Oktavija Đaković-Rode1, Dragan Palmović1 and Ilonka Kosanović2
1Dr. Fran Mihaljević University Hospital for Infectious Diseases, and 2Department of Epidemiology, Zagreb Institute of Public Health, Zagreb, Croatia
SUMMARY : The participation of hospital health care workers (HCWs) in the hepatitis B (HB) continuous vaccination program at the Sestre milosrdnice University Hospital in Zagreb is described. The HB vaccination program with Engerix-B vaccine (20 mg per dose) at the mentioned hospital started in 1992. Data on the primary vaccination coverage during the 1992-1993 and 1994-1998 periods and booster doses received upon the completion of the primary vaccination series are presented. During the first period, vaccination was organized once or twice weekly, and during the second period once a month on different hospital wards. Before the first action in 1992, 920 HCWs underwent testing for HBV markers (HbsAg, anti-HBs and anti-HBc). A total of 111 (12.1%) pretested individuals were excluded from the vaccination program because of positive HBV markers. During the 1992-1993 period, 58.1% of the hospital HCWs received three doses of vaccine, while during the 1994-1998 period 49.2% of the subjects completed the primary series of vaccination. The protective value of immunization should be assessed by anti-HBs titer determination, to allow a more precise booster dose timing.
Key words: Hepatitis B, prevention and control; Occupational diseases, prevention and control; Personel, hospital;
Occupationally acquired hepatitis B (HB) infection is a major cause of disease among health care workers (HCWs) and other hospital personnel who come in contact with blood and body fluids1-7. Worldwide, there may be about 300 million hepatitis B virus (HBV) carriers. It is estimated that 50% of the world's population have had contact with HBV and about 10% of them have developed persistent infection8-13.
Because of the extremely high viral load of
>108/mL, even the slightest trace of serum or other body substance such as saliva, ejaculate, vaginal secretion, or menstrual blood may cause transmission. Because of the low infectious dose, the risk of HBV infection is especially high in the individuals who have occupational contact with human blood or other body substances, and in patients with
chronic diseases due to frequent iatrogenic interventions. In these persons, transmission is induced through the injured skin and intact mucous membrane, by needles or other medical
devices9-11.
The spectrum of clinical HBV infection manifestations include acute hepatitis B, asymptomatic chronic lobular hepatitis B, chronic active hepatitis B, liver cirrhosis, and primary hepatocellular carcinoma8-10.
General protective measures against HBV infection include regular use of gloves, protective masks, protective goggles and plastic aprons, and correct safety procedures for handling pathologic material strictly used all the time, safe needle handling, and implementation of good laboratory practice. The specific measure of immunization with hepatitis B vaccine plays the most important role in self-protection against HBV. HBV infection and its complications are prevented by immunization1,5-7,14-17.
Since 1994, the vaccination against HB has been obligatory in Croatia for high risk groups, e.g., HCWs, children of HBV carrier mothers, patients on hemodialysis, sexual partners of HBsAg positive individuals, staff at institutions for mentally handicapped, drug addicts, and hemophiliacs. Since 1999, all sixth-grade school children in Croatia have to be vaccinated against HBV with three intramuscular vaccine doses according to the schedule 0 (initial), 1 and 6 months1,17-22.
In this paper, we describe the participation of hospital HCWs in the HBV vaccination program, conducted at the Sestre milosrdnice University Hospital in Zagreb. The results of prevaccination HB marker determination performed in 1992, data on primary vaccination coverage during the 1992-1993 and 1994-1998 periods, and on revaccination during the 1996-1998 period are presented and compared.
Since 1992, continuous active immunization against HBV has been performed at the Sestre milosrdnice University Hospital in Zagreb. The first programmed action started in April 1992 and lasted till February 1993. At that time, Croatian hospitals received large HB vaccine donations. All HCWs employed at the Sestre milosrdnice University Hospital had an opportunity to receive vaccination, especially those occupationally exposed to blood or other possible infective body substances. To provide comprehensive information on the issue of HBV infection and on the possibility of its prevention, a lecture on HB and protective measures against this infection was held and a brief report on HB vaccination was distributed to all hospital wards.
Before their inclusion in the vaccination program in 1992, 920 HCWs had their HBV markers (HBsAg, anti-HBs, and anti-HBc) determined at the Croatian Institute of Transfusion Medicine. The inclusion criteria for vaccination were negative findings for all the three markers. In subjects with positive HBsAg and anti-HBc, medical treatment was initiated. Those who exhibited signs of previous HBV infection (HBsAg negative, anti-HBc, and/or anti-HBs positive) were not vaccinated.
During the first organized HB vaccination, a team from the Department of Epidemiology, Zagreb Institute of Public Health, came and vaccinated HCWs at the Hospital once or twice weekly. From 1993, continuous vaccination was organized on different wards once a month at definite time between shifts, so that all those interested could take part in the vaccination program at their working places. Written information about the time and place of the next vaccination was distributed to all wards.
The vaccination was carried out with Engerix-B vaccine (Smith&Kline, Beecham). The Engerix-B vaccine was administered intramuscularly in the deltoid region, in a single dose of 20
mg HBsAg. Primary vaccination consisted of three intramuscular doses of vaccine according to schedule 0 (initial), 1 and 6 months from the date of the first dose, or 0, 1 and 2 months where there was an immediate risk of infection. Since the second schedule yields lower peak antibody levels, it was recommended that the booster dose be given 6 to 12 months after the first vaccine dose. The subjects who received three doses of vaccine, regardless of the between-dose interval, were considered completely vaccinated.
The difference in the seroprevalence of HBV markers among women and men was analyzed by
c2-test.
The program of vaccination against HB at the Sestre milosrdnice University Hospital in Zagreb started in 1992 and initial results were published in 199723. As a result of pretesting, 111 (12.1%) individuals were excluded from the vaccination program during the 1992-1993 period. In this group, seven (0.8%) HCWs were found to be HBV carriers (HBsAg positive), i.e. two at internal medicine, and one at neurosurgery, gynecology, ophthalmology, nuclear medicine and pediatrics each, whereas 104 (11.3%) had signs of previous HBV infection (anti-HBs and/or anti-HBc positive). No history of jaundice was reported. At the Departments of Pathology and of Neuropsychiatry as well as in all laboratories, no asymptomatic individuals with positive HBV markers were detected, however, the number of pretested persons was extremely small. Of the remaining HCWs tested, 809 were seronegative at baseline. These data are presented in Table 1.
The prevalence of HBV positivity among HCWs according to gender is presented in Table 2. Positive HBV markers were detected in 84 (11.1%) of 755 women and 27 (16.4%) of 165 men tested. No significant difference in the prevalence of positive HBV markers between men and women was found by c2-test (c2=3.50; p>0.05).
During the 1992-1993 period, the vaccination was initiated in 583 eligible HCWs. Of these HCWs, 339 (58.1%) received complete vaccine series, i.e. three doses of the vaccine, while 244 (41.9%) did not complete vaccination, i.e. received only one or two doses at inappropriate time. In terms of starting the vaccination series, the best compliance was recorded at neurosurgery (82.2% of all HCWs employed at the department), followed by pediatrics (69.6%) and ENT (61.6%). The lowest participation rate was recorded at neuropsychiatry (0.5%) and physiatry (3.5%). The highest proportion of HCWs who had completed vaccination during this period of time was observed at internal medicine. In the same time, 60 (41.1%) of the HCWs from this department started but did not complete the vaccination series, while at pediatrics only 18 (22.2%) HCWs did not receive all the three doses of vaccine (Table 3).
A total of 923 HCWs participated in the continuous vaccination program at the Sestre milosrdnice University Hospital during the second period observed, from 1994 till 1998. In this period, 454 (49.2%) HCWs completed the primary series of vaccination. In terms of starting the vaccination series, the best compliance was achieved at pulmonology (77.8% of all HCWs employed at the department) and pediatrics (75.2%), followed by neurosurgery (73.0%). The lowest participation rate was recorded at physiatry. The highest number of persons who started and completed the primary series of vaccination in this period was recorded at internal medicine, followed by neuropsychiatry. The lowest participation rate of HCWs who completed primary vaccination series in this period was observed at physiatry (22.2%), followed by urology (30.4%), ENT (35.7%), and anesthesiology (38.5%). The number of individuals who completed the primary vaccination series during the 1994-1998 period was higher than during the1992-1993 period. The difference between these two groups is statistically significant (c2=686.15; p<0.01).
Table 2. Sex distribution of HBV positive markers
Table 3. Response to HBV vaccination program
Table 4. HBV revaccination during the 1993-1998 and 1996-1998 periods
The first attempt of vaccination against HBV was initiated in 1981. In Croatia, the use of active immunization started in 1987. The HCWs who daily come in contact with human blood or other body substances are at a risk of acquiring HBV infection and should be vaccinated5-8,20.
Immunization is strongly recommended for people at risk: HCWs, children of HBV carrier mothers, relatives and close contacts of chronic HBV carriers, patients on hemodialysis, residents and staff of institutions for mentally handicapped, intravenous drug abusers, and hemophiliacs20.
The World Health Organization has recommended the vaccination against HB of all children worldwide during the first year of life, as a measure of HBV infection reduction, but problems still exist. Many countries with a high prevalence rate have financial limitations, whereas some countries with a low prevalence rate do not consider early childhood vaccination to be necessary9-11,24. Since 1999, all sixth-grade school children in Croatia have to be vaccinated against HB with three intramuscular doses according to the schedule 0 (initial), 1 and 6 months, as a measure of HBV infection reduction18. Moreover, everyone who is or will be in occupational contact with blood or other body substances from other persons, whether directly or indirectly, should be offered free of charge vaccination against HB by their employer or teaching institution21-24. In our programmed vaccination, the vaccine was free, the vaccination was organized at working places, however, the rate of participation could not be considered satisfactory.
The number of new HBV infections is difficult to determine, because most infections are subclinical, even those that eventually lead to chronic hepatitis. It is almost certain that acute hepatitis is under-reported, so the true number is probably two or three times higher. Serologic
markers indicating exposure to HBV were detected in 12.1% of subjects. In these persons, vaccination was not performed. In addition, predetermination of HBV markers revealed seven (0.8%) chronic HBV carriers, who needed further examination by a hepatologist, and so did their close family members. Similar data have been reported
elsewhere5,6,25-27. In Croatia, there are about 1% of
chronic HBV carriers in the total population. Publications on HBV immune status among HCWs in Croatia report on about 13% of HCWs to be positive for some of the HBV markers, 1.8% of them being chronic HBV
carriers7,26.
In HCWs, the risk of acquiring HBV infection is even up to four-fold risk found in the general population, and rises with continuous work in high-risk settings1. By successive introduction of vaccination against HB in HCWs from 1987, the rate of acute HB as an occupational disease considerably decreased. As an illustration, during 1994 and 1995, only six HCWs with acute HB were hospitalized at Dr. Fran Mihaljevi} University Hospital for Infectious Diseases2-7,15,28, as compared with a total of 18 HCWs with HB hospitalized in 1986.
The transmission of HBV from patients to medical staff is a well known risk, however, a reverse route is also well documented. In some hospital acquired HBV infections, patients were infected during surgery or some other invasive procedure from HCWs who were HBV carriers29,30. The persons with positive HBV markers had no history data of jaundice, which is consistent with our investigation. This fact appears to mask the significance of the risk of HBV infection transmission from such individuals to those who are in close contact with them. Moreover, even 10% of those with positive antibodies to HBV may have chronic hepatitis C31,32.
Determination of anti-HBc should be performed in all subjects before vaccination. If anti-HBc is positive, the subject's serum sample should be additionally tested. If anti-HBc is negative, vaccination should be started, following the schedule of the vaccine manufacturers. If there is a high probability for HBV infection to be already present, the person should be tested for HBsAg, even if negative for anti-HBc. An HBsAg positive person should not be vaccinated, although accidental vaccination is not known to be harmful. It should be noted that HBsAg may be detected in serum for several days after vaccination28,32.
Determination of the immune status for HBV infection in high risk individuals by testing for HBsAg, anti-HBs and anti-HBc before vaccination identifies chronic HBV carriers as well as those with previous HBV infection. These individuals should not undergo vaccination but should be examined by a hepatologist, and so should be their close family members. The possibility of a past or ongoing HBV infection exists among these persons, thus pretesting is necessary, according to many international and Croatian experts, before initiating active immunization5,14,26,32.
Beside general protective measures against HBV infection, which include regular use of gloves, protective masks, goggles and plastic aprons, safe needle handling, correct procedures of handling pathologic material, and good laboratory practice, a very important role is played by the specific measure of immunization with HB vaccine1. The HBV vaccine used in our hospital consists of recombinant surface antigen proteins. The first vaccines were prepared from human plasma, treated to inactivate the infectious virus. The second generation vaccines are recombinant proteins obtained by cloning and expressing the surface antigen gene in microorganisms10,12. Inadequate knowledge about the second or third generation HB vaccines, which have no relation to plasma or any blood products, may be one of the reasons why some employees decline vaccination.
Energix-B is a recombinant DNA HB vaccine containing purified virus surface antigen. It is indicated for active immunization against HBV infection. The vaccine against HB is used in non-immunocompromised individuals according to the schedule of 0, 1 and 6 months. When rapid protection is required, or after exposure, a shortened schedule of 0, 1 and 2 months, and a fourth dose after 6 or 12 months should be used. If the recombinant HB vaccine is administered within 48 hours from an accidental exposure to HBsAg positive blood (incidents), according to the schedule of 0, 1, 2 and 6 months, an equal protection is achieved if the HB vaccine is given in combination with HB-immunoglobulin (HBIG)4-7,26,33.
Because of the long incubation period of HB, an unrecognized infection may be present at the time of vaccination. The vaccine may not prevent hepatitis in such cases, however, it will not worsen the condition either. In some persons, seroconversion upon the completion of the vaccination series fails, i.e. they do not develop protective antibodies after the vaccine administration. Older age is one of the reasons, however, obesity and smoking can also account for the failure of seroconversion.
Semiquantitative anti-HBs marker testing 4-8 weeks after the third dose should control the immune response. A detectable level of anti-HBs is a marker of protection. The detection limit is 1 to 5 IU/L; 10 IU/L are considered a marker of protection. People with less (<10 IU/mL) or no anti-HBs should immediately undergo revaccination with another
dose14, two doses at one-month
interval16,26,28, or three doses according to the schedule of 0, 3 and 6
months36. Low responders with less than 100 IU/L should
be revaccinated after one year, an all others after 8 years if the special risk is still present. A booster dose after the 0, 1 and
6-month primary vaccination schedule will, on an average, probably not be required earlier than 5 years later. Since the peak antibody levels reached after the shorter 0, 1 and 2-month primary vaccination schedule are lower, it is recommended that the booster dose be given at 12 months after the first dose of the vaccine. The next booster will probably not be required before another 8
years12,14,34,35.
Because of the diversity of individual responses to the vaccine and time dependent decrease in the antibody level, it can be recommended that patients with a titer less than 100 IU/L be boosted. It is assumed that immune memory is adequate for long-term protection, even when the level of circulating antibodies has fallen below 10 IU/L32,35.
It would be useful to detect HBV markers upon the completion of HBV vaccination. The individuals at an increased risk of HBV infection should know their immune status against HBV. The main problems in HB vaccination, as in our action, are the employees' declination of vaccine and neglecting appropriate vaccination intervals26. Since the period between the second and third dose is long (5 months), persons often forget the exact term for the receipt of the third dose and present too late. We wish to emphasize that persons who have received only two HB vaccine doses can develop icteric HB a few years after the primary infection. Examples are cases of two surgeons treated at Dr. Fran Mihaljevi} University Hospital for Infectious Diseases in Zagreb in 1994 (personal communication).
HCWs often change their working places, which further complicates the record-keeping system. Hospital committee for prevention and control of hospital infections18 should record the HB serostatus as well as acceptance or declination of vaccination and seroconversion of HCWs. So, when the employees want to change their working place, they have to present their vaccination data. This could be one of the measures for HB reduction among HCWs.
In conclusion, efforts to control the risk of HBV infection among HCWs are complicated by accidental contacts with infected blood. Active immunization of susceptible individuals with HB vaccine should be the optimal strategy to reduce HBV infection in this high risk occupation. Financial limitations sometimes make preimmunization testing for HB markers impossible, however, it is necessary to check seroconversion after immunization. Continuous education about HBV transmission, HB vaccine and vaccination programs, use of protective devices, safe needle handling, correct safety procedures for handling pathologic material applied all the time, good laboratory practice, and permanent vaccination are the only way to avoid occupational HB infection.
Correspondence to: Oktavija Đaković-Rode, M.D., Dr. Fran Mihaljević University Hospital for Infectious Diseases, Mirogojska 8, HR-10000 Zagreb, Croatia
Received June 16, 1999, accepted in revised form February 3, 2000
1. DOEBBELING BN. Protecting the health care workers from infection and injury. In: WENZEL RP, ed. Prevention and control of nosocomial infections, 3rd Ed. New York: William & Wilkins, 1997:398-409.
2. DIENSTAG JL. Occupational exposure to hepatitis B virus in hospital personnel: infection or immunization? Am J Epidemiol 1982;115:26-39.
3. DOUCHIN M, SHOUVAL D. Occupational and non-occupational hepatitis B virus infection among hospital employees in Yerusalem: a basis for immunization strategy. Br J Ind Med 1992;49:620-5.
4. MANSOUR AM. Which physicians are at high risk for needle stick injuries? Am J Infect Control 1990;18:208-10.
5. PALMOVIĆ D, BUREK V, KOŠUTI]Ć Z. Rizik stjecanja hepatitis B virusne infekcije kod zdravstvenih radnika. Liječ Vjesn 1985;107:484-9.
6. PALMOVIĆ D. Zaštita zdravstvenih radnika nakon slučajne ekspozicije virusu hepatitisa B. Liječ Vjesn 1988;110:484-9.
7. PALMOVIĆ D, CRNJAKOVIĆ-PALMOVIĆ J. Prevention of hepatitis B (HBV) infection in health-care workers after accidental exposure: a comparison of two prophylactic schedules. Infection 1993;21:42-5.
8. PALMOVIĆ D. Virusni hepatitis. Medicus 1995;4:141-8.
9. LEE WM. Hepatitis B virus infection. N Engl J Med 1997;337:1733-45.
10. SHAPIRO CN, MARGOLIS HS. Hepatitis B epidemiology and prevention. Epidemiol Rev 1990;12:221-7.
11. TIMBURY MC. Notes on medical virology, 8th Ed. New York: Churchill Livingstone 1997:127-38.
12. PAVER KW, MORTIMER PP. An overview of hepatitis viruses. Clin Microbiol Infect Dis 1996;2:132-41.
13. BURK RD, HWANG LY, HO GYE, SHAFRITZ DA, BEASLEY RP. Outcome of perinatal hepatitis B virus exposure is dependent on maternal virus load. J Infect Dis 1994;170:1418-23.
14. GARDNER P, SCHAFFNER W. Immunization of adults. N Engl J Med 1993;328:1252-8.
15. PARKER G, JENKINS S. Hepatitis B and admission to medical school policy. BMJ 1996;313:856-7.
16. PALMOVI] D, GOLUBI] D, VURU[I] B, KOVA^I]-PETROVI] A. Spre~avanje hepatitis B virusne infekcije u osoba visokog rizika u Medicinskom centru ^akovec. Liječ Vjesn 1993;115:90-4.
17. Pravilnik o načinu provođenja imunizacije, seroprofilakse, kemoprofilakse protive zaraznih bolesti, te o osobama koje se podvrgavaju toj obvezi. Narodne novine 1994;23:660-5.
18. Program obaveznog cijepljenja u 1999. Godini. Ministarstvo zdravstva Republike Hrvatske. Okru`nica br. 534-01-98-1, 1998.
19. ZUCKERMAN AJ. Developing new hepatitis immunization strategies. Gut 1996;38(Suppl 12):S60-S62.
20. FENN P, GRAY A, McGUIRE A. An economic evaluation of universal vaccination against hepatitis B virus. J Infect 1996;32:197-204.
21. HOLLAND PV. Strategies for prevention of viral hepatitis in the United States. Int Hepatol Commun 1996;5:3-9.
22. WOODRUF BA. Progress toward integrating hepatitis B vaccine into routine infant immunization schedules in the United States, 1991 through 1994. Pediatrics 1996;97:798-803.23
. ĐAKOVIĆ-RODE O, PALMOVIĆ D, KOSANOVIĆ I. Zaštita djelatnika Kliničke bolnice "Sestre milosrdnice" od infekcije virusom hepatitisa B. Liječ Vjesn 1997;119:226-30.
24. CHEN HL. Seroepidemiology of hepatitis B virus infection in children. Ten years of mass vaccination in Taiwan. JAMA 1996;276:906-8.
25. PALMOVIĆ D. Akutni hepatitis B na području Zagreba. Lijec Vjesn 1987;109:211-6.
26. PALMOVIĆ D, CRNJAKOVIĆ-PALMOVIĆ J. Vaccination against hepatitis B: results of the analysis of 2000 population members in Croatia. Eur J Epidemiol 1994;10:541-7.
27. PALMOVIĆ D, VITAS B, DOKO A, BELAVIĆ @, RAČKI Lj. Rezultati cijepljenja hepatitis B vakcinom bolesnika i osoblja Centra za dijalizu u Karlovcu. Liječ Vjesn 1989;111:400-4.
28. YASSI S. Anti-HBs protection in hospital workers vaccinated against hepatitis B: policy implication of a pilot study. Br J Ind Med 1990;47:645-6.
29. HEPTONSTALL J. Outbreaks of hepatitis B infection associated with infected surgical staff. Community Dis Rep 1991;1:511-4.
30. MADLLEY CR. Transmission of nosocomial virus infections by health care workers. Curr Opin Infect Dis 1993;6:511-4.
31. WONG V, WREGHITT TG, ALEXANDER GJM. Prospective study of hepatitis B vaccination in patients with chronic hepatitis C. BMJ 1996;312:1336-7.
32. GERLICH WH, CASPARI G, UY A, THOMSSEN R. A critical appraisal of anti-HBc, HBV DNA and anti-HCV in the diagnosis of viral hepatitis. Biotest Bull 1991;4:283-93.
33. VODOPIJA I, LJUBIČIĆ M, BAKLAIĆ Ž, SVJETLIČIĆ M, MIHALJEVIĆ I, PALMOVIĆ D. Post-exposure prophylaxis for hepatitis B. Lancet 1989;2:1161-2.
34. LOUTHER J, FELDMAN J, RIVERA P, VILLA N, DEHOVITZ J, SEPKOWITZ KA. Hepatitis B vaccination program at a New York City hospital: seroprevalence, seroconversion and declination. Am J Infect Control 1998;26:423-7.
35. TILZEY AJ. Hepatitis B vaccine boosting the debate continues. Lancet 1995;345:1000-1.
36. McDERMOTT AB, COHEN SBA, ZUCKERMAN JN, MADRIGAL JA. Hepatitis B third-generation vaccines: improved response and conventional vaccine non-response _ evidence for genetic basis in humans. J Viral Hepatitis 1998;5(Suppl 2):9-11.
O. Đaković-Rode, D. Palmović i I. Kosanović
Opisano je sudjelovanje zdravstvenih radnika u organiziranoj kontinuiranoj akciji cijepljenja protiv hepatitisa B (HB) u Kliničkoj bolnici "Sestre milosrdnice" u Zagrebu. Organizirano cijepljenje protiv HB cjepivom Engerix-B (20 mg po dozi) u KB "Sestre milosrdnice" započelo je 1992. godine. Prikazani su podaci o cijepljenim osobama u razdobljima od 1992.-1993. i 1994.-1998. godine. Cijepljenje se provodilo na različitim bolničkim odjelima, u prvom razdoblju jedanput ili dvaput na tjedan, a u drugom razdoblju jedanput na mjesec. Prije početka cijepljenja 1992. godine biljezi za HB (HbsAg, anti-HBs i anti-HBc) bili su provjereni u 920 osoba. Ukupno je 111 (12,1%) testiranih ispitanika isključeno iz programa cijepljenja zbog pozitivnih biljega HB. U razdoblju od 1992.-1993. godine, 58,1% ispitanika primilo je tri doze cjepiva, dok je u razdoblju od 1994.-1998. godine potpuno cijepljeno 49,2% zdravstvenih radnika. Preporuča se odrediti postignutu razinu titra anti-HBs protutijela, kako bi se što točnije moglo odrediti vrijeme docjepljivanja.
Ključne riječi: Hepatitis B, prevencija i kontrola; Profesionalne bolesti; prevencija i kontrola; Osoblje, bolnica