Short versus standard schedule Hepatitis B vaccination to injecting drug users in prisons and drug treatment centres

N Fisker, P Brehm Christensen

Dep. of Clinical Immunology.
Odense University Hospital (Denmark)




IDUs constitute a high risk group for HBV infection, both in prison and in society in general. Infection rates amongst this group are 100 times higher than amongst the general population. The recognition of this high risk factor of HBV amongst IDUs is generally accepted, and the Danish authorities recommend preventive vaccination for IDUs against HBV 56. Unfortunately, new IDUs are infrequently in contact with health services and consequently are rarely offered the opportunity to receive vaccination. Several Danish drug treatment centres have offered vaccination to high risk adult IDUs for some time, whereas in prisons this service has only recently been made available. An added difficulty is that IDUs are not often willing to embark on and maintain a vaccination program. This may be one of the reasons why only 2% of Danish IDUs are vaccinated against HBV1.

However, studies carried out amongst IDUs have found that between 21 and 65% of them have spent time in prison 31, although many IDUs did not spend sufficient time as inmates to receive the three vaccinal doses according to the standard program. This meant that treatment according to the accepted standard program was infrequently completed. It is commonly believed that a possible alternative is a "high-speed" program of three doses applied in a period of three weeks. This leads to the possibility of raising program completion to over 80%, However, this type of treatment may be less effective for seroprotection.

This study does not set out to validate the effectiveness of different vaccination programs. The vaccines used in these cases have been fully evaluated and results taken from vaccination programs amongst young healthy adults are comparable. The aim of this paper is to study compliance with different vaccination HBV programs that are offered to IDUs in prison. The use of data taken from studies of healthy individuals offers little in the way of useful information for this paper.

Consequently, this paper puts forward the question as to which program should be offered to IDU inmates. In this study, we have included information provided by drug treatment centres about seroprotection so as to establish better estimates. Obviously this can not provide answers to vaccination compliance in prison. But the individuals receiving assistance in treatment centres have similar problems as regards the percentage of response to vaccination and frequency of infection.

Key Words: Hepatitis B, Vaccination, Prison




Hepatitis B (HBV) constitutes a major health problem to injecting drug users (IDUs) in Scandinavia as in the rest of the world. As vaccines against hepatitis B are available these infections are potential preventable even when transmission cannot be avoided. In a newly concluded survey of Danish prisoners only 2% of identified IDU prisoners were vaccinated against HBV.1

There are three major problems with vaccination of IDUs. 1) Many IDUs become infected with HBV early in their injecting career before they are offered vaccination. 2) A low compliance to standard vaccination schedule among IDUs, and 3) A low efficacy among IDUs compared to healthy young adults.





In a review by Levine, the worldwide HBV prevalence among 9566 IDUs was 74% (range 38- 99.2) with 9% HBsAg positive.2 The prevalence of HBV has probably decreased since the middle eighties and seems to follow the tendency in the general population, only at a much higher level.3-4 Cyclic outbreaks of HBV have been repeatedly reported, supposed to reflect the gradual accumulation of new susceptible IDUs.2, 5-6

Three Danish studies of hepatitis among IDUs have recently been concluded.1, 7-8 Results are in agreement and give an average prevalence for Danish IDUs of 66.0% [95% confidence 62-70%] for HBV. The prevalence of hepatitis B markers (and markers of other bloodborne infections) increases with duration of drug use.1, 9.

Tres estudios daneses sobre hepatitis entre UDIs han concluido recientemente1, 7-8. Los resultados son similares y observan una prevalencia de infección por VHB promedio para los UDIs daneses de 66,0% [I.C. 95% = 62-70%]. La prevalencia de los marcadores de hepatitis B (y de otras infecciones de transmisión parenteral) se incrementa con el tiempo de consumo de droga1, 9.


Incidence studies among IDUs are difficult to perform due to problems with recruitment and compliance.2 Most studies have been performed in drug treatment centres and are not necessary applicable to IDUs outside of treatment. Table I summaries studies on transmission rates among IDUs. These incidence studies show elevated levels of viral transmission compared to the general population (where reported incidence is in the order of 100 times lower).

Studies mentioned in Table I and additionally studies with incidence rates gives a reported range of HBV incidence of 0-24/100 py, with a mean incidence of 12.1/100 py [95% C.I. 10.4-13.9].

The average incidence calculates might overestimate current transmission rates among IDUs because of the decreasing incidence over time.





The literature of serological studies from prison populations has produced a broad range or results. In general the prevalence increases with the proportion of IDUs in the survey and with the level of serological markers in the general population. With these reservations prevalence of HBV has been found among 10-73% of tested with 0-15% HBsAg positive. 15-19 Among non-IDU prisoners prevalence is much lower, 1-3 times the prevalence in the general population.17, 26

In Scandinavia variable results have been found. In Norway 0-8% of prisoners were HBsAg positive (13.1% among IDUs) and 20-30% had past HBV infection, compared to 4.1% in the general population. 17, 22 Likewise, in a recent survey, 9,3% among IDU prisoners in the Danish State prison of Nyborg were HBsAg positive and 55% had past infection compared to 0,5% and 13% respectively among non- IDU prisoners.1 A survey among IDUs from Stockholm’s remand prison performed in 1994 is shown in Table II.9


Reported incidence in prison studies (Table III) is significantly lover than among IDUs studied outside. The only exception is a study where the incidence is a mixture of transmission in and outside prison.30 There may be several reasons for the lower incidence in prison: not all prisoners included are IDUs and several studies have an overrepresentation of longterm prisoners. These are believed to have less frequent risk behavior.31 A third factor is that most studies of IDU outside prison are older than the prison studies and therefore must be anticipated to have higher incidence due a falling incidence during the last decade.14

It is a constant finding that IDU and young age is related to seroconversion. But interestingly Crofts found a "protective" effect of prison against hepatitis C seroconversion. This is supported by the lower incidence in prison, but it could also be due to a confounding effect of age or IDU in this study.30 The inverse relation to age is the opposite of what has been found by most cross sectional studies. These findings are not in disagreement, but reflects that surveys investigate cumulated exposure.



Vaccine against HBV has been available since 1982 were the first plasma-derived vaccines were licensed. These vaccines were formalin-inactivated extracts of HBsAg particles from healthy hepatitis B carriers. This vaccine was extensively evaluated in clinical trials and found to be both immunogenic and protective.36 The efficacy trials of this vaccine established the seroprotective level of immunity to be 10 IU/l of anti-HBs. Above this level no clinical illness or chronic carriers were found, although subclinical infection did occur.37-39 The next generation vaccine was genetically engineered by expressing the entire S-gene in a bacterial or yeast vector, thereby avoiding possible viral contamination.

It proved to have the same high efficacy (95% of young healthy adults seroprotected by the 0,1,6 month regime) as the plasma-derived vaccines, but has for ethical reasons not been evaluated against placebo.40-41

Table IV compares resent studies of the anti-HBs response among healthy adults after three doses of vaccine. The four first rows are with the standard schedule that has been shown to induce seroprotection among 95% of young healthy adults. A possible reason for the lower response rates in the two US studies was that serology test were performed later than one month after last dose. Lower vaccine response in healthy populations has been found among males, smokers, obese and a decreasing immune response is seen with increasing age.36

The rest of Table IV shows the effect of accelerated regimes with data of seroprotection after the third dose. Most of the studies incorporated a booster after one year because of lower antibody titers achieved by the accelerated schedule. As anti- HBs >10 IU/l at month 7 after the standard regime has been proven to protect against clinical hepatitis B, this table indicates that a booster dose may not be necessary.

Table V summaries recent IDU vaccination trials. In some but not all IDUs have a lower compliance and seroprotection rate after a standard regime. The picture for the accelerated regimes is not clear: some found the same seroprotection level, while others found a markedly lower responsrate. This may partly be due to anti-HBs test performed already at month 3 or only after 9-10 month when the anti-HBs titer might be increasing respectively decreasing as compared to month 7. Also if anti-HBc positives are included in vaccination trials this could overestimate vaccine response rates.1 Although a poorer vaccination response cannot be excluded with an accelerated regimen, this could be compensated by a higher compliance with short schedules.



Swedish and Danish IDUs prisoners are offered Hepatitis B vaccine according to accepted guidelines (month 0, 1, and 6).




Engerix B®, the most commonly used Hepatitis B vaccine in Denmark is authorized in Denmark according to normal guidelines with 3 doses given a month 0, 1 and 6 and an accelerated treatment with 4 doses for newly exposed individuals. (month 0, 1, 2, and 12). The vaccine could also be applied by means of 3 doses during days 0, 7, and 21 on certain occasions. In this case one memory dose per year is recommended55.




1.Christensen P. B. Ph.D. thesis in preparation. 1999. University of Southern Denmark, Odense University.

2.Levine OS. Vlahov D. Nelson KE. Epidemiology of hepatitis B virus infections among injecting drug users: seroprevalence, risk factors, and viral interactions. Epidemiol. Rev. 1994; 16: 418-36.

3. Kielland KB. Siebke JC. Hepatitis A-, B- and Cmarkers among Norwegian drug addicts in the period 1975-89. Hepatitt A-, B- og C-markorer hos norske stoffmisbrukere i perioden 1975-89. Tidsskr. Nor. Laegeforen. 1991; 111: 821-4.

4.Haglind P. Iwarson S. [A notable decrease of hepatitis B in Stockholm and Gothenburg but not in Malmo-Lund] Kraftig minskning av hepatit B i Stockholm och Goteborg, men ej i Malmo-Lund. Lakartidningen. 1989; 86: 517-med.

5. Christenson B. [Transmission of hepatitis B-a model for the evaluation of future HIV epidemic outbreaks] Spridningen av hepatit B—en modell for skattning av den framtida HIV-epidemin. Lakartidningen. 1987; 84: 4037-8, 4041.

6.Christenson B. Epidemiology of hepatitis B in Sweden. J.Infect. 1987; 15: 269-77.

7.Kristensen E. and Ankerstjerne N. Projekt HIV/HEP-Test. AIDS-Sekretariatet, Århus Amt. 1-36. 1998. Århus, Arhus Amt.

8.Fuglsang T. Fouchard J. and Ege P. Projekt Blodprøve. 1998.

9.Krook A. Albert J. Andersson S. Biberfeld G. Blomberg J. Eklund I. et al. Prevalence and risk factors for HTLV-II infection in 913 injecting drug users in Stockholm, 1994. J. Acquir. Immune. Defic. Syndr. Hum. Retrovirol. 1997; 15: 381-6.

10.Van-Ameijden EJ. Van-den-Hoek JA. Mientjes GH. Coutinho RA. A longitudinal study on the incidence and transmission patterns of HIV, HBV and HCV infection among drug users in Amsterdam. Eur. J. Epidemiol. 1993; 9: 255-62.

11. Levine OS. Vlahov D. Brookmeyer R. Cohn S. Nelson KE. Differences in the incidence of hepatitis B and human immunodeficiency virus infections among injecting drug users. J. Infect. Dis. 1996; 173: 579-83.

12. Crofts N. Aitken CK. Incidence of bloodborne virus infection and risk behaviours in a cohort of injecting drug users in Victoria, 1990-1995. Med. J. Aust. 1997; 167: 17-20.

13. Hagan H. McGough JP. Thiede H. Weiss NS. Hopkins S. Alexander ER. Syringe exchange and risk of infection with hepatitis B and C viruses. Am.J Epidemiol. 1999; 149: 203-13.

14. Broers B. Junet C. Bourquin M. Deglon JJ. Perrin L. Hirschel B. Prevalence and incidence rate of HIV, hepatitis B and C among drug users on methadone maintenance treatment in Geneva between 1988 and 1995. AIDS 1998; 12: 2059-66.

15. Chiaramonte M. Trivello R. Renzulli G. Zampieri L. Fanecco A. Floreani A. et al. Hepatitis B virus infection in prisons. A seroepidemiological survey in prisoners and attending staff. J. Hyg. Lond. 1982; 89: 53-8.

16. Gaube J. Feucht HH. Laufs R. Polywka S. Fingscheidt E. Muller HE. [Hepatitis A, B and C as desmoteric infections] Hepatitis A, B und C als desmoterische Infektionen. Gesundheitswesen. 1993; 55: 246-9.

17. Hurlen B. Jacobsen N. Hurlen P. Hepatitis B serum markers and oral health in a group of Norwegian male prisoners. Acta Odontol. Scand. 1984; 42: 53-8.

18. Mero E. Steuer W. [Incidence of hepatitis B virus markers in prisoners]Vorkommen von Hepatitis- B-Virus-Markern bei Gefangenen. Offentl.Gesundheitswes. 1983; 45: 252-4.

19. Pinducciu G. Arnone M. Piu G. Usai M. Melis A. Pintus L. et al. [Prevalence of hepatitis virus (HBV and HCV) and HIV-1 infections in a prison community]. Ann. Ig 1990; 2: 359-63.

20. Martelli CM. de Andrade AL. Cardoso Dd. Sousa LC. Silva S. de Sousa MA. et al. [Seroprevalence and risk factors for hepatitis B virus infection by AgHBs and anti-HBs markers in prisoners and prime blood donors]. Rev. Saude Publica 1990; 24: 270-6.

21. Crovari P. Cassini U. Infante D. Guano F. Icardi GC. Auteri G. et al. Prevalence of infections caused by AIDS and hepatitis B viruses in jailed people. Boll. Ist. Sieroter. Milan. 1985; 64: 367-70.

22. Hurlen B. Siebke JC. Stensland A. Viral hepatitis among prisoners in Norway. NIPH. Ann. 1980; 3: 129-32.

23. Melico SA. Pombo V. Pereira A. Lopes R. Corte RR. Seroepidemiological survey of transmissible infections in Portuguese prisoners. AIDS 1991; 5: 780-1.

24. del Olmo JA. Llovet F. Rodrigo JM. Molina J. Aparisi L. Serra MA. et al. Prevalence of liver disease and infection by hepatitis B, delta virus, and human immunodeficiency virus in two Spanish penitentiaries. Med Microbiol. Immunol. (Berl) 1990; 179: 43-8.

25. Acedo A. Campos A. Bauza J. Ayala C. Jover M. Herrero L. et al. HIV infection, hepatitis, and syphilis in Spanish prisons. Lancet 1989; 2: 226.

26.Anda RF. Perlman SB. D’Alessio DJ. Davis JP. Dodson VN. Hepatitis B in Wisconsin male prisoners: considerations for serologic screening and vaccination. Am. J. Public Health 1985; 75: 1182-5.

27. Prefontaine RG. Chaudhary RK. Seroepidemiologic study of hepatitis B and C viruses in federal correctional institutions in British Columbia. Can.Dis. Wkly. Rep. 1990; 16: 265-6.

28. Espinoza P. Bouchard I. Buffet C. Thiers V. Pillot J. Etienne JP. [High prevalence of infection by hepatitis B virus and HIV in incarcerated French drug addicts]. Gastroenterol. Clin. Biol. 1987; 11: 288-92.

29. Levine OS. Vlahov D. Koehler J. Cohn S. Spronk AM. Nelson KE. Seroepidemiology of hepatitis B virus in a population of injecting drug users. Association with drug injection patterns. Am. J. Epidemiol. 1995; 142: 331-41.

30. Crofts N. Stewart T. Hearne P. Ping XY. Breshkin AM. Locarnini SA. Spread of bloodborne viruses among Australian prison entrants. BMJ. 1995; 310: 285-8.

31. Dolan K. AIDS, drugs and risk behavior in prison: State of the art. In Nelles J. Fuhrer A. eds. Harm reduction in Prison, pp. 213-39. Berne: Peter Lang AG. European Academic Publisher, 1997.

32. Kelley PW. Redfield RR. Ward DL. Burke DS. Miller RN. Prevalence and incidence of HTLV-III infection in a prison. JAMA 1986; 256: 2198-9.

33. Decker MD. Vaughn WK. Brodie JS. Hutcheson- RH J. Schaffner W. The incidence of hepatitis B in Tennessee prisoners. J. Infect. Dis. 1985; 152: 214-7.

34. Hull HF. Lyons LH. Mann JM. Hadler SC. Steece R. Skeels MR. Incidence of hepatitis B in the penitentiary of New Mexico. Am. J. Public Health 1985; 75: 1213-4.

35. Keppler K. Nolte F. Stöver H. Übertragungen von Infektionskrankheiten im Strafvollzug - Ergebnisse einer Untersuchung in der JVA für Frauen in Vechta. Sucht 1996; 42: 98-107.

36. Eddleston A. Modern vaccines. Hepatitis. Lancet 1990; 335: 1142-5.

37. Hadler SC. Francis DP. Maynard JE. Thompson SE. Judson FN. Echenberg DF. et al. Long-term immunogenicity and efficacy of hepatitis B vaccine in homosexual men. N. Engl. J. Med. 1986; 315: 209-14.

38. Szmuness W. Stevens CE. Harley EJ. Zang EA. Alter HJ. Taylor PE. et al. Hepatitis B vaccine in medical staff of hemodialysis units: efficacy and subtype cross-protection. N. Engl. J. Med. 1982; 307: 1481-6.

39.Wainwright RB. Bulkow LR. Parkinson AJ. Zanis C. McMahon BJ. Protection provided by hepatitis B vaccine in a Yupik Eskimo population-results of a 10-year study. J. Infect. Dis. 1997; 175: 674-7.

40. Jilg W. Lorbeer B. Schmidt M. Wilske B. Zoulek G. Deinhardt F. Clinical evaluation of a recombinant hepatitis B vaccine. Lancet 1984; 2: 1174-5.

41. Ring-Larsen H. [Engerix-B, hepatitis B vaccine produced by means of a recombinant DNA technic]. Ugeskr. Laeger 1990; 152: 1917-9.

42.Wood RC. MacDonald KL. White KE. Hedberg CW. Hanson M. Osterholm MT. Risk factors for lack of detectable antibody following hepatitis B vaccination of Minnesota health care workers. JAMA 1993; 270: 2935-9.

43. Roome AJ. Walsh SJ. Cartter ML. Hadler JL. Hepatitis B vaccine responsiveness in Connecticut public safety personnel. JAMA 1993; 270: 2931-4.

44. Jepsen LS. Thomsen AC. [Preventive hepatitis B vaccination of hospital staff] Profylaktisk hepatitis B vaccination af et hospitalspersonale. Ugeskr. Laeger 1992; 154: 2421-3.

45. Hess G. Hingst V. Cseke J. Bock HL. Clemens R. Influence of vaccination schedules and host factors on antibody response following hepatitis B vaccination. Eur. J. Clin. Microbiol. Infect. Dis. 1992; 11: 334-40.

46. Marchou B. Excler JL. Bourderioux C. Salaun J. Picot N. Yvonnet B. et al. A 3-week hepatitis B vaccination schedule provides rapid and persistent protective immunity: a multicenter, randomized trial comparing accelerated and classic vaccination schedules. J. Infect. Dis. 1995; 172: 258-60.

47. Bock HL. Scher T. Scheiermann N. Baumgarten R. Wiese M. Dutz W. et al. Accelerated Schedule for Hepatitis B Immunization. J Travel. Med 1995; 2: 213-7.

48.Wahl M. Hermodsson S. Iwarson S. Hepatitis B vaccination with short dose intervals-a possible alternative for post-exposure prophylaxis? Infection 1988; 16: 229-32.

49. Rodrigo JM. Serra MA. Aparisi L. Escudero A.Gilabert MS. García F. et al. Immune response to hepatitis B vaccine in parenteral drug abusers. Vaccine 1992; 10: 798-801.

50. Mezzelani P. Venturini L. Turrina G. Lugoboni F. Des JD. High compliance with a hepatitis B virus vaccination program among intravenous drug users. J. Infect. Dis. 1991; 163: 923-med.

51. Rumi M. Colombo M. Romeo R. Boschini A. Zanetti A. Gringeri A. et al. Suboptimal response to hepatitis B vaccine in drug users. Arch. Intern. Med. 1991; 151: 574-8.

52. Salassa B. Macor A. Zucco M. Nigra E. Spezia C. Soranzo ML. [Anti hepatitis B immunization in drug addicts: Establishing a schedule]. G. Mal Infett. Parassit. 1994; 46: 24-31.

53. Rotily M. Vernay VC. Bourliere M. Galinier PA. Rousseau S. Obadia Y. HBV and HIV screening, and hepatitis B immunization programme in the prison of Marseille, France. Int. J. STD. AIDS 1997; 8: 753-9.

54. Bayas JM. Bruguera M. Martín V. Vidal J. Rodes J. Salleras LY. Hepatitis B vaccination in prisons: the Catalonian experience. Vaccine 1993; 11: 1441-4.

55. Lægemiddelstyrelsen. Produktresumé for Engerix- B, injektionsvæske (vaccine). 1998. Lægemiddelstyrelsen. 56. SundhedsStyrelsen. Hepatitisvejledning. VEJ nr 15000 af 31/01/1996.


  • No hay Refbacks actualmente.