Originalia J. D. Kark, E. Witztum, H. Mazkin, E. Nili, Y. L. Danon The Three-year Incidence of Non-B Viral Hepatitis Morbidity in a Controlled Trial of Pre-exposure Immune Serum Globulin Prophylaxis Summary: A trial of pre-exposure immune serum glo- bulin (ISG) vs. the prevailing policy of post-exposure ISG for the prevention of viral hepatitis was under- taken among 23,447 male and female military recruits in Israel, an endemic area for hepatitis A virus infec- tion. We are reporting on the three-year follow-up of the incidence of non-B hepatitis among 12,835 male recruits, half of whom had been allocated to receive ISG on their first day of service, while the other half served as a non-vaccinated ("regular care") control group. Over the three-year period the overall cumula- tive incidence in the intervention group was half that of the control group (3.6 per 1000 vs. 7.2 per 1000; Zusammenfassung: Morbiditiit an nicht-B-Virushepati- tis fiber drei Jahre in einer kontrollierten Studie zur Im- munglobulinprophylaxe vor Exposition. 23 447 mann- liche und weibliche Rekruten in Israel, einem Hepati- tis-A-Endemiegebiet, wurden in eine Vergleichsstudie zur Immunglobulin(ISG)-Prophylaxe vor Exposition versus fiblicher Immunglobulingabe nach Exposition einbezogen. Wir berichten fiber die Inzidenz der nicht- B-Hepatitis bei 12 835 mfinnlichen Rekruten in einer Beobachtungszeit von drei Jahren; die eine Hfilfte der Rekruten erhielten ISG am ersten Tag ihres Milit~ir- dienstes, die andere diente als nicht geimpfte ,,fibli- che" KontroUgruppe. Ober den Zeitraum von drei Jahren war die kumulative Gesamtinzidenz an Hepati- tis in der Prophylaxegruppe halb so hoch wie in der Kontrollgruppe (3,6 auf 1000 im Vergleich zu 7,2 auf p = 0.0037). Protection was virtually absolute for up to nine months' follow-up. ISG may have provided pro- longed partial protection well in excess of six to nine months. Between 10 to 18 months, half as many cases occurred in the intervention group as in the controls. By 18 months the difference in incidence between the study groups had reached a plateau and was highly sig- nificant (p = 0.002). Between 19 and 36 months the case increment in the two groups was similar. The be- nefit of receiving pre-exposure ISG remained evident three years after inception of the trial in this indigen- ous military population living in an endemic area. 1000; p = 0,0037). Neun Monate lang bestand prak- tisch vollkommener Schutz vor Hepatitis durch ISG, das m6glicherweise fiber sechs bis neun Monate hinaus noch einen partieUen Schutz gew/ihrte. In der Prophy- laxegruppe traten 10-18 Monate nach Beginn der Stu- die nur halb so viele F~ille von Hepatitis auf wie in der Kontrollgruppe. Nach 18 Monaten hatte die unter- schiedliche Inzidenz in den beiden Gruppen ein Pla- teau erreicht; die Differenz war hochsignifikant (p = 0,002). Im Zeitraum zwischen 19 und 36 Monaten nach Studienbeginn war die Zunahme von Krankheitsf~illen in beiden Gruppen vergleichbar. Drei Jahre nach Be- ginn der Studie war der Nutzen einer ISG-Prophylaxe vor Exposition ffir diese in einem Hepatitis-A-Ende- miegebiet lebende Milit~irbev61kerung noch eindeutig erkennbar. Introduction Hepatitis A is a potentially serious problem in the Israel Defence Forces (IDF). This problem has been effectively limited by the widescale use of post-exposure immune se- rum globulin (ISG) (1). In the past, the first months of military service in the IDF were associated with a dispro- portionately higher incidence of hepatitis than subsequent periods of exposure. Post-exposure ISG was frequently used during this period. Hepatitis A is hyperendemic in Israel (2). On the day of induction into military service 60-70% of the males are anti-HAV positive. This propor- tion differs in those whose fathers or paternal grandfa- thers were born in North Africa or the Middle East (85%) and in those who originated from Europe (40%) (3). Not- withstanding the high rate of anti-HAV positivity at the beginning of military service, epidemic hepatitis was a severe problem among IDF personnel in the past. Large- scale outbreaks occurred in cyclic patterns. Overt epi- demic cycles have disappeared following the aggressive use of post-exposure prophylaxis in the IDF (Figure 1) (1). However, the relatively high level of endemicity in the IDF, and in the country as a whole, remained a persis- tent threat and made a pre-exposure prophylaxis trial nec- essary. Received: 7 June 1983/Accepted: 12 December 1983 J. D, Kark, M.D., Ph.D., Department of Social Medicine, Hadassah Medical Organizationand the Hebrew University-Hadassah School of Public Healthand Community Medicine,Faculty of Medicine,Ein Ka- rein, Jerusalem, Israel, and Israel DefenceForces MedicalCorps; E. Witztum, M.D., H. Mazkin, M.D., E. Nili, D.V.M., Y. L. Danon, M.D,, Israel Defence Forces MedicalCorps. Infection 12 (1984) Nr. 4 © MMV MedizinVerlag GmbH M~nchen,Mianchen1984 19 / 251