https://orcid.org/0000-0003-1467-2724
Figures
Abstract
Background
Hepatitis B vaccination is recommended for all children at birth within 24 hours or during childhood.
Objective
This study was aimed to evaluate protective efficacy of hepatitis B vaccine and estimate the sero-prevalence of hepatitis B virus infection among vaccinated children.
Materials and methods
A community-based cross-sectional study was conducted from March, 2021 to October, 2021 in Debre Markos town. A simple random sampling technique was used to select 165 fully vaccinated children aged 5–12 years old. A serum sample was used to determine hepatitis B surface antigen (HBsAg), anti-hepatitis B core antibody (anti-HBc), anti-hepatitis B surface antibody titer (anti-HBs) using ELISA.
Results
The seroprevalence of HBsAg and anti-HBc anti-body was found to be 4.2% and 4.8% respectively. Of 165 fully vaccinated children, 129 (78.2%) had anti-HBs titer ≥ 10 mIU/ml. Among 129 sero-protected children, 76 (58.9%) were hypo-responders whereas the rest 53 (41.1%) were good responders. Those children within the age group of 5–7 years were 2.9 times (AOR: 2.873, 95% CI: 1.156, 7.141) (P<0.023) more likely to respond to HBV vaccine. Multivariate logistic regression revealed that children who were born from HBV positive mothers (AOR 3.917, 95% CI: 1.456, 5.365, P<0.027) and those who had history of injectable medications (AOR 9.232, 95% CI: 1.503, 11.697, P<0.016) were more likely to be HBsAg positive. Children who had history of hospital admission (AOR 6.973, 95% CI: 1.495, 8.530, P<0.013) were more likely to be anti-HBcAb positive.
Citation: Adugna A, Demeke G, Toru M, Tsehay D, Esmael A, Mihret A, et al. (2023) Reduced protective efficacy of hepatitis B vaccine among fully vaccinated children in Ethiopia. PLoS ONE 18(7): e0288355. https://doi.org/10.1371/journal.pone.0288355
Editor: Gizat Almaw, Animal Health Institute, Ethiopia, ETHIOPIA
Received: February 20, 2023; Accepted: June 25, 2023; Published: July 7, 2023
Copyright: © 2023 Adugna et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All relevant datasets used and/or analysed during the current study are within the paper.
Funding: The author(s) received no specific funding for this work.
Competing interests: The authors have declared that no competing interests exist.
Introduction
According to the World Health Organization, one-third of the global population has serological markers of active HBV infection. More than 350 million are chronic carriers with HBV [1–3] and 1.2 million die annually from liver cancer [4, 5]. Africa has the second biggest quantity of persistent HBV carriers next to Asia and considered as a region of extraordinarily endemicity [6]. With 60 million people who are chronically infected due to perinatal transmission [7, 8]. Vertical transmission to neonates results in persistent infection in more than 90% of children [9]. Babies born from mothers with HBsAg and HBeAg markers have 90% a probability of infection [10], and 15 to 25% may die from hepatocellular carcinoma in their life time [11]. In Ethiopia according to the previous seroepidemiological survey of Addis Ababa, 7% of individuals had HBsAg, and 70% had at least one HBV marker [12].
Nowadays, about 194 countries have performed HBV vaccination program for infants [13]. After complete vaccination the non-responder, hypo-responder, and good- responder may exist with an anti-HBs titer less than 10 mIU/ml, between 10–100 mIU/ml, and greater than100 mIU/ml respectively [14, 15]. In Ethiopia, HBV vaccination is part of the pentavalent [DPT-HiB-HepB] vaccine which has been introduced to the national Expanded Program for Immunization (EPI) in 2007. According to EPI schedules, HBV vaccine is given at 6, 10, and 14 weeks of age after delivery [16]. However, the vaccine is not always protective against HBV due to different reasons including viral, host immune and genetics, socio demographic, cultural and programmatic factors [17, 18].
Due to those factors, 15–50% of the vaccinated children may have undetetctable concentrations of anti-hepatitis B surface antibody after 5–15 years of vaccination and 10% still could be susceptible to HBV infection [19, 20]. In Ethiopia, pentavalent vaccine coverage is increasing and has reached to 90%. However, studies still show susceptibility to HBV infection despite high vaccine coverage [21]. There is limited data on seroprevalence and vaccine efficacy among fully vaccinated children in Ethiopia. Thus; this study aimed to estimate seroprevalence of HBV infection, evaluate the protective efficacy of HB vaccine, and identify associated factors for reduced vaccine efficacy among fully vaccinated children in Debre Markos town, Northwest Ethiopia.
Materials and methods
Study design, period and setting
A community-based cross-sectional study was conducted among hepatitis B vaccinated children in Debre Markos town, Amhara regional state, Northwest Ethiopia, from March 2021 to October 2021. Based on the report from East Gojjam Zone administrative office, the number of children < 15 years was 18,345 of which the number of girls and boys were 10,020 and 8,325 respectively.
Inclusion an exclusion criteria
All hepatitis B fully vaccinated children whose ages were from 5–12 years and live in Debre Markos town were considered as source population and those hepatitis B fully vaccinated children whose ages were from 5–12 years, who fulfilled
eligibility criteria and were found at home during the data collection period were taken as study population. All hepatitis B vaccinated children who volunteered to participate in the study, whose parents or legal guardians volunteered to give assent and those children who took full dose of hepatitis B vaccine [as evidenced by showing vaccination card] were included in the study. Those study participants who did not complete the full dose of the hepatitis B vaccine, who or whose parents were severely sick (as unable to give assent on behalf of their children) during the data collection period and could not give blood samples were excluded from the study.
Sample size determination and sampling techniques
The sample size was calculated using single population proportion formula by taking 89% (0.89) of the prevalence in vaccine response derived from a study done in Addis Ababa, Ethiopia [22]. By considering a prevalence of 89%, 5% margin of error, 95% confidence interval and 10% non-response rate
n = (1.96)2/ (0.05)2 *0.89*0.11 = 150
Where
n = sample
Z = 1.96 at 95% C.I
p = prevalence = 0.89
q = 1-p = 1–0.89 = 0.11
d = margin of error = 0.05
Non-response rate = 10% of 150 = 10%*150 = 10 ∕ 100*150 = 15
Therefore, the final sample size (n) was calculated as n = 150+15 = 165.
Simple random sampling technique was used to recruit the study participants from March, 2021 to October, 2021 until the required sample size was obtained among hepatitis B vaccinated children at the selected kebeles in Debre Markos town. Debre Markos Town has 11 kebeles out of them 5 kebeles (45%) were selected by lottery method so as to keep representativeness. Then total sample size was allocated proportionally to each kebeles depending on the total number of vaccinated children from 5 to 12 years of age. One child was selected randomly (lottery method) from those households having two and more children.
Data collection procedures
After the participant’s family agreed to take part in the study and signed on informed written assent form, socio-demographic characteristics and associated factors data were collected by using a pretested semi-structured questionnaire. Each child’s weight and height were measured and body mass index was calculated in percentile. Authors were blind and had no information about the study participants during or after data collection.
Laboratory procedures
Five ml of venous blood was aseptically collected from each study participant from March, 3/25/2021 to October, 10/5/2021 and transported to Debre Markos blood bank laboratory within one hour. Serum was then separated by centrifugation, and stored at -20°C until transported to Armauer Hansen Research Institute (AHRI) for analysis. Serum level of HBsAg, anti-HBcAb, and anti-HBs were determined using sandwich Enzyme-Linked Immunosorbent Assay (ELISA), where antigens/monoclonal antibodies were used both for capture and detection [BIO-RAD, Monolisa, France]. For the determination of anti-HBs level, quantitative type of sandwich ELISA was used. The test kits have a clamed sensitivity of 100% and specificity of 99.28%. Each test procedure was performed according to the manufacturer’s instruction [https://www.bio-rad.com/].
Data processing and analysis
After checking the data completeness, data were entered into- Epidata software version 3.1 and exported to SPSS software version 25 for analysis. The results were presented as tables and figure. Binary logistic regression was used to show the association between dependent and independent variables. In bivariate logistic regression, a p-value <0.25 were candidates for multivariate logistic regression. Multivariate logistic regression was used in terms of adjusted odds ratio (AOR) with 95% confidence intervals and a p-value < 0.05 was considered statistically significant.
Ethical consideration and consent to participate.
This study was ethically approved by the research and ethical committee of College of Health Science, Debre Markos University with reference number (HSC/R/C/Ser/PG/CO/277/12/13). It was performed in accordance with the relevant guidelines and regulations. Written informed assent was taken from the participant’s guardian and consent was obtained from all participants.
Results
Socio-demographic characteristics
A total of 165 children with the age range of 5–12 years participated in this study. The median age of the study participants was 8.00 ± 2.58. About 45.5% of the study participants were found within the age group of 5–7 years and the majority of them 89/165 (53.9%) were males. One hundred and fifty (90.9%) of participants were from urban area (Table 1).
Sero-positivity of HBsAg and anti-HBc
The overall positivity of HBsAg among all study participants was 7/165 (4.2%) (95% CI: 1.0–5.0). Of seven children who were positive for HBsAg, 6/7 (85.7%) of them were males. Furthermore, the prevalence of HBsAg positivity in 5–7 years children was 5/7 (71.4%). The overall prevalence of anti-HBc antibodies among the study participants was 8/165 (4.8%) (95% CI: 2.0–6.0). From the total prevalence of anti-HBc antibodies, 4/8 (50.0%) was from female participants. About 4/8 (50.0) % anti-HBc antibody prevalence was from children whose ages were found within the age group of ≥ 11 years (Table 2).
Distribution of HBsAg and anti-HBcAb
Of the total prevalence of HBsAg, about 14.3% was from children who were born from mothers with previous history of HBV infection. The prevalence of HBsAg among obese children was 2/7(28.6%). The prevalence of anti-HBc antibody among children with previous history of injectable medication was 1/8(12.5%) (Table 3).
Seroprotection level of HBV vaccine
Among vaccinated children, 129/165 (78.2%) (95% CI: 72.0–85.0%) of them had anti-HBs titer ≥ 10 mIU/ml. Out of this, 76 (58.9%) were hypo-responders (with anti-HBs titer of 10–100 mIU/ml) whereas the rest 53(41.1%) were good responders (with anti-HBs titer of >100).
Factors associated with HBsAg and anti-HBcAb positivity
In multivariable logistic regression, children born to mothers with HBV infection were 3.9 times (AOR: 3.917, 95% CI: 1.456, 5.365) (P<0.027) more likely to be HBsAg seropositive as compared to those who were born to mothers without previous history of HBV infection. Children who had previous history of injectable medications were 9 times (AOR: 9.232, 95% CI: 1.503, 11.697) (P<0.016) more likely to be HBsAg positive than those without previous history of injectable medications (Table 4). Moreover, children who had previous history of hospital admission were 6.9 times (AOR: 6.973, 95% CI: 1.495, 8.530) (P<0.013) more likely to be anti-HBc antibody positive as compared to their counterparts.
Discussion
The overall sero-positivity of HBsAg among vaccinated children from 5–12 years was 4.2% (95% CI: 1.0–5.0). This result tells us the study area is found under the category of intermediate endemicity for HBV infection [23]. This finding is consistent with similar studies conducted in Hawassa (4.4%), Gondar (4.2%), Jimma (2.1%), and Harar (1.1%), [24–27]. It is also comparable with other studies conducted in low and high income countries [28–35]. However, the seroprevalence of HBsAg in the present study is relatively higher than the results reported among vaccinated children from Addis Ababa (0.4%) [36], Uzbekistan-Japan (0.8%) [37], Iran (0.6%) [38], Italy (0.6%) [39], Egypt (0.6%) [40], and Dakahleya-Egypt (0.4%) [41] and lower than the result reported from china (20.49%) [42]. These variation may be due to difference in host genetic factors, ethnicity, cultural practice, socioeconomic status, family history of HBV and structural difference including clinical practice, immunization coverage of HBV vaccine, inclusion of birth dose of HBV vaccine within 24 hours, and type of laboratory method used for HBsAg detection. According to our study, males were more susceptible to HBV infection (6.7 vs 1.3%) than females.
Previous history of child’s mother for HBV infection and child’s injectable medications were identified as important determinants for HBV infection. This is in accordance with the findings reported from Hawassa [24]. This might be due to vertical transmission of HBV infection for those children born to HBV infected mothers and there was unsafe utilization of medical equipment during therapeutic injections [43, 44].
The overall seroprevalence of anti-HBc positivity in this study was 4.8% (95% CI: 2.0–6.0) which is comparable with previous results reported from Addis Ababa (5.6%) [36] and Gondar (6.3%) [25] and other similar studies elsewhere [31, 34, 38, 45, 46]. On the other hand, the current finding of anti-HBc seroprevalence is relatively higher than the previous findings reported from Jimma (1.1%) [26], Niakhar-Senegal (1.5%) [35], and Dakahleya-Egypt (0.11%) [41]. In contrast, higher prevalence were reported from Hawassa city (19.5%) [24] and other country; Gambian Villages (10.2%) [33]. This variations may be difference in; geographical area, age range of study participants, vaccination rate of HBV vaccine, income level, socio cultural practices, and inclusion of birth dose of HBV vaccine within 24 hours. In this study, children who had history of hospital admission were more likely to be anti-HBc antibody positive. This might be due to the horizontal transmission of the virus from the hospital environment.
The seroprotection level of hepatitis B vaccine among 5–12 years children in this study was 78.2% (95% CI: 72.0–85.0%) which is low since safe and effective HBV vaccine has a protection level of 98 to100% according to WHO report [47]. This figure is in line with results reported from Italy (79.2%) [38] and Yemen (72.2%) [48], and relatively lower than studies conducted in China (88.3%) [45], Cameroon (97.5%) [49], and Senegal (87%) [50] and higher than the findings reported from India (68%) [51], Burkina Faso (61.6%) [52], Egypt (57.7%) [41], and Ethiopia which ranges from 32.2–58.4% [25, 36, 53]. The disparity might be due to; differences in cold chain system of the vaccine, differences in nutritional status, age groups, and different extent of exposure to natural boosters.
The protective levels of HBV vaccine in this study seemed higher among females than males (53.5 vs 46.5%) though not statistically significant and is in agreement with the study conducted in Yemen (75.7% vs 68.4%) [48], and Addis Abeba (54.7% vs 53.9%) [36] and could be related to a stronger innate, humoral, and cell-mediated immune responses to viral vaccines in females than males [54].The protective levels of HBV vaccine (≥10 mIU/ml anti-HBs antibody) were decreased from 49.6 to 29.5.6 to 20.9% as the age of the child increased from age group 5–7 to 8–10 and ≥ 11 years respectively which is similar with figures reported from Kurdistan Region-Iraq [55], and Addis Ababa [36]. These differences in the age groups were statistically significant in the present study and children who were found within the age group of 5–7 years were 2.9 times more likely to respond to HBV vaccine as compared to those whose ages were in 8–10 and ≥ 11 years and this is due to the concentration of vaccine-induced anti-HBs levels in the vaccinated children will decline as the time of vaccination increases [56].
In conclusions, the seroprevalence of hepatitis B infection was intermediate among vaccinated children in the study area. Mother’s HBV status was significantly associated with HBsAg positivity. There should be regular early screening of vaccinated children for HBV infection. The protective efficacy of HBV vaccine in the present study was low. Thus, determination of levels of anti-HBs antibodies should be done, and then booster doses must be given for non-responders to increase the concentration of anti-HBs levels and prevent waning immunity.
Limitations of the study: Even though this study has paramount public health importance, it was done with small sample size. As a result, it is difficult to infer seroprevalence of HBV infection and seroprotection of HBV vaccine to the entire population with this sample size.
Acknowledgments
We acknowledge DebreMarkos town health office, health extension workers and study participants.
References
- 1. Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. The lancet 2012, 380(9859):2095–2128. pmid:23245604
- 2. Rapti I, Hadziyannis S: Risk for hepatocellular carcinoma in the course of chronic hepatitis B virus infection and the protective effect of therapy with nucleos (t) ide analogues. World journal of hepatology 2015, 7(8):1064. pmid:26052395
- 3. Hu K-Q, Pan CQ, Goodwin D: Barriers to screening for hepatitis B virus infection in Asian Americans. Digestive diseases and sciences 2011, 56(11):3163–3171. pmid:21861105
- 4. Abdulla SA, Abdulla ZA: Effect of an educational program on nurses’ knowledge and practices toward Hepatitis B virus in emergency hospitals in Erbil City. Zanco Journal of Medical Sciences (Zanco J Med Sci) 2014, 18(1):618_624–618_624.
- 5. Negero A, Sisay Z, Medhin G: Prevalence of Hepatitis B surface antigen (HBsAg) among visitors of Shashemene General Hospital voluntary counseling and testing center. BMC research notes 2011, 4(1):1–5. pmid:21303563
- 6. Kim H, Shin AR, Chung HH, Kim MK, Lee JS, Shim J-J, et al. Recent trends in hepatitis B virus infection in the general Korean population. The Korean journal of internal medicine 2013, 28(4):413. pmid:23864799
- 7. Wild CP, Hall AJ: Primary prevention of hepatocellular carcinoma in developing countries. Mutation Research/Reviews in Mutation Research 2000, 462(2–3):381–393. pmid:10767647
- 8. Sylla BS, Wild CP: A million africans a year dying from cancer by 2030: what can cancer research and control offer to the continent? International journal of cancer 2012, 130(2):245–250. pmid:21796634
- 9. Ganem D, Prince AM: Hepatitis B virus infection—natural history and clinical consequences. New England Journal of Medicine 2004, 350(11):1118–1129. pmid:15014185
- 10.
Chang M-H: Hepatitis B virus infection. In: Seminars in fetal and neonatal medicine: 2007: Elsevier; 2007: 160–167.
- 11. Lam N-C, Gotsch PB, Langan RC: Caring for pregnant women and newborns with hepatitis B or C. American family physician 2010, 82(10):1225–1229. pmid:21121533
- 12. Abebe A, Nokes D, Dejene A, Enquselassie F, Messele T, Cutts F: Seroepidemiology of hepatitis B virus in Addis Ababa, Ethiopia: transmission patterns and vaccine control. Epidemiology & Infection 2003, 131(1):757–770.
- 13.
WHO:https://immunizationdata.who.int/pages/coverage/hepb.html?code=global & group=who_regions & antigen=hepb_bdall&year=accessed on 12/14/2022.
- 14. Tong NKC, Beran J, Kee SA, Miguel JL, SanNchez C, Bayas JM, et al. Immunogenicity and safety of an adjuvanted hepatitis B vaccine in pre-hemodialysis and hemodialysis patients. Kidney international 2005, 68(5):2298–2303. pmid:16221232
- 15. Cooper CL, Davis HL, Angel JB, Morris ML, Elfer SM, Seguin I, et al. CPG 7909 adjuvant improves hepatitis B virus vaccine seroprotection in antiretroviral-treated HIV-infected adults. Aids 2005, 19(14):1473–1479. pmid:16135900
- 16.
MOH:https://www.moh.gov.et/site/initiatives-4-col/expanded program_on immunization accessed on 12/14/2022.
- 17. Huang M-L, Liao W-L, Ho M-S: HBV serological markers of vaccinated children in remote areas of Taiwan: emphasis on factors contributing to vaccine failure. Vaccine 2007, 25(34):6326–6333. pmid:17629600
- 18. Bogale HA, Amhare AF, Bogale AA: Assessment of factors affecting vaccine cold chain management practice in public health institutions in east Gojam zone of Amhara region. BMC public health 2019, 19(1):1–6.
- 19. Leuridan E, Van Damme P: Hepatitis B and the need for a booster dose. Clinical Infectious Diseases 2011, 53(1):68–75. pmid:21653306
- 20. Yonghao G, Jin X, Jun L, Pumei D, Ying Y, Xiuhong F, et al. An epidemiological serosurvey of hepatitis B virus shows evidence of declining prevalence due to hepatitis B vaccination in central China. International Journal of Infectious Diseases 2015, 40:75–80. pmid:26456567
- 21.
WHO:https://immunizationdata.who.int/pages/coverage/HEPB.html?Code=Eth&antigen=hepb3&year, accessed on 12/14/ 2022.
- 22. Tsega E, Horton J, Nordenfelt E, Hansson B, Tafesse B, Wolde-Hawariat G, et al. Antibody levels in Ethiopian children five years after vaccination with two different doses of hepatitis B vaccine: Is there a need for booster vaccine? Canadian journal of gastroenterology 1998, 12(1):57–60. pmid:9544413
- 23. Alter MJ: Epidemiology of hepatitis B in Europe and worldwide. Journal of hepatology 2003, 39:64–69. pmid:14708680
- 24. Argaw B, Mihret A, Aseffa A, Tarekegne A, Hussen S, Wachamo D, et al. Sero-prevalence of hepatitis B virus markers and associated factors among children in Hawassa City, southern Ethiopia. BMC infectious diseases 2020, 20(1):1–7. pmid:32698884
- 25. Ayalew G: Seroprotection level of Hepatitis B vaccine among children living in Gondar town, Northwest Ethiopia. Ethiop med j(Online) 2019:139–146.
- 26. Kedir R, Taye BD, Kassa T, Teshager L, Aseffa A, Howe R, et al. sero-prevalence of hepatitis B virus infection and sero-protection of hepatitis B vaccine among children in jimma town, southwest Ethiopia. Ethiopian medical journal 2019.
- 27. Usman S, Seyoum B, Mengiste B, Tarekegne A, Bekele F, Mihret A, et al. Serum levels of anti-hepatitis B surface antigen and HBV associated factors among vaccinated and unvaccinated children in Harar, eastern Ethiopia: A community-based study. Ethiopian medical journal 2019.
- 28. Børresen ML, Koch A, Biggar RJ, Ladefoged K, Melbye M, Wohlfahrt J, et al. Effectiveness of the targeted hepatitis B vaccination program in Greenland. American journal of public health 2012, 102(2):277–284. pmid:21940914
- 29. Nguyen TH, Vu MH, Nguyen VC, Nguyen LH, Toda K, Nguyen TN, et al. A reduction in chronic hepatitis B virus infection prevalence among children in Vietnam demonstrates the importance of vaccination. Vaccine 2014, 32(2):217–222. pmid:24284410
- 30. Odusanya O, Alufohai F, Meurice F, Wellens R, Weil J, Ahonkhai V: Prevalence of hepatitis B surface antigen in vaccinated children and controls in rural Nigeria. International Journal of Infectious Diseases 2005, 9(3):139–143. pmid:15840454
- 31. Sami SM, Salama II, Hassanin AI, Hamid ATA, Abd El Haliem NF, Ibrahim NA: Hepatitis B infection, seroprotection, and anamnestic response among children vaccinated during infancy in Beni-Suef, Egypt. Medical Research Journal 2014, 13(2):86–92.
- 32. Dassah S, Sakyi SA, Frempong MT, Luuse AT, Ephraim RK, Anto EO, et al. Seroconversion of hepatitis B vaccine in young children in the Kassena Nankana district of Ghana: a cross-sectional study. PloS one 2015, 10(12):e0145209. pmid:26716979
- 33. Mendy M, Peterson I, Hossin S, Peto T, Jobarteh ML, Jeng-Barry A, 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(3):e58029. pmid:23533578
- 34. Chongsrisawat V, Yoocharoen P, Theamboonlers A, Tharmaphornpilas P, Warinsathien P, Sinlaparatsamee S, et al. Hepatitis B seroprevalence in Thailand: 12 years after hepatitis B vaccine integration into the national expanded programme on immunization. Tropical Medicine & International Health 2006, 11(10):1496–1502. pmid:17002723
- 35. Perieres L, Coste M, Ndiour S, Halfon P, Sokhna C, Ba E, et al. Hepatitis B vaccination status and vaccine immune response among children in rural Senegal. European Journal of Public Health 2019, 29(Supplement_4):ckz185. 592.
- 36. Teshome S, Biazin H, Tarekegne A, Abebe T, Bekele F, Mihret A, et al. Antibody response against hepatitis B virus after vaccination and seroprevalence of HBV in children in Addis Ababa, Ethiopia. Ethiopian medical journal 2019.
- 37. Avazova D, Kurbanov F, Tanaka Y, Sugiyama M, Radchenko I, Ruziev D, et al. Hepatitis B virus transmission pattern and vaccination efficiency in Uzbekistan. Journal of medical virology 2008, 80(2):217–224. pmid:18098129
- 38. Hashemi S, Moghadami M, BAGHERI LK, Alborzi A, Mahboudi A: The efficacy of hepatitis B vaccination among school age children in Southern Iran. 2010.
- 39. Mele A, Tancredi F, Romanò L, Giuseppone A, Colucci M, Sangiuolo A, et al. Effectiveness of hepatitis B vaccination in babies born to hepatitis B surface antigen-positive mothers in Italy. The Journal of infectious diseases 2001, 184(7):905–908. pmid:11509998
- 40. Shatat H, Kotkat A, Farghaly A, Omar S, Zayton S: A study of hepatitis B vaccine efficacy 10 years after compulsory vaccination in Egypt. The Journal of the Egyptian Public Health Association 2005, 80(5–6):495–508. pmid:17187739
- 41. Hamid ATA, Said ZN: Persistence of protection to hepatitis B vaccine and response to booster dose among children and adolescents in Dakahleya-Egypt. Egyptian Journal of Immunology 2014, 21(1):13–26. pmid:25204041
- 42. Li X, Xu Y, Dong Y, Yang X, Ye B, Wang Y, et al. Monitoring the efficacy of infant hepatitis B vaccination and revaccination in 0-to 8-year-old children: Protective anti-HBs levels and cellular immune responses. Vaccine 2018, 36(18):2442–2449. pmid:29588118
- 43. Khan AJ, Luby SP, Fikree F, Karim A, Obaid S, Dellawala S, et al. Unsafe injections and the transmission of hepatitis B and C in a periurban community in Pakistan. Bulletin of the World Health Organization 2000, 78:956–963. pmid:10994278
- 44. Ma L, Alla NR, Li X, Mynbaev OA, Shi Z: Mother‐to‐child transmission of HBV: review of current clinical management and prevention strategies. Reviews in medical virology 2014, 24(6):396–406. pmid:24956038
- 45. Fagundes GD, Tabalipa FdO, Silva Jd: Antibody levels in children after 10 years of vaccination against hepatitis B: a brazilian community-based study. Revista da Sociedade Brasileira de Medicina Tropical 2012, 45:260–262. pmid:22535004
- 46. Mele A, Tancredi F, Romano L, Giuseppone A, Colucci M, Sangiuolo A, et al. Effectiveness of hepatitis B vaccination in babies born to hepatitis B surface antigen-positive mothers in Italy. The Journal of infectious diseases 2001, 184(7):905–908. pmid:11509998
- 47.
WHO:https://www.who.int/news-room/fact-sheets/detail/hepatitis-b accessed on 12/10/2022.
- 48. 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. Hepatitis research and treatment 2017, 2017. pmid:28367327
- 49. Anutebeh EN, Tatah L, Feteh VF, Aroke D, Assob JC, Choukem SP: Immune response to hepatitis B vaccine following complete immunization of children attending two regional hospitals in the Southwest region of Cameroon: a cross sectional study. BMC Infectious Diseases 2021, 21(1):1–8.
- 50. Lee KH, Shim KS, Lim IS, Chae SA, Yun SW, Lee NM, et al. Changes in hepatitis B virus antibody titers over time among children: a single center study from 2012 to 2015 in an urban of South Korea. BMC pediatrics 2017, 17(1):1–8.
- 51. Alexander AM, Prasad JH, Abraham P, Fletcher J, Muliyil J, Balraj V: Evaluation of a programme for prevention of vertical transmission of hepatitis B in a rural block in southern India. The Indian journal of medical research 2013, 137(2):356. pmid:23563380
- 52. Sanou AM, Ilboudo AK, Meda CZ, Togozia A, Coulibaly A, Cisse A, et al. Hepatitis B vaccination in Burkina Faso: prevalence of HBsAg carriage and immune response in children in the western region. The Journal of Infection in Developing Countries 2018, 12(11):1002–1008. pmid:32012131
- 53. Kedir R, Taye BD, Kassa T, Teshager L, Aseffa A, Howe R, et al. Seroprevalence of hepatitis B virus infection and seroprotection of hepatitis B vaccine among children in Jimma town, southwest Ethiopia. Ethiopian medical journal 2019.
- 54. Klein SL, Jedlicka A, Pekosz A: The Xs and Y of immune responses to viral vaccines. The Lancet infectious diseases 2010, 10(5):338–349. pmid:20417416
- 55. Hassan RS, Bayati AH: Evaluation of the Effectiveness of Hepatitis B Vaccination in Children Aged 1 to 14 Years in Sulaimani City. Journal of Kurdistan Board of Medical Specialties 2018, 4(2).
- 56. Roznovsky L, Orsagova I, Kloudova A, Tvrdik J, Kabieszova L, Lochman I, et al. Long-term protection against hepatitis B after newborn vaccination: 20-year follow-up. Infection 2010, 38(5):395–400. pmid:20589522