Fungal Infection Trust Aspergillus Newsletter June 2018
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Highlights of this month...

Two point-of-care tests for invasive aspergillosis launched

It has been a dream for many years for doctors to be able to make a quick diagnosis of invasive aspergillosis (IA) at the bedside. Characteristically diagnosis of IA is difficult, complex and slow, requiring several days before a definitive conclusion. Those days are often precious time that would be better spent treating IA, every day giving a better chance of improving patient survival.

It is with excitement then we can say that two point-of-care diagnostic devices are now available that will assist rapid diagnosis with results delivered in 30 minutes. Both tests detect Aspergillus cell wall antigen using a lateral flow device and a drop of serum or BAL fluid. In tests, the IMMY kits were capable of correctly detecting IA in 25/26 serum samples and 25/28 BAL samples.

A third kit is also emerging that will detect IA in a drop of urine - see MycoMed Technologies
 
News

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A case report has been published in Emerging Infectious Disease Volume 24, Number 8 August 2018 that for the first time detects A.fumigatus spores in the proximity of an ICU patient with acute invasive aspergillosis. The spores were detected in the air filters of the room the patient was housed in and are shown to emanate from the airways of the patients.

The British Lung Foundation highlighted the need for a UK National Plan for Lung Disease during their recent 'Breathe Easy Week', the need for which is highlighted by their 2017 report 'Estimating the economic burden of respiratory illness in the UK'

Dr Tanu Singhal has given us permission to host the Fungal Infection Study Forum (Mumbai), which we are doing on the pan-fungal LIFE-Worldwide website.


Communication and Digital Content Officer 

The Science and Medical Communications team at the National Aspergillosis Centre, producing newsletters, blog articles and other communications for researchers, clinicians and patients will shortly be advertising for a new post.


An enthusiastic, broadly-trained clinician is sought to contribute to the care of patients with complex infection problems, including aspergillosis (National Aspergillosis Centre), non-tuberculous mycobacterial infection, and community-acquired infection, as well as consulting on other complex infection problems (heart and lung transplant, cystic fibrosis, ICU, surgical infection, ECMO etc). A growing OPAT service yields many challenging cases. The successful applicant will join 6 existing ID consultants.

Articles


A. fumigatus responsive T cells have potential to be used as a diagnostic marker for patients with invasive aspergillosis (IA), however, experiments that showed elevated levels in patients with IA also showed very variable levels in control subjects that had no IA, making interpretation of the result difficult. This paper addresses at least part of the cause of that control variability.

The authors have found that the number of A. fumigatus responsive T cells in healthy adults correlates with the amount of environmental exposure that each individual experiences. It is quite striking how little exposure to environmental sources of Aspergillus is needed to cause an increase in T cell numbers, and it is also striking that those exposed to heavy mould contamination of their homes who we might expect to have high numbers of responsive T cells had, in fact, very variable numbers of responsive T cells.

More work is needed but this work may lead to the development of a test for environmental exposure to mould spores -  a test that is sorely needed when those people living in mouldy homes get sick and we need to get evidence of their level of exposure.


Serum levels of voriconazole have long been known to be very variable. Reasons include nonlinear pharmacokinetics, drug:drug interaction with CYP 450, polymorphism of CYP450 and inflammation-mediated downregulation of P450 isoenzymes.

In this study a patient with CNS aspergillosis is treated with voriconazole and multiple dose changes were required to keep trough levels within acceptable therapeutic boundaries. The patient had been given rifampicin prior to starting voriconazole, the impact of which on the pharmacokinetics of voriconazole persisted for at least 13 days. Progressive increases in dose eventually led to a sudden increase in serum levels at day 74, presumably due to saturation of liver mechanisms for metabolism of voriconazole.

This study emphasises the need for continued therapeutic dose monitoring in patients taking voriconazole, particularly if they have been given rifampicin.


Previous research had demonstrated that giving antifungal medication to severe asthmatics with fungal sensitivity helped reduce their symptoms sufficiently to allow a reduction in corticosteroids medication with minimal impact on some asthma symptoms.

This paper identified candidates for antifungal therapy using fungal sputum cultures in a population of moderate to severe asthmatics. It finds that those subjects given antifungal medication had improved asthma control, increased peak expiry flow and markedly reduced IgE levels and blood eosinophil counts.

CONCLUSION: Antifungals help control symptoms in a subset of asthmatics with culture-proven airway mycosis. Additional randomized clinical trials are warranted to extend and validate these findings.


This paper identifies the essential importance of part of the immune system (a lectin receptor MelLec) that detects a type of melanin found in fungal spores and other melanised fungal structures. The in-vivo distribution of this receptor are limited to the lungs in mice, suggesting an important role in removing pathogens from inhaled air.

Mutation of MelLec (also expressed in humans) demonstrated that it was essential to prevent disseminated infection by A. fumigatus in mice. MelLec, therefore, recognizes an immunologically active component commonly found on fungi and has an essential role in protective antifungal immunity in both mice and humans.
 
Reviews

 
A recent review of 42 epidemiological studies by Dr Felix Bongomin and colleagues showed that the causative agent of onychomycosis (nail infection) was Aspergillus spp. in 1-35% of cases overall, but more frequently among the elderly and those with diabetes (up to 71%). Toenails were affected 25x more often than fingernails.  
 

In this systematic review, the authors assessed the available evidence for the use of serum galactomannan at baseline as a prognostic marker, and the predictive value of serum galactomannan kinetics after initiation of antifungal therapy. Overall, serum galactomannan at baseline and galactomannan kinetics appear to be good predictors of therapy response and survival. However, breakpoints for predicting therapy failure and validation in different patient populations are still lacking.

Veterinary


Itraconazole can be cost prohibitive in brand name form; therefore, compounded and generic products are often used as alternatives. Itraconazole blood concentrations have not been studied in clinical patients receiving these formulations.

Itraconazole bioassay was performed on serum/plasma from 95 dogs and 20 cats receiving itraconazole (compounded from bulk powder, generic pelletized, or brand name) for systemic mycosis treatment. No statistical difference was observed between itraconazole concentrations in the generic and brand name groups. Forty animals (95.2%) in the compounded group had subtherapeutic (<1.0 µg/mL) values. All cats in this group (n = 10) had undetectable itraconazole concentrations. Some animals in the generic and brand name groups had subtherapeutic values (12.5 and 12.1%, respectively) or potentially toxic values (>10 µg/mL; 37.5 and 24%, respectively). Compounded itraconazole should be avoided, but generic itraconazole appears to serve as a reasonable alternative to brand name itraconazole. Therapeutic drug monitoring may be beneficial in all cases. 
 
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Patients & Carers

Patient Meetings

The Aspergillus community/patient group meeting normally meets on the first Friday of each month at the Altounyan Suite, North West Lung Centre, Manchester at 1.30pm BST/GMT. If you can't make it in person, you are welcome to listen in to our Facebook Broadcast

If you want a text reminder when each meeting is approaching (UK only) then send us an email at admin@aspergillus.org.uk with your mobile phone number.

Online Meetings

If you would like to listen or chat with fellow patients and a NAC staff member we are running a successful online meeting every week! We are a chatty group of 8 - 12 most weeks. If you have a computer or smartphone you will be able to join in using Zoom - download of this software is free and easy. Just click on https://zoom.us/j/243782379. This meeting is at 11am GMT every Thursday (UHT+1 in the summer)

Join our Facebook Groups

Our Aspergillosis Support Facebook Group has over 1300 members and is a safe place to meet and talk to other people with aspergillosis.

We also have a Facebook group for carers, friends and family of someone who is affected by the disease - join here

To find our regional and international groups, search the following terms within Facebook: 'aspergillosis'; 'aspergillus'; 'ABPA'
Fungal Infection Trust, PO Box 482, Macclesfield, Cheshire SK10 9AR