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.

Drug companies are paying Australian doctors millions of dollars a year to fly to overseas conferences and meetings, give talks to other doctors, and to serve on advisory boards, our research shows.

Our team analysed reports from major drug companies, in the first comprehensive analysis of its kind. We found drug companies paid more than A$33 million to doctors in the three years from late 2019 to late 2022 for these consultancies and expenses.

We know this underestimates how much drug companies pay doctors as it leaves out the most common gift – food and drink – which drug companies in Australia do not declare.

Due to COVID restrictions, the timescale we looked at included periods where doctors were likely to be travelling less and attending fewer in-person medical conferences. So we suspect current levels of drug company funding to be even higher, especially for travel.

What we did and what we found

Since 2019, Medicines Australia, the trade association of the brand-name pharmaceutical industry, has published a centralised database of payments made to individual health professionals. This is the first comprehensive analysis of this database.

We downloaded the data and matched doctors’ names with listings with the Australian Health Practitioner Regulation Agency (Ahpra). We then looked at how many doctors per medical specialty received industry payments and how much companies paid to each specialty.

We found more than two-thirds of rheumatologists received industry payments. Rheumatologists often prescribe expensive new biologic drugs that suppress the immune system. These drugs are responsible for a substantial proportion of drug costs on the Pharmaceutical Benefits Scheme (PBS).

The specialists who received the most funding as a group were cancer doctors (oncology/haematology specialists). They received over $6 million in payments.

This is unsurprising given recently approved, expensive new cancer drugs. Some of these drugs are wonderful treatment advances; others offer minimal improvement in survival or quality of life.

A 2023 study found doctors receiving industry payments were more likely to prescribe cancer treatments of low clinical value.

Our analysis found some doctors with many small payments of a few hundred dollars. There were also instances of large individual payments.

Why does all this matter?

Doctors usually believe drug company promotion does not affect them. But research tells a different story. Industry payments can affect both doctors’ own prescribing decisions and those of their colleagues.

A US study of meals provided to doctors – on average costing less than US$20 – found the more meals a doctor received, the more of the promoted drug they prescribed.

Another study found the more meals a doctor received from manufacturers of opioids (a class of strong painkillers), the more opioids they prescribed. Overprescribing played a key role in the opioid crisis in North America.

Overall, a substantial body of research shows industry funding affects prescribing, including for drugs that are not a first choice because of poor effectiveness, safety or cost-effectiveness.

Then there are doctors who act as “key opinion leaders” for companies. These include paid consultants who give talks to other doctors. An ex-industry employee who recruited doctors for such roles said:

Key opinion leaders were salespeople for us, and we would routinely measure the return on our investment, by tracking prescriptions before and after their presentations […] If that speaker didn’t make the impact the company was looking for, then you wouldn’t invite them back.

We know about payments to US doctors

The best available evidence on the effects of pharmaceutical industry funding on prescribing comes from the US government-run program called Open Payments.

Since 2013, all drug and device companies must report all payments over US$10 in value in any single year. Payment reports are linked to the promoted products, which allows researchers to compare doctors’ payments with their prescribing patterns.

Analysis of this data, which involves hundreds of thousands of doctors, has indisputably shown promotional payments affect prescribing.

US research also shows that doctors who had studied at medical schools that banned students receiving payments and gifts from drug companies were less likely to prescribe newer and more expensive drugs with limited evidence of benefit over existing drugs.

In general, Australian medical faculties have weak or no restrictions on medical students seeing pharmaceutical sales representatives, receiving gifts, or attending industry-sponsored events during their clinical training. They also have no restrictions on academic staff holding consultancies with manufacturers whose products they feature in their teaching.

So a first step to prevent undue pharmaceutical industry influence on prescribing decisions is to shelter medical students from this influence by having stronger conflict-of-interest policies, such as those mentioned above.

A second is better guidance for individual doctors from professional organisations and regulators on the types of funding that is and is not acceptable. We believe no doctor actively involved in patient care should accept payments from a drug company for talks, international travel or consultancies.

Third, if Medicines Australia is serious about transparency, it should require companies to list all payments – including those for food and drink – and to link health professionals’ names to their Ahpra registration numbers. This is similar to the reporting standard pharmaceutical companies follow in the US and would allow a more complete and clearer picture of what’s happening in Australia.

Patients trust doctors to choose the best available treatments to meet their health needs, based on scientific evidence of safety and effectiveness. They don’t expect marketing to influence that choice.

Barbara Mintzes, Professor, School of Pharmacy and Charles Perkins Centre, University of Sydney and Malcolm Forbes, Consultant psychiatrist and PhD candidate, Deakin University

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