Directors' Blog

Down in Otago, researchers’ focus on microbiology fundamentals is leading New Zealand’s fight against drug resistant pathogens.

In May 2016 the UK government’s Review on Antimicrobial Resistance (AMR) published its final report, summarising the Review’s findings from two years of analysis. The conclusions, whilst welcomed by the scientific community, chimed with what leading researchers, such as the University of Otago’s Professor Greg Cook, have more or less been saying for over a decade. Namely, that AMR is already a global problem (including here in Aotearoa New Zealand) and that it will take a concerted effort with governments, scientists and pharmaceutical companies working together to solve it. In the meantime the report recommended taking steps that could help prevent the rise and spread of AMR. These, in essence, can be boiled down to the three R’s of antimicrobials: Refine, Reduce and Replace, and it is these three R’s that research in Prof Cook’s laboratory focuses on.

Refining the use of antibiotics basically means using the right drugs, to treat the right bugs, at the right time. In order to achieve that, healthcare workers need rapid diagnostic tests which will tell them whether the bug their patient has is already resistant to antibiotics, and if so, to which ones. The Cook lab is part of an international collaboration between Otago and South East Asia whereby the team is trying to establish whole genome sequencing (WGS) of the tuberculosis (TB)-causing bacterium, Mycobacterium tuberculosis, as a route to faster diagnoses. WGS allows researchers to analyse the genome of AMR bacteria, looking for genetic markers that indicate which antibiotics will work and those to which the bacterium is resistant.

The second of the three R’s, Reduce, is aimed at using fewer antibiotics to lower levels of AMR in our society and in the environment. An unfortunate Catch 22 experienced in antibiotic use is that, the more you use an antibiotic, the faster resistance will arise. Around the world there are many countries that use huge numbers of antibiotics in farming. In the Unites States alone roughly 70% of antimicrobials used each year are used on animals. Luckily for us, New Zealand is one of the lowest users of antibiotics in farming worldwide but still, there’s room for improvement.

In the dairy industry, when a cow’s udder becomes infected (know as mastitis) it’s more often than not due to a bacterial infection and treatment involves a course of antibiotics, such as penicillin. Moreover, whenever a cow is treated with antibiotics its milk can’t be used and needs to be discarded. Treatment and discarded milk cost the New Zealand dairy industry over $280 million a year. In this scenario, prevention really is better than the cure, for all of us. By joining forces with a leading animal remedy company, Deosan, as well as chemists from the University of Auckland, Prof Cook and co-lead investigator Dr Adam Heikal are heading up a team dedicated to finding new bio-active, sanitising molecules to help stop dairy herds developing mastitis in the first place, thereby reducing the farmers’ antibiotic needs.

Sanitisers for dairy cows are already widely used but the bioactive molecules they contain are also used extensively in hospitals across the country and around the world. To reduce the chances of resistance to these molecules arising on the farm, and spreading to the clinic it’s vital the new molecules, specifically for farm use, are discovered and developed. That forms one part of the final R, Replace.

The search for new antimicrobials is a never-ending one. As fast as new drugs are discovered, resistance starts to evolve. For this reason, the Cook lab invests heavily in screening large libraries of chemical compounds and natural products against problem bacteria, looking for new antimicrobial drug targets. However whole organisms, even those as small as a bacterial cell, are extremely complex. To reduce the levels of complexity, once a new antimicrobial target is identified, using either reverse genetics or a good old-fashioned experimental process of elimination, the target can be purified away from the organism and studied in greater detail. Three-dimensional structures can guide researchers to make more potent, more specific drugs. Recently, the Cook lab published the first bacterial structure of a protein long thought to be a drug target for tuberculosis treatment. The challenge now is to understand, at a molecular level, the enzyme’s inner workings and to ultimately inhibit its mode of action, leading to the design of a new antimicrobial drug.

The combination of all these research activities, as well as extensive international and industrial collaborations, help the Cook lab keep New Zealand at the forefront of antimicrobial discovery.

Check out some of the data about tuberculosis and vaccinations for whooping cough from the Figure.NZ team:
https://figure.nz/chart/0tUNDA6VMX0x6W5z
https://figure.nz/chart/AzwxPvVYJbh0lrcY-7fKh6eHZQCbjqKme 
InfectedNZ data board: https://figure.nz/@InfectedNZ/public

About

Adam Heikal PhD is a former Research Fellow in the Department of Microbiology and Immunology, University of Otago. He continues to work in AMR and antimicrobial discovery at the School of Pharmacy, University of Oslo and remains in close collaboration with Prof Cook as co-Principal Investigator on projects related to the New Zealand Agritech sector. Follow Adam on LinkedIn.

What is InfectedNZ?

Hey, Aotearoa. It’s time we had a chat about infectious diseases and what we’re going to do about the looming antimicrobial armageddon. That’s why we’ve asked leading health, social and economic researchers, and people with personal stories, to help us get real about our vulnerability and discuss solutions. Follow their blogs right here at tepunhahamatatini.ac.nz and watch the conversation spread across social media with #infectedNZ.

Backing it all up, wherever possible, is data from the good folk at Figure.NZ. Their super duper charts are based on data sourced from public repositories, government departments, academics and corporations. Check out their #infectedNZ data board and sign-up to create your very own data board on any topic that floats your boat.

We are nearing a crisis point in our use (and, sadly, misuse) of antibiotics. Indeed, the World Health Organisation recently described humanity as being in “a race against time” to develop antibiotics against multi-drug resistant superbugs [i]. If we cannot find effective new antibiotics soon, we may be faced with a return to the 1920s pre-antibiotic era, where people routinely died of the most mundane things, like a scratch from a rose thorn while gardening.

A couple of important contributing factors have been the widespread prescription of antibiotics for patients with viral infections, and failure of patients to complete courses of antibiotics once they start feeling better. Because antibiotics don’t work against viruses, the first scenario does nothing to treat disease but does place all of our hundreds of species of natural gut microbes under a “selective pressure”, such that any that evolve the ability to resist the antibiotic will hang around while those around them are killed. Even though these microbes may actually be good for us, bacteria are unbelievably good at passing genes to one another, so new resistance genes may quickly find their way to dangerous disease-causing bacteria. The second scenario, though, provides an even more direct route to dangerous drug-resistant bugs. If we stop a course of antibiotics when only 99% of the disease-causing bacteria have been killed, the remaining 1% – which will include those most naturally resistant to the antibiotics – may come charging straight back at us.

The good news is, we have learned a lot over the past 70 years about how to better use antibiotics to slow the development of resistant bacteria. The bad news is that in that time we have burned our way through nearly all of the antibiotics discovered to date.

Dr Jeremy Owen and I lead a team at Victoria University that is taking two different approaches to try and get new antibiotics into the developmental pipeline. We are particularly interested in molecules known as ‘non-ribosomal peptides’ and ‘polyketides’. These molecules are commonly antibiotics that are made by bacteria to defend themselves against other microbes. They are built inside the bacteria by enzymes – highly specialised little nano-machines that link together to form an assembly line, with each section of the assembly line responsible for adding on a specific part of the antibiotic molecule in a Lego-like fashion (see illustration).

The enzymatic assembly lines that make non-ribosomal peptide and polyketide antibiotics are made up of discrete subunits that each play a precise role in recognising and joining different parts of the final product molecule, passing it down the line, and ultimately releasing it. Image credit: JVE Chan-Hyams, modified from DF Ackerley ‘Cracking the non-ribosomal code’ Cell Chem Biol 2016 23(5): 535-7.

One of our team’s approaches is to re-engineer the assembly line in the hope that we can build analogues of existing antibiotics that may get around the resistance mechanisms that disease-causing bacteria have evolved. We have developed approaches to swap out different sections (labelled 1-4 in the Illustration) of an assembly line that makes a particular molecule and replace them with other sections that cause a slightly different ‘Lego part’ to be added into the product molecule. This has been a really fascinating engineering problem, and we have learned a lot about how the assembly lines work, but this line of work is still in its infancy and for now remains a very difficult and inefficient way of making a new drug candidate.

Our more pragmatic approach has been to try and find previously undiscovered antibiotic molecules from nature. The majority of antibiotics in use today were discovered by growing bacteria isolated from different soils around the globe, and testing the different molecules they naturally secrete. From the 1940s to 1960s this was a highly productive approach, but thereafter researchers struggled to find anything new – the same sets of molecules just kept cropping up time and time again. In recent times we have realised that only a very small proportion of soil bacteria – under one percent! – can be grown effectively outside of their natural environment. It is therefore extremely likely that the remaining 99% produce some very effective antibiotics that we have previously been unable to access.

To get around the problem that we cannot presently grow most soil bacteria in the lab, we instead go straight to their DNA, purified directly from the soil. We have developed and optimised several different strategies to ‘fish out’ clusters of gene that encode the types of assembly line pictured in the Illustration. These effectively act as blueprints that tell a cell how to make one particular antibiotic. Taking advantage of the fact that bacteria are so good at swapping bits of DNA, we and others have shown that you can transfer these blueprints to a new host – a bacterium that we can grow in the lab – and a surprising amount of the time it will gain the ability to produce a new antibiotic! Luckily for us, most antibiotic gene clusters not only encode the assembly line needed to make an antibiotic, but also a means for defending the host cell against any toxic effects.

This is still a new line of research in New Zealand, but before he returned home in 2015, Jeremy successfully used similar approaches at The Rockefeller University in New York. There he discovered, produced, and tested a number of previously unknown molecules, including novel antibiotics and compounds with anti-cancer potential (see paper one and two on the Proceedings of the National Academy of Sciences USA. We already have indications that NZ soils are rich in equally promising new drug candidates, and are working hard to pull some of those out. However, rigorous testing standards mean that even if we do find new antibiotics that work well in people, it will likely be at least ten years before any of these enter clinical use. Nevertheless, it is critical to keep the discovery pipelines flowing if we are to avert the crisis foreseen by the World Health Organisation and numerous other medical organisations around the globe.

[i] Bulletin of the World Health Organization 2011;89:88–89. doi:10.2471/BLT.11.030211

Associate Professor David Ackerley and colleagues from Victoria University Wellington recently featured on the cover of a leading international journal with an image of bacteria grown in the shape of New Zealand. The cover related to their work investigating the potential of engineering improved antibiotics.

About

Associate Professor David Ackerley is from the School of Biological Sciences at Victoria University Wellington. A major theme of his research is directed evolution, artificial acceleration of rates of mutation and recombination in genes and genomes, and selection of variants with improved qualities. David is also an Associate Investigator for the Maurice Wilkins Centre of Molecular Biodiscovery.

What is InfectedNZ?

Hey, Aotearoa. It’s time we had a chat about infectious diseases and what we’re going to do about the looming antimicrobial armageddon. That’s why we’ve asked leading health, social and economic researchers, and people with personal stories, to help us get real about our vulnerability and discuss solutions. Follow their blogs right here at tepunhahamatatini.ac.nz and watch the conversation spread across social media with #infectedNZ.

Backing it all up, wherever possible, is data from the good folk at Figure.NZ. Their super duper charts are based on data sourced from public repositories, government departments, academics and corporations. Check out their #infectedNZ data board and sign-up to create your very own data board on any topic that floats your boat.

Heart defects are collectively the commonest abnormality in newborn babies. About one infant in every 150 has some form of defect; a hole in the heart, or parts of the heart underdeveloped or in the wrong place. Four hundred children every year undergo heart surgery in New Zealand at the Starship Children’s hospital, and another 250 undergo keyhole (cardiac catheter) interventions. Currently over 97% survive their operation, including the most complicated cases and most severely ill infants. Most leave the hospital well, with a neat “zipper” scar down the front of their chest which will gradually fade to a pale white line.

The very first heart operation in the world, in 1895 in Norway, was on a 24 year old man. He survived the surgery, but died several days later from overwhelming infection. It was relatively simple surgery but there were no antibiotics at that time.

These days, surgeons introduce goretex to patch holes, plastic and metal valves to replace faulty valves, and electrical pacemakers to keep a stable rhythm. Operations are done in state-of-the-art operating rooms with controlled air flow, and great efforts are taken to keep the operating field sterile. Even so, internationally about one in five patients (20%) get an infection early after the surgery, most commonly in the lungs or in the surgical wound. 3% overall get an immediately life threatening infection such as one around the heart, or in the blood. When treated with a course of antibiotics, they can fully expect to recover. Today, it is rare for a child to die from such post-surgical  infection, even in severe cases.

So what would happen without antibiotics? Modern children’s heart surgery has never been performed without the availability of antibiotics, so, in truth, it is impossible to know for sure how many infants and children would die or suffer prolonged illness or disfigurement without them.  We can be sure that 3% will die from their severe infections. Given that around 20% will get an infection, we can guess that the post-operative ward would be an entirely different place. It would be a place of rampant bacterial infection, pus draining from open wounds, chest walls never healing properly, and some children staying for many weeks or months. Infected children and their visiting family would have to be isolated from other children. And it would be a place of death. The vulnerable very sick newborns would succumb in large numbers. And it will be a painful and often foul-smelling death.

The spectre of infection would hang over every procedure. Hospitals in general will be a place of death and suffering more than hope and recovery. So the threshold for doing an operation will go up. Parents will naturally be too scared to allow their child to undergo what today would be a routine procedure. Children therefore will suffer the consequences of their heart problem for longer; suffering shortness of breath, poor energy and unable to take part in sport. Some would be unable even to get to school. Infants in heart failure would not gain weight and may die from chest infections.

I am also imagining myself in a world without antibiotics. I could be confined to a wheel chair, because my hip surgery would have been inadvisable given the high risk of infection. That nasty infected boil I once had from a mosquito bite would possibly have disfigured and damaged much of my right hand, a hand I need to perform heart procedures.

I hope that what we heart specialists do now for the children we care for represents merely the dawn of even greater things. But if we don’t get more antibiotics, and use them wisely, it may be that future parents and their children will be longing for the past golden age of children’s heart surgery and intervention; 2016.

About

Jonathan Skinner is a paediatric cardiologist/electrophysiologist and Auckalnd’s Starship Children’s Hospital and an Honorary Professor of Paediatrics Child and Youth Health at the University of Auckland.

What is InfectedNZ?

Hey, Aotearoa. It’s time we had a chat about infectious diseases and what we’re going to do about the looming antimicrobial armageddon. That’s why we’ve asked leading health, social and economic researchers, and people with personal stories, to help us get real about our vulnerability and discuss solutions. Follow their blogs right here at tepunhahamatatini.ac.nz and watch the conversation spread across social media with #infectedNZ.

Backing it all up, wherever possible, is data from the good folk at Figure.NZ. Their super duper charts are based on data sourced from public repositories, government departments, academics and corporations. Check out their #infectedNZ data board and sign-up to create your very own data board on any topic that floats your boat.

Last week was World Antibiotic Awareness week, an initiative of the World Health Organization (WHO) to raise awareness and understanding of antimicrobial resistance. To follow-up, here at Te Pūnaha Matatini we are having a week-long conversation about the health, social, economic, and environmental impacts of infectious diseases in Aotearoa New Zealand. In this post, I want to touch on what antimicrobial resistance is, and what a future without antimicrobial medicines could look like.

What is antimicrobial resistance and what is causing it?
Antimicrobials are chemicals that kill or stop the growth of microbes. But as microbes is the generic term for a multitude of life forms which differ in their genetic make-up, life-styles and habitats, so antimicrobials can be divided into different categories depending on what they target. Some antimicrobials work against all microbes, but others are more specific. Antivirals only work against particular viruses, antifungals only work against particular fungi and antibiotics only work against particular bacteria.

Antimicrobial resistance is when microbes develop the ability to stop antimicrobials from affecting them. As most microbes replicate themselves and their genetic material fairly rapidly (some can divide in just a few minutes), and they can grow to large numbers (easily reaching population sizes in the billions if they have the right conditions), there are plenty of opportunities for resistant mutants to arise purely by chance. These mutants can then grow quite happily in the presence of the antimicrobial. This happens wherever microbes encounter antimicrobials – in human and veterinary medicine, in agriculture, but also in sewage systems and out in the wider environment. More worryingly is when microbes gain the ability to share resistance between each other on mobile bits of genetic material. Then they don’t even need to be in the presence of the antimicrobial agent – they just need to meet the right kind of resistant microbe!

A major factor in the development of resistance is the misuse and overuse of antimicrobials. So being used when they aren’t needed, or not being used correctly. Another worry is the use of similar antimicrobials in human medicine and in agriculture. For example, a fungus commonly found in soil has become resistant to the antifungal pesticides used in gardening and agriculture. Because similar antifungals are used in human medicine, these resistant fungi are now able to cause almost untreatable infections in some vulnerable hospital patients. And these patients can become infected just by being in a bed next to an open window that looks out onto a garden!

Is antimicrobial resistance something we should be worried about?
Yes. Experts predict that within the next decade we will run out of antimicrobial medicines to treat many common infections. Part of the reason we are in this position is that most of the pharmaceutical industry pulled out of antimicrobial research decades ago, so the medicine cupboard is basically empty. Similarly, the vast majority of government and charity funding around the world has gone on researching non-communicable diseases. Any new antimicrobial compound discovered today could take a decade of development and testi before it would be available for doctors to use. The situation is a catastrophe on a par with global warming.

What are the most concerning examples of resistant strains of infectious diseases?
The major resistant bacteria that are circulating around the world are extended-spectrum beta-lactamase (ESBL) expressing strains of Escherichia coli and Klebsiella pneumoniae, which are of particular concern in hospitals, and some strains of Mycobacterium tuberculosis which causes the lung disease TB. There are an increasing number of strains of these bacteria that are sensitive to just one or two antibiotics, and some strains that are pretty much untreatable. Another resistant organism of growing concern globally is Neisseria gonorrhoeae which causes gonorrhoea. While most men with gonorrhoea will have symptoms when they have the disease, half of women can be asymptomatic so won’t know they are infected. Importantly, untreated gonorrhoea can lead to infertility.

What’s happening in New Zealand?

We wanted to show you the data, but can’t. It is publicly available on the web but Figure.NZ were denied permission to turn it into nice charts for you to see. What we can say is that the extremely resistant strains of E. coli, K. pneumoniae and M. tuberculosis we see here are mainly coming into New Zealand from countries like India, China, and those in south-east Asia. This is going to be an area to watch, especially given the importance of countries like China for trade and tourism in New Zealand.

N. gonorrhoeae is also one for us to watch as highly resistant strains have been reported in Australia. In New Zealand, gonorrhoea is not a notifiable disease so the only data we have is based on the voluntary provision of the numbers of diagnosed cases from laboratories and sexual health and family planning clinics. In 2014, that number was 3,038, with 977 of these cases in young people under the age of 19. Less than half of sexually active young people report using condoms which would protect them from infection. If we end up with a completely untreatable strain of N. gonorrhoeae taking hold in New Zealand this could have a huge impact on our future fertility.

The last organism of concern here is Methicillin Resistant Staphylococcus aureus (also known as MRSA) which is very much a problem of our own making. Over the last few years there has been a huge increase in the number of skin and soft tissue infections caused by S. aureus in New Zealand (1). Alongside this, there has been a huge increase in prescriptions for a topical antibiotic called fusidic acid. As a consequence, one of the major clones of S. aureus now causing disease in New Zealand is an MRSA clone which is resistant to fusidic acid (2).

Major misconceptions about antibiotics
There are a number of major misconceptions about antibiotics. Lots of people don’t know that bacteria and viruses are very different life-forms. This means that antivirals don’t work on bacteria, and antibiotics don’t work on viruses. In countries where antibiotics are available without prescription, many people confuse antibiotics with pain-killers, so will take antibiotics for things like a headache!

Another common misconception is that it is us that become resistant to antibiotics, rather than the microbes. Perhaps this is a misunderstanding between how antibiotics work (by killing the bacteria directly), versus what happens when we are vaccinated (our immune system is primed to recognise and fight off the invader).

But the biggest misconception is that people who don’t take antibiotics, or who take them very rarely, won’t be affected by antibiotic resistant bacteria – that the antibiotics will still work for them. It doesn’t matter if you’ve never had a course of antibiotics, or if you’ve had several, it all depends on the bacteria you get infected with. Similarly, healthy people who have never had a course of antibiotics could still have antibiotic-resistant superbugs living happily up their noses or in their guts. They can easily spread from person to person, or can be picked up while travelling overseas.

What does a future without antimicrobials look like?

A future without antimicrobials will affect us all; rich and poor, young and old. In a world without antimicrobials, previously treatable infections will once again become deadly, or may require amputation to stop them in their tracks. Because antimicrobials are also used to prevent infection in vulnerable people, it will also become life threateningly risky to do routine operations like caesarean sections and joint replacements, and treatments like chemotherapy for cancer.

Margaret Chan, Director-General of the World Health Organization, called antimicrobial resistance “…the end of modern medicine as we know it”.  In a series of reports commissioned by the UK’s former Prime Minister David Cameron, economist Sir Jim O’Neill has estimated that without urgent action, antimicrobial resistance will kill 10 million people a year by 2050, more than will die from cancer. O’Neill has also put an economic cost on the issue, estimating that inaction will cost the world’s economy 100 trillion USD by 2050.

What should we be doing to combat antimicrobial resistance?
Combatting antimicrobial resistance requires a global effort to stop the overuse and misuse of antimicrobials in human and veterinary medicine, and in agriculture. It requires governments, philanthropists, charities and industry to invest serious money into antimicrobial discovery and development and research into new ways to combat infectious diseases. We also need quicker and better ways to diagnose infectious diseases so that patients can receive the right treatment as soon as possible.

Equally important is that we have a national conversation about how we all, the public, health workers, policymakers and the agricultural sector, can contribute to solving this global crisis from right here in New Zealand. I hope you’ll participate in this important discussion. Follow #infectedNZ on Twitter or Facebook, or leave a comment below.

References:

1. Williamson DA, Zhang J, Ritchie SR, Roberts SA, Fraser JD, Baker MG (2014). Staphylococcus aureus infections in New Zealand, 2000-2011.Emerg Infect Dis. 2014 Jul;20(7):1156-61. doi: 10.3201/eid2007.131923.
2. Williamson DA, Monecke S, Heffernan H, Ritchie SR, Roberts SA, Upton A, Thomas MG, Fraser JD (2014). High usage of topical fusidic acid and rapid clonal expansion of fusidic acid-resistant Staphylococcus aureus: a cautionary tale. Clin Infect Dis. 2014 Nov 15;59(10):1451-4. doi: 10.1093/cid/ciu658.

About:

Dr Siouxsie Wiles is Deputy Director of Te Pūnaha Matatini. She describes herself as a microbiologist and bioluminescence enthusiast. Head of the Bioluminescent Superbugs Lab at the University of Auckland, Siouxsie combines her twin passions to understand infectious diseases.

What is InfectedNZ?

Hey, Aotearoa. It’s time we had a chat about infectious diseases and what we’re going to do about the looming antimicrobial armageddon. That’s why we’ve asked leading health, social and economic researchers, and people with personal stories, to help us get real about our vulnerability and discuss solutions. Follow their blogs right here at tepunhahamatatini.ac.nz and watch the conversation spread across social media with #infectedNZ.

Backing it all up, wherever possible, is data from the good folk at Figure.NZ. Their super duper charts are based on data sourced from public repositories, government departments, academics and corporations. Check out their #infectedNZ data board and sign-up to create your very own data board on any topic that floats your boat.

The fungi are a vast and distinctive kingdom of organisms that make up a significant component of most land ecosystems, intimately linked with bacteria, plants, and animals. Fungi cannot make their own food, so they live on or within their food, be that dead wood or leaves, overmature fruit, or a living plant or animal. In these habitats, a fungus competes with other life forms including other fungi and also bacteria. Some species of fungi have adapted to growth in hostile habitats, while others developed biochemical defences to fight off competitors. The awareness and application of these fungal defences has revolutionised modern medicine.

The idea that a substance could be used as a ‘magic bullet’ to target disease causing organisms dates from the late 19^th Century. In 1909 Nobel prize winner Paul Ehrlich and his team effectively began the science of drug discovery when they developed the organic arsenic compound Salvarsan to treat syphilis. But it wasn’t until the chance discovery of antibacterial action by fungi that antibiotics became one of humanity’s major medical advances.

Alexander Fleming is credited with the discovery and naming of penicillin. In 1928 he returned from holiday to St Mary’s Hospital, London, to find previously living cultures of the bacterium Staphylococcus aureus contaminated and killed by a mould fungus Penicillium notatum. Fleming kept the fungal culture but wasn’t able to purify and stabilise penicillin. This achievement was left to Florey, Chain & Heatley at Oxford University. Subsequent researchers in the UK and USA perfected the production by fermentation and later chemical synthesis, enabling a revolution in medical intervention to counter previously lethal conditions such as pneumonia, septicaemia, and gangrene.  Before antibiotics, bacterial infection of a skin wound often led to growth of bacteria that overwhelmed the body’s immune system. In World War 1, for example, more than 1 in 10 soldiers injured in battle died of infected wounds.

Penicillium digitatim. Image courtesy Peter Buchanan

The life-saving success of penicillin led to intensive research, especially until 1970, to discover new antimicrobial compounds produced by fungi and filamentous bacteria. This gave us antibiotics such as cephalosporin produced from Cephalosporium; neomycin, tetracycline and streptomycin (to initially control tuberculosis (TB)) from Streptomyces (Actinobacteria), and antifungals such as griseofulvin from Penicillium griseofulvin.

Since 1970, there have been very few new types of antibiotics discovered. At the same time, disease-causing bacteria have evolved to become resistant to our medicines, making currently available antibiotics less and less effective. Even worse, bacteria evolve antibiotic resistance much faster than the pace of new antibiotic discovery. Unfortunately, the major pharmaceutical companies have diverted research funds to more profitable drug development for chronic diseases rather than for bacterial infections. There’s an urgent need to develop new responses to overcome antibiotic-resistant superbugs, and so avoid a return to pre-penicillin days when an infected cut could be lethal.

This has been the motivation for a number of new research initiatives seeking novel antibiotics and other means to control bacterial infection. New Zealand’s national living culture collection of fungi and plant-associated bacteria is a research resource for national benefit, managed by Landcare Research. Bevan Weir, as Curator of the International Collection of Microorganisms from Plants (ICMP), is collaborating with Siouxsie Wiles and her University of Auckland postgraduate students seeking new antibiotic compounds from among the 20,000 cultures of fungi and bacteria. The New Zealand collection began in the 1950s, and includes many native species that have not previously been investigated for antibiotic production.

References
Livermore DM 2011. Discovery research: the scientific challenge of finding new antibiotics. J. Antimicrob. Chemother. 66: 1941–1944.

Moore D, Robson GD, Trinci PJ 2011. 21^st Century Guidebook to Fungi. Cambridge University Press, Cambridge.

Overbye KM, Barrett JF 2005.  Antibiotics: where did we go wrong? Drug Discovery Today 10: 45-52.

About

Peter Buchanan works for Landcare Research as Science Team Leader for a group of 30 science staff researching New Zealand’s most diverse groups of terrestrial organisms – the fungi, bacteria, invertebrates, and plants. Landcare Research is custodian of five national biological collections including the NZ Fungal Collection (PDD) and Culture Collection of Fungi and Bacteria (ICMP). Peter’s research interests are in fungal conservation, wood decay fungi, applied uses of fungi, and science education.

What is InfectedNZ?

Hey, Aotearoa. It’s time we had a chat about infectious diseases and what we’re going to do about the looming antimicrobial armageddon. That’s why we’ve asked leading health, social and economic researchers, and people with personal stories, to help us get real about our vulnerability and discuss solutions. Follow their blogs right here at tepunhahamatatini.ac.nz and watch the conversation spread across social media with #infectedNZ.

Backing it all up, wherever possible, is data from the good folk at Figure.NZ. Their super duper charts are based on data sourced from public repositories, government departments, academics and corporations. Check out their #infectedNZ data board and sign-up to create your very own data board on any topic that floats your boat.

One thing is clearer than ever:  the wellbeing of animals, humans and the environment is inseparable and, on a global scale, no issue represents this complex relationship better than the rise of antimicrobial resistance.

The medical discovery that revolutionised our ability to treat disease in humans and animals is becoming its own worst enemy. The pressure is on the veterinary and medical communities internationally to find solutions. It’s a ‘One Health’ issue in its purest form.

Last year the New Zealand Veterinary Association (NZVA) tackled the issue of antimicrobial resistance (AMR) head-on. It challenged the veterinary profession, farmers, pet owners, government and industry to rethink the use of antibiotics for animals. It set an aspirational vision that “by 2030 New Zealand Inc. will not need antibiotics for the maintenance of animal health and wellness”.

It’s a big ask, and not necessarily a vision that everyone immediately supports. It’s also a carefully worded statement acknowledging that while the science is complex and sometimes contradictory, everyone in essence agrees that the more we use these valuable medicines, the more likely resistance will be selected for. It also acknowledges that the issue the veterinary profession must address most urgently is to reduce, refine, and replace the use of antimicrobials for maintenance (prophylactic and metaphylactic use) while maintaining their therapeutic use to protect the wellbeing of our animals.

The science of AMR is challenging, challenged, and still emerging, which means the issue is poorly understood by most people. What is poorly understood by even the scientific community is that, when measured against the estimated biomass of animals in the country, New Zealand is already the third lowest user of antibiotics for animals in the OECD.

Moreover, data published this year showed that while the average use of antibiotics in animals is 9.4mg active ingredient/kg biomass, the human use is 121mg active ingredient/kg biomass, 12.9 times higher and the 16^th highest of the countries compared. This is a simple indicator of comparative use in what we all acknowledge to be a scientifically complex issue (we must, for example, also consider the critically important nature of the actives used in veterinary medicine and that many of these actives are for veterinary use only), but it reflects how effective regulation and control by veterinarians over prescribing practices is maintaining New Zealand in a position of world leadership in the stewardship of these vital medicines.

Dr Stephen Page, an internationally recognised veterinary pharmacologist, has proposed that the previous Hypercene era of profligate antimicrobial use is moving in to the Hypocene, era of over restraint. This is an inevitable step, he says, before the human and veterinary professions reach the Eucene, the era of appropriate use.

This may well be. In order to navigate to the Eucene, we must ensure that scientific evidence is used as the basis of any regulatory or stewardship changes made to address society’s growing concerns around antimicrobial usage. We must also ensure that access to these vital medicines is maintained to responsibly treat bacterial disease, for the wellbeing of animals, humans, and the environment.

Reference
Hillerton JE, Irvine CR, Bryan MA, Scott D, Merchant SC (2016). Use of antimicrobials for animals in New Zealand, and in comparison with other countries. New Zealand Veterinary Journal, Forthcoming articles, pp 1-7, Mar 2016.

About

Callum Irvine is an experienced vet and the Head of Veterinary Services for the New Zealand Veterinary Association (NZVA) where he champions veterinary leadership and advocates on behalf of the veterinary profession. Through his role he promotes science based policy development across all areas of veterinary science.

What is InfectedNZ?

Hey, Aotearoa. It’s time we had a chat about infectious diseases and what we’re going to do about the looming antimicrobial armageddon. That’s why we’ve asked leading health, social and economic researchers, and people with personal stories, to help us get real about our vulnerability and discuss solutions. Follow their blogs right here at tepunhahamatatini.ac.nz and watch the conversation spread across social media with #infectedNZ.

Backing it all up, wherever possible, is data from the good folk at Figure.NZ. Their super duper charts are based on data sourced from public repositories, government departments, academics and corporations. Check out their #infectedNZ data board and sign-up to create your very own data board on any topic that floats your boat.

“Only clean water and antibiotics have had an impact on childhood death and disease that is equal to that of vaccines” –  World Health Organization (WHO).

Spanish flu (an H1N1 swine flu) 1918. This is a mass grave at Waikumete Cemetery in West Auckland

In the 20^th century, when most of you reading this were born, nearly 1.7 billion people died from infectious diseases.

Most of the diseases in this sobering infographic are now vaccine preventable through the creative collective brilliance of many scientists. Smallpox, influenza, diarrhoea (rotavirus), whooping cough, meningitis, tetanus, Hepatitis B, rabies, and measles are the diseases responsible for carrying off most of those 1.7 billion people.

While the First World War raged for over four years and took the lives of 16,697 New Zealanders, in 1918 influenza took about half as many in the space of just two months (8600 New Zealanders died).

So how many lives have vaccines saved? I have never been able to find an overall total, but one bunch of scientists (ScienceHeros.com) estimate that Edward Jenner alone was responsible for saving 530 million lives. In other words, that is how many deaths from smallpox are estimated to have been prevented. I thought that sounded like a lot before I remembered that the estimate for the 20^th century alone is about 300-500 million so maybe this is actually a conservative estimate although I have not been able to find any convincing estimates on this. Imagine inventing something that saved half a billion lives!

That made me think of another major killer – measles.

Already this century the WHO has estimated that measles vaccine alone has saved over 17 million lives. A couple of doses at a cost of about $NZ1 works a treat. And if you think measles never really hurt any Kiwis then I suggest you have a look at this New Zealand timeline and contemplate how small the population was during these years. In 1900 we numbered little more than 700,000

The man responsible for this impressive achievement is Maurice Hilleman who developed a measles vaccine which is estimated to have saved 118 million lives since the 1960s. Every country in the world uses measles vaccine and the disease is on track for global elimination. That is one hell of a legacy, but Hilleman didn’t finish there. He developed over 40 vaccines including those against influenza, mumps, hepatitis A and B, chickenpox, meningococcal, and Haemophilus influenza type B, How many more lives do these account for?

The infectious landscape in NZ is very different today than it was. Once upon a time, before air travel, if someone infectious got on a boat they had either died or recovered by the time they arrived here some 135 days later. New Zealand’s isolation made her a natural quarantine zone.

But in the end this did not stop the importation of infectious diseases and as more people came so did their diseases. The first documented outbreak of a now vaccine preventable disease was an influenza outbreak in 1817-20. From then on epidemics occurred regularly, decimating family sizes and disproportionality affecting Māori to the point where the population had halved by the late 1800s.

If one examines the chronology of events major enough to affect the health and size and life expectancy of the New Zealand population since 1850, it is striking how many of these are either infectious epidemics (negative effect) or the introduction of a vaccine (positive effect). (Editor’s note: the Statistics New Zealand website may be down due to 14 November earthquake).

The chronology starts with an influenza epidemic in 1852-3. In 1873 there was a notable pertussis epidemic with 356 deaths noted and the very next year a measles epidemic taking 344 children along with diphtheria killing 481 in the same year. These four diseases go on to appear as major events every few years. Today they are all preventable but still not curable.

Watch: Everything you want to know about immunisation but were afraid to ask.

A timeline of epidemics affecting New Zealand  shows almost all of the most dangerous diseases (those that carried off the most people) are now be vaccine preventable. These diseases in order of first appearance in NZ were:

• 1817 Influenza
• 1835 Measles
• 1863 Scarlet fever, aka strep throat
• 1872 Diphtheria
• 1872 Smallpox (only the once in 1872)
• 1873 Pertussis
• 1874 Typhoid
• 1875 TB
• 1900 Plague
• 1916 Polio
• 1921 Meningitis (probably meningococcal disease)
• 1939 Rubella
• 1971 Hepatitis A
• 1983 HIV/AIDS
• 1997 Campylobacteriosis
• 2009 H1N1 swine flu

Most of these (with the exception of smallpox) caused repeated epidemics every 3 – 5 years until their respective vaccines were introduced. The bold ones are vaccine preventable to a greater or lesser extent.

While New Zealand never really suffered from smallpox, in part thanks to isolation, it was not until the introduction of the first national immunisation programme that sickness and death from these infectious stopped.

Enter vaccination
In 1926 the first vaccine was introduced into New Zealand. Diphtheria vaccine became available to schools and orphanages, but it was not until 1941 that it became routine for all children under seven years old. Below is what happened next:

Number of cases of diphtheria and diphtheria mortality, 1916–2013. Source: Ministry of Health and the Institute of Environmental Science and Research.

The next cab off the vaccine rank to be introduced into New Zealand was Tetanus after 1940, however it was not until 1958 this became routine.

At this time we also began vaccinating against pertussis and the mortality rate plunged.

Numbers of cases of poliomyelitis, 1915–2013. Source: Ministry of Health and the Institute of Environmental Science and Research

Polio vaccine arrived in 1956 and shortly after the disease was eliminated in New Zealand.

Today
We have controlled these diseases through an effective immunisation programme which now reaches more of New Zealand’s children than ever before. In 1991 only about 56% of New Zealand children were fully vaccinated. This was a national shame, second from the bottom of all the OECD countries. Today we are awesome with around 94% of New Zealand children fully vaccinated against 11 diseases, soon to be 12. This puts us near the top of the OECD countries.

Twelve diseases we protect NZ children against before they are two years of age are:

• Diphtheria
• Tetanus
• Pertussis
• Polio
• Haemophilus influenza type B (a cause of meningitis)
• Hepatitis B
• Measles
• Mumps
• Rubella
• Pneumococcal disease
• Rotavirus
• Varicella (chickenpox) from 2017

Data for graphs are based on frequency of epidemics noted in the NZ historical records and the number of deaths noted in epidemics. The number of cases has been extrapolated by the estimates of mortality in the pre-vaccine era (JAMA 2007;298(18):2155-2163)

But
In New Zealand, vaccines have not been universally embraced. People have forgotten what these diseases are and what they did to families.

Wellington Cemetery

Today myths about vaccines circulate widely on social media where opponents actively seek to discredit the vaccination programme. While falsehood flies around the world on Twitter in one second the truth can have a hard time catching up, and by then the damage has been done. Confidence in life-saving vaccines has been shattered through deceit.

The evolution of a vaccine programme is predicable. The Chen graph below may be old now, but it sums up the evolution of vaccine programmes beautifully. First there is disease. A vaccine comes along and the disease declines. People start freaking out about (usually perceived not real) adverse events and lose confidence in the vaccine. Coverage declines, disease comes back. People realise disease is bad and they should never have stopped vaccinating, coverage improves. Disease declines again.

Bob Chen’s fabulous graph. Vaccine (1999) 17 Supp 3. S41-S46

I wonder what the families who watched their children die from these diseases would think about those that actively seek to prevent people immunising their children? An opportunity they never had.

Vaccines have changed people’s perception of what a normal life expectancy is. Today the single biggest threat to preventing these, and many more diseases, is a lack of commitment to and a lack of confidence in vaccines. Many people perceive vaccines to carry a much greater risk than they do. Despite the fact that vaccines are one of the safest public health interventions ever developed this is not always the perception.

Check out more data about vaccines and hospitalisations from the Figure.NZ team:
https://figure.nz/@InfectedNZ/public
https://figure.nz/chart/AzwxPvVYJbh0lrcY-ss9cb1hXRe2y2C4x
https://figure.nz/chart/bn2ytKLMXjW0wUIk

About

Helen Petousis-Harris is a vaccinologist. Her background is predominantly biological sciences, and she did her PhD in vaccinology. She has an appointment as a Senior Lecturer in the Department of General Practice and Primary Health Care at the University of Auckland’s Faculty of Medicine and Health Sciences. She and has worked at the Immunisation Advisory Centre at the University of Auckland since 1998 where she has developed a passion for all things vaccine. Current favourite diseases are pertussis, pneumococcal disease, measles, meningococcal, HPV and gonorrhoea. Could be persuaded to turn attention to shingles.

What is InfectedNZ?

Hey, Aotearoa. It’s time we had a chat about infectious diseases and what we’re going to do about the looming antimicrobial armageddon. That’s why we’ve asked leading health, social and economic researchers, and people with personal stories, to help us get real about our vulnerability and discuss solutions. Follow their blogs right here at tepunhahamatatini.ac.nz and watch the conversation spread across social media with #infectedNZ.

Backing it all up, wherever possible, is data from the good folk at Figure.NZ. Their super duper charts are based on data sourced from public repositories, government departments, academics and corporations. Check out their #infectedNZ data board and sign-up to create your very own data board on any topic that floats your boat.

Chlamydia is not a very sexy topic… it should be though, because it’s caught by having sex. It’s surprising how many young people don’t know how common chlamydia is. It’s easy to treat but it’s so much easier to prevent by using condoms when having oral, anal, or vaginal sex.

I’m a Nurse Practitioner for children and young people and also a Senior Lecturer at the University of Auckland. I work in a general practice clinic where we also provide health services for young people by going into three high schools.

Recently I’ve been asking young people about the best way to get information about STIs out to their age group. Chlamydia is a big problem for young people in New Zealand. In 2013 we tested 246 people between 15 and 18 years old who were seeking sexual health care for chlamydia. We found that 36% were positive. What people don’t realise is that chlamydia rarely causes any unpleasant symptoms, but it can have a lifelong consequence of infertility. So when you want to have a baby you can’t because your tubes (both male and female) are clogged up from past chlamydia infections.

Chlamydia is most commonly found in young people aged 15 – 29 years. Young women have higher rates than young men, but that may be due to women getting tested more frequently. What is most concerning is that young Māori women have rates 2-3 times higher than NZ Europeans.

“Social media like on Facebook, Instagram, Twitter and stuff” would be the best way to spread the word, said one group of 16 – 18 year old girls I asked (amidst chatter about whether you could get pregnant if you were the girl on top).

“You should start a movement or like have a campaign,” was another suggestion. They also said that they should be more educated about it and that it should be compulsory for Years 9 to 13. “They do it in intermediate [learn about sexual health] but that’s when they’re like really immature and they don’t listen.”

When asked what would help them learn about STIs, the girls thought that they should be “grossed out as much as you can” by showing them horrible pictures of infections and by getting testimonials from people who’ve had an STI. Scare tactics work, they said, because people don’t believe it will happen to them. “Come to the schools and talk to us in assemblies and put posters up with pictures, not heaps and heaps of words,” were a couple of suggestions. “Get on to Facebook to start a campaign like #saynotochlamydia or #chlamydiaisnotourfuture.”

“Could you handle being grossed out by pictures [of STIs]?” I asked a group of 16 – 18 year old boys. “Yeah, if they see pictures and realise they may have it, they’d wanna get a check up.” There was a suggestion that it could be featured in Shortland Street, depicting ordinary people getting an STI. “You should get someone who’s had chlamydia to talk about it,” said one boy. In this group we then went on to talk about the symptoms you might get if you had an STI, closely followed by the different sizes, shapes, colours and flavours of condoms that a boy called Kevin [pseudonym] had.

As a country we ratified a Treaty called the United Nations Convention on the Rights of the Child (UNCRC) back in 1993. Article 12 of the UNCRC states that children have the right to an opinion in all matters that affect them. As we know that chlamydia predominantly infects children and young people, they should have a say in how they are taught about the issue. My sessions with young people talking about STIs both individually and in groups have always been informative and very helpful from a health professional perspective. I often quote the saying from Phillip McMillan Bowse who was a contributor to England’s Eden project: “If you want to achieve the impossible – give it to the young, because they don’t know it can’t be done.”

About

Dr Karen Hoare is a Nurse Practitioner for children and young people and also a Senior Lecturer at the University of Auckland.

What is InfectedNZ?

Hey, Aotearoa. It’s time we had a chat about infectious diseases and what we’re going to do about the looming antimicrobial armageddon. That’s why we’ve asked leading health, social and economic researchers, and people with personal stories, to help us get real about our vulnerability and discuss solutions. Follow their blogs right here at tepunhahamatatini.ac.nz and watch the conversation spread across social media with #infectedNZ.

Backing it all up, wherever possible, is data from the good folk at Figure.NZ. Their super duper charts are based on data sourced from public repositories, government departments, academics and corporations. Check out their #infectedNZ data board and sign-up to create your very own data board on any topic that floats your boat.

My name is Nick Pattison and I would like to share with you a citizen science investigation that I was involved in with my previous school Rongomai Primary, called the Healthy Homes Project. The project was created out of conversations between  myself and other community members in Otara about the state of local housing in South Auckland, and was magnified at the time by the death of a two-year-old girl in Otara with poor health conditions linked to her damp state home. Something needed to be done.

Dr. Peter Buchanan and students at Landcare Research. Photo taken by Nick Pattison.

I contacted COMET for support and they provided a wonderful project manager, Dr. Sarah Morgan who helped run the project. She contacted local high schools to see if any would be interested in collaborating with us to have students test their homes to investigate the types and amounts of mould. Nicole Stevens from Manurewa High agreed to use her health academy, and at that time there had been no data gathered on South Auckland homes.

The project kicked off with a visit to the local Landcare Research facility, where my students met with researchers to learn how to collect test swab samples and to analyse them for the presence of mould. They then co-designed the method of the investigation. The project included really cool aspects of science – mycology (the study of fungi), modern genetic sequencing, and using microscopes and lab equipment not available in schools. Each student went home after this training and lab induction session and took swab samples from their bedrooms, the living room, the kitchen, and two other rooms of their choice.

The key results from the project

• 18 out of 22 homes were mouldy, and all had the right temperature and humidity to grow mould;
• the mould was readily recovered in a form that was likely to cause harm;
• three different yeasts described as “emerging human pathogens” were found;
• bacteria recovered from some of the homes was resistant to antibiotics; and
• Landcare Research says the homes with the yeasts and the antibiotic-resistant bacteria will need further investigation.

Landcare Research, which helped analyse the samples from the homes of 22 students, did not expect some of the results. Plant pathologist Dr Stanley Bellgard helped the students with their project, Nirvana Healthcare sponsored the project by giving them swabs, and SouthSci funding, which is the South Auckland pilot of the Participatory Science Platform, an initiative under Curious Minds, allowed us to purchase tools called an ibutton to measure temperature and humidity, and produce communication material to share our work.

In the houses, the mould spores were actively in the air and these are the things that we inhale. Mostly it’s not an issue because we are healthy and our wellbeing is intact and these moulds generally don’t have an impact on us. But if we are mentally stressed, physiologically stressed, malnourished or suffering dehydration, or have some predisposition to disease, then these moulds can induce a downward spiral of health.

Fourteen different kinds of mould were found across 18 of the 22 houses the students lived in, but when we looked at some of the yeasts we recovered, they really surprised us because we found three different yeasts that were emerging human pathogens.

Finding yeasts in the study had not been considered but they did have the potential to cause harm. Mr Bellgard said these yeasts, which included Candida parapsilosis and Rhodotorula, were linked to ill-health when combined with other complications, but there was another big surprise to come. We recovered three bacteria that had antibacterial resistance. This was also quite a surprising find beyond the yeast being a threat to health. These antibiotic resistant bacteria can be really, really challenging, especially in a hospital environment.

We deliberately did not look at whether the homes were private or state houses as we’re not trying to stereotype any group within our community and anonymity in scientific research for personal safety is very important. We just want to look at all homes to make sure they are healthy. We wanted the results to be anonymous, so no one could be targeted as having a ‘dirty’ or ‘unhealthy’ home.

The study also revealed the coldest home a student lived in – as measured on a September day at 6am – was 12°C. According to the Asthma Foundation, there is an increased risk of respiratory disease when homes fall below 16°C. The highest humidity recorded was 85 percent.

Rongomai Primary student Junior Wilson. Photo: RNZ / Kim Baker Wilson.

One of my students from Rongomai, Junior Wilson, aged 11, unveiled some of the findings on stage at a Manurewa High School prizegiving. Afterwards he gave interviews for RadioNZ, New Zealand Herald, Stuff, and Manukau Courier amongst others. Since the investigation we were successful in obtaining an Unlocking Curious Minds grant to work with Manurewa High, Landcare Research, and Otago University to investigate the amount of dust mites in homes as this acts as a more reliable model for the health condition of homes.

About

Nick Pattison is the Director of STEM Kauri Flats

What is InfectedNZ?

Hey, Aotearoa. It’s time we had a chat about infectious diseases and what we’re going to do about the looming antimicrobial armageddon. That’s why we’ve asked leading health, social and economic researchers, and people with personal stories, to help us get real about our vulnerability and discuss solutions. Follow their blogs right here at tepunhahamatatini.ac.nz and watch the conversation spread across social media with #infectedNZ.

Backing it all up, wherever possible, is data from the good folk at Figure.NZ. Their super duper charts are based on data sourced from public repositories, government departments, academics and corporations. Check out their #infectedNZ data board and sign-up to create your very own data board on any topic that floats your boat.