- Email: [email protected]
SPONDWENI VIRUS INFECTION IN A FOREIGN RESIDENT OF UPPER VOLTA
1306
diarrhoea seen clinical and
recently in Perth presented similarly histological features consistent
with with inflammatory bowel disease.2 Treatment should be considered in patients with prolonged diarrhoea when Aeromonas spp. have been isolated from faeces. In such patients trimethoprim is the most appropriate antimicrobial agent. 12 Other drugs, such as oxytetracycline, chloramphenicol, and the third-generation cephalosporins are effective in vitro,12 and may be appropriate (depending on the clinical picture), especially in adults. Many of our colleagues helped make this work possible; in particular, we thank Mr Douglas Peck, Mrs Jannice Beaman, Dr R. Hill, Mrs Christine Bundell, and Dr Michael Dibley. The departments of microbiology and medical records and hospital nurses also helped with the study. This study was supported by the National Health and Medical Research Council and by the TVW Telethon Foundation. Correspondence should be addressed to M. G., G.P.O. Box D.184, Perth, 6001, Western Australia. REFERENCES
Chipman DC. Clinical involvement of Aeromonas hydrophila Canad Med Assn J 1979; 120: 942-46. 2. Goodwin CS, Harper WS, Stewart JK, Gracey M, Burke V, Robinson J. Enterotoxigenic Aeromonas hydrophila and diarrhoea in adults. Med J Aust (in press). 3. Sanyal SC, Singh SJ, Sen PC. Enteropathogenicity of Aeromonas hydrophila and Plesiomonas shigelloides. J Med Microbiol 1975; 8: 195-98. 4. Burke V, Robinson J, Berry RJ, Gracey M. Detection of enterotoxins of Aeromonas hydrophila by a suckling-mouse test. J Med Microbiol 1981; 14: 401-08. 5. Graevenitz A von, Zinterhofer L The detection of Aeromonas hydrophila in stool specimens. Health Lab Sci 1970; 7: 124-27. 6. Overman TL, D’Amato RF, Tomfohrd E. Incidence of oxidase-variable strains of Aeromonas hydrophila. J Clin Microbiol 1979; 9: 244-47 7. Hazen TC, Fliermans CB, Hirsch RP, Esch GW. Prevalence and distribution of Aeromonas hydrophila in the United States. Appl Envir Microbiol 1978; 36: 731-38. 8. Lupo L, Strickland E, Dufour A, Cabelli V. The effect of oxidase positive bacteria on total coliform density estimates. Health & Lab Sci 1977; 14: 117-21. 9. Kaper JB, Lockman H, Colwell RR Aeromonas hydrophila and toxigenicity of isolates 1. Trust TJ,
10.
11, 12.
from an estuary. J Appl Bact 1981; 50: 359-77. Rippey SR, Cabelli V. Occurrence of Aeromonas hydrophila in limnetic environments: relationship of the organism to trophic state Microbial Ecology 1980; 6: 45-54. Rahman SAFM, Willoughby JMT. Dysentery-like syndrome associated with Aeromonas hydrophila Br Med J 1980; 281: 976 Richardson CJL, Robinson JO, Wagener LB, Burke B. In vitro susceptibility of Aeromonas spp to antimicrobial agents J Antimicrob Chemoth 1982; 9: 267-74.
SPONDWENI VIRUS INFECTION IN A FOREIGN RESIDENT OF UPPER VOLTA MARTIN S. WOLFE
Office
of Medical Services,
Department of State, Washington,
D. C.
20520, U.S.A. CHARLES H. CALISHER Arbovirus Reference Branch, Division of Vector-Borne Viral Diseases, Centers for Disease Control, Fort Collins, Colorado 80522, U.S.A.
KAREN MCGUIRE American
Embassy, Ouagadougou, Upper Volta
Spondweni virus is a mosquito-borne flavivirus previously reported to cause human disease in Southern and West Africa. A serologically confirmed case of Spondweni virus infection in a U.S. citizen residing in Upper Volta is reported. Symptoms included fever, chills, headache, myalgia, nausea, and rash. A greyish mucoid lining was present on the posterior pharynx. The differential diagnosis included rickettsial infection, leptospirosis, typhoid fever, and numerous viral illnesses including Lassa fever. Evidence of Spondweni virus infection was also found in two other U.S. citizens residing in Gabon and Cameroon. Spondweni virus might be a cause of acute febrile illness throughout West Africa, and its presence should be considered in the differential diagnosis of febrile illness and in antibody surveys in that region. Summary
Introduction flavivirus (family human disease in Southern and West Africa. It has been isolated from the blood of a child in Nigeria,1 has caused two accidental febrile laboratory infections in South Africa,2 and has caused a
SPONDWENI virus is
Togaviridae) reported
a
mosquito-borne
to cause
febrile illness in a volunteer. Reported symptoms included brief fever, headache, and malaise. The virus has repeatedly been isolated from mosquitoes in South Africa, and antibody surveys suggest that it is widely distributed in Africa.4 We report here a serologically confirmed case of Spondweni virus infection in a U.S. citizen residing in Upper Volta. Additional evidence that Spondweni virus is a human pathogen in other areas of West Africa is provided.
Case-report 40-year-old American man, presented
Patient 1, a 1979, with severe headache, dizziness,
Nov. 16, aches, pain
on
nausea, muscle
behind his eyes, and sensitivity to light. Since Oct. 1 he had been working on a cattle-grazing project in Bitou, a small village in south-eastern Upper Volta, near the borders of Ghana and Togo and 500 km from the capital, Ouagadougou. He and a colleague lived in tents and spent all but their sleeping hours out of doors. They lived in camp 3 or 4 nights per week and returned to Ouagadougou for weekends. It was after the rainy season, and insects were in abundance and described as a biting nuisance. The patient was well until the morning of Nov. 15, when he awoke with a severe headache and myalgia, but he drove from Ouagadougou to Bitou. He became worse that day and was forced to return to Ouagadougou the following day, where he sought medical attention from one ofus (K. M.). On initial examination he appeared weak and prostrated. His body temperature was 37-4°C, pulse rate 68/min, and respiration rate 20/min. A fine maculopapular rash, which did not blanch on pressure, was seen across the bridge of his nose, over the cheeks, over the neck, and lightly across the chest and back; the appearance was that of a severe sunburn. The sclerae were red, and conjunctivitis and photophobia were present. The left buccal gland was red and swollen. There was no nuchal rigidity, but he could not lift his leg off the bed more than 60 degrees without experiencing pain in the lower back. Ear examination showed no abnormality. Lymph glands were not enlarged. The lungs were clear. The heart showed normal sinus rhythm. The abdomen was soft, and liver and spleen were not palpable. He had severe pain in his knees, elbows, and lower spine. Neurological examination was within normal limits. Laboratory results initially were: white-blood-cell count 12 600/mm3 with 73% polymorphs, 26% lymphocytes, l070 monocytes, and no eosinophils. Erythrocyte sedimentation rate (Wintrobe) at 1 h was 42 mm and at 2 h 83 mm. Haematocrit was 41%. Malarial parasites were not observed in thick or thin blood smears. Urine was negative. 2 h later his headache was worse and he felt dizzy and slightly disorientated. He developed chills; temperature 38.6°C, pulse rate 78/min, blood pressure 130/78 mm Hg. He vomited bilious material and was given prochlorperazine 10 mg i.m. The maculopapular rash appeared to be more red and was more prominent across the upper chest and trapezius area of the back. Aspirin 650 mg and
dextropropoxyphene 65 mg were administered. A physician suspected possible rickettsial or arbovirus infection. The patient was started on ampicillin 3 g/day, but after one dose he was changed to tetracycline 2 g/day for 10 days. He spent the next 2 days in bed, and his temperature ranged between 37 - 2°C and 37-8°C. Nausea continued, but there was no vomiting. Headache persisted but was relieved by aspirin and dextropropoxyphene. He was seen again on Nov. 19 by K. M. His headache was less severe, he had anorexia but no nausea, and he had lost 6 Ib (2 - 7 kg). He had a sore throat and joint pain. The rash had spread to his legs and was slightly pruritic. Temperature was 3730C and blood pressure 108/80 mm Hg. The rash was faint over his face and trunk but had involved the legs, appearing as brownish-red 2 mm flat spots sparsely spread over the legs. Sclerae were red and photophobic.
The posterior pharynx had a greyish mucoid lining, which bled when touched. A throat culture was taken, but no pathogenic bacteria were isolated. The lesion on his left buccal gland was now pinhead-sized and covered with a black blister. Joints were painful but not swollen or red. White-blood-cell count was 8600/mm3 with 63% polymorphs, 33% lymphocytes, 307o monocytes, and 1%
eosinophils. When seen again on Nov. 23 he felt much improved. His appetite better and his joints hurt less. His eyes hurt when he read and were still light-sensitive. Vital signs were normal. The rash was now very faint, and his throat was now normal. When last seen on Nov. 26, he was free of signs and symptoms. Complete blood count and urine were normal. Stool was positive for Ascaris lumbricoides eggs, and he was treated with pyrantel embonate. A final serum collection was made on Dec. 17. The patient had lived in Africa for the past 20 years working in livestock management. His last yellow-fever immunisation had been in December, 1975. He had received 5 ml of immune globulin in October, 1979. was
Serological Testing For haemagglutination-inhibition and complement-fixation tests the methods of Clarke and Casals5and Casey6were used. Serumwere done with Vero dilution/plaque-reduction neutralisation tests cells and a technique published previously.7 Acute serum drawn on Nov. 16 and conventional sera drawn on Nov. 19 and 23 and Dec. 17 were tested with a battery ofarboviruses including many known to occur in Africa: flaviviruses Spondweni, Banzi, dengue-1, dengue-2, Uganda S, West Nile, yellow fever, Zika, Ntaya, Usutu, and Murray Valley encephalitis; alphaviruses Chikungunya, Sindbis, and Ross River; bunyaviruses Bunyamwera, Ilesha, Tahyna, and Bwamba; Thogoto, Nyando,Tataguine, Zinga, Bangui, Orungo, and Sandfly fever (Naples). These tests demonstrated fourfold or greater rise in haemagglutination-inhibiting antibody titres to Spondweni and other flaviviruses, fulfilling the accepted criteria for confirmed serological diagnosis with one of these agents (see table). However, high-titre complement-fixing antibody to Spondweni virus indicated that that was the aetiological agent of his illness. Serological tests for rickettsial infections, carried out at the Centers for Disease Control, were negative.
Discussion
al.8 described
a hitherto unknown a pool of 49 Taeniorvirus from neurotropic arthropod-borne in Tongaland, collected hynchus (Mansonioides) uniformis South Africa. The name applied to this agent was that of the small native district of Spondweni, where it was encountered.8 The same group also detected Spondwenivirus neutralising antibodies in sera of residents of Tongaland. The distribution of humoral immunity was very uneven, and it was speculated that this might be associated
In 1955 Kokernot
et
’
with the distribution of either a non-human host or an arthropod vector. The agent had probably become active in the area only recently.9 During laboratory investigations in South Africa two members of staff became ill, and Spondweni virus was isolated from one of them. One had fever (37 - 8°C), generalised aches and pains, rigors, and vertigo; the other had fever (38’ 9 ° C), severe headache, weakness, nausea, and slight epistaxis. The only other confirmed case of Spondweni virus infection in man was reported by Macnamara in Eastern Nigeria in 1952 during an epidemic of jaundice.’ A virus, originally reported as Zika virus, was isolated from a 10-yearold African girl complaining of fever and headache who, when examined on the fifth day of her illness, had a temperature of38-2°C. She was not jaundiced. She was reported to be completely recovered 6 weeks later. Macnamara had based his diagnosis on the finding that his isolate was neutralised to some extent by a reference Zika immune serum. At that time Spondweni virus had not yet been described. On subsequent study at the Rockefeller Virus Laboratory in New York the virus was conclusively shown to be a strain of Spondweni.’ Using the virus isolated from the Nigerian case, Bearcroft infected a volunteer.Infection took the form ofashort-term fever to 38 - 0°C, without evidence of involvement of any particular tissue or viscus, and it resembled closely the condition observed in the girl in eastern Nigeria. In both cases fever and headache were the only obvious manifestations. The white-blood-cell count in Bearcroft’s case was essentially the same before and during infection, at 6500-8500/mm3, with a normal differential count. Virus isolation from man has been reported in Mozambiqueland Cameroon, 12 and serological evidence for Spondweni virus infections in man has been confirmed in Angolal3 and Botswana.l4 The virus has been isolated from several mosquito species, including Mansonia uniformis, Aedes circumluteolus, M. africana, Ae. cumminsii, Eretamapodites silvestrisJ Ae. fryeri, and Ae. fowleri. Antibody has been found in domestic livestock, but neither the maintenance cycle nor the veterinary significance of Spondweni virus infection is understood. The present case in Upper Volta is the first reported occurrence of Spondweni virus in Africa north and west of eastern Nigeria, extending the previously recognised range of this virus by approximately 700 km. Presenting symptoms in this case, previously described in the other recognised cases, included fever, headache, myalgia, chills, and nausea. The patient also had arthralgias, retro-orbital pain, conjunctivitis, photophobia, and vomiting. Of particular interest was the occurrence of a red maculopapular rash, initially over the
RESULTS OF HAEMAGGLUTINATION-INHIBITION (HI), COMPLEMENT-FIXATION (CF), AND SERUM-DILUTION/PLAQUE-REDUCTION NEUTRALISATION (N) TESTS WITH SERA FROM 2 SUBJECTS LIVING IN WEST AFRICA
* - = < 1:10
(HI). t - = < 1:8
(CF).
Blank indicates
not
tested.
1308
face, neck, and chest, which in 3 days spread to the trunk and extremities and disappeared after 10 days. This rash and the general clinical picture led to a presumptive diagnosis of a rickettsial infection, but serological tests were negative. Other findings were a greyish mucous lining on the posterior pharyngeal wall, which bled when touched, and a "blood blister" lesion over the buccal gland. These findings were not described in the other cases. Laboratory abnormalities included an initial white-cell count of 12 600/mm3, with a slight left shift (73% polymorphs and 26% lymphocytes), and an elevated sedimentation rate. Urinalysis was normal. Liverfunction tests and blood-chemistry analysis could not be done. The differential diagnosis in this case included rickettsial infections, leptospirosis, typhoid fever, and numerous viral illnesses. The clinical picture, especially the sore throat with a greyish pharyngeal exudate, could have represented Lassa fever. Lassa fever has not been confirmed in Upper Volta, but Frame found complement-fixing antibodies to Lassa fever in some missionaries from Upper Volta. 15 Contrary to the findings with Lassa fever, however, was the prominent rash in this case. In the rare instance that a Lassa-fever patient presents with a rash it is a faint maculopapular or petechial rash.16 Also the leucocyte count is characteristically low in early Lassa fever. 17 In 1978 Woodruff et al. found evidence of past infection with 10 identifiable viruses in sera from 86 travellers to Britain from tropical Africa, but none with Spondweni.18 During the period in which the patient’s sera were being tested, paired sera from two other male U.S. citizens, for whom limited clinical data are available, were also tested. One patient (patient 2), a 22-year-old man resident in Gabon for 6 months, presented on Dec. 23, 1980, with a 1-day history of fever, headache, and meningismus. Spinal fluid contained 143 lymphocytes/mm33 and the leucocyte count was 4800/mm3; he had transient (48 h) pareses of both the left oculomotor and right abducens nerves. With sera collected on Jan. 9 and May 7, 1981, we were able to demonstrate a monospecific rise in titre to Spondweni virus (see table). The other patient, who became ill in Cameroon on Nov. 13,1980, had a 4-fold fall in neutralising antibody to Spondweni but not other flaviviruses. Spondweni virus might be a cause of acute febrile illness throughout West Africa. It should be considered and searched for in the differential diagnosis of febrile illness and in antibody surveys in that region. We thank Dr Gerald Brunetn (Ouagadougou), Dr Eugene Sillman (Gabon), and Mr J. S. Lazuick and Mr D. J. Muth (Fort Collins) for their help, Dr Thomas P. Monath for advice and encouragement, and Mrs Betty Jane Markowitz and Mrs Patsy Galyardt for preparing the manuscript. ,
Correspondence should be addressed to M.
S. W.
REFERENCES on three cases of human infection during an epidemic of jaundice in Nigeria. Trans Roy Soc Trop Med Hyg 1954, 48: 139-45. 2 McIntosh BM, Kokernot RH, Patterson HE, De Meillon B Isolation of Spondweni virus from four species of culicine mosquitoes and a report of two laboratory infections with the virus. S Afr Med J 1961; 35: 647-50 3 Bearcroft WGC Zika virus infection experimentally induced in a human volunteer Trans Roy Soc Trop Med Hyg 1956; 50: 442-48. 4. Woodruff AW. Medicine in the tropics. Edinburgh: Churchill Livingstone, 1974: 331. 5. Clarke DH, Casals J Techniques for hemagglutination and hemagglutinationinhibition with arthropod-borne viruses Am J Trop Med Hyg 1958, 7: 561-73. 6. Casey HL. Part II. Adaptation of LBCF method to microtechnique. In: Standardised diagnostic complement fixation method and adaptation to micro test. Publ Hlth Monogr no 74. Public Health Service publication no. 1228. Washington, D.C. U.S. Government Printing Office, 1965.
1 Macnamara FN. Zika
virus
A report
Preliminary Communication BLOOD CREATINE KINASE ISOENZYME BB IN BOXERS C. E. G. BRAYNE* S. P. CALLOWAY†
L. DOW* R.
J. THOMPSON‡
*Department of Medicine, Whittington Hospital, Highgate Hill, London N19; †Department of Psychiatry, Royal Free Hospital, London NW3; and ‡Department of Clinical Biochemistry, Addenbrooke’s Hospital, Cambridge
Creatine kinase isoenzyme BB (CK-BB) is found in high concentrations in the brain. Normally concentrations in blood are undetectable or low. Blood concentrations of CK-BB were measured in 16 boxers before and after a fight and in 16 track cyclists before and after a race. Blood CK-BB rose to significantly higher concentrations in the boxers than in the cyclists. The number of blows received to the head was estimated in half the boxers and correlated significantly with the rise in CK-BB. This increase in blood CK-BB may indicate disruption of the blood-brain barrier. This may be one of the mechanisms accounting for brain damage in boxers.
Summary
INTRODUCTION
THE punch drunk syndrome was first described in 19281 and there have been many subsequent descriptions of the long-term effects of boxing. 2-5 Those who fight from an early 2 age as amateurs or low-level professionals are at highest risk.2 In animals even small traumas will cause serious damage if they follow one another at short intervals.5-8 In boxing a punch may have a considerable impact even when there is no knock-out.9 Creatine kinase isoenzyme BB is an enzyme found in high concentrations in the brain, where it is produced by astrocytes. Normally blood concentrations of the enzyme are undetectable or low. This isoenzyme may be
Calisher CH Mathews JH. Serum dilution neutralisation test for California group virus identification and serology J Clin Micrabiol 1976; 4: 503-10. 8. Kokernot RH, Smithburn KC, Muspratt J, Hodgson B. Studies on arthropod-borne viruses of Tongaland. VIII. Spondweni virus, an agent previously unknown, isolated from Taeniorhynchus (Mansonioides) uniformis Theo. S Afr J Med Sci 1957; 7.
Lindsey HS,
22: 103-12. 9. Smithburn KC, Kokernot RH, Heymann CS, Weinbren MP, Zentkowsky D Neutralising antibodies for certain viruses in northern Natal. S Afr Med J 1959, 33: 555-61. 10 Theiler M, Downs WG The arthropod-borne viruses of vertebrates. An account of the Rockefeller Foundation virus program 1951-1970. New Haven and London Yale University Press, 1973: 174. 11. Kokernot RH, Smithburn KC, Gandara AF, McIntosh BM, Keymann Provas de neutralizacaô com soros de individuos residentes em Moçambique contra determinados virus isolados em Africa transmitidos por artropodes. An Inst Med Trop (Lisboa) 1960, 17: 201-30. 12. Brottes M, Rickenbach A, Bres P, Salaun J-J, Ferrara L. Les arbovirus au Cameroun. Isolements a partir de moustiques Bull WHO 1966; 35: 881-85 13. Kokernot RH, Casaca VMR, Weinbren MP, McIntosh BM. Survey for antibodies against arthropod-borne viruses in the sera of indigenous residents of Angola. Trans Roy Soc Trop Med Hyg 1965; 59: 563-70 14 Kokernot RH, Szlamp EL, Levitt J, McIntosh BM. Survey for antibodies against arthropod-borne viruses in the sera of indigenous residents of the Caprivi Strip and Bechuanaland Protectorate. Trans Roy Soc Trop Med Hyg 1965; 59: 553-62. 15. Frame JD Surveillance of Lassa fever in missionaries stationed in West Africa Bull WHO 1975; 52: 593-98. 16. Frame JD, Baldwin JM, Gocke DJ. Troup JM. Lassa fever, a new virus disease of man from West Africa. I. Clinical description and pathological findings Am J Trop Med Hyg 1970; 19: 670-76. 17. Monath TP, Casals J. Diagnosis of Lassa fever and the isolation and management of patients. Bull WHO 1975; 52: 707-15 18. Woodruff AW, Bowen ETW, Platt GS. Viral infections in travellers from tropical Africa. Br Med J 1978; i 956-58.
CS.
diarrhoea seen clinical and
recently in Perth presented similarly histological features consistent
with with inflammatory bowel disease.2 Treatment should be considered in patients with prolonged diarrhoea when Aeromonas spp. have been isolated from faeces. In such patients trimethoprim is the most appropriate antimicrobial agent. 12 Other drugs, such as oxytetracycline, chloramphenicol, and the third-generation cephalosporins are effective in vitro,12 and may be appropriate (depending on the clinical picture), especially in adults. Many of our colleagues helped make this work possible; in particular, we thank Mr Douglas Peck, Mrs Jannice Beaman, Dr R. Hill, Mrs Christine Bundell, and Dr Michael Dibley. The departments of microbiology and medical records and hospital nurses also helped with the study. This study was supported by the National Health and Medical Research Council and by the TVW Telethon Foundation. Correspondence should be addressed to M. G., G.P.O. Box D.184, Perth, 6001, Western Australia. REFERENCES
Chipman DC. Clinical involvement of Aeromonas hydrophila Canad Med Assn J 1979; 120: 942-46. 2. Goodwin CS, Harper WS, Stewart JK, Gracey M, Burke V, Robinson J. Enterotoxigenic Aeromonas hydrophila and diarrhoea in adults. Med J Aust (in press). 3. Sanyal SC, Singh SJ, Sen PC. Enteropathogenicity of Aeromonas hydrophila and Plesiomonas shigelloides. J Med Microbiol 1975; 8: 195-98. 4. Burke V, Robinson J, Berry RJ, Gracey M. Detection of enterotoxins of Aeromonas hydrophila by a suckling-mouse test. J Med Microbiol 1981; 14: 401-08. 5. Graevenitz A von, Zinterhofer L The detection of Aeromonas hydrophila in stool specimens. Health Lab Sci 1970; 7: 124-27. 6. Overman TL, D’Amato RF, Tomfohrd E. Incidence of oxidase-variable strains of Aeromonas hydrophila. J Clin Microbiol 1979; 9: 244-47 7. Hazen TC, Fliermans CB, Hirsch RP, Esch GW. Prevalence and distribution of Aeromonas hydrophila in the United States. Appl Envir Microbiol 1978; 36: 731-38. 8. Lupo L, Strickland E, Dufour A, Cabelli V. The effect of oxidase positive bacteria on total coliform density estimates. Health & Lab Sci 1977; 14: 117-21. 9. Kaper JB, Lockman H, Colwell RR Aeromonas hydrophila and toxigenicity of isolates 1. Trust TJ,
10.
11, 12.
from an estuary. J Appl Bact 1981; 50: 359-77. Rippey SR, Cabelli V. Occurrence of Aeromonas hydrophila in limnetic environments: relationship of the organism to trophic state Microbial Ecology 1980; 6: 45-54. Rahman SAFM, Willoughby JMT. Dysentery-like syndrome associated with Aeromonas hydrophila Br Med J 1980; 281: 976 Richardson CJL, Robinson JO, Wagener LB, Burke B. In vitro susceptibility of Aeromonas spp to antimicrobial agents J Antimicrob Chemoth 1982; 9: 267-74.
SPONDWENI VIRUS INFECTION IN A FOREIGN RESIDENT OF UPPER VOLTA MARTIN S. WOLFE
Office
of Medical Services,
Department of State, Washington,
D. C.
20520, U.S.A. CHARLES H. CALISHER Arbovirus Reference Branch, Division of Vector-Borne Viral Diseases, Centers for Disease Control, Fort Collins, Colorado 80522, U.S.A.
KAREN MCGUIRE American
Embassy, Ouagadougou, Upper Volta
Spondweni virus is a mosquito-borne flavivirus previously reported to cause human disease in Southern and West Africa. A serologically confirmed case of Spondweni virus infection in a U.S. citizen residing in Upper Volta is reported. Symptoms included fever, chills, headache, myalgia, nausea, and rash. A greyish mucoid lining was present on the posterior pharynx. The differential diagnosis included rickettsial infection, leptospirosis, typhoid fever, and numerous viral illnesses including Lassa fever. Evidence of Spondweni virus infection was also found in two other U.S. citizens residing in Gabon and Cameroon. Spondweni virus might be a cause of acute febrile illness throughout West Africa, and its presence should be considered in the differential diagnosis of febrile illness and in antibody surveys in that region. Summary
Introduction flavivirus (family human disease in Southern and West Africa. It has been isolated from the blood of a child in Nigeria,1 has caused two accidental febrile laboratory infections in South Africa,2 and has caused a
SPONDWENI virus is
Togaviridae) reported
a
mosquito-borne
to cause
febrile illness in a volunteer. Reported symptoms included brief fever, headache, and malaise. The virus has repeatedly been isolated from mosquitoes in South Africa, and antibody surveys suggest that it is widely distributed in Africa.4 We report here a serologically confirmed case of Spondweni virus infection in a U.S. citizen residing in Upper Volta. Additional evidence that Spondweni virus is a human pathogen in other areas of West Africa is provided.
Case-report 40-year-old American man, presented
Patient 1, a 1979, with severe headache, dizziness,
Nov. 16, aches, pain
on
nausea, muscle
behind his eyes, and sensitivity to light. Since Oct. 1 he had been working on a cattle-grazing project in Bitou, a small village in south-eastern Upper Volta, near the borders of Ghana and Togo and 500 km from the capital, Ouagadougou. He and a colleague lived in tents and spent all but their sleeping hours out of doors. They lived in camp 3 or 4 nights per week and returned to Ouagadougou for weekends. It was after the rainy season, and insects were in abundance and described as a biting nuisance. The patient was well until the morning of Nov. 15, when he awoke with a severe headache and myalgia, but he drove from Ouagadougou to Bitou. He became worse that day and was forced to return to Ouagadougou the following day, where he sought medical attention from one ofus (K. M.). On initial examination he appeared weak and prostrated. His body temperature was 37-4°C, pulse rate 68/min, and respiration rate 20/min. A fine maculopapular rash, which did not blanch on pressure, was seen across the bridge of his nose, over the cheeks, over the neck, and lightly across the chest and back; the appearance was that of a severe sunburn. The sclerae were red, and conjunctivitis and photophobia were present. The left buccal gland was red and swollen. There was no nuchal rigidity, but he could not lift his leg off the bed more than 60 degrees without experiencing pain in the lower back. Ear examination showed no abnormality. Lymph glands were not enlarged. The lungs were clear. The heart showed normal sinus rhythm. The abdomen was soft, and liver and spleen were not palpable. He had severe pain in his knees, elbows, and lower spine. Neurological examination was within normal limits. Laboratory results initially were: white-blood-cell count 12 600/mm3 with 73% polymorphs, 26% lymphocytes, l070 monocytes, and no eosinophils. Erythrocyte sedimentation rate (Wintrobe) at 1 h was 42 mm and at 2 h 83 mm. Haematocrit was 41%. Malarial parasites were not observed in thick or thin blood smears. Urine was negative. 2 h later his headache was worse and he felt dizzy and slightly disorientated. He developed chills; temperature 38.6°C, pulse rate 78/min, blood pressure 130/78 mm Hg. He vomited bilious material and was given prochlorperazine 10 mg i.m. The maculopapular rash appeared to be more red and was more prominent across the upper chest and trapezius area of the back. Aspirin 650 mg and
dextropropoxyphene 65 mg were administered. A physician suspected possible rickettsial or arbovirus infection. The patient was started on ampicillin 3 g/day, but after one dose he was changed to tetracycline 2 g/day for 10 days. He spent the next 2 days in bed, and his temperature ranged between 37 - 2°C and 37-8°C. Nausea continued, but there was no vomiting. Headache persisted but was relieved by aspirin and dextropropoxyphene. He was seen again on Nov. 19 by K. M. His headache was less severe, he had anorexia but no nausea, and he had lost 6 Ib (2 - 7 kg). He had a sore throat and joint pain. The rash had spread to his legs and was slightly pruritic. Temperature was 3730C and blood pressure 108/80 mm Hg. The rash was faint over his face and trunk but had involved the legs, appearing as brownish-red 2 mm flat spots sparsely spread over the legs. Sclerae were red and photophobic.
The posterior pharynx had a greyish mucoid lining, which bled when touched. A throat culture was taken, but no pathogenic bacteria were isolated. The lesion on his left buccal gland was now pinhead-sized and covered with a black blister. Joints were painful but not swollen or red. White-blood-cell count was 8600/mm3 with 63% polymorphs, 33% lymphocytes, 307o monocytes, and 1%
eosinophils. When seen again on Nov. 23 he felt much improved. His appetite better and his joints hurt less. His eyes hurt when he read and were still light-sensitive. Vital signs were normal. The rash was now very faint, and his throat was now normal. When last seen on Nov. 26, he was free of signs and symptoms. Complete blood count and urine were normal. Stool was positive for Ascaris lumbricoides eggs, and he was treated with pyrantel embonate. A final serum collection was made on Dec. 17. The patient had lived in Africa for the past 20 years working in livestock management. His last yellow-fever immunisation had been in December, 1975. He had received 5 ml of immune globulin in October, 1979. was
Serological Testing For haemagglutination-inhibition and complement-fixation tests the methods of Clarke and Casals5and Casey6were used. Serumwere done with Vero dilution/plaque-reduction neutralisation tests cells and a technique published previously.7 Acute serum drawn on Nov. 16 and conventional sera drawn on Nov. 19 and 23 and Dec. 17 were tested with a battery ofarboviruses including many known to occur in Africa: flaviviruses Spondweni, Banzi, dengue-1, dengue-2, Uganda S, West Nile, yellow fever, Zika, Ntaya, Usutu, and Murray Valley encephalitis; alphaviruses Chikungunya, Sindbis, and Ross River; bunyaviruses Bunyamwera, Ilesha, Tahyna, and Bwamba; Thogoto, Nyando,Tataguine, Zinga, Bangui, Orungo, and Sandfly fever (Naples). These tests demonstrated fourfold or greater rise in haemagglutination-inhibiting antibody titres to Spondweni and other flaviviruses, fulfilling the accepted criteria for confirmed serological diagnosis with one of these agents (see table). However, high-titre complement-fixing antibody to Spondweni virus indicated that that was the aetiological agent of his illness. Serological tests for rickettsial infections, carried out at the Centers for Disease Control, were negative.
Discussion
al.8 described
a hitherto unknown a pool of 49 Taeniorvirus from neurotropic arthropod-borne in Tongaland, collected hynchus (Mansonioides) uniformis South Africa. The name applied to this agent was that of the small native district of Spondweni, where it was encountered.8 The same group also detected Spondwenivirus neutralising antibodies in sera of residents of Tongaland. The distribution of humoral immunity was very uneven, and it was speculated that this might be associated
In 1955 Kokernot
et
’
with the distribution of either a non-human host or an arthropod vector. The agent had probably become active in the area only recently.9 During laboratory investigations in South Africa two members of staff became ill, and Spondweni virus was isolated from one of them. One had fever (37 - 8°C), generalised aches and pains, rigors, and vertigo; the other had fever (38’ 9 ° C), severe headache, weakness, nausea, and slight epistaxis. The only other confirmed case of Spondweni virus infection in man was reported by Macnamara in Eastern Nigeria in 1952 during an epidemic of jaundice.’ A virus, originally reported as Zika virus, was isolated from a 10-yearold African girl complaining of fever and headache who, when examined on the fifth day of her illness, had a temperature of38-2°C. She was not jaundiced. She was reported to be completely recovered 6 weeks later. Macnamara had based his diagnosis on the finding that his isolate was neutralised to some extent by a reference Zika immune serum. At that time Spondweni virus had not yet been described. On subsequent study at the Rockefeller Virus Laboratory in New York the virus was conclusively shown to be a strain of Spondweni.’ Using the virus isolated from the Nigerian case, Bearcroft infected a volunteer.Infection took the form ofashort-term fever to 38 - 0°C, without evidence of involvement of any particular tissue or viscus, and it resembled closely the condition observed in the girl in eastern Nigeria. In both cases fever and headache were the only obvious manifestations. The white-blood-cell count in Bearcroft’s case was essentially the same before and during infection, at 6500-8500/mm3, with a normal differential count. Virus isolation from man has been reported in Mozambiqueland Cameroon, 12 and serological evidence for Spondweni virus infections in man has been confirmed in Angolal3 and Botswana.l4 The virus has been isolated from several mosquito species, including Mansonia uniformis, Aedes circumluteolus, M. africana, Ae. cumminsii, Eretamapodites silvestrisJ Ae. fryeri, and Ae. fowleri. Antibody has been found in domestic livestock, but neither the maintenance cycle nor the veterinary significance of Spondweni virus infection is understood. The present case in Upper Volta is the first reported occurrence of Spondweni virus in Africa north and west of eastern Nigeria, extending the previously recognised range of this virus by approximately 700 km. Presenting symptoms in this case, previously described in the other recognised cases, included fever, headache, myalgia, chills, and nausea. The patient also had arthralgias, retro-orbital pain, conjunctivitis, photophobia, and vomiting. Of particular interest was the occurrence of a red maculopapular rash, initially over the
RESULTS OF HAEMAGGLUTINATION-INHIBITION (HI), COMPLEMENT-FIXATION (CF), AND SERUM-DILUTION/PLAQUE-REDUCTION NEUTRALISATION (N) TESTS WITH SERA FROM 2 SUBJECTS LIVING IN WEST AFRICA
* - = < 1:10
(HI). t - = < 1:8
(CF).
Blank indicates
not
tested.
1308
face, neck, and chest, which in 3 days spread to the trunk and extremities and disappeared after 10 days. This rash and the general clinical picture led to a presumptive diagnosis of a rickettsial infection, but serological tests were negative. Other findings were a greyish mucous lining on the posterior pharyngeal wall, which bled when touched, and a "blood blister" lesion over the buccal gland. These findings were not described in the other cases. Laboratory abnormalities included an initial white-cell count of 12 600/mm3, with a slight left shift (73% polymorphs and 26% lymphocytes), and an elevated sedimentation rate. Urinalysis was normal. Liverfunction tests and blood-chemistry analysis could not be done. The differential diagnosis in this case included rickettsial infections, leptospirosis, typhoid fever, and numerous viral illnesses. The clinical picture, especially the sore throat with a greyish pharyngeal exudate, could have represented Lassa fever. Lassa fever has not been confirmed in Upper Volta, but Frame found complement-fixing antibodies to Lassa fever in some missionaries from Upper Volta. 15 Contrary to the findings with Lassa fever, however, was the prominent rash in this case. In the rare instance that a Lassa-fever patient presents with a rash it is a faint maculopapular or petechial rash.16 Also the leucocyte count is characteristically low in early Lassa fever. 17 In 1978 Woodruff et al. found evidence of past infection with 10 identifiable viruses in sera from 86 travellers to Britain from tropical Africa, but none with Spondweni.18 During the period in which the patient’s sera were being tested, paired sera from two other male U.S. citizens, for whom limited clinical data are available, were also tested. One patient (patient 2), a 22-year-old man resident in Gabon for 6 months, presented on Dec. 23, 1980, with a 1-day history of fever, headache, and meningismus. Spinal fluid contained 143 lymphocytes/mm33 and the leucocyte count was 4800/mm3; he had transient (48 h) pareses of both the left oculomotor and right abducens nerves. With sera collected on Jan. 9 and May 7, 1981, we were able to demonstrate a monospecific rise in titre to Spondweni virus (see table). The other patient, who became ill in Cameroon on Nov. 13,1980, had a 4-fold fall in neutralising antibody to Spondweni but not other flaviviruses. Spondweni virus might be a cause of acute febrile illness throughout West Africa. It should be considered and searched for in the differential diagnosis of febrile illness and in antibody surveys in that region. We thank Dr Gerald Brunetn (Ouagadougou), Dr Eugene Sillman (Gabon), and Mr J. S. Lazuick and Mr D. J. Muth (Fort Collins) for their help, Dr Thomas P. Monath for advice and encouragement, and Mrs Betty Jane Markowitz and Mrs Patsy Galyardt for preparing the manuscript. ,
Correspondence should be addressed to M.
S. W.
REFERENCES on three cases of human infection during an epidemic of jaundice in Nigeria. Trans Roy Soc Trop Med Hyg 1954, 48: 139-45. 2 McIntosh BM, Kokernot RH, Patterson HE, De Meillon B Isolation of Spondweni virus from four species of culicine mosquitoes and a report of two laboratory infections with the virus. S Afr Med J 1961; 35: 647-50 3 Bearcroft WGC Zika virus infection experimentally induced in a human volunteer Trans Roy Soc Trop Med Hyg 1956; 50: 442-48. 4. Woodruff AW. Medicine in the tropics. Edinburgh: Churchill Livingstone, 1974: 331. 5. Clarke DH, Casals J Techniques for hemagglutination and hemagglutinationinhibition with arthropod-borne viruses Am J Trop Med Hyg 1958, 7: 561-73. 6. Casey HL. Part II. Adaptation of LBCF method to microtechnique. In: Standardised diagnostic complement fixation method and adaptation to micro test. Publ Hlth Monogr no 74. Public Health Service publication no. 1228. Washington, D.C. U.S. Government Printing Office, 1965.
1 Macnamara FN. Zika
virus
A report
Preliminary Communication BLOOD CREATINE KINASE ISOENZYME BB IN BOXERS C. E. G. BRAYNE* S. P. CALLOWAY†
L. DOW* R.
J. THOMPSON‡
*Department of Medicine, Whittington Hospital, Highgate Hill, London N19; †Department of Psychiatry, Royal Free Hospital, London NW3; and ‡Department of Clinical Biochemistry, Addenbrooke’s Hospital, Cambridge
Creatine kinase isoenzyme BB (CK-BB) is found in high concentrations in the brain. Normally concentrations in blood are undetectable or low. Blood concentrations of CK-BB were measured in 16 boxers before and after a fight and in 16 track cyclists before and after a race. Blood CK-BB rose to significantly higher concentrations in the boxers than in the cyclists. The number of blows received to the head was estimated in half the boxers and correlated significantly with the rise in CK-BB. This increase in blood CK-BB may indicate disruption of the blood-brain barrier. This may be one of the mechanisms accounting for brain damage in boxers.
Summary
INTRODUCTION
THE punch drunk syndrome was first described in 19281 and there have been many subsequent descriptions of the long-term effects of boxing. 2-5 Those who fight from an early 2 age as amateurs or low-level professionals are at highest risk.2 In animals even small traumas will cause serious damage if they follow one another at short intervals.5-8 In boxing a punch may have a considerable impact even when there is no knock-out.9 Creatine kinase isoenzyme BB is an enzyme found in high concentrations in the brain, where it is produced by astrocytes. Normally blood concentrations of the enzyme are undetectable or low. This isoenzyme may be
Calisher CH Mathews JH. Serum dilution neutralisation test for California group virus identification and serology J Clin Micrabiol 1976; 4: 503-10. 8. Kokernot RH, Smithburn KC, Muspratt J, Hodgson B. Studies on arthropod-borne viruses of Tongaland. VIII. Spondweni virus, an agent previously unknown, isolated from Taeniorhynchus (Mansonioides) uniformis Theo. S Afr J Med Sci 1957; 7.
Lindsey HS,
22: 103-12. 9. Smithburn KC, Kokernot RH, Heymann CS, Weinbren MP, Zentkowsky D Neutralising antibodies for certain viruses in northern Natal. S Afr Med J 1959, 33: 555-61. 10 Theiler M, Downs WG The arthropod-borne viruses of vertebrates. An account of the Rockefeller Foundation virus program 1951-1970. New Haven and London Yale University Press, 1973: 174. 11. Kokernot RH, Smithburn KC, Gandara AF, McIntosh BM, Keymann Provas de neutralizacaô com soros de individuos residentes em Moçambique contra determinados virus isolados em Africa transmitidos por artropodes. An Inst Med Trop (Lisboa) 1960, 17: 201-30. 12. Brottes M, Rickenbach A, Bres P, Salaun J-J, Ferrara L. Les arbovirus au Cameroun. Isolements a partir de moustiques Bull WHO 1966; 35: 881-85 13. Kokernot RH, Casaca VMR, Weinbren MP, McIntosh BM. Survey for antibodies against arthropod-borne viruses in the sera of indigenous residents of Angola. Trans Roy Soc Trop Med Hyg 1965; 59: 563-70 14 Kokernot RH, Szlamp EL, Levitt J, McIntosh BM. Survey for antibodies against arthropod-borne viruses in the sera of indigenous residents of the Caprivi Strip and Bechuanaland Protectorate. Trans Roy Soc Trop Med Hyg 1965; 59: 553-62. 15. Frame JD Surveillance of Lassa fever in missionaries stationed in West Africa Bull WHO 1975; 52: 593-98. 16. Frame JD, Baldwin JM, Gocke DJ. Troup JM. Lassa fever, a new virus disease of man from West Africa. I. Clinical description and pathological findings Am J Trop Med Hyg 1970; 19: 670-76. 17. Monath TP, Casals J. Diagnosis of Lassa fever and the isolation and management of patients. Bull WHO 1975; 52: 707-15 18. Woodruff AW, Bowen ETW, Platt GS. Viral infections in travellers from tropical Africa. Br Med J 1978; i 956-58.
CS.