Highlights of this month...
New test based on melt curve technology
Fast and accurate diagnosis of fungal infections is notoriously challenging. Molecular methods using PCR (polymerase chain reaction) work by amplifying small stretches of fungal DNA (‘amplicons’) and examining their properties.
One such property that has not been sufficiently explored is the ‘melt profile’, which measures how the two DNA strands of the amplicon separate at different temperatures. The resulting profiles can produce surprisingly unique fingerprints even between closely-related species, making this a potentially very accurate test.
A study by Lu et al.
analysed 243 clinical isolates from a wide variety of species based on a DNA sequence called ITS, which is often called the ‘universal barcode’ because it occurs in every living species. The technique clearly distinguished between many species and even strains of yeast, including Aspergillus flavus
, A. fumigatus
and A. terreus
This exhibit at the Manchester Science Festival shone the spotlight on UK research that is helping to improve the prevention, diagnosis and treatment of mycoses
The family-oriented exhibition engaged members of the public in an app-based role-playing game, amongst a variety of other drop-in activities and visual media.
The successful event was organised by the University of Manchester Fungal Infection Group(MFIG), and supported by the National Aspergillosis Centre, FungiBrain, and the NHS Mycology Reference Centre. MFIG report that the app-based game was rated 8.8/10 by attendees, and that people selected dressing up, time with researchers and interactivity as some of their favourite elements.
8th Advances Against Aspergillosis
Plans are well underway for the next AAA in Lisbon, Portugal on 1-3 February 2018. Having run bi-annually since 2004 AAA is established as the biggest and best forum for detailed and dedicated discussion of Aspergillus diagnosis, treatment, and research.
Organisers hope to hold another event at the conference for patients, this time providing translations to the host language for local participants, Portuguese.
Some of the highlights are:
Aspergillosis is well known in immunocompromised patients, but there is less awareness of it among critically ill patients with normal immune systems. Influenza-associated aspergillosis (IAA) is underdiagnosed because the clinical presentation is somewhat different to ‘typical’ cases of aspergillosis, but early diagnosis and treatment are crucial for patient survival.
Two groups recently looked at rates of IAA in intensive care units (ICUs). A Spanish group
found around 1% of patients admitted to ICUs for flu were also infected with Aspergillus
, and that these patients were significantly more likely to die. A Dutch group
found around 16% of flu patients in ICUs also had aspergillosis, and that some of these strains were resistant to azole antifungals. Furthermore, they found that the mortality rate was around 60% (slightly higher than the previously reported rate of 47%), and that the patients who survived tended to be the ones who started antifungal treatment earlier.
Increasing awareness of the signs and symptoms of IAA could potentially help ICU staff to initiate antifungal treatment earlier and reduce mortality rates.
An international group have investigated the fungal pathogen Aspergillus terreus in terms of its prevalence and susceptibility to the antifungal amphotericin B. 38 centres from 21 countries provided data for the study from 7116 patients, and found 5.2% of patients with mould positive cultures in this study were infected with A. terreus (and that almost 15% of these patients were infected with cryptic species).
As A. terreus species display polyene resistance, the authors of the study surveyed amphotericin B susceptibility. Amphotericin B minimum inhibitory concentrations ranged from 0.125 - 32mg/L, and was higher (2 – 32 mg/L) in cryptic species. The authors used epidemiological data in conjunction with the A. terreus isolates to confirm the wide geographical distribution and general resistance of these species to amphotericin B, and their role in the pathogenesis of various different types of aspergillosis.
This study, by researchers from the Hans Knöll Institute and Friedrich Schiller University, builds on the fact that antifungal compounds effect fungal cells in various ways, including triggering the fungal cell to accumulate reactive oxygen species (ROS) to levels which are not conducive to fungal cell function. The study aimed to further investigate the role of ROS in the antifungal nature of three compounds: itraconazole, terbinafine and amphotericin B.
The researchers found that the antifungal compounds studied were all able to trigger intracellular ROS production in Aspergillus fumigatus. This is thought to be a secondary action of these therapeutic compounds, which primarily affect fungal cells through disruption of cell walls.The authors also found that A. fumigatus can avoid antifungal-triggered ROS accumulation by altering its mitochondrial activity. Therefore, by working around one of the ‘killing mechanisms’ of antifungal drugs, A. fumigatus can change to reduce the effectiveness of antifungal treatment.
Children with acquired or congenital immunodeficiencies are at increased risk of fungal lung infections. CT/MRI imaging is crucial for diagnosis as well as for monitoring response to treatment and detecting adverse events, but some of the classic diagnostic signs (halo sign, air crescent sign) may not appear in children.
This review presents a series of cases in children (ages 8 months to 16 years) with a variety of underlying immune conditions such as ALL and cystic fibrosis. Clearly illustrated with many CT scans, it covers clinical and radiological features of the major fungal lung infections in children, particularly Aspergillus, Pneumocystis and Candida, as well as their differential diagnoses.
In this study, researchers evaluated the pharmacokinetics of voriconazole in a group of African penguins. These species are particularly susceptible to respiratory fungal disease when kept in captivity, and treatment failure with itraconazole, due to resistant Aspergillus strains, is not uncommon.
In the single dose trial, the penguins received an oral voriconazole suspension of 5mg/kg, whereas in a separate, multiple dose trial, the penguins received 5mg/kg daily for 8 consecutive days in fish. Blood samples were collected at various time points after dosing.
The single dose schedule produced a relatively short time of peak concentration (Tmax) of 0.4 hours (in contrast to longer Tmax in other bird species). The multi-dose trial with fish prolonged the Tmax, probably because of delayed absorption. The half-life of the drug was almost 11 hours in this species, which is long in comparison to other bird species, and may suggest that accumulation is likely in African penguins with extended dose periods. The authors suggest that an oral dose of 5mg/kg voriconazole daily could be safe and effective in African penguins, but caution against accumulation and ensuing toxicity.
Health Literacy and Mental Health
As October 17 was designated 'Health Literacy Month', the blog posts on our patients' website have focussed on talking to others about aspergillosis, and on mental health.
These posts are supported and promoted by the ever-expanding aspergillosis Facebook groups, which prompt useful and supportive conversations between patients, directed and moderated by NAC staff members. These groups also help to identify the most useful topics for patient communications and provide useful feedback on these communications.
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 live Facebook Broadcast.
If you want a text reminder when each meeting is approaching (UK only) then send us an email at firstname.lastname@example.org with your mobile phone number.
If you would like to listen or chat with fellow patients and a NAC staff member we are running a successful Skype meeting every week! We are a chatty group of 8 - 12 most weeks but we can accommodate up to 24. If you have a computer or smartphone you will be able to join in - just click on https://join.skype.com/nbubWMUM8teC and you will be asked to register, then taken to the group. The Skype meeting is at 11am GMT (NOTE Change to GMT this month) every Thursday.
Join our Facebook Groups
We also have a Facebook group for those who are caring for someone who is affected by the disease - join here