Wednesday, 31 July 2013

Toxins in Dog & Cat Food

Our pets rely on us (in the main) to provide their food. Many of us know one or two foods that we should not feed to a pet as their digestive and metabolic systems are not adapted to our diet - they are essentially carnivores whereas we eat a variety of foods, both meat and vegetable.

Some will be aware that there are occasional problems with mycotoxins in foods sold for pets to which they are susceptible. Perhaps the food has become mouldy during storage or perhaps the food has been made with a bad batch of food that was rejected for human consumption.
There has long been a theory that some stored foods that are toxic (eg raisins) might be toxic because they become contaminated by mycotoxins which do us no harm but which some animals find poisonous.

This overview of toxic foods is written for Veterinary professionals but many pet owners would benefits from reading it as there may well be foods that you were not aware were poisons to your pet - I certainly learned a lot!

References

Mycotoxins in pet food: a review on worldwide prevalence and preventative strategies.


Tuesday, 30 July 2013

Aflatoxins in Food & Vulnerability to AIDS

Frequency of AIDS in Africa


Mycotoxin contamination of food is a widespread problem in parts of the developing world (1,2) especially where local farmers do not have adequate facilities to dry crops prior to storage, storage is inadequate, crops are damaged while in the field or simply farmers lack money or knowledge/awareness of the potential problems and how to avoid them.

Even if the dangers of eating mouldy food is well known there can be a need to eat the food if it is the only food available for some poor communities. Consequently exposure to mycotoxins such as aflatoxin is known to be many times that found in the more developed world (3) and symptoms of exposure are widespread eg. stunted growth, liver cancer.

A new research report suggests that a diet containing high levels of aflatoxin has less obvious consequences but no less lethal. In some parts of Africa AIDS is circulating in the population at high frequency - up to 15% of the general population aged 15 - 49. At high dose rates of aflatoxin there is evidence that our immune systems are suppressed. The research group set out to try to show if there is a correlation between suffering from AIDS and having a diet high in aflatoxin.

The results are quite clear - the amount of aflatoxin in the bodies of people suffering from AIDS correlates with the number of HIV virus' circulating in their bodies. As they eat more mouldy food so they become more infected with the virus. HIV also causes immune suppression so we have a vicious cycle of destruction of the immune system of the affected people. The authors suggest that this may be a factor in the initiation of the infection.

These people are a victim twice over - once from poverty and a poor diet, the second time when they are left exposed to a deadly virus with only a weakened immune system to fight it with.

References
  1. Aflatoxins claim victims in Africa
  2. New biocontrol agent for Aspergillus contamination of peanuts
  3. Improved Health through Aflatoxin Management in African Foods

Wednesday, 24 July 2013

Antifungal Therapy Improved Outcomes for Chronic Pulmonary Aspergillosis

The latest research carried out at the National Aspergillosis Centre in Manchester, UK with the aid of over a hundred patients has been published. This research is made far stronger by the involvement and enthusiasm of our patients.

Al-shair et al. (2013) have conducted a detailed study comparing the long term use of different antifungals to treat Chronic Pulmonary Aspergillosis (CPA) patients. Assessments were taken quarterly over 12 months.
It should be noted that patients with untreated CPA usually experience deterioration of their health, so the fact that the researchers recorded an overall 68 - 71% of patients either stabilising or improving is hugely encouraging. This outcome was consistent even with those who were most ill when starting antifungal therapy.

Quoting from the paper:
"Mean age was 59 years and 45% were female. Overall, patients with CPA had substantial health status impairment at baseline. After treatment, 47-50% gained substantial health improvement with a reduction of score of 14 at both 6 and 12 months, while 32% deteriorated with a rise of 11 and 14 scores after 6 and 12 months of treatment and observation respectively, and 21% were not much different (stable).
Patients gained therapeutic benefit irrespective of their illness severity where >50% of those who had “poor” and “very poor” at baseline improved with reduction of ≥4 scores after 6 months of treatment. Replicating this analysis using much wider scale, we found that at least 50% of “poor/very poor” health status category at baseline improved significantly to “fair” or “good/very good” categories."
Other conclusions in the paper were that posaconazole gave slightly better outcomes compared with voriconazole, and voriconazole was a little better than itraconazole

Quoting from the paper:
“Posaconazole (Noxafil, Merck) appeared slightly better than voriconazole (Vfend, Pfizer) which in turn was better than itraconazole (Sporanox, Janssen/Ortho Biotech); 50% and 62% of our patients were improved after 6 and 12 months of posaconazole, compared with 43% and 50% with voriconazole and 39% and 43% with itraconazole.”

These results are strong and very encouraging  for the future treatment of this form of aspergillosis with antifungal drugs.


Wednesday, 17 July 2013

Valley fever: Another Inhaled Fungal Infection


The BBC have reported on a very particular fungal disease that is based in a particular area of the US.
Rather like other chronic fungal infections coccoidioidomycosis can often go unnoticed for some time, but once it is diagnosed and treated with antifungal drugs it improves but doesn't go away - Valley fever is another incurable respiratory fungal infection.

Typically found in people who live or have visited some extremely dry areas of the Americas (Arizona, California, Utah, New Mexico and Texas, plus Mexico and Argentina), Valley fever is inhaled in the dust.

  • Two out of three infected people experience no symptoms
  • Others get flu-like symptoms lasting a month
  • One in 20 gets pneumonia and in one in 100 cases it infects the brain - with potentially fatal results
Prior to 2000 cased were rare and no-one really knows why the number of cases has risen so much


The report mentions:
Professor John Galgiani has studied the illness for 30 years and founded the Valley Fever Center for Excellence at the University of Arizona in Tucson. He estimates there is a 3% chance of infection if you spend a year in a highly endemic area, and only a 1% chance of getting sick.
But people can become infected in the most improbable ways however long the odds, he says. The wife of a scientist in the San Francisco Bay area contracted it after she shook out the jeans he had been wearing on a trip to the San Joaquin Valley.Dr Galgiani thinks the increase in cases is partly due to better reporting and partly population growth, but says differing weather conditions lead to yearly variations - 2012 is looking like it will have fewer infections than 2011. If dry follows wet, that means a lot of airborne fungal spores.
He doubts that increased construction in the desert plays a part. "It's actually hard to show that human activity has any effect. Many endemic areas are quite sparse and looking at who comes into the clinic, it's not overly represented by construction [workers]."
There's nothing you can do to mitigate risk, he says. Masks, for example, can't prevent a single spore being breathed in, but increased awareness will mean earlier diagnoses and better health outcomes.




Monday, 15 July 2013

International genomics

The accelerating speed with which we can read the DNA sequence of ourselves and most other organisms on earth is busily generating vast amounts of data. Applications are far reaching and have been reported in this blog before:



Many countries are exploring the building of large collections of sequences that will allow them to learn a lot about the precise genetics of their populations and then to tailor medical treatment of each individual accordingly - see personalised medicine

For some medical conditions that we know are rare eg Chronic Pulmonary Aspergillosis (CPA) there may be difficulty finding enough patients to optimise research aims in any one collection of genomic data, or any one country. It is important therefore that genomic data can be shared between collections, but so far there has been no coordinated collaboration between all research groups so inevitably there will be differences between what data is stored, how it is stored, what tools are used and so on. This makes collaboration difficult and slow, so a new group has been formed to ensure that this doesn't happen.

 Global Alliance to Enable Responsible Sharing of Genomic and Clinical Data 

The repercussions of collaborative research will affect everything from customized cancer treatment to the unprecedented tracking of infectious agents, according to the alliance’s white paper. And it’s all possible because the cost of genetic sequencing has plummeted in a decade.
“I could now do your whole exome [part of the DNA that codes for proteins] for less than $1000,” says Siminovitch. “And that’s down from the billions of dollars that it would have cost to do it in the year 2000.”
Siminovitch is hopeful that genetic research will help her understand why the first drug she gives for rheumatoid arthritis, methotrexate, doesn’t work on 30% of her patients. “It takes six months to a year to realize that. If I can test for the genetic reason why they don’t respond, I can predict that ahead of time and treat the patient appropriately,” she says. 
More than 70 organizations in over 40 countries have signed a nonbinding “letter of intent” to build the alliance. In the fall, according to Goodhand, representatives of these organizations, which include universities, hospitals, research centres and advocacy groups, will have the opportunity to make their participation formal by signing a memorandum of understanding.

Thursday, 11 July 2013

Miraculous Cure For Nun With Aspergillosis?

This article originally appeared on a website run by the Catholic Church

A BEATIFICATION MIRACLE OF MOTHER MAŁGORZATA SZEWCZYK (Catholic Informative Agency)

 A miraculous healing from a fatal illness of one of nuns of Our Lady of Sorrows, working in Oświęcim, contributed to the beatification of Mother MaŁgorzata Szewczyk – a founder of the Convent of Daughters of Our Lady of Sorrows. The beatification miracle of Mother Małgorzata Szewczyk concerns healing from pulmonary aspergillosis which took place in 1975.

After confirming this dangerous and incurable disease at that time, the nun was operated on unsuccessfully twice. Intensive treatment did not eliminate the high temperature and festering fistula. A very hard clinical condition of the ill nun remained for 18 months.

Deprived of hope by doctors, the sister started praying to the founder of her convent. On the novena, other sisters and her closest family joined in. Just at that time, there was an unexpected, complete and permanent healing. The miraculously healed nun had performed her duties as a sacristan in the church of the nuns of Our Lady of Sorrows in Oświęcim for 34 years, where there is a grave of Małgorzata Szewczyk.

 The case was being analysed by a medical consultation and the Commission of Theologians and Cardinals in the Congregation of Canonization Issues in Rome and was recognized as inexplicable from the medical perspective. On 20 December 2012 pope Benedict XVI promulgated a decree recognizing the authenticity of the miracle through the intercession of Mother Małgorzata Szewczyk. The papal decision finished the process which had started in 1993, at the Metropolitan Curia in Cracow.

Tuesday, 9 July 2013

Micafungin Approved for Infants for Fungal Infection

Micfungin is one of the newer antifungal drugs available for the treatment of fungal infections and is used to treat aspergillosis in some cases. It follows on from the release of a series of antifungals over the last 10-20 years; itraconazole, caspofungin, voriconazole, posaconazole, but this new drug is all the more important because it isn't from the case class of drugs as three out of four of the drugs listed.

This means that it should make an ideal alternative to the commonly used azole drugs when an infection becomes resistant or the patient is intolerant to the side effects of one of the other drugs. It may also offer the possibility of 2 target combination treatment were the doctor exploits the use of two drugs that each attack different parts of the fungus at the same time. This is can be more successful and exploited in other types of infection.

Micafungin is an echinocandin (as is caspofungin) which is known to be effective against Aspergillus and Candida, 2 fungal pathogens that frequently infect people and as such has had approval since 2008 in Europe (2006 in the US) for those infections.

It does however - as all echinocandins do, need adminstering in hospital, making it more expensive to use. The cost of the drug is also high. The benefits seem to be that micafungin and other echinocandins can be much safer to use compared with other antifungals. This is reflected in the approval this week of micafungin for use in very small children.

Micafungin use in children - a review

Monday, 8 July 2013

New Micro-array's Allow Us to Test 1200 Fungal Cultures at a Time

Not that long ago multiwell plates were used to assay large numbers of fungal cultures. The maximum usual numbers of wells was 96 and each had to be inoculated and allowed to grow so as to get enough cells to test in each well. This was a process that could take several days.



A new type of microarray has now been developed that allows 1200 tiny (30nl) cultures to be used to test for antifungal activity, 28 antifungal drugs at a time. The reduction in size of each culture is 2000 fold thus processing time can be much faster and throughput can be hugely increased.

This paper demonstrates that this technology is equivalent to the 'full sized' cultures for this purpose. In this example they tested drugs against the ability of the fungal pathogen Candida to form a biofilm, but it also claimed to work well for filamentous fungi such as Aspergillus.

The benefits of this technology is that it allows us the quickly, cheaply and accurately carry out testing of thousands for new drugs at a much faster rate than was possible before. New targets and new drugs stand a much better chance of being discovered more quickly.

Friday, 5 July 2013

Mycotoxins in Feed - A Worldwide Survey


The regular survey of the number of samples of foodstuffs has been published for November and December 2012 and as usual it is a reminder that mycotoxins of all types are never far away from our diet. There are strictly permitted low levels allowed in our food so testing is carried out on thousands of samples every month in order to find out which batches to permit into our food chain and which are not.

If we look at the figures we can see that technically sophisticate countries such as the EU and USA have generally much lower numbers of positive (contaminated) samples compared with samples from poorer continents such as Africa but the difference isn't that great in overall terms with only two or three-fold differences in numbers in most cases. Despite all that technology the fungi continue to grow in our food!

We can conclude that we all eat a little mycotoxin most days, albeit at very low levels. There are areas of the world where ingested levels can be much higher and mycotoxicosis is not uncommon - see Food Mycotoxins.

It is worth noting the the levels noted for mycotoxin in human urine which are thought to come from food are similar to the levels detected in people exposed to moulds in damp homes (2 - 15 ng/ml). This may throw some doubt on the validity of concluding that those people are ill because of the mycotoxin they breathe in when in fact they could be eating it in very similar quantities.

Wednesday, 3 July 2013

Farewell Mick Ashton


There have been many articles over the last week in the UK of the death of the leader of the 'Time Team' TV programme that has played a large part in popularising archeology and revealed vast amounts of information about the history of the people who have lived in the UK over thousands of years to the general public. The programme has been profoundly successful, interesting and long lived - only now coming to the end of its run after 20 years.

Mick Ashton was a hugely talented communicator and archeologist and played a major part in the success of Time Team series, no doubt inspiring the interest of future generations of archeologists. Interest from the public is such that there are waiting lists to participate in archeological digs that are held all around the UK to allow amateurs to discover details of the history of their locality. The British Archeology Magazine pays its own tribute here. Gone are the days when objects dug up were of interest only to specialists and museums!

What is less well know about Mick is that he suffered from aspergillosis and asthma, presumably Allergic Bronchopulmonary Aspergillosis (ABPA). This would have made working with soil rather more difficult than it is for most of us! This has been reported in a number of places so sadly in death Mick has added to his prodigious achievements by reminded everyone about a lesser-known illness that we think affects 25 000 people in the UK alone, and is probably heavily under diagnosed.

RIP Professor Ashton

Monday, 1 July 2013

False Positive Galactomannan Test after Ice-Pop Ingestion

An unusual case history has recently been presented in the New England Journal for Medicine. A patient was given a stem cell transplant and as is normal was then monitored closely for infection as vulnerability to infection is high at this point. Monitoring for fungal infection is routinely carried out using a direct assay to detect fungal cell wall components (galactomannan) in the patients blood - if found it would suggest that the patient had a fungal infection somewhere in their body that was releasing tiny particles of cell wall into their blood.
Over the next 4 weeks signs of fungal infection were not present (see fig 1 above), however during week 5 the test started to pick up signs of apparent infection - see days 32, 34 and 36 above. The galactomannan test is very reliable and no causes of false positive results where found so treatment was begun for fungal infection using an antifungal drug.

The patient had no other signs of infection despite extensive testing (CT scans, sputum, PCR), raising suspisions that something was wrong with this diagnosis. The only food item being consumed by the patients at this time were frozen fruit flavoured water in the form of ice-pops. On testing it was found that these drinks  contained significant amounts of fungal growth (Penicillin) and as the amounts detected declined soon after it was assumed that this was the source of a false positive galactomannan test result and the drinks were stopped.

The authors caution fellow doctors that other foodstuffs could potentially cause false positives as they also contain types of galactomannans. These can include the types of food given to similar patients as cooling drinks, ice cream etc.

In this case unnecessary antifungal medication was administered which can complicate treatment and cause severe side effects so it would have been better to avoid giving it.

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