, 1977 3. KLEIN E, STOLL HL, MILGROM H, et
al: Tumors of the skin. VI. Study on effects of local administration of 5fluorouracil in basal-cell carcinoma. J Invest Dermatol 47: 22, 1966 4. KLEIN E: Tumors of the skin. IX.
Local cystostatic therapy of cutaneous and mucosal premalignant and malignant lesions. NY State J Med 68: 886, 1968 5. KLEIN E, STOLL HL, MILLER E, et al: The effects of 5-fluorouracil (5-FU) ointment in the treatment of neoplastic dermatoses. Dermatologica 140: 21, 1970 6. WEIN AJ, BENSON GS: The treatment of urethral condyloma acuminatum with 5-fluorouracil cream. Urology 9: 413, 1977 7. LEwis RJ, BENDL BJ: Erythroplasia of Queyrat: report of a patient successfully treated with topical 5-fluorouracil. Can Med Assoc J 104: 148, 1971 8. DRETLER SP, KLEIN LA: The eradica-
tion
of
intraurethal
condylomata
acuminata with 5 per cent 5-fluorou-
racil cream. I Urol 113: 195, 1975 9. KESSEL D, HALL TC: Influence of ribose donors on the action of 5fluorouracil. Cancer Res 29: 1749,
1969
Powassan virus meningoencephalitis: a case report MICHAEL S. WILsoN,* MB, CH B, DCH, DRCOG; BRIAN A. WHERRETT,* MD, CM, FRCP[C]; M.S. MAHDY,t MPH, D Sc
Powassan virus is a tick-borne member of the flavivirus genus (group B arboviruses) of the Togaviridae family. It was first isolated by McLean and Donohue in 1958 from a 5-year-old boy from Powassan, Ont.' Forest rodents, such as groundhogs, chipmunks, squirrels, snowshoe hares and porcupines, were found to be the main reservoirs of the virus. Ixodes ticks in Canada and Ixodes and Dermacentor ticks in the United States were found to be the vectors of the 2 virus. In this paper we present a From *the department of pediatrics, Queen's University, Kingston, Ont. and tthe laboratory services branch, Ontario Ministry of Health, Toronto Reprint requests to: Dr. Brian A. Wherrett, Department of pediatrics, Queen's University, Kingston, Ont. K7L 3N6
case of Powassan virus meningoencephalitis and discuss the clinical picture in relation to that of other cases reported in the literature.
Case report Clinical course A 13-month-old girl was admitted to Kingston General Hospital Aug. 22, 1977 with a 4-day history of anorexia, lethargy, fever (temperature 38 to 390C) and a rash. She had been treated with penicillin. Three weeks before the illness started she had been bitten by a tick over the right eyebrow. The family cat was under treatment for tick infestation and had apparently carried the tick to the child. The cat was subsequently found to have Powassan virus antibodies. At the time of examination she had a temperature of 400C, was
320 CMA JOURNAL/AUGUST 4, 1979/VOL. 121
lethargic, and had slight neck stiffness and an erythematous morbilliform rash over the legs and arms. The hemoglobin value was 12.9 g/dl and the Leukocyte count was 17.7 x 10./l (55% were neutrophils, 32% lymphocytes, 11 % monocytes and 2% band forms). The cerebrospinal fluid was clear and colourless; the neutrophil and lymphocyte counts were 17.5 x 10./l and 3.6 x 10./l respectively, and the serum total protein and blood glucose concentrations were 30 and 83 mg/dl respectively. A diagnosis of partially treated pyogenic meningitis was made, and intravenous therapy with ampicillin, 400 mg/kg and chloramphenicol, 100 mg/kg daily was started. No organism was cultured from the cerebrospinal fluid or the urine. Staphylococcus aureus (coagulasenegative) was cultured from the
Table 1-Titron of antibody' to Powassan virus in serum of child with meningoencephalitis Antibody; titret Date HI CF Aug. 24, 1977 10 8 Sept. 30, 1977 140 128 Oct 2L, 1917 160 128 July 24, 1978 80 128 *141 = hemagglutlnat1on.inhlbiting; CF = complement-fIxIng. tReciprocal of dilution; confirmed by the National Arbovirus Reference Service, Toronto.
gested the possibility that these animals were infected with Powassan virus or a closely related flavivirus. Discussion The 14 recorded cases of Powassan virus meningoencephalitis are listed in Table II. The cases reported from New York State between 1971 and 1975 were apparently acquired in predominantly rural counties in the central eastern part of the state (R. Deibel: personal communication, 1978). In one case an 82-year-old farmer died of the disease, and the virus was isolated from his brain. A 10-year-old girl with a diagnosis of encephalitis became psychotic 4 weeks after the onset of the illness; the psychosis persisted for 4 months. Powassan virus antibodies have also been detected in humans without a history of illness in Ontario IO.11 British Columbia,'2"3 New York State4 and Mexico.'4 We believe that our patient had Powassan virus meningoencephalitis because the clinical features were similar to those of proven cases and because of the seroconversion to Powassan virus antigen only. Furthermore, the tick bite was the result of close contact with a tickinfested cat that was found to have hemagglutination-inhibiting antibodies to Powassan virus. The family's pet dog had both hemagglutination-inhibiting and complementfixing antibodies to Powassan virus. Provided that the antibodies detected in the family pets did not reflect a heterologous response to another flavivirus, this would be
the first report, to our knowledge, suggesting infection of such animals with Powassan virus.
Conclusion Powassan virus infection can cause an acute neurologic disease with severe sequelae. Although rare, it should be considered in cases of unexplained meningoencephalitis. The increase in serum antibody titres may be slow, and follow-up serologic testing should be done up to 6 wceks after the onset of symptoms to make the diagnosis. It may be that family pets (dogs and cats) can be infected with Powassan virus or a closely related flavivirus. We thank Dr. M.W. Partington, department of pediatrics, Queen's University, for his interest and assistance, Dr. M.J. O'Shaughnessy, director of the Kingston Public Health Laboratory, for kindly arranging to have the specimens tested in Toronto, Mrs. Edith Bansen for her technical support, and Hanna Dodwell for her patience and efforts in typing the manuscript.
References 1. MCLEAN DM, DONOHUE WL: Pow-
assan virus: isolation of virus from a fatal case of encephalitis. Can Med Assoc 1 80: 708, 1959 2. CHERNESKY MA: Powassan virus transmission by ixodid ticks infected
after feeding on viremic rabbits injected intravenously. Can I Microbid 15: 521, 1969 3. GOLDFIELD M, AUSTIN SM, BLACK
HG, et al: A non-fatal human case of Powassan virus encephalitis. Am I Trop Med Hyg 22: 78, 1973 4. SMITH R, WOODALL JP, WHITNEY
E, et al: Powassan virus infection. Am I Dis Child 127: 691, 1974 5. RosslER E, HARRISON RJ, LEMIEUX
B: A case of Powassan virus encephalitis. Can Med Assoc J 110: 1173, 1974 6. DEIBEL R,
FLANAGAN TD,
SMITH
V: Central nervous system infections in New York State. Etiologic and epidemiologic observations. 1974. NY State J Med 75: 2337, 1975 7. Powassan encephalitis with shoulder girdle involvement. Can Dis Wkly Rep 2: 85, 1976 8. DEIBEL
R, FLANAGAN TD,
SMITH
V: Central nervous system infections. Etiologic and epidemiologic observations in New York State, 1975. NY State J Med 77: 1398. 1977 9. Powassan encephalitis -. Ontario. Can Dis Wkly Rep 2: 202, 1976 10. MCLEAN DM, MCQUEEN EJ, PETITE
HE, et al: Powassan virus: field investigations in northern Ontario, 1959 to 1961. Call Med Assoc J 86: 971, 1962 11. MCLEAN
DM,
MACPHERSON
LW,
WALKER SJ, Ct al: Powassan virus: surveys of human and animal sera. Am J Public Health 50: 1539, 1960 12. KETTYLS GD, VERRALL VM, WIL-
TON LD, et al: Arbovirus infections in man in British Columbia. Can
Med Assoc J 106: 1175, 1972 13. MCLEAN DM, BERGMAN SKA, GODDARD EJ, et al: North-south distribution of arbovirus reservoirs in British Columbia, 1970. Can J Public Health 62: 120, 1971 14. Arthropod borne viral disease, in United States-Mexico Border Public Health Association Conference Report. Public Health Rep 77: 140, 1962
Addendum Since this paper was submitted for publication another case of encephalitis due to Powassan virus has occurred, in an 18-year-old girl in Ontario. The history suggests that the girl was infected in the area of Buckhorn Lake, in central Ontario (D.R. Crapper, L. Spence and H. Artsob: personal communication, 1979).
Ticks' tags The tick is a "blood-sucking acarid parasite of the suborder Ixodides, superfamily Ixodoidea". This vampire-like creature can have a soft or a hard body - at least the latter doesn't leave a mess when you scratch at it. Among the varieties of tick is the Adobe tick - this of course comes from tropical countries and lives chiefly on the inhabitants of mud huts. Then there is the Bandicoot tick - found only on coots that have learnt to walk too soon. Ticks find it easier to climb up bandy legs than straight ones. There is also the beady-legged winter horse tick if your horse has beady eyes don't worry, only the legs count. Ticks also inhabit dogs. There are American dog, British dog and brown dog ticks. When buying a dog make sure that it is oriental and has absolutely no brown hair.* CMA JOURNAL/AUGUST 4, 1979/VOL. 121
323
We have recently increased the concentration of 5-FU to 150 mg in 1000 ml of saline and have completed three 5-day irrigations in 10 patients, with no side effects being noted. Since we have no data on the optimum dose of 5-FU used in this manner we propose to do a trial with this concentration, using each patient as his or her own control, to see if we can influence the recurrence rate. This study was supported by grant 273 from the Ontario Cancer Treatment and Research Foundation. References 1. GREENE LF, HANASH KA, FARROW
GM: Benign papilloma or papillary carcinoma of the bladder. J Urol 110: 205, 1973 2. BARNES RW, DICK AL, HADLEY HL,
et al: Survival following transurethral resection of bladder carcinoma. Cancer Res 37: 2895, 1977 3. KLEIN E, STOLL HL, MILGROM H, et
al: Tumors of the skin. VI. Study on effects of local administration of 5fluorouracil in basal-cell carcinoma. J Invest Dermatol 47: 22, 1966 4. KLEIN E: Tumors of the skin. IX.
Local cystostatic therapy of cutaneous and mucosal premalignant and malignant lesions. NY State J Med 68: 886, 1968 5. KLEIN E, STOLL HL, MILLER E, et al: The effects of 5-fluorouracil (5-FU) ointment in the treatment of neoplastic dermatoses. Dermatologica 140: 21, 1970 6. WEIN AJ, BENSON GS: The treatment of urethral condyloma acuminatum with 5-fluorouracil cream. Urology 9: 413, 1977 7. LEwis RJ, BENDL BJ: Erythroplasia of Queyrat: report of a patient successfully treated with topical 5-fluorouracil. Can Med Assoc J 104: 148, 1971 8. DRETLER SP, KLEIN LA: The eradica-
tion
of
intraurethal
condylomata
acuminata with 5 per cent 5-fluorou-
racil cream. I Urol 113: 195, 1975 9. KESSEL D, HALL TC: Influence of ribose donors on the action of 5fluorouracil. Cancer Res 29: 1749,
1969
Powassan virus meningoencephalitis: a case report MICHAEL S. WILsoN,* MB, CH B, DCH, DRCOG; BRIAN A. WHERRETT,* MD, CM, FRCP[C]; M.S. MAHDY,t MPH, D Sc
Powassan virus is a tick-borne member of the flavivirus genus (group B arboviruses) of the Togaviridae family. It was first isolated by McLean and Donohue in 1958 from a 5-year-old boy from Powassan, Ont.' Forest rodents, such as groundhogs, chipmunks, squirrels, snowshoe hares and porcupines, were found to be the main reservoirs of the virus. Ixodes ticks in Canada and Ixodes and Dermacentor ticks in the United States were found to be the vectors of the 2 virus. In this paper we present a From *the department of pediatrics, Queen's University, Kingston, Ont. and tthe laboratory services branch, Ontario Ministry of Health, Toronto Reprint requests to: Dr. Brian A. Wherrett, Department of pediatrics, Queen's University, Kingston, Ont. K7L 3N6
case of Powassan virus meningoencephalitis and discuss the clinical picture in relation to that of other cases reported in the literature.
Case report Clinical course A 13-month-old girl was admitted to Kingston General Hospital Aug. 22, 1977 with a 4-day history of anorexia, lethargy, fever (temperature 38 to 390C) and a rash. She had been treated with penicillin. Three weeks before the illness started she had been bitten by a tick over the right eyebrow. The family cat was under treatment for tick infestation and had apparently carried the tick to the child. The cat was subsequently found to have Powassan virus antibodies. At the time of examination she had a temperature of 400C, was
320 CMA JOURNAL/AUGUST 4, 1979/VOL. 121
lethargic, and had slight neck stiffness and an erythematous morbilliform rash over the legs and arms. The hemoglobin value was 12.9 g/dl and the Leukocyte count was 17.7 x 10./l (55% were neutrophils, 32% lymphocytes, 11 % monocytes and 2% band forms). The cerebrospinal fluid was clear and colourless; the neutrophil and lymphocyte counts were 17.5 x 10./l and 3.6 x 10./l respectively, and the serum total protein and blood glucose concentrations were 30 and 83 mg/dl respectively. A diagnosis of partially treated pyogenic meningitis was made, and intravenous therapy with ampicillin, 400 mg/kg and chloramphenicol, 100 mg/kg daily was started. No organism was cultured from the cerebrospinal fluid or the urine. Staphylococcus aureus (coagulasenegative) was cultured from the
Table 1-Titron of antibody' to Powassan virus in serum of child with meningoencephalitis Antibody; titret Date HI CF Aug. 24, 1977 10 8 Sept. 30, 1977 140 128 Oct 2L, 1917 160 128 July 24, 1978 80 128 *141 = hemagglutlnat1on.inhlbiting; CF = complement-fIxIng. tReciprocal of dilution; confirmed by the National Arbovirus Reference Service, Toronto.
gested the possibility that these animals were infected with Powassan virus or a closely related flavivirus. Discussion The 14 recorded cases of Powassan virus meningoencephalitis are listed in Table II. The cases reported from New York State between 1971 and 1975 were apparently acquired in predominantly rural counties in the central eastern part of the state (R. Deibel: personal communication, 1978). In one case an 82-year-old farmer died of the disease, and the virus was isolated from his brain. A 10-year-old girl with a diagnosis of encephalitis became psychotic 4 weeks after the onset of the illness; the psychosis persisted for 4 months. Powassan virus antibodies have also been detected in humans without a history of illness in Ontario IO.11 British Columbia,'2"3 New York State4 and Mexico.'4 We believe that our patient had Powassan virus meningoencephalitis because the clinical features were similar to those of proven cases and because of the seroconversion to Powassan virus antigen only. Furthermore, the tick bite was the result of close contact with a tickinfested cat that was found to have hemagglutination-inhibiting antibodies to Powassan virus. The family's pet dog had both hemagglutination-inhibiting and complementfixing antibodies to Powassan virus. Provided that the antibodies detected in the family pets did not reflect a heterologous response to another flavivirus, this would be
the first report, to our knowledge, suggesting infection of such animals with Powassan virus.
Conclusion Powassan virus infection can cause an acute neurologic disease with severe sequelae. Although rare, it should be considered in cases of unexplained meningoencephalitis. The increase in serum antibody titres may be slow, and follow-up serologic testing should be done up to 6 wceks after the onset of symptoms to make the diagnosis. It may be that family pets (dogs and cats) can be infected with Powassan virus or a closely related flavivirus. We thank Dr. M.W. Partington, department of pediatrics, Queen's University, for his interest and assistance, Dr. M.J. O'Shaughnessy, director of the Kingston Public Health Laboratory, for kindly arranging to have the specimens tested in Toronto, Mrs. Edith Bansen for her technical support, and Hanna Dodwell for her patience and efforts in typing the manuscript.
References 1. MCLEAN DM, DONOHUE WL: Pow-
assan virus: isolation of virus from a fatal case of encephalitis. Can Med Assoc 1 80: 708, 1959 2. CHERNESKY MA: Powassan virus transmission by ixodid ticks infected
after feeding on viremic rabbits injected intravenously. Can I Microbid 15: 521, 1969 3. GOLDFIELD M, AUSTIN SM, BLACK
HG, et al: A non-fatal human case of Powassan virus encephalitis. Am I Trop Med Hyg 22: 78, 1973 4. SMITH R, WOODALL JP, WHITNEY
E, et al: Powassan virus infection. Am I Dis Child 127: 691, 1974 5. RosslER E, HARRISON RJ, LEMIEUX
B: A case of Powassan virus encephalitis. Can Med Assoc J 110: 1173, 1974 6. DEIBEL R,
FLANAGAN TD,
SMITH
V: Central nervous system infections in New York State. Etiologic and epidemiologic observations. 1974. NY State J Med 75: 2337, 1975 7. Powassan encephalitis with shoulder girdle involvement. Can Dis Wkly Rep 2: 85, 1976 8. DEIBEL
R, FLANAGAN TD,
SMITH
V: Central nervous system infections. Etiologic and epidemiologic observations in New York State, 1975. NY State J Med 77: 1398. 1977 9. Powassan encephalitis -. Ontario. Can Dis Wkly Rep 2: 202, 1976 10. MCLEAN DM, MCQUEEN EJ, PETITE
HE, et al: Powassan virus: field investigations in northern Ontario, 1959 to 1961. Call Med Assoc J 86: 971, 1962 11. MCLEAN
DM,
MACPHERSON
LW,
WALKER SJ, Ct al: Powassan virus: surveys of human and animal sera. Am J Public Health 50: 1539, 1960 12. KETTYLS GD, VERRALL VM, WIL-
TON LD, et al: Arbovirus infections in man in British Columbia. Can
Med Assoc J 106: 1175, 1972 13. MCLEAN DM, BERGMAN SKA, GODDARD EJ, et al: North-south distribution of arbovirus reservoirs in British Columbia, 1970. Can J Public Health 62: 120, 1971 14. Arthropod borne viral disease, in United States-Mexico Border Public Health Association Conference Report. Public Health Rep 77: 140, 1962
Addendum Since this paper was submitted for publication another case of encephalitis due to Powassan virus has occurred, in an 18-year-old girl in Ontario. The history suggests that the girl was infected in the area of Buckhorn Lake, in central Ontario (D.R. Crapper, L. Spence and H. Artsob: personal communication, 1979).
Ticks' tags The tick is a "blood-sucking acarid parasite of the suborder Ixodides, superfamily Ixodoidea". This vampire-like creature can have a soft or a hard body - at least the latter doesn't leave a mess when you scratch at it. Among the varieties of tick is the Adobe tick - this of course comes from tropical countries and lives chiefly on the inhabitants of mud huts. Then there is the Bandicoot tick - found only on coots that have learnt to walk too soon. Ticks find it easier to climb up bandy legs than straight ones. There is also the beady-legged winter horse tick if your horse has beady eyes don't worry, only the legs count. Ticks also inhabit dogs. There are American dog, British dog and brown dog ticks. When buying a dog make sure that it is oriental and has absolutely no brown hair.* CMA JOURNAL/AUGUST 4, 1979/VOL. 121
323
