Tuesday, 17 December 2013

Longer Lasting Christmas Trees - Better for Those Allergic to Aspergillus.

It was announced a few years ago in this blog that it is a good idea to minimise the amount of time a 'live' freshly cut Christmas tree spends in your home before moving it outside. This is because just as with any other cut plant it is gradually dying (even though it may appear to be far from it) and will start to generate fungal spores as it starts to decompose - which would be bad news if you are sensitive to fungal spores such as Aspergillus.

We now have two additions to that advice.

  1. Recent research is working on ways to make a cut Christmas tree last longer once moved indoors. If we can delay the decomposition process then we can prolong the amount of time before it starts to produce too many spores. 
It has been known for many years that many plants release a signal when wounded & dying in the form of the gas ethylene. It seems to function as a hormone to trigger lots of different events including ripening. This is the basis of advice to keep ripening bananas away from other fruit as the ethylene released by the banana will accelerate the ripening of other fruit and cause spoilage.

The Canadian group researching ethylene and its influence on early needle drop of Christmas trees have managed to block the effect of ethylene and have lengthened the cut life of the tree two-fold. Such a tree could stay in a home of people who are sensitive to fungi for twice as long.

    2. If you have an artificial tree remember that during use and storage it needs to be kept dust free to reduce the amount of fungal growth as dust is an excellent food for moulds and is very good at absorbing moisture from the air.

Take care and have a very Happy Christmas!

Monday, 16 December 2013

Economic burden of lung diseases in Europe exceeds €370 billion and commonly is complicated by fungal disease

A joint publication by the European Lung Foundation and European Respiratory Society provides detailed statistics on lung health in Europe. 1 in 8 deaths in the EU are as a result of respiratory disease and 6 million people are admitted to hospital each year. It is estimated for several diseases that this represents the “tip of the iceberg”, as many disease deaths are improperly recorded.

The report concludes that there are almost 10 million people under the age of 45 living with asthma in Europe, of which approximately 1 million have severe asthma which difficult to manage clinically. It is thought that around 50% of patients with severe asthma have sensitisation to various fungi (SAFS), of which Aspergillus fumigatus is the most common.

 Moderate or severe COPD is present in 5-10% of the European population (25-50 million people). This results in around 300,000 deaths in Europe every year. The majority of this burden comes from lifelong cigarette smokers, of which 40-50% will develop COPD in their lifetime. Invasive aspergillosis in COPD is thought to affect about 1.2% of the 3,600,000 people admitted to hospital each year; about 34,000 people. It carries an 85% mortality. Chronic pulmonary aspergillosis also affects COPD patients.

 Previously the prevalence of cystic fibrosis in the EU was estimated at around 37,000 cases. Allergic bronchopulmonary aspergillosis (ABPA) affects about 15% of teenagers and adults with cystic fibrosis. The report summarises that 15% of these patients are hospitalised at least once per year. Approximately 200 people with CF will undergo a lung transplant every year, although this figure is rising.

Interstitial lung diseases (ILD) are a collection of over 300 diseases, but mostly made up of idiopathic pulmonary fibrosis and sarcoidosis. Together they account for 50% of all ILDs in Europe, with hospitalisation and death rates peaking at 40 and 2.5 per 100,000 respectively. Aspergillosis is a common complication of fibrosing sarcoidosis, with a predicted prevalence of almost 166,000 people in Europe. 

The total economic burden of respiratory disease was estimated at €379.6 billion, with COPD and asthma causing over €200 billion of this. 


Thursday, 12 December 2013

Detecting Hidden Chronic Respiratory Deaths

Statistics of what types of disease are causing the most deaths (and how many deaths result)  in an area of the world are important for governments and other authorities to calculate what provisions to make for the healthcare in each country. Those that cause high death rates are likely to receive priority for higher funding and drug companies are likely to respond by investing in research to produce appropriate drugs if they can see that there is a large enough market for it to get a return on its investment.

In areas of the world where health services are well funded, widely available and have a long history of well organised research into the use of those services healthcare data has been routinely collected for many years.

This is not the case in parts of the world where there are barriers to the use of healthcare provision due to factors like cost & distance. People get ill and die possibly without ever seeing a healthcare worker in for example rural areas of large countries like India, where there are 10 million deaths per year. Cause of death is often not recorded and this valuable information used to be lost. Estimates of causes of death nationwide are made by organisations such as the World Health Organisation based on the recorded causes of deaths of people who died in hospital - but this may be vastly different to the rates of cause of death in the very different rural areas where risks could be quite different.

An initiative was launched in 1997 by Canadian researcher Prabhat Jha to address this shortcoming. In the absence of official figures he realised that a reasonable impression of cause of death could be attained by talking to relatives about the symptoms noted leading up to the death. These 'verbal autopsies' have now been carried out throughout India and have reached 1 million records to date.

The results of this survey when compared with WHO figures suggest that in particular there are far more cases of malaria and snake bite than are currently recorded, but others differ too.

'Correcting' existing figures to take in for account these new mortality figures we can see that in a country like India there is massively more chronic respiratory disease (6 fold high frequency) and TB (90 fold higher frequency) in age range 30 - 69 compared with high income countries (e.g. UK, USA), while there is less cancer.

Such figures strongly suggest that the demand for drug development in those areas is far higher than previously thought and hopefully this will open the way for due consideration of higher investment by drug companies, individual countries and international communities.

Thursday, 5 December 2013

Cryptococcuc gattii - Killer or Accident of Evolution?

A recent copy of the journal Scientific American reported on the strange incident of hundreds of dead dolphins suddenly being washed up on the shore of a remote island of the Pacific North West, their lungs filled with yeast!

This fungus family is well know to us and we have used it for thousands of years to help us make food & drink, so we know it is usually a benign friend, occasionally causing an irritating, superficial infection in many of us (Thrush) and sometimes causing serious infection but certainly nothing like this had been seen before.

This island infection outbreak spread to pets and even people, but this particular yeast had never been found on this island before nor anywhere close by - it is a native of the tropics which are many thousands of miles south of this island. So why did it suddenly become a virulent pathogen?

After a lot of work scientists have found this species living in places they weren't expecting to find it. It sounds like the yeast is quite widely present around the world and one reason for its spread north might be global warming. Perhaps the warmer environment is making it possible for some fungi to spread, perhaps the animals that live in those areas are becoming more vulnerable to infection because of climate change but regardless there does seem to be a trend to increasing numbers of fungal infections in some parts of the world.

Amoeba (magnified many times)
So why did it suddenly gain the ability to infect humans? Like many fungi it has a natural home in the rotting material on the ground and in that environment it has predators e.g. amoeba. Scientists are theorising that as the yeast develops the means to avoid being eaten by amoeba it may also have quite unwittingly also developed the means to avoid parts of the immune systems of animals, as parts of our immune system contains cells that look and act just like amoeba.A strain of yeast (C gattii) that can evade amoeba might also be able to avoid similar cells in the immune system of animals, and humans!

See a schematic of the infection cycle here.

This C. gattii outbreak is ongoing and work to discover how it happened is also ongoing.

Read the full article in Scientific American

Wednesday, 4 December 2013

Press Release: Antifungal Drugs Increase 'flu Susceptibility

Common anti-fungal drug deactivates protein that protects against flu in mice

Researchers have found that a commonly used anti-fungal treatment increases susceptibility to severe influenza infection in mice. This treatment deactivates an important protein that protects against viral infections such as influenza.

Amphotericin B is an important anti-fungal treatment for people with already suppressed immune systems such as cancer patients and bone marrow transplant patients. Cells and mice treated with Amphotericin B lost the protective effects of IFITM3, a protein critical for protecting against viral infection. This increased their susceptibility to influenza infection.

“This is an important discovery and the consequences for patients on certain anti-fungal treatments should now be investigated,”
says Professor Paul Kellam, author from the Wellcome Trust Sanger Institute.
“Preventative flu vaccinations, rapid antiviral therapy or alternative anti-fungal treatment could be offered to these patients when at risk of flu infection.”

The team discovered that when cell samples were treated with Amphotericin B, the protective effects of IFITM3 were rendered inactive. This allowed the influenza virus to easily infect the cells.
“When we treated lung cancer cells with the anti-fungal drug, we saw the anti-viral protection from IFITM3 pretty much disappear” 
explained Christopher Chin, co-first author from the University of Massachusetts Medical School.

To fully understand the affects Amphotericin B has on IFITM proteins, the team treated mice with the anti-fungal drug. Once the mice contracted influenza, they displayed the same flu symptoms as mice completely lacking the protective ifitm3 gene. In the absence of the influenza virus, the mice treated with the Amphotericin B showed no signs of illness.

Previous studies from the Sanger Institute found that people who have a genetic variant in the IFITM3 gene are more susceptible to severe influenza than people without the variant.
This research indicates that patients undergoing Amphotericin B anti-fungal treatments could potentially lose the protective effects of IFITM3. The loss of IFITM3 could increase the risk of flu infections in patients with already compromised immune systems.

“Sometimes a very useful drug can also have unforeseen effects,”

says Dr Abraham Brass, senior author in the Microbiology and Physiological Systems Dept. at University of Massachusetts Medical School.
“We now see that a major part of the body‟s natural defences to influenza virus is rendered inactive by Amphotericin B in cells and mice. It‟s our hope that reporting the consequences of this interaction may stimulate further translational studies and potentially guide patient care.”

The researchers agree that further work is now needed to evaluate if this effect has any clinical significance for patients receiving Amphotericin B-based treatments.

“It's a fascinating study, and vital that we now work out if these effects in mice are also seen in people,”
says Professor Peter Openshaw, Director of the Centre for Respiratory Infections, Imperial College London.
“Patients on amphotericin often have complicated medical conditions and may be immune supressed; we need to work out if the treatments these patients were getting for other conditions made their influenza worse, as seen in the mice. If this is the case, we need to vaccinate those at risk, use these treatments sparingly and give antiviral drugs as early as possible when flu is developing. Clinical studies are urgently needed”.
This research was part of an ongoing collaboration between University of Massachusetts Medical School and the Wellcome Trust Sanger Institute.

Full article here

Father of Genomics: Fred Sanger Dies Leaving the World a Far Better Place

Without a doubt one of the greats of British science and the world, Fred Sanger invented a relatively simple, reliable and quick technique that allowed thousands of labs around the world to carry out DNA sequencing.
The consequences of that work are difficult to comprehend and a vast amount of subsequent work on living organisms has since been carried out using Sanger's technique.

Sanger reads DNA sequence

As an example, if we search the research paper database Pubmed with the words 'dna sequence' we find that in 1977 (the year Sanger published his technique) there were 1000 papers published. 10 years later there were 10 000 papers being published per year, and since 1995 there have been 35 000 research papers published per year. Sanger sequencing continued to be the most used technology until highly intensive automation was possible using robots to manipulate samples and very powerful computers to assemble sequences in around 2005.

The amount of papers published reflects the amount of gene sequencing that has been carried out - also see the figure below (from this paper) showing us the exponential rise in numbers of sequences submitted to public record (Genbank) since 1982.

Sanger made a second huge contribution to sequencing when he invented shotgun sequencing, a refinement that speeded up the process of generating sequence radically, enabling the practical use of his techniques to sequence entire genomes.

The invention of a technique to sequence large amounts of DNA triggered the start of the effort to sequence the DNA of entire organisms - i.e. their genomes. First small viruses (5400 base pairs, achieved in 1977 by Sanger himself), then more complex eukaryotes (12.5 million base pairs, achieved in 1996) and finally ourselves, humans (3 billion base pairs, achieved in 2001). The human genome is predicted to transform medicine and our understanding of ourselves and all human kind. The prospect of personal genome-driven medicine is looming large as new sequencing techniques drive costs down. That work will lead directly to improvements in the prevention and treatment of many illnesses including aspergillosis and other fungal infections.

For these achievements alone Sanger was awarded the Nobel prize in 1980 but his story is more extraordinary than that. This was his second Nobel prize, the first being achieved for the first sequencing of a protein, insulin. He remains one of only four people to win two Nobel Prizes.

Since 1993 the Sanger name has been given to the hugely successful Wellcome Institute housing the Human Genome Project in Cambridge, UK and his name is used extensively elsewhere in the world.

It isn't too much to say that a fair proportion of our hopes for the future of British (and worldwide) science, medicine,  improvements in our quality of life & health and much more rests on the solid foundations built using the tools fashioned by Fred Sanger.

Sanger's own description of the early years of DNA sequencing
BBC report of his death
What impact did Fred Sanger have on our lives?
A history of genome sequencing

Mushrooms Create Their Own Breeze

Journal Scientific American has reported a mushroom mystery and the story of how the solution was discovered. We have thought for a long time that when a mushroom or other fungal fruiting body starts producing spores they are dispersed on air currents, so it was assumed that anything from a breeze to a strong wind would be needed to move the spores around.

Puff ball releasing cloud of spores
However it was then noted that mushrooms were able to disperse spores even in the absence of wind - in completely still air! This was a mystery - how could this be possible as few fungal fruiting bodies have any obvious sort of mechanism to project spores. There are one or two exceptions - puff balls for example are large bags of air that forcibly eject spores when the puff ball is struck with a drop of rain, but these are exceptions to the rule!

Emilie Dressaire et. al. have reported the finding that a mushroom can actively cool the air surrounding them and consequently create upward air currents eminating from the mushroom itself, and spores are carried away in those air currents.

So even in the stillest of air, a mushroom can effectively disperse its own spores far and wide!

The author of the Scientific American story (Katherine Harmon) has released an audio podcast describing the finding

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