27 April 2018
This article originally appeared in the New Zealand Herald, written by Science Reporter Jamie Morton.
It's a disgusting but true fact that humans have long lived with parasites that dwell within our bodies, feeding off us and sometimes causing sickness and disease.
Today, it's estimated a billion people are infected by these parasitic worm infections, mostly in developing nations.
They routinely infect humans through the skin - usually the foot - before migrating to the lungs and eventually establishing themselves in the gut where they can persist for years, feeding off blood.
That can lead to iron and blood deficiency in the human host, affecting growth and development, as well as fatigue in general weakness.
But it wasn't always just poorer countries affected by them - and it was only in relatively recent times that western populations shed the worms they'd long carried.
"We were evolved to carry parasites all of the time - from birth to death," explained Professor Graham Le Gros, a world-leading immunologist and the director of Wellington's Malaghan Institute of Medical Research.
"The simple introduction of sanitation and drugs that cleared the worms from our intestine stopped the reinfection cycle, and we essentially became worm-free overnight."
Some of these parasites are much more ghastly than others.
The tapeworm can grow up to 15m long and live inside a human for three decades.
But the hookworm, measuring just a few millimetres and estimated to affect 500 million people, is barely noticeable if in small enough numbers.
"If you have zero to 25 hookworms, you won't feel a thing and you'll be completely asymptomatic - but if you go from 25 to 50, you'll start to have a bit of tummy grumbling," Le Gros explained.
"If you have 100 worms, you start to feel ill - and if you have 500, you'll be looking seriously sick."
Hookworms were once notorious for infecting coal miners, whose sallow skin had been initially thought to have been caused by coal dust, before it was revealed poor sanitation and the resulting parasites had been to blame.
In badly-affected countries of the tropics and subtropics, hookworms are the leading causes of maternal and child morbidity, although cases are rarely fatal.
In susceptible children, hookworms cause intellectual, cognitive and growth retardation, intrauterine growth retardation, prematurity, and low birth weight among newborns born to infected mothers.
An accidental discovery
In a newly published study, funded by the Health Research Council of New Zealand, Malaghan researchers have discovered a link between asthma and hookworm therapy that could open the door to potential new treatments.
While traditional thinking had been that blood feeding only occurred once the parasites entered the gut, postdoctoral researcher Tiffany Bouchery used a pre-clinical model to demonstrate that this actually began happening as soon it was inside the body.
"What we've found, quite unexpectedly, is that the worm starts blood feeding as soon as it enters the body, in the first three days of infection," Le Gros said.
"This insight could lead to new ways of targeting the species of hookworm that commonly infect humans, because once it is in the gut it's very hard to deal with."
Using this insight, the team used quinolones — antimalarial drugs — to inhibit the parasites' ability to blood feed even before it reached the gut, preventing them from growing and persisting in the body.
The drug inhibits the iron-detoxification pathway which allows the worm to safely process iron in the blood.
"While not what we set out to find, this piece of research is very exciting."
In terms of its potential and where it could lead, improved therapies for the billion people suffering from hookworm would be a major milestone in the fight against tropical diseases.
"It also gives us a deeper mechanistic insight into how other worms may be similarly affected when they first start migrating into the body and how we might use this knowledge to work with worms to our advantage."
The findings suggested that further investigation of the iron-detoxification pathway could one day lead to the development of other drugs or vaccine targets against hookworm.
Other research has even used hookworms themselves an agent to fight pathogens and disease.
In one Australian study, 12 human participants were each experimentally infected with hookworm, and then given gradually increasing doses of gluten to reveal how the parasites could reduce the symptoms of cealiac disease.
"There are also interesting studies that show multiple sclerosis can be reduced if you have parasite infections," Le Gros said.
"And when we talk about worms being good or bad, it depends how many you've got, obviously.
"But maybe they could teach us much more about how to use our immune systems."
That of course didn't mean that we should all be allowing small numbers of worms to jump back onboard.
"But if we learn what the worms actually do, we could avoid the blunderbuss approach and maybe we could solve things like Crohn's disease, by shooting down inflammatory conditions like the worms do."
'The future of human health'
Speaking ahead of the awareness-raising Day of Immunology, being marked around the world on April 29, Le Gros said science was now on the cusp of exciting breakthroughs in our fight against disease, as knowledge of our immune system grows exponentially.
Our immune system is a complex system of structures and processes that has evolved to protect us from disease.
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Every day, our bodies are under attack from a wide variety of foreign and potentially infectious organisms, such as bacteria, viruses and parasites.
Molecular and cellular components of our immune system travel around our bodies, patrolling for invading organisms and responding when necessary.
Our body has two main types of immune responses – innate and adaptive.
The innate immune system consists of cells and proteins that are present and ready to mobilise and fight microbes at the site of infection. Innate immunity has a number of set strategies for recognising and dealing with infections, without the need to be trained to recognise them.
The adaptive immune system is unable to respond instantly to infections, and needs time to adapt to recognise them.
Having learned to respond, it was then able to remember particular germs that have infected the body previously so that when, or if, such infections try to infect the body again, the system is able to respond effectively with speed and precision.
Immunology was the branch of biomedical science that dealt directly with it, and included research into the development of the immune system, as well as its daily functions and dysfunctions.
Le Gros called it the "future of human health".
"It's game-changing," he said.
"As we better understand how our immune system works, and how it can be harnessed to fight disease, we're poised for new, gentler and more effective treatments for cancer, asthma and allergy, multiple sclerosis, Alzheimer's, gut disease and many other debilitating diseases."
Vaccines and immunisations had already given a glimpse of the power of immunotherapy – teaching the immune system to fight disease by mimicking a natural infection.
"What is less well known, is that our immune system can also protect us from developing non-infectious diseases such as cancer.
"And research has shown that our immune system plays an important role in the development of allergic disorders and in many common disorders not traditionally viewed as immunologic, including metabolic and neurological diseases such as Alzheimer's."
Last year, the Malaghan Institute took the first step in developing New Zealand's answer to the latest in cancer vaccines.
CAR-T cell therapy was a revolutionary new approach to fighting cancer by redirecting a patient's own immune cells to impart long-lasting protection against the disease.
"Later this year, through a collaboration with an international biotech group Hunan Zhoatai Medical Group, we're aiming to conduct our first small CAR-T clinical trials, with the goal of developing a more effective and longer-lasting way to fight certain cancers."
Understanding the virtuous relationship between the immune system, our food environment and the macro and microorganisms that live in and on us is was also a big focus for the institute this year.
"By undertaking research into the basic biology of the immune system and developing immunotherapies and vaccines that supercharge the immune system, or down regulate overactive immune responses, our scientists are striving to make a genuine difference to the way we treat disease in this country."