Friday, 30 September 2011

NewsBite: Combination Antifungal Drug Trial Disappoints

Reuters article: Pharmaceutical company Pfizer's trial featured two of their antifungal drugs given together to treat invasive aspergillosis. Vfend (voriconazole) and Eraxis (anidulafungin) given together appeared to show some improvement over using Vfend alone but the data was not statistically significant in the final analysis.

Monday, 26 September 2011

Breath testing for 2-pentylfuran as a diagnostic test for pulmonary aspergillosis- an update

Breath testing methods to diagnose pulmonary aspergillosis is attractive because of the proximity of the infection (lung) and simplicity of obtaining samples for treatment. The detection of volatile organic compounds in the breath has been reported previously and 2-pentylfuran was isolated as a potential marker for aspergillus infections (link), also this compound is not produced by normal mammalian metabolism.
In May 2011, we ran a blog reporting initial data by Chambers et al that 2 pentylfuran could be detected in two immunocompromised patients with Aspergillus fumigatus infections. Initial studies also suggested that some foods which give rise to 2-pentylfuran may give false positive readings which would interfere with the tests.
A further report from the same group of researchers has determined new limits and possibilities for the potential breath test.
Of 45 foodstuffs tested 10 gave detectable 2-pentylfuran. Levels were highest from soymilk, lower from pumpkin, rolled oats, tinned asparagus, tinned beans and marmite. No 2-pentylfuran was detected from antifungal medicines. No difference in the time of day of testing or in relation to fasting or not, was observed. However the breath test could be accurately conducted on people who had ingested 2-pentylfuran positive foods - without an overnight fast -by simply rinsing the mouth with water - and waiting 30 mins or more before carrying out the breath test. The lower limits of detection were around 1 attogram of 2-pentylfuran.
This latest data decreases the problem of false positive results for this potentially diagnostic test.

Thursday, 22 September 2011

Newsbite: New species in Aspergillus section Terrei

Three new species have been described in the section Aspergillus terrei. These have been identified by sequence analysis of parts of the beta-tubulin and calmodulin genes and the ITS region. The identification of hepatotoxic and neurotoxic metabolites are identified amongst many other metabolites produced by this species. more

Friday, 16 September 2011

NewsBite: Ochratoxin detected in 20% of Chronic Rhinosinusitis patients

Researchers in the New York University School of Medicine checked 18 patients for a range of mycotoxins. All specimens were negative for aflatoxin, deoxynivalenol, zearalenone, and fumonisin. Four (22%) of 18 specimens were positive for ochratoxin. The clinical significance of this finding remains to be determined.

Thursday, 15 September 2011

Advance in Prevention of Medical Implant Infections

Medical implants such as heart valves and catheters commonly fail because of fungal infections of the implant which form a biofilm - a thin viscous layer that forms on the surfaces of the device which resists the absorption of antifungal drugs and therefore effectively protects fungi growing within the film.
This is a major cause of failure of these devices and often require the surgical removal of the device in order to clean up the infection. Mortality following some types of infection is as high as 30% so this is a highly important issue for both doctor and patient.

Robbins et. al. have discovered an effective treatment target that may effectively prevent the ability of biofilms to protect the fungus in the future. Heat shock protein (Hsp90) has already been directly implemented in drug resistance and here it is shown that if the amount of Hsp90 expression in the fungus is reduced then biofilm formation is greatly reduced and resistance to antifungals also prevented.

Yeasts are the most common infecting fungus in this situation. Once the expression of Hsp90 was prevented by genetic deletion it became vulnerable to antifungal treatment by the azole group of antifungals.

Aspergillus is the most lethal infecting organism in this situation, but once Hsp90 expression had been prevented it became more vulnerable to treatment with the new echinocandin group of antifungal drugs.

This study used isolates of fungi that had had Hsp90 expression genetically altered and also tested the effect of treating infections in mice with drugs that inhibit Hsp90. This research suggests that if we could develop new drugs to downregulate Hsp90 expression (or possibly even use existing drugs if appropriate e.g. if toxicity is low) then we could treat infections using a combination of Hsp90 inhibitor and antifungal to bring about a much more effective elimination of the fungal infection, hopefully without the need for surgery.

Hsp90 inhibitors already exist that may be directly testable in human experiments so perhaps we will see a  introduction of this technique in the not to distant future.

Friday, 9 September 2011

Hurricane Irene causes Explosion in Mould Counts

Hurricanes are of course associated with high winds and a lot of rain and flooding. Measurements of airborne mould levels in the outside air before and after Irene struck show mold at 100-fold normal levels, peaking at up to 10 000 spores per cubic metre.
The air indoors is also vulnerable to increases in mould as the hurricane pushes humidity levels up and of course causes physical damage allowing rain to enter many properties along with large scale flooding. Some water ingress is obvious and can be dealt with but other leaks could be hidden e.g. in wall spaces and under the floor and these can cause just as much damage. It is important to dry, clean and remediate as soon as possible.

Symptoms of problems caused by increases in airborne moulds are those of respiratory discomfort especially for those with pre-existing breathing problems such as asthma and bronchitis and of course allergies to moulds. After Hurricane Katrina had blown itself out and destroyed many thousands of homes in New Orleans in 2005 some people seemed to develop 'Katrina Cough' which was almost certainly caused by irritation caused by the large amount of airborne dust including moulds.
NB It follows that any people with a compromised immune system should take more care than most, avoiding the worse effected areas and using HEPA grade facemasks to avoid breathing in microrganisms.

There is also some evidence that exposed people's sensitivity to moulds was not hugely effected by Hurricane Katrina. Rabito tested the sensitivity of hundreds of residents of New Orleans for sensitivity to moulds in the months and years after Katrina. One third reported mould damage to their homes and continued to live there during remediation work so we would expect them to have been quite heavily exposed to airborne moulds - figures reported in this paper mention levels up to 500 000 spores per cubic metre of indoor air. However only 10% showed any sensitivity to moulds and this did not differ greatly from the sensitivity levels found in residents of undamaged homes. Mold sensitivity did not correlate with damage to homes or the level of mould in those homes.

Consequently: Are we imagining Katrina Cough?

The authors go on to admit that their study does not capture several groups of ill people e.g. those who are not responsive to mould will also probably have symptoms of respiratory irritation - these symptoms are might still be caused by moulds using a mechanism other than allergy.
They also admit that they could not check if the patients they tested were resident in New Orleans at the time the hurricane struck - so this study lacks precision. Likewise the study depended on people being able to afford to be tested and thus missed the least well off part of the population.
This was a rather 'rough & ready' study that did not show gross effects caused by high mould counts in indoor air, but its limitations do not allow it to rule out all health problems caused by moulds and other airborne irritants in contaminated homes, especially those of the poorest people in New Orleans.

We can probably expect similarities in the health problems experienced by people living in New Orleans  and those effected by Hurricane Irene and moulds may well play their part in causing them.

CDC recommendations for cleaning up in the aftermath of a Hurricane

Thursday, 1 September 2011

Pandemic influenza A and development of aspergillosis in immunocompromised patients

A report has highlighted the need for awareness of the possibility of developing invasive aspergillosis in severely immunocompromised patients, following hospitalisation due to infection with pandemic influenza A strain.
In 2010 the new strain of influenza - H1N1 resulted in a pandemic, with acute respiratory infection and a high mortality.
This report identifies 5 out of 57 patients who were immunosuppressed because of leukaemia treatment or transplantation, who required hospitalization due to influenza A (H1N1), then went on to develop invasive aspergillosis. The case reports indicate a higher level of frequency of invasive aspergillosis in these two high risk groups (8.8%), compared to other reported levels - raising the question of whether infection with H1N1 predisposes this patient at risk group, to developing invasive aspergillosis. This may be supported by the fact that no aspergillosis cases were seen amongst any haemotology - stem cell transplant patients.
Implementing preventative measures against infection with influenza A, H1N1 and prompt action by clinicians to consider a diagnosis of aspergillosis, is essential for these patients.

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