GAtherton

Fungal biofilm structure and its indications in invasive aspergillosis

Microorganisms can group together on a surface to form collections of cells called biofilms; one example of this is dental plaque. Grouping together as a community protects these cells from environments which they may not be able to survive alone, such as the wrong pH or a lack of water or oxygen. Biofilms may be made up of many different species of microorganism and these species may be varied further by strain. In a recent paper, Caitlin Kowalski and colleagues at the Geisel School of Medicine at Dartmouth, USA, studied the ability of Aspergillus fumigatus biofilms to grow in low oxygen environments and cause invasive aspergillosis in mice.  

Kowalski and colleagues exposed A. fumigatus to low levels of oxygen, which reflect the levels found in the lesions where the fungus grows in the lung, in order to identify genes and mechanisms involved in allowing the pathogen to grow under these conditions. They then discovered a specific mutation which allowed the strain to both grow better in low oxygen, but also cause disease better under these conditions. It remains to be discovered how this particular mutation allows the strain to grow more successfully and be more virulent in low oxygen. However in other fungal biofilms, for example the yeast Candida albicans, the colony can form wrinkles which improve oxygen penetration. Understanding how the structure of biofilm colony growth reflects advantages in the ability of the fungus to cause disease may allow clinicians and scientists to better predict the progression of disease and improve patient care.

Find out more:

• Fungal biofilm morphology impacts hypoxia fitness and disease progression.
• How fungal biofilm structure impacts lung disease

by GAtherton

Side effects of long-term azole therapy

Azole antifungals are the first-line of treatment or prophylaxis for many fungal infections. They are often administered long-term (weeks to months), which can be associated with a number of adverse effects. In patients receiving several medications, it can be difficult to identify whether antifungals are contributing to, or causing particular symptoms; recognition of common side effects, leading to treatment discontinuation or management, is therefore key to reducing symptoms and reversing toxicity.  A recent review by Dr Lydia Benitez and Dr Peggy Carver summarises these effects and their frequency:

Key points the authors highlight:

• Liver toxicity, generally reversible, is common with all azoles.
• Hormone-related adverse effects are observed with select azoles; these include hair loss, breast enlargement, decreased libido, impotence, and (rarely) adrenal insufficiency (beware drug interactions with inhaled and oral steroids).
• Patients with fair skin on voriconazole should use liberal amounts of broad spectrum UV protectants and wear sun protective clothing, avoid excess sunlight, and undergo frequent monitoring of skin as phototoxic reactions progressing to development of skin cancer has been associated with long-term use.
• Therapeutic drug monitoring may be utilized to minimise neuropathies in specific patient populations on voriconazole, as neuropathies are more common with higher concentrations and doses. Its role in preventing other long-term toxicities is less clear.

Azoles are a valuable resource in the treatment and prophylaxis for fungal infections. Despite being associated with a number of adverse effects, they are safer and more active than alternatives. Thorough knowledge of the side effects they may cause is therefore important, so that they can be recognised and managed promptly.

Read the paper here: Benitez, L.L. & Carver, P.L. Drugs (2019) 79: 833

by GAtherton

Vitamin D deficiency may increase the risk of Amphotericin B-related kidney toxicity

Amphotericin B (AmB) is the drug of choice for the treatment
of many fungal infections.  Despite this,
the drug can cause several serious side effects, one of which being nephrotoxicity
(toxicity to the kidneys). Conventional AmB can be adapted into a lipid
emulsion preparation, which can reduce the risk of nephrotoxicity, while
preserving its efficacy and remaining a lower cost option. Unfortunately this
does not solve the problem, and nephrotoxicity remains an issue for many
patients.

Vitamin D deficiency has been found to be a major problem worldwide, and can increase the risk of kidney-related disease, including drug-induced nephrotoxicity. A recent study by Daniela Ferreira and colleagues at the University of Sao Paulo looked at standard and vitamin D-deficient rats and found that the deficient rats treated with AmB presented with impaired renal function. This suggests that vitamin D deficiency may play a key role in the development of AmB-induced nephrotoxicity. Therefore, the authors state that it is essential to monitor levels of vitamin D in patients treated with both conventional and lipid formulations of AmB, in order to reduce the development of kidney disease.

Read the full paper here

by GAtherton

New diagnostic tool paves the way for faster and earlier diagnosis of chronic pulmonary aspergillosis

A new screening test kit will speed up diagnosis of chronic pulmonary aspergillosis (CPA) say researchers from the University of Manchester. The test, available commercially from LDBio diagnostics, is very simple and needs no power source or equipment and therefore is likely to be very useful in resource poor settings.

CPA is a fungal disease associated with lung damage caused by other conditions including TB which is prevalent in low to middle income countries. CPA can get progressively worse over time and so early diagnosis is crucial to improve patient outcomes.

The team from the University of Manchester and the NHS Mycology Reference Centre, based at Wythenshawe Hospital, tested the LDBio Aspergillus ICT kit on blood samples collected from 154 CPA patients identified at the National Aspergillosis Centre in Manchester and 150 healthy volunteers. They found that the test had improved sensitivity (91.6%) and specificity (98.0%) for diagnosis of CPA in UK patients compared to existing diagnostic tests.

Limitations of current diagnostic procedures include high cost, long turn-around times, poor reproducibility and variations in performance. The new test is cheap, fast, reproducible and reliable. Therefore it is particularly useful in low to middle income countries where CPA diagnostics are a necessity for early recognition of CPA complicating TB, and to distinguish between these similarly presenting conditions.

Professor David Denning, Professor of Infectious Diseases in Global Health at the University of Manchester and Director of the National Aspergillosis Centre at the Manchester University NHS Foundation Trust said:

"With over 7 million people suffering TB in the lungs each year and 5-10% of them later getting the fungal infection aspergillosis in the lungs, a simple cost-effective test for aspergillosis is sorely needed. This new test fulfils these basic requirements and we are delighted to report that its diagnostic performance surpasses all the older tests as well. A real win-win for early diagnosis and reducing lung scarring and death." 

The findings were published this month in the Journal of Clinical Microbiology.

Citation:

Evaluation of LD Bio Aspergillus ICT lateral flow assay for IgG and IgM antibody detection in chronic pulmonary aspergillosis. Elizabeth Stucky Hunter, Malcolm D. Richardson, David W. Denning. Journal of Clinical Microbiology Jun 2019, JCM.00538-19; DOI: 10.1128/JCM.00538-19

Read the paper!

by GAtherton