Wednesday, 22 July 2009

Malaria causes aspergillosis

Plasmodium falciparum ring-forms and gametocytes in human blood.
A case of a malaria sufferer who subsequently developed aspergillosis has been reported in the scientific media.
Malaria is caused by the invasion of the victims blood by tiny parasites called Plasmodium with several different species being involved. These parasites multiply within the red blood cells of the host causing a variety of symptoms including anaemia (i.e. lack of red blood cells), fever, chills, nausea, flu-like illness, and, in severe cases, coma, and death.
The disease is carried by one particular type of mosquito and is a major health problem in some parts of the world, mainly sub-saharan Africa. One to three million people a year die of malaria with hundreds of millions infected. It is known that one of the mechnisms that the malaria parasite uses to avoid being detected and removed by the hosts immune system is to
inhibit at least on part of the immune system - phagocytes.

cannot normally infect people with normal, efficient immune systems. Even if that immune system is damaged Aspergillosis (i.e. infection by Aspergillus) is not common and is very rare except in the most extreme cases of immunocompromisation e.g. after transplant or during treatment of some cancers - malaria does not cause extreme immunocompromisation.

In this case however a patient who is otherwise completely healthy but who has malaria has become infected and there are four other cases quoted, all of whom died. In this case the patient was successfully treated with an antifungal medication and completely recovered. This is the first recorded incidence of a successful intervention of this type of case.

More oral amphotericin developments

Old dog (new trick?)
We featured a story a few months back which was based on the development of a variant of amphotericin which could be taken by mouth rather than as now by intravenous injection (IV). There are a number of advantages to taking a drug orally, not the least of which is convenience for the patient (they can administer their own drug at home) but also includes reducing the number of visits to hospital as IV has to be done under close medical supervision.

It turns out that there is more than one oral amphotericin drug under test. This article mentions a drug currently known as iCo-009 which has already been extensively researched (though it looks like all of the currently published work is based on animal models) and found to be promising. Human trials are the next step.

There is more work to do before this or other new variants of amphotericin B comes to the clinic but these are hopeful signs of the development of new uses for older drugs which can only be a good thing for all concerned.

Tuesday, 21 July 2009

Recognition for Aspergillus expertise

Rob Samson - Honorary Doctor of Swedish University of Agricultural Sciences (Uppsala)
The Swedish University of Agricultural Sciences in Uppsala confer on Prof. Dr. Rob Samson the degree of Honorary Doctor of Agricultural Sciences at the Faculty.

The Faculty's motivation is as follows: Dr Rob Samson, CBS - KNAW, Utrecht, Holland is a world leading specialist on the taxonomy of Aspergillus and Penicillium species. Some of these fungi occur as spoilage organisms and potential mycotoxin producers in food and feed. Other species have important roles in the biotech industry, while still others are used in the production of mould-fermented foods (roquefort and camembert cheese, salami and soya sauce). A correct identification to species level is essential for bom food safety and industrial process quality.

Dr Samson has developed stable taxonomic systems based on morphological, chemical and molecular criteria mat are fundamental to fungal identification. His basic research in fungal taxonomy has led to studies of Aspergillus and Penicillium in relation to food, biotechnology, indoor air quality and medicine. Dr Samson has organised international courses on "Identification of food-borne fungi" with numerous SLU participants.

He has also written richly illustrated textbooks that are used by hundreds of SLU students every year. In conclusion Dr Samson's research and pedagogic skills are of excellent international Standard, which has been and will be of large and central importance for the faculty. The conferment ceremony, will take place in Uppsala October 3 2009.

Friday, 17 July 2009

Drug resistance fears over killer fungal disease

Treatments for the most common airborne fungal disease are proving less effective due to increased resistance to the anti-fungal drugs used to combat infections.

Aspergillosis is an incurable disease of the lungs caused by fungal Aspergillus. It is treated using compounds called azoles but researchers at The University of Manchester have found that the fungus has been able to mutate making treatment ineffective.

The research, published in the prestigious US journal Emerging Infectious Diseases, showed that 13 out of 14 affected patients recently treated by the team did not respond to therapy and that numerous mutations were responsible.

Lead researcher Professor David Denning, whose clinic is based at the University Hospital of South Manchester, said that most of the fungus strains, or isolates, were completely resistant to all oral antifungals, leading the doctors to resort to long-term intravenous therapy.

"While the very first azole-resistant isolates were identified in the late 1980s in California, the first UK resistant Aspergillus wasn’t found until 1999 and now we have dozens,” said Professor Denning, who is Director of the National Aspergillosis Centre.

“Antifungal resistance rates have been rising since 2004 and stood at 17% in 2007, a trend that has continued into 2008 and 2009. Patients from all over the UK were found to have resistance, mostly related to long-term treatment of incurable Aspergillus disease."

In 2008, workers in Nijmegen in the Netherlands reported a similar rise in resistance, related to a single resistance mutation, also found in Aspergillus grown from soil. They suggest that extensive azole use in agriculture may be responsible. About one third of all fungicide use in farming is azoles.

Currently, the only class of antifungal that can be used orally for Aspergillus infection and allergy are the azoles, principally itraconazole, voriconazole and posaconazole.

“We also found cross-resistance to voriconazole (65%) and posaconazole (74%) in those isolates we tested that were resistant to itraconazole,” said Professor Denning. “The result depends on the particular mutation conferring resistance.

“Patients can be treated with intravenous amphotericin B or caspofungin, but these are not useful when patients leave hospital, or have allergic aspergillosis."

Report we quote was published in full by Manchester University

Wednesday, 8 July 2009

First trial for new antifungal begins

It has been mentioned elsewhere in this blog that the search for new antifungals is important and ongoing. Particularly important are antifungals that have different modes of action when compared to existing antifungals so it is encouraging that a local company here in Manchester, UK have announced the first tests are under way of their new antifungal which has a novel target of activity:
F2G Limited, the Manchester UK based antifungal drug discovery and development company, today announced the initiation of a Phase I clinical study of FG3622, the company’s lead antifungal drug candidate.

The Phase 1 trial is a randomised, placebo-controlled study designed to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of FG3622. 100 healthy volunteers will be enrolled in the trial which will evaluate single as well as multiple ascending doses of FG3622 which will be administered orally. This clinical trial is the first-in-human study in the global development of FG3622 and will be conducted in the UK.

FG3622 is the first of a new generation of novel class systemic antifungal agents active by both oral and intravenous administration to enter the clinic. The mechanism of action, discovered by scientists at F2G, involves the selective inhibition of a fungal enzyme and is completely distinct from any other class of marketed antifungal agent. The compound displays highly potent activity against a wide range of clinically significant moulds including the common pathogen Aspergillus fumigatus which is the leading cause of Invasive Aspergillosis, a serious, debilitating disease associated with very high mortality rates despite current therapy options.

Plenty of work to do yet before this is proven to be useful but this is another example of a growing list of new options becoming available to treat fungal infection.

Monday, 6 July 2009

FDA revise guidelines for rheumatoid arthritis drug Leflunomide

The Food and Drug Administration (FDA) in the United States has issued a safety update for a drug used to treat active rheumatoid arthritis. They now recommend that all patients must be screened for tuberculosis and other pulmonary infections such as aspergillosis prior to taking Leflunomide due to the risk that the drug will increase the chances that these infections will get worse.

Medications with immunosuppressive potential, such as leflunomide, may increase patient susceptibility to opportunistic infections, particularly tuberculosis (including extrapulmonary disease), Pneumocystis jiroveci pneumonia, and aspergillosis.

The FDA notes that leflunomide has not been studied in patients with a positive tuberculin screen result, and the safety of leflunomide in those with latent infection remains unknown. Patients with a positive test result should be treated by standard medical practice before starting leflunomide therapy.

Leflunomide is indicated to reduce signs and symptoms of disease, inhibit structural damage, and improve physical function in patients with active rheumatoid arthritis.

Friday, 3 July 2009

Composting 'scaremongering'??

Industrial scale composting is expanding quickly in the UK and across europe as alternatives to disposing of waste via landfill are explored more vigorously.

Composting is mainly done via open 'windrows' where piles of rotting vegetable matter are left in the open air and turned mechanically at regular intervals. Each turning releases vast clouds of fungals spores, principally Aspergillus fumigatus, an important human pathogen and allergen. Those clouds are rapidly dispersed into the air and diluted such that a safe distance from the composting site should be achievable.

How safe is this practice to both the workers at the composting site and to people living close by? Newspaper articles contend that composting is not yet carried out under completely safe conditions, a story based on a recent paper by Drew which found that risk analyses at most UK locations where composting is carried out were inadequate.
A rebuttal was issued by pro-composting groups here calling the newspaper stories 'scaremongering' and suggesting that living close to a composting site is no more a risk to health than a walk in the woods:
anyone who walks through a wood especially in the autumn will be exposed to higher levels of these spores than living near a compost site.

I would suggest that it is impossible or impractical to identify individuals who's health is at risk from breathing in fungal spores. Those individuals can include those with poor immune systems & asthmatics. That risk is probably increased if increased number of spores are breathed in therefore until it is possible to warn all people at risk a large margin for safety should be used when setting boundaries for minimising health risks. Risk analyses need to be of a consistently high standard.

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