Research Article - Current Pediatric Research (2018) Volume 22, Issue 1
Response to the provision of hepatitis B booster in children aged 10-15 years with non-protective anti-Hbs titer.
Novie Homenta Rampengan*
Department of Pediatrics, Faculty of Medicine, Sam Ratulangi University, Indonesia.
- Corresponding Author:
- Novie Homenta Rampengan
Jl. Raya Tanawangko Malalayang II Lingkungan III
Manado 95115, North Sulawesi, Indonesia
E-mail: [email protected]
Accepted date: March 21, 2018
Introduction: Several studies have demonstrated that titer of protective anti-HBs (≥ 10 mIU/ml) begins to wane at age 10 and declines rapidly due to age. Approximately 10% of Indonesia's population was infected with hepatitis B. Objective: To determine the response to the provision of Hepatitis B vaccine among children aged 10-15 years with titer of non protective anti-HBs. Method: Consecutive study conducted from October to December 2015 among the children aged 10-15 years from 10 schools in Tuminting Regency, North Sulawesi. Before study conducted, titer of anti-HBs was checked with the result titer of non-protective anti-HBs (<10 mIU/ml). The inclusion criteria was Parents signed inform consent, the children were administered a booster dose of hepatitis B immunization and were rechecked within 1-3 months after administration. The study was approved by Ethic Commitee of Medical Faculty of Sam Ratulangi University. Result: A total 74 out of 82 children who had non-protective titer of anti-HBs complied with inclusive criteria. 60 children (81.1%) got protective titer of anti-HBs after receiving a booster dose of hepatitis B immunitation. While 14 children (18.9%) got non-protective titer of anti-HBs (non-responder). Among 60 children who got protective titer of anti-HBs, only 4 children (6.7%) were found with titer of anti-HBs ranging 10-100 mIU/ml (hyporesponder) and 56 children (93.3%) were found with titer of anti-HBs >100 mIU/ml (good responder). Conclusion: Provision of a booster dose of hepatitis B to the non-protective children presented a good result.
Hepatitis B Virus (HBV) infection is highly prevalent in the society. There are 240 millions people are suffered from chronic infection of Hepatitis B and 780.000 death every year from causes both chronic and accute Hepatitis B infections . In areas of high endemicity, such as Southeast Asia, Africa and Brazil, more than 8% of the population are detected as Hepatitis B patients . Indonesia with 235 millions of population is included into high endemicity areas because 9,4% among the population are Positive-Hepatitis B [3,4]. In areas of high endemicity, the infection is often aquired during the preschool years and transmitted vertically from mother to the infant or horizontally from HB-carrier who lives in the same house with the infant .
Primary Hepatitis B vaccination could prevent Hepatitis B virus infection with rate as high as 90% to 95%.6 In Indonesia, since 2006, HB-0 HB-0 monovalent vaccine (uniject) has been given after the birth. It has been continued by receiving combination of DTwP/HB/HIB vaccine at age 2, 3 and 4 months [6,7]. Although vaccines have been given for a long period of time, According to the data from Ministry of Health of Indonesia in 2013, presentage of HB-0 administration is only 79.1% and DPT-HB-3 is 75.6% . Immune system memory remain until 15 years after hepatitis B initial administration. However, several studies have demonstrated that titer of protective anti-HBs (≥ 10 mIU/ml) begins to wane at age 10 and declines rapidly due to age [9,10]. This, for sure, increases the risk of hepatitis B exposure, moreover approximately 10% of Indonesia's population is infected with hepatitis B. Therefore, booster hepatitis B vaccine is needed for prevention of hepatitis B infection.
The aim of the study was to determine the response to the provision of Hepatitis B vaccine among children aged 10- 15 years with titer of non protective anti-HBs.
Materials and Methods
The study design was consecutive study among the children aged 5-15 years from 10 schools (Elementary, Junior, and Senior High School) in Tuminting Regency, Manado, North Sulawesi. It was an advanced study from previous study. The previous study showed that among 105 children who were observed, only 23 children had titer of protective anti-HBs and 82 children did not have titer of non-protective anti-HBs . The inclusion criteria was parents signed inform consent, children were administered a booster dose of HBS and were rechecked within 1-3 months after administrations. The study was approved by Ethics Commitee of Medical Faculty of Sam Ratulangi University.
2 ml of blood sample was drawn by needle connected to vacuumtainer. Then, Titer of anti-HBs from the sample was checked using Chemiluminescent Microparticle Immunoassay (CMIA). Titer of anti-HBs levels <10 mIU/ ml was categorized as non-responder and titer of anti- HBs levels ≥ 10 mIU/ml was categorized as responder. Responder was determined into hyporesponder (titer of anti-HBs levels 10-100 mIU/ml) and good responder (titer of anti-HBs levels >100 mIU/ml) . Data was analyzed by using descriptive analysis and Chi-square of SPSS ver. 22.
A total 74 out of 82 children whom had titer of nonprotective anti-HBs from previous study complied with the inclusive and exclusive criteria. There were 8 children excluded from the study. Three of them did not receive a boster dose of hepatitis B vaccine. Five of them, eventhough they were administered with a dose of titer of anti-HBs, did not show up for rechecking the titer of anti- HBs within 1-3 months after administrations. 74 children who complied the criteria of the study consisted of 17 male (23%) and 57 female (77%). Thus, They were determined into various range of age. There were twelve of ten years old (16.2%), twelve of eleven years old (16.2%), eleven of twelve years old (14.9%), 15 of 13 years (20.3%), 12 of 14 years (16.2%) and 12 of 15 years old (16.2%). There were 60 children (81.1%) had protective titer of anti-HBs (titer of anti-HBs ≥ 10 mIU/ml) after receiving a booster dose of hepatitis B immunization, while 14 children (18.9%) had non-protective titer of anti-HBs (titer of anti-HBs < 10 mIU/ml). Among the children who were protective, four children (6.7%) had titer of anti-HBs between 10- 100 mIU/ml (hyporesponder) and 56 children (93.3%) had titer of anti-HBs >100 mIU/ml (good responder). 14 out of 56 children who were good responder had titer of anti-HBs >1000 mIU/ml. Table 1 shows characteristic of the subject of the study.
|Characteristic||Total (%), n=74|
|Titer of Anti-HBs|
|< 10 mIU/ml||14 (19.7)|
|10-100 mIU/ml||4 (5.4)|
|> 100 mIU/ml||56 (74.9)|
Table 1: Characteristic of subjects
Analysis of titer of anti-HBs according to age and sex could be seen on Table 2. In age group, There was no significant differences between respondents who have protective titer of anti-HBs with respondents who had non-protective titer of anti-HBs (p=0.490) as well as the mean of age between protective and non-protective subjects (p=0.457). Nevertheless, there was no significant relationship of sex between subjects with protective titer of anti-HBs and subjects with non-protective titer of anti-HBs (p=0.220).
|Age, n (%)|
|10 years||2 (14.3)||10 (16.7)||0.49|
|11 years||2 (14.3)||10 (16.7)|
|12 years||2 (14.3)||9 (15.0)|
|13 years||4 (28.5)||11 (18.2)|
|14 years||2 (14.3)||10 (16.7)|
|15 years||2 (14.3)||10 (16.7)|
|Age mean (SD), years||12.59±1.71||12.17±1.78||0.457|
|Sex, n (%)|
|Male||5 (35.7)||12 (20,0)||0.22|
|Female||9 (64.3)||48 (80.0)|
Table 2: Analysis of titer of anti-HBs according to age and sex
Primary hepatitis B vaccination could prevent hepatitis B virus infection with rate as high as 90% to 95%. Seroprotection has been estimated to persist atleast for 15 years eventhough titer of anti-HBs has been dramatically decline to negative. Someone is still clinically protected from chronic hepatitis B because the immune memory would give in vitro protection. Therefore, booster hepatitis B immunization is not nessesary for the children who has received a complete hepatitis B (3-4 times) . However, the fact in the field shows that eventhough hepatitis B immunization has been conducted since 1997 in Indonesia, there is no prevalance change of 10 % of hepatitis B patients. according to task force of Indonesian Pediatric Society (IPS), immune hepatitis B booster administration could be given to the children with age 10-12 years if the level content of protection has not been reached yet (titer of anti-HBs <10 mIU/ml) .
The study was continuous study from previous study with 82 children (respondents). Total 74 out of 82 children were eligible to be the subjects of the study. The subjects consisted of 17 males (23%) and 57 females (77%). 12 out of 17 males had protective titer of anti-HBs, while 48 out of 57 females had protective anti-HBs.However, there was no statistically signifficant differences among two sex groups. It is similar to the study conducted by Cheang et al.  where the result showed that sex did not affect hepatitis B seroprotective and immune reponse after primary hepatitis B vaccine. However, the finding is at variance with the finding from the study by Giltay et al.  which revealed that female showed antibody reponse higher than male, where male showed number of lymphocyte T declined higher than female and also igM and igG serum content of male was lower than female. Besides, it could be affected by sexual hormone, such as estrogen, progesterone, and testosterone which are different betwen male and female .
The study showed that there was no difference of protection level in age 10-15 years group with protection mean of 80%. It was supported by statistical analysis which did not show any significant differences. It is similar to the study carried out by Rampengan et al.  but at varience with the study conducted by Whittle et al.  which displayed that titer of anti-HBs effectiveness was affected by age, effectiveness of anti-HBs titer reduction was equal to the age of respondents.
The study was found out that among 74 of the subjects who received a booster dose of hepatitits B, 14 subjects (19.7%) had non-protective titer of anti-HBs (<10 mIU/ ml) and 60 subjects (80.3%) had protective titer of anti- HBs (≥ 10 mIU/ml). Among subjects who were protective, 4 subjects (6.7%) had titer of anti-HBs between 10 to 100 mIU/ml (hyporesponder) and 56 subjects (93.3%) had titer of anti-HBs >100 mIU/ml (good responder). 19.7% non-responder was found in this study. It was displayed that immune response formed was affected not only by immune response of patients but also could be afftected by another factors, such as quality and quantity of vaccine (administration method, dose, frequency of administrations, adjuvant and type of vaccine) and genetical factor which was not observed in the study . According to immunitation task force of Indonesian Pediatric Society, children who are non-responders could received 3 times of hepatitis B initial administrations (0,1, and 6 months) which is considered 40% of non-responder children could form strong antibody of ant i-HBs. If there is no seroconvertion after 3 times immunitation of hepatitis B, 2 doses of hepatitis B immunition could be considered given to the patients .
Approximately 10% of Indonesia's population was infected with hepatitis B. Provision of a booster dose of hepatitis B to the non-protective children presented a good result.
- Jhaveri R. Prevention of hepatitis B virus vertical transmission: time for the next step. Pediatrics 2015; 135: e1286-1287.
- World Health Organization. Department of Communicable Diseases Surveillance and Response- Hepatitis B.
- Fahmi JU. The problem of viral hepatitis in Indonesia. In: A comprehensive review of viral hepatitis in children. Jakarta: Child Health Department, Indonesia University 2000.
- Chen S, Chang M. Epidemiology and natural history of hepatitis B in children. In: Jonas M, editors. Viral hepatitis B in children unique features and opportunities. New York: Humana Press; 2010.
- Hidayat B, Pujiarto P, Gunardi H. Hepatitis B. In: Ranuh IGN, Suyitno H, Hadinegoro SR, Kartasasmita C, Ismoedijanto, Soedjatmiko, editor. Immunization Guidelines in Indonesia. 5th edn. Jakarta: Badan Penerbit Ikatan Dokter Anak Indonesia; 2014. p. 247-53.
- Hadinegoro SR. Immunization schedule. In: Ranuh IGN, Suyitno H, Hadinegoro SR, Kartasasmita C, Ismoedijanto, Soedjatmiko, editor. Immunization Guidelines in Indonesia. The fifth edition. Jakarta: Badan Penerbit Ikatan Dokter Anak Indonesia 2014: 54-58.
- Rampengan NH, Hadinegoro SR, Karyanti MR. Hepatitis B seroprotection in children aged 10-15 years after completion of basic hepatitis B immunization. Paediatr Indones 2017; 57: 77-84.
- Salama II, Sami SM, Salama SI, et al. Persistence of protection to hepatitis B vaccine and response to booster dose among children and adolescents in Dakahleya, Egypt. Egypt J Immunol 2014; 21: 13-26.
- Dahifar H. Immunogenicity of Cuban hepatitis B vaccine in Iranian children. Arch Iranian Med 2004; 7: 89-92.
- Cheang HK, Wong HT, Ho SC, et al. Immune response in infants after universal hepatitis B vaccination: a commnity based study World Health Organization. Hepatitis B vaccines: WHO position paper-recommendations. Vaccine. 2010; 28: 589-590.
- Giltay E, Fonk J, Blomberg B, et al. In vivo effects of sex steroids on lymphocyte responsiveness and immunoglobulin levels in humans. J Clin Endocrinol Metab 2000; 85: 1648-1657.
- Bouman A, Heineman M, Faas M. Sex hormones and the immune response in human. Hum Reproduct Update 2005; 11: 411-423.
- Whittle H, Jaffar S, Wansbrough M, et al. Observational study of vaccine efficacy 14 years after trial of hepatitis B vaccination in Gambian children. British Med J 2002; 32: 1-5.
- Matondang BS, Siregar SP, Akib AAP. Immunology aspect of immunization. In: Ranuh IGN, Suyitno H, Hadinegoro SR, Kartasasmita C, Ismoedijanto, Soedjatmiko, editor. Immunization Guidelines in Indonesia. The fifth edition. Jakarta: Badan Penerbit Ikatan Dokter Anak Indonesia 2011: 24-37.