Immune response to hepatitis B vaccine in a group of health care workers in Sri Lanka

Open AccessPublished:July 01, 2013DOI:https://doi.org/10.1016/j.ijid.2013.04.009

      Summary

      Health care workers (HCWs) are considered at high risk of acquiring the hepatitis B virus (HBV). Seroconversion rates after vaccination against HBV among HCWs have not previously been available in Sri Lanka. In the current study, the response to HBV surface antigen (HBsAg) vaccine was assessed in a selected group of HCWs by testing for antibodies against HBsAg (anti-HBs). This was a retrospective descriptive study to measure the anti-HBs levels, using an ELISA, in an immunized group of HCW referred to Department of Microbiology, Faculty of Medicine, University of Peradeniya, Sri Lanka. Among the 342 participants, 9.9% (n = 34) were non-responders. Female participants had a significantly higher immune response (94.7%) than males (p < 0.05). The results of the study found no significant decline in the immune response with time (p > 0.05). Post HBsAg vaccination immunity in HCW in Sri Lanka is similar to that of global rates with similar gender variation. Anti-HBs levels should be tested in all HCW following HBsAg vaccination so that necessary precautions can be taken.

      Keywords

      1. Introduction

      Hepatitis B virus (HBV) infection is an important occupational risk to health care workers (HCW). HBV infection can be prevented through HBV surface antigen (HBsAg) vaccination. Testing for evidence of protective immunity to HBsAg vaccination is essential, as some vaccinees do not develop sufficient levels of antibodies against HBsAg (anti-HBs).
      • Szmuness W.
      • Stevens C.E.
      • Zang E.A.
      • Harley E.J.
      • Kellner A.
      A controlled clinical trial of the efficacy of the hepatitis B vaccine (Heptavax B): a final report.
      An anti-HBs titer of < 10 mIU/ml is regarded as non-responsiveness to HBsAg vaccination.
      • Zuckerman J.N.
      • Sabin C.
      • Craig F.M.
      • Williams A.
      • Zuckerman A.J.
      Immune response to a new hepatitis B vaccine in healthcare workers who had not responded to standard vaccine: randomised double blind dose–response study.
      Anti-HBs levels between 10 and 100 mIU/ml are regarded as hypo-responsiveness and levels >100 mIU/ml are taken as a high level of immunity. An anti-HBs level of >10 mIU/ml is generally considered as protective against HBV infection.
      • Zuckerman J.N.
      • Sabin C.
      • Craig F.M.
      • Williams A.
      • Zuckerman A.J.
      Immune response to a new hepatitis B vaccine in healthcare workers who had not responded to standard vaccine: randomised double blind dose–response study.
      However, data on the anti-HBs response to HBsAg vaccination are not available in Sri Lanka, although Sri Lanka has been practicing HBV vaccination in HCWs for more than 20 years. In the current study we tested the response to HBsAg vaccination in a group of HCWs by detecting the levels of anti-HBs.

      2. Methods

      The study population consisted of 342 HCWs vaccinated with a standard course of HBsAg vaccination. The anti-HBs level was measured using a commercially available ELISA (Murex anti-HBs, Germany). Data were analyzed categorically for gender, antibody titer, age, and the time elapsed since the last dose of the vaccination against anti-HBs levels using Minitab, version 14. Comparisons were made using cross-tabulation with the Chi-square test, and a p-value of <0.05 was considered statistically significant.

      3. Results

      The study population comprised 152 (44.4%) females and 190 (55.6%) males. Of the total participants, 325 (65.0%) had received all three doses of vaccination and the rest had received two doses only. Fifteen (4.4%) participants had taken the booster dose in addition to their three-dose regimen vaccination. Overall, 9.9% of the vaccinees did not develop a sufficient anti-HBs response; 23.7% had an anti-HBs titer between 10 and 100 mIU/ml and the rest (66.4%) had an anti-HBs titer of >100 mIU/ml (Figure 1). The anti-HBs response was significantly higher in females when compared to males (p = 0.027). Interestingly, no significant association was found between age and the immune response (p = 0.923) (Table 1) for both genders. The anti-HBs titers were similar in the group of participants who had received two doses and those who had received three doses of the HBV vaccination, however all those (n = 15) who had received a booster dose exhibited titers >100 mIU/ml. The time elapsed between the last dose of vaccination and the time of assessment of anti-HBs levels ranged from 2 months to 14 years. It was evident that immunity against HBV had not reduced significantly over the time (p = 0.304) (Table 2).
      Figure thumbnail gr1
      Figure 1Descriptive characteristics of the study cohort including gender, age, doses of HBsAg immunization received, duration after the last dose of the HBsAg immunization, and the quantity of anti-HBs detected by a ELISA, as described in the Methods.
      Table 1Gender and age groups of the study population
      Characteristics<10 mIU/ml

      n (%)
      10–100 mIU/ml

      n (%)
      >100 mIU/ml

      n (%)
      p-Value
      Gender
       Male26 (13.7)46 (24.2)118 (62.1)0.027
       Female8 (5.3)35 (23.0)109 (71.7)
      Age, years
       <3018 (9.2)45 (23.0)133 (67.9)0.923
       30–358 (11.3)19 (26.8)44 (62.0)
       >358 (10.7)17 (22.7)50 (66.7)
      Table 2Time elapsed between the last dose of vaccination and the time of assessment for immunity
      Time elapsedNo protection

      (<10 mIU/ml)

      n (%)
      Protection

      (>10 mIU/ml)

      n (%)
      p-Value
      <1 year16 (7.88)187 (92.12)0.304
      1–7 years13 (13.13)86 (86.87)
      >7 years5 (12.50)35 (87.50)

      4. Discussion

      The global level for a poor immune response to HBV immunization in a given population is 5–10%.
      • Szmuness W.
      • Stevens C.E.
      • Zang E.A.
      • Harley E.J.
      • Kellner A.
      A controlled clinical trial of the efficacy of the hepatitis B vaccine (Heptavax B): a final report.
      In our study 9.9% of HCWs did not develop a protective level (<10 mIU/ml) of anti-HBs, suggesting our results are compatible with global levels. The percentage of male non-responders (13.7%) was higher than their female counterparts (5.3%) and similar findings have been reported in previous studies.
      • Zeeshan M.
      • Jabeen K.
      • Ali A.N.
      • Ali A.W.
      • Farooqui S.Z.
      • Mehraj V.
      • et al.
      Evaluation of immune response to hepatitis B vaccine in health care workers at a tertiary care hospital in Pakistan: an observational prospective study.
      • Wood R.C.
      • McDonald K.L.
      • White K.E.
      • Hedberg C.W.
      • Hanson M.
      • Osterholm M.T.
      Risk factor for lack of detectable antibody following hepatitis B vaccination of Minnesota health care workers.
      Smoking and certain genetic factors have been proposed as probable reasons for a poor immune response to HBV immunization in men; however, these were not evaluated in our study.
      It has been shown that when the age at vaccination is >40 years, the rate of seroconversion to anti-HBs is less, whereas when the age at vaccination is <40 years, seroconversion to anti-HBs is higher than in the former subset.
      • Zeeshan M.
      • Jabeen K.
      • Ali A.N.
      • Ali A.W.
      • Farooqui S.Z.
      • Mehraj V.
      • et al.
      Evaluation of immune response to hepatitis B vaccine in health care workers at a tertiary care hospital in Pakistan: an observational prospective study.
      • Lim W.L.
      • Wong D.A.
      • Cheng K.C.
      Immune response to hepatitis B vaccine in health care workers in Hong Kong.
      However, no association between age at vaccination and the rate of seroconversion to anti-HBs was found in the current study; this might be because the majority of our study population was younger than 40 years of age.
      Previous studies have demonstrated that the protection given by HBV vaccine during childhood and adulthood lasts at least 15–22 years in immunocompetent individuals.
      • McMahon B.J.
      • Dentinger C.M.
      • Burden D.
      • Zanis C.
      • Peters H.
      • Hurlburt D.
      • et al.
      Antibody levels and protection after hepatitis B vaccine: results of a 22-year follow-up study and response to a booster dose.
      • Leuridan E.
      • Van Damme P.
      Hepatitis B and the need for a booster dose.
      • McMahon B.J.
      • Bruden D.L.
      • Petersen K.M.
      • Bulkow L.R.
      • Parkinson A.J.
      • Nainan O.
      • et al.
      Antibody levels and protection after hepatitis B vaccination: results of a 15-year follow-up.
      Our findings also show that the immunity against HBV does not decline with time. Hence the need for a booster after 7–10 years is not necessary in immunologically competent healthy adults, as reported in a recent comprehensive review.
      • Leuridan E.
      • Van Damme P.
      Hepatitis B and the need for a booster dose.
      In agreement with the findings of the recent review, some of the participants in our study had an anti-HBs level >100 mIU/ml even 14 years after the last dose of HBV vaccination. The immune response to the standard HBsAg immunization in HCWs (∼90%) was similar to that observed in HCWs in other parts of the world. Moreover, there were non-responders who remain susceptible to HBV infection. The findings of our study provide a base for testing for anti-HBs in vaccinees in Sri Lanka.

      Acknowledgements

      This study was funded from the annual allocations for the Department of Microbiology, Faculty of Medicine, University of Peradeniya, Sri Lanka.
      Conflict of interest: No conflict of interest to declare.

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