Introduction Of Hepatitis B Virus Vaccination Research Articles

Prevalence and trends of hepatitis B and C virus biomarkers in Zimbabwe: comparative analyses of a nation’s blood-donor surveillance data and meta-analyses of population studies

Background The disproportionate burden of viral hepatitis, particularly hepatitis B virus (HBV) is experienced by people living in low-resourced sub-Saharan Africa, where the estimated prevalence is 3–7 times the global average. Therefore to inform policy, we describe the seroprevalence and trends of hepatitis C (HCV) and HBV biomarkers: anti-HCV antibody and hepatitis B surface antigen (HBsAg), respectively, in Zimbabwe. Methods We analysed data from 181,248 consecutive blood-donors, examined between January 2015 through December 2018. Additionally, we conducted a comprehensive literature review using PubMed and African Journals Online databases, meta-analysing selected papers from Zimbabwe, published between 1970 and 2020, that met specific criteria. Results Overall age-standardized prevalence rate (ASPR) for anti-HCV was 8.67 (95%CI, 0.25–17.09) per 100,000, while that for HBsAg was 2.26 (95%, 1.89–2.63) per 1000 blood-donors, per year. Meta-analysis of 9 studies comprising 220,127 persons tested for anti-HCV revealed ASPR of 0.05% (95% 0%–0.19%) in blood-donors and 1.78% (95%CI, 0.01%–5.55%) in the general population, for an overall pooled ASPR of 0.44 (95%CI, 0.19%–0.76%). 21 studies comprising 291,784 persons tested for HBsAg revealed ASPR of 0.65% (95%CI, 0.31%–1.00%) in blood-donors and 4.31% (95%CI, 1.77%–6.50%) in the general population for an overall pooled ASPR of 4.02% (95%CI, 3.55%–4.48%), after HBV vaccine introduction. HBsAg prevalence was significantly higher before HBV vaccine introductions. Conclusions The prevalence of HBV is decreasing, consistent with the introduction of HBV vaccination, while HCV prevalence is increasing in Zimbabwe. This highlights the need for Improved blood-donor screening and more informative biomarker studies, particularly among repeat donors and children.

Prevalence and Trends of Hepatitis B and C Virus Biomarkers in Zimbabwe: Analyses of a Nation's Blood-Donor Surveillance Data, 2015 Through 2018, Plus Systematic Review and Meta-Analyses of Population Studies

Background: To inform national policy, we sought to describe the seroprevalence and trends of hepatitis C virus (HCV) and hepatitis B virus (HBV) biomarkers. Methods: We analysed data for 181,248 consecutive blood-donors, aged 16-75 years, examined between January 2015 through December 2018. We calculated the age-standardized prevalence rate (ASPR) of anti-HCV antibody and hepatitis B surface antigen (HBsAg) biomarkers. We also searched PubMed and African Journals Online databases, and meta-analysed selected papers from Zimbabwe published between 1970 and 2020 that reported on HBsAg and anti-HCV prevalence and met set criteria. Findings: There were 22 (11 for each sex) blood-donors seropositive for anti-HCV, accounting for an overall ASPR of 8·67 (95%CI, 0·25 – 17·09) per 100, 000 blood-donors, while 593 (414 males, 193 female) seropositive for HBsAg accounted for 2·26 (95%, 1·89 – 2·63) per 1,000 blood-donors. Mean ASPR for anti-HCV and HBsAg significantly increased 2·9-folds and 50%, p 41 years age-group, while for 16-20 age-group, HBsAg declined 0·06 per 1,000 donors per year, consistent with childhood HBV vaccinations introduced 25-years earlier. Meta-analysis of 9 studies comprising 220,127 persons tested for anti-HCV revealed ASPR of 0·05% (95% 0% - 0·19%) in blood-donors and 1·78% (95% 0·01% - 5·55%) in the general population, for an overall pooled ASPR of 0·44 (95%CI, 0·19% – 0·76%). 21 studies comprising 291,784 persons tested for HBsAg revealed ASPR of 0·65% (95%CI, 0·31% - 1·00%) in blood-donors and 4·31% (95%CI, 1·77% - 6·50%) in the general public for an overall pooled ASPR of 4·02% (95%CI, 3·55% - 4·48%), after HBV vaccine introduction, which were all significantly higher before HBV vaccine introductions. Interpretation: HBV prevalence is falling, consistent with introduction of HBV vaccination, while HCV prevalence is increasing in Zimbabwe. Improved blood-donor screening and studies with more informative biomarkers’, especially among repeat donors and children, are needed. Funding: None to declare. Declaration of Interest: None to declare. Ethical Approval: Ethical approval for this study was obtained from NBSZ (NBSZ006/2019) and Medical Research Council of Zimbabwe (MRCZ/E/261).

Hepatitis B vaccination status and vaccine immune response among children in rural Senegal

Abstract Background Hepatitis B vaccination during childhood is key to reduce the prevalence of Hepatitis B virus (HBV) infection. In Senegal, a highly endemic country, the three-dose hepatitis B vaccine and the birth dose vaccine were introduced in the Expanded Programme on Immunization (EPI) in 2004 and 2016 respectively. This study aimed to determine chronic HBV infection prevalence, hepatitis B vaccination status and vaccine immunity among children in Senegal. Methods A cross-sectional study including HBV screening was conducted at home among children aged 6 months to 15 years (i.e. born after the introduction of the HBV vaccine in the EPI) in the rural zone of Niakhar. Dried Blood Spot (DBS) samples were collected for the detection of HBsAg, anti-HBc Ab and anti-HBs Ab using chemoluminescence. Vaccination status was assessed using information on vaccination cards. Detectable vaccine immunity was defined with an adjusted DBS threshold of DOI≥0.36 IU/mL (corresponding to 10 IU/mL in venous blood sampling). Results Between October and December 2018, 455 children were enrolled. Preliminary results show that 7/455 (1.5%) had been in contact with HBV (positive anti-HBc Ab) and 5/455 (1.1%) had chronic HBV infection (positive HBsAg). Only 161/455 (35.4%) children had a vaccination card available. Among those, 150/161 (93.2%) received at least 3 doses of hepatitis B vaccine, of which 83/150 (55.3%) had detectable vaccine immunity. The proportion of children with detectable vaccine immunity was significantly higher in children <5 years than in children aged 5-9 and 10-15 (72.3% versus 47.3%, p = 0.006 and 72.3% versus 14.3%, p < 0.001). Conclusions Preliminary results suggest a low prevalence of HBV chronic infection among children born after the introduction of HBV vaccination in Senegal. However, detectable vaccine immunity rapidly decreases with age among vaccinated children, signalling a need for further studies on the immune response to HBV vaccination in this context. Key messages HBV chronic infection is low among children born after the introduction of HBV vaccination in Senegal. Further studies on the immune response to HBV vaccination in this context are needed.

Hepatitis B virus vaccination status of sixth year medical students

Background Hepatitis B virus (HBV) infection can associate a high risk of progression to chronic hepatitis, particularly when infection occurs at younger ages. For this particular reason, newborn vaccination has been introduced in national immunization schedules in countries where the infection has a medium to high prevalence. We assessed the vaccination status of students in their final year of medical university training during 20112013. This category is at risk of professional exposure to HBV and given the timeline of introduction of HBV vaccination in Romania, they probably have not been vaccinated at birth, but rather during middle or high school education.

Relationship between age and prevalence of hepatitis B infection in first-year university students in Hong Kong

To determine the effect of age on the prevalence of hepatitis B virus (HBV) infection during a routine screening programme of first-year students enrolled in Health Sciences Studies at the Chinese University of Hong Kong from 2001 to 2009. In a retrospective cohort study, data on the hepatitis B surface antigen (HBsAg) status was retrieved from the University Health Service and analysed according to the age of the student at testing and year of birth. Of the 2,688 students enrolled in the study group, 79 (2.9 %) tested positive for HBsAg. The prevalence increased significantly from 0.9, 2.3, 4.3 to 5.5 % for those tested at age ≤ 18, 19, 20 and ≥ 21 years, respectively (p < 0.001). On logistic regression analysis, taking age ≤ 18 years and year of birth before 1983 (before the availability of HBV vaccination) as the reference group, HBV infection increased progressively with age, with an adjusted odds ratio of 3.36 [95 % confidence interval (CI) 1.01-11.23], 6.04 (95 % CI 1.74-20.98) and 11.61 (95 % CI 3.20-42.13) for age 19, 20 and ≥ 21 years, respectively. There was no significant change in the odds ratio after adjustment for the year of birth before and after introduction of the vaccination programme. Among the university students enrolled in our study, the overall prevalence of HBV infection before and after the introduction of HBV vaccination was lower than the 10 % found in the general population. There was, however, a significant progressive increase with age at testing from ≤ 18 to ≥ 21 years, suggesting a previously overlooked contribution of horizontal transmission to the high prevalence of HBV infection found in our adult population.

Abstract CN05-01: Viral and Dietary Factors in Declining Liver Cancer Mortality in Qidong, China

Abstract Liver cancer is the third leading cause of cancer mortality globally. In endemic areas of sub-Saharan Africa and southeast Asia liver cancer largely arises from both chronic infection with hepatitis B virus (HBV) and the ingestion of aflatoxin-contaminated foods such as corn and groundnuts. While synergistic interactions between these viral and chemical carcinogens have been observed in prospective cohort studies in China, the effects of primary prevention against both of these factors has not been examined. Mortality rates from liver cancer by birth cohort in Qidong, China were compared to timelines in the region for the introduction of HBV vaccination and to mandated, wholesale changes in staple foodstuffs from corn to rice. Levels of aflatoxin-albumin adducts in archived serum samples collected in Qidong from 1989 to 2012 were quantified by isotope dilution mass spectrometry as measures of carcinogen exposure. Halving of mortality rates from liver cancer are seen between birth cohorts from the 1960s and 1980s for residents 34 years old and younger. However, prevalence of HBsAg positivity was unchanged in these cohorts as all were born prior to implementation of universal HBV vaccination of newborns. Changing agricultural policies from a planned to a market-oriented economy in the early 1980s led from corn to rice based diets and dramatic decreases in aflatoxin exposures in Qidong. Substantial declines in liver cancer morality in birth cohorts occurring prior to the introduction of a universal HBV vaccination program in Qidong highlight the importance of altered food policies as a means for rapid risk reduction, especially amongst the ∼350 million HBV carriers, many of whom reside in endemic areas. Supported by NIEHS ES 006052 and National Science and Technology of China 2008ZX10002-015. Citation Format: Thomas W. Kensler. Viral and dietary factors in declining liver cancer mortality in Qidong, China. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr CN05-01.

Seroprevalence of hepatitis B and C infection markers among children and adolescents in the southern Brazilian region

I read with interest the article published by LIVRAMENTO et al. in your journal recently. Hepatitis B virus (HBV) infection is one of the most common infectious diseases globally. HBV vaccination has changed the epidemiology in most countries in the world. LIVRAMENTO et al. reported the prevalence of HBsAg 0.76% and total anti-HBc 1.02%, respectively and the copositivity between HBsAg and total anti-HBc was verified in 0.76% of the analyzed samples. I would like to add some information regarding this subject. First of all I would like to draw the readers’ attention to the fact that in Brazil, prevalence of HBV is much higher than reported by LIVRAMENTO et al.. However, it cannot be denied that the introduction of HBV vaccination in 1996 as a National Immunization Program in Brazil could impact the prevalence of the disease. To find the impact of HBV vaccination in the Brazilian community, in this study it was necessary to know the age of the infected cases. There were three cases with HBs Ag positivity, therefore we assume that they had been born before the introduction of the national immunization program in Brazil. It is recommended that the study be continued or be carried out in other parts of the country, to see if the result will be different. HBV is more common in people like prisoners and knowing the risk factors of the infected ones can help the policy makers to better design the strategies to control HBV infection in the community. Intensifying HB vaccination of high risk groups and surveillance of hepatitis B infected subjects will further decrease the frequency of the disease in Brazil. Fortunately no Hepatitis C virus (HCV) infected cases were reported by LIVRAMENTO et al. which confirms that the risk factors for acquiring HCV in the Brazilian population is not high enough to detect the HCV infection in their study group.

Impact of universal vaccination on intrafamilial transmission of hepatitis B virus

To control hepatitis B virus (HBV) infection, a nationwide vaccination program was launched in 1984 and resulted in a significant reduction in the rate of persistent infection of children. However, the relative contribution of vaccination to the intrafamilial clustering of HBV infection remains unclear. The rate of intrafamilial HBV transmission in vaccinated children was investigated. Eighty-four sera from vaccinated children were enrolled and HBV serum markers were determined. The modes of intrafamilial HBV transmission were investigated by history taking and serological assay, and confirmed by genotyping and phylogenetic analysis. The results showed 66 (78.6%) vaccinated children born to hepatitis B surface antigen (HBsAg)-negative parents were HBsAg-negative. Eighteen vaccinees were born to HBsAg-positive parents; four (21.4%) of the children were HBsAg-positive. According to the parents' HBsAg status, three patterns of HBsAg-positive parents were identified. Serological analysis showed that three of 15 children born to HBsAg-positive mother (pattern I) and one of two children born to HBsAg-positive father became infected (pattern II). The remaining one child was HBsAg negative with both parents positive for HBsAg (pattern III). Genotyping and phyogenetic analysis confirmed the mode of intrafamilial transmissions. Sequence analysis of S and pre-S genes showed that HBV isolates of HBsAg-positive vaccinees were variants; no G145R but G145A and other substitutions were found. In conclusion, this small study showed that both maternal and paternal transmissions are important of the intrafamilial spread of HBV infection. In addition, the introduction of HBV vaccination has resulted in a reduction of intrafamilial transmission, but a study of a large population is needed.

Chronic hepatitis B virus infection in Asian countries.

Of the estimated 50 million new cases of hepatitis B virus (HBV) infection diagnosed annually, 5-10% of adults and up to 90% of infants will become chronically infected, 75% of these in Asia where hepatitis B is the leading cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC). In Indonesia, 4.6% of the population was positive for HBsAg in 1994 and of these, 21% were positive for HBeAg and 73% for anti-HBe; 44% and 45% of Indonesian patients with cirrhosis and HCC, respectively, were HBsAg positive. In the Philippines, there appear to be two types of age-specific HBsAg prevalence, suggesting different modes of transmission. In Thailand, 8-10% of males and 6-8% of females are HBsAg positive, with HBsAg also found in 30% of patients with cirrhosis and 50-75% of those with HCC. In Taiwan, 75-80% of patients with chronic liver disease are HBsAg positive, and HBsAg is found in 34% and 72% of patients with cirrhosis and HCC, respectively. In China, 73% of patients with chronic hepatitis and 78% and 71% of those with cirrhosis and HCC, respectively, are HBsAg positive. In Singapore, the prevalence of HBsAg has dropped since the introduction of HBV vaccination and the HBsAg seroprevalence of unvaccinated individuals over 5 years of age is 4.5%. In Malaysia, 5.24% of healthy volunteers, with a mean age of 34 years, were positive for HBsAg in 1997. In the highly endemic countries in Asia, the majority of infections are contracted postnatally or perinatally. Three phases of chronic HBV infection are recognized: phase 1 patients are HBeAg positive with high levels of virus in the serum and minimal hepatic inflammation; phase 2 patients have intermittent or continuous hepatitis of varying degrees of severity; phase 3 is the inactive phase during which viral concentrations are low and there is minimal inflammatory activity in the liver. In general, patients who clear HBeAg have a better prognosis than patients who remain HBeAg-positive for prolonged periods of time. The outcome after anti-HBe seroconversion depends on the degree of pre-existing liver damage and any subsequent HBV reactivation. Without pre-existing cirrhosis, there may be only slight fibrosis or mild chronic hepatitis, but with pre-existing cirrhosis, further complications may ensue. HBsAg-negative chronic hepatitis B is a phase of chronic HBV infection during which a mutation arises resulting in the inability of the virus to produce HBeAg. Such patients tend to have more severe liver disease and run a more rapidly progressive course. The annual probability of developing cirrhosis varies from 0.1 to 1.0% depending on the duration of HBV replication, the severity of disease and the presence of concomitant infections or drugs. The annual incidence of hepatic decompensation in HBV-related cirrhosis varies from 2 to 10% and in these patients the 5-year survival rate drops dramatically to 14-35%. The annual risk of developing HCC in patients with cirrhosis varies between 1 and 6%; the overall reported annual detection rate of HCC in surveillance studies, which included individuals with chronic hepatitis B and cirrhosis, is 0.8-4.1%. Chronic hepatitis B is not a static disease and the natural history of the disease is affected by both viral and host factors. The prognosis is poor with decompensated cirrhosis and effective treatment options are limited. Prevention of HBV infection thorough vaccination is still, therefore, the best strategy for decreasing the incidence of hepatitis B-associated cirrhosis and HCC.

The cost of integrating hepatitis B virus vaccine into national immunization programmes: a case study from Addis Ababa

National programmes of hepatitis B virus (HBV) vaccination are recommended by the World Health Organization for all countries. Countries suffering the highest burden of HBV disease are those most needy of universal vaccination, but are frequently of very low income and resources for health care are scarce. The introduction of HBV vaccination would inevitably stretch these resources further even with support of donor agencies. Thus an assessment of the cost-effectiveness of HBV vaccination is desirable to assist in decision making about resource allocation. We describe here a method for estimating the additional costs of introducing HBV vaccination into the Expanded Programme on Immunization (EPI) at a national level. Of fundamental importance is that this method enables costs to be assessed prior to the introduction of vaccination. We illustrate the method using a study carried out at the sub-national level, in the city of Addis Ababa, Ethiopia, but which can be expanded countrywide. The method, in brief, involved the use of a number of questionnaires which could be used to estimate the costs associated with the EPI programme from a large sample of the static clinics as well as from central sources. Since unit costs were collected along with the quantities of resources used and estimates of the capacity used for certain facilities (such as refrigerators), the additional cost of introducing HBV vaccine could be estimated largely by extrapolation of the resources used in vaccinating against diphtheria/pertussis/tetanus vaccine (which, similar to HBV vaccine, requires three doses). The estimation of costs is only part of the information required to make decisions on resource allocation, and should be used in association with measures of the burden of disease due to the infection in the community and effectiveness of the control programme at reducing this burden. The prediction of the latter, based upon a sound epidemiological understanding of the infection, is the subject of a forthcoming paper.