|Year : 2020 | Volume
| Issue : 1 | Page : 15-19
Anti-Hepatitis B surface antibody response and levels in hepatitis B vaccinated children in diyala province, Iraq
Abdulrazak S H. Hasan1, Mustafa Mahmood Mustaf2
1 Department of Community Medicine, College of Medicine, University of Diyala, Baquba, Diyala Province, Iraq
2 Diyala Directory of Health, Iraqi Ministry of Health, Baquba, Diyala Province, Iraq
|Date of Submission||08-Mar-2019|
|Date of Decision||12-Mar-2019|
|Date of Acceptance||21-Jul-2019|
|Date of Web Publication||29-Jun-2021|
Abdulrazak S H. Hasan
Department of Medicine Microbiology, College of Medicine, University of Diyala, Baquba, Diyala Province
Source of Support: None, Conflict of Interest: None
Background: Hepatitis B virus (HBV) vaccination was one of the success stories of the 20th century. It is highly effective and safe and was incorporated into national immunization programs of countries worldwide. Objectives: The objective of the study as to explore the response rate and titers of anti-HBs antibodies among children 1–14 years old immunized with HB vaccine in Baquba city Diyala province. Vaccinees and Methods: This cross-sectional study was conducted in Baquba City, the center of Diyala province, Iraq for the period July 20, 2016–March 20, 2017. A total of 452 children were enrolled, 247 (54.6%) were males and 205 (45.4%) were females, with an age range of 1–14 years. All were previously immunized with genetically engineered HBV vaccine (Euvax B, Korea), with a dose of 10 μg of HBsAg/0.5 ml intramuscularly. Venous blood samples were collected aseptically; sera were separated and subjected for the detection of HBsAg, anti-HBs antibody titer, HBe Ag, and total antibody and anti-HBc total antibody using Enzyme-Linked Immunosorbant assays (ACON, Foresight-USA). A preconstructed questionnaire form was prepared including information of sociodemographic, health, and vaccination status. Statistical analysis was done using the Statistical Package for the Social Science (SPSS), Version 23. P < 0.05 was considered statistically significant. Results: The overall anti-HBs Ab positivity rate was 75.66% (95% confidence interval was 71.5%–79.6%), with a mean anti-HBs Ab titers range (10.1–673.4 mIU/ml). However, the titer was failed to reach the protective level in 110 (24.34%) vaccinees. The highest anti-HBs Ab positivity rate among children received 1 or 2 vaccine dose is significantly higher among those after <1-year duration (80.0%, P = 0.043), while the mean anti-HBs Ab titer is insignificantly highest among the same group of children (43.7 mIU/ml, P = 0.24). The highest anti-HBs Ab positivity rate among children received three vaccine doses is significantly higher among those after <1-year duration (91.3%, P = 0.003), and similarly the highest mean of anti-HBs Ab titer is insignificant higher among the same children group (81.3 IU/ml, P = 0.2). Regarding those children received four vaccine doses, the anti-HBs Ab positivity rate and the mean anti-HBs Ab titer are significantly higher among children after <1 year (89.9%, P = 0.004 and 97.7 IU/ml, P < 0.001), respectively. Finally, the anti-HBs Ab positivity rate after five vaccine doses was insignificantly higher after 1–3-year duration (72.4%, P = 0.15), while the highest mean anti-HBs Ab titer was significantly higher among those with <1-year duration (55.0 IU/ml, P < 0.041). Conclusion: Universal hepatitis B vaccination is generally produce high rate of protection among children and the highest anti-HBs antibody titer was achieved through 3 or 4 doses after <1-year postvaccination.
Keywords: Anti-HBs Ab, hepatitis B virus infection, hepatitis B virus vaccine
|How to cite this article:|
H. Hasan AS, Mustaf MM. Anti-Hepatitis B surface antibody response and levels in hepatitis B vaccinated children in diyala province, Iraq. IRAQI J COMMUNITY MED 2020;33:15-9
|How to cite this URL:|
H. Hasan AS, Mustaf MM. Anti-Hepatitis B surface antibody response and levels in hepatitis B vaccinated children in diyala province, Iraq. IRAQI J COMMUNITY MED [serial online] 2020 [cited 2021 Nov 29];33:15-9. Available from: http://www.journalijcm.org/text.asp?2020/33/1/15/319643
| Introduction|| |
Like many other countries, Iraq was adopted the WHO's recommendation and introduced the recombinant Hepatitis B virus (HBV) vaccine for newly born in the Iraqi Expanded Program of Immunization (IEPI) since 1994. HBV infection is a worldwide leading cause of a wide spectrum of liver disease ranging from acute to chronic hepatitis, cirrhosis, and hepatocellular carcinoma., Infection with HBV in infancy or early childhood may lead to a high rate of chronic carriers (25%–90%), while it is markedly decreased during adulthood (5%–10%). In most endemic areas, infection occurs mainly during early childhood and mother-to-infant transmission accounts for approximately 50% of the chronic infection., Effective vaccines have been available for over 20 years, and vaccination has proved highly successful in reducing the disease burden, the development of the carrier state, and the HB-related morbidity and mortality in the countries where vaccination has been implemented.,
In Diyala province, an early seroepidemiological study of HBV infection conducted for the period from 1989 to 2002 found that the grand prevalence of HBsAg positivity rate among blood donors was 1.5%, and the highest positivity rate was among hemophilia patients (42.5%). Subsequent seroprevalence study during the period from 2003 to 2008 found a similar high HBsAg positivity rate with a significantly higher infection rate among male and the age group of 20–29 years. In a clinicoserological study on acute icteric patients, it was found that 75.8% of these patients were positive for different viral markers including 20.9% were positive for HBsAg, and 38.4% and 7.7% of those HBsAg-positive patients were also positive for anti-HBc IgM and anti-HDV antibody, respectively. Intrafamilial clustering was seems to be one of unique features of HBV infection in Diyala, as the overall prevalence of HBsAg among household contacts was 14.2%, suggesting that it may contribute for maintaining the endemicity of the disease in Diyala community. Other fascinating results were those reported the presence of a relatively high rate of occult HBV infection incriminating the occult HBV infection, at least in part, for the perpetuation of infection in the community. Surprisingly, even an outbreak of HBV infection was occurred in a rural district in 2004 which was linked to the exposure-prone practices carried out by private HCWs. Finally, a population-based survey for detection of HBV infection in 2013 found that the overall HBsAg positivity rate among general population was 0.65, while the anti-HBc IgM and total antibody positivity rates were 3.67% and 9.56%, respectively.
Different studies conducted to assess the efficacy of HBV vaccine through determination of anti-HBsAb titers had yielded variable protection rates.,,, In a previous study in Baghdad to evaluate HBV vaccine among children 1–10 years found that 77.2% of children received three primary vaccine doses had protective level of anti-HBs Ab. Finally, in a recent study in Diyala province, the HBV vaccine was proven to be efficacious in the majority of vaccinees Therefore, this study was designed to explore the response rate and titers of anti-HBs antibodies among children 1–14 years old immunized with HB vaccine in Baquba city Diyala province.
| Vaccinees and Methods|| |
This cross-sectional study was conducted in Baquba City, the center of Diyala province for the period July 20, 2016–March 20, 2017. A total of 452 HBV vaccinated children were enrolled randomly from those attending primary health-care centers. 247 (54.6%) were males and 205 (45.4%) were females, with an age range of 1–14 years. All were previously immunized with genetically engineered HBV vaccine (Euvax B, Korea), with a dose of 10 μg of HBsAg/0.5 ml (children vial) intramuscularly.
The durations (period of time in years elapsed since the last vaccine dose up to the time of sample collection) were extended from <1 to >4 years. Venous blood samples were collected aseptically; sera were separated and subjected for the detection of HBsAg, anti-HBs antibody titer, HBe Ag, and total antibody and anti-HBc total antibody using enzyme-linked immunosorbant assays (ACON, Foresight-USA). Further inclusion criteria were that the HBsAg, HBeAg, and anti-HBc total antibodies should be negative. According to the WHO criteria, HBV vaccinees were considered positive, only if they had ≥10.0 mIU of anti-HBs Ab/mL of their sera. A preconstructed questionnaire form was prepared including information of sociodemographic, health, and vaccination status.
The human privacy was respected by taken the participants or their parent's consent. Furthermore, this study was approved by the Ethical Committee in the College of Medicine-Diyala University. Statistical analysis was done using the Statistical Package for the Social Science (SPSS), version 23 (It is international software for statistical analysis, USA). P < 0.05 was considered statistically significant.
| Results|| |
The results showed that 342 of the vaccinated children were anti-HBs Ab positive with an overall positivity rate 75.66% (95% confidence interval for prevalence of anti-HBs Ab 71.5%–79.6%). They were grouped as positive according to the WHO criteria (HBV vaccinees were considered positive, only if they had ≥10.0 mIU of anti-HBs Ab/mL of their sera) the range of anti-HBs Ab titers among current participants was 10.1–673.4 mIU/ml, [Table 1].
The anti-HBs Ab positivity rate by duration since last dose of the vaccine stratified by the number of vaccine doses was shown in [Table 2]. The highest anti-HBs Ab positivity rate among 41 children administered 1 or 2 vaccine is among those with <1-year duration (80.0%), and the lowest positivity rate is among those with 4 years or more duration (33.3%). The difference is statistically significant (P = 0.043). Similarly, the mean anti-HBs Ab titer is highest among those children with <1-year duration (43.7 mIU/ml), while the least mean titer is among those with 4 years or more duration (16.6 mIU/ml). Nevertheless, the difference is statistically insignificant (P = 0.24). In addition, the means of anti-HBs Ab titer among the three categories are above the protective level (≥10 IU/ml), and that the overall anti-HBs Ab positivity rate (those with ≥10 IU/ml Ab titer) is 58.5%.
|Table 2: Anti-HBs Ab positivity rate and titer after 1-2 vaccine doses by duration|
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The highest anti-HBs Ab positivity rate among children administered three vaccine doses is among those after <1-year duration (91.3%), and the lowest positivity rate is among those with 4 years or more duration (56.3%). The difference is statistically significant (P = 0.003). However, the positivity rates of anti-HBs Ab among different categories after three vaccine doses are generally higher than those after one or two vaccine doses[Table 3]. The overall anti-HBs Ab positivity rate in this group of participants is 83.6% . The highest mean of anti-HBs Ab titer is among those children with <1-year duration (81.3 IU/ml), whereas the lowest mean titer is among those with 1–3-year duration (37.2 IU/ml). The difference is statistically insignificant (P = 0.2). Of note, the means of anti-HBs Ab titer among the three categories are above the protective level (≥10 IU/ml). It is also clear that the mean titers in the three categories are generally higher than its counterparts of those children administered one or two vaccine doses.
|Table 3: Anti-HBs Ab positivity rate and titer after 3 vaccine doses by duration|
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The highest anti-HBs Ab positivity rate among children administered four vaccine is among those children after <1 year (89.9%), and the lowest positivity rate is among those children after 4 years or more duration (86.0%). The difference is statistically significant (P = 0.004). It is also clear that the positivity rates among those children after 3 and 4 years or more are becoming higher compared to their counterpart after three vaccine doses. The overall anti-HBs Ab positivity rate in this group of children is 76.0% [Table 4]. On the other side, the highest mean anti-HBs Ab titer is among those children with <1-year duration (97.7 IU/ml), while the lowest titer is among those with 4 years and more (17.8 IU/ml). The difference is statistically significant (P < 0.001). Another worthy interpretation is that comparing to those received three vaccine doses [Table 4], the mean anti-HBs Ab titers are falling down rapidly after 1–3 years and 4 years and more (28.8 IU/ml and 17.8 IU/ml), respectively.
|Table 4: Anti-HBs Ab positivity rate and titer after 4 vaccine doses by duration|
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In [Table 5], although the anti-HBs Ab positivity rate among those children after 1–3 year duration is higher than those after <1 year and after 4 years and more duration (72.4%, 71.4% and 37.5%, respectively), the difference among the three categories is statistically insignificant (P = 0.15). Moreover, the positivity rates in the three categories after five vaccine doses are generally lower than that after three [Table 4] or four vaccine doses [Table 4]. Of note, the overall anti-HBs Ab positivity rate in this group of children is 67.7% [Table 4]. Similarly, the highest mean anti-HBs Ab titer is among those children with <1-year duration (55.0 IU/ml), while the lowest titer is among those with 4 years and more (12.3 IU/ml). The difference is statistically significant (P < 0.041). In this group of children, the overall mean anti-HBs Ab titers in the three categories are generally lower than those received three and four vaccine doses [Table 4], respectively.
|Table 5: Anti-HBs Ab positivity rate and titer after 5 vaccine doses by duration|
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| Discussion|| |
Like many other countries, Iraq was adopted the WHO's recommendation and introduced the recombinant HBV vaccine for newly born in the IEPI since 1994. Fortunately, countries of Eastern Mediterranean Region have made notable achievements, improving coverage from only 6% in 1992 to 83% in 2014. Member states adopted a hepatitis B control target in 2009 to reduce chronic HBV infection prevalence to <1% among children aged <5 years by 2015. The importance of the present study may be streaming from two roots; first, the relatively high prevalence of HBV infection, particularly the occult infection, as reported by the local epidemiological survey. Second, the urgent need for evaluation of HBV vaccination program as it is universally implemented since more than 20 years ago. The study design was arranged to be comprehensive in evaluating the efficacy of HBV vaccine and more importantly, all participants were negative for HBs Ag, HBe Ag, anti-HBc total antibodies, and anti-HBe total antibodies, to exclude the breakthrough HBV infection.
Based on the WHO criteria, the study found that overall positivity rate of protected children is 75.66%. The present results are much closer to previous study conducted in Baghdad, which reported that 77.2% of children received three primary vaccine doses. This result is also consistent with other studies from surrounding countries.,,,, Moreover, the protection rate obtained in this study is within the range of HBV vaccine protection rate worldwide, since upon reviewing meta-analytic studies published between 1987 and 2015 assessed the seroprotection among healthy newborns, children, adolescents, and adults, the overall median seroprotection rate was 98% (range 52%–100%)., Therefore, the current study is strongly support the notion that there is a universal consensus regarding the protection rates of HBV vaccine against HBV infection.
The worldwide evidences of the efficacy of the DNA recombinant HB vaccine certainly related to its unique technology of preparation, since it is the first genetically engineered vaccine., It is worth to mention that anti-HBs Ab-positive vaccinees in this study had a range of anti-HBs Ab titers (10.1–167,428 mIU/ml). Hence, the present study is in agreement with numerous studies worldwide., Logically, as the protection rate increased in the community, the infection rate should be dropdown, and this is what actually evident from cumulative studies worldwide.,,
The present study has emerged many important outcomes; first, after any number of vaccine doses, the anti-HBs Ab positivity rate was significantly higher after <1-year duration. Second, the anti-HBs Ab positivity rate was fading down as the duration increase, i.e., being the lowest after 4 years or more after any given number of doses. Third, the highest anti-HBs Ab positivity rate after 4 years or more was among those administered four vaccine doses (68% of those participants received 4 vaccine doses were still positive for anti-HBs Ab and protective against HBV infection after 14 years). Therefore, this study is highly recommended the vaccination schedule of three primary vaccine doses plus one booster dose and considered it as the ideal one. Hence, in this regard, the present results are compatible with previous study. Furthermore, it is worth to mention that the present results are in agreement with other studies in Egypt and Yemen, respectively,, and strongly support the notion that time since vaccination and a low peak response were the strongest risk factors for HBV infections.
The effect of duration after one or two, three, four, and five vaccine doses was found to have multioutcomes: first, regardless the number of vaccine doses, the mean anti-HBs Ab titer was higher as the duration since last vaccine doses was shorter (<1 year), and thereafter it decline gradually as the duration prolonged (4 and more years), affirming that as the duration since last vaccine dose is shorter as the antibody titer is higher and vice versa. Second, again regardless the number of vaccine doses, the mean anti-HBs Ab titers after different categories of duration were never below the protective levels (≥10 IU/ml), indicating the efficaciousness of the vaccine in provoking high and prolonged antibody titer. Third, the highest anti-HBs Ab titer was after <1-year duration among those administered 4 vaccine doses (97.7%, P < 0.001). However, surprisingly, the mean titer of anti-HBs Ab was dropped down rapidly after the fifth vaccine dose, in all categories of duration, suggesting that a vaccination schedule of three primary doses at infancy (0, 2, and 4 month schedule) followed by fourth booster dose (18 months) is the perfect schedule as the titer of anti-HBs Ab is concern. Similar results have been reported by other studies.,, More precisely, the present study is totally consistent with that of La Fauci et al., (2016) who affirm the importance of recommend anti-HBV vaccination at a young age, ideally during childhood in accordance with the national vaccination policy. These facts are also reported by many other studies.,, Moreover, it has been found that the percentage of memory CD4 + T-cells secreting interferon-gamma, and those secreting interleukin-4 were higher among participants with serum anti-HBs >100 mIU/ml than those having <10 mIU/ml or absent. More interestingly, in vaccinees with anti-HBs Ab titer <10 IU/ml after complete primary vaccine at infancy, the immune effect of a three dose booster revaccination is good, and the booster-induced immune response was correlated with the prebooster titer, indicating the need for a course of booster vaccination. However, there are other studies denied the requirement of booster vaccine dose for children under 15 years old,,, or till the age of 16 years.
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| References|| |
Liang TJ. Hepatitis B: The virus and disease. Hepatology 2009;49 suppl: s 13- 21.
Te HS, Jensen DM. Epidemiology of hepatitis B and C viruses: A global overview. Clin Liver Dis 2010;14:1-21.
Chang MH. Hepatitis B virus infection. Semin Fetal Neonatal Med 2007;12:160-7.
Whittaker G, Herrera JL. Hepatitis B in pregnancy. South Med J 2014;107:195-200.
Michel ML, Tiollais P. Hepatitis B vaccines: Protective efficacy and therapeutic potential. Pathol Biol (Paris) 2010;58:288-95.
Romano L, Paladini S, Galli C, Raimondo G, Pollicino T, Zanetti AR. Hepatitis B vaccination. Hum Vaccin Immunother 2015;11:53-7.
Hasan AS, Omer AR, Al-Mashhadani JI. Seroepidemiological study of hepatitis B virus infection among blood donors and risky groups in Diyala. Iraqi J Commun Med 2006;19:14-8.
Al-Jebori AS, Hasan AS, Al-Duliami AA. Seroprevalence of hepatitis B and hepatitis C virus infections in Diyala province during. Diyala J Pure Sci 2010;6:292-302.
Hasan AS, Al-Duliami BN, Jabar FA. Clinical and serological markers of acute viral hepatitis in Diyala. Iraqi J Commun Med 2005;18:355-60.
Hasan AS. Intrafamilial clustering of HBV infection. Iraqi J Commun Med 2005;18:134-9.
Hasan AS. Prevalence of antibodies to Hepatitis B virus antigens and occult Hepatitis B virus infection in blood donors. Diyala J Med 2012;3:57-61.
Hasan AS. Outbreak of hepatitis B virus infection in a rural community in Diyala. J Diyala 2004;18:45-52.
Al-Taie WS, Ali EA, Hasan AS, Noaman NG, Al-Jobori FA, Hithaf NF, et al
. Seroepidemiology of hepatitis B and hepatitis C virus infections in Diyala province: A population based survey. Int J Curr Microbiol Appl Sci 2014;3:449-60.
Elian F, Shubair M. Evaluation of the efficacy of hepatitis B vaccine in different age groups of immunized children in Gaza strip. Islamic Univer J 2006;14:91-103.
Eldesoky A, Mosaad Y, Zakria Y, Hamdy S. Protective immunity after hepatitis B vaccination. Arab J Gastroenterol 2009;10:68-71.
Hashemi SA, Moghadmi M, Lankarani KB, Aiborzi A, Mahbudi A. The efficacy of hepatitis B vaccination among school children in South Iran. Iranian Red Cres Med J 2010;12:45-8.
Shamsizadeh A, Makvandi M, Shoshtari G. Prevalence of anti-hepatitis B surface antibody among children in Ahvaz, Iran, five years after vaccination. Jundishapur J Microbiol 2011;4:49-54.
Al-Thwani AN, Al-Rashed NA, Omer AR. Evaluation of hepatitis B virus vaccination among children in Baghdad city. Iraqi J Biotech 2008;7:198-209.
Hasan AS, Mustaf MM. The efficacy of hepatitis B vaccine among children in Baquba-Diyala province. Iraqi J Commun Med 2018;30:176-81.
Allison RD, Teleb N, Al Awaidy S, Ashmony H, Alexander JP, Patel MK. Hepatitis B control among children in the eastern mediterranean region of the world health organization. Vaccine 2016;34:2403-9.
Makhlouf NA, Farghaly AM, Zaky S, Rashed HA, Abu Faddan NH, Sayed D, et al.
The efficacy of hepatitis B vaccination program in upper Egypt: Flow cytometry and the evaluation of long term immunogenicity. J Med Virol 2016;88:1567-75.
Schillie SF, Murphy TV. Seroprotection after recombinant hepatitis B vaccination among newborn infants: A review. Vaccine 2013;31:2506-16.
Kao JH. Hepatitis B vaccination and prevention of hepatocellular carcinoma. Best Pract Res Clin Gastroenterol 2015;29:907-17.
Abara WE, Collier MG, Teshale EH. Impact of universal infant hepatitis B vaccination in the US-affiliated Pacific Islands. Vaccine 2017;35:997-1000.
Jamebozorgi BM, Keshavarz J, Nemati M, Hossainabad MS, Rezayati MT, Ghaderi NM, et al
. The persistence of anti-HBs antibody and anamnestic response 20 years after primary vaccination with recombinant hepatitis B vaccine at infancy. Hum Vaccin Immunother 2014;10:3731-6.
Alfaleh F, Alshehri S, Alansari S, Aljeffri M, Almazrou Y, Shaffi A, et al
. Long-term protection of hepatitis B vaccine 18 years after vaccination. J Infect 2008;57:404-9.
Mendy M, Peterson I, Hossin S, Peto T, Jobarteh ML, Barry JA, et al.
Observational study of vaccine efficacy 24 years after the start of hepatitis B vaccination in two Gambian villages: No need for a booster dose. PLoS One 2013;8:e58029.
Zanetti A, Parlato A, Romanò L, Desole MG, Ferrera G, Giurdanella F, et al
. Challenge with a hepatitis B vaccine in two cohorts of 4-7-year-old children primed with hexavalent vaccines: An open-label, randomised trial in Italy. Vaccine 2012;30:5770-5.
Alssamei FA, Al-Sonboli NA, Alkumaim FA, Alsayaad NS, 'Al-Ahdal MS, Higazi TB, et al
. Assessment of immunization to hepatitis B vaccine among children under five years in rural areas of taiz, yemen. Hepat Res Treat 2017;213.
La Fauci V, Riso R, Facciola A, Ceccio C, Lo Giudice D, Calimeri S, et al
. Response to anti-HBV vaccine and 10-year follow-up of antibody levels in healthcare workers. Public Health 2016;139:198-202.
Teoharov P, Kevorkyan A, Petrova N, Baltadzhiev I, Van Damme P. Immune memory and immune response in children from Bulgaria 5-15 years after primary hepatitis B vaccination. Pediatr Infect Dis J 2013;32:51-3.
Zanetti AR, Romano L, Giambi C, Pavan A, Carnelli V, Baitelli G, et al
. Hepatitis B immune memory in children primed with hexavalent vaccines and given monovalent booster vaccines: An open-label, randomised, controlled, multicentre study. Lancet Infect Dis 2010;10:755-61.
Chang MH. Impact of hepatitis B vaccination on hepatitis B disease and nucleic acid testing in high-prevalence populations. J Clin Virol 2006;36 Suppl 1:S45-50.
Sami SM, Salama II, Abdel-Latif GA, El Etreby LA, Metwally AI, Abd El Haliem NF. Hepatitis B Seroprotection and the Response to a challenging dose among vaccinated children in red sea governorate. Open Access Maced J Med 2016;4:219-25.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]