Before the COVID pandemic, the World Health Organization (WHO) had made a list of priority infectious diseases. These were felt to pose a threat to international public health, but where research was still needed to improve their surveillance and diagnosis. In 2018, “disease X” was included, which signified that a pathogen previously not on our radar could cause a pandemic.

While it’s one thing to acknowledge the limits to our knowledge of the microbial soup we live in, more recent attention has focused on how we might systematically approach future pandemic risks.

Former US Secretary of Defense Donald Rumsfeld famously talked about “known knowns” (things we know we know), “known unknowns” (things we know we don’t know), and “unknown unknowns” (the things we don’t know we don’t know).

Although this may have been controversial in its original context of weapons of mass destruction, it provides a way to think about how we might approach future pandemic threats.

Influenza: a ‘known known’

Influenza is largely a known entity; we essentially have a minor pandemic every winter with small changes in the virus each year. But more major changes can also occur, resulting in spread through populations with little pre-existing immunity. We saw this most recently in 2009 with the swine flu pandemic.

However, there’s a lot we don’t understand about what drives influenza mutations, how these interact with population-level immunity, and how best to make predictions about transmission, severity and impact each year.

The current H5N1 subtype of avian influenza (“bird flu”) has spread widely around the world. It has led to the deaths of many millions of birds and spread to several mammalian species including cows in the United States and marine mammals in South America.

Human cases have been reported in people who have had close contact with infected animals, but fortunately there’s currently no sustained spread between people.

While detecting influenza in animals is a huge task in a large country such as Australia, there are systems in place to detect and respond to bird flu in wildlife and production animals.

It’s inevitable there will be more influenza pandemics in the future. But it isn’t always the one we are worried about.

Attention had been focused on avian influenza since 1997, when an outbreak in birds in Hong Kong caused severe disease in humans. But the subsequent pandemic in 2009 originated in pigs in central Mexico.

Coronaviruses: an ‘unknown known’

Although Rumsfeld didn’t talk about “unknown knowns”, coronaviruses would be appropriate for this category. We knew more about coronaviruses than most people might have thought before the COVID pandemic.

We’d had experience with severe acute respiratory syndrome (SARS) and Middle Eastern respiratory syndrome (MERS) causing large outbreaks. Both are caused by viruses closely related to SARS-CoV-2, the coronavirus that causes COVID. While these might have faded from public consciousness before COVID, coronaviruses were listed in the 2015 WHO list of diseases with pandemic potential.

Previous research into the earlier coronaviruses proved vital in allowing COVID vaccines to be developed rapidly. For example, the Oxford group’s initial work on a MERS vaccine was key to the development of AstraZeneca’s COVID vaccine.

Similarly, previous research into the structure of the spike protein – a protein on the surface of coronaviruses that allows it to attach to our cells – was helpful in developing mRNA vaccines for COVID.

It would seem likely there will be further coronavirus pandemics in the future. And even if they don’t occur at the scale of COVID, the impacts can be significant. For example, when MERS spread to South Korea in 2015, it only caused 186 cases over two months, but the cost of controlling it was estimated at US$8 billion (A$11.6 billion).

The 25 viral families: an approach to ‘known unknowns’

Attention has now turned to the known unknowns. There are about 120 viruses from 25 families that are known to cause human disease. Members of each viral family share common properties and our immune systems respond to them in similar ways.

An example is the flavivirus family, of which the best-known members are yellow fever virus and dengue fever virus. This family also includes several other important viruses, such as Zika virus (which can cause birth defects when pregnant women are infected) and West Nile virus (which causes encephalitis, or inflammation of the brain).

The WHO’s blueprint for epidemics aims to consider threats from different classes of viruses and bacteria. It looks at individual pathogens as examples from each category to expand our understanding systematically.

The US National Institute of Allergy and Infectious Diseases has taken this a step further, preparing vaccines and therapies for a list of prototype pathogens from key virus families. The goal is to be able to adapt this knowledge to new vaccines and treatments if a pandemic were to arise from a closely related virus.

Pathogen X, the ‘unknown unknown’

There are also the unknown unknowns, or “disease X” – an unknown pathogen with the potential to trigger a severe global epidemic. To prepare for this, we need to adopt new forms of surveillance specifically looking at where new pathogens could emerge.

In recent years, there’s been an increasing recognition that we need to take a broader view of health beyond only thinking about human health, but also animals and the environment. This concept is known as “One Health” and considers issues such as climate change, intensive agricultural practices, trade in exotic animals, increased human encroachment into wildlife habitats, changing international travel, and urbanisation.

This has implications not only for where to look for new infectious diseases, but also how we can reduce the risk of “spillover” from animals to humans. This might include targeted testing of animals and people who work closely with animals. Currently, testing is mainly directed towards known viruses, but new technologies can look for as yet unknown viruses in patients with symptoms consistent with new infections.

We live in a vast world of potential microbiological threats. While influenza and coronaviruses have a track record of causing past pandemics, a longer list of new pathogens could still cause outbreaks with significant consequences.

Continued surveillance for new pathogens, improving our understanding of important virus families, and developing policies to reduce the risk of spillover will all be important for reducing the risk of future pandemics.

This article is part of a series on the next pandemic.

Allen Cheng, Professor of Infectious Diseases, Monash University

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

Hundreds of thousands of people worldwide are taking drugs like Ozempic to lose weight. But what do we actually know about them? This month, The Conversation’s experts explore their rise, impact and potential consequences.

Drugs like Ozempic are very effective at helping most people who take them lose weight. Semaglutide (sold as Wegovy and Ozempic) and tirzepatide (sold as Zepbound and Mounjaro) are the most well known in the class of drugs that mimic hormones to reduce feelings of hunger.

But does weight come back when you stop using it?

The short answer is yes. Stopping tirzepatide and semaglutide will result in weight regain in most people.

So are these medications simply another (expensive) form of yo-yo dieting? Let’s look at what the evidence shows so far.

It’s a long-term treatment, not a short course

If you have a bacterial infection, antibiotics will help your body fight off the germs causing your illness. You take the full course of medication, and the infection is gone.

For obesity, taking tirzepatide or semaglutide can help your body get rid of fat. However it doesn’t fix the reasons you gained weight in the first place because obesity is a chronic, complex condition. When you stop the medications, the weight returns.

Perhaps a more useful comparison is with high blood pressure, also known as hypertension. Treatment for hypertension is lifelong. It’s the same with obesity. Medications work, but only while you are taking them. (Though obesity is more complicated than hypertension, as many different factors both cause and perpetuate it.)

Therefore, several concurrent approaches are needed; taking medication can be an important part of effective management but on its own, it’s often insufficient. And in an unwanted knock-on effect, stopping medication can undermine other strategies to lose weight, like eating less.

Why do people stop?

Research trials show anywhere from 6% to 13.5% of participants stop taking these drugs, primarily because of side effects.

But these studies don’t account for those forced to stop because of cost or widespread supply issues. We don’t know how many people have needed to stop this medication over the past few years for these reasons.

Understanding what stopping does to the body is therefore important.

So what happens when you stop?

When you stop using tirzepatide or semaglutide, it takes several days (or even a couple of weeks) to move out of your system. As it does, a number of things happen:

• you start feeling hungry again, because both your brain and your gut no longer have the medication working to make you feel full

• blood sugars increase, because the medication is no longer acting on the pancreas to help control this. If you have diabetes as well as obesity you may need to take other medications to keep these in an acceptable range. Whether you have diabetes or not, you may need to eat foods with a low glycemic index to stabilise your blood sugars
• over the longer term, most people experience a return to their previous blood pressure and cholesterol levels, as the weight comes back
• weight regain will mostly be in the form of fat, because it will be gained faster than skeletal muscle.

While you were on the medication, you will have lost proportionally less skeletal muscle than fat, muscle loss is inevitable when you lose weight, no matter whether you use medications or not. The problem is, when you stop the medication, your body preferentially puts on fat.

Is stopping and starting the medications a problem?

People whose weight fluctuates with tirzepatide or semaglutide may experience some of the downsides of yo-yo dieting.

When you keep going on and off diets, it’s like a rollercoaster ride for your body. Each time you regain weight, your body has to deal with spikes in blood pressure, heart rate, and how your body handles sugars and fats. This can stress your heart and overall cardiovascular system, as it has to respond to greater fluctuations than usual.

Interestingly, the risk to the body from weight fluctuations is greater for people who are not obese. This should be a caution to those who are not obese but still using tirzepatide or semaglutide to try to lose unwanted weight.

How can you avoid gaining weight when you stop?

Fear of regaining weight when stopping these medications is valid, and needs to be addressed directly. As obesity has many causes and perpetuating factors, many evidence-based approaches are needed to reduce weight regain. This might include:

• getting quality sleep
• exercising in a way that builds and maintains muscle. While on the medication, you will likely have lost muscle as well as fat, although this is not inevitable, especially if you exercise regularly while taking it

• addressing emotional and cultural aspects of life that contribute to over-eating and/or eating unhealthy foods, and how you view your body. Stigma and shame around body shape and size is not cured by taking this medication. Even if you have a healthy relationship with food, we live in a culture that is fat-phobic and discriminates against people in larger bodies
• eating in a healthy way, hopefully continuing with habits that were formed while on the medication. Eating meals that have high nutrition and fibre, for example, and lower overall portion sizes.

Many people will stop taking tirzepatide or semaglutide at some point, given it is expensive and in short supply. When you do, it is important to understand what will happen and what you can do to help avoid the consequences. Regular reviews with your GP are also important.

Read the other articles in The Conversation’s Ozempic series here.

Natasha Yates, General Practitioner, PhD Candidate, Bond University

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