AbstractIntroduction: Health Care Workers (HCW) are at an escalating risk of acquiring blood borne pathogens. Of all, HBV is the one which is vaccine preventable but still sizeable proportion of HCWs never get vaccinated. Further, awareness about HBV and vaccine compliance are poor. The level of immunity after vaccination,  in this population is also  not known. AIM: To study the sero prevalence of HBsAg, anti HBs among vaccinated and unvaccinated HCWs. Materials & Methods: A total of 208 blood samples were collected from HCWs (104 vaccinated and 104 non-vaccinated) from May – July 2011 and tested for anti HBs and HBsAg by ELISA.            Results: Of the 104 vaccinated only 28(27%) had all three doses. Among the  vaccinated 61% (17/28 Three doses), 43% (17/40 Two doses) and  47%  (17/36 single dose) had >100mIU/mL. Of the 104 non- vaccinated, 10 (10%) had >100mIU/mL. Among the vaccinated, 69% (35/51) of <60 kg wt and 30% (16/53) of > 60 kg had more than 100mIU/mL. Of the 52 male, 14(27%)  and among the 52 female, 37(71%) had >100mIU/mL.  Among the fully vaccinated, within 5 years of vaccination, 65%(13/20) and 50% of  more than 5years of vaccination (4/ 8) had > 100mIU/mL.One  incompletely vaccinated and   another one in non vaccinated were positive for HBsAg. Conclusion: This study highlights poor compliance of HBV among HCW. Steps need to be taken to create awareness and the vaccination should be made mandatory for all the persons in health care settings.

Key words: HCW, HBsAg, anti HBs, vaccine compliance, protective level

Introduction

                                                   Health Care workers (HCW) are at an escalating risk of acquiring blood borne pathogens like hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV) and so on. The prevalence of HBV infection in HCWs depends upon its prevalence in general population. In India, the estimated prevalence rate of HBV in the healthy general population is around 4.7%, which places India in an intermediate endemicity zone. [1,2] HBV has been demonstrated to survive in dried blood, at room temperature, on environmental surface for a long time.[3,4,5] HBV is more infectious than HIV owing to high number of infectious particles / ml of blood, even 0.00001 ml of blood can transmit HBV.[3] The risk of HBV in an unvaccinated person from a single HBV infected needle stick injury ranges from 6-30%.[5] Acute HBV infections are mostly asymptomatic and 6-10% of acute HBV leads on to chronic carrier state which in turn progresses to chronic hepatitis, cirrhosis liver and hepatocellular carcinoma. To cap it all, HDV can superimpose with HBV and increase life threatening complications. [4] Of all the blood borne viruses, HBV is the one which is vaccine preventable but still sizeable proportion of HCWs never get vaccinated. Further awareness about HBV compared to HIV, and vaccine compliance are poor among HCW. The level of immunity after vaccination, in this population is also not known. With this background, we studied the sero prevalence of HBsAg, anti HBs among vaccinated and unvaccinated HCWs.

 

 

Materials and methods

                                     A total of 208 blood samples were collected from HCWs (Medical & paramedical students, Interns & laboratory technicians) from May – July 2011 at Govt medical college & hospital. Of this, 104 were vaccinated (3, 2 and single doses) against HBV and another 104 were non-vaccinated. Serum was separated and stored at -20◦C. Samples were tested for anti HBs titre by quantitative and HBsAg by qualitative ELISA (Antisurase B and Surase B from General Biologicals, Taiwan respectively). Institutional ethical committee approval,   informed consent and filled in proforma were obtained before blood collection. All statistical analysis was done by using Chi square test

Results

                                       Of the 208 HCWs, 104 were vaccinated and the remaining 104 were non vaccinated. Among the vaccinated, 28(27%), 40(38%) and 36(35%) had three, two and single dose respectively. Among the vaccinated 61% (17/28 Three doses), 43% (17/40Two doses) and 47% (17/36 single dose) had >100mIU/mL. Of the 104 non vaccinated 10 (10%) had >100mIU/mL. (Table1) The protection level among vaccinated was highly significant compared to non vaccinated group. (p value 0.001) but among the vaccinated, the protection level between the fully vaccinated and incompletely vaccinated was not significant.(p value 0.05).                     

                                                              

                                                         Of the 104 vaccinated, 51(49%) were <60 kg, and the remaining 53 (51%) were > 60 kg. In this, 69% (35/51) of <60 kg wt and 30% (16/53) of > 60 kg had more than 100mIU/mL. Of the 52 male, 10 (19%) were <60 kg and 42(81%) were > 60 kg. Of this 50% (5/10) of <60 kg and 21% (9/42) of >60 kg had >100mIU/mL. Immune response in HCW < 60 kg was highly significant compared to > 60kg group (p value 0.001). Of the 52 female, 41(79%) were < 60 kg and 11 (21%) were > 60 kg. Among this, 73% (30/41) of <60 kg and 64% (7/11) of >60 kg had >100mIU/mL .Of the 52 male 14(27%) and among the 52 female, 37(71%) had >100mIU/mL. (Table2) The protection level in female was highly significant, compared to male (p value 0.001).                                                 

                                   Among the fully vaccinated, 65% (13/20) of within 5 years of vaccination and 50% (4/8) of more than 5years of vaccination had >100mIU/mL. Five years after vaccination, 50% (4/8 Three doses), 36% (4/11Two doses) and 33% (3/9-single dose) had >100mIU/mL. (Table 3) Even among the fully vaccinated group, the protection level significantly decreases after 5 years of vaccination. (p = 0.05)  

                                    One incomplete vaccinated and another one in non vaccinated were positive for HBsAg and both had < 10mIU/mL of anti HBs

Discussion

                                       Out of 104, only 28 (27%) had all three doses which shows the compliance of HB vaccination in HCW was poor. The low compliance was also observed by Vinothkumaradithyaa et al  at Madurai   (45%) and Biju et al  (26%) at Mumbai. [7,8] This poor compliance may be attributed to lack of awareness ,multiple doses , prolonged duration to complete the course , high cost and personal  reasons like movement, pregnancy and other illness.                                    

                                      Generally the protective level of anti HBs is considered as >10 mIU/mL, but some  countries like UK recommend as >100 mIU/mL.[9,10]  A healthy vaccinee who develops an anti-HBs titre of <100 IU/mL is considered to be unprotected and at risk of HBV.A titre of anti-HBs between 10 and 100 IU/mL takes no account of immune memory and cell-mediated immune responses to HBsAg.[11]  Since the  risk is high we considered >100mIU/mL as protective level for HCW in our study. 

                                       Among the vaccinated 61% (17/28 Three doses), 43% (17/40Two doses) and 47% (17/36 single dose) had >100mIU/mL. This shows that even with incomplete vaccination some developed seroprotection which may be due to individual immune response. Initial antibody titre, 2 months after the third dose of vaccination was not known, hence we could not label them as non responders, hyporesponders or who had decreasing antibody titre as  years advanced. Different studies have demonstrated that a small proportion of healthy individuals receiving the hepatitis B (HB) vaccine do not produce protective levels of anti-HBs antibody, a phenomenon which could be linked to certain human leukocyte antigen (HLA) class-II alleles or haplotypes. [12] 

                                      Of the 104 non-vaccinated, 10 (10%) had >100mIU/mL. Luiz A S et al stated that almost 20% of those who were not vaccinated had already acquired natural immunity through previous contact with HBV, and probably if they continued to be exposed, though at a low intensity this would mean that they would acquire increased immunization instead of infection. [13]  

                                      In the vaccinated, 69% (35/51) of <60 kg wt and 30% (16/53) of > 60 kg had more than 100mIU/mL.This indicates that obesity results in poor antibody response and immunity maintenance. [14]  

                                  Of the 52 male 14(27%) and among the 52 female, 37(71%) had >100mIU/mL.This shows that there was decreased immune response among male gender. Hepatitis B vaccines are highly immunogenic, but have decreased immunogenicity associated with increasing age, obesity, smoking, male gender and presence of chronic disease in older adults. [15]In this study, 41(79%) female were below 60 kg. This shows that the gender and weight play major role in immunogenicity.

                                        Among the fully vaccinated, within 5 years of vaccination 65%(13/20) and 50% (4/8)of more than 5years of vaccination  had > 100mIU/mL. But the accumulated data from other studies indicate that protection is dependent on immune memory, rather than declining anti-HBs responses. Following a complete course of vaccination, booster doses are unnecessary if initial antibody response is go

  In the studies to date, the antiHBs is measurable for 7 years or longer. The NHMRC currently recommends that at-risk individuals be revaccinated every 5 years, without a retest for anti-HBS titres. [11] David siebert et al suggested that it may be necessary to revaccinate high-risk hypo-responders more frequently than the currently recommended 5 years interval. Recommendation of booster dose is still   under debate. Hence, the practice of any one organisation will be based on the frequency, type and degree of exposure to HBV within the population under its care.

                                   One incomplete vaccinated and another one in non vaccinated  were positive for HBsAg. Since HBsAg status before vaccination was not known, we could not confirm whether the   infection was acquired before or after vaccination.

Conclusion

                                                       HBV markers (HBsAg, anti HBs, and anti HBc) need to be tested prior to the vaccination. Two months after the 3rd dose of vaccination anti HBs level should be estimated to assess the immune response. Since 30-50% of the people having anti HBs below the protective level may respond to a second series, they should have   a second course and reevaluated for anti HBs level. All non responders even after second series should be educated about the risk, transmission and prophylaxis of HBV. This study highlights poor compliance of HBV among HCW. Steps need to be taken to create awareness and vaccination should be made mandatory for all the persons in health care settings.

Acknowledgment :

 Conflicts of interest: NIL 

 Sources of funding and support   : NIL

References

1. Anjali Singh , Shikha Jain . Prevention of Hepatitis B; knowledge and practices among Medical students . Healthline  ISSN 2229-337X; July-December 2011;2 ( 2 ):8 -11.

2. Thyagarajan SP, Jayaram S, Mohanavalli B. Prevalence of HBV in the general population of India. In: Sarin SK, Singhal AK editors. Hepatitis B in India: Problems and Prevention. (CBS publishers,New Delhi)1996:5-16. 

3. Ananthanarayan and Paniker’s, Text Book of Microbiology. 8th edition, 536-548.

4. Robinson WS.Hepatitis B virus and  hepatitis D virus. Mandell, Douglas and Bennett’s Principles and Practice of  Infectious Diseases, (Churchill Livingstone, Philadelphia )5th edition, volume 2, 2000: 1652-85.

5. Francisco Alvarado-Ramy et al. New guidelines for occupational exposure to blood-borne viruses. Cleveland Clin J of Medicine May 2003 ; 70 (5): 457-465.

6. Sharma R, Rasnia SK, Verma A, Saudan. Study of prevalence and response to needle stick injuries among health care workers in a tertiary care hospital in Delhi, India. Indian J of community medicine. 2010; 35(1): 74-77.

7.Vinothkumaradithyaa A, Srinivasan M, Sankarasubramanian R.A, Uma A, Ananthalakshmi I, Thirumalaikolundhusubramanian P,Kanagasundaram P. Hepatitis B vaccination among medical students of Madurai Medical College.Indian J of Community medicine . Jan2008;33(1):67-68.

 8. Biju I.K, Sattar A, Kate M et al .Incidence and awareness of Hepatitis B Infection among medical and paramedical students. Indian J of Gastroenterology 2002; Supplement 1 A: 104- 5.

9. Kane M , Banatvala  J, DaVilla G,  Esteban R,Franco E,Goudeau A,et al. Are booster immunizations needed for life long  hepatitis B immunity ?(consensus statement )Lancet 12th February 2000;355(9203):561-5.

10. Jane N Zuckerman, Caroline Sabin, M Craig Fiona, A Williams, Arie J Zuckerman. 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 February 1997; 314 : 329. 

11. David Siebett ,Stephen Locarnini. Hepatitis B: issues in laboratory diagnosis and vaccination”. Australian Prescriber 1998;21:72-5.

12. Amirzargar AA, Mohseni N, Shokrgozar MA, Arjang Z, Ahmadi N, Yousefi Behzadi M,Amanzadeh A, Shokri F.HLA-DRB1, DQA1 and DQB1 alleles and haplotypes frequencies in Iranian healthy adult responders and non-responders to recombinant hepatitis B vaccine. Iran J Immunol. June 2008 ;5(2):92-9.

13. Luiz A.S. Ciorlia1 and Dirce M.T. Zanetta. Hepatitis B in Healthcare Workers: Prevalence ,Vaccination and Relation to Occupational Factors. The Brazilian Journal of Infectious Diseases2005;9(5):384-389. 

14. Prathibha Bandaru, Hemalatha Rajkumar, and Giridharan Nappanveettil Altered or Impaired Immune Response to Hepatitis B Vaccine in WNIN/GR-Ob Rat: An Obese Rat Model with Impaired Glucose Tolerance. International Scholarly Research Net work (ISRN) Endocrinology2011:1-7.

15. Averhoff F, Mahoney F, Coleman P, Schatz G, Hurwitz E, Margolis H. Immunogenicity of hepatitis B Vaccines. Implications for persons at occupational risk of hepatitis B virus infection. Am J Prev Med. July1998 ;15(1):1-8.

16.Banatvala JE,Van Damme P.Hepatitis Bvaccine -do we need boosters?J.ViralHepat.Jan.2003 ;10(1):1-6.

 

 

 

 

 

 

   Table1

                       Anti HBs titre with number of doses of HB vaccine in

                                vaccinated and  non vaccinated group

No of vaccinerecipients         Quantitation of Anti HBsAg  titre
 <10mIU/m(%)

 

11- 100mIU/m(%)

 

101-1000mIU/mL(%)

 

>1000mIU/mL(%) Total Protected >100mIU/mL(%) 
 3doses     (n=28)    08(28)     03 (11)  15(54)  02   (7) 28    17(61)
 2 doses   ( n=40)     20 (50)     03(7) 11(28)   06(15) 40   17(43)
 1dose      (n=36)   15 (42)    04 (11) 14(39)  03 (8) 36    17(47)
 Total  vaccinated       (n = 104)    43(41)  10 (10)  40 (38)   11(11) 104    51(49)
Non vaccinated            (n=104)     92(88)  02(2)   08 (8)  02(2) 104    10(10)

 

 

                                                                                                                 

 

 

 

 

 

 

 

 

 

Table 2

                    Anti HBs titre with sex and body weight among vaccinated group

Anti HBs(mIU/mL)          <60kg           >60kg          Total
  M(%)   F(%) Total(%)   M(%)   F(%) Total(%)   M   F Total
<10 4 6 10 30 3 33 34 9 43
10-100 1 5 6 3 1 4 4 6 10
101-1000 4 24 28 6 6 12 10 30 40
>1000 1 6 7 3 1 4 4 7 11
Total 10(19) 41(79) 51(49) 42(81) 11(21) 53(51) 52 52 104
Protected>100 mIU/mL

 No(%)

05(50) 30(73) 35(69) 09(21) 07(64) 16(30) 14(27) 37(71) 51(49)

 

                                                        M- Male   F- Female

 

 

 

 

 

 

 

 

 

 

 

 

                               

 

 

 

Table 3

          Anti HBs titre with number of doses and years after vaccination

Vaccinated  <10mIU/mL 11-100mIU/mL 101-1000 mIU/mL >1000mIU/mL 100mIU/mL
     <5yr    >5yr      <5yr        >5yr     <5yr 

         

 >5yr     <5yr   >5yr   <5yr(%) >5yr(%)
3 doses  (n=28)     04  03  03  01  10  03  03   01  13(65) 04(50)
2 doses  ( n=40)     14  06  02  01  08  04  05   00 13(45) 04(36) 
1 dose    (n=36) 10  06  03  00 12  03  02  00 14(52) 03(33)
Total 28  15  08  02  30  10  10  01  40(53) 11(39)
Protected>100 mIU/mL                     40+11=  51

 

 

 

 

 

 

NEONATAL SEPTICAEMIA BY BETA-LACTAMASES PRODUCING MULTIRESISTANT ORGANISM – CAUSE OF CONCERN, Nachhatarjit Singh , Pavneet Kaur, Aruna Aggarwal
COMPARATIVE STUDY OF CONVENTIONAL MEDIA AND LOW NUTRIENT MEDIA FOR THE MICROBIOLOGICAL DIAGNOSIS OF ENDOPHTHALMITIS.