Wednesday, 25 June 2014

Another Breakthrough at the National Aspergillosis Centre

Medical student Jo Armstead
At the end of her third year at medical school Jo Armstead spent last summer at the National Aspergillosis Centre (NAC) at University Hospital of South Manchester, Wythenshawe, Manchester carrying out research into the proportion of people with the genetic disorder Cystic Fibrosis (CF) who also have an infection with the fungus Aspergillus.

It was known that people with CF have an increased chance of getting aspergillosis - recorded mainly as ABPA and that perhaps 10 - 15% of all CF patients have this allergic infection, and more will eventually get the more invasive chronic pulmonary aspergillosis (CPA) but here at NAC we have argued for the existence of further types of infection (Aspergillus bronchitis) that are present in CF patients and which worsen the prognosis for CF. 

Jo's work took those estimates and applied them on a world wide scale in order to get a fuller picture of the number of cases of aspergillosis there may well be across the globe. These new estimates present a startling picture of nearly 50% of all adult CF patients actually having an Aspergillus infection. 

The implications of this are quite clear - if we have previously estimated that only 10-15% of CF patients have an Aspergillus infection then 35-40% of patients are not being treated for an Aspergillus infection they may have. We know the treatment of ABPA with antifungal medication has several benefits to the patient and this study suggests such treatment (amongst other additional treatments) may well be warranted for more CF patients than previously thought, bringing about a big shift in how CF may be managed in future.

Tuesday, 24 June 2014

Boy Overcomes Fungal Infections While Fighting Cancer

This is a heartwarming story that gives hope to many others parents of children who are fighting leukaemia. As part of the treatment for leukaemia the immune system of the patient (i.e. the part located in the blood) is removed and replaced with healthy non-cancerous cells. These bone marrow transplants have revolutionised treatment for leukaemia in children and it is now a highly successful therapy.

NB The first physician to perform a successful human bone marrow transplant on a disease other than cancer was Robert A. Good at the University of Minnesota in 1968. [41]. In 1975, John Kersey, M.D., also of the University of Minnesota, performed the first successful bone marrow transplant to cure lymphoma. His patient, a 16-year-old-boy, is today the longest-living lymphoma transplant survivor. [42]
Effective though these transplants are, there is a short period of time when the patient is vulnerable  to infection. At that time infection by the fungus Aspergillus can happen and is difficult to treat. It is difficult to imagine the trauma of a parent looking after a child who is successfully treated for leukaemia over several weeks or even months but who then is afflicted with a serious fungal infection.

However in this case the child (Blake) was successfully treated for Aspergillosis using a combination of antifungal drugs and surgery to remove the infected lung lobe and all was well for the following several months. Incredibly that was not the end of the story for Blake and Aspergillosis. Following a routine checkup another fungal mass was detected in his brain and this was potentially an even more serious infection than his lung infection, but Blake recovered.

After 150 days in hospital Blake is now in remission, taking antifungal medication every day to ward off further infection. Blake was chosen by Golisano Childrens Hospital as one of their five Miracle Kids for 2014.

Thursday, 19 June 2014

How do Veterinarian's Recognise Mytoxin Poisoning in Poultry?

A useful short article intended to help vets recognise poisoning of poultry and to prove their presence to farmers. Oral lesions, Proventriculosis and gizzard erosion, Intestinal & liver damage, Bruises and kidney lesions and testing carcasses are covered.

Original article written Manuel Contreras, veterinarian at Special Nutrients, USA.

 A common concern facing feed mills and poultry production facilities around the world consists of determining if the mycotoxins present in feed ingredients or in the rations are affecting performance. Producers that have already decided to use anti-mycotoxins additives, wonder if their decision is economically wise. Considering that mycotoxins detection in feed frequently provides inconsistent results, due to their uneven distribution, one practical approach for evaluation is the identification of lesions in the slaughter houses.
This search will confirm their presence for companies that may have any doubts about their existence and will also serve to demonstrate if the preventive measures taken are effective. In this article we will review some of the macroscopic changes present in the birds affected by mycotoxins with the objective of offering another tool to evaluate their incidence. It is important to emphasize that besides evaluating these lesions, performance results must be taken into consideration in any type of evaluation.
Read the full article here 

Wednesday, 18 June 2014

European Food Safety Regulatory Body (EFSA) Assesses Food Enzymes for Toxicity and Allergenicity

Large fermentors
Many food processes use enzymes during the production of food. Common examples are alchohol production that uses enzymes from yeast to ferment sugars to make beer, the same organisms are important to enable bread to rise and much more (1,2). These are well known processes that have been in use for thousands of years, but fungi are widely used to ferment many more substances to manufacture other food components.

The above Wiki link describes the following:

Food fermentation has been said to serve five main purposes:[12]
  • Enrichment of the diet through development of a diversity of flavors, aromas, and textures in food substrates
  • Preservation of substantial amounts of food through lactic acidalcoholacetic acid, and alkaline fermentations
  • Biological enrichment of food substrates with protein, essential amino acids, and vitamins
  • Elimination of antinutrients
  • A decrease in cooking time and fuel requirement

Somewhat surprisingly the safety of these products have not been assessed formally by the EU (though countries do regulate individually) so this is about to be organised and carried out by EFSA for the 300 existing enzymes.

Many of these foodstuffs are produced by fermentation with Aspergillus. Interestingly the original article mentions this specifically as one assessmetn already completed:

The application relates to a type of food enzyme known as a xylanase. This xylanase is used in starch processing, the distillation of alcoholic drinks and baking processes. It is produced through the fermentation of a strain of Aspergillus oryzae which has a long history of safe use. However, Aspergillus is also known to produce undesirable compounds called mycotoxins as secondary metabolites. The Aspergillus used to produce this food enzyme has been genetically modified to prevent or reduce the formation of these unwanted products. EFSA has conducted a full risk assessment — including an evaluation of toxicity and allergenicity — and found no safety concerns at the proposed uses and use levels.
While on the one hand it might be seen as outrageous that mycotoxin production has not been formally measured before now(!) it is good that there is now clear compliance in relation to food safety. It is equally helpful that these products are also going to be tested for allergenicity - so those people suffering from allergy to Aspergillus (e.g. ABPA patients and 50% of severe asthma patients)  are to be better protected and reassured.



Tuesday, 17 June 2014

Substantial Underdiagnosis of Aspergillosis in Cystic Fibrosis Patients in 30 Countries Across the World

ABPA in Cystic Fibrosis adults
Aspergillus spp. can lead to allergic bronchopulmonary aspergillosis (ABPA), Aspergillus sensitisation and Aspergillus bronchitis in Cystic Fibrosis patients, however it was not known how often this happens. This question was partially answered recently (Baxter et.al. 2013) using a large sample of the UK CF population and found the following proportions:

  • ABPA (17.7%)
  • Aspergillus sensitisation (14.6%) 
  • Aspergillus bronchitis (30%)


This new paper extends Baxter et.al. and based on its figures estimates the burden of aspergillosis and ABPA cases in adult CF patients in 30 countries that report CF.

Quoting:
Of the 76,201 estimated CF patients worldwide (not including India), 37,714 were >18 years. The proportion of adults to children varied from 63% in Norway to 20% in Brazil. ABPA caseload in adults is anticipated to be 6,675 cases of which only 2,221 cases (33%) are currently recorded, indicating substantial underdiagnosis. The ABPA diagnosis rate compared with estimated rates varies by country from 101% (France) to 14.5% (Greece), although genetic variation could account for genuine differences compared with the UK. Aspergillus bronchitis is not currently recognised or recorded in CF registries but there are an anticipated 10,988 adult cases.
Aspergillus sensitisation, associated with increased bronchiectasis and reduced FEV1, affects an anticipated 5,506 patients without ABPA or Aspergillus bronchitis. Together ABPA and Aspergillus bronchitis are estimated to affect 17,989 adults, 47.7% of the adult CF population.
ABPA also occurs in children and teenagers and 984 cases were documented in registries. Diagnosed ABPA rates by age were available for the ECFS registry, USA, UK, Ireland, Belgium and Netherlands. The rate was <1% under 4 years, and increased throughout childhood and adolescence, with marked variation between countries. Newly published diagnostic criteria and methods should facilitate better recognition of aspergillosis in CF, allowing better CF disease control.
Newly published diagnostic criteria and methods should facilitate better recognition of aspergillosis in CF, allowing better CF disease control.

Full article

Monday, 16 June 2014

The Danger of Mycotoxins for Horse Husbandry

Mouldy feed
A very nice article warning people who look after horses to be vigilant with their feed. If it gets a bit damp and mouldy there are potential danger to your horses health caused by mycotoxins. Not all fungi contaminating feed do this but those that do are common. The amount of mycotoxin produced in a given situation is very variable and toxic levels are rare. Your horse is very good at detoxifying contaminated feed but if it is regularly fed poor feed it will suffer.

The article does not mention the people working with mouldy feed can also suffer ill health as a result of inhaling the many millions of fungal spores that are released into the air as a result of disturbing the feed - and also if straw bedding is not cleaned out quickly enough and becomes mouldy. Relatively mild allergies, sinusitis are common and will not go away if contact with mouldy material is maintained every day. A few people will become acutely allergic and require hospital attention. People with asthma are particularly vulnerable to serious respiratory reactions, occasionally fatal..

Quoting:
Did you know there are toxic substances tucked away in your horse’s feed and forage? You can’t see them, and you can’t eradicate them, but chances are these compounds, called mycotoxins, are present. Specific molds and fungi produce mycotoxins in soils, grains, and forages when environmental conditions are favorable. Once produced, they are generally very stable and will persist for a long time during storage. Horses that consume grains and forages contaminated by mycotoxins can suffer from a variety of health issues. As horse owners we should be particularly concerned, says Max Hawkins, PhD, nutritionist with Alltech’s mycotoxin management team, because mycotoxins inhibit protein synthesis, which negatively impacts the animal’s physiology and ability to function and repair tissues.
The molds that produce mycotoxins are visible on contaminated feed. However, the mycotoxins can still be present after the mold dies or falls off the feed. These molds can be classified as either field fungi, which grow on plants while they are still rooted in the ground, or storage fungi, which develop after plants are harvested and stored. Field fungi require high moisture conditions (20-21% moisture), while storage molds can grow at lower moisture levels (13-18%). Forage and feed producers and property managers should monitor both moisture and temperature levels carefully so they can be aware of the potential for mycotoxin-producing molds to form. Horse owners should learn to recognize the signs of mycotoxin exposure so they can have their veterinarian out to assess the horse, diagnose the problem, and start a recovery plan.

How Harmful are They?

It is near-impossible to find grain, pasture, and hay that is completely mold- and mycotoxin-free. In a 2010 study, German researchers Liesener et al. found at least one type of mycotoxin in each of 62 samples of commercial horse feeds, with many samples having more than one. However, the levels present were well below dangerous. So instead of taking on the impossible task of eliminating mycotoxins, owners should focus their efforts on minimizing their horses’ exposure to these elements.
Fortunately, harmful levels of some mycotoxins are rarely seen. In addition, most horses will avoid moldy (and potentially mycotoxin-containing) forages because they are not palatable. The molds and mycotoxins found in grains, however, often do not affect palatability, so nutritionists and veterinarians find these the most concerning. It is also important to realize, says Hawkins, that a feed containing low levels of several different mycotoxins might be just as detrimental to a horse’s health and performance as a single mycotoxin at a “toxic” level. Some problems stemming from mycotoxin consumption are acute (immediate), while others are chronic (long-term). It all depends on the type and amount of mycotoxin the horse ingests.
Other factors that affect toxin response include age, workload, stress level, nutritional status, and immune status. A healthy adult show horse or broodmare that consumes a diet with low to moderate mycotoxin levels over a long time might exhibit clinical signs such as decreased athletic performance and/or breeding capability with no other observable issues.
Other general signs include appetite loss, weight loss, unthriftiness, respiratory issues, increased susceptibility to infectious diseases (poor immune function), and poor growth rate.

Read the rest of the article here

Friday, 13 June 2014

Increasing incidence of invasive aspergillosis in France

A new population-based analysis by Bitar et al. at the Institute of Health Surveillance, Paris, reveals an increasing incidence of invasive fungal infections (IFIs) in France. Using a national hospital database, inclusive of more than 95% of French hospitals, hospital stays from 2001-2010 were reviewed for invasive fungal infections.

From 35,876 IFI cases, invasive aspergillosis (IA) accounted for over a quarter, and alongside Candida spp. infections made up the majority of mortality—together accounting for over 87% of deaths. However the study also showed that IA fatality is reducing by 1.4% per year, despite overall incidence of IFIs–including IA–in the general population increasing by 1.5%.

The study reveals worrying trends that increasing numbers of immunocompromised patients are being affected by IFIs. Whilst the overall trend of reducing mortality in IA is a positive, future work needs to find a way of managing at-risk populations to reduce the number of cases.

Friday, 6 June 2014

An Intergovernmental Panel on Antimicrobial Resistance Called For



A recent report in the journal Nature calls for globally coordinated action to control the use of antimicrobial drugs in order to prevent the rise of resistance. The World Health Organisation published a detailed document on the increase of antibiotic resistance around the world in April 2014:

Quoting
Antimicrobial resistance (AMR) threatens the effective prevention and treatment of an ever-increasing range of infections caused by bacteria, parasites, viruses and fungi. An increasing number of governments around the world are devoting efforts to a problem so serious that it threatens the achievements of modern medicine. A post-antibiotic era – in which common infections and minor injuries can kill – far from being an apocalyptic fantasy, is instead a very real possibility for the 21st Century. This WHO report, produced in collaboration with Member States and other partners, provides for the first time, as accurate a picture as is presently possible of the magnitude of AMR and the current state of surveillance globally.
The report makes a clear case that resistance to common bacteria has reached alarming levels in many parts of the world and that in some settings, few, if any, of the available treatments options remain effective for common infections. Another important finding of the report is that surveillance of antibacterial resistance is neither coordinated nor harmonized and there are many gaps in information on bacteria of major public health importance.
Strengthening global AMR surveillance is critical as it is the basis for informing global strategies, monitoring the effectiveness of public health interventions and detecting new trends and threats. As WHO, along with partners across many sectors moves ahead in developing a global action plan to mitigate AMR, this report will serve as a baseline to measure future progress.



Antifungal drug resistance

It is important to point out that just as combating antibiotic resistance by regulating use across the world is going to be a vitally important factor in preserving their effectiveness for as long as possible, there is also an emerging threat of resistance to antifungal medication, some of it thought to be caused by widespread use of antifungal chemicals (that closely resemble those used to treat human infections) to control. Control of the use of agricultural antifungal chemicals is difficult as to do so threatens the food supply of many countries. Here too global coordination is needed, and the WHO report mentions this too.




Tuesday, 3 June 2014

PEGylated Uricase in Gout

The gout demon 1799
One of the many enzymes manufactured by Aspergillus fermentation is uricase. Uricase is an enzyme that helps to remove the chemical uric acid (naturally made in a wide range of organisms during purine production). Humans do not have any uricase activity in their bodies - the gene is present but it has been switched off many years ago during our evolution.

This leaves humans vulnerable to the accumulation of urea in their bodies. This condition is known as gout.

One treatment for gout is the artificial provision of uricase (made by Aspergillus), however once injected the enzyme is rapidly broken down by our immune system as it is quickly recognised as a 'non-human' protein. Researchers are investigating attaching the enzyme to a large 'protective' molecule such as polyethylene glycol (PEG) in order to extend its half life and improve efficacy. Success has been limited but useful.

Original article


Monday, 2 June 2014

Boy, 9, beat leukaemia but died after lung infection caused by building work at Birmingham Children's Hospital

Patients who are undergoing treatment for some cancers are vulnerable to infection and they often have an immune system with a severely reduced ability to work well for some time.

In this case a young boy has had his cancerous blood cells replaced by healthy cells (donated by his brother). As part of the process his blood cells are removed (thus hopefully eliminating his cancer) and there is a wait before his new healthy cells can provide an adequate immune system. During that time such patients are vulnerable to all infections but some infections are more difficult to treat than others - Aspergillus for example is easy to breathe in and very tough to treat until the immune system recovers.

There is evidence that suggests that building works in the area of a hospital is associated with an increase in the numbers of Aspergillus infections. Many hospitals have specific policies on dealing with the consequences of building works.

In the case in this report it was found that the hospital and its staff failed to take adequate notice of the threat imposed by local building works with tragic consequences.

Such deaths are avoidable, awareness of the association of building works and aspergillosis needs to be improved - staff, management and contractor.


Adapting Aspergillus for Use in Manufacturing Processes

Bioreactor facility
Aspergillus species and other fungus are intensively used in industry for the production of chemicals useful in food e.g. citric acid, gluconic acid and commercially important enzymes eg glucosamylase, pactinase. To do this the fungus is incubated in large growth containers (bioreactors) into which food is regularly added - and due to the ubiquitous appetites of fungi that food can be waste from other food industries eg mussel processing watewater! This can make the use of fungi very efficient in terms of cost and natural resources.

There is constant work carried out to make this process more efficient and less costly as of course profits can be maximised and product costs cut.

Long threads of filamentous fungus
One problem with the use of filamentous fungi in bioreactors is that the long threadlike structure of Aspergillus tends to encourage clogging and tends to wrap itself around the impellers used to ensure growth medium is circulated sufficiently. This demands the use of more expensive reactor designs.

Individual threads also tend to break in rapidly circulating media, killing some threads and thus reducing yield.

In order to alleviate these problems it would be helpful if we could change the fungus to grow as much shorter threads. Research has shown that the long threads are encouraged by genes responsible for polarized growth. In its natural environment these genes would be used to direct growth towards food without wasting energy going off in other directions! In a bioreactor these genes are not needed as the fungus is always surrounded by food.

This recent paper shows us the results of  switching off the polarizing genes in Aspergillus when using it in a bioreactor. The fungus now grows as small pellets rather than long threads and remarkably production of the commercial enzyme has increased by over 80%. It isn't difficult to see the importance of this discovery - cheaper products, less waste, cheaper to manufacture.



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