Monday, 29 April 2013

Aspergillus Genome Annotation Completed

Many readers will be aware that we are currently undergoing a huge process that may well end up reading every gene from the DNA of every interesting organism on earth. This is now possible thanks to the advanced and rapid sequencing technology currently available - this has every chance of revolutionising many parts of our lives including medicine.

However reading the DNA is only part of the problem that has to be solved before we can make best use of this technology. The DNA sequences are just anonymous strings of bases until they are assigned a function. Fortunately we know the sequences and function of many thousands of genes so we can compare all new genes to these sequences in the hope of finding a match and therefore finding out what each new gene does - if it has the same sequence as a gene with a known function then the chances are it also has that function. This is a process known as annotation.

Once we can assign a function to most genes we can arrange them in likely metabolic pathways so that we can start to work out how each organism works! It will be some time before we can actually do this but annotation is a big step to the desired end.

This recent publication shows that annotation has been successfully achieved for several of the most important Aspergillus genomes; fumigatus, nidulans, niger and oryzae, and the annotation has largely been validated manually which is still the best guarantor of quality. This represents another large step forward on Aspergillus research, the use of Aspergillus for industrial processes & food, and our understanding of the human health issues associated with this ubiquitous fungus



Thursday, 25 April 2013

FDA Reviewing Posaconazole Pill

An application for selling a pill form of posaconazole is being reviewed by the Food and Drug Administration.

Also known as Noxafil, posaconazole is already distributed in a liquid form, given to patients at high risk of fungal infections due to severely weakened immune systems. In this form it is approved for patients aged 13 and older.

Merck & Co is seeking for approval to sell a once-a-day treatment in the form of a pill in both the USA and Europe with further plans to apply for approval in other countries.

Patient testing resulted in a small number suffering liver complications. including liver failure and death. Common side effects have been reported as being fever, diarrhoea and nausea. It has also been advised not to be taken in those already on immune-suppressing medicines, statins, calcium channel blockers, medicines taken for irregular heart rhythms and many others.

Despite the negatives associated with this form of medication, less invasive methods of taking medications are widely desired by many patients.

Global burden of ABPA with asthma and its complication CPA in adults

Asthma can be complicated by allergic bronchopulmonary aspergillosis (ABPA) which may itself be complicated by chronic pulmonary aspergillosis (CPA). Despite this, global burdens of these have never been estimated.

Using the country-specific prevalence of asthma from the Global Initiative for Asthma report and applying it to population estimates, the adult asthma cases were calculated and an estimation of the burdens of ABPA and CPA were calculated by World Health Organisation (WHO) region.

Prevalence rates were estimated using two methods whereby the Global INiative on Asthma (GINA) report was employed, using their assertions of prevalence of clinical asthma was 50% of the self reported wheezing rate and a second method whereby the mean prevalence of current wheezing in children was 88% of that recorded in adults in the countries which participated in both studies. The prevalence of ABPA in adults with asthma was found to be 2.5% using five referral cohorts.

By using the following calculation the Total CPA complicating ABPA was estimated:

Asthma cases per 100,000 population per country x % of asthma in adults x proportion with cavities likely to be CPA 10% (best estimate), ranges 7-20% = Total CPA complicating ABPA

Results from the study estimated 4,837,000 patients with asthma, develop ABPA (2.5% of worldwide asthma sufferers).

By WHO region, the ABPA estimates are:

Europe: 1,062,000
America: 1,461,000
Eastern Mediterranean: 351,000
Africa: 389,900
Western Pacific: 823,200
South East Asia: 720,400

A population of 411,100 of those with CPA complicating ABPA has also been estimated; making it more common that originally thought.

Such a high prevalence justifies the need for improved case detection and further investigation into the conditions to ascertain greater accuracy regarding prevalence rates in different populations (locations, ethnic groups).

Original article

Wednesday, 17 April 2013

Post-Sandy Guidance for the Treatment of Mould in the Home


Article originally posted on the Office of the Governor of New Jersey website:
The New Jersey Department of Health today released a Mold Guidelines for New Jersey Residentspamphlet created to provide direction to residents on addressing mold in homes in the aftermath of Superstorm Sandy. In addition, the Department is announcing a series of training classes in cooperation with the UMDNJ School of Public Health to assist homeowners, volunteers and public health and building code officials in mold removal and assessment.  
“As New Jersey recovers and rebuilds from Superstorm Sandy, mold and its remediation may become a significant issue for many New Jersey residents,” said Mary E. O’Dowd, New Jersey Health Commissioner. “Although molds are common in our environment, mold may become a problem when it grows inside homes. These guidelines were developed to better inform homeowners on how to ensure their homes are cleaned and remediated properly to avoid mold problems now and in the future.” 
 Molds can cause staining of walls and ceilings and can affect building components causing property damage. Exposure to mold can cause nasal and throat irritation, coughing or wheezing, eye irritation, or, in some cases, skin irritation.  
The pamphlet addresses a number of topics including mold-related health concerns, how to inspect for mold and tools and techniques for clean-up. For example: 
  • If mold is visually apparent, resources should be used to correct any moisture problems and clean up mold contamination rather than testing.
  • For smaller areas less than 10 square feet that have been affected by mold growth, a homeowner or business owner may be capable of performing the work, but for larger areas greater than 100 square feet, a qualified contractor who has experience in mold or environmental contamination may be required.
  • Those performing remediation work need to be protected with gloves, a respirator, protective clothing and goggles. 
The pamphlet also includes checklists on inspection services and mold remediation to help guide residents in steps they should take when addressing mold problems in their home.
 A copy of the brochure [pdf 595kB]

Organic Fruit Juice Contaminated by Mycotoxin

In what may form a warning for the organic food industry this recent story follows the withdrawal from sale of a few batches of organic fruit juice. Tests had shown it contained slightly more than the permitted levels of the fungal mycotoxin patulin (56ppb versus the regulation limit of 50ppb) which results from contamination by fungus and growth.

Organic juices are of course usually only treated with a relatively short lived mild heat (pasteurisation) in order to reduce the contamination of the juice with microbes including fungi. It is suggested that this minimised the loss of nutrients in the drink and thus maximises its health-giving properties. The inference of this article is that this treatment though effective is perhaps not as effective as adding preservatives.

There are no known cases of sickness caused by this batch of juice and indeed exceeded permitted levels of toxin by such a small amount is unlikely to cause problems - patulin is a known carcinogen (cancer causing) and can be lethal to some animals but only at 30 000ppb. The permitted levels of patulin in food leave plenty of room for a wide safety margin.

Perhaps organic juice manufacturers need to be more aware of the importance of contamination and the dangers of higher mycotoxin levels and take a little more care in order to prevent this happening again.

Aspergillus fumigatus Regulates Growth, Metabolism, and Stress Resistance in Response to Light

It is known that light has an influence on some fungal pathogens and their ability to infect their host so it was important to ascertain whether this was also true of Aspergillus fumigatus - the most important species responsible for aspergillosis.

This recent paper shows that light does fundamentally effect many aspects of the growth & regulation of virulence of A. fumigatus., opening the possibility that this might be able to be used to fight infection.

Quoting from the paper:
Considerable effort has been taken to understand how the mold pathogen Aspergillus fumigatus senses its environment to facilitate growth within the immunocompromised host. Interestingly, it was shown that the deletion of a blue light photoreceptor in two divergent fungal pathogens,Cryptococcus neoformansFusarium oxysporum, leads to an attenuation of virulence in their respective animal infection models. This suggests that light signaling pathways are conservatively involved in the regulation of fungal pathogenesis. However, an understanding of whether and how A. fumigatus responds to light is lacking. Here we demonstrate that this organism coordinates broad aspects of its physiology with the photic environment, including pathways known to be involved in virulence, such as carbohydrate metabolism and oxidative stress resistance. Moreover, the photoresponse of A.fumigatus differs in notable ways from the well-studied modelAspergillus nidulans. Therefore, this work should represent a general advancement in both photobiology and A.fumigatus research communities.

Friday, 12 April 2013

AIHA Position: Statement Mold and Dampness in the Built Environment

Damp in homes is a known hazard to human health, potentially increasing the severity of asthma, allergy, sinusitis and several other illnesses that are sensitive to biological dusts & damp. There has been much mention in the media of these illnesses and problems with houses that are damp and mouldy and a consequent proliferation of the amount of remediation work that has to be done.

As in any free market many companies have sprung up to accommodate this demand but there has been a lack of unbiased guidance for all concerned as to what extend expensive remediation is required, Clearly those that stand to benefit financially from such work are unlikely to be best placed to advise!

In some quarters there is confusion as to what is contamination that has to be removed - there are well publicised stories of whole houses being demolished because of mould contamination. There is also a lot of confusion about what illnesses can be caused by a damp home and what is causing them. Science is slowly providing answers for doctors but what about those in the front line of house inspection & remediation?

The American Industrial Hygiene Association have published a statement outlining their vision for the assessment and remediation of damp buildings in a new document. It is a very clear attempt to set the standards of qualification required of inspectors and remediators at an appropriately high level to ensure the protection of the householder and we can only applaud that intent.

It also sets out a principle that the remediator and assessor should be independent and one should not be able to directly recommend the other. I think that that could be an important step to reduce the chances that the householder will be deceived into paying more than is needed. An independent inspector should also reinforce the requirement that the remediator does a good job and charges appropriate fees.

This is surely a step forward in how we aim to deal with the assessment & remediation of damp homes & other buildings.

AIHA Press Release & Statement available here

Thursday, 11 April 2013

Itraconazole Toxicity and Cardiac Health Problems

Itraconazole is an antifungal drug used widely to treat fungal infections and is active against Aspergillus, Candida and Cryptococcus. It is effective and now much cheaper as it has passed out of the period of time granted to its inventor to exclusively sell it - there are now several competing manufacturers. It seems to be an increasingly useful and used drug now it has become more accessible which is a good thing in the main but this makes it increasingly important that this drug is properly understood and its very severe potential side effects appreciated and guarded against.

These are the warnings published by the World Health Organisation

Risk of congestive heart failure 
The agency says that while the available evidence suggests that the risk of heart failure with short courses of itraconazole is low in healthy, young patients, prescribers should exercise caution when prescribing the drug to at-risk patients. Amendments to the product information of all itraconazole formulations have been made to reflect this information.
Risk to pregnant women
By April 2000 the UMC had received 43 case reports from 5 countries regarding the use of itraconazole by pregnant women. 25 of these pregnancies ended in embryonic or foetal death. The remaining 19 reports described a variety of congenital malformation or neonatal disorders. In the 38 reports in which the route of administration was specified the drug was taken orally. The data suggested that:1. inspite of the approved recommendations and warnings itraconazole is being taken by pregnant women for minor indications,2. reported human experience seems to lend support to the experimental evidence that itraconazole is teratogenic,3. there is a predominance of abortion, and4. more firm warnings may be needed in the product information.Although not apparent from the UMC reports, a further question of interest was if itraconazole might decrease the reliability of oral contraceptives and so lead to unintended exposure in pregnancy.

Care thus needs to be taken about which patients are prescribed itraconazole, adequate monitoring needs to be put in place if needed and sufficient advice given with the drug to ensure the patient is aware of the risks involved.

Homeopathy

http://www.anh-usa.org/homeopathy-under-attack-in-california/

Wednesday, 10 April 2013

Newsbite: US Meningitis Outbreak Index Case Details

The New England Journal of Medicine has published the index case for the fungal meningitis outbreak. This is the first typical case reported in the outbreak and it describes infection by Aspergillus fumigatus. There are clear images of the consequences of the injection of contaminated steroid - infection of the central nervous system including the brain more...

Thursday, 4 April 2013

Contaminated Injectable Steroid Still Causing Health Problems


Readers may remember some 6 months ago there was a serious accidental release of vials of steroid medication intended for injection that were contaminated with fungi. There were hundreds of cases of fungal meningitis as a result as steroids are often injected into the spine to relieve pain.

You may be surprised to know that new cases are still being identified - this illustrates the ability of fungi to 'hide' from doctors and their diagnostic tests for long periods of time.

Quoting from the original article:


Feeling unusually lethargic in January, Terry Trost wrote off her melancholy as seasonal depression, but she later found out that it was something much worse. 
After five months of lab tests coming back inconclusive, Trost found out in February that she is among 730 people nationwide who have fungal meningitis. The illness is potentially deadly, and it is caused by exposure to tainted back pain medications that were distributed in 23 states from coast to coast. The drugs, manufactured by the New England Compounding Center in Massachusetts, were supplied to six clinics in Indiana, including OSMC Outpatient Surgery Center in Elkhart. 
Trost and her daughter, Nicole Kovach, received injections to relieve back pain on Sept. 26 at OSMC. That evening, batches of medications were recalled for contamination.

Naturally this is a warning to anyone who had similar spinal injections on or before October 2012 in the areas of the US effected by contaminated steroid solutions to remain vigilant for the warning signs mentioned in this report (lethargy, severe headaches and more), but it is also a warning to us all (doctors and patients) that fungi can be very difficult to detect and treat and that better ways of diagnosing serious fungal infections are still needed.

Wednesday, 3 April 2013

Dairy Scare in Romania

The dairy producer Danone has withdrawn several products from the market in Romania after they suspected they could be contaminated with aflatoxins toxic carcinogenic substances. they also blocked 75 tonnes of products after they were found to contain these contaminants delivered from one of their suppliers.

"Milk containing carcinogenic aflatoxins, some imported from Hungary and the rest processed in Romania, has been identified and removed from the market"..."the products which Danone asked to be withdrawn are Musli Yoghurt, sour cream and natural yoghurt."
Quoted from the original article on romania-insider.com

The discovery was due to testing across the food supply industry and despite this news scaring off Romanians from the products,  the food safety authority has stressed that the products on shop shelves are safe for consumption.


Anti-fungal formulations in plastic products - Tackling the threat of resistance

Symphony Environmental Technologies have developed anti-bacterial (d2p (AB)) and anti-fungal (d2p (AF)) formulations that can be put into plastic products to help prevent the spread of infection.

These new formulations have been tested against a number of organisms including MRSA, E. coli and Aspergillus niger. d2p (AF) has been shown to inhibit the growth of fungi, bacteria, mildew and algae that can lead to discolouration, staining and odours.

By incorporating these into packaging, it can increase shelf-life of products (e.g. bread), and reduce the need for preservatives whilst still retaining the functional properties of the plastics. These formulations can be put into products that are the most likely to transfer microbes such as table tops, kitchen utensils, WC seats and even credit cards.

"If we can no longer rely on antibiotics we have to deal with the bacteria before they get into our bodies" said Michael Laurier, Symphony's CEO.
This development is a creative leap into combating the threat of resistances to antibiotics and anti-fungals.

Further information

Watch the commercial sales video

Reduced Poultry Mortality


It has been found that by treating maize with aflasafe (a commercial product containing strains of Aspergillus that do not produce aflatoxins), a bio-control product for controlling aflatoxin, it can reduce the mortality rates of poultry by 43.9% in addition to other benefits.

Scientists from the International Institute of Tropical Agriculture (IITA) and the University of Ibadan found that treatment also led to a 10.4% drop in food intake and a 3.3% increase in feed conversion ratio when compared to typical methods within the industry.

Produced by toxigenic strains of Aspergillus flavus, aflatoxins have become a menace in developing countries, contaminating about 25 per cent of grains produced in the region. Aftermaths of consuming aflatoxin-contaminated grains include stunting in children, liver cancer, and even death.

The use of aflasafe treated feed will mean that poultry farmers will no longer need to use aflatoxin binders in feeds and it can provide a cheaper and and safer solution within the poultry sector.

Such science-led solutions have come to the rescue of the poultry industry leading the way for a bright future.

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