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HUMAN RABIES VACCINES INDUCE NEUTRALISING ANTIBODIES AGAINST THE EUROPEAN BAT RABIES VIRUS (DUVENHAGE)
515 t
details of the embryo transfer technique1,2 has enabled us to reduce the tubal pregnancy rate to 6-3% of clinical pregnancies in the past 12 months. 22% of our ectopic pregnancies were in patients who would not normally be offered comual sealing on Fishel’s criteria. Ectopic pregnancy in an IVF programme should not pose the dangers it does when it happens in the general pregnant population, providing that an ultrasound scan is done three weeks after embryo transfer. All 11 ectopic pregnancies in our programme to date who had a scan three weeks after transfer were diagnosed before bleeding or rupture occurred. Unfortunately, this does not apply to the 4 patients who had a concurrent intrauterine pregnancy and this small group still poses diagnostic problems. Hallam Medical Centre, London W1N 5LR; and Department of Obstetrics and Gynaecology,
VINAY SHARMA STUART CAMPBELL BRIDGETT MASON
King’s College Hospital, London SE5
1 Craft I, McLeod F, Edmonds K. Embryo transfer, ectopic pregnancy, and preliminary tubal occlusion. Lancet 1981; ii: 1421. 2. Yovich JL, Turner SR, Murphy AJ. Embryo transfer technique as a cause of ectopic pregnancies m IVF. Fertil Steril 1985; 44: 318-22.
HUMAN RABIES VACCINES INDUCE NEUTRALISING ANTIBODIES AGAINST THE EUROPEAN BAT RABIES VIRUS (DUVENHAGE)
SIR,—Three rabies virus isolates obtained from bats of unidentified species found in the maritime northern part of West Germany in 1968 (Hamburg), 1970 (Stade), and 1982 (Bremerhaven)l have been characterised by monoclonal antibodies as being closely related, but not identical, to the Duvenhage virus.2,3 This virus, first isolated in South Africa, is the prototype strain of serotype 4 of the genus Lyssavirus (rabies group) of the rhabdoviruses.One isolate obtained in Poland in June, 1985, and ten isolates obtained in Denmark during the last four months of 1985,5 all from bats of the species Eptesicus serotinus, have been characterised as identical to the earlier German bat isolates. The virus isolated in a case of human rabies observed in October, 1985, in Finland6 has been found to be distinct from the above bat isolates.7 There thus exists now in Europe a definite risk of human exposure to rabies infection of bat origin and we need to know if commercially available human rabies vaccines induce immunity against this serotype of rabies virus. Studies in mice immunised with the PM strain of fixed rabies virus had revealed poor protection against the German bat viruses,2 so we thought it important to find out if people immunised with rabies vaccines and in whom specific rabies neutralising antibodies had developed, also had antibodies neutralising the newly identified European bat rabies virus (Duvenhage). The study was done at the request of the Division of Communicable Diseases, Veterinary Public Health, World Health
Organisation. The human sera were provided by Prof I. Vodopija of the Zagreb Institute of Public Health. The volunteers had been vaccinated with the newly proposed abbreviated schedule for post-exposure rabies treatment-namely, two doses on day 0 with single doses on days 7 and 21.8 Five commercially available rabies vaccines were used: human diploid cell (PM strain), purified vero rabies (PM), purified duck embryo (PM), fetal bovine kidney cell TABLE I-NEUTRALISING ANTIBODY TITRES AGAINST EUROPEAN
BAT RABIES VIRUS (DUVENHAGE) IN SERA OF VOLUNTEERS VACCINATED AGAINST RABIES
TABLE II—NEUTRALISING ANTIBODY TITRES AGAINST RABIES CVS VIRUS AND EUROPEAN BAT RABIES VIRUS
(DUVENHAGE) IN RABIES (RIGH)
IMMUNE GLOBULINS OF HUMAN ORIGIN
*Anthmetic mean of quadruplicate titration.
(PV), and purified chick embryo cell (Flury-LEP) vaccines. Antibodies were titrated in serum samples taken on days 7 and 28 by the rapid fluorescent focus inhibition test (RFFIT) using in parallel the challenge virus standard (CVS) rabies virus and the Stade isolate of European bat rabies virus (Duvenhage) supplied by Dr L. G. Schneider of the Federal Institute for Animal Virus Diseases, Tiibingen, West Germany. In the absence of a reference preparation of human immune serum neutralising Duvenhage virus, a reference human antirabies serum with a titre of 10 IU/ml was used: this serum had a titre of 7-8 arbitrary units/ml against the Stade virus. All five vaccines induced high titres of antibodies neutralising Duvenhage virus, whatever the strain of fixed virus or the cell culture type used for the production of the vaccines (table i). Lower levels of antibodies are detectable at day 7, indicating an early immune response. Four batches of rabies immune globulin of human origin (RIGH) (’Imogam’; Merieux) and one concentrated preparation of RIGH (Blood Transfusion Centre, Nancy) were titrated (table n): all five lots of RIGH had high neutralising activity against the Duvenhage virus: the titres, expressed in arbitrary units, are about two-thirds of the titres expressed in IU against the CVS rabies virus for the imogam and slightly higher for the concentrated RIGH preparation. We conclude that in cases of human contamination by a rabid bat in Europe, post-exposure treatment with rabies vaccine and RIGH should be administered according to the WHO recommendations,9 as for contamination by rabid terrestrial mammals. Rabies Unit (WHO Collaborating Centre for Rabies), Institut Pasteur, 75724 Paris, France
MONIQUE LAFON MONIKA HERZOG PIERRE SUREAU
1. Schneider LG. A new case of bat-rabies in Germany. Rabies Bull Europe 1982, 4: 17-18. 2. Schneider LG. Antigenic variants of rabies virus. Comp Immun Microbiol Infect Dis
1982; 5: 101-07. et al. Application of monoclonal antibodies for epidemiological investigations and oral vaccination studies. In: Rabies in the tropics. Berlin: Springer-Verlag, 1985: 47-59. 4. WHO. Advances in rabies research. In: WHO Expert Committee on Rabies’: seventh report. Tech Rep Ser WHO 1984; 709: 9-10. 5. Mollgaard S. Bat-rabies in Denmark. Rabies Bull Europe 1985; 4: 11 6. Lumio J, et al. Human rabies of bat origin in Europe. Lancet 1986; i: 378. 7. Bitsch V, et al. Bat rabies-Europe. MMWR 1986; 35: 430-32. 8. Vodopija I, et al. Towards a new regimen structure for post-exposure rabies immunisation. Outline of the 2-1-1 approach. In: Vodopija I, et al, eds. Improvements in rabies post-exposure treatment. Zagreb Institute of Public Health, Zagreb, 1985: 167-70. 9. WHO. Prevention of rabies m man. In: WHO Expert Committee on Rabies’ seventh report. Tech Rep Ser WHO 1984, 709: 27-34.
3. Schneider LG,
ALCOHOL AND HAEMORRHAGIC STROKE
SIR,—We would like to add our call for moderation in the use of alcohol
*HDCV = human
diploid cell, PVRV--purified vero rabies, PDEV = purified duck embryo, FBKC=fetal bovine kidney cell, and PCEC=punfied chick embryo cell. n == number of vaccines tIn arbitrary unitsiml, expressed
as
geometric
mean titre
(and range).
that expressed in your Aug 2 editorial on alcohol and stroke. The Honolulu Heart Program has provided one of the most comprehensive evaluations of this association and found it to be strong, graded, and consistent. The lack of to
haemorrhagic
details of the embryo transfer technique1,2 has enabled us to reduce the tubal pregnancy rate to 6-3% of clinical pregnancies in the past 12 months. 22% of our ectopic pregnancies were in patients who would not normally be offered comual sealing on Fishel’s criteria. Ectopic pregnancy in an IVF programme should not pose the dangers it does when it happens in the general pregnant population, providing that an ultrasound scan is done three weeks after embryo transfer. All 11 ectopic pregnancies in our programme to date who had a scan three weeks after transfer were diagnosed before bleeding or rupture occurred. Unfortunately, this does not apply to the 4 patients who had a concurrent intrauterine pregnancy and this small group still poses diagnostic problems. Hallam Medical Centre, London W1N 5LR; and Department of Obstetrics and Gynaecology,
VINAY SHARMA STUART CAMPBELL BRIDGETT MASON
King’s College Hospital, London SE5
1 Craft I, McLeod F, Edmonds K. Embryo transfer, ectopic pregnancy, and preliminary tubal occlusion. Lancet 1981; ii: 1421. 2. Yovich JL, Turner SR, Murphy AJ. Embryo transfer technique as a cause of ectopic pregnancies m IVF. Fertil Steril 1985; 44: 318-22.
HUMAN RABIES VACCINES INDUCE NEUTRALISING ANTIBODIES AGAINST THE EUROPEAN BAT RABIES VIRUS (DUVENHAGE)
SIR,—Three rabies virus isolates obtained from bats of unidentified species found in the maritime northern part of West Germany in 1968 (Hamburg), 1970 (Stade), and 1982 (Bremerhaven)l have been characterised by monoclonal antibodies as being closely related, but not identical, to the Duvenhage virus.2,3 This virus, first isolated in South Africa, is the prototype strain of serotype 4 of the genus Lyssavirus (rabies group) of the rhabdoviruses.One isolate obtained in Poland in June, 1985, and ten isolates obtained in Denmark during the last four months of 1985,5 all from bats of the species Eptesicus serotinus, have been characterised as identical to the earlier German bat isolates. The virus isolated in a case of human rabies observed in October, 1985, in Finland6 has been found to be distinct from the above bat isolates.7 There thus exists now in Europe a definite risk of human exposure to rabies infection of bat origin and we need to know if commercially available human rabies vaccines induce immunity against this serotype of rabies virus. Studies in mice immunised with the PM strain of fixed rabies virus had revealed poor protection against the German bat viruses,2 so we thought it important to find out if people immunised with rabies vaccines and in whom specific rabies neutralising antibodies had developed, also had antibodies neutralising the newly identified European bat rabies virus (Duvenhage). The study was done at the request of the Division of Communicable Diseases, Veterinary Public Health, World Health
Organisation. The human sera were provided by Prof I. Vodopija of the Zagreb Institute of Public Health. The volunteers had been vaccinated with the newly proposed abbreviated schedule for post-exposure rabies treatment-namely, two doses on day 0 with single doses on days 7 and 21.8 Five commercially available rabies vaccines were used: human diploid cell (PM strain), purified vero rabies (PM), purified duck embryo (PM), fetal bovine kidney cell TABLE I-NEUTRALISING ANTIBODY TITRES AGAINST EUROPEAN
BAT RABIES VIRUS (DUVENHAGE) IN SERA OF VOLUNTEERS VACCINATED AGAINST RABIES
TABLE II—NEUTRALISING ANTIBODY TITRES AGAINST RABIES CVS VIRUS AND EUROPEAN BAT RABIES VIRUS
(DUVENHAGE) IN RABIES (RIGH)
IMMUNE GLOBULINS OF HUMAN ORIGIN
*Anthmetic mean of quadruplicate titration.
(PV), and purified chick embryo cell (Flury-LEP) vaccines. Antibodies were titrated in serum samples taken on days 7 and 28 by the rapid fluorescent focus inhibition test (RFFIT) using in parallel the challenge virus standard (CVS) rabies virus and the Stade isolate of European bat rabies virus (Duvenhage) supplied by Dr L. G. Schneider of the Federal Institute for Animal Virus Diseases, Tiibingen, West Germany. In the absence of a reference preparation of human immune serum neutralising Duvenhage virus, a reference human antirabies serum with a titre of 10 IU/ml was used: this serum had a titre of 7-8 arbitrary units/ml against the Stade virus. All five vaccines induced high titres of antibodies neutralising Duvenhage virus, whatever the strain of fixed virus or the cell culture type used for the production of the vaccines (table i). Lower levels of antibodies are detectable at day 7, indicating an early immune response. Four batches of rabies immune globulin of human origin (RIGH) (’Imogam’; Merieux) and one concentrated preparation of RIGH (Blood Transfusion Centre, Nancy) were titrated (table n): all five lots of RIGH had high neutralising activity against the Duvenhage virus: the titres, expressed in arbitrary units, are about two-thirds of the titres expressed in IU against the CVS rabies virus for the imogam and slightly higher for the concentrated RIGH preparation. We conclude that in cases of human contamination by a rabid bat in Europe, post-exposure treatment with rabies vaccine and RIGH should be administered according to the WHO recommendations,9 as for contamination by rabid terrestrial mammals. Rabies Unit (WHO Collaborating Centre for Rabies), Institut Pasteur, 75724 Paris, France
MONIQUE LAFON MONIKA HERZOG PIERRE SUREAU
1. Schneider LG. A new case of bat-rabies in Germany. Rabies Bull Europe 1982, 4: 17-18. 2. Schneider LG. Antigenic variants of rabies virus. Comp Immun Microbiol Infect Dis
1982; 5: 101-07. et al. Application of monoclonal antibodies for epidemiological investigations and oral vaccination studies. In: Rabies in the tropics. Berlin: Springer-Verlag, 1985: 47-59. 4. WHO. Advances in rabies research. In: WHO Expert Committee on Rabies’: seventh report. Tech Rep Ser WHO 1984; 709: 9-10. 5. Mollgaard S. Bat-rabies in Denmark. Rabies Bull Europe 1985; 4: 11 6. Lumio J, et al. Human rabies of bat origin in Europe. Lancet 1986; i: 378. 7. Bitsch V, et al. Bat rabies-Europe. MMWR 1986; 35: 430-32. 8. Vodopija I, et al. Towards a new regimen structure for post-exposure rabies immunisation. Outline of the 2-1-1 approach. In: Vodopija I, et al, eds. Improvements in rabies post-exposure treatment. Zagreb Institute of Public Health, Zagreb, 1985: 167-70. 9. WHO. Prevention of rabies m man. In: WHO Expert Committee on Rabies’ seventh report. Tech Rep Ser WHO 1984, 709: 27-34.
3. Schneider LG,
ALCOHOL AND HAEMORRHAGIC STROKE
SIR,—We would like to add our call for moderation in the use of alcohol
*HDCV = human
diploid cell, PVRV--purified vero rabies, PDEV = purified duck embryo, FBKC=fetal bovine kidney cell, and PCEC=punfied chick embryo cell. n == number of vaccines tIn arbitrary unitsiml, expressed
as
geometric
mean titre
(and range).
that expressed in your Aug 2 editorial on alcohol and stroke. The Honolulu Heart Program has provided one of the most comprehensive evaluations of this association and found it to be strong, graded, and consistent. The lack of to
haemorrhagic