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tag:theconversation.com,2011:/institutions/the-peter-doherty-institute-for-infection-and-immunity-2255/articles The Peter Doherty Institute for Infection and Immunity 2019-04-17T06:37:25Z tag:theconversation.com,2011:article/115293 2019-04-17T06:37:25Z 2019-04-17T06:37:25Z Explainer: what is Candida auris and who is at risk?

First recognised ten years ago, Candida auris is a fungus within the genus Candida. From shutterstock.com

We've recently heard a lot about Candida auris, a deadly, multidrug-resistant fungus emerging around the world. This pathogen has been labelled the new "fungal superbug" and poses a significant threat to public health.

C. auris tends to infect people with weakened or compromised immune systems. It thrives on the skin where it persists for long periods.

It also sheds into the patient's environment – commonly a hospital or aged care home – and sticks to and survive on surfaces very well.

In hospitals, invasive fungal infections, particularly candidiasis caused by C. auris, can jeopardise patient safety and worsen outcomes after cancer treatment or surgery.

But it's tricky to diagnose, and, importantly, C. auris has a resistance profile that can make it very difficult to treat.

Many people who get sick with an infection caused by C. auris won't survive.

   Read more: A frenemy fungus provides clues about a new deadly one

How common is this deadly fungus?

C. auris was first identified in 2009 in Japan.

Infections have since been reported in a range of countries, but the prevalence of C. auris has likely been underestimated in most places. This is because it's hard to identify, and surveillance programs, where they exist, may not capture all cases.

The Centres for Disease Control and Prevention in the United States report that 617 cases of C. auris have been detected in the US.

 <img alt="" src="https://images.theconversation.com/files/269453/original/file-20190416-147525-1xpqzyv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/269453/original/file-20190416-147525-1xpqzyv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=285&fit=crop&dpr=1 600w, https://images.theconversation.com/files/269453/original/file-20190416-147525-1xpqzyv.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=285&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/269453/original/file-20190416-147525-1xpqzyv.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=285&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/269453/original/file-20190416-147525-1xpqzyv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=358&fit=crop&dpr=1 754w, https://images.theconversation.com/files/269453/original/file-20190416-147525-1xpqzyv.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=358&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/269453/original/file-20190416-147525-1xpqzyv.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=358&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
 Countries from which Candida auris cases have been reported as of February 2019. CDC

Australia has had very few cases, and the cases we have seen have mainly been acquired overseas.

The Victorian health department notes hospital stays in a number of affected areas such as the UK, India, Pakistan, China, South Africa and parts of the US may pose a risk.

How does it manifest and how is it diagnosed?

C. auris seems to most commonly colonise and infect people who are already sick or have compromised immune systems, such as cancer or transplant patients, or hospitalised patients who are very young or very old.

Risk factors include suppression of the immune system (such as via medication after organ transplants to prevent organ rejection), recent surgery, diabetes, and the presence of an in-dwelling medical device such as a catheter.

   Read more: Deadly frog fungus has wiped out 90 species and threatens hundreds more

The presence of the fungus on the body, called colonisation, doesn't necessarily cause illness.

But invasive candidiasis (that is, invasive infection with Candida species) can infect the bloodstream (candidemia), central nervous system and internal organs.

When the infection spreads to the bloodstream, it can manifest as sepsis, with symptoms including fever, rapid breathing, muscle pain, and confusion.

Just like serious bacterial infections, C. auris may form abscesses in different parts of the body and may require surgery.

 <img alt="" src="https://images.theconversation.com/files/269505/original/file-20190416-147508-180wcfm.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/269505/original/file-20190416-147508-180wcfm.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=340&fit=crop&dpr=1 600w, https://images.theconversation.com/files/269505/original/file-20190416-147508-180wcfm.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=340&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/269505/original/file-20190416-147508-180wcfm.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=340&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/269505/original/file-20190416-147508-180wcfm.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=428&fit=crop&dpr=1 754w, https://images.theconversation.com/files/269505/original/file-20190416-147508-180wcfm.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=428&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/269505/original/file-20190416-147508-180wcfm.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=428&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
 C. auris spreads in hospitals and other health-care settings. From shutterstock.com

It can be difficult to diagnose fungal infections and accurately identify the species that has caused the infection. C. auris is very similar to other common fungi of the Candida genus and can be misidentified.

In most Australian hospitals, we use a blood culture diagnostic test. This is time-consuming and relies on specialists to accurately identify the pathogen.

Alternatives such as molecular diagnostic tests are not routinely used in many hospitals due to their cost, and, even when they are, they may not be able to accurately identify the type of fungus that has caused the infection.

However, these tests are improving and will become more widely available soon.

Outcomes for people who contract C. auris

Patients with weakened immune systems who have candidemia or invasive candidiasis have a 30-60% chance of dying after becoming infected.

But it can be very difficult to tell if these patients die from their infection, or die with their infection, given infection typically occurs when a person is already very sick.

   Read more: Explainer: why do we get fungal nail infections and how can we treat them?

Another problem is that treatment with antifungal drugs is routinely delayed. The time between the taking of a blood sample and the delivery of a test result often extends beyond 48 hours, which can lead to delayed or inappropriate treatment (because the cause of infection is still unknown).

Delaying antifungal therapy is associated with an increased risk of death.

For these reasons, we need better tests to diagnose fungal infections.

Why resistance has developed

C. auris has developed resistance to several different antifungal drugs.

While its resistance profile varies geographically, C. auris is almost universally resistant to fluconazole, a dependable drug in the azole class of antifungal drugs – one of the four main classes of existing antifungal drugs.

We need to learn more about this, but it's been suggested the prevalence of antifungal use in the environment contributes to the acceleration of resistance.

For example, in the presence of azole-based pesticides, we've seen the emergence of azole-resistant Aspergillus, another genus of fungi. Resistant strains then reproduce in the soil, and infections may be contracted from spores in the air that are inhaled.

Similar processes may also have led to the emergence of resistant C. auris, but we don't know this for sure.

   Read more: Five of the scariest antibiotic-resistant bacteria in the past five years

How can we control it?

C. auris is notoriously hard to clear. It poses enormous challenges for hospital cleaning and infection control.

In addition to disinfectants with antifungal activity, hydrogen peroxide vapour or UV light are now also used, when feasible, to clean contaminated environments.

Australia is on high alert, and hospitals screen patients who may have been exposed.

But we need continued vigilance, co-ordinated efforts to stop its spread in hospitals, and to diagnose it early. We also need to use antifungal agents wisely in human health and the environment.

This article has been updated to refer to Candida auris as "multidrug-resistant" rather than "antibiotic-resistant".

Monica Slavin receives funding from National Health and Medical Research Council and Melbourne Health foundation and has received funding from Victorian State Government Fight Cancer foundation and Cancer Council. She has also received research and educational grants from Merck, Gilled and Pfizer

Karin Thursky receives funding from NHMRC

Arjun Rajkhowa and Megan Crane do not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.
 Candida auris is a fungus which breeds most commonly in health-care settings. It's cause for concern because it's hard to detect, and is resistant to many anti-fungal drugs. Monica Slavin, Head, Department Infectious Diseases, Peter MacCallum Cancer Centre, Peter MacCallum Cancer Centre Arjun Rajkhowa, Project officer, Department of Medicine and Radiology, University of Melbourne Karin Thursky, Professor, The Peter Doherty Institute for Infection and Immunity Megan Crane, Research and Operations Manager, The National Centre for Infections in Cancer, Peter MacCallum Cancer Centre Licensed as Creative Commons – attribution, no derivatives. tag:theconversation.com,2011:article/105647 2018-10-25T05:53:43Z 2018-10-25T05:53:43Z We have so many ways to pursue a healthy climate – it's insane to wait any longer

Opportunities to help drive the energy transition are everywhere - even in Western Australia's remote salt pans. Peter C. Doherty, Author provided

As a broadly trained life scientist, my concern about climate change isn't the health of the planet. The rocks will be just fine! What worries me is a whole spectrum of "wicked" challenges, from sustaining food production, to providing clean water, to maintaining wildlife diversity and the green environments that ensure the survival of complex life on Earth.

What's more, as a disease and death researcher, I think of climate change as equivalent to lead poisoning: slow, cumulative, progressive and initially silent but, if not treated in time, causing irreversible, catastrophic damage.

The link between climate change and human health is obvious. The likely success of Dr Kerryn Phelps in the Wentworth byelection also suggests the informed public gets it. More broadly, Doctors for the Environment Australia has campaigned vigorously against Adani's proposed Queensland coal mine, and has very strong student chapters. Young people are energised and, as they mature and take power, the political and legal situation regarding energy generation could change very quickly.

   Read more: Infographic: here's exactly what Adani's Carmichael mine means for Queensland

The world's oldest medical journal, The Lancet, has a high-profile commission that will report every two years until 2030 on the broad-ranging issue of climate and human health. The journal has just published a letter from just about every leading Australian medical scientist working in a relevant area that protests the federal government's contemptuous dismissal of the latest report from the Intergovernmental Panel on Climate Change.

   Read more: The UN's 1.5°C special climate report at a glance

Astronauts have shown us how incredibly fragile the atmosphere looks from space. The idea that we should wait for things to get worse before taking action to protect it seems insane.

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 Apollo 8 gave us a valuable perspective on our planet. NASA

We need legislators who can think and act for the long term. This issue is simply too big for individuals or volunteer groups. Unless politicians are prepared to put a substantial price on greenhouse emissions, it's difficult to see how a capitalist economic system can move us forward. Clean coal? The US 45Q tax reform, which offers credits for carbon capture and storage projects, suggests we would need a carbon price of at least US$50 a tonne to make this technology economically feasible.

Australia's governments at every level could be acting now to promote the planting of vegetation, including less readily combustible tree species. We could be embracing, and funding, energy efficiency while constructing all new buildings – especially hospitals and large apartment complexes – in ways that protect their inhabitants. A realistic carbon tax could pay for some of that, while also stimulating jobs and growth and providing investment certainty.

Some moves are already being made in the right direction. The Gorgon gas project is planning to extend its strategy to inject carbon dioxide into the ground rather than releasing it to the atmosphere. CSIRO's new hydrogen economy roadmap shows how (with the endorsement of Chief Scientist Alan Finkel) we can develop gas exports based on hydrogen rather than natural gas, to supply emerging markets in countries such as Japan.

   Read more: The science is clear: we have to start creating our low-carbon future today

A more familiar export product is wood. Planting and harvesting trees mimics nature's mechanism for storing carbon. Perhaps it's time for CSIRO and the universities to reinvest in developing wood technologies that displace concrete for at least some forms of construction. Modular wooden houses could also easily be moved away from low-lying areas hit by river flooding and sea level rise.

My wife Penny and I recently joined a small organised tour that took us more than 5,000km around Western Australia. That made us very aware of competing realities. On one hand, we have the human constructs of community, politics and economy. On the other is the reality of nature, imposed by the laws of physics and the fact that all life systems have evolved to live within defined environmental "envelopes".

Apart from the glorious WA wildflowers and extensive wheat fields, the prominence of mining was very clear. Metals are essential for just about any renewable energy strategy, although the massive amounts of diesel burned in the extraction process are clearly an issue. Could that transition to carbon-neutral biodiesel?

WA also has extensive coastal salt pans: might they be used, perhaps with pumped seawater, to cultivate algae for biofuel production? And, in the face of a global obesity pandemic, the best thing we could do with sugar cane is to convert it to biofuels.

If ethanol is bad for internal combustion engines, perhaps we should revisit external combustion? In WA, we went to the HMAS Sydney memorial in Geraldton. Like all big ships of her time, the Sydney was powered by steam turbines. Turbine power generation could be part of a mix driving electric/wind ships of the future.

Our WA trip also made us very conscious of the complex ecosystems that, in the end analysis, sustain all life. Plants use chemical signals (plant pheromones) to "talk" among themselves, to other species, and to the insects they attract for pollination. Some plants rely for reproduction on a single insect species. If the insects die, they die. We're currently in the sixth mass extinction – this one caused by humans. As temperatures ramp up, rainfall patterns change, and firestorms grow stronger and more frequent, the effects will be terminal for many species.

   Read more: Earth's sixth mass extinction has begun, new study confirms

With much of our land unsuited to agriculture, Australia is the biggest solar collector on Earth. Visiting WA also made us very aware of the enormous, untapped wind potential on the west coast. Apart from battery storage, making hydrogen from seawater offers an obvious strategy for dealing with both the remoteness of generation sites and the variability of supply from renewables, while also returning oxygen to the atmosphere. We could be the clean energy giants!

None of this will happen without the help of major corporations that have the wealth and power to influence governments, along with the globalised structure that facilitates the development and implementation of solutions. What's very encouraging is that many of the multinationals are now moving forward to develop strategies for supplying global energy needs while minimising greenhouse gas emissions. There's no way they want to be the "tobacco villains" of the 21st century!

This is an adapted version of a speech given in Melbourne on October 24 at the international ghgt-14 meeting.

Peter C. Doherty is a member of the Scientific Committee of Doctors for the Environment Australia and a board member of the Melbourne Sustainable Society Institute.
 Nobel Prizewinning health researcher Peter Doherty reflects on the challenge of delivering a healthy climate for the world. From hydrogen power to wooden skyscrapers, the options are endless, but all require leadership. Peter C. Doherty, Laureate Professor, The Peter Doherty Institute for Infection and Immunity Licensed as Creative Commons – attribution, no derivatives. tag:theconversation.com,2011:article/102334 2018-09-02T20:10:08Z 2018-09-02T20:10:08Z Dismissed under Mussolini, later Nobel prize winner – the importance of scientist Rita Levi-Montalcini

Rita Levi-Montalcini celebrates her 100th birthday in 2009.  Presidenza della Repubblica Italiana/Wikimedia Commons , CC BY

Peter Doherty was invited to deliver the 2015 Rita Levi-Montalcini Lecture at BergamoScienza, an Italian science festival.

In this extract from his new book The Incidental Tourist, Peter explains how Rita was a true hero of 20th century science.

Rita Levi-Montalcini (1909–2012) grew up in Turin, a two-hour drive from Bergamo, Italy.

While we never met, my early background in brain pathology (she was a developmental neurobiologist) and the fact that she was a prominent public advocate for science (and supporter of BergamoScienza) meant that I was well aware of her.

Levi-Montalcini was a co-recipient (with Vanderbilt University's Stanley Cohen) of the 1986 Nobel Prize in Physiology or Medicine, and was also appointed by the president of Italy as Senator for Life (from 2001) in the upper house of the national Parlamento della Republica Italiana.

There is no doubt that Levi-Montalcini spoke out strongly for the value of looking at public policy through the prism of actual evidence – although, as with any scientist who deals directly with politicians, there must have been a high level of mutual incomprehension.

Even so, given that many of the profound changes in our world are driven by science and technology, along with the ethical challenges that new knowledge raises for both policy and the law, finding some mechanism for getting at least a small measure of scientific understanding into politics does seem like a reasonable idea.

   Read more: Australia needs boldness and bravery from Karen Andrews, the new minister for industry, science and technology

At least until recently, Britain appointed leading scientists (including Sydney Boys High School/University of Sydney-educated Bob May and Geelong Grammar/University of Melbourne-trained Alec Broers) to the House of Lords.

Few professional scientists will take up the challenge of seeking elected office, although Germany's Angela Merkel, a physics PhD, is a notable exception.

There were also three PhD physicists, Rush Holt, Bill Foster and Vernon Ehlers, in the 110th (2007–09) US Congress.

Qualifying first as an MD, Levi-Montalcini was dismissed from her assistant professorship in anatomy at the University of Turin when Benito Mussolini's National Fascist Party passed a 1938 law banning all Jews from academic appointments.

Having some family resources, and maybe as a result of good luck and a move from Turin to Florence, she and her twin sister Paola (a well-known artist) avoided the fate of being transported to Auschwitz.

Fellow Turin scientist and author, the industrial chemist Primo Levi, did not, and he describes in If This is a Man how he survived that ordeal due to his technology skills.

   Read more: 70 years on, Primo Levi's If This is A Man is still a powerful reminder of what it means to be human

Continuing to do investigative work in a laboratory set up in her bedroom, Levi-Montalcini spent much of the second world war focused on the factors that determine nerve growth in chick embryos. Even in wartime, it was possible to get hold of fertilised hens' eggs!

In my field, a great deal of important virology and immunology research was done initially with chick embryos (especially by Sir Macfarlane Burnet, as I described in Sentinel Chickens: What birds tell us about our health and our world). But I was only peripherally aware of Levi-Montalcini's work with developing chicks until, seeking to acknowledge her achievements at the beginning of my Bergamo lecture, I looked into her career more closely.

As often happens when I read about the lives and contributions of leading biologists of an earlier era, I find a record of dedication and intellectual clarity based on simple, elegant experimentation and insight. She was continuing a great Italian tradition.

The science of embryology began in the 17th century when, working in Bologna, Marcello Malpighi described the progression he saw when he examined chick embryos at different stages of development.

   Read more: I've always wondered: can two chickens hatch out of a double-yolk egg?

Early vertebrate evolution followed common pathways for birds and for us and, even in an era where human dissection was forbidden, the all-controlling Church of Rome could hardly object to cracking open hens' eggs.

Remarkably, some religious fundamentalists believe that embryology, in the words of US Republican Congressman (2007–15) Paul Broun, "lies straight from the pit of hell"!

Given that such research just describes what's actually there, it's hard to comprehend a mindset that finds the most obvious realities of biology to be obnoxious. Remarkably, Broun is a medical doctor!

After the liberation of northern Italy in April 1945, Levi-Montalcini volunteered her medical services to help the allies in Florence.

She then moved to the United States to continue her focus on nerve growth in the research group led by eminent émigré German/Jewish developmental biologist Viktor Hamburger at the Washington University of St Louis. There she also began her professional association with biochemist Stan Cohen, her co-Nobel Prizewinner.

Appointed as full professor at Washington University in 1958, Levi-Montalcini was, by 1961, directing the Research Centre for Neurobiology in Rome.

Thereafter, while continuing her US collaborations, she saw out her research career in Italy.

Peter C. Doherty does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.
 Born in Italy in 1909, Levi-Montalcini avoided being transported to Auschwitz as a young woman and rose to prominence as a neurobiologist. She was a co-recipient of the 1986 Nobel Prize for Medicine. Peter C. Doherty, Laureate Professor, The Peter Doherty Institute for Infection and Immunity Licensed as Creative Commons – attribution, no derivatives. tag:theconversation.com,2011:article/91351 2018-05-29T19:51:17Z 2018-05-29T19:51:17Z The bugs we carry and how our immune system fights them

The immune system has to establish which cells belong to us and which are foreign, no mean feat.  www.shutterstock.com

This article is part of a three-part package exploring immunity and infectious diseases around the world. Read the other articles here.

Human beings are large, complex, multicellular, multi-organ systems. We reproduce slowly and rely on a breadth of mechanisms that allow us to control the myriad of rapidly replicating, simple life forms that have evolved to live in or on us.

The system of defence is referred to collectively as immunity.

The word itself comes from the Latin immunis, describing the status of returned soldiers (Genio immunium) in the Roman state who were, for a time, exempt from paying taxes.

Our immunity protects us from many illnesses, including some forms of cancer. New cancer therapeutics, called immunotherapies, work by boosting our immune cells to fight cancer cells that have found ways to evade them.

The immune system is divided into two interactive spheres, the much older "innate" sphere, and the more recently evolved "adaptive" sphere. A primary challenge for the very specifically targeted cells that form the basis of adaptive immunity is to distinguish "self" (our own body cells and tissues) from "non-self" – the foreign invaders. When that goes wrong, we can develop autoimmune diseases such as multiple sclerosis or rheumatoid arthritis.

   Read more: Explainer: what are autoimmune diseases?

The organisms we carry around with us

The human body is host to many organisms over a lifetime. Some are dangerous to health (pathogens), some are benign, and some are necessary for proper functioning.

Most of the genetic material we carry around with us is "non-self": principally harmless bacteria (called "commensals") that live in the gastrointestinal tract.

Traditionally, studies focused on the "bad bugs" in our gut that cause diarrhoea and dysentery. But more recently, we're learning there are also good guys. And there's a general consensus we need to know more about the "microbiome", the mass of bacteria in any "clinically normal" gut.

Gut bacteria provide essential vitamin B12 and when they die, release myriad proteins that will be broken down into amino acids, which the body needs. About 30% of our poo is comprised of dead bacteria.

Apart from our microbiome, normal human beings also have a substantial "virome". Viruses differ from bacteria (which are cells in their own right) in that they are much simpler and can only replicate in living cells.

The greatest number of viruses we carry around are the "bacteriophages", which infect the commensal bacteria in our gut. Not all "phages" are, however, benign. For example, the toxin that causes human diphtheria is encoded in the genome of a bacteriophage.

There's also a spectrum of viruses that persistently infect our body tissues. The most familiar are herpes viruses, like those that cause cold sores (H. simplex) and shingles (H. zoster). Both viruses hide out in the nervous system and are normally under immune control. They re-emerge to cause problems as a consequence of tissue stress (such as a sunburnt lip) or as immunity declines with age (shingles). This is why a booster shingles vaccine is recommended for the elderly.

   Read more: Essays on health: microbes aren't the enemy, they're a big part of who we are

Our innate and adaptive immune systems

The innate system ranges from processes as basic as phagocytosis (ingestion of bacteria), to molecules like the interferons produced by any virus-infected cell that can limit replication. Such innate systems are found right across the evolutionary spectrum and don't target specific pathogens.

The much younger adaptive immune system is what we stimulate with vaccines. A property of small white blood cells called lymphocytes, it divides broadly into two lineages: the B cells and T cells. These bear the extraordinarily diverse and very specific immunoglobulin (Ig) and T cell receptor (TCR) recognition molecules that detect invading pathogens (bacteria, virus, fungi and so on).

The immunoglobulins bind to "non-self" (foreign) proteins called "antigens", while the T cell receptors are specifically targeted to "self" transplantation molecules.

The assassins of the immune system are then switched on; the killer T cells that eliminate virus-infected (or cancer) cells. Also activated are the "helper" T cells that secrete various molecules to "help" both the B cells and killer T cells differentiate and do their work.

   Read more: Explainer: what is the immune system?

How does our immune system learn and remember?

All lymphocyte responses work by massive cell division in the lymph nodes (the "glands" in our neck that swell when we get a sore throat). This process is started by small numbers of "naive" B and T cells that haven't encountered the invader before, and only stops when the foreign invader is eliminated.

The B cells differentiate into large protein-secreting cells called plasma cells, which produce the protective antibodies (immunoglobulins) that circulate for years in our blood.

Most of the T cells die off after they've done their job, but some survive so they can remember how to target specific invaders. They can be rapidly recalled to their "killer" or "helper" function.

Prior infection or the administration of non-living or "attenuated" (to cause a very mild infection) vaccines sets up the memory so protective antibodies are immediately available to bind (and neutralise) pathogens like the polio or measles virus. While immune T cells are rapidly recalled to "assassin" status and eliminate pathogen-infected cells.

As you may have gathered from this very brief and far too simplified account, the immune system is extraordinarily complex. And it's also very finely balanced with, for example, cross reactive responses to bacterial proteins sometimes setting us up for autoimmune diseases.

   Read more: No, combination vaccines don't overwhelm kids' immune systems

Another example of autoimmunity is rheumatoid arthritis, which can be triggered by blood-borne chemicals from tobacco smoke that modify "self" transplantation molecules in the joints.

And when we talk about the possible effects of the microbiome, or the "too clean" hypothesis, we're discussing how exposure to bacteria and viruses can modify that immune balance in ways that directly affect our wellbeing. This is a very active area of research which, given the underlying complexity, presents scientists with big challenges as we seek to reach verifiable conclusions.

Peter C. Doherty is a Chief Investigator on an NHMRC Program grant focused on immunity to the influenza viruses. He chairs the board for the ARC Centre of Excellence for Convergent Bio-NanoScience and Technology, and is a member of advisory boards for Doctors for the Environment Australia, the Melbourne Sustainable Society Institute and the International One Health Initiative.
 Nobel laureate Peter Doherty explains immunity. Peter C. Doherty, Laureate Professor, The Peter Doherty Institute for Infection and Immunity Licensed as Creative Commons – attribution, no derivatives. tag:theconversation.com,2011:article/94514 2018-04-18T04:40:35Z 2018-04-18T04:40:35Z Explainer: what's new about the 2018 flu vaccines, and who should get one?

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

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$10-A$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.

 <img alt="" src="https://images.theconversation.com/files/215147/original/file-20180417-101497-1qm9u9o.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/215147/original/file-20180417-101497-1qm9u9o.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=397&fit=crop&dpr=1 600w, https://images.theconversation.com/files/215147/original/file-20180417-101497-1qm9u9o.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=397&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/215147/original/file-20180417-101497-1qm9u9o.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=397&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/215147/original/file-20180417-101497-1qm9u9o.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=499&fit=crop&dpr=1 754w, https://images.theconversation.com/files/215147/original/file-20180417-101497-1qm9u9o.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=499&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/215147/original/file-20180417-101497-1qm9u9o.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=499&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
 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.

Unfortunately, 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.

The WHO Collaborating Centre for Reference and Research on Influenza in Melbourne is supported by the Australian Government Department of Health.
 While not perfect, the seasonal flu vaccine is the best way to protect against influenza. There are a few changes to the flu vaccine and what is available this year. Here's what you need to know. Kanta Subbarao, Professor, The Peter Doherty Institute for Infection and Immunity Licensed as Creative Commons – attribution, no derivatives. tag:theconversation.com,2011:article/94656 2018-04-10T11:15:07Z 2018-04-10T11:15:07Z What is hepatitis A and how can you get it from eating frozen fruit?

Imported frozen pomegranate seeds have been linked to hepatitis A infections in NSW. from www.shutterstock.com

Seven people in New South Wales have been diagnosed with hepatitis A after eating imported frozen pomegranate seeds from Coles. Although still under investigation, the company responsible for production recalled the implicated product as a precaution.

Around 40,000 packs of Creative Gourmet Frozen Pomegranate Arils have been sold since hitting the shelves in September 2017. NSW Health is advising consumers to immediately dispose of any in their possession.

What is hepatitis A?

Hepatitis A is a virus that infects the liver. Symptoms usually take 15-50 days to develop after initial infection and typically last for several weeks or sometimes longer.

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

Symptoms can range from fever, weakness, tiredness, loss of appetite, nausea, muscle aches, vomiting and jaundice (yellow discolouration of the eyes and skin). Sometimes there are no symptoms, particularly among young children.

Liver failure and death from hepatitis A are very rare but occasionally occur among those with existing chronic health conditions, especially those that affect the liver. Hepatitis A vaccination is recommended for those living with hepatitis B and C.

How does it spread?

Hepatitis A is spread when a person ingests faecal matter from an infected person. This can occur through person-to-person contact (including through sexual or even seemingly trivial household contact), or consumption of contaminated food and water.

Hepatitis A is quite an infectious virus. Only microscopic amounts of poo are needed to infect people and cause symptoms. People living in the same house with a person with hepatitis A have an increased risk of acquiring hepatitis A unless receiving preventive interventions.

The virus can survive on hands and other surfaces such as cooking utensils and plates for hours. So it's important to ensure that infected people properly wash their hands after using the toilet, and completely avoid handling food.

Hepatitis A infections occur infrequently in Australia, with the number of cases detected dropping profoundly in the last 20 years. Most infections are in people who have travelled in countries where hepatitis A transmission is common due to poor sanitation and lack of access to safe water.

When outbreaks occur, they are due to contaminated foods, as we saw with the frozen pomegranate seeds, or person-to-person transmission. This is the case for the current outbreak in Victoria, which has predominantly been spread between sexual partners, although other routes of transmission have also occurred.

 <img alt="" src="https://images.theconversation.com/files/214038/original/file-20180410-75793-12boag.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/214038/original/file-20180410-75793-12boag.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/214038/original/file-20180410-75793-12boag.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/214038/original/file-20180410-75793-12boag.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/214038/original/file-20180410-75793-12boag.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/214038/original/file-20180410-75793-12boag.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/214038/original/file-20180410-75793-12boag.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
 Hepatitis A can survive on your hands for hours, so it's important to wash thoroughly to prevent transmission. from www.shutterstock.com

How is it treated?

Although hepatitis A can cause significant illness, the body usually recovers without treatment and becomes immune to future infections.

A highly effective hepatitis A vaccine has been available for decades, and once fully vaccinated (two vaccinations spaced at least six months apart), you're protected for life.

Has this happened before?

Pomegranates have been linked to outbreaks internationally but not in Australia.

Past food-related outbreaks in Australia have occurred in oysters, lettuce, semi-dried tomatoes and frozen berries.

Imported frozen berries from the same producer implicated in the pomegranate associated outbreak were recalled due to linked cases of hepatitis A in 2015 and again in 2017.

These outbreaks led to some questions regarding the screening and regulations of imported food coming into Australia and prompted new regulations by the Department of Agriculture, requiring the producer of imported berries to be declared. The Department of Agriculture and Food Standards Australia New Zealand (AFANZ) also issued guidance and recommendations to ensure industry producers are compliant with Australia's food standards.

Microbiological screening tests for imported berries currently only involves testing for the intestinal bacterium E.Coli.

Why is this happening again?

Contamination of pomegranates, berries and other food products with hepatitis A can occur at several points of production, through:

the use of contaminated water during irrigation

the processing and cleaning stages, or

handling by people infected with hepatitis A who may not have washed their hands prior to processing and packaging the fresh product.

Both pomegranates and berries require large amounts of water and handling for processing, so it's not surprising these types of outbreaks have occurred in Australia and across the world.

These outbreaks tend to be reported in countries such as Australia with low rates of hepatitis A. This is because there are more susceptible people in the population who aren't immune from natural infections earlier in life. Also, these countries tend to have better functioning surveillance systems and relatively good access to health care.

Freezing fruit does not inactivate the hepatitis A virus, which remains stable and able to cause human infections when consumed. Heat can kill the virus, however the berries need to stay heated at 85 degrees Celsius for at least one minute.

Should I be worried?

Although this imported frozen pomegranate product has been linked to hepatitis A, no fresh (or Australian-produced) pomegranate has been connected with the recent hepatitis A cases.

If you have eaten any of the implicated pomegranate seeds within the last few weeks and are experiencing any symptoms, see your doctor for a blood test and don't forget to wash your hands.

Benjamin Cowie receives funding from the Australian Government Department of Health, the Victorian Government Department of Health and Human Services, the Royal Melbourne Hospital Office for Research, and the Cooperative Research Centre for Spatial Information.

Nicole Romero receives funding from the Australian Government Department of Health and the Victorian Government Department of Health and Human Services.
 Hepatitis A is a virus that infects the liver. Symptoms usually take 15-50 days to develop after initial infection and typically last for several weeks or sometimes longer. Benjamin Cowie, Director, WHO Collaborating Centre for Viral Hepatitis, The Peter Doherty Institute for Infection and Immunity Nicole Romero, Epidemiologist, WHO Collaboating Centre for Viral Hepatitis, The Peter Doherty Institute for Infection and Immunity Licensed as Creative Commons – attribution, no derivatives. tag:theconversation.com,2011:article/93853 2018-03-26T19:01:01Z 2018-03-26T19:01:01Z Climate policy is a fiendish problem for governments – time for an independent authority with real powers
From global epidemics to global economic markets to the global climate, understanding complex systems calls for solid data and sophisticated maths. My advice to young scientists contemplating a career in research is: "If you're good at maths, keep it up!"

I'm no mathematician – my research career has focused largely on the complexities of infection and immunity. But as recently retired board chair of the ARC Centre of Excellence for Climate System Science, I've been greatly informed by close contact with mathematically trained meteorologists, oceanographers and other researchers, who analyse the massive and growing avalanche of climate data arriving from weather stations, satellites and remote submersibles such as Argo floats.

   Read more: Why Australians need a national environment protection agency to safeguard their health

My perception, based on a long experience of science and scientists, is that these are outstanding researchers of impeccable integrity.

Among both the climate research community and the medically oriented environmental groups such as the Climate and Health Alliance and Doctors for the Environment Australia with which I have been involved, there is increasing concern, and even fear, about the consequences of ever-climbing greenhouse gas levels in the atmosphere.

The growing climate problem

Following the thinking of the late Tony McMichael, a Canberra-based medical epidemiologist who began studying lead poisoning and then went on to become a primary author on the health section of the Intergovernmental Panel on Climate Change's five-yearly assessment reports, I have come to regard human-induced global warming as similar in nature to the problem of toxic lead poisoning.

Just like heavy metal toxicity, the problems caused by atmospheric greenhouse gases are cumulative, progressive and ultimately irreversible, at least on a meaningful human timescale.

Regrettably, this consciousness has not yet seeped through to enough members of the Australian political class. The same lack of engagement characterises current national politics in Russia and the United States – although some US states, particularly California, are moving aggressively to develop alternative energy sources.

The latter is true for much of Western Europe. China and South Korea too are committed both to phasing out coal and to leading the world in wind and solar power technology. In collaboration with the US giant General Electric, South Korean and Japanese companies are working to develop prefabricated (and hopefully foolproof) small nuclear reactors called SMRs.

At this stage, China (currently the world's biggest greenhouse gas emitter) is humanity's best hope – if it indeed holds to its stated resolve.

Political paralysis

Politically, with a substantial economic position in fossil fuel extraction and export, Australia's federal government seems paralysed when it comes to taking meaningful climate action. We signed on to the Paris Agreement but, even if we meet the agreed reductions in emissions, precious little consideration is given to the fossil fuels we export for others to burn. And while much of the financial sector now accepts that any new investments in coalmines will ultimately become "stranded assets", some politicians nevertheless continue to pledge tax dollars to fund such projects.

What can be done? Clearly, because meaningful action is likely to impact both on jobs and export income, this is an impossible equation for Australia's elected representatives.

Might it help to give them a "backbone" in the form of a fully independent, scientifically and economically informed statutory authority, endowed with real powers? Would such an initiative even be possible under Australian law?

Realising that reasoned scientific and moral arguments for meaningful action on climate change are going nowhere fast, some 41 Australian environmental organisations sought the help of the Australian Panel of Experts on Environmental Law (APEEL) to develop the case for a powerful, independent Commonwealth Environmental Commission (CEC) linked to a National Environmental Protection Agency (NEPA).

This week in Canberra, at the culmination of a two-year process, the environmental groups will present their conclusions, preceded by a more mechanistic analysis from the lawyers.

In very broad terms, the new agencies would do for environmental policy what the Reserve Bank does for economic decisions. That is, they would have the power to make calls on crucial issues (whether these be interest rates or air pollution limits) that the government cannot veto.

Of course, that would require a government that is willing to imbue them with such power in the first place.

   Read more: Australia needs stricter rules to curb air pollution, but there's a lot we could all do now

While it's a good bet that developing such a major national initiative will, at best, be a long, slow and arduous process, it is true that (to quote Laozi): "A journey of a thousand miles begins with a single step."

What is also clear is that "business as usual" is not a viable option for the future economy, defence and health of Australia.

Peter C. Doherty is currently funded as a chief investigator on an NHMRC Program Grant focused on immunity to the influenza A viruses. He is a member of the scientific committee for Doctors for the Environment, Australia and and the advisory committee for the Melbourne Sustainability Society Institute.
 Scientific problems require evidence-led solutions. A new proposal to create a federal environmental decision-making body would take some of the politics out of climate policy. Peter C. Doherty, Laureate Professor, The Peter Doherty Institute for Infection and Immunity Licensed as Creative Commons – attribution, no derivatives. tag:theconversation.com,2011:article/82446 2017-10-02T00:44:51Z 2017-10-02T00:44:51Z Drug resistance: how we keep track of whether antibiotics are being used responsibly

Some patients may be prescribed antibiotics as preventatives, rather than to treat infections. from www.shutterstock.com.au

While we know increasing numbers of bacteria all over the world are becoming more resistant to existing antibiotics, we need to learn more about how antibiotics are being used in healthcare settings.

We know overuse and inappropriate use of antibiotics contribute to resistance, so it's important we monitor antimicrobial use and develop strategies to improve practice. Australia now has a national strategy to do so.

Importantly, a national surveillance report provides an overview of annually-updated data and analyses from relevant programs. This covers drug consumption in participating hospitals, appropriateness of use in participating hospitals, and prescribing data from GPs and residential aged-care facilities.

   À lire aussi : We know _why_ bacteria become resistant to antibiotics, but _how_ does this actually happen?

While some programs provide representative estimates of drug consumption, the National Antimicrobial Prescribing Survey (NAPS) is unique, in that it assesses the quality of individual patient prescriptions. This means it looks at whether prescriptions were compliant with clinical practice guidelines for the given indications (including drug choice and dose), and whether the overall drug use was appropriate and safe.

Assessing these factors helps to identify areas of inappropriate use and inform changes in clinical practice.

What the surveys found

In 2013-14, 151 hospitals (132 public and 19 private) from all states and territories participated in the NAPS. From that, 12,800 prescriptions for antimicrobial drugs were analysed. In 2015-16, 281 hospitals (213 public and 68 private) participated in the audit, and 22,021 prescriptions for antimicrobial drugs were analysed.

In 2015, on average, 40% of patients in hospitals were administered an antibiotic. Of these, 72% were found to have needed them as they were prescribed, and 35% had a review- or stop-date documented.

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 A survey found 22% of antibiotic use in hospitals was inappropriate. from www.shutterstock.com

Overall, 23% of prescriptions for antibiotics for hospitalised patients were deemed to be non-compliant with prescribing guidelines (40% in 2013-14), and 22% were assessed as inappropriate (29% in 2013-14).

   À lire aussi : FactCheck: Is Australia's use of antibiotics in general practice 20% above the OECD average?

Specific areas that needed attention were identified. In 2015, 40% of prescriptions for the prevention of surgical site infections were assessed as inappropriate. This was mainly because of incorrect duration (30%) and incorrect dose or frequency (28%), or because they were given for a procedure that does not require antibiotics to be used as preventatives (22%). Knowing these common errors means we can give feedback to doctors and, in some cases, help clarify guidelines or develop new ones.

Why does over-prescribing happen?

There are complex reasons why therapeutic drugs, including antibiotics, are sometimes inappropriately prescribed. These can include institutional or systemic cultures that have been in place for a long time. Knowledge gaps are an issue. Despite access to good-quality prescribing guidelines in hospitals, guidelines may not be consulted frequently. The fear of missing infections or adverse outcomes may contribute to excessive or inappropriate treatment.

Sometimes, a lack of resources means staff don't have the time to review a diagnosis and adjust treatments in a timely way. Some staff may recognise inappropriate use but are fearful about speaking up or contradicting another doctor. Cultural factors such as medical hierarchies can define the workflow in hospitals.

Until recently, there may have been a view that antibiotics "do no harm" and that prescribing "just in case", or giving more than is necessary, has no consequence.

   À lire aussi : Long courses, confusion and culture: why we're losing the fight against antibiotic resistance

What can we do about it?

There are no quick fixes when it comes to improving antibiotic prescribing, but concerted efforts can lead to change. Much progress has already been made in several countries, and Australia has been a leader in initiatives aimed at using antibiotics properly and responsibly in hospitals.

Programs aimed at improving antibiotic use are referred to as "antimicrobial stewardship". Australian hospitals were early adopters and initiators of antimicrobial stewardship programs.

It's widely recognised that alongside education and training for individual doctors, setting up systems that support better decision-making within hospitals is key to enhancing patient safety and care. Many Australian hospitals have decision-support and approval systems to monitor and control when and how antibiotics are used. This is sometimes coupled with post-prescription reviews by teams of experts, although this should happen more.

   À lire aussi : Use them and lose them: finding alternatives to antibiotics to preserve their usefulness

Regular auditing and feedback allow problem areas to be identified and strategies to be developed. The NAPS enables pharmacists and doctors in one facility to compare their performance with that of similar facilities.

In addition to providing a national overview of hospital prescribing and helping facilities monitor their performance over time, the NAPS serves to increase awareness of guidelines and appropriate prescribing in hospitals.

Through regular surveillance and the adoption of stewardship programs, we know we can improve antibiotic prescribing and patient care in hospitals.

Dr. Rod James, Caroline Chen, Sonia Koning, and Robyn Ingram of the National Antimicrobial Prescribing Survey program, and Dr. Arjun Rajkhowa from the National Centre for Antimicrobial Stewardship, contributed to this article.

Kirsty Buising is the deputy director of the National Centre for Antimicrobial Stewardship (University of Melbourne) and director of the Guidance Group (Royal Melbourne Hospital).

Karin Thursky is the director of the National Centre for Antimicrobial Stewardship (University of Melbourne) and the Guidance Group (Royal Melbourne Hospital). The National Centre for Antimicrobial Stewardship is an Australian National Health and Medical Research Council (NHMRC) Centre of Research Excellence.
 We know overuse and inappropriate use of antibiotics contribute to resistance, so it's important we develop strategies to improve practice. Kirsty Buising, Associate Professor, The Peter Doherty Institute for Infection and Immunity Karin Thursky, Professor, The Peter Doherty Institute for Infection and Immunity Licensed as Creative Commons – attribution, no derivatives. tag:theconversation.com,2011:article/83495 2017-09-21T01:05:00Z 2017-09-21T01:05:00Z I've always wondered: why is the flu virus so much worse than the common cold virus?

Flu seems to be more deadly than colds, here's why.  from www.shutterstock.com.au

This is an article from I've Always Wondered, a new series where readers send in questions they'd like an expert to answer. Send your question to firstname.lastname@example.com

I've always wondered why the influenza virus is more potent and dangerous than the common cold virus. They're both viruses, but what makes the influenza worse that it causes more deaths? - Junting Yeung

Thanks for the question Junting, and we have certainly seen a pretty bad year for flu in Australia. More than 160,000 people have been confirmed to have the flu this year, ranging from mild to severe, and some even causing death. So why is it the flu can cause death but we don't generally hear of colds doing the same?

What is the cold virus?

In contrast to flu, which is caused by variants of a family of genetically related influenza viruses, the "common cold" is caused by more than 200 different viruses, many of which are unrelated.

   Baca juga: H1N1, H5N1, H7N9? What on earth does it all mean

Not all common cold viruses are created equally, and the course of a "cold" depends to a degree on which cold virus a person is afflicted by. These viruses share a tendency to infect and replicate most effectively in the cooler environment of the upper airway, including the ears, nose, throat and sinuses.

Rhinovirus is the most common virus responsible, and tends to cause an infection of the upper airway, lasting a few days and improves on its own. Typically, rhinovirus binds to a receptor on the surface of cells in the nose and sinuses. This allows the virus to enter cells, start to replicate, and causes infected cells to produce molecules that lead to inflammation. These inflammatory molecules are thought to be responsible for the symptoms associated with the common cold; runny or blocked nose, sore throat and cough.

Infection is sometimes further complicated by inflammation in the sinuses and middle ear infection. Sometimes, infection can have no symptoms at all.

But infection can be more severe in patients with an impaired immune system, including those with cancer, on medications to suppress the immune response, or those undergoing a bone marrow transplant. Plus, the common cold may exacerbate or contribute to the development of chronic airway diseases, like asthma.

 <img alt="" src="https://images.theconversation.com/files/186539/original/file-20170919-32019-dwvuq9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/186539/original/file-20170919-32019-dwvuq9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/186539/original/file-20170919-32019-dwvuq9.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/186539/original/file-20170919-32019-dwvuq9.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/186539/original/file-20170919-32019-dwvuq9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/186539/original/file-20170919-32019-dwvuq9.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/186539/original/file-20170919-32019-dwvuq9.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
 Cold viruses tend to be self-limiting, meaning they go away by themselves. from www.shutterstock.com

What is the flu?

The illness you get when you catch influenza (the flu) varies widely, and depends on the person infected (the host), the virus, and secondary bacterial infections that may follow infection with the virus. The flu virus can infect both the upper and lower respiratory tract, which in part explains its ability to cause severe disease.

Other medical conditions, age and a weakened immune system also play a big part in how much the flu virus will affect the host. Plus, a person's genetic makeup may predispose them to a more severe inflammatory response, known as a "cytokine storm". Inflammation is a normal response that allows our body to fight infection and heal damaged tissue. Paradoxically, too much inflammation makes the illness from flu worse by causing more swelling and tissue destruction.

For the flu virus to bind to and infect cells in our respiratory tract it uses a molecule called "hemagglutinin". Bird and swine flu strains, which cause pandemics in humans may have a haemagglutinin molecule on their surface that preferentially binds to receptors in the lower respiratory tract, including the tiny air sacs (alveoli). These alveoli are responsible for transferring oxygen into and taking carbon dioxide out of the blood stream.

   Baca juga: Have you noticed Australia's flu seasons seem to be getting worse? Here's why

 <img alt="" src="https://images.theconversation.com/files/186541/original/file-20170919-32071-mtlgdw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/186541/original/file-20170919-32071-mtlgdw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=362&fit=crop&dpr=1 600w, https://images.theconversation.com/files/186541/original/file-20170919-32071-mtlgdw.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=362&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/186541/original/file-20170919-32071-mtlgdw.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=362&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/186541/original/file-20170919-32071-mtlgdw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=455&fit=crop&dpr=1 754w, https://images.theconversation.com/files/186541/original/file-20170919-32071-mtlgdw.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=455&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/186541/original/file-20170919-32071-mtlgdw.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=455&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
 The flu affects your upper and lower respiratory tract, and can cause subsequent bacterial infections, making it potentially dangerous. Demet/Flickr, CC BY

Infection and inflammation in the alveoli, can significantly impact the ability of the lungs to give the body enough oxygen. Also, the haemagglutinin molecule rapidly changes during and between flu seasons. Since haemagglutinin is an important target our immune system uses to protect against flu, this change means that infection or immunisation in one flu season doesn't usually prevent future infection. Our immune system only learns to fight off that specific strain, and not the one with the new mutations. This is why it's important to get immunised for flu every year.

The final aspect making flu so severe is that it makes you more likely to get bacterial infections, by weakening some of the natural defences of the respiratory tract. This includes damage to the surface of the airway, exposing molecules that bacteria can adhere to, and damaging the "mucociliary elevator"- tiny hair-like sturctures in the airway that catch and expel bacteria and mucus from the respiratory tract. These bacterial infections lead to further damage to lung tissue, more inflammatory cells, and can cause severe problems in your respiratory system. It is thought that most of the 100 million deaths that occurred during the Spanish flu pandemic of 1918 were due, at least in part, to secondary bacterial infection.

So why are there more flu deaths?

Both the common cold and flu can cause similar respiratory illnesses, and exacerbate underlying medical conditions. Important in both cold and flu is how the person's immune system is functioning, and the part of the airway infected.

In patients with flu, infection of both the upper and lower respiratory tract, the resulting local and systemic inflammatory response evoked by the virus, and the secondary consequences of infection are important determinants of how sick we get.

And these are in turn dependent on a combination of viral, bacterial and patient factors, including how effectively the virus infects, replicates and triggers the immune response, and the ensuing tissue inflammation and damage. Together, these can mean a person with the flu can have a spectrum of illness, from no symptoms at all to being potentially fatal.

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David Griffin tidak bekerja, menjadi konsultan, memiliki saham, atau menerima dana dari perusahaan atau organisasi mana pun yang akan mengambil untung dari artikel ini, dan telah mengungkapkan bahwa ia tidak memiliki afiliasi selain yang telah disebut di atas.
 Why is it the flu virus is so deadly compared to the common cold virus? David Griffin, Advanced Trainee, Infectious Diseases and General Medicine, The Peter Doherty Institute for Infection and Immunity Licensed as Creative Commons – attribution, no derivatives. tag:theconversation.com,2011:article/81672 2017-08-02T20:19:44Z 2017-08-02T20:19:44Z Dr G. Yunupingu's legacy: it's time to get rid of chronic hepatitis B in Indigenous Australia
News of the tragic death of Dr G. Yunupingu last week in Darwin at only 46 years of age has again highlighted the unacceptable gap in life expectancy between Aboriginal and Torres Strait Islanders and other Australians. Yunupingu had been living with chronic hepatitis B since early in life, and experienced complications of this condition including liver and kidney disease.

Hepatitis B infections, which can lead to liver disease and cancer, are unacceptably high in Indigenous Australians. In Northern Australia, 10-20% of the Indigenous population is infected with the virus. Eliminating the impact of this infection in Indigenous Australians would make a substantial contribution to closing the gap in life expectancy.

Hepatitis B in Indigenous Australia

Hepatitis B is the most prevalent form of viral hepatitis worldwide. It's also the leading cause of liver cancer. Interestingly, hepatitis B used to be known as the "Australia Antigen" as it was first discovered in Australian Aboriginal people in the 1960s.

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

Hepatitis B is around ten times more prevalent in Indigenous communities than in the rest of Australia. Of the nearly 240,000 Australians estimated to be living with chronic hepatitis B, over 20,000 are thought to be Indigenous people. New infections with hepatitis B remain three times as common in Indigenous people as in non-Indigenous Australians.

The chance of developing chronic hepatitis B depends on an individual's age at the time of infection. Around 90% of those who were exposed as infants develop chronic hepatitis B, but only 5% of those who were exposed as adults will develop chronic infection. Most people living with chronic hepatitis B were infected as young children – often, through mother-to-child transmission at the time of birth. This is why vaccination during infancy is particularly important.

The prevalence of chronic (long-term) hepatitis B in Indigenous Australians varies significantly between regions. It is most prevalent in remote areas of Australia, with the Northern Territory having the highest prevalence of any Australian jurisdiction. Around 1.8% of the NT population live with the disease.

The prevalence of hepatitis B and other communicable diseases such as skin infections and influenza in Indigenous communities is intensified by the social, economic, environmental and political situation in which Indigenous Australians find themselves.

Liver disease

In some people, chronic hepatitis B can cause severe liver scarring (cirrhosis) or liver cancer. Less commonly, hepatitis B can damage other parts of the body, including the kidneys and blood vessels.

Chronic liver disease contributes significantly to the Indigenous life expectancy gap. Liver cancer is the fastest-increasing cause of cancer deaths in Australia. In 2016, it was the sixth-most-common cause of cancer deaths. However, for Indigenous people it is the second-most-common cause of cancer-related death after lung cancer.

   Read more: Three charts on: cancer rates in Australia, where liver cancer is on the rise while other types fall

Compared to non-Indigenous Australians living in the NT, the rate of death due to liver cancer is six times greater in Indigenous Australians.

Cure is rare with liver cancer, and most Indigenous Australians die within a few months of being diagnosed. In the NT, a range of factors contribute to the unequal burden of liver cancer in Indigenous Australians, but hepatitis B is the most important cause.

Hepatitis B vaccine is one way

A safe, effective vaccine for hepatitis B has been provided for all infants in Australia since 2000 – and in the Northern Territory since 1990. As a result, new hepatitis B infections in children born since 2000, as well as those who received adolescent catch-up vaccination from 1998 onwards, have fallen markedly.

However, funded hepatitis B vaccine for Indigenous adults is available only in some states and territories. This limits access for Indigenous people who remain at much higher risk of infection. A recent study suggested a funded catch-up vaccination program for Indigenous adults could rapidly eliminate disparity in hepatitis B incidence.

Vaccination has no effect for those who already have chronic hepatitis B. It is believed over 90,000 Australians living with hepatitis B have never been diagnosed and are unaware of their infection. Only 15% of those infected are receiving treatment or monitoring for their condition.

Unlike hepatitis C, hepatitis B is not yet curable, but current treatments are very well tolerated and effective at preventing liver disease and liver cancer. The profound lack of access to treatment and care among Indigenous people contributes to the disproportionate impact of hepatitis B on this population.

   Read more: Australia leads the world in hepatitis C treatment – what's behind its success?

Other ways to reduce infections

An example of innovative care has been operating in Dr G. Yunupingu's home community of Galiwin'ku for over five years. Under the management of Miwatj Health, an Aboriginal community-controlled health organisation, a hepatitis specialist visits regularly three to four times per year.

The specialist brings necessary diagnostic equipment and effectively provides a "one-stop shop" for individuals living with hepatitis B in Galiwin'ku. Just as importantly, a local healthcare practitioner champions the cause of hepatitis B treatment and elimination. Those infected are contacted and encouraged to see the specialist team.

Several other regions in the world with large Indigenous populations and high hepatitis B prevalence, such as Alaska and New Zealand, have developed programs to test most of the population and identify those with hepatitis B infections. Affected individuals are offered regular follow-up and care to prevent cirrhosis and liver cancer.

When delivering such care to Indigenous communities, it's essential to develop trust and ensure culturally appropriate approaches. Also important is partnering with communities and their health workers to develop new ways of building awareness of hepatitis B as an important health issue.

With comprehensive public health initiatives, long-term commitment to funding and policy – including significant workforce development to ensure as many people as possible are tested and appropriately followed up – the impact of hepatitis B on Indigenous communities can be eliminated.

Benjamin Cowie receives funding from the Australian Government Department of Health, the Victorian Government Department of Health and Human Services, the Royal Melbourne Hospital Office for Research, and the Cooperative Research Centre for Spatial Information.

Steven Tong receives funding from the National Health and Medical Research Council and has received funding from Gilead for Hepatitis B related research projects.

James Ward does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.
 Hepatitis B rates in Indigenous communities are ten times higher than the rest of Australia. Eliminating the infection from Indigenous Australia can make a significant contribution to closing the gap. Benjamin Cowie, Director, WHO Collaborating Centre for Viral Hepatitis, The Peter Doherty Institute for Infection and Immunity James Ward, Associate Professor, Infectious Diseases Research Aboriginal and Torres Strait Islander Health, South Australian Health & Medical Research Institute Steven Tong, Associate Professor, The Peter Doherty Institute for Infection and Immunity Licensed as Creative Commons – attribution, no derivatives. tag:theconversation.com,2011:article/75460 2017-07-27T20:14:40Z 2017-07-27T20:14:40Z Why are only some viruses transmissible by blood and how are they actually spread?

The most important blood borne viruses for human health are the human immunodeficiency virus (HIV), Hepatitis B and Hepatitis C. from www.shutterstock.com.au

This week we're running a series in collaboration with the Australian Red Cross Blood Service looking at blood: what it actually does, why we need it, and what happens when something goes wrong with the fluid that gives us life. Read other articles in the series here.

Since the 1980s, most of us have been aware we need to be careful when coming into contact with the blood of others, because some viruses can be transmitted in this way. But why is it only some viruses are transmissible by blood, and how does the virus actually move from person to person?

Viruses are non-living, infectious agents that use our own cells to function and replicate. Unlike bacteria and fungi, they can't do this on their own, and must find an appropriate host cell they can enter and replicate in.

Blood-borne viruses are those found at levels that can be detected in an infected person's blood. They can be passed from person to person by blood, and in some cases other bodily fluids, including semen and breast milk. They can be transmitted from an infected person by intravenous drug use, a needle stick injury with contaminated needles, blood transfusions and sexual intercourse. They can also be transmitted from mother to child, before, during or even after birth.

The most important blood borne viruses for human health are the human immunodeficiency virus (HIV), Hepatitis B and Hepatitis C. These viruses persist in the blood long-term or for life.

 <img alt="" src="https://images.theconversation.com/files/171296/original/file-20170529-25201-1bhyruv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/171296/original/file-20170529-25201-1bhyruv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=900&fit=crop&dpr=1 600w, https://images.theconversation.com/files/171296/original/file-20170529-25201-1bhyruv.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=900&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/171296/original/file-20170529-25201-1bhyruv.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=900&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/171296/original/file-20170529-25201-1bhyruv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1130&fit=crop&dpr=1 754w, https://images.theconversation.com/files/171296/original/file-20170529-25201-1bhyruv.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1130&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/171296/original/file-20170529-25201-1bhyruv.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1130&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
 Most of us know blood-borne viruses can be spread by intravenous drug use and needle stick injuries. from www.shutterstock.com.au

Many other viruses may be found briefly in blood, but they generally don't persist and are not considered significant "blood-borne" pathogens. Any infectious agent with a blood-borne, or "viraemic" phase has the potential for blood borne transmission, and so may be important for blood transfusions.

For many infections, this viraemic period persists until the immune system is able to cure the infection by killing all infected cells. For some viruses, including Zika and Dengue, the viraemic phase lasts a matter of days. For other viruses such as Hepatitis B and C, or HIV, this viraemic phase persists.

Treatment of blood-borne viruses aims to stop the virus replicating. If a blood-borne virus is not detectable in blood, then a person is generally considered non-infectious.

How viruses spread through blood

HIV infection can occur when a person is exposed to this virus. Typically, this involves sexual contact or direct blood to blood contact, either via an open wound or penetration of skin by a contaminated needle.

The virus then travels to the lymph nodes, where it enters cells of the immune system called "T cells". Here, a cat and mouse battle begins. The virus and immune system use complex tactics to outsmart each other.

Perhaps the greatest of these tricks belong to HIV; the virus incorporates itself into the DNA of host T cells, and hides from the immune system in protected sites, such as the central nervous system. This makes it impossible to clear the virus from the body completely, and without treatment HIV remains detectable in blood.

The cells responsible for attacking the virus instead produce new virus particles and attack other, infected, T cells. Without treatment, this leads to destruction of the immune system, unusual infections and a syndrome known as the acquired immune deficiency syndrome (AIDS), which is almost invariably fatal.

In contrast, influenza is spread by respiratory droplets. Virus particles are transmitted when an infected person coughs or sneezes. Droplets are inhaled by a new host, the virus binds to target receptors on the respiratory tract surface, and replicates in cells of the respiratory tract.

Unlike HIV, influenza cannot insert itself into the host's genes. Instead, the immune system detects infection, turns off viral reproduction and clears infected cells. While medications are available to aid this process, they are often unnecessary, as the immune system is often able to cure influenza independently. Previous influenza infection or vaccination provides some immune memory and provides protection and faster immune clearance of the virus.

Influenza can be found in the blood for a brief period of time, particularly in severe cases, when the person is showing symptoms of flu. Although blood transfusions are not routinely tested for influenza infection, blood donors are asked not to donate if they are unwell.

Transmission via transfusion

Blood transfusions are an important, lifesaving component of modern medicine. But this technology is associated with a small degree of risk, including blood-borne virus transmission.

In Australia, blood transfusions are extremely safe, made secure by legislative, scientific, and practical measures. Legislation precludes certain groups of individuals from donating blood, with a view to minimising the chance of a person with a blood-borne virus donating.

Donated blood is tested for the most important blood-borne viruses, including HIV, Hepatitis B and Hepatitis C. These tests are highly sensitive, and detect close to 100% of these infections.

Blood products destined for recipients with weakened immune systems, like transplant recipients, are tested for additional viruses that are not considered problematic in most people.

Practically, a number of important safeguards are also in place to ensure that the right person gets compatible blood, at the right time.

The journey of blood.

Read other articles in the series:

Essays on blood: why do we actually have it?

From animal experiments to saving lives: a history of blood transfusions

Explainer: what's actually in our blood?

Blood groups beyond A, B and O: what are they and do they matter?

What can go wrong in the blood? A brief overview of bleeding, clotting and cancer

Blood tests and diagnosing illness: what can blood tell us about what's happening in our body?

The authors do not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.
 Why is it only some viruses are transmissible by blood, and how does the virus actually move from person to person? David Griffin, Advanced Trainee, Infectious Diseases and General Medicine, The Peter Doherty Institute for Infection and Immunity Thomas Schulz, Infectious diseases and general physician, The Peter Doherty Institute for Infection and Immunity Licensed as Creative Commons – attribution, no derivatives. tag:theconversation.com,2011:article/78101 2017-07-09T19:55:38Z 2017-07-09T19:55:38Z Four of the most lethal infectious diseases of our time and how we're overcoming them

Spanish flu killed more people than the Great War that preceded it. And tuberculosis even more than that.  from www.shutterstock.com.au

This is the first article in a four part series looking at how infectious diseases have influenced our culture and evolution, and how we, in turn, have influenced them.

In 2013, the World Health Organisation declared antibiotic resistance was a threat to global health security. It can seem hard to believe that in the 21st century infectious diseases remain such a profound existential risk. But this declaration highlights the ever-lingering threat of infectious diseases and our dependence on antibiotics to stave off their impact on human and animal health and industry.

It also reminds us to appreciate antibiotics as one of many advances in infectious diseases and public health during the past century, and reflect on some of the greatest, still persistent, infectious disease challenges facing us today.

Here we explore our past and present struggles with four of the most significant infectious diseases human beings have faced, some of the progress we've made in prevention and treatment, and possible future directions.

 <img alt="" src="https://images.theconversation.com/files/173514/original/file-20170613-603-1w4fr48.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/173514/original/file-20170613-603-1w4fr48.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=518&fit=crop&dpr=1 600w, https://images.theconversation.com/files/173514/original/file-20170613-603-1w4fr48.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=518&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/173514/original/file-20170613-603-1w4fr48.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=518&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/173514/original/file-20170613-603-1w4fr48.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=651&fit=crop&dpr=1 754w, https://images.theconversation.com/files/173514/original/file-20170613-603-1w4fr48.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=651&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/173514/original/file-20170613-603-1w4fr48.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=651&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
 Infectious disease deaths. Reprinted with permission from Macmillan Publishers Ltd: Nature. Paulson T. Epidemiology: a mortal foe. Nature 2013;502(7470):S2-3, copyright 2013

Tuberculosis

Tuberculosis (or TB) has been responsible for the death of more people than any other infectious disease in history; over a billion deaths in the past 200 years. Its origin is unclear, but it infects a number of other species, including cattle.

Today, about a third of the world's population is thought to be infected with TB, in its dormant form. This means the bacteria is present but it's controlled by the immune system, the infected person has no symptoms, and it can't be spread to others. The bacteria will reactivate in a small proportion of people and they may develop symptoms including fever, sweats, weightloss, fatigue, cough, and haemoptysis (coughing up blood).

TB occurs in every country, including Australia, but mostly occurs in people born in countries where TB is more common, due to the reactivation of dormant TB infection. Patients with weakened immune systems due to chemotherapy, HIV or other medical illnesses are at higher risk of TB.

In 2015, there were 10.4 million new cases of TB, and 1.8 million TB-related deaths around the world, with the vast majority of cases in developing countries. The infection and death rate have been declining internationally since the early 1900s.

Long before the availablility of treatment options, improvements in sanitation, housing, and vaccination led to a reduction in the rates of TB in some countries. But antibiotics made it a curable disease; without them, up to 70% of people with active infection die from TB.

But treatment is complicated, and typically involves taking four medications for two months, then two medications for a further four months. These medications are not without side effects, and can be poorly tolerated. Unfortunately, when medications are not taken or prescribed properly, the TB bacteria can become resistant to these treatments.

In recent years, drug-resistant TB has been documented all over the world, but is much more common in people previously treated for TB, and in Russia, China and India.

Treatment of resistant TB is much more complicated, takes longer, is more prone to failure, and often uses more toxic drugs. New rapid tests can diagnose TB, and whether or not the bacteria will be resistant to our first-line drugs.

A vaccine for TB has been available for around a century, but is most effective in preventing severe TB infection in children. The vaccine's efficacy is much less clear in adults.

Despite advances in treatment, tuberculosis continues to occur disproportionately in the developing world. Although progress is being made, ongoing and increased political and financial support is essential to ensure coordinated diagnosis, surveillance and care strategies, and universal access to these. Similarly, continued investment is needed for the development of new tools to detect and treat TB.

Smallpox

Smallpox was caused by the variola virus, which plagued humanity for millennia and had a lasting impact on human history. As late as the 1960s, smallpox was still endemic in Asia and Africa, with an estimated two million deaths occurring annually.

Smallpox was spread easily between people by sneezing or shared contact, leading swiftly to the characteristic disfiguring pustular lesions on the skin. The disease was severe, with about 30% of affected people dying, while the rest were left with complications associated with infection. These included a multitude of scars, blindness, infections and arthritis.

 <img alt="" src="https://images.theconversation.com/files/173912/original/file-20170615-510-c0icq3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/173912/original/file-20170615-510-c0icq3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=673&fit=crop&dpr=1 600w, https://images.theconversation.com/files/173912/original/file-20170615-510-c0icq3.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=673&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/173912/original/file-20170615-510-c0icq3.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=673&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/173912/original/file-20170615-510-c0icq3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=846&fit=crop&dpr=1 754w, https://images.theconversation.com/files/173912/original/file-20170615-510-c0icq3.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=846&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/173912/original/file-20170615-510-c0icq3.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=846&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
 A Palestinian smallpox victim in the early 20th century. from www.shutterstock.com

Those who survived, however, were generally protected from reinfection. Building on observations that milkmaids were protected from smallpox, Edward Jenner, an 18th century British physician, developed and popularised a technique called "vaccination" whereby he deliberately inoculated a patient with cowpox, a closely related virus the milkmaids were exposed to. This led to protection from smallpox.

While a popular origin story, alternative approaches to protection, such as inhaling dried smallpox lesions, had likely been practised in China and India for many years previously, and had already been introduced into the United Kingdom. However, inoculation with smallpox came with a risk of severe infection in a significant number of recipients, and Jenner's safer approach was adopted for larger scale immunisation programs.

In 1980, smallpox became the first, and so far only, human infectious disease to be declared eradicated by the World Health Organisation. This came about via a coordinated international response, led by an Australian microbiologist, Frank Fenner. This involved mass-vaccination, along with public health surveillance and preventative measures, which aimed to educate communities, and identify and contain individual cases.

The last case of smallpox was reported in Somalia in 1977, with the unfortunate death of medical photographer Janet Parker in 1978 serving as a final warning of this deadly condition.

Smallpox may be gone as a disease, but the variola virus controversially remains, kept secure in laboratories in Russia and the US. Concern has emerged about the prospect of smallpox as a weapon of bioterrorism. The impact of such an event could be devastating, given people are no longer routinely immunised against smallpox.

HIV/AIDS

In the early 1980s, a small number of gay men in the United States started presenting with unusual infections, previously only seen in people with severe immune deficiencies. Over the subsequent years, the human immunodeficiency virus (HIV) was discovered, and its global burden was recognised.

The virus, which had most likely originated in primates in Africa, had probably been infecting humans for close to a century, and had spread across the globe. Untreated HIV causes a slow destruction of the infected person's immune system, leading to a plethora of opportunistic infections and cancers, known as the acquired immunodeficiency syndrome (AIDS).

Without treatment, almost all people with HIV progress to AIDS, and die. At its peak in the 1990s, around 1,000 Australians a year died from HIV/AIDS.

HIV/AIDS mobilised western communities to act like never before. In Australia, a grassroots campaign led by communities most deeply affected resulted in a number of public health interventions and legislative changes. This included safe sex campaigns, needle exchange programs, and mandatory condom use and STI testing for commercial sex workers.

 <img alt="" src="https://images.theconversation.com/files/173920/original/file-20170615-25000-1nbagi9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/173920/original/file-20170615-25000-1nbagi9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=401&fit=crop&dpr=1 600w, https://images.theconversation.com/files/173920/original/file-20170615-25000-1nbagi9.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=401&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/173920/original/file-20170615-25000-1nbagi9.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=401&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/173920/original/file-20170615-25000-1nbagi9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=504&fit=crop&dpr=1 754w, https://images.theconversation.com/files/173920/original/file-20170615-25000-1nbagi9.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=504&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/173920/original/file-20170615-25000-1nbagi9.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=504&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
 HIV campaigns provided a good lesson in involving those most at-risk in health interventions. from www.shutterstock.com

These changes led to reductions in rates of new HIV cases, while global investment in research and public health led to the development of "antiretroviral" drugs, which stopped the virus from replicating, helped control HIV infection, and markedly reduced the risk of progression to AIDS.

To date, about 40 million people have died from AIDS, and an estimated 36.7 million are living with HIV. Nevertheless, most people affected by HIV in western countries live a long and healthy life.

Although an effective vaccine for HIV is not available, progress is being made in diagnosis, reducing transmission and improving the health of those affected.

Treating those with HIV to a point where the virus isn't detectable in their blood reduces the possibility of onward transmission by 90-95%. And it leads to numerous individual health benefits for the infected individual. In contrast, uninfected people at high risk of contracting the virus can take antiviral medications known as pre-exposure prophylaxis that prevent infection. These have shown to be highly effective if taken properly.

There are hopes these treatments will end the epidemic by 2030.

Influenza

It's easy to forget about the danger of influenza. In most cases, this virus is responsible for a respiratory illness of varying severity that generally doesn't require treatment. However, influenza has been responsible for more deaths in the last century than HIV/AIDS.

Usually, seasonal influenza outbreaks occur annually and affect around four million people, with about 250,000 deaths worldwide. Typically older patients, with pre-existing illnesses such as heart failure or chronic lung disease, and pregnant women are at the greatest risk of death.

Many people have a degree of immunity, due to vaccination or previous infection. It's worth noting that although safe, the influenza vaccine is imperfect; it's developed using strains of influenza virus circulating in winter, in the opposite hemisphere, and is about 50% effective at preventing infection. But vaccination is still an important strategy to protect those at risk of most severe infection. It reduces hospital admission and symptomatic infection.

Occasionally, an influenza virus not usually seen in humans is transmitted from its reservoir in aquatic birds, poultry or pigs, to humans. As a consequence, those exposed have no natural immunity, and are not protected by the vaccine at all. If this virus evolves to readily infect and spread between humans, it can have devastating consequences.

In the last century, this has happened several times, with numerous fatalities. The Spanish influenza pandemic of 1918 led to the deaths of more than 40 million people; more than double the number of fatalities in the First World War in the preceding four years. It progressively spread around the globe, with the modernisation of transport and trade systems, and mass-movement of military troops.

In more recent times, smaller outbreaks have occurred, with bird flu and swine flu. There is an ever-lingering threat of a repeat influenza pandemic, due to the industrial scale farming of chickens and pigs, that are also susceptible to infection and the close proximity of humans to these animals.

Due to the rapid and fluid movement of people around the globe for business and leisure, a new pandemic virus could easily be transported around the world. In recent years, countries have stockpiled influenza medications and vaccines in preparation for a possible influenza pandemic.

These are only four of the infectious diseases that have shaped the last century. In reality, there are a number that could have been included in this list of threats including polio, malaria, cholera and syphilis.

Each of these diseases is very different, and as such, our responses to them have been very different too. In part this is because quite different organisms cause these infections, but it's also because the social context in which diseases happen is critical.

If we are to save the world from the threat of infectious diseases, we need to learn the lessons of past outbreaks, including the value of international collaboration, perseverance and commitment to humanity.

 <img alt="" src="https://images.theconversation.com/files/176558/original/file-20170703-32607-pq54nk.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/176558/original/file-20170703-32607-pq54nk.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=1181&fit=crop&dpr=1 600w, https://images.theconversation.com/files/176558/original/file-20170703-32607-pq54nk.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=1181&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/176558/original/file-20170703-32607-pq54nk.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=1181&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/176558/original/file-20170703-32607-pq54nk.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1484&fit=crop&dpr=1 754w, https://images.theconversation.com/files/176558/original/file-20170703-32607-pq54nk.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1484&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/176558/original/file-20170703-32607-pq54nk.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1484&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
  The Conversation, CC BY-ND

Read the other instalments in the series:

How infectious diseases have driven human evolution

How we change the organisms that infect us

How infectious diseases have shaped our culture, habits and language

The authors do not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.
 Here we explore our past and present struggles with the most significant infectious diseases human beings have faced. David Griffin, Advanced Trainee, Infectious Diseases and General Medicine, The Peter Doherty Institute for Infection and Immunity Justin Denholm, Associate Professor, Melbourne Health Licensed as Creative Commons – attribution, no derivatives. tag:theconversation.com,2011:article/77725 2017-06-21T04:13:57Z 2017-06-21T04:13:57Z Speaking with: Peter Doherty about infectious disease pandemics
Humans have had to deal with infectious diseases for centuries. Ancient Greeks and Egyptians suffered from smallpox, leprosy and tuberculosis. And when an outbreak occurs, it can be devastating.

Pandemics like the Black Plague, Spanish Flu and HIV have killed millions of people around the world.

While improved sanitation and a better understanding of how infections spread has helped halt some pandemics, we are never truly safe. Recent outbreaks of Ebola in Western Africa and the Zika virus in the Americas show how vulnerable we are.

William Isdale speaks with Melbourne University Professor and Nobel prize winner Peter Doherty about how infectious diseases start and spread, and what can be done by governments, health organisations and individuals to minimise the threat of a pandemic.

Subscribe to The Conversation's Speaking With podcasts on iTunes, or follow on Tunein Radio.

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William Isdale does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.
 William Isdale speaks with the University of Melbourne's Professor Peter Doherty about infectious disease pandemics. William Isdale, Research Assistant, Melbourne Law School, University of Melbourne Licensed as Creative Commons – attribution, no derivatives. tag:theconversation.com,2011:article/76476 2017-04-20T23:32:58Z 2017-04-20T23:32:58Z Peter Doherty: why Australia needs to march for science

March for Science events will be held across the world on April 22 2017.  from www.shutterstock.com

The following article is adapted from a speech to be delivered at the Melbourne March for Science on Saturday 22 April, 2017.

The mission posted on the March for Science international website states:

The March for Science champions robustly funded and publicly communicated science as a pillar of human freedom and prosperity. We unite as a diverse, nonpartisan group to call for science that upholds the common good and for political leaders and policy makers to enact evidence based policies in the public interest. The March for Science is a celebration of science.

To me, it seems the reason concerned people across the planet are marching today is that, at least for the major players in the English-speaking world, there are major threats to the global culture of science.

Why? A clear understanding of what is happening with, for example, the atmosphere, oceans and climate creates irreconcilable problems for powerful vested interests, particularly in the fossil fuel and coastal real estate sectors.

Contrary to the data-free "neocon/trickle down" belief system, the observed dissonance implies that we need robust, enforceable national and international tax and regulatory structures to drive the necessary innovation and renewal that will ensure global sustainability and a decent future for humanity and other, complex life forms.

Here in Australia, the March for Science joins a global movement initiated by a perceived anti-science stance in Donald Trump's administration.

Trump's 2018 budget proposal

In the USA, President Trump's proposed budget for 2018 incorporates massive cuts to the National Science Foundation (NSF), National Oceanographic and Atmospheric Administration (NOAA), the United States Environmental Protection Agency (EPA) and the National Institutes of Health (NIH).

And, though it in no sense reflects political hostility and deliberate ignorance, British scientists are fearful that Brexit will have a terrible impact on their funding and collaborative arrangements.

How does this affect us in Australia? Why should we care? The science culture is international and everyone benefits from progress made anywhere. NOAA records, analyses and curates much of the world's climate science data. A degraded EPA provides a disastrous model for all corrupt and regressive regimes.

Science depends on a "churn", both of information and people. After completing their PhD "ticket", many of our best young researchers will spend 3-5 years employed as postdoctoral fellows in the USA, Europe and (increasingly) the Asian countries to our north, while young American, Asian and European/British scientists come to work for a time with our leading scientists.

The proposed 2018 US President's budget would, for example, abolish the NIH Fogarty International Centre that has enabled many young scientists from across the planet to work in North America. In turn, we recruited "keepers" like Harvard-educated Brian Schmidt, our first, resident Nobel Prize winner for physics and current Vice Chancellor of the Australian National University (ANU).

We might also recall that – supported strongly by Prime Ministers JJ Curtin and RG Menzies – the ANU (with 3 Nobel Prizes to its credit) was founded as a research university to position us in science and international affairs.

Not a done deal, yet

What looks to be happening in the US is not a done deal.

The US political system is very different from our own. The Division of Powers in the US Constitution means that the President is in many respects less powerful than our PM.

Unable to introduce legislation, a President can only pass (or veto) bills that come from the Congress. Through to September, we will be watching a vigorous negotiation process where separate budgets from the House and the Senate (which may well ignore most, if not all, of the President's ambit claims) will develop a "reconciled" budget that will be presented for President Trump's signature.

How March for Science might help

The hope is that this international celebration of science will cause US legislators, particularly the more thoughtful on the right of politics, to reflect a little and understand what they risk if they choose to erode their global scientific leadership.

There are massive problems to be solved, along with great economic opportunities stemming from the development of novel therapies and new, smart "clean and green" technologies in, particularly, the energy generation and conservation sector.

Ignoring, or denying, problems does not make them go away. Whether or not the message is welcome, the enormous power of science and technology means we can only go forward if future generations are to experience the levels of human well-being and benign environmental conditions we enjoy today.

There is no going back. The past is a largely imagined, and irretrievable country.

Peter C. Doherty is a founding board member of The Conversation, and is funded by an NHMRC Program Grant investigating immunity to the influenza A viruses. He will soon step down as Board Chair for the ending ARC Centre of Excellence for Climate Systems Science, and serves in that capacity on the ARC Centre of Excellence in Convergent Bio-Nano Science and Technology. His most recent book (2015) is 'The Knowledge Wars'.
 In its broadest sense, the March for Science aims to cause US legislators to reflect a little and understand what they risk if they choose to erode their global scientific leadership. Peter C. Doherty, Laureate Professor, The Peter Doherty Institute for Infection and Immunity Licensed as Creative Commons – attribution, no derivatives. tag:theconversation.com,2011:article/68225 2016-11-07T23:40:54Z 2016-11-07T23:40:54Z Australian law needs a refresher on the science of HIV transmission

Recent improvements in medical management of HIV infection are not well understood in the legal sector.  www.shutterstock.com

Being diagnosed with HIV is a confronting experience.

However the stigma associated with HIV infection – a hangover from its social and medical history – is responsible for an exaggerated perception of transmission risk through sex, and the harms of living with HIV infection.

In our consensus statement published this week in the Medical Journal of Australia, we detail the latest evidence on HIV transmission risk and recent advances in HIV prevention and treatment.

We propose that legal cases relating to HIV transmission should be considered in light of such evidence, and that alternatives to prosecution such as the public health management approach are often appropriate.

HIV infection no longer a death sentence

There have been many advances in HIV diagnosis, prevention and treatment since the identification of the first AIDS cases in the early 1980s.

In the initial days of the AIDS epidemic, patients would, after a number of years, develop serious infections and other illnesses due to their immune deficiency, usually resulting in death. When the first treatments became available, they bought time but often at the cost of serious medication side-effects, and complicated treatment regimens involving many tablets each day.

While it remains a serious infection, HIV is now a disease that can be effectively managed through medical treatment, regular health monitoring and healthy lifestyle. For many people with HIV, treatment involves taking only a single pill each day. Those taking antiviral therapy can expect to live a normal life, in good health, with a life expectancy similar to their HIV-negative counterparts.

These great improvements, familiar to those working in health, are not as well understood in the legal sector.

Prosecutions for HIV infection

Unlike other diseases, HIV has a long and uneasy relationship with criminal law. In the early years of the epidemic, the stigma around HIV, the fact that it was almost always fatal, and unfounded fears about its potential use as a weapon led to the criminalisation of HIV transmission and exposure.

Since 1991, there have been more than 38 criminal prosecutions for HIV transmission or exposure during sex in Australia. Despite the significant improvements in health and longevity of people living with HIV, the rate of criminal prosecutions has not decreased.

The courts have shown an understanding of the effectiveness of condoms: no one who has used condoms has been convicted. However, people continue to be prosecuted, including for "exposing" others to the risk of HIV infection, even in the absence of actual transmission. This occurs despite the relatively low per-act risk of HIV transmission and the fact that for most people the harms of HIV infection are far less serious than they once were.

New approaches to limit HIV transmission

HIV is actually difficult to transmit. Sexual transmission occurs during only about 1% (or less) of penetrative sexual encounters, even when a condom is not used and the HIV-positive person is not on treatment.

HIV prevention messaging in the early days of the epidemic focused on sexual abstinence and condom use. However, prevention messaging is now more nuanced and has expanded to include new ways of reducing HIV transmission risk. A not insignificant number of people at risk of HIV infection choose to have sex without using a condom, which is why developing alternative methods of HIV prevention have been prioritised in recent years. Such research has delivered game-changing results: "treatment as prevention" and "pre-exposure prophylaxis".

Treatment as prevention refers to the greatly reduced risk of HIV transmission as a result of HIV-positive people taking antiviral treatment, which suppresses replication of the virus in the infected person's body. When a person with HIV has a very low viral load (unmeasurable levels of HIV in the blood), the risk of sexual transmission becomes very low. In fact, there has never been a documented case of HIV transmission from a person with an undetectable viral load.

Pre-exposure prophylaxis describes the use of antiviral medication by an HIV-negative person as a way of preventing HIV infection. Pre-exposure prophylaxis is a very effective means of preventing HIV transmission, with only isolated cases of transmission identified among people applying this approach. This groundbreaking new strategy is available in Australia via limited pilot programs, and is being evaluated for Pharmaceutical Benefits Scheme listing.

How the law treats people with HIV

Criminal laws relating to HIV transmission and exposure vary from state to state, but a common factor is that people with HIV are expected to take "reasonable precautions" to prevent transmission. Condom use has long been accepted as meeting this threshold.

The evidence now supports acceptance of treatment as prevention (for the positive partner) and/or pre-exposure prophylaxis (for the negative partner) as meeting the same standard. And the limited harms of HIV infection as a consequence of acts involving low to negligible risk of transmission mean HIV cases generally do not belong in criminal courts.

There is an alternative. All states and territories have health protocols for managing allegations of risky behaviour. This public health approach – involving education, case management and, where required, behavioural orders and isolation – is a much more effective way of protecting public health.

As researchers and clinicians, we are intimately aware of the impact an HIV diagnosis can have. We have all supported patients coming to terms with an HIV diagnosis; many of us having had the painful task of delivering that devastating news.

The criminal law has a role to play, particularly should there ever be a case where a person deliberately transmits HIV.

However, with the advances of recent years in both prevention and treatment, authorities need to be more familiar with latest scientific and medical evidence, and consider alternatives to prosecution such as the public health management approach.

Elizabeth Crock, Australasian Society for HIV, Viral Hepatitis and Sexual Health Medicine, co-authored the consensus statement.

Andrew Grulich has given expert evidence in legal cases involving HIV transmission.

Nothing to disclose.

David Cooper, David Nolan, Levinia Crooks, Mark Boyd, Michelle Giles, and Sharon Lewin do not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.
 HIV diagnosis is devastating for patients and their families. But the infection is no longer a death sentence, and should not be prosecuted as such say experts. Mark Boyd, Professor, Chair of Medicine, University of Adelaide Andrew Grulich, Professor and Program Head, UNSW David Cooper, Scientia Professor of Medicine and Director, Kirby Institute, UNSW David Nolan, Adjunct Professor, Institute for Immunology and Infectious Disease , Murdoch University Levinia Crooks, Adjunct Associate Professor, La Trobe University Michelle Giles, Associate Professor, Department of infectious diseases and Dept of Obstetrics and gynaecology, Monash University Sharon Lewin, Director, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne and Royal Melbourne Hospital and Consultant Physician, Department of Infectious Diseases, Alfred Hospital and Monash University, The Peter Doherty Institute for Infection and Immunity Trent Yarwood, Infectious Diseases Physician, Senior Lecturer, James Cook University and, The University of Queensland Licensed as Creative Commons – attribution, no derivatives. tag:theconversation.com,2011:article/64979 2016-10-02T19:16:08Z 2016-10-02T19:16:08Z 20 years on, what impact has the Nobel Prize for medicine had on our immune systems?

The science is now used to tackle a range of diseases. tuthelens/Shutterstock

This time of year, Australians obsess over an annual spectacle that celebrates the achievements of our most gifted citizens – though usually, they're fixating on their respective football codes.

But an even bigger prize is up for grabs tonight – the Nobel Prize in Physiology or Medicine. It's the first of a big week celebrating the international heroes who receive Nobel Prizes for a range of disciplines, from physics, to economics, to literature.

Twenty years ago, the Nobel Prize in Physiology or Medicine was awarded jointly to Peter Doherty and Rolf Zinkernagel "for their discoveries concerning the specificity of the cell mediated immune defence".

What did they find?

Doherty and Zinkernagel made their Nobel-winning discovery while working at Canberra's Australian National University (ANU) in the early 1970s. Doherty, a veterinarian from Queensland, had only just returned to Canberra to set up a laboratory as an independent scientist. Zinkernagel had come to the ANU from Switzerland in 1973 to do his PhD.

The pair happened to share a lab and started talking. A year later, they co-authored two landmark papers in Nature, the Rolls-Royce journal for scientists in all disciplines globally.

Doherty and Zinkernagel had discovered how one critical part of the immune system, the T-cell, recognised and killed virus-infected cells. These killer T-cells patrol our bodies looking for foreign enemies – such as infections or cancer cells – and then move in to attack.

What Doherty and Zinkernagel discovered was the exquisite elegance with which the killer T-cells recognise the enemy.

They proved a radical new idea of how T-cells worked by recognising an "altered self": the enemy (for example, a virus) could only be recognised when it was presented in combination with the body's own machinery.

The body's protein alone or the virus alone didn't generate the molecular target for the killer T-cell to recognise.

Sounds simple, but the concept was revolutionary.

 <img alt="" src="https://images.theconversation.com/files/139534/original/image-20160928-725-1pygwmo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/139534/original/image-20160928-725-1pygwmo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=428&fit=crop&dpr=1 600w, https://images.theconversation.com/files/139534/original/image-20160928-725-1pygwmo.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=428&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/139534/original/image-20160928-725-1pygwmo.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=428&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/139534/original/image-20160928-725-1pygwmo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=538&fit=crop&dpr=1 754w, https://images.theconversation.com/files/139534/original/image-20160928-725-1pygwmo.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=538&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/139534/original/image-20160928-725-1pygwmo.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=538&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
 Doherty and Zinkernagel discovered how killer T-cells recognise the enemy. Tischenko Irina/Shutterstock

At the time, Doherty and Zinkernagel were studying mice infected with a virus called lymphocytic choriomeningitis virus (LCMV). But they and others went on to demonstrate that exactly the same process is used to tackle diseases as diverse as influenza, HIV and cancer. The implications of their findings have been spectacular and far-reaching.

In Doherty's Nobel speech, given in 1996 in Stockholm, he credited for his success the local intellectual environment in Canberra, the excellence in immunology across Australia and that there was "time to discuss and think things through" in the pre-fax, pre-email days. I suspect there was a bit more to it!

What does it mean for patients?

Doherty and Zinkernagel's insights into how killer T-cells recognise the enemy proved crucial for understanding how viral infections are controlled. More practically, this understanding now shapes modern treatment strategies for cancer and the design of vaccines.

To recover from the common flu, for example, we need T-cells and antibodies, another arm of the immune system. And recent findings by Katherine Kedzierska, a former trainee with Doherty, have shown how T-cell "memory" protects us against the flu.

Following HIV infection, as in flu, people also generate loads of antibodies and killer T-cells. Neither get rid of HIV completely in anyone. But in some people with the right genetic make-up and the right virus, they manage to keep the virus under control.

The explanation? These so-called "elite controllers" make stunningly potent killer T-cells that are able to recognise part of the HIV virus together with part of the body's immune system.

This finding in HIV-infected elite controllers has revamped our approach to searching for a successful HIV vaccine. We don't have one yet, but most think that generating effective killer T-cells will be critical.

Great strides have been made in the last few years about how to harness killer T-cells for cancer therapy. These drugs have literally just hit the clinic – only 12 months ago in Australia – with some spectacular results.

 <img alt="" src="https://images.theconversation.com/files/139535/original/image-20160928-716-1q1u6l2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/139535/original/image-20160928-716-1q1u6l2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/139535/original/image-20160928-716-1q1u6l2.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/139535/original/image-20160928-716-1q1u6l2.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/139535/original/image-20160928-716-1q1u6l2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/139535/original/image-20160928-716-1q1u6l2.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/139535/original/image-20160928-716-1q1u6l2.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
 Cancer immunotherapy has just become available. CI Photos/Shutterstock

In cancer (and in chronic infections such as HIV and indeed LCMV), killer T-cells can become exhausted. They are massively outnumbered by the enemy and they surrender.

New drugs can now revitalise these exhausted T-cells, returning them to their fighting-fit selves. These drugs have transformed the outlook for some cancers, such as melanoma and lung cancer, but only in some people. There are still many puzzles to be solved in this new era of immunotherapy.

What's next?

After 14 years in the United States working at St Jude Children's Research Hospital in Memphis, Doherty returned to Australia and the University of Melbourne in 2002. He continued to train and mentor generations of scientists, many of whom still work on killer T-cells and how they tackle viruses like influenza.

The tools of modern immunology have changed. But the principles of good science – intense curiosity to solve a problem, asking the right question and planning the right experiments – are the same now as in 1973.

In 2014, the Doherty Institute was opened. As patron and namesake, Peter still loves to talk science and to interact with young researchers. A joint venture between the University of Melbourne and Royal Melbourne Hospital, the institute has more than 700 staff, all working on infection and immunity.

From basic discovery research, through to clinical and translational research and public health, the institute has the vision to improve health globally through discovery research and the prevention, treatment and cure of infectious diseases. To achieve this ambitious goal, we will use the same principles of great science, "time to talk and think things through" and the humanitarian values of its namesake to continue Peter's legacy.

Tonight when we hear the next inspiring stories from the winner of the 2016 Nobel Prize in Medicine or Physiology, we should be immensely proud of what Peter Doherty and our own scientists have achieved – and what's yet to come.

Thanks to Professor Andrew Brooks and Associate Professor Katherine Kedzierska for helpful discussions and input.

Sharon Lewin receives funding from the National Health and Medical Research Council, the National Institutes for Health, The Wellcome Trust and the American Foundation for AIDS Research and investigator initiated research funding from Viiv, Merck and Gilead Sciences.
 Peter Doherty's Nobel Prize-winning insights proved crucial for understanding how viral infections are controlled. Sharon Lewin, Director, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne and Royal Melbourne Hospital and Consultant Physician, Department of Infectious Diseases, Alfred Hospital and Monash University, The Peter Doherty Institute for Infection and Immunity Licensed as Creative Commons – attribution, no derivatives. tag:theconversation.com,2011:article/54739 2016-07-28T01:49:44Z 2016-07-28T01:49:44Z Explainer: the A, B, C, D and E of hepatitis

The thing all five viruses have in common is they can cause mild to very severe liver damage. wk1003mike/Shutterstock

Hepatitis means inflammation of the liver. While we usually think of hepatitis A to E viruses, anything that causes inflammation or damage to the liver can be considered as a form of hepatitis.

Hepatitis A, B, C, D and E are very different viruses. Hepatitis A is genetically closer to the common cold than it is to hepatitis B, for example. Hepatitis C is closer to the virus that causes dengue fever.

The thing all five have in common is they can cause mild to very severe liver damage.

Viral hepatitis caused around 1.45 million deaths in 2013, making it the seventh leading cause of death world-wide; 96% of these were due to hepatitis B and C.

Hepatitis A

Hepatitis A is spread by contaminated food and water, and from person to person via faecal transmission, particularly in household settings.

Hippocrates first described epidemics of diarrhoea and jaundice as far back as the fifth century BCE.

Although hepatitis A can cause significant illness, the body usually recovers without treatment and becomes immune to future infections.

Vaccines can prevent hepatitis A; these are recommended for travellers and other groups at particular risk of infection. Vaccination given early after exposure can also prevent hepatitis A from developing.

Hepatitis B

This is the most prevalent form of viral hepatitis worldwide. It's also the leading cause of liver cancer.

An estimated 250 million people live with hepatitis B worldwide. Around 220,000 Australians are thought to be living with chronic hepatitis B.

Hepatitis B can be transmitted from person to person through sex or blood-to-blood contact. But most people living with chronic (long-term) hepatitis B acquired it at birth from their mother, or early in life. Following infection, the chance of developing chronic hepatitis B in infancy is around 90%, but falls to 5% among adults.

A safe and highly effective vaccine has been available for hepatitis B since the 1980s. It has been provided for all infants born in Australia since May 2000.

In China, the proportion of children aged under five who had chronic hepatitis B fell from 9.7% in 1992 to 1% in 2006 after a vaccination program was introduced. The program has prevented millions of deaths from liver cancer and liver cirrhosis in China alone.

Effective antiviral treatments are also available for chronic hepatitis B. These can prevent liver damage and liver cancer from occurring. But even in a well-resourced country such as Australia, only a minority of people needing treatment and care for hepatitis B are receiving it.

Hepatitis C

This is the most common cause of viral hepatitis in Australia; an estimated 230,000 people live with chronic infection.

Hepatitis C is the leading cause of liver cancer and liver transplants nationally.

Most hepatitis C infections in Australia were acquired through unsafe injecting drug use. But in some low-resource countries, ongoing transmission of hepatitis C in health care settings is a major problem.

Around 80% of people infected with hepatitis C develop chronic infection; those who do clear the infection naturally remain susceptible to future infections.

No vaccine for hepatitis C is available.

On March 1, new treatments were listed on the Pharmaceutical Benefits Scheme (PBS). Although expensive, these treatments represent a huge advance and are a cost-effective way to prevent both new infections and deaths due to existing hepatitis C infections. With cure rates of the order of 90% with 8-24 weeks of tablets, and minimal side effects, these agents have the potential to drastically reduce the impact of hepatitis C.

The real key to unlocking this potential is the very liberal access criteria the Commonwealth government has applied to these treatments. As a result, uptake of treatment for hepatitis C in Australia has risen more than 20-fold.

Hepatitis D

Hepatitis D is a satellite virus that can only infect people who also have hepatitis B.

It is estimated that approximately 5% of people living with hepatitis B globally also have hepatitis D, which can lead to more severe liver disease.

Hepatitis E

Hepatitis E, like hepatitis A, is spread through contaminated food and water.

The first outbreak of hepatitis E infection acquired in Australia was reported earlier this year.

While hepatitis E is usually relatively mild, it can cause serious illness late in pregnancy, with a death rate of up to 20% among pregnant women in their third trimester.

A vaccine against hepatitis E has been developed but is currently licensed only in China.

While viral hepatitis remains a substantial public health challenge in Australia and world-wide, with political will, adequate investment and global partnerships, the world can eliminate viral hepatitis by 2030.

Benjamin Cowie receives funding from the Australian Government Department of Health, the Victorian Government Department of Health and Human Services, and the Royal Melbourne Hospital Office for Research.
 Hepatitis A, B, C, D and E are very different viruses. Hepatitis A is genetically closer to the common cold than it is to hepatitis B. Hepatitis C is closer to the virus that causes dengue fever. Benjamin Cowie, Director, WHO Collaborating Centre for Viral Hepatitis, The Peter Doherty Institute for Infection and Immunity Licensed as Creative Commons – attribution, no derivatives. tag:theconversation.com,2011:article/61525 2016-07-21T00:34:59Z 2016-07-21T00:34:59Z Weekly Dose: Truvada, the drug that can prevent HIV infection

PrEP works by preventing susceptible cells becoming infected with HIV. Truvada blocks the HIV virus from making copies of itself. Marc Bruxelle/Shutterstock

Pre-exposure prophylaxis, or PrEP, is the administration of antiviral drugs to a person not infected with HIV to prevent infection.

The only licensed version of PrEP is a daily oral tablet called Truvada®, which contains a combination of two antiretroviral drugs: tenofovir disoproxil fumarate (300mg) and emtricitabine (200mg).

Other strategies for delivery are being developed, including injections and topical applications with vaginal rings or gels. Other antivirals are also being tested for PrEP, but here we'll focus on Truvada.

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History of PrEP

Antiretroviral therapy was first introduced as a life-saving treatment for people with HIV in 1996. Researchers then tested antiretrovirals similar to Truvada on monkey models to see if they could prevent infection with simian immunodeficiency virus, the monkey equivalent of HIV. They were successful.

The first large clinical trial to show PrEP was effective in humans, iPrEX, compared daily Truvada to a placebo, or a sugar tablet, in men who have sex with men. The trial, which ran from 2007 to 2009, showed overall efficacy of 44%. This means the HIV infection rate in gay men who were given the pill was reduced by 44% compared to men who were given the placebo.

Efficacy rates increased to more than 92% in participants who had detectable levels of Truvada in their blood, indicating they adhered to the strict daily treatment regimen.

Subsequent trials have shown similar efficacy of more than 86% using event-driven PrEP in men who have sex with men. This means taking the drug prior to and following sex. Among people who inject drugs, daily PrEP had an efficacy rate of 50%.

Clinical trials in heterosexual women of both oral and topical PrEP have had mixed findings, with some studies being stopped early due to no evidence of benefit. But women in these studies were often not taking the medication. In other studies of heterosexual women, PrEP reduced HIV transmission by up to 76%.

All studies have clearly demonstrated that efficacy was directly related to adherence. Users benefited only if they consistently took the medications or consistently used topical PrEP.

Efficacy is estimated to be as high as 99% in men who have sex with men who take Truvada daily.

Availability

PrEP was licensed in the US in 2012 and was registered by the Therapeutic Goods Administration in Australia in May 2016. The Pharmaceutical Benefits Advisory Committee is evaluating whether PrEP will be listed and subsidised on the Pharmaceutical Benefits Scheme.

Newer forms of PrEP being evaluated include injections of antivirals such as cabotegravir, as well as topical administration of antivirals, including the vaginal ring containing the antiviral dapivirine and monoclonal antibodies.

Monoclonal antibodies are not drugs but they can bind to a virus and eliminate the capacity for the virus to infect a cell.

None of these strategies are currently licensed.

How it works

PrEP works by preventing susceptible cells becoming infected with HIV. Truvada blocks the HIV virus from making copies of itself.

When starting PrEP, it takes at least seven days to reach high levels of protection against HIV for men who have sex with men and also for women.

When stopping PrEP, people should continue using PrEP for four weeks after the last significant exposure.

It's important to note that PrEP doesn't protect against other sexually transmitted infections (STI) or pregnancy.

Truvada is, however, also active against hepatitis B virus and may have some activity against the herpes simplex virus too.

Problems and controversies

Although scientists demonstrated the efficacy of PrEP in 2010, it has taken several years for this preventative measure to be used in clinical practice. The main controversy has been related to cost and who pays.

Concerns have also been raised about a reduction in safer sex, but the majority of studies have not shown a decrease in condom use, or an increase in STIs. But even in the context of increased STIs, the benefit in PrEP reducing new HIV infections is clear.

Side effects

The main side-effects of Truvada are gastrointestinal. These tend to diminish after the first few months of PrEP. It occasionally causes headaches and fatigue.

Regular screening of kidney function is performed for people receiving PrEP as the drug can impair kidney function. But this is reversible. Very rarely, PrEP can lead to more severe kidney dysfunction.

Some bone thinning has been reported, but this is also reversible.

Cost

The cost of PrEP depends on the source of supply. In Australia, Truvada can be purchased from the manufacturer, Gilead, and costs A$750 per month.

Generic forms are available from overseas manufacturers, which may cost A$158 for three months, or more. Having a valid Australian prescription, completed by a registered medical practitioner and completing all the paperwork will facilitate the process for delivery.

Some state governments are running large studies to demonstrate the effectiveness of PrEP. In these studies, medication is free except in Victoria.

The authors acknowledge helpful discussions and contributions from Mr Bill Whittaker, National Association of People Living with HIV in Australia.

* This article originally said generic forms of the drug were available from overseas for $158 per month rather than $158 for a three-month supply. This has now been corrected.

Sharon Lewin receives funding from the NHMRC, the National Institutes for Health, Wellcome Trust, American Foundation of AIDS research, the University of Malaya, the Danish Medical Council, the Australian Centre for HIV and Hepatitis and investigator-initiated company funded studies from Merck, Gilead and ViiV. She is a member of the International AIDS Society.

Edwina Wright receives funding from a research grant from NIH, a Career Development Fellowship from the National Health and Medical Research Council of Australia, research funding from the Victorian Department of Health and unrestricted research funds from Gilead, Abbott, Janssen Cilag and Boehringer Ingelheim. She has also received funding that has been used for research purposes only from ViiV, Merck, Gilead, and Abbott for consultancy work, payment for lectures from ViiV and payment for developing educational resources for ViiV and Gilead. The study drug for the VicPrEP study has been donated by Gilead Sciences.
 Efficacy is estimated to be as high as 99% in men who have sex with men who take Truvada daily. Sharon Lewin, Consultant Physician, Department of Infectious Diseases, Alfred Hospital & Director, The Peter Doherty Institute for Infection and Immunity Edwina Wright, Associate Professor, Monash University Licensed as Creative Commons – attribution, no derivatives. tag:theconversation.com,2011:article/62482 2016-07-20T20:04:52Z 2016-07-20T20:04:52Z Climate policy needs a new lens: health and well-being
As the new Australian parliament takes the reins, health groups are moving to ensure that health minister Sussan Ley addresses a major health threat in this term of government: climate change.

Largely ignored by successive federal governments, the health risks from climate change are increasingly urgent. One or two degrees of warming at a global level may not sound like much, but if you take many organisms (including humans) too far outside their comfort zone, the consequences are deadly.

The Climate and Health Alliance – a coalition of concerned health groups, researchers, academics and professional associations – is calling on the Australian government to develop a national strategy for climate, health and well-being.

How climate change affects health

Major increases in ill-health are anticipated from continued climate change. These include:

greater rates of injuries, disease and deaths associated with more intense heatwaves, fires and other extreme weather events;

increased risks of infectious and food- and water-borne diseases;

health consequences arising from lost work capacity because of extreme weather;

harmful effects on community mental health; and

increasing air pollution.

 <img alt="" src="https://images.theconversation.com/files/131176/original/image-20160720-7910-alj431.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/131176/original/image-20160720-7910-alj431.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=598&fit=crop&dpr=1 600w, https://images.theconversation.com/files/131176/original/image-20160720-7910-alj431.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=598&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/131176/original/image-20160720-7910-alj431.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=598&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/131176/original/image-20160720-7910-alj431.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=751&fit=crop&dpr=1 754w, https://images.theconversation.com/files/131176/original/image-20160720-7910-alj431.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=751&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/131176/original/image-20160720-7910-alj431.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=751&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
  World Health Organisation

In February 2009, by which time global average temperatures had increased by less than one degree, Victoria experienced temperatures between 12-15 degrees above the average. That single heatwave caused the devastating Black Saturday bushfires. It was also responsible for a 62% increase in deaths, from both direct heat-related illnesses and the exacerbation of other chronic medical conditions.

During this five-day event, ambulances had a 46% increase in demand. Emergency departments experienced an eightfold increase in heat-related presentations, a 2.8-fold increase in cardiac arrests, and a threefold increase in patients dead on arrival.

Heat doesn't just affect the very old and very young. A recent international report shows that a billion workers globally are being exposed to extreme heat. This reduces productivity and puts lives at risk.

Global warming is also causing dramatic ecosystem collapse, such as the loss of corals on the Great Barrier Reef, and the recent death of thousands of hectares of mangroves in northern Australia. These will impact on fish stocks and food supply – and therefore, adequate nutrition – for communities that depend on these resources.

Preparing the health sector for climate change

Federal policymakers in Australia have failed recognise the health threat of climate change or offer robust and effective national policy solutions to tackle it. Governments in the United Kingdom and the United States, in contrast, are helping communities prepare for climate change. They are also investing in measures to promote climate resilience in the healthcare sector.

Like all services, the health sector is vulnerable to the direct consequences of extreme weather events such as fires, floods, heatwaves, and storms. These events can disrupt supply chains, electricity services, and water supplies; compromise the safety and quality of food services; suddenly and dramatically increase service demand; and interfere with service delivery through adverse impacts on personnel.

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 High-emissions activities such as burning coal for energy produce harmful air pollution. www.shutterstock.com

When Hurricane Sandy hit New York in 2012, many hospitals were forced to evacuate because of flooding; others were unable to function. Many lost electrical power, and some had back-up generators that failed due to flooding. Subsequent investigations reveal a lack of climate preparedness in the healthcare system.

A case study of multiple hospital evacuations during the event revealed that the health system experienced prolonged increased patient volume, displaced staff, and disrupted telecommunications. This created chaos as evacuated patients were transferred with little accompanying information about their diagnosis or required care.

The Climate and Health Alliance has proposed a national healthcare standard for "climate resilience", to ensure the Australian healthcare sector and its workforce are adequately prepared for climate-related health threats.

Time for policy commitment

As well as the obvious national interest, there is now an obligation under the Paris climate agreement for nations to consider their citizens' "right to health" in the context of climate policy. There is also an obligation to ensure that the health benefits from climate mitigation are reflected in climate policy choices.

These benefits are potentially huge. A recent US study estimated the savings on healthcare spending from carbon-reduction policies can be more than ten times the cost of policy implementation.

While there is strong evidence emerging in the international literature about the health benefits from strategies to cut emissions, that work is yet to be done in Australia.

As a signatory of the Paris Agreement, the Australian government must now apply a "health lens" to all of its climate policies. The Climate and Health Alliance is today calling for Australia to develop a national strategy for climate, health and well-being, which would allow Australia to:

adequately respond to the risks to health from climate change;

support the health sector to build climate resilience and transition to low-carbon operations;

promote education and awareness about climate change and health among the health professions and the wider community, so both can be better prepared;

strengthen climate and health research to identify population groups and communities particularly vulnerable to health risks from climate change and develop strategies to reduce those risks; and

invest in research to quantify the health benefits of different emissions-reduction scenarios to guide climate policy choices.

Current Australian carbon reduction commitments are inadequate to limit global warming to a safe level, and climate policies do not reflect the risks or opportunities for health. Lives are being put at risk.

We need a coordinated national response, with leadership from the health minister, but involving all portfolios, to protect the health of all people in Australia from climate change.

Fiona Armstrong is the Executive Director of the Climate and Health Alliance which receives funding for its sustainable healthcare program from its international partner, Health Care Without Harm.

Peter C. Doherty receives funding from the NHMRC to work on immunity to the influenza A viruses. He is in his final year as chair of the advisory board for the ARC Centre of Excellence for Climate Systems Science and serves on the board for the Melbourne Sustainable Society Institute. He is a Board Member of The Conversation.
 As the new Australian parliament takes the reins, health groups are moving to ensure the new health minister addresses a major health threat in this term of government: climate change. Fiona Armstrong, Associate, Melbourne Sustainable Societies Institute, University of Melbourne; Sessional Lecturer, School of Public Health and Human Biosciences, La Trobe University Peter C. Doherty, Laureate Professor, The Peter Doherty Institute for Infection and Immunity Licensed as Creative Commons – attribution, no derivatives. tag:theconversation.com,2011:article/62570 2016-07-20T13:12:33Z 2016-07-20T13:12:33Z A cure for HIV: what science knows, and what it doesn't

This human T cell (blue) is under attack by HIV (yellow), the virus that causes AIDS. T cells play a critical role in the body's immune response. Seth Pincus, Elizabeth Fischer and Austin Athman, National Institute of Allergy and Infectious Diseases, National Institutes of Health

Antiretroviral therapy has revolutionised the lives of people living with HIV. In many countries, the life expectancy for someone living with the virus is now almost the same as someone who isn't infected.

But antiretroviral therapy is not a cure. When it is stopped, the virus rebounds within a few weeks in almost all infected individuals – even after many years of suppressive therapy.

So HIV research continues to search for a cure. The focus is on understanding where and how HIV persists on antiretroviral therapy. These insights are then used to develop therapies that will ultimately enable us to cure HIV infection – or allow people living with HIV to safely stop antiretroviral therapy and keep the virus under control.

Theoretical possibility

There has been a substantial increase over the past decade in our understanding of where and how HIV persists when someone is on antiretroviral therapy. It is now clear that integration of the HIV genome into long-lived resting cells is a major barrier to a cure. This state is called HIV latency.

The virus can also persist on antiretroviral therapy in other forms. In both monkey models of HIV and in HIV-infected individuals on antiretroviral therapy, the virus has been found in T follicular helper cells, which are found in a specialised compartment in the lymphoid tissue. These cells are found in a part of the lymph node where penetration of immune fighting cells, or cytotoxic T cells, is limited.

In some tissues, antiretrovirals may not penetrate well. This could also contribute to persistence. Finally, there is also some evidence that, in at least some individuals and some sites, the virus may still be replicating at very low levels.

To date there has been just one case of a cure for HIV. This was in the context of haematopoietic stem cell transplantation for leukaemia with HIV-resistant donor cells. This is clearly not a feasible curative strategy for HIV. But what we have learnt is that the complete eradication of HIV is theoretically possible. Similar approaches have been tried, but no others have yet been successful. All six individuals receiving a similar transplant died of infection or cancer relapse within 12 months of transplantation.

Other case reports have confirmed that haematopoietic stem cell transplantation, even from a regular stem cell donor, can drastically reduce the frequency of infected cells. But when antiretroviral therapy was subsequently discontinued, the virus still rebounded – though it took months and not weeks.

These cases demonstrate that although reducing the frequency of latently infected cells might delay time to viral rebound, there's a need for continued effective immune surveillance against HIV to keep whatever remains in check.

Gene therapy

Using gene therapy to either make a cell resistant to HIV or to literally remove it from the cell is now being actively investigated. The initial target of gene therapy was CCR5. This same gene is missing in some rare individuals who are naturally resistant to HIV.

There have been safe clinical trials of gene therapy that eliminate the CCR5 gene and make other cells resistant to HIV. But a lot of work still needs to be done to increase the numbers of gene-modified cells.

Other work, still at the stage of test-tube experiments, uses gene scissors to target the virus itself. This approach might be trickier than targeting CCR5. This is because the virus can rapidly mutate and change its genetic code so that the gene scissors no longer work.

Other options

By starting antiretroviral therapy very early – within days to weeks of infection – it is possible to substantially reduce the number of latently infected cells. This also helps preserve immune function. Although not an option for the majority of HIV-infected individuals who are diagnosed too late, early diagnosis and treatment could be an effective strategy to maintain immune control for some patients.

Several years ago, French investigators described that post-treatment control was possible in up to 15% of individuals treated within months of infection. These data remain a little controversial, as in other cohorts post-treatment control is far less common. We still don't fully understand what factors are important for post-treatment control, but it seems that the nature of the immune system is critically important.

Interestingly, post-treatment control may differ in different ethnic groups. A recent report from Africa suggests that post-treatment control could occur at far higher frequencies in African populations than in Caucasians.

And the early treatment of infants may potentially shift the virus from hiding in long-lived to short-lived T cells. Understanding the differences in where the virus persists in children and in adults could provide important insights into novel strategies to find a cure for HIV.

'Shock and kill'

Activating the expression of HIV proteins in latently infected cells by drugs called latency-reversing agents could drive the elimination of virus-expressing cells through immune- or virus-mediated cell death. This approach is usually referred to as "shock and kill".

A substantial body of research has helped identify latency-reversing agents that have now been tested in experimental clinical trials. These studies demonstrated that although HIV expression can be induced in patients on suppressive antiretroviral therapy, this did not reduce the frequency of infected cells. In other words, shock but no kill.

Ongoing studies are looking at ways to augment the killing of these cells by boosting the immune system, for example through vaccines or medications that trigger suicide of the infected cells.

Prevention and boosting immune responses

Cure research is likely to benefit from the very significant investment in vaccines that have been developed to protect people from getting infected. Some of these could work in a cure too. These vaccines are now being investigated in the setting of clinical trials in infected individuals on antiretrovirals.

There have been spectacular recent advances in the treatment of some cancers using drugs that boost the immune response. These are called immune checkpoint blockers.

These drugs reinvigorate exhausted T cells so they can move into action – against cancer cells and in the same way, against HIV-infected cells. These drugs are now in the clinical trial stage in HIV-infected patients being treated for different cancers.

Another way to boost the immune system is to trigger a very primitive immune response designed to respond to infections. These drugs are called toll-like receptor (TLR) agonists. In monkeys, TLR-7 agonists stimulate latently infected cells and an effective immune response. This leads to a modest reduction in infected cells. Clinical trials are now under way in HIV-infected individuals on antiretrovirals.

Other interventions are needed

A successful strategy is likely to need two components: reducing the amount of virus that persists on antiretroviral treatment and improving long-term immune surveillance to target any residual virus. Far more work must be done on an HIV cure in low-income settings to better understand the effects of different HIV strains, the effects of co-infection and the impact of host genetics.

Lessons from other fields, particularly oncology, transplantation and fundamental immunology are all relevant to inform the next advances needed in cure research. Finally, we have to ensure that any intervention leading to a cure is cost effective and widely available.

The implementation of combination antiretroviral therapy in the mid-1990s is still regarded as one of the most remarkable achievements in modern medicine. Life-long antiretroviral therapy remains the single best option for any person infected with HIV. Finding a cure for HIV remains a major scientific challenge, but many believe it to be within the realm of possibility and it will hopefully play an important role in seeing an end to HIV.

This is an edited version of an article that appeared in Spotlight, a quarterly South African health publication.

Sharon Lewin receives funding from the NHMRC, the National Institutes for Health, Wellcome Trust, American Foundation of AIDS research, the University of Malaya, the Danish Medical Council, the Australian Centre for HIV and Hepatitis and investigator-initiated company funded studies from Merck, Gilead and ViiV. She is a member of the International AIDS Society.

Thomas Aagaard Rasmussen ne travaille pas, ne conseille pas, ne possède pas de parts, ne reçoit pas de fonds d'une organisation qui pourrait tirer profit de cet article, et n'a déclaré aucune autre affiliation que son poste universitaire.
 HIV research continues to search for a cure. The focus is on developing therapies to cure HIV infection or allow people with HIV to safely stop antiretroviral therapy and keep the virus under control. Sharon Lewin, Consultant Physician, Department of Infectious Diseases, Alfred Hospital & Director, The Peter Doherty Institute for Infection and Immunity Thomas Aagaard Rasmussen, Clinical Research Fellow, The Peter Doherty Institute for Infection and Immunity Licensed as Creative Commons – attribution, no derivatives.