Tuesday, 29 January 2013

Aspergillus Contamination of Crops and Global Warming

Crops are known to be vulnerable to infection by Aspergillus and other moulds when they are stressed. Stressors include lack of water, temperature and insect & wind damage. All are fairly common in areas of the world where extremes of climate occur - in the main these areas are found towards the middle half of large areas of lands, well away from the mediating effects of the sea (location of main crops worldwide).

Consequences of global warming
There is some suggestion that at least some of these areas are gradually experiencing higher temperatures and increased drought conditions, and this is thought to be due to global warming caused by burning fossil fuels and releasing excessive CO2 into our atmosphere. If this is true - and most scientists are now in support of this conclusion - then this situation is only going to gradually get worse. Some areas will become warmer, some colder, some dryer - it seems most will experience greater extremes of climate and some of these will stress crops.

Once infected with Aspergillus and other fungi crops tend to accumulate mycotoxin contamination as the same dry conditions tend to also stimulate mycotoxin production. In the US alone in 2011 the value of crops dropped $190 million due to mycotoxin contamination, but finance aside there is a clear threat to the food supply of the world as nearly all of these crops are ultimately for human consumption.

This article points out two threats in particular. In developing countries testing of crops for mycotoxins isn't extensive and there have even been allegations that contaminated produce has been sold to those countries as it is cheaper on world markets, and cleaner grain produced in those countries is sold abroad (for higher prices) while the grain that is more contaminated is retained for domestic use. Secondly and possibly of more direct interest to US readers (and those in other developed countries) is that testing of grain and other products for mycotoxins isn't completely efficient. Some batches of grain are allowed through which exceed permitted levels and as the effects of global warming increase those batches are likely to have more toxins in them. Overall the amount of mycotoxin entering the food production industry is going to rise.

Steps are being taken to reduce the amount of mycotoxins present on stressed plant crops. Inoculating crops with fungi that cannot produce mycotoxins has been successful  and the breeding of plants that are resistant to fungal attack (1, 2) is under active development.

Monday, 28 January 2013

Oral Sex and Aspergillosis?

(a) Image of laryngoscopy when the patient first came to our hospital in September 21, 2009 (b) Image of laryngoscopy after 30 days of antifungal treatment in October 21, 2009, (c) SEM observation of the focus tissue, (d) Histopathological examination (HE, ×400), (e) The slide culture of the isolate (methylene blue, ×400).

There have been a few descriptions of Aspergillus infecting people who apparently have a completely healthy immune system. These mostly describe instances when someone has inhaled a cloud of fungal spores when opening a bag of gardening compost and then subsequently become very ill. Post mortem reveals extensive invasive aspergillosis.

Other examples of vulnerable people include those with immunocompromising conditions such as AIDS or genetic disorders such as Chronic Granulomatous Disorder and people with pre-existing lung damage from infections like Tuberculosis.

All of these are explainable and remain very rare as our healthy immune systems are able to defeat all but the most serious infections. When infections occur they are very slow growing as the fungus 'battles' with our immune system and usually emanate from an area in the infected host that has a weakened immune system - lung scar tissue for example, or occasionally a fold in part of our sinus'.

This report suggests that there might be other small hidden populations that could be vulnerable to infection. Far from convincing but intriguingly a single patient who has a completely normal immune system contracted a rare form of aspergillosis at the back of their throat. Treatment with itraconazole quickly cleared up the infection but there were few clues as to why this person became infected. The researchers have alluded to a comment that she made that she was accustomed to regular oral sex with her male partner(s). They claim that there might be a link between this practice and the Aspergillus infection but that is not substantiated.

A further observation is made by the research group that reported cases of laryngeal aspergillosis (only 50 cases recorded since 1969)  have occurred mainly in younger (sexually active) women over the last 10 years. Previously the victims have been mainly older men.

This is one to monitor over the next few years rather than take too seriously just yet!

Thursday, 24 January 2013

Genetic Susceptibility to ABPA in Cystic Fibrosis

What causes susceptibility of certain individuals to infection by aspergillus is largely unknown, Infections such as allergic bronchopulmonary aspergillosis (ABPA) and chronic pulmonary aspergillosis (CPA) are known to infect significant numbers of people (estimated at 5 million ABPA worldwide, 400 000 CPA) but infection in sufferers of cystic fibrosis are proportionally higher with up to 10% of all CF patients infected.

Genetics are thought to play a part in susceptibility both for those with and without CF, but clearly having CF is a major risk factor for ABPA. Nonetheless 90% of those with CF do not get ABPA so there are presumably further risk factors to take in for account.

We know the following (quoted from Cystic Fibrosis Foundation):
ABPA is more common in males and adolescents. It is also common in people who:
  • Have decreased lung function
  • Wheeze
  • Have allergies
  • Have asthma
  • Are positive for Pseudomonas species

These may act as clues - perhaps indicators of ABPA but also possible indicators of a genetic susceptibility to ABPA in some CF patients.

This paper suggest that there are particular genes associated with ABPA in CF patients which occur more frequently in those with the particular gene variant than those without. Quoting the conclusion in the paper:

a correlation exists between HLA-DRB1*15:01, -DRB1*11:04, DRB1*11:01, -DRB1*04 and -DRB1*07:01 alleles, and ABPA-CF susceptibility and suggest that HLA-DQB1*02:01 is an ABPA-CF resistance allele.
This means that CF patients could be screened for the presence of the ABPA resistance gene variant and if found appropriate prophylactic action could be taken. This could help minimise the occurence of ABPA in CF patients which would be a big step forward in improving management of that disorder.

Wednesday, 23 January 2013

Newsbite: The Battle Between Ourselves and Aspergillus - What We Know So Far

A new review summarises what we currently know about the interactions between Aspergillus and our immune cells - why sometimes one may win over the other. It is worth noting that this is all summarising work carried out on isolated cells in the laboratory so may not fully represent the true situation in our bodies more...

Tuesday, 22 January 2013

Social Housing Damp and Mould Problem

There seems to be a recurring issue of problems with damp and mould growth in homes that are provided by a large organisation such as councils and housing associations in the UK. The problems are often poor design, poor installation of modifications such as insulation, poor maintenance, slow response to requests for repair and lack of prioritising mould as a cause of a severe health problem (read a recent example here).

The education of the occupants of a building is important too as their normal living activities can generate large amounts of moisture and they need to understand that ventilation is important  - open windows when taking a shower, don't dry clothes on radiators inside a house is mould is a problem in that house are just two examples of steps that an occupier can take to help reduce damp. There is not generally a single cause of damp in a home.

There is another important large group of people who are dependent on a 'remote' authority to repair their homes. The military house large numbers of individuals and families in homes that are provided on bases and close by and there again we tend to see problems with damp and moulds. In the US we have recently found out that part of the problem was that of large companies being paid to provide new homes but no-one having  responsibility to monitor the state of those homes as they were used. The result was that occupants faced with moulds could complain but no-one was monitoring the backlog of repairs needed and they would build up.

The US government has taken steps to resolve this problem by adding into a new law (National Defense Authorization Act) that has just come into force the requirement for the military to monitor the health status & repair of all of its homes.

Hopefully we are seeing the gradual improvement of all social housing so as to avoid damp and mould

Friday, 18 January 2013

The Development of Safer Medicines

Modern medicines have to be tested on animals to try to ensure that they are safe before they go to being 'tested' on people. This has long been the view of various animal rights groups and it has also long been stated by those supporting the use of animals for experimentation that their use cannot be substituted.

The cold facts are that over 300 000 people a year are still killed in the US and Europe despite all the animal testing. Over 90% of drugs that make it through animal testing subsequently fail, many due to toxic effects not identified by animal testing - so this is an expensive problem as well as highly inefficient as a safeguard for human health. There are examples of modern drugs that were so toxic to humans that volunteers were severely injured when testing them for the first time. As a consequence most of these trials are said to have moved to India (where regulation is less strict) and it is reported that thousands of people have died in India since 2006.

We clearly have a moral and financial need to improve the accuracy and predictive efficiency of how we test new drugs for toxicity.

Body on a chip research

A recent article in New Scientist by the seems to be saying that times are starting to change. There are now some alternatives to the use of animals that are at least partially viable and need further use to develop. Examples include (quoting the NS article)

These techniques include: human tissue created by reprogramming cells from people with the relevant disease (dubbed "patient in a dish"); "body on a chip" devices, where human tissue samples on a silicon chip are linked by a circulating blood substitute; many computer modelling approaches, such as virtual organs, virtual patients and virtual clinical trials; and microdosing studies, where tiny doses of drugs given to volunteers allow scientists to study their metabolism in humans, safely and with unsurpassed accuracy. Then there are the more humble but no less valuable studies in ethically donated "waste" tissue.
Most of these look like they need a lot more development but with ever increasing power given to us to analyse the human body (genome sequencing, expression analysis, Proteome studies) they may no longer be 'pie in the sky' dreams. These techniques may start to provide real alternative to some animal testing - possible small scale to begin with but given the rather poor record of animal testing when trying to predict toxicity they may become an additional tool fairly quickly.

One problem is that animal testing is compulsory throughout most of the pharmaceutical development world, so until laws can be changed animals cannot be replaced. At our best guess, this is going to be a gradual process.

Wednesday, 16 January 2013

Cinderella Diseases Get Fewer New Drugs

There is a group of diseases that is neglected as they seem to offer less potential for profit for the major drug companies. (see dndi.org).

The new MSF analysis finds that although neglected diseases have been estimated to account for roughly 11% of the world’s global disease burden, in the last decade these illnesses garnered only 4% of the world’s new therapies and 1.2% of new chemical entities. If new drugs were distributed on the basis of disease burden, neglected diseases would have received 89 new products instead of 37, says Strub-Wourgaft. But the future may look a little brighter. The new analysis estimates that, given the current pipeline, as many as 4.7 new products could be approved each year for neglected diseases through 2018. “There have been encouraging signs compared to the last report,” Balasegaram says, but “we’re still far behind where we want to be.”
There have been efforts by governments around the world to try to redress this problem by supporting research and development of new drugs for these diseases over the last 10 years - including fungal diseases - but as yet there is apparently no sign of an increase in the number of new drugs emerging.
The new analysis, presented today at a symposium in New York, shows that of the 850 new therapies and vaccines approved by the US Food and Drug Administration, the European Medicines Agency and other agencies between 2000 and 2011, 37 focused on neglected diseases, and just four of those were new chemical entities. The work builds on a pioneering paper published in 2002 by members of the Drugs for Neglected Diseases Working Group, which counted 1,393 new drug approvals—16 of which focused on neglected diseases—between 1975 and 1999 (Lancet 359, 2188–2194, 2002). According to DNDi, 11 of those 16 drugs could be considered new chemical entities. The numbers suggest that although the rate of approvals for drugs for neglected diseases has gone up, the rate of approvals for new chemical entities seems to have remained relatively flat.
Some suggest that as drug development takes over 10 years then we will now start to see the number of new drugs for neglected diseases start to rise (after 10 years of investment by governments) but others note that drug development funds have been cut by governments as they focus funds on basic research once again while money is short in the global recession.

Original Report

Tuesday, 15 January 2013

Geomicrobiology and Aspergillus

Lichens growing on a rock (algae & fungi growing together)
With thanks to Gadd & Raven (2010)

All kinds of microbes, including Aspergillus can contribute actively to geological phenomena, and central to many such geomicrobial processes are transformations of metals and minerals.

Microbes have a variety of properties that can effect changes in metal speciation, toxicity and mobility, as well as mineral formation or mineral dissolution or deterioration.

Such mechanisms are important components of natural biogeochemical cycles for metals as well as associated elements in biomass, soil, rocks and minerals, e.g. sulfur and phosphorus, and metalloids, actinides and metal radionuclides.

Apart from being important in natural biosphere processes, metal and mineral transformations can have beneficial or detrimental consequences in a human context. Bioremediation is the application of biological systems to the clean-up of organic and inorganic pollution, with bacteria and fungi being the most important organisms for reclamation, immobilization or detoxification of metallic and radionuclide pollutants.

This is a relatively new field of study so we have added a section to the Aspergillus Website (Geomicrobiology on the Aspergillus Website) that contains our collection of articles on Aspergillus taken from this area of research. Some summaries/reviews are linked from the main page but all articles are searchable - there are currently 71 articles in the collection but more will be added.


Wednesday, 9 January 2013

If We Didn't Have Pathologists...

The Royal College of Pathologists of Australia (RCPA) have released a humorous reminder of how important pathologists and the study of pathology are to us all. If we did not have accurate ways to diagnose an illness how would we decide how to treat the illness?

If Pathologists didn't exist

where would the answers come from?

Investigate some of the alternatives by clicking on this link

Tuesday, 8 January 2013

Hunter-Killer Fungus

Fossilised nematode worm
Most of us will be aware that fungi can be found in patches on wallpaper or in compost heaps where they are able to grow through plant material and slowly digest it as long as there is an adequate source of water to enable the fungus to grow.
Some of us will be aware that fungi can infect animal tissue that has been damaged or has inadequate protection from the hosts immune system. This usually means a slow invasion of scar tissue that takes place over many years - though of course if the immune system is completely removed invasion can happen more rapidly.

But did you know that some fungi can actively hunt and kill wild prey and have been doing so for many millions of years?

Nematode worms are widespread across the world, living in most habitats ranging from the ice caps of our polar regions to the steamy heat of our equatorial jungles and account for 90% of the life forms in the deepest parts of our oceans.

There are many forms that parasitise us too! So perhaps we are not too upset to hear that these worms are the prey of specialised fungi. Modern day carnivorous fungi are well characterised and trap their prey by forming looped structures that the worm gets caught up in. The worm is subsequently digested.

Recent investigators have found trapped worms and carnivorous fungi in prehistoric amber that is over 145 million years old so it is apparent that this is an ancient tactic employed by some fungi to take advantage of one of the worlds most plentiful food sources.


Monday, 7 January 2013

Ash Fungus Sequence Data Released

Ash blight (common name Chalara, scientific name Hymenoscyphus pseudoalbidus) is a fungal infection that mainly affects Ash trees. This infection threatens large numbers of trees that are indigenous and very common in the UK and may well lead to severe scarring or death of most trees.

The Ash blight fungus has been rapidly part-sequenced and the resulting genetic data published. For speed the researchers have concentrated on expressed sequences (RNA) i.e. those that are switched on while infecting the tree. Researchers at the UK's Sainsbury Laboratory and John Innes Centre have accomplished this important advance for the fight against this invading pathogen in a matter of weeks and have now released the genetic sequences to enable other researchers to help with the task of finding a weakness we can exploit.

This is an example of 'crowd sourcing' for research which is intended to allow as many scientists around the world as possible to quickly participate in the effort to discover why this strain of Chalara is proving so destructive when there are very closely related strains that are commonly found on Ash trees throughout the UK which cause little damage.

'Crowd sourcing' is intended to allow progress to be as rapid as possible and was famously (and successfully) used during the E. coli outbreak in Germany in 2011 and is essentially a sophisticated form of social media (GitHub). Scientists can safely contribute to the research knowing that their contributions are recorded and protected as the system automatically records who says what & contributes what and when it was mentioned. Traditionally scientists have to be careful what they say to other scientists until their work is published (as that is the accepted form of establishing who was first to make a discovery for example) and that can take many months. However with this system precedence is clear and thus multiple groups can freely collaborate, potentially accelerating research.

Report from the Sainsbury Laboratory

Earlier comment on Ash blight by Aspergillus blog

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