Friday, 23 December 2011

Layman's Description of Gene Therapy to Treat Genetic Disorders

People, often children, that live with some genetic disorders are vulnerable to infection by Aspergillus. Chronic Granulomatous Disorder and Cystic Fibrosis are two such disorders but there are more.

This video is aimed at patients & carers of people who live with genetic disorders and decribes how new Gene Therapy techniques aim to provide new treatments for these illnesses.

Wednesday, 21 December 2011

Air-borne Fungi are More Diverse Than We Thought

Sir Alexander Fleming receiving the Nobel Prize in 1945
 The fungus Sir Alexander Fleming isolated (his famous 'lucky' observation) in 1928 which was the first step in the process that brought us antibiotics, and for which Fleming won the Nobel Prize is in the news once again. That fungus was intensively studied 80 years ago and identified as Penicillium chrysogenum and then put into storage.

The Imperial College team
Modern techniques for the identification of fungi are far superior to those available in the 1930's & 40's and a research group at his original place of work St Mary's College - now part of Imperial College, London have shown that those that identified Fleming's fungus got it slightly wrong but in the process have revealed to us a far more complex picture of this fungal species that we realised existed.

It turns out that Flemings isolate is not P. chrysogenum but is a very closely related species which has yet to be named. The species P. chrysogenum is in fact a group of four closely related species.

This discovery highlights that fungi are extremely diverse micro-organisms - as soon as you think you have one categorised several more subgroups are found. It also highlights the importance of understanding this diversity as after Fleming's initial observation many thousands of isolated of P.chrysogenum were analysed for their ability to produce penicillin and only after a lot of work was a suitable isolate found to work on an industrial scale. If they had known then what we know now perhaps that would have been more easily achieved.

For the future our new understanding of fungal biodiversity (including that of Aspergillus) may well lead to new drugs and products.

Friday, 16 December 2011

Patients Die as Aspergillosis is Misdiagnosed as Tuberculosis

Progressive appearance of lung cavities caused by Tb
Tuberculosis (Tb) has a long and terrible history as mankind has fought it for hundreds if not thousands of years. Before the advent of antibiotics it killed millions of people and animals when it was commonly referred to as 'consumption'. 200 years ago it accounted for one in four of all deaths in England, but by the 1980's that had fallen to 5000  deaths per year. More recently that number has started to slowly  rise as the infectious bacteria (Mycobacterium tuberculosis) started to acquire resistance to the antibiotics used against it.

Despite all these advances Tuberculosis today infects or has infected one third of the population of the world (though not all go on to develop Tb) and new infections occur roughly one every second!

Precisely because Tb is such a common infection doctors have to cope with huge numbers of patients, particularly in the developing world. There is a well established routine once doctors see a typical chest X-ray - give antibiotics and continue to monitor and little more is done about it - but unfortunately there is a hidden killer lurking that effects over 1 million people throughout the world.

Macrophage eating Tuberculosis bacteria
Chronic Pulmonary Aspergillosis (CPA) is a fungal disease that can grow in damaged parts of our lungs, evading our immune systems using scar tissue as a 'shield' to avoid detection. It looks very like, or is identical to Tb when doctors look at it on a chest X-ray and has very similar symptoms initially. Doctors mistake it for Tb and prescribe antibiotics as is standard practice.
Unfortunately fungi (e.g. Aspergillus fumigatus) that are as at home in the warm recesses of our lungs as they are in their more natural habitat of compost heaps are not effected by antibiotics and overmore are helped if the patient has poor body weight, diabetes, smokes or has AIDS. If not given correct treatment (antifungal medication) the prognosis is that 50% of those infected will die inside 5 years.

This recent article attempts to highlight this deadly problem and to ask for doctors to look a little more closely at their cases of Tb and how they progress and to consider Chronic Pulmonary Aspergillosis as a real alternative diagnosis. more...

Wednesday, 14 December 2011

Newsbite: Aspergillus hazardous problem in ceramic workers

Ceramic workers are at a high risk of developing respiratory problems as they are exposed to high levels of respirable dust containing silica and high microbial counts, including high Aspergillus counts.
The aim of the study was to study the percentage of ceramic workers with positive Aspergillus (A.) through polymerase chain reaction (PCR) and specific IgE (sIgE) for the different Aspergillus species. PCR and specific IgE (sIgE) for the different Aspergillus species (A. flavus, A. fumigatus and A. niger) were estimated in 40 ceramic workers and 56 control subjects.
 Results revealed that 32.5% of the workers’ sputum was PCR positive for Aspergillus. About 69.2% of them were A. flavus positive, 15.4% A. niger positive, 7.7% A. fumigatus positive and 7.7% A. flavus and A. fumigatus positive. more...

Friday, 9 December 2011

Beep! Beep! Defining the Fungal Barcode for Aspergillus

Many species of fungi including Aspergillus are very difficult to distinguish from one another. They can lack distinct structures, many having very simple forms and many lack sexual forms thus removing one long standing method used to distinguish species from each other i.e. their ability to interbreed.

A more modern way to distinguish species is to look at their DNA sequence. We have started to sequence entire genomes (the complete DNA sequence of an organism) but as yet this is still quite slow and requires a lot of effort and money to carry out - there has to be a quicker, cheaper, more flexible way to tell one species from another.

The ability to distinguish Aspergillus species is very important for several reasons including:

  • to distinguish between medically important (i.e. potentially dangerous) and unimportant (safer) Aspergillus species in the air, in a clinic, in homes, in our lungs
  • to distinguish between species likely to produce mycotoxin when growing on food or growing in damp buildings
  • to improve taxonomy for scientific identification, speed up research, we will get a better idea of the numbers of different species in our environment e.g. in our drinking water
DNA barcoding is a quick, cheap method than can be used on large numbers of samples in a short time. It is a powerful 'quick screen' once you have identified a series of short DNA sequences that are unique to each  species. Short DNA sequences are easy to work with and require minimal equipment to look at, all of which would be portable or available in a small laboratory at little cost - this makes this technique attractive to people working away from large laboratories, and in poorer countries - in other words the vast majority of the world.

Fungal barcoding is an ongoing research effort but a recent news report suggests that breakthroughs have been made in the search for unique short sequences in fungi including Aspergillus species. Reports at the recent International Barcode of Life conference in Australia suggest that an area of the genome of most fungi contains DNA sequences that are unique in most species. More work is yet to be done to make this discovery useful to us all but this is a big step forward.

Thursday, 8 December 2011

Special notice: Take Care with your Christmas Tree to Avoid Aspergillus

It is worth reminding everyone at this time of year of a study published in 2007 on the amount of mould spores brought into the home by people who purchase freshly cut Christmas trees to decorate for the holiday period. There is no problem for a few days but as the tree starts to die and deteriorate it was shown to be responsible for the production of many thousands of spores - it is after all slowly dying plant tissue which forms the main course of any Aspergillus meal.

If you must have a cut tree and you are sensitive to Aspergillus or other moulds, or perhaps you are immunocompromised and vulnerable to infection then ensure your tree is freshly cut, install it a few days before Christmas and remove it after Boxing Day! more...

Wednesday, 7 December 2011

Newsbite: Keep Your Wild Birds free from Aspergillosis

At this time of year in the Northern Hemisphere it is common for millions of people to feed wild birds in their gardens in order to enjoy seeing their antics. It is important to keep all feeders clean and dry and food fresh in order to avoid moulds including Aspergillus growing on the foods as the birds can be poisoned by toxins produced by mouldy food. There is also a possibility, especially when they are stressed in poor weather or after long flights of birds contracting aspergillosis after inhaling spores. more...

Friday, 2 December 2011

Over a Million Cases of Chronic Pulmonary Aspergillosis Misdiagnosed and Untreated

Press release from the National Aspergillosis Centre: 

Researchers have discovered that over a million people worldwide diagnosed with TB go on to develop an incurable but manageable fungal infection which is usually left untreated because it is mistaken for a recurrence of the disease.

In a new report published today*, the researchers from University of Manchester (UK) and University of Toronto (CA), say because the X-ray features and symptoms are so similar doctors often misdiagnose and prescribe the wrong treatment which can lead to tens of thousands of unnecessary deaths. The fungal infection responsible, chronic pulmonary aspergillosis (CPA), evades the immune system in the lungs progressing slowly and may lie undetected for years until symptoms (weight loss, tiredness, coughing and bleeding) start to develop. By then it is often too late to treat successfully. 50 per cent of all patients who develop it are unlikely to survive for more than five years, a similar outlook to many cancers.

Now, the report’s authors are calling on the World Health Organisation and others to provide awareness training, particularly for medics in Africa, India and China where under diagnosis of CPA is even more common than in Western countries because of the burden of TB.

The team was led by Professor David Denning, Director of the National Aspergillosis Centre at the University Hospital of South Manchester. He says the report highlights huge global variations in frequency and survival (see the table below). “For example, only 17 per cent of referred CPA patients in Manchester had underlying TB compared with 93 per cent in Korea. This variation reflects differences in diagnosis and inappropriate therapy – or none at all. Identifying CPA early in patients is only possible by means of
microbiological testing for Aspergillus antibodies.”

Professor Donald Cole, Associate Professor & Division Head of Global Health at the University of Toronto’s Dalla Lana School of Public Health is an expert in environmental and public health. He believes doctors have probably underestimated the worldwide burden of CPA. “We based our estimates on WHO data but the information is robust in some countries but not others. Under reporting is common, especially in countries such as China.”

Professor Ian Jacobs is Director of MAHSC – a partnership between the NHS in Manchester and the University of Manchester - and has recently included global health as a focus for its work. He is backing the call for WHO and the leaders of countries in Asia and Africa to take action. “TB is a major scourge worldwide, and to find that over a third of a million people each year then develop an incurable and ultimately fatal fungal complication – which could be diagnosed and treated – demands action. It must also follow that misdiagnosis of TB must be common with patients dying of chronic fungal infection of the lung.”

Notes to Editors

About Aspergillosis

Aspergillus is an airborne fungus that everyone breathes in daily. In those who are immunosuppressed, for example, those undergoing organ transplantation or treatment for haematological malignancies it causes a disease called invasive aspergillosis (IA)). In those with damage in their lungs such as tuberculosis or COPD, it can cause chronic pulmonary aspergillosis a slowly progressive and destructive disease of the lungs. In those with asthma or cystic fibrosis it can cause an allergic condition of the lungs with wheeze, mucous plugging of the airways and loss of lung function called allergic pulmonary aspergillosis.
There are estimated to be over 200,000 IA cases annually worldwide and over 10M patients at risk. Mortality rates vary by patient group ranging from 30% to 85%. For CPA there are estimated to be over 3M cases (as demonstrated in part by this report). For ABPA in asthma there are estimated to be over 4M patients worldwide.

NewsBite: Anti-Malarial Drug Works Well as an Antifungal

Artemesinin, an antimalarial drug, have previously been reported as having some antifungal activity. Gautam et. al. have attempted to identify its molecular targets and have found it has an synergistic relationship with itraconazole, such that together they work better than either apart. This could well be a hint that the target for this antifungal activity is novel and functionally different from currently available antifungal drugs, thus making it a   potential startpoint for a new class of antifungal drugs. more...

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