Medical Impact Of The Vaccine
Taiwan was the first country to begin with universal childhood vaccination in 1984. At that time, the rate of perinatal transmission was extremely high leading to a nation-wide HBsAg carrier rate of ca. 10%. Twenty years later only 1.2% of those borne after beginning of the vaccination campaign were HBsAg carriers. Although HCC is mainly a disease of advancing years, the impact of the vaccination quickly became apparent in children and adolescents because its incidence dropped significantly from 0.57 to 0.17 in 100,000 person years in that age group after the beginning of mass vaccination. Thus, the hepatitis B vaccine was the first successful vaccine against a specific form of cancer . Similar observations were reported from other parts in the world. In low prevalence countries like Italy the vaccination has probably contributed to a very strong decrease of hepatitis B incidence.
Observations in Taiwan and Thailand or in high risk groups of other countries suggest that the protection becomes weaker within 20 years but the immune memory is good enough to mitigate the infection in the ca. 23% of those infected. Those with no or with low anti-HBs are still protected against HBV disease but they get a clinically silent infection with transient HBs antigenemia, or anti-HBc seroconversion or increase of the anti-HBs titer. The necessity or timing of later booster injections is a matter of debate.
Why A Variety Of Hepatitis B Vaccine Schedules Have Been Used
Generally, the recommended number of doses of hepatitis B vaccine required to induce protective immunity varies by product and with the age of the recipient. Historically, the standard 3-dose hepatitis B vaccine series has consisted of 2 priming doses administered 1 month apart and a third dose administered 6 months after the first dose. Today, the WHO recommends multiple options for adding hepatitis B vaccine to existing infant immunization schedules. Several options are considered to be appropriate for infants: 1 birth dose followed by either 2 doses of monovalent or hepatitis B containing combination vaccine at 1 and 6 months of age or at 2, 4, and 6 months of age or at 3, 5, and 11 months of age or at 8, 12, 16 weeks and 12 or 15 months or at 6, 10, and 14 weeks of age, according to the WHOs Expanded Programme on Immunization schedule . Currently, a variety of hepatitis B vaccine schedules have been used successfully worldwide. In general, preference is given to effective options that require minimal additional visits for immunization, to increase compliance and to reduce the logistics burden.
Significance Of Igm Antibodies To Hbcag
Anti-HBc total antibody assays were useful to determine whether a patient ever had contact to HBV but this marker could not distinguish whether the infection was acute or persistent or resolved. It had been long known that the early immune response against an infectious agent induced antibodies of the immunoglobulin class M , whereas weeks or months later the antibodies belonged mainly to immunoglobulin class G . It was therefore only necessary to determine the immunoglobulin class M of the antibodies to distinguish between a fresh and an old infection. This used to be costly and laborious, as biophysical methods were needed to separate IgG and IgM. It was a break-through for virus diagnostics when a very simple test principle was developed for IgM Anti-HAV by Bertram Flehmig and independently by the author of the present paper for IgM Anti-HBc : covering the solid phase with an antibody against IgM and consequently using it to capture the IgM from the sample. The HAV-Ag or HBcAg is then added and, if bound by specific IgM, detected with a labeled antibody. Today, this test principle is standard for assay of most antiviral IgM antibodies.
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Identification Of The Hbv Receptors
In 1987, Mary Ann Sells and George Acs succeeded in generating the stably HBV-transfected hepatoma cell line HepG2.2.15 which was permissive for replication of infectious HBV and has been crucial for many studies on HBV, in particular for development of antiviral drugs . But this and similar cell lines did not facilitate the search for the factors mediating efficient attachment and entry of HBV. Many publications claimed to have detected functional receptors for HBV, but the search for them remained unsuccessful for decades. Only recently, Camille Sureau could prove by a meticulous mutational analysis that the previously by J. P. Allain identified heparansulfate proteoglycan binding capacity of the small HBsAg protein is essential for infectivity and that the binding sites coincide with neutralizing epitopes of HBsAg . However, this receptor cannot explain the peculiar species specificity of HBV because it is present in livers of all mammalians.
Relation To Hepatitis B
At first, Blumberg believed that AuAg was indeed a polymorphic serum protein like the lipoprotein antigen which he had discovered before. But soon the evidence accumulated that it might have something to do with hepatitis, which Blumberg first revealed in a publication in 1967 , page 100. Parallel to that, Alfred Prince was specifically looking for a serum hepatitis antigen in the blood of hepatitis B patients and reported on it in 1968, but soon he realized that it was identical to AuAg . Subsequently, various groups confirmed that Au/SH-Ag was actually a marker for acute or chronic hepatitis B and that there were apparently healthy Au/SHAg carriers.
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Serologic Testing Of Vaccine Recipients
Prevaccination Serologic Testing
Vaccination of persons immune to HBV because of current or previous infection or HepB vaccination does not increase the risk for adverse events. However, in populations that have high rates of previous HBV infection, prevaccination testing might reduce costs by avoiding vaccination of persons who are already immune. Prevaccination testing consists of testing for HBsAg, anti-HBs, and anti-HBc. Serologic testing should not be a barrier to vaccination of susceptible persons, especially in populations that are difficult to access. Testing is not a requirement for vaccination, and in settings where testing is not feasible, vaccination of recommended persons should continue. The first dose of HepB vaccine should typically be administered immediately after collection of the blood for serologic testing. Prevaccination testing is recommended for household, sexual, or needle-sharing contacts of HBsAg-positive persons HIV-positive persons persons with elevated ALT/ AST of unknown etiology hemodialysis patients MSM and past or current PWID.
Serologic testing is not recommended before routine vaccination of infants, children, or adolescents.
Postvaccination Serologic Testing
- Persons who do not respond to the first HepB series should complete a second series on a 0, 1, 6 month schedule
- Retest anti-HBs 12 months after completion of second series
Why I Recommend Hepatitis B Vaccination To All My Patients
Sandra Adamson Fryhofer, MD
Editors Note: This report has been updated to reflect information on hepatitis B vaccines that became available after the video was recorded.
This transcript has been edited for clarity.
Hello. I’m Dr Sandra Fryhofer. Welcome to Medicine Matters. The topic: the new hepatitis B vaccination recommendations for 2022. Here’s why it matters.
Each year, more than 20,000 people in the United States contract acute hepatitis B, with healthcare costs of more than a billion dollars. As many as 40% of them have complications. Hepatitis B can lead to chronic hepatitis infection and liver cancer, and 15%-25% of those infected will die prematurely of cirrhosis or liver cancer. This is needless suffering and death.
Hepatitis B infection is vaccine preventable. We have several vaccine versions to choose from, and they work. The older, three-dose hepatitis B vaccine preparations are more than 90% protective. Immunity is durable, lasting at least three decades.
Two newer vaccines are now available, but only for those aged 18 or older. One of them, Heplisav, contains a new adjuvant, CpG 1018. Its two-dose series can be completed in just 1 month.
For Medicine Matters. I’m Dr. Sandra Fryhofer.
Unusual Structure Of Hbv Dna
Robinson had described the nucleic acid of HBV as a small circular double-stranded DNA but he found that the HBV DNA was profoundly different from that of other DNA viruses. In contrast to polyoma- or papillomaviruses the circular DNA was not covalently closed but had a nick in one strand and a variable gap in the other . As could be shown by the author in 1980, the 5ends of the DNA strands were blocked, in case of the longer minus strand by a at that time unidentified protein . All hepadnavirus species have this genome structure . The mechanism by which these structures were generated appeared enigmatic.
How Far Have We Got
Some exciting research is underway around the world, including the recent identification of the cell receptor which allows the virus to infect the body. This has enabled studies of the complete virus replication cycle including the viral reservoir that is untouched by current therapies.
New approaches to a possible cure include mechanisms to block the virus entry into the cell and to stop the virus from making the proteins it needs to replicate and infect new cells.
Studies are also underway to enhance patients immune responses so their own natural defences can control or even eliminate the virus. This is similar to immunotherapies already being used to treat some cancers.
Its likely a hepatitis B cure will require a dual-pronged approach, directly targeting the virus while also enhancing the immune response in people who are infected.
The goal is to reduce the amount of virus in the body and restore the persons immune responses. This is called a functional cure and is similar to what happens when a person naturally gets rid of the virus. It would also mean they didnt need to take drugs any more.
Some of these approaches are now in early stage human clinical trials. More than 30 drugs have been developed and are being tested in people with chronic hepatitis B. However, much more work needs to be done to achieve a cure.
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Transmission By Close Contact
Intravenous injections occur only in medicine or illegal drug use and here contaminations with miniscule traces of infectious blood may transmit HBV, e.g. by re-use of syringes. With the general introduction of single use devices for most invasive procedures transmissions of HBV have become rare. But incorrect procedures leading to hepatitis B outbreaks still occur, in particular during blood glucose testing and many other medical procedures. In normal life, small wounds and intimate mucocutaneous contact may allow transmission from a highly viremic person to others. Epidemiological experience shows that this danger is high when the values exceed 107 viruses/mL plasma, but it is nearly non-existent when lower than 105/ml.
Are Hepatitis B Virus Infections Easily Avoided
Large quantities of hepatitis B virus are present in the blood of people with hepatitis B in fact, as many as one billion infectious viruses can be found in a milliliter of blood from an infected individual. Therefore, hepatitis B virus is transmitted in the blood of infected individuals during activities that could result in exposure to blood, such as intravenous drug use, tattooing, or sex with people who are infected. However, it is also possible to catch hepatitis B virus through more casual contact, such as sharing washcloths, toothbrushes or razors. In each of these cases, unseen amounts of blood can contain enough viral particles to cause infection. In addition, because many people who are infected don’t know that they are infected, it is very hard to avoid the chance of getting infected with hepatitis B virus.
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Cdc Global Immunization Strategic Framework
In 2021, CDC released the Global Immunization Strategic Framework 2021-2030, which provides a roadmap to achieving progress toward a world where everyone is protected from vaccine-preventable diseases , such as hepatitis A and hepatitis B.
Three Goals are core immunization program capacities that CDC seeks to strengthen:
- Prevent VPDs by strengthening immunization services.
- Detect VPDs by supporting and improving disease surveillance systems.
- Respond to and prepare for VPD outbreaks.
Two Goals are cross-cutting capacities:
- Sustain immunization program capacities over time.
- Innovate to increase immunization program impact through research and evaluation.
Hbv Transmission To And From Health Care Workers
In the past, the risk of acquiring an HBV infection by performing exposure-prone procedures was so high that after several decades of professional activity the majority of health care workers showed markers of previous or ongoing HBV infection. Thus, many physicians became victims of their professional activities, were highly infectious HBV carriers and thereafter a threat for the patients on whom they performed exposure prone procedures. Since the 1970s, there have been numerous reports on HBV transmissions from health care workers with high viremia to patients, usually during surgery. Most critical were thorax, gynecological and oral surgery. The medical community was sluggish to draw the necessary consequences. Initially, the supervising authorities recommended only that HBV carriers should wear double gloves while doing surgery and be particularly cautious.
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What Are The Treatment Options For Hepatitis B
Currently, there is no specific antiviral treatment recommended for persons with acute hepatitis B disease as approximately 95% of infected immunocompetent adults recover spontaneously. Specific treatment is available to support people with chronic HBV infection. The main goal of the available care is to maintain comfort, relieve symptoms, and prevent patients from passing the infection to others. However, notably, not all patients with chronic HBV need to be on medication . Patients with active signs of liver disease may benefit the most from current treatment. The Food and Drug Administration has approved for the treatment of chronic hepatitis B interferon- and oral antiviral agents . Present treatment for chronic hepatitis B can slow or prevent the progression of cirrhosis, reduce the incidence of liver cancer, and improve long term survival and quality of life, but are not curative. Therefore, most people who start hepatitis B treatment must continue for life. The side effects of the therapies and required regular monitoring increases the difficulty and complexity of patient management. Hence, hepatitis B vaccination is plan A in the fight against hepatitis B. Vaccination is, compared to other interventions, an economically attractive option, both in terms of cost-effectiveness and benefit-cost ratios .
I Discovered I Was Hepatitis B Positive At The Age Of 27
Lutamaguzi Emmanuel, 27 is the executive director of the Hepatitis Aid Organization. Lutamagusi who is living positively with Hepatitis B virus got to know of his status in 2016.
He was going to travel abroad when he decided to do comprehensive tests including screening for Hepatitis B as a travel requirement.
The results indicated that he was positive with Hepatitis B. Immediately, the doctor referred him to a private health facility to do a confirmatory test. It was costly right from the consultation fees to the tests which he could hardly afford.
Later, Lutamaguzi opened up to his friends, workmates and family member but the stigma and discrimination was too much because most of them thought the disease was simply spread by close contact with him.
At the time he also had little knowledge on Hep B Virus. So he decided to search and read about it. From time to time he engaged different health care providers but realized there was a big knowledge gap amongst them too. One of them enrolled him on Ceptrine for 6 months but he was discontinued after a month by a colleague at Uganda Cancer Institute where his viral load was tested at a subsidized fee.
Later, Lutamaguzi met with colleagues supporting Hepatitis B elimination and was linked to facilities that offer the services for free. It was after, that he set up the Hepatitis Aid Organization.
Every 28th of July, Uganda joins the rest of the world to commemorate world hepatitis B-day.
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The Discovery Of The Hepatitis C Virus
The non-A, non-B hepatitis virus was identified in 1989 by scientists at a California biotechnology company called Chiron who were collaborating with investigators at the Centers for Disease Control and Prevention . The research confirmed that this was a new virusnow officially called the hepatitis C virus, or HCV. This was a landmark advance in medicine that allowed for development of tests to detect HCV, which were rapidly applied to screen blood donations. Over the next few years, as the testing improved, HCV was effectively eliminated from the blood transfusion supply. The identification of HCV also led to further studies, undertaken by NIAID- and NIDDK-funded researchers and others, to determine its molecular structure. This was crucial for the design of drugs that would specifically interact with components of the virus and inhibit its replication. The identification of the virus also allowed for a more accurate diagnosis and a better sense of its prevalence in fact, it was eventually determined that HCV was the most common cause of chronic hepatitis, cirrhosis, and liver cancer in the Western world.
Discovery Of The Dane Particle
AuAg, however, was not a prion-like agent. While inspecting AuAg immune complexes under the EM in 1970, David S. Dane discovered that AuAg appeared not only on the small pleomorphic particles, but also on larger, virus-like objects 42nm in size with a clearly visible inner core . Shortly thereafter, in 1971, his British colleague June Almeida was able to release the core particles from the so-called Dane particles by treatment with mild detergent, and showed by immune EM that hepatitis B patients formed antibodies against this core antigen . This strongly suggested that the Dane particles were the actual virus causing hepatitis B. AuAg was obviously the surface antigen of the virus envelope, and was named HBsAg thereafter. The infected hepatocyte forms the HBsAg protein in large surplus and secretes it in addition to the complete virus as round or filamentous noninfectious particles of about 20nm in diameter into the blood leading to an approximately three-thousand fold excess of these subviral particles .2). This was the reason that the Dane particles could not be recognized in AuAg preparations purified by ultracentrifugation or size chromatography.
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