Human pre-exposure rabies immunization with suckling mouse brain vaccine.

HUMAN PRE-EXPOSURE RABIES IMMUNIZATION 561 Human pre-exposure rabies immunization with suckling mouse brain vaccine EDUARDO FUENZALIDA 1 Since the development of non-encephalitogenic rabies vaccines (Koprowski et al., 1952; Peck et al., 1955), several studies have been carried out on human pre-exposure immunization (Anderson et al., 1960; Dieterich et al., 1961; Fox et al., 1957; Schnur- renberger et al., 1961, 1967; Tierkel & Sikes, 1967). In the light of these results, the WHO Expert Com- mittee on Rabies (1966) has recommended this type of prophylaxis for high-risk personnel, such as labo- ratory personnel working with rabies virus, veteri- narians, dog handlers, and field naturalists. The principal disadvantage of the pre-exposure schedule recommended by the WHO Expert Com- mittee is that it takes at least 3 months to obtain a satisfactory immunological response as determined by antibody titre. There are times when it would be useful to be able to accelerate this response, such as when a new employee is engaged to work in a rabies laboratory or as a dog handler. Suckling mouse brain vaccine (SMBV) (Fuen- zalida & Palacios, 1955) was chosen for this study because it has the highest antigenic titre of vaccines currently in use for human immunoprophylaxis and it is relatively free of the encephalitogenic factor. A schedule of three doses was chosen because a preliminary study carried out with small groups of volunteers, using 1, 2, 3, or 5 vaccine doses, showed that all the sera from persons who had received 3 or 5 doses had antirabies neutralizing antibodies 21 days after starting immunization, while with those who had received 1 or 2 doses it was necessary to admi- nister an additional dose of vaccine after a further 25 days. The antibody responses after 5 doses were no higher than those obtained with 3 doses (Godoy, 1967). This paper reports the results obtained with 3 doses of vaccine in 61 persons, as well as some responses produced by a booster dose given to some of these individuals one year or more after the primary immunization. 1 Pan American Zoonoses Center, Pan American Health Organization, Ramos Mejia, Buenos Aires, Argentina. Materials and methods Vaccine. Different lots ofSMBV were used during the study: all of them passed the Habel potency test (Habel, 1966). Volunteers. Sixty-one adults, male and female, working or being trained at the Pan American Zoo- noses Center, as well as a small group of persons working for other institutions and interested in re- ceiving preventive rabies immunization, volunteered for this study. Vaccination schedule. Each volunteer was given three 2-ml doses of 1% SMBV, subcutaneously, on alternate days. A 1-ml booster dose was given 1 year or more after the first dose. Blood samples and seroneutralization. Initially, 10-20-ml blood samples were obtained from each volunteer before vaccination and, when available, on days 21, 90, 240, and 365 after the first vaccine dose. During the latter part of the study, blood samples were also obtained 10 days after the first vaccine dose. In those individuals given a booster dose of vaccine, a sample was taken shortly before the injec- tion and another sample 8 days after this dose. The sera obtained were incubated for 30 min at 560C and kept at -20°C until the SN test was per- formed. This test was carried out in accordance with the technique described by Atanasiu (1966), against 20-70 LD50 of the standard challenge virus strain. Threefold or fivefold series of dilutions were each inoculated into groups of 5 adult mice. Results No antibodies were detected in the sera obtained prior to vaccination (Table 1). In general, primary immunization was well tolerated. Of the 61 volun- teers who received 3 doses of vaccine, several were dropped from the study after 21 days, either because they left the Center or because they received addi- tional vaccine because of exposure to rabies. The SN titres of the sera taken at the different in- tervals are presented in Table 1. It is interesting to note that at 21 days, 58 of the 61 volunteers had positive antibody titres, and that in all except 2 of 2831D BRIEF COMMUNICATIONS/NOTES Table 1. Serum neutralization antibody titres of sera from 61 volunteers following immunization with 3 doses of suckling mouse brain vaccine administered within 5 days No. days between No. of Reciprocal of SN antibody titres %first dose of vaccine and blood sampling persons <2 2-5 6-25 26-125 126-625 positive 0 61 61 - - - - 0 10 38 11 2 7 18 1 71 21 61 3 - 9 23 26 95 90 35 2 2 4 23 4 94 240 29 6 1 1, 8 3 79 365 25 7 2 7 8 1 72 Table 2. The effect of a 1 -ml booster dose of suckling mouse brain vaccine on the level of SN antibodies in persons vaccinated previously with 3 doses Reciprocal of serum neutralization titre at: a Idenifiction No. of monthsIdentifica after first dose 21 days after before 8 days after 6 months first dose booster booster after booster M.C.P. M.I.R. M.C.A. A.C. LL. A.S. W.S. B.V. E.P. M.B. H.S. R.G. J.A. 8 10 12 12 12 12 12 12 12 16 16 15 17 181 357 b 181 114 486 342 213 206 31 162 243 54 17 b H.R. 17 181 A.M. 18 93 F.F. 19 338 C.C. 20 45 N.B. 21 104 A.A. 24 58 A.M. 25 93 M.M. 30 250 b D.M. 30 240 J.c. 38 59 b a = not done; 0 = no antibodies at 1 2 dilution. 38 44 31 19 5 0 32 45 0 18 0 3 >162 18 25 2 3 10 18 280 3 3 698 >4 374 >4 374 > 625 45 200 >15 625 >15 625 1 400 6 990 >15 625 >3 125 >1 458 210 >1 458 >3125 >15 625 1 400 1 160 1 640 >6 995 8 470 6 990 1 400 486 162 338 160 1 000 125 160 66 328 238 808 65 >625 125 160 1 230 328 3 125 b These persons received 0.25 ml of vaccine, intradermally, 25 days after the first dose. 562 HUMAN PRE-EXPOSURE RABIES IMMUNIZATION 563 the 35 volunteers retested at 90 days the positive titres had persisted. The results of a first booster 1 year or more after the first dose of vaccine are limited to observations made on 23 volunteers (Table 2). The very high antibody titres obtained following these booster doses are particularly striking. Discussion The schedules of human prophylactic immuniza- tion currently recommended are based on obtaining a secondary immune response by spacing the inter- vals between inoculations, but this study has shown that three 2-ml doses of SMBV within 5 days pro- duced antibody levels as high as those reported in other studies using other vaccines and a longer im- munization schedule. REFERENCES Anderson, G. R., Schnurrenberger, P. R., Masterson, R. A., & Wentworth, F. H. (1960) Amer. J. Hyg., 71, 158-167 Atanasiu, P. (1966) Quantitative assay and potency test of antirabies serum. In: Laboratory techniques in rabies, Geneva, pp. 167-172, (World Health Organization Monograph Series, No. 23) Dieterich, W. H., Shelton, D. F., & Jenevein, E. P., Jr (1961) J. Amer. vet. med. Ass., 139, 99-1004 Fox, J. P., Koprowski, H., Convell, D. P., Black, J., & Gelfand, H. M. (1957) Bull. Wld Hith Org., 17, 869-904 Fuenzalida, E. & Palacios, R. (1955) Bol. Inst. bact. Chile, 8, 3-10 Godoy, A. M. de (1967) Arch. Fsc. Vet. (Minas Gerais), 19, 121-128 Habel, K. (1966) Habel test for potency. In: Laboratory techniques in rabies, Geneva, pp. 140-143 (World Health Organization Monograph Series, No. 23) Koprowski, H., Black, J., & Nelsen, D. J. (1954) J. Immu- nol., 72, 94-106 Peck, P. F., Powell, H. M., & Culbertson, C., G. (1955) J. Lab. clin. Med., 45, 679-683 Schnurrenberger, P. R., Anderson, G. R., Russell, J. H., & Wentworth, F. H. (1961) Amer. J. Hyg., 74, 1-6 Schnurrenberger, P. R., Anderson, G. R., & Russell, J. H. (1967) Bull. Wld Hlth Org., 37, 547-551 Tierkel, E. S. & Sikes, R. K. (1967) J. Amer. med. Ass., 201, 911-914 WHO Expert Committee on Rabies (1966) Wld Hlth techn. Org. Rep. Ser. No. 321 Epidemiological survey of rubella immunity in Iran S. SAIDI 1 Previous epidemiological studies in different parts of the world have demonstrated antibody to rubella in about 50% of children aged 6-8 years and in more than 80% of women of childbearing age. The antibody rates were significantly lower in the island, isolated, and rural populations investigated (Rawls et al., 1967; Dowdle et al., 1970). This survey was carried out to determine the age incidence of rubella in females and the immune status of the women of childbearing age in urban and rural areas of Iran. Materials and methods Sera. A total of 1 559 blood specimens were col- lected by venepuncture or by finger prick according 1 Associate Professor, Department of Epidemiology and Pathobiology, School of Public Health, University of Tehe- ran. Iran. to the method described by Chin et al. (1966); 731 sera were from school-age girls or from girls aged between 8 months and 15 years attending clinics or health centres in Teheran. From women of child- bearing age attending clinics and health centres and from high-school and college girls, 508 sera were obtained in Teheran, a city of about 3 million in- habitants, and 320 sera were collected in rural areas in the north and northwest of Iran. The age of these women ranged from 16 to 45 years. Sera were stored at -20°C prior to examination. Parallel titration of rubella haemagglutination-inhibition antibodies in several paired samples of blood obtained by vene- puncture and by finger prick gave similar results with a variation in titre of no more than twofold, the venous samples giving the higher titre. Haemagglutination-inhibition (HI) test. HI tests were carried out according to the method described 2831E