|Year : 2018 | Volume
| Issue : 3 | Page : 397-400
Evaluation of immune response to hepatitis B vaccine in healthcare workers at a tertiary care hospital
Praveena Basireddy1, Surekha Avileli2, Nagajyothi Beldono2, Swarna Latha Gundela2
1 Department of Microbiology, Government Medical College, Anantapuramu, Andhra Pradesh, India
2 Department of Microbiology, Kurnool Medical College, Kurnool, Andhra Pradesh, India
|Date of Web Publication||14-Nov-2018|
Dr. Surekha Avileli
Department of Microbiology, Kurnool Medical College, Kurnool, Andhra Pradesh
Source of Support: None, Conflict of Interest: None
Purpose: Healthcare workers (HCWs) are at high risk of acquiring hepatitis B virus (HBV) infection through occupational exposure which is preventable through hepatitis B vaccination. 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). Methods: Blood samples were collected in all HCWs, who have received the complete schedule of hepatitis B vaccination and anti-HBs levels, were assessed quantitatively in sera using ELISA. Results: The age range of the study participants was 20–55 years. The mean months after the last dose of vaccination were 60.36. Among the 85 participants, 96.5% (n = 82) have protective immunity to hepatitis B. The anti-Hbs response was similar in both male and female (P > 0.05). There was a decline in immune response as the age was increasing (P < 0.05). The results of the study found a significant decline in the immune response with time (P < 0.05). The anti-Hbs response was declined with smoking habit (P < 0.05) and with increasing body mass index (P < 0.05). Conclusion: Post-HBsAg vaccination immunity to hepatitis B was 96.5% in HCW and was similar to that of global rates. Increasing age, time period, smoking habit, and overweight were associated with decreased immunity. Many studies are needed in developing newer HBV vaccines with very high immunogenicity. Giving highly immunogenic vaccine to HCWs will ensure safety at work by reducing nosocomial transmission which is very much desired in a resource-limited country.
Keywords: Anti-hepatitis B virus surface antigen levels, healthcare workers, hepatitis B virus, hepatitis B virus surface antigen vaccine
|How to cite this article:|
Basireddy P, Avileli S, Beldono N, Gundela SL. Evaluation of immune response to hepatitis B vaccine in healthcare workers at a tertiary care hospital. Indian J Med Microbiol 2018;36:397-400
|How to cite this URL:|
Basireddy P, Avileli S, Beldono N, Gundela SL. Evaluation of immune response to hepatitis B vaccine in healthcare workers at a tertiary care hospital. Indian J Med Microbiol [serial online] 2018 [cited 2020 Jun 6];36:397-400. Available from: http://www.ijmm.org/text.asp?2018/36/3/397/245377
| ~ Introduction|| |
Hepatitis B is the most important occupational infectious disease. Transmission of hepatitis B from patients to healthcare workers (HCWs) and from HCWs to patients has been described. According to the WHO, 5.9% of HCWs are each year exposed to blood-borne HBV infections corresponding to about 66,000 HBV infections in HCWs worldwide.
Hepatitis B virus (HBV) infection can be prevented through HBV surface antigen (HBsAg) vaccination. Vaccine efficacy studies have demonstrated protection against acute and chronic disease in immunocompetent vaccine responders. The schedules for vaccination approved by most regulatory authorities which are as follows: 0,1 and 6 months ( first dose followed by a dose 1 month and 6 months after the first) and 0, 1, 2 and 12 months ( first dose followed by a dose 1 month, 2 months and 12 months after the first). The '0, 1, 2 and 12 months' schedule should be considered when rapid protection is required in high-risk groups such as HCWs. Protective antibody titres are achieved in almost all recipients by 3 months. To ensure an enduring high antibody titre following rapid vaccination, a fourth dose must be given at 12 months. For routine immunisation, the '0, 1 and 6 months' schedule is less costly and provides excellent antibody titres and duration of protection.
Testing for evidence of protective immunity to HBsAg vaccination is essential, as some vaccinated HCWs do not develop sufficient levels of antibodies against HBsAg (anti-HBs). An anti-HBs level of >10 mIU/ml, is considered as protective against HBV infection. An anti-HBs titre of <10 mIU/ml is regarded as non-responsiveness to HBsAg vaccination. Anti-HBs levels between 10 and 100 mIU/ml are regarded as hyporesponsiveness, and levels >100 mIU/ml are taken as a high level of immunity.
Smoking, obesity, aging, chronic medical conditions, male sex, genetic factors and immunosuppression are associated with a decrease in immune response., The current study is aimed to evaluate immune response to HbsAg vaccination in HCWs and the factors associated with decreased immune response.
| ~ Methods|| |
This was a cross-sectional study conducted from April 2013 to 2014 in a tertiary care hospital after obtaining the Institutional Ethical Clearance. All HCWs, who have received the complete standard course of intramuscular HBsAg vaccination, were included in the study population. Known HBsAg positive HCWs, were excluded from the study.
With 99% confidence level and absolute allowable error of 5%, the minimum sample size required is 77. Hence, 85 sample sizes were taken. The study population consisted of 85 HCWs. The anti-HBs level was measured in the collected serum samples using a commercially available ELISA (New Medical Biological Service, S. R. L., Opera, Milano, Italy). Data were analysed categorically for gender, age, time elapsed since the last dose of vaccination, smoking habit and body mass index (BMI) against anti-HBs levels using SPSS 20 software. Comparisons were made using cross tabulation with the Chi-square test, and P < 0.05 was considered statistically significant.
| ~ Results|| |
The study population comprised 45 (52.95%) females and 40 (47.05%) males. Of the total 258 participants, 85 (32.9%) had received all three or five doses of vaccination and the rest had received two doses only. 21 (24.7%) participants had taken booster doses in addition.
Overall, 96.5% of the vaccinated HCWs developed protective immunsity to hepatitis B. Of these 20.0% had an anti-HBs titre between 10 and 100 mIU/ml and the rest (76.5%) had an anti-HBs titre of >100 mIU/ml. 3.5% of the vaccinated HCWs did not develop a sufficient anti-HBs response [Table 1]. The anti-HBs response was similar in both male and female (P = 0.70) [Table 1]. There was a decline in immune response as the age was increasing.(P = 0.007) [Table 1]. The time elapsed between the last dose of vaccination and the time of assessment of anti-HBs levels ranged from 6 months to 19 years. It was evident that immunity against HBV had reduced significantly overtime (P = 0.004) [Table 1]. The anti-HBs response was declined with smoking habit (P = 0.004) and with increasing BMI (P = 0.00004) [Table 1]. The anti-HBs response was not affected by the vaccination schedule (0, 1 and 6 schedule or 0, 1, 2 and 12 months' schedule) and number of booster doses [Table 1].
|Table 1: Assessment of various parameters in response to hepatitis B virus surface antigen vaccination|
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| ~ Discussion|| |
The age range of the study participants was 20–55 years, with mean and standard deviation being 31.17 and 7.12, respectively, in male and 29.04 and 9.36 in female. The mean BMI was 22.65, and the standard deviation was 1.71 in male. In the female, the mean and standard deviation of BMI were 21.42 and 2.42, respectively.
In this study, 96.5% have protective immunity to hepatitis B suggesting our results are compatible with Varshochi et al. and Thomas et al. who showed 98.54% and 98.89% protective immunity, respectively. Chakrabarthy et al., Chathuranga et al. and Nagamani et al. showed 100%, 91.1% and 100% protective immunity, respectively.
No association between gender and the rate of seroconversion to anti-HBs was found in the current study as in some studies. Some authors have found a poor response in males than in females. The effect of gender could be explained by the greater weight of men; however, others have shown that males have a lower response rate even after correcting the weight. In this study, as there was no much difference in mean BMI of male and female probably the immune response was not affected.
Poor anti-HBs response was seen as the age was increased from as low as 35 years in our study concurrence with previous studies. Theoretically, this age effect could be due to a decrease in lymphocyte proliferation activity.
The time elapsed between the last dose of vaccination and the time of assessment of anti-HBs levels ranged from 6 months to 19 years. The mean months after the last dose of vaccination were 60.36. Our findings show that the anti-HBs level significantly declines with time as in previous studies. Although antibody titre declines with time, it should be reasonable to the level of 10 mIU/ml at any time for ensuring immunoprotection among vaccinated individuals.
Smoking is strongly associated with a poor response rate to hepatitis B vaccine as shown by this study and others., The probable reason could be lower immunoglobulins in smokers than in nonsmokers. Smoking is known to impair dendritic cell function.
With increased BMI from >25, the immune response was decreased in the current study. In some studies, a significant association was found, and in some no significant association was found, between BMI and the immune response.
The limitation of our study was inability to study genetic factors. Another limitation was immunocompromised vaccinated HCWs not there in our study participants; hence, we could not evaluate protective immunity in them.
The findings of our study provide a base for testing for anti-HBs in hepatitis B vaccinated HCWs in India as very few studies were there in India. Although the current vaccines are highly effective, the protective immune response rate is substantial in elderly, smokers, obese individuals and those with chronic hepatic or chronic renal diseases. A lot of research is still needed in developing newer vaccines from ongoing works such as incorporating HBV DNA sequences coding for pre-S1 and pre-S2 protein in hepatitis B vaccine and improvement of the adjuvants to make the vaccine more immunogenic. The poor response to hepatitis B vaccine can be improved by a different route of vaccine administration, increased dose and frequency of vaccination. Other approaches include hepatitis B DNA vaccination with plasmid DNA encoding HBsAg or administration of HBsAg-pulsed blood dendritic cells. More studies are needed to confirm these findings.
| ~ Conclusion|| |
Protective immune response to hepatitis B vaccine among HCWs is 96.5%. Increasing age, increasing duration since vaccination, smoking habit and overweight are associated with decreased protective immune response to hepatitis B. Many studies are needed in developing newer HBV vaccines with very high immunogenicity. Giving highly immunogenic vaccine to HCWs will ensure safety at work by reducing nosocomial transmission which is very much desired in a resource-limited country.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| ~ References|| |
Harpaz R, Von Seidlein L, Averhoff FM, Tormey MP, Sinha SD, Kotsopoulou K, et al.
Transmission of hepatitis B virus to multiple patients from a surgeon without evidence of inadequate infection control. N Engl J Med 1996;334:549-54.
Prüss-Ustün A, Rapiti E, Hutin Y. Estimation of the global burden of disease attributable to contaminated sharps injuries among health-care workers. Am J Ind Med 2005;48:482-90.
Leuridan E, Van Damme P. Hepatitis B and the need for a booster dose. Clin Infect Dis 2011;53:68-75.
In: Hepatitis B as an Occupational Hazard B2 – Hepatitis B as an Occupational Hazard; 1994.
McMahon BJ, Dentinger CM, Bruden 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. J Infect Dis 2009;200:1390-6.
Varshochi M, Mahmodian R. Infectious diseases and tropical medicine research center, department of infection control nurse, cardiovascular research center, faculty of medicine, Tabriz University of medical sciences, Tabriz, Iran. Am J Immunol 2011;7:12-6.
Zuckerman JN, Sabin C, Craig FM, Williams A, Zuckerman AJ. Immune response to a new hepatitis B vaccine in healthcare workers who had not responded to standard vaccine: Randomised double blind dose-response study. BMJ 1997;314:329-33.
Averhoff F, Mahoney F, Coleman P, Schatz G, Hurwitz E, Margolis H, et al.
Immunogenicity of hepatitis B vaccines. Implications for persons at occupational risk of hepatitis B virus infection. Am J Prev Med 1998;15:1-8.
Shaw FE Jr., Guess HA, Roets JM, Mohr FE, Coleman PJ, Mandel EJ, et al.
Effect of anatomic injection site, age and smoking on the immune response to hepatitis B vaccination. Vaccine 1989;7:425-30.
Thomas RJ, Fletcher GJ, Kirupakaran H, Chacko MP, Thenmozhi S, Eapen CE, et al
. Prevalence of nonresponsiveness to an indigenous recombinant hepatitis B vaccine: A study among South Indian health care workers in a tertiary hospital. J Med Microbiol 2015;33 Suppl S1:32-6.
Chakraborty B, Bashar T, Roy K, Noor R, Rahman MM. Persistence of anti-HBs antibody and immunological memory in healthy individuals vaccinated with hepatitis B vaccine Stamford. J Microbiol 2011;1:2074-5356.
Chathuranga LS, Noordeen F, Abeykoon AM. Immune response to hepatitis B vaccine in a group of health care workers in Sri Lanka. Int J Infect Dis 2013;17:e1078-9.
Nagamani R, Naidu A, Jayanthi SR. Study of hepatitis b surface antibodytitres in female medical students post vaccination. Int J Curr Microbiol Appl Sci 2017;6:1053-9.
Perera J, Perera B, Gamage S. Seroconversion after hepatitis B vaccination in healthy young adults, and the effect of a booster dose. Ceylon Med J 2002;47:6-8.
Senden TF. Response to intradermal hepatitis B vaccination: Differences between males and females? Vaccine 1990;8:612-3.
Zeeshan M, Jabeen K, Ali AN, Ali AW, Farooqui SZ, 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. BMC Infect Dis 2007;7:120.
Whittle HC, Maine N, Pilkington J, Mendy M, Fortuin M, Bunn J, et al.
Long-term efficacy of continuing hepatitis B vaccination in infancy in two Gambian villages. Lancet 1995;345:1089-92.
Mahoney FJ. Update on diagnosis, management, and prevention of hepatitis B virus infection. Clin Microbiol Rev 1999;12:351-66.
Struve J, Aronsson B, Frenning B, Granath F, von Sydow M, Weiland O, et al.
Intramuscular versus intradermal administration of a recombinant hepatitis B vaccine: A comparison of response rates and analysis of factors influencing the antibody response. Scand J Infect Dis 1992;24:423-9.
Andersen P, Pedersen OF, Bach B, Bonde GJ. Serum antibodies and immunoglobulins in smokers and nonsmokers. Clin Exp Immunol 1982;47:467-73.
Hogg N. Nicotine has suppressive effects on dendritic cell function. Immunology 2003;109:329-30.
Rottinghaus ST, Poland GA, Jacobson RM, Barr LJ, Roy MJ. Hepatitis B DNA vaccine induces protective antibody responses in human non-responders to conventional vaccination. Vaccine 2003;21:4604-8.
Kim JJ, Ayyavoo V, Bagarazzi ML, Chattergoon MA, Dang K, Wang B, et al
. In vivo
engineering of a cellular immune response by coadministration of IL-12 expression vector with a DNA immunogen. J Immunol 1997;158:816-26.