Association of Routine Hepatitis B Vaccination and Other Effective Factors with Hepatitis B Virus Infection: 25 Years Since the Introduction of National Hepatitis B Vaccination in Iran.

Background: One of the main health problems in the world is hepatitis B virus (HBV) infection. Vaccination and other factors can affect HBV infection. As various effective factors have been reported in different regions and studies, this study aimed to investigate the association between HBV infection and routine vaccination and other effective factors 25 years since the launch of the national vaccination program in Iran. Methods: This cross-sectional study, conducted in 2017 in Shiraz (Iran), investigated factors such as demographic variables such as gender, education, and occupation, vaccination status, and the potential risk factors for HBV infection. Hepatitis B surface antigen (HBsAg) and anti-hepatitis B core antibody (HBc Ab) tests were performed to determine HBV infection status. The data were analyzed using R software (version 3.5.2), using multivariate logistic regressions and machine learning methods. The level of significance was considered below 0.05. Results: A total of 2720 individuals were enrolled in the study (194 cases with HBV infection). Based on the logistic regression analyses, factors such as a family history of the disease (OR=2.53, P<0.001), vaccination (OR=0.57, P=0.004), a history of high-risk behaviors (OR=1.48, P=0.022), and occupation (OR=1.80, P=0.035) were significantly associated with HBV infection. Based on the conditional tree method, a family history of infection (P<0.001) and vaccination (P=0.023) were two important factors in classifying individuals for HBV infection. Conclusion: Based on the different methods applied in this study, HBV infection was affected by factors such as a family history of the disease, national HBV vaccination, and occupation. It appears that HBV vaccination, launched by the Iranian Ministry of Health and Medical Education in 1993, has reduced HBV infection.

Decrease in the prevalence of hepatitis B and D virus infections in an endemic area in Peru 23 years after the introduction of the first pilot vaccination program against hepatitis B.

In 1991, Peru launched the first vaccination program against hepatitis B in children aged under 5 years in the hyperendemic [hepatitis B virus (HBV) and hepatitis D virus (HDV)] province of Abancay. We conducted a cross-sectional study to determine the prevalence of HBV and HDV infections, 23 years after the launch of the vaccination program, as well as the post-vaccine response against hepatitis B in terms of prevalence of hepatitis B surface antibody (anti-HBs ≥10 mUI/ml). Among 3165 participants aged from 0 to 94 years, the prevalence rates of hepatitis B surface antigen (HBsAg), and hepatitis B core antibody (total anti-HBc) were 1.2% [95% confidence interval (CI) 0.85-1.64%], and 41.67% (95% CI 39.95-43.41%), respectively. The prevalence rate of anti-HBs at protective levels (≥10 mUI/ml) in individuals who HBsAg and anti-HBc negative was 66.36% (95% CI 64.15-68.51%). The prevalence rate of HBsAg in children aged <15 years was nil, and among adult HBsAg carriers, the prevalence of hepatitis D antibody (anti-HDV) was 5.26% (2/38; 95% CI 0.64-17.74). These findings showed that HBV prevalence has changed from high to low endemicity, 23 years following implementation of the vaccination program against hepatitis B, and HDV infection was not detected in those aged <30 years.

Hepatitis B vaccine in celiac disease: yesterday, today and tomorrow.

Some studies showed that in celiac patients the immunological response to vaccination is similar to that one found in general population except for vaccine against hepatitis B virus (HBV). The non-responsiveness to HBV vaccine has also been described in healthy people, nevertheless the number of non-responders has been demonstrated to be higher in celiac disease (CD) patients than in healthy controls. Several hypothesis explaining this higher rate of unresponsiveness to HBV vaccine in CD patients have been described, such as the genetic hypothesis, according with CD patients carrying the disease-specific haplotype HLA-B8, DR3, and DQ2, show a lower response to HBV vaccine both in clinical expressed CD patients and in healthy people carrying the same haplotype. On the other hand, it has been demonstrated that the gluten intake during the vaccination seems to influence the response to the same vaccine. Moreover, it has been demonstrated a possible genetic predisposition to hepatitis B vaccine non-responsiveness likely due to the presence of specific human leukocyte antigen haplotypes and specific single nucleotide polymorphism in genes of cytokine/cytokine receptors and toll like receptors, but the pathogenic mechanism responsible for this low responsiveness still remains unclear. The aim of this review is to focus on the possible pathogenic causes of unresponsiveness to HBV vaccine in CD patients and to propose an alternative vaccination schedule in order to improve the responsiveness to HBV vaccine in this at-risk patients.

The twenty-year story of a plant-based vaccine against hepatitis B: stagnation or promising prospects?

Hepatitis B persists as a common human disease despite effective vaccines having been employed for almost 30 years. Plants were considered as alternative sources of vaccines, to be mainly orally administered. Despite 20-year attempts, no real anti-HBV plant-based vaccine has been developed. Immunization trials, based on ingestion of raw plant tissue and conjugated with injection or exclusively oral administration of lyophilized tissue, were either impractical or insufficient due to oral tolerance acquisition. Plant-produced purified HBV antigens were highly immunogenic when injected, but their yields were initially insufficient for practical purposes. However, knowledge and technology have progressed, hence new plant-derived anti-HBV vaccines can be proposed today. All HBV antigens can be efficiently produced in stable or transient expression systems. Processing of injection vaccines has been developed and needs only to be successfully completed. Purified antigens can be used for injection in an equivalent manner to the present commercial vaccines. Although oral vaccines require improvement, plant tissue, lyophilized or extracted and converted into tablets, etc., may serve as a boosting vaccine. Preliminary data indicate also that both vaccines can be combined in an effective parenteral-oral immunization procedure. A partial substitution of injection vaccines with oral formulations still offers good prospects for economically viable and efficacious anti-HBV plant-based vaccines.

Development and introduction of a ready-to-use pediatric pentavalent vaccine to meet and sustain the needs of developing countries--Quinvaxem®: the first 5 years.

Quinvaxem(®) injection (DTwP-HepB-Hib fully-liquid combined vaccine) is a ready-to-use, preservative-free, fully-liquid combined vaccine containing diphtheria and tetanus toxoids, Bordetella pertussis inactivated cellular suspension, hepatitis B surface antigen (HBsAg), and Haemophilus influenzae type b conjugated oligosaccharide. The vaccine was the first ready-to-use, fully-liquid pentavalent vaccine to gain WHO pre-qualification status in 2006. The immunogenicity and safety of Quinvaxem(®) was assessed in four clinical trials and a large post-marketing surveillance study. Quinvaxem(®) was found to be highly immunogenic in each of the primary vaccination studies and was also shown to be suitable as a booster with the advantage that it could be given concomitantly with measles vaccine. Quinvaxem(®) has become a cornerstone in EPI vaccination programs. To further support the needs of EPI vaccination processes and developing countries, a simple, all-in-one, compact, prefilled, auto-disabled Uniject(®) injection system has been chosen and optimized as a potential new presentation for Quinvaxem(®). Hopefully, Quinvaxem(®) in the Uniject(®) presentation will help vaccination programs in developing countries to achieve more.

Public health policy for management of hepatitis B virus infection: historical review of recommendations for immunization.

Chronic hepatitis B virus (HBV) infection is the leading cause of cirrhosis, liver failure, and liver cancer, and an estimated 620,000 persons die annually from HBV-related liver disease (Goldstein et al., 2005; World Health Organization, 2000). Immunization with the HBV vaccine is the most effective means of preventing HBV infection and its consequent acute and chronic liver diseases such as cirrhosis and hepatocellular carcinoma. The HBV vaccine has been used against HBV in the United States since 1982 (Centers for Disease Control and Prevention, 1982); during the last 25 years, HBV vaccine policy continued to evolve in response to public health issues and epidemiologic data. Although the number of newly acquired HBV infections has substantially declined as a result of implementation of a national immunization program, the prevalence of chronic HBV infection remains high. The purpose of this article is to review the epidemiology of HBV, provide a historical review of health policies for HBV immunization, and summarize the recent evidence-based public health guidelines for management of HBV infection in the United States.

Advances in viral hepatitis: 50 years of Australian gastroenterology.

Viral hepatitis classification, treatments and pathogenesis has been increasingly defined over the past 50 years. Australian researchers have made significant contributions in the areas of viral hepatitis A vaccine development, treatment outcomes for chronic hepatitis B and C, the role of liver transplantation and the pathogenesis of injury and disease progression. This review outlines some of these contributions.

[French specificities in the history of vaccination. The end of an exception?]. / Les particularités françaises de l'histoire de la vaccination. La fin d'une exception?

Five years after the National Health minister launched the vaccination program against hepatitis B in 1994, French public health experts are not satisfied by the coverage rate among young people. Is this stagnation related to the controversial way the program was initially managed and to the debate that has raged on the link between the vaccine and multiple sclerosis? Is the popular reaction of distrust specific to the vaccine or does it reveal a growing concern towards the whole vaccinal enterprise? More generally, is it the end of the almost unconditional French acceptance of vaccines? A historical retrospective on the history of vaccination in the country of Louis Pasteur.

Legend of hepatitis B vaccination: the Taiwan experience.

Hepatitis B, a disease entity currently affecting more than 350 million persons worldwide, is also a serious health problem in Taiwan. Liver cirrhosis and hepatoma, which are both closely correlated with hepatitis B, are among the 10 leading causes of death in Taiwan. A mass hepatitis B vaccination program, conducted by the government of Taiwan, was started in 1984. Prior to this vaccination program, a series of viral epidemiological surveys, transmission pattern studies, and pilot immunization trials proved the clinical, economic, and strategic benefits of mass immunization, thus providing the impetus for the implementation of this mass vaccination program. The success of this program has led to a decline in hepatitis B carrier rates among children in Taiwan from 10% to <1%. Furthermore, the mortality rate of fulminant hepatitis in infants and the annual incidence of childhood hepatoma have also decreased significantly in recent years. This is one of the most remarkable success stories in the field of public health.

[Give all children vaccine against hepatitis B!]. / Vaccinera alla barn mot hepatit B! Invandring från högendemiska länder har gjort att risken för smittspridning ökar.

The number of individuals with chronic hepatitis B in Sweden has increased, mainly due to new immigrant groups. A safe and effective hepatitis B vaccine exists which allows a flexible dosing schedule. Most countries in the world adheres to the WHO recommendations to include this vaccine in the childhood vaccination regimen. This has led to a substantial drop in morbidity and mortality from hepatitis B virus infections in high endemic regions such as Taiwan. Sweden should consider changing its vaccination policy, including the vaccination of high risk groups only, and consider vaccination of all infants.

Vaccines in historic evolution and perspective: a narrative of vaccine discoveries.

The sciences of vaccinology and of immunology were created just two centuries ago by Jenner's scientific studies of prevention of smallpox through inoculation with cowpox virus. This rudimentary beginning was expanded greatly by the giants of late 19th and early twentieth centuries biomedical sciences. The period from 1930 to 1950 was a transitional era with the introduction of chick embryos and minced tissues for propagating viruses and Rickettsiae in vitro for vaccines. Modern era vaccinology began about 1950 as a continuum following notable advances made during the 1940s and World War II. Its pursuit has been based largely on breakthroughs in cell culture, bacterial polysaccharide chemistry, molecular biology and immunology, which have yielded many live and killed viral and bacterial vaccines plus the recombinant-expressed hepatitis B vaccine. The present paper was presented as a lecture given(1) on August 30, 1999 and recounts, by invitation, more than five-and-half decades of vaccine research from the venue of personal experience and attainment by the author. The paper is intentionally brief and truncated with focus only on highlights and limited referencing. Detailed recounting and referencing are given elsewhere in text references [Hilleman MR. Six decades of vaccine development - a personal history. Nat. Med. 1998;4 (Vaccine Suppl.): 507-14] and [Hilleman MR. Personal historical chronicle of six decades of basic and applied research in virology, immunology and vaccinology. Immunol. Rev. (in press)]. This narration will have achieved its purpose if it provides a background of understanding and guidelines that will assist others who seek to engage in creation of new vaccines.