Did you know that mosquitoes kill more humans each year than any other animal? It is hard to believe that something so small can cause such global devastation, and yet it’s true.
Mosquitoes transmit a range of pathogens which cause deadly diseases, resulting in massive global morbidity (the condition one suffers when affected with a disease) and mortality (death).
In this regard, a mosquito is classified as a ‘vector’. A vector is a living organism that is able to pass on a pathogen from one animal or human to another. Most commonly, these are blood-feeding arthropods such as mosquitoes, ticks, fleas, sandflies and blackflies.
Our expert in the area of vector-borne diseases is Dr Lara Herrero, a Research Leader at the Institute for Glycomics. In this blog article, Dr Herrero takes us on a deep dive into the subject and how her research is tackling various diseases caused by vectors.
So, what are vector-borne diseases and what pathogens cause vector-borne diseases?
Vector-borne, disease-causing pathogens include parasites, viruses, bacteria and even helminths (worms). These pathogens cause a range of human and animal diseases.
Currently, the biggest vector-borne killer of humans is malaria. Malaria is a parasitic disease caused by the plasmodium parasite. There are over 200 million new cases of malaria infection and nearly half a million people die each year from the disease. For more information on malaria click here.
The second biggest vector-borne disease killer is dengue, caused by the dengue virus. There are four dengue viruses (dengue serotype 1 through 4), each with the ability to cause the predominant clinical presentations, dengue fever, dengue haemorrhagic fever and dengue shock syndrome. Over 3 billion people currently live in dengue-endemic areas, with estimates of around 96 million clinical cases each year.
How do these vectors transmit disease to cause infection in humans?
In order to transmit disease, these vectors need to feed on one animal/human that has the pathogen, and then carry this pathogen to another animal/human. The pathogen is transmitted in the blood-feeding process.
What is the difference between vector borne diseases and alphaviruses?
Alphaviruses are a group of viruses primarily transmitted by mosquitoes, which can be found on all continents (except Antarctica, of course). So, alphaviral diseases are types of vector-borne disease.
Are there specific environments/climates, regions or countries where these types of diseases are most prevalent?
Vector-borne diseases are more common in tropical and subtropical areas, with diseases that disproportionately affect the poorest populations. In the past decade, major outbreaks of dengue, malaria, chikungunya, yellow fever and Zika have caused havoc around the world, disrupting lives, and burdening communities.
What does your research specifically focus on?
My research focuses on vector-borne emerging diseases with a primary interest in alphaviruses such as chikungunya virus, Ross River virus and Barmah forest virus. We try to use a One Health approach to make advancements in understanding and treating vector-borne diseases, which combines field work, modelling and lab-based research.
What are the symptoms of Ross River virus infection?
In the initial stages, Ross River virus infection can cause what we would call ‘non-specific’ symptoms, like those common to many viral illnesses such as fever and a rash. This is why the Ross River virus-induced disease used to be called Ross River fever. However, the illness can be much more than just fever.
As the infection progresses, the arthritis (joint inflammation), arthralgia (joint pain) and myalgia (muscle pain) become the key manifestations. It is the chronic myalgia and arthralgia that can affect people for months to years, disrupting lives and incomes.
Nowadays, we refer to the constellation of symptoms caused by Ross River virus infection ‘RRV-induced rheumatic disease’ or ‘RRV-induced arthropathy.’
How is the Ross River virus transmitted?
The Ross River virus is mosquito-transmitted, but what makes this virus particularly tricky is that it has adapted to being transmissible by over 30 known mosquito species. This makes the virus harder to manage and control in the environment.
Are there any effective drugs or a vaccine available to combat Ross River virus?
There are no human licensed vaccines to prevent Ross River virus (or any alphavirus), so the best prevention is avoiding the bite of an infected mosquito. If you’re unlucky enough to contract Ross River, traditionally you would have to rely on non-specific therapies like non-steroidal anti-inflammatories which can only be taken in short courses and have a range of bad side effects.
Can you tell us about your new drug to treat viral arthritis caused by Ross River virus which has successfully completed phase II clinical trials?
We have recently successfully repurposed a drug approved for the treatment of cystitis for the treatment of Ross River virus-induced disease.
The drug is pentosan polysulfate (PPS), and it has a strong 60-year history safety profile. Preclinical studies have shown that PPS in a mouse model significantly reduced joint inflammation and cartilage damage.
Phase II clinical trails in humans showed that 72.7% of PPS treated patients at their three-month follow-up showed near remission of symptoms in contrast to patients who were administered with a placebo (14.3%).
What is drug repurposing?
Drug repurposing is a process of identifying new therapeutic use(s) for existing or available drugs. This process, in some cases, allows for rapid translation to market as these drugs have usually undergone extensive safety profiling, a vital requirement to get a drug approved for use in people. This process can allow for a drug to be available in a shorter time frame, rather than the 12-15+ years for traditional drug discovery and development.
The current COVID-19 pandemic has illustrated the urgent need for treatments for severe viral infections.
What is the next stage of this clinical trial?
Paradigm Biopharmaceuticals Ltd, a commercially focussed drug repurposing company based in Australia, is the company bringing this drug to market. The next stage indicated by Paradigm is providing access to patients via GP clinics who are able to use the TGA Special Access Scheme. Subsequently, following full clinical assessment, use of the drug against viral-induced arthritis would be approved by the TGA.
To find out more, click here.
Could this treatment be effective against other alphaviruses, like chikungunya virus?
Our preclinical work so far suggests that this treatment will also be effective against chikungunya, which is an exciting finding because the global burden of chikungunya is in the millions.
ABOUT THE AUTHOR
Dr Lara Herrero is a scientifically and medically trained NHMRC Research Fellow, studying the glycobiology of vector-borne diseases with a focus on mosquito-transmitted viruses. She obtained her PhD in 2008 studying human enteroviruses at the University of Western Australia/Telethon Kids Institute, before spending time in industry as a Senior Research officer at Phylogica Ltd (PYC Therapeutics Ltd). Although this was a productive period in terms of gaining industry experience and developing an interest and expertise in target discovery and early-stage commercialisation, Dr Herrero decided to return to academic research as a research fellow at the University of Canberra researching alphaviral arthritis, a topic true to her heart having struggled with Ross River virus arthralgia herself. In late 2010, Dr Herrero moved to the Institute for Glycomics at Griffith University where she developed her current research interest: how carbohydrates on viruses and cells affect pathogenesis. Dr Herrero is currently a Research Leader at the Institute for Glycomics where she runs a lab of four full time members, including a Post-Doctoral researcher and three PhD students.