E-mail: prapan.j@cmu.ac.th Study of hepatitis B vaccination to students whom firstly demonstrated anti-HBs negative or titer < 10 mIU/ml 1Prapan Jutavijittum*, 1Amnat Yousukh, 2Siriboon Yavichai, 2Kulyapa Yoonut, 3Nisarat Apichartpiyakul, 4Tsutomu Masaki AND 5Masaaki Tokuda 1Dept. of Pathology, 2Health Promotion Unit, 3Microbiology Unit, Central Laboratory, 2,3Maharaj Nakorn Chiang Mai Hospital, 1,2,3Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand, 4Dept. of Cell Physiology, 5Department of Gastroenterology and Neurology, 4,5Faculty of Medicine, Kagawa University, Kagawa, Japan E-mail: prapan.j@cmu.ac.th

Introduction Worldwide, different hepatitis B (HB) vaccines, dosages and vaccination schedules are used. Vaccination shall be given at 0, 1, and 6-month intervals. An antibody to HB surface antigen (anti-HBs) titer of ≥ 10 mIU/ml is considered to be protective. Anti-HBs < 10 mIU/ml after completion of the 1st vaccine series is called “non-responders”. In Thailand, nation-wide infant vaccination against hepatitis B virus started in 1992. HB vaccine was given along with other vaccines at birth, 2 and 6 months of age.

Introduction Coverage of HB vaccination for infants ranged from 71.2 to 94.3%, average of 82.3%.[1] – has reached > 95% since 1999 The antibody response to hepatitis B vaccine is 90% in healthy adults and 95% of infants, children, and adolescents. Titres of anti-HBs after a complete vaccination schedule decline with time to low or undetectable levels, but is not considered as loss of protection. [1] Jutavijittum P, Jiviriyawat Y, Yousukh A, Hayashi S, Toriyama K. Evaluation of a hepatitis B vaccination program in Chiang Mai, Thailand. Southeast Asian J Trop Med Public Health 2005; 36: 207-12.

Introduction Healthcare personnel are regarded as a high-risk group for contracting HB infection because of exposure to blood and body fluids. Therefore HB vaccination is recommended for non-immune healthcare personnel. Pre-booster check is still worthwhile to identify HB carriers among newly recruited healthcare personnel born after adoption of neonatal HB immunization.[2] [2] Chan PK, Ngai KL, Lao TT, Wong MC, Cheung T, Yeung AC, Chan MC, Luk SW. Response to booster doses of hepatitis B vaccine among young adults who had received neonatal vaccination. PLoS One 2014;9(9):e107163.

Introduction In Thailand, infants who have received nation- wide hepatitis B immunization in 1992 are now young adults joining the healthcare disciplines or at entrants to medical and nursing schools. This study aimed to know effectiveness of HB vaccination from the persons who birth at the starting time of the integration of HB vaccine into the EPI and to evaluate HB revaccination response of whom firstly demonstrated anti-HBs negative or titer < 10 mIU/ml.

Materials AND Methods In 2013, first year students of Chiang Mai University were tested for the presence of HBsAg and quantitative levels of anti-HBs. Whom tested negative for HBsAg and anti- HBs negative or titer < 10.0 mIU/ml were called back for 3-dose course of HB revaccination. 124 male & 284 female (249 medical students & 159 nurse students) are enrolled in our study blood samples were taken at 8-10 months after the 1st dose of HB revaccination

Results AND discussions Of 408 persons (age 17-19 years, mean age 18.16±0.44 years) 3 (0.7%) : HBsAg-positive  0.7% became HBsAg carriers 2 (0.8%) : anti-HBc positive  0.8% were infected and recovered from HBV infection Thai experience underlines the impact of the universal HB vaccination programme, which greatly reduced numbers of HB acute cases and of HBsAg carriers in children aged < 15 years (from 5%-6% in 1988 to 0.7% in 2004).[3] [3] FitzSimons D, Hendrickx G, Vorsters A, Van Damme P. Hepatitis B vaccination: a completed schedule enough to control HBV lifelong? Milan, Italy, 17-18 November 2011. Vaccine 2013;31(4):584-90.

Results AND discussions 332 (81.4%) : anti-HBs negative or titer < 10 mIU/ml 76 (18.6%) : anti-HBs titer ≥ 10 mIU/ml The overall positive rate for anti-HBs among young university entrants was 30.4%.[2] [2] Chan PK, Ngai KL, Lao TT, Wong MC, Cheung T, Yeung AC, Chan MC, Luk SW. Response to booster doses of hepatitis B vaccine among young adults who had received neonatal vaccination. PLoS One 2014;9(9):e107163. Long-term follow up studies of infant vaccination showed that anti-HBs become negative in 15%-50% among the vaccine responders within 5 to 10 years.[4] [4] Meireles LC, Marinho RT, Van Damme P. Three decades of hepatitis B control with vaccination. World J Hepatol 2015;7(18):2127-32.

Dose-response of HB revaccination among the students whom firstly demonstrated anti-HBs negative or titer < 10 mIU/ml TABLE 1. Dose-Response of HB Revaccination HB revaccination Anti-HBs titers Negative or < 10 mIU/mL ≥ 10 mIU/mL 1 dose course 2/2 (100.0%) 0/2 ( 0%) 2 dose course 0/8 ( 0%) 8/8 (100.0%) 3 dose course 5/236 ( 2.1%) 231/236 ( 97.9%) Total count 7/246 ( 2.8%) 239/246 ( 97.2%)

Results AND discussions Among the complete 3-dose course of HB revaccinated subjects, only 5/236 (2.1%) have failure to raise anti-HBs ≥ 10 mIU/mL. 14.5% of the students had anti-HBs levels of < 10 mIU/mL after a single dose booster suggesting lost of memory immunity.[2] [2] Chan PK, Ngai KL, Lao TT, Wong MC, Cheung T, Yeung AC, Chan MC, Luk SW. Response to booster doses of hepatitis B vaccine among young adults who had received neonatal vaccination. PLoS One 2014;9(9):e107163. Supplementary HB vaccination of healthy hypo- and non-responders after HB vaccination induced an anti-HBs titer greater than 10 mIU/mL in 38% after one and in 75% after 3 additional doses.[5] [5] Roukens AH, Visser LC. Hepatitis B vaccination strategy in vaccine low and non-responders: a matter of quantity of quality? Hum Vaccin. 2011 Jun;7(6):654- 7. Epub 2011 Jun 1.

Results AND discussions Non-responders are considered to be unprotected against HBV infection. Children vaccinated as newborns or infants who retained anti-HBs >10 mIU/mL fell from ~75% at age 5 years to ~20% at age 20 years, very few have shown evidence of HBV infection. .[3] [3] FitzSimons D, Hendrickx G, Vorsters A, Van Damme P. Hepatitis B vaccination: a completed schedule enough to control HBV lifelong? Milan, Italy, 17-18 November 2011. Vaccine 2013;31(4):584-90. Base on the current scientific evidence, there is consensus that there is no need to administer booster doses of HB vaccine to ensure long- term protection in immunocompetent subjects

Conclusion AND Suggestion The young adults whom firstly demonstrated anti-HBs negative or titer < 10 mIU/ml required at least 2-dose course of HB vaccination to achieve protective levels of anti-HBs. Long time after infant HB vaccination: Pre- booster check and HB revaccination should be provided to some high-risk individuals, e.g., healthcare workers, joining healthcare disciplines, couples of HBV carriers. The Ministry of Public Health should reconsider for booster of HB vaccine in practice.