We have a vaccine for hepatitis B but here’s why we still need a cure



Around 5% of adults and 90% of babies who contract hepatitis B go on to have life-long infection that can only be managed with regular medication.
Ronald Rampsch/Shutterstock

Peter Revill, The Peter Doherty Institute for Infection and Immunity and Margaret Littlejohn, Melbourne Health

Hepatitis B is blood-borne virus that packs a punch. Worldwide, more than 1.3 billion people have been infected with hepatitis B, and 257 million people have developed a life-long infection. This includes 240,000 Australians, many of whom are Indigenous.

Globally, transmission most commonly occurs from mother to baby or in early life. But it’s possible to be infected in adulthood, through sex or blood-to-blood contact.

Most people who are infected in adulthood develop a short infection which their immune response controls. But in around 5% of adults and 90% of babies, the immune response is ineffective and chronic infection develops.




Read more:
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Hepatitis B virus causes almost 40% of all liver cancer, which is the fifth most common cancer and the second leading cause of cancer-related death worldwide.

Australian discovery

Hepatitis B virus was discovered in the serum of an Indigenous Australian in 1965 and was first known as the “Australia antigen”.

This quickly led to the development of an effective vaccine in the 1980s, which is now available worldwide. The vaccine has been given to Australian infants since May 2000.

(If you weren’t vaccinated as a baby, you might want to consider doing so through your GP, particularly if you plan to travel to Asia and Africa where hepatitis B is common.)

Unfortunately the vaccine doesn’t do anything for the 240,000 or so Australians who currently live with chronic hepatitis B. Only around 60% of these people have been diagnosed; the rest don’t know they’re infected and don’t receive appropriate care.

How is it currently treated?

There is no cure for chronic hepatitis B virus.

In most cases, treatment requires taking a pill every day for life to remain effective and to reduce the risk of liver cancer. Even then, it doesn’t eliminate the risk.

Chronic hepatitis B hasn’t been cured so far in part because current therapies have failed to destroy the viral reservoir, where the virus hides in the cell.

This is in contrast to hepatitis C virus, which has no such viral reservoir and can now be cured with as little as 12 weeks of treatment.




Read more:
In contrast to Australia’s success with hepatitis C, our response to hepatitis B is lagging


Despite the huge human and economic toll of chronic hepatitis B, research to cure the disease remains underfunded. There is a misconception that because there is a vaccine, hepatitis B is no longer a problem.

The availability of effective cures for the unrelated hepatitis C virus has also led people to believe that “viral hepatitis” is no longer a problem.

Experts estimate that liver cancer deaths will substantially increase in coming decades without a cure for hepatitis B, despite deaths from most cancers decreasing.

Hepatitis B causes 40% of all liver cancer.
Napocska/Shutterstock

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.




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Explainer: the A, B, C, D and E of hepatitis


It’s 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 person’s 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 didn’t 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.The Conversation

Peter Revill, Senior Medical Scientist at VIDRL, Royal Melbourne Hospital, The Peter Doherty Institute for Infection and Immunity and Margaret Littlejohn, Medical Scientist, Melbourne Health

This article is republished from The Conversation under a Creative Commons license. Read the original article.

The 2019 flu shot isn’t perfect – but it’s still our best defence against influenza



Early indications are that the vaccine has been a reasonably good match in the 2019 season.
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Lauren Bloomfield, Edith Cowan University

Over recent months, reports of “a horror flu season” causing serious illness and death have dominated the headlines.

The high number of cases has led some people to question the effectiveness of the flu vaccine, and whether it’s worth getting if it doesn’t guarantee you won’t get the flu.

The flu vaccine is designed to cover the strains of the flu anticipated to circulate during the season. But even with the most sophisticated scientific processes, determining the right strains to include in the vaccine isn’t 100% foolproof.




Read more:
When’s the best time to get your flu shot?


Sometimes the virus undergoes major genetic changes or “mutations” in a relatively short space of time. Reports of a “mutant strain” this year means there’s concern some people might catch a strain the vaccine hasn’t protected against.

It’s too soon to tell the full extent of the effects of this mutation on how well the vaccine has worked. But the 2019 vaccine is showing early signs of being a good match for the common strains of the flu circulating this season.

What’s in a name?

Influenza or “flu” isn’t just one virus; different strains circulate each season.

Flu viruses that cause seasonal epidemics in humans fit under one of two major groups: influenza A or B.

Most flu vaccines protect against four strains of influenza.
Image Point Fr/Shutterstock

Influenza A is further broken down into strains or subtypes based on surface proteins called hemagglutinin (H) and neuraminidase (N).

We’re currently concerned about two subtypes which cause outbreaks in humans: A/H1N1pdm09 and A/H3N2.

Influenza B viruses are similarly categorised into strains based on two distinct lineages: B/Yamagata and B/Victoria.

Understanding the circulating strains is important because it gives us clues as to which age groups will likely be worst affected. Influenza A/H3, for example, has historically been associated with higher rates of disease in people aged 65 and over.

But the circulating strains are also important because they inform how the vaccine will be developed. A good match between the vaccine strains and what is circulating will mean the vaccine offers the best possible protection.

So how do we decide which flu strains are covered by the vaccine?

Every year, a new vaccine is produced to cover the strains that are predicted to be circulating in the northern and southern hemispheres. The World Health Organisation (WHO) uses a range of measures to determine which strains should be included in the vaccine.

Many of us who were vaccinated this year would have received a quadrivalent vaccine. This means it covered four strains in total: two strains of influenza A, and two strains of influenza B.

People aged 65 and over are offered a “high-dose” trivalent vaccine, which covers both A strains, and one B strain.




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High-dose, immune-boosting or four-strain? A guide to flu vaccines for over-65s


The Australian Influenza Vaccine Committee (AIVC) reviews the results and makes recommendations for the Australian vaccine, which in 2019 covered the following strains:

  • an A/Michigan/45/2015 (H1N1)pdm09-like virus
  • an A/Switzerland/8060/2017 (H3N2)-like virus
  • a B/Colorado/06/2017-like virus (Victoria lineage) – not included in the trivalent vaccine recommendation
  • a B/Phuket/3073/2013-like virus (Yamagata lineage).

Do we always get it right?

The basic premise of forecasting is that it’s a “best guess”. It’s a highly educated guess, based on analysis and evaluation, but it’s not a guarantee.

The effectiveness of a vaccine depends on a number of factors, only some of which are within our control. While the choice for the vaccine is made on the best evidence available at the time, the viruses circulating in the population undergo changes as they replicate, known as antigenic “drift” and “shift”.

Flu viruses change every year so researchers have to make an educated guess about which ones might circulate.
Image Point Fr/Shutterstock

If the changes are only small, we can still get good cross-protection.

Less frequently, a big genetic “shift” happens. If this occurs after vaccine development has started and the strains have been chosen, we are dealing with a so-called “mutant flu” and the vaccine will likely not be a good match.

So is this year’s vaccine is working?

Data available for this year are showing the majority of influenza cases in Australia have been influenza A – with some states reporting more H3N2 than H1N1, and others reporting a more even mix of both.

The WHO Collaborating Centre in Victoria is also reporting that the majority of specimens of all four strains they’ve tested this year appear to be similar to the vaccine strains.




Read more:
We can’t predict how bad this year’s flu season will be but here’s what we know so far


While early indications are that the vaccine has been a good match in the 2019 season, the WHO Collaborating Centre has also recently confirmed there has been a mutation in the A/H3N2 strain this season.

It’s not clear yet if this mutation will have a significant impact on vaccine effectiveness, but it may at least partially explain the high case numbers we’ve seen so far.

Large vaccine effectiveness studies done at the end of the flu season will help assess the impact of this mutation. In the meantime, a mismatch on only one strain means the vaccine will still provide reasonable protection against other circulating strains.

It’s still worth being vaccinated

In the same way wearing a seat belt is no guarantee we won’t be injured in a car accident, a flu vaccine is no guarantee we won’t develop influenza this season.

A person’s underlying susceptibility, due to factors such as their age and health, will also influence how well a vaccine works.




Read more:
Kids are more vulnerable to the flu – here’s what to look out for this winter


But the flu shot remains a safe and reasonably effective strategy to reduce your risk of serious illness.

While flu epidemics remain complex, advice to prevent flu transmission remains simple. Regularly washing our hands, covering our mouth when we cough or sneeze, and staying home when we’re unwell are things we can all do to help stop the spread.The Conversation

Lauren Bloomfield, Lecturer, School of Medical and Health Sciences, Edith Cowan University

This article is republished from The Conversation under a Creative Commons license. Read the original article.

You can’t get influenza from a flu shot – here’s how it works


You might feel a bit off after your flu shot but this doesn’t last long.
Rawpixel.com/Shutterstock

Allen Cheng, Monash University and Katherine Kedzierska, University of Melbourne

Influenza is a moving target for vaccines. Each year, up to four different strains circulate, and they are constantly evolving to escape our immune system.

So rather than childhood jabs giving long lasting immunity, we need annual flu shots to provide optimal protection against influenza.

But while you might sometimes get sick after having a flu shot, it’s a myth that having a flu shot can give you the flu.

A quick history of the flu vaccine

Influenza vaccines were first developed in the 1930s and 1940s, starting with the isolation of the influenza virus.

Back then, we learned there were many different influenza strains. To be effective, early research showed the vaccine needed to be matched to the circulating strains, and to be able to stimulate a response from the immune system.




Read more:
When’s the best time to get your flu shot?


The process to produce modern influenza vaccines now occurs on a much more refined and industrial scale. Hundreds of thousands of influenza viruses are collected by hundreds of national influenza centres around the world.

From these, four strains are selected for the annual flu vaccine, based on the viruses that are circulating at that time, how well the vaccines activate the immune system, how the strains are evolving, and the effectiveness of previous vaccines.

Modern flu vaccine development is slow and labour-intensive process.
hotsum/Shutterstock

Most modern vaccines are manufactured by growing large quantities of live virus – mostly in chicken eggs or less commonly animal cells – which are then purified, deactivated and split into smaller components. These vaccines are inactive and cannot replicate.

There are also two new “enhanced” vaccines that are used in older people, who don’t tend to respond as strongly to vaccines: Fluzone High Dose and Fluad, which is designed to better stimulate immunity and draw immune cells to the site of vaccination.




Read more:
High-dose, immune-boosting or four-strain? A guide to flu vaccines for over-65s


How the immune system fights the flu

The human immune system has several strategies to protect against infection. For viral infections such as influenza, the key strategy is known as adaptive immunity. This part of the immune system can “remember” previous exposure to pathogens.

When you get an influenza infection, the virus enters and hijacks the machinery of the host cell to replicate itself, before releasing these copies to infect more cells.

T lymphocyte cells of the immune system can recognise this viral incursion. T cells protect against further spread of the virus by activating pathways that cause infected cells to trigger a “suicide” process.

Another strategy the body uses is to produce antibodies, which are molecules produced by B cells that recognise components of the viral capsule. These antibodies work by sticking to the surface of the influenza virus to prevent it spreading and facilitating disposal.

Flu shots help mount a quicker defence

On a first exposure to a pathogen, our B cells take at least two weeks to ramp up production of antibodies. However, on subsequent challenges, antibody production occurs much more quickly.

Influenza vaccines harness this arm of the immune system, known as “humoral” immunity. By “practising” on viral components, vaccines allow the immune system to react more quickly and effectively when faced with the real virus.

The flu shot takes about two weeks to start protecting you against influenza.
DonyaHHI/Shutterstock

So why do you sometimes get sick after a flu shot?

There are several reasons why you might feel a bit off after getting your flu shot.

First, your flu shot only protects you against influenza and not other respiratory illness which might causes similar cold or flu symptoms. This includes RSV (respiratory syncytial virus), which is common in late autumn and early winter.




Read more:
Sick with the flu? Here’s why you feel so bad


Second, stimulating the immune system can result in symptoms similar to that of influenza, although much milder and short-lived. These include local inflammation (redness, pain or swelling at the site of the vaccine) and more general symptoms (fever, aches and pains, tiredness).

Third, vaccine-induced protection isn’t complete. In some years, the vaccine is not well matched to circulating strains. Usually this is due to mutations that may develop in circulating strains after the vaccine strains are selected.

The flu vaccine also doesn’t “kick in” for two weeks after vaccine administration. In some people, particularly those who are older and those who have weakened immune systems, antibody production is not as strong, and the level of protection is lower.

Despite this, studies have consistently shown that vaccinated people are less likely to get influenza or complications from the flu than those who aren’t vaccinated.




Read more:
Flu vaccine won’t definitely stop you from getting the flu, but it’s more important than you think


A better way to protect against the flu

A problem with current vaccines is the reliance on eggs, which results in a relatively slow and labour-intensive production process.

Current work is aiming to speed up this process by using different technologies so that vaccine manufacturers can react more quickly to changes in circulating viruses.

The “holy grail” for influenza vaccines is to stimulate an effective immune response to a component of influenza that doesn’t change each year, so annual vaccination is not required.

These efforts have proved elusive so far.




Read more:
The Holy Grail of influenza research: a universal flu vaccine


A better strategy might be to harness T cell immunity. Recent work has shown that a type of T cell, known as “killer” T cells, can recognise other parts of the influenza virus, and therefore can provide broad protection against seasonal and pandemic strains.

But while we wait for a better alternative, getting an annual flu shot is the best way to avoid the flu.The Conversation

Allen Cheng, Professor in Infectious Diseases Epidemiology, Monash University and Katherine Kedzierska, Academic, Microbiology and Immunology, University of Melbourne

This article is republished from The Conversation under a Creative Commons license. Read the original article.

The flu vaccine is being oversold – it’s not that effective



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The protection of the flu vaccine is minimal, and may not be worth it.
from shutterstock.com

Chris Del Mar and Peter Collignon, Australian National University

Winter has started, and with it, flu season. Inevitably, all of us (young, old and sick) have been implored to be immunised against influenza, with some eligible for a subsidised vaccine. And people are heeding the message, to the point that there is now a shortage of available vaccines.

At the same time, findings from three important Cochrane reviews on the effectiveness of the influenza vaccination aren’t consistent with the advice we’re been given.

Cochrane reviews are independent systematic reviews, which are comprehensive analyses of most of the literature relevant to a research topic. Cochrane reviews summarise the results in a multitude of studies, and are regularly updated to absorb new research.

These three Cochrane reviews have been recently updated, as well as stabilised, which is what happens when it looks as if it seems unlikely new research would be published that would change the conclusions.

What the reviews found

The first Cochrane review looked at the effects of the influenza vaccine in healthy adults from 25 studies conducted over single influenza seasons in North America, South America, and Europe between 1969 and 2009. It found the vaccine reduced the chance of getting laboratory confirmed influenza from 23 cases out of 1,000 to 9 cases out of 1,000.

While this seems to be a reduction of more than 50%, that seems less optimistic expressed in absolute terms.

The infection rate in adults drops from 2% per year to 1%. You could say that’s halved, but it effectively only drops by 1%. So this means that out of every 100 healthy adults vaccinated, 99 get no benefit against laboratory confirmed influenza.




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What you need to know to understand risk estimates


The second Cochrane review – which looked at trials in children over single influenza seasons in the US, Western Europe, Russia, and Bangladesh between 1984 and 2013 – found similar results.

The third Cochrane review looked at vaccines for the elderly in nursing homes. It found much less good evidence, with only one randomised trial – considered the gold standard in clinical trials as it establishes causation rather than correlation.

While observational studies (that draw inferences from a population to establish associations) have been done to show benefits of the vaccines, bias means we cannot rely on their results.

There are also potential harms from influenza vaccines noted in the reviews. They range from serious (a neurological disease called Guillain Barre) through to moderate (fevers, in children especially – some of which will cause febrile convulsions), and trivial (a sore arm for a couple of days).

Why are we so scared of the flu?

There is a special concern about influenza from a public health point of view. This comes about from its potential to cause pandemics. The first in modern history was the Spanish influenza pandemic of 1918-19, when tens of millions of people died worldwide.

There’s good evidence to show face masks protect against influenza.
from shutterstock.com

There have also been been several, less severe pandemics. These include the most recent swine flu that, although while affecting some (unexpected) groups of people (including pregnant women, those who were obese, and had asthma), caused little more effect on the overall population than the usual seasonal influenza.




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Public health experts worry about another pandemic that can be more harmful and contagious, which could be devastating. But it’s important to note the vast majority of deaths from Spanish influenza were from secondary bacterial infections and predated the antibiotic era.

The reasons influenza virus has this ability to cause new pandemics comes from its instability – it changes genetically easily, making it more difficult for our immune systems to recognise newer strains. The effect is that new vaccines must be prepared every year for a best-guess at next year’s virus, and we need vaccination every year.

Influenza can also undergo a more radical change, such as when a new form of the virus emerges from an animal host (wild or domesticated birds or pigs, for example). This moving target makes it more difficult to vaccinate against – especially with the genetic shifts of pandemics. Just when we need protection most, vaccines can provide it least.

So what, if not the vaccine?

There are physical barriers that can prevent the spread of influenza. These are the masks (to reduce the spread of aerosol-borne virus particles), hand washing (to reduce the spread if virus from hands onto shared surfaces), and quarantine measures (isolating infected people to reduce their infectivity).




Read more:
I’ve always wondered: why many people in Asian countries wear masks, and whether they work


The ConversationThere is now reasonable evidence such measures reduce infections considerably. It might take a bit of effort to change the psyche of Australians to make wearing a facemask acceptable if you have an acute respiratory infection. Even the heroic “soldiering on to work” (or school) with your virus needs to be reversed as a public health act.

Chris Del Mar, Professor of Public Health and Peter Collignon, Professor, infectious diseases and microbiology, Australian National University

This article was originally published on The Conversation. Read the original article.

Explainer: what’s new about the 2018 flu vaccines, and who should get one?


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The flu shot is free for at-risk groups, and available to others for around $10-$25.
Shutterstock

Kanta Subbarao, The Peter Doherty Institute for Infection and Immunity

As winter draws closer, many Australians are wondering whether this year’s influenza season will be as bad as the last, and whether they should get vaccinated.

For most of us, influenza (the flu) is a mild illness, causing fever, chills, a cough, sore throat and body aches, that lasts several days. But some people – especially the elderly, young children and those with chronic diseases – are at risk of serious and potentially deadly complications.

While not perfect, the seasonal influenza vaccine is the best way to protect against influenza viruses. It’s free for at-risk groups, and available to others for around A$10A$25 (plus a consultation fee if your GP doesn’t bulk bill). In some states people can also get influenza vaccines from pharmacies.

Different viruses

There are four influenza viruses that cause epidemics: two type A viruses, called A/H1N1 and A/H3N2 and two type B influenza viruses, called B/Yamagata and B/Victoria viruses. All four cause a similar illness called influenza.

In any season, one of the viruses may dominate, or two or even three viruses could circulate.




Read more:
Influenza: The search for a universal vaccine


Last year’s influenza seasons in Australia and the United States were caused by A/H3N2, while B/Yamagata viruses predominated in Asia, and a mix occurred in Europe.

Influenza A/H3N2 viruses cause more severe epidemics that affect the entire population, from the very young to the very old.

In contrast, influenza B and A/H1N1 viruses tend to cause disease in children and young adults, respectively, sparing the elderly.

Developing the vaccine

Although influenza activity around the world is monitored throughout the year, influenza viruses mutate continuously and we can’t predict which virus will dominate. For this reason, the influenza vaccine includes components that are updated to protect against all four influenza A and B viruses.

Vaccination is the best option to prevent influenza and is offered in the autumn, in anticipation of influenza season in the winter. Typically, the influenza season begins in June, peaks by September and can last until November.

For best protection, you need a flu vaccine each year. Roberty Booy, Head of the Clinical Research team at the National Centre for Immunisation Research and Surveillance, explains why (via the Australian Academy of Science).

It takes about two weeks for the vaccine to induce immunity and the resulting protection lasts about six months.

The 2017 influenza season was severe in all states except WA. The epidemic began earlier than usual, there were more reported cases than in previous years, and there were a large number of outbreaks in residential care facilities in several jurisdictions.




Read more:
Here’s why the 2017 flu season was so bad


Who is most affected?

People of all ages can get influenza but some people are at greater risk of severe illness and complications that require hospitalisation. These groups include:

  • older adults who are over 65 years of age
  • children aged under five years and especially children under one
  • pregnant women
  • Aboriginal and Torres Strait Islander persons
  • people with severe asthma or underlying health conditions such as heart or lung disease, low immunity or diabetes.
Anyone can get a flu vaccine but some people have to pay for it.
Shutterstock

While the National Immunisation Program provides vaccines free of charge for the groups listed above, anyone who wants to reduce their risk of influenza can get vaccinated.

What’s new this year?

There are two notable changes.

One change is that several states (Tasmania, Victoria, New South Wales, Queensland, Western Australia and the ACT) are now offering free vaccination for children under five years of age.




Read more:
Thinking about getting your child the flu vaccine? Here’s what you need to know


This is important because children are prone to severe illness and they spread the virus to their contacts, at home and in daycare. Previously, only WA offered children the influenza vaccine free of charge.

The second change is “enhanced” vaccines are available for adults over the age of 65. The standard influenza vaccine is not optimally effective in older adults.

Two products have been developed to improve the immunity offered by the vaccine: one is a high-dose vaccine four times the strength of the standard vaccine and the second is an “adjuvanted” vaccine, that contains an additive that boosts the immune response to the vaccine.




Read more:
Here’s what you need to know about the new flu vaccines for over-65s


These vaccines have been available in other countries for many years but are being introduced in Australia for the first time in 2018. Older adults will be offered one of the two enhanced vaccines for free.

What happens if you still get influenza?

Even if you’re vaccinated, you can still get influenza.

The effectiveness of the seasonal influenza vaccine varies and is usually around 40-50%. But last year’s vaccine was only around 33% effective overall, because it was not effective against the A/H3N2 virus though it was effective against the A/H1N1 and influenza B viruses.

While vaccines are given ahead of time to prevent influenza, antiviral drugs are available via GP prescription for people who get infected.

The antiviral drugs for influenza are most effective when taken within two days of illness and are only effective against influenza viruses. But they’re not effective against other respiratory viruses that cause colds and respiratory symptoms.

Influenza is a contagious virus that spreads through contact with respiratory secretions that are airborne (such as coughs and sneezes) or that contaminate surfaces (after wiping a runny nose, for instance). If you have influenza, stay home to avoid spreading the virus.

The ConversationUnfortunately, we can’t predict whether the 2018 influenza season will be mild or severe. Once we know which virus or viruses are circulating, we may be in a better position to predict how severe the season will be for older adults.

Kanta Subbarao, Professor, The Peter Doherty Institute for Infection and Immunity

This article was originally published on The Conversation. Read the original article.