Highlights of this month...
World's 1st CPA guidelines presented at European Respiratory Meeting
The guidelines describe the 5 clinical phenotypes of CPA and how to diagnose and manage these patients.
The guidelines support the strong message that CPA needs action and antifungals are the cornerstone of treatment for this condition which therefore should include therapeutic drug monitoring.
The objective of antifungal therapy in CPA patients would be 4 fold: to control infection, arrest pulmonary fibrosis, prevent haemoptysis and improve the quality of life.
The publication of these guidelines in a few weeks time, will assist and guide the training of medical professionals working with CPA patients and improve patient outcome.
Life Worldwide tell us that 15 papers were simultaneously published in October
on the estimated burden of all serious fungal diseases in Belgium, Czech Republic, Denmark, Hungary, Nepal, Qatar, Tanzania, Trinidad and Tobago, Uganda, Germany, Mexico, Senegal, Tanzania, Ukraine, Vietnam and that posters on burden from Mozambique, Madagascar, Pakistan, Algeria, Venezuela, Serbia, Greece, Portugal and France were presented at 7th TIMM, Lisbon, Portugal
. This is a milestone - the fungal disease for 5 billion people are now presented and/or published.
As we go to press
a paper (Pisa etal
2015) has emerged that claims to demonstrate quite convincingly that fungi and fungal elements (not Aspergillus
) are present in the brain tissue of Alzheimers patients. Whilst this is not an entirely new observation this is the first time hyphal-like structures have been demonstrated and the authors mention two cases where patients believed to have Alzheimers were treated successfully with antifungal medication.
lung colonisation has been demonstrated to correlate with faster lung
function loss in these patients, but it also looks like those who have a
poorer lung function also have increased likelyhood of a fungal lung
colonisation (Noni et al 2015).
It isn't difficult to imagine that the two could go hand in hand with very undesirable consequences.
Low rates of homologous recombination have broadly encumbered genetic
studies in the fungal pathogen Aspergillus fumigatus. The CRISPR/Cas9
system of bacteria has recently been developed for targeted mutagenesis
of eukaryotic genomes with high efficiency and, importantly, through a
mechanism independent of homologous repair machinery. As this new
technology has not been developed for use in A. fumigatus, Fuller et al.(2015) sought to
test its feasibility for targeted gene disruption in this organism. As a
proof-of-principle, they first demonstrate that CRISPR/Cas9 can indeed be
used for high-efficiency (25-53%) targeting of the A. fumigatus polyketide synthase gene (pksP), as evidenced by the generation of
colorless (albino) mutants harboring the expected genomic alteration. They
further demonstrate that the constitutive expression of the Cas9
nuclease by itself is not deleterious with respect to A. fumigatus growth or virulence, thus making the CRISPR system compatible with
studies involved in pathogenesis.
The aim of this study by Peghin et al.(2015)was to assess the outcome and tolerability of
prophylactic nebulized liposomal amphotericin B (n-LAB) in lung
transplant recipients (LTR) and the changing epidemiology of Aspergillus
spp. infection and colonization.
lung allograft dysfunction (CLAD) was associated with Aspergillus spp. colonization and infection (HR 24.4, 95% CI 14.28-41.97; P = 0.00). Only
2.9% of patients presented adverse effects, and 1.7% required
discontinuation. Long-term administration of prophylaxis with n-LAB has
proved to be tolerable and can be used for preventing Aspergillus spp. infection in LTR. Over the last years, the incidence of Aspergillus spp. colonization and infection has decreased, but species with reduced
amphotericin susceptibility or resistance are emerging. CLAD is
associated with Aspergillus spp. colonization and infection.
Aspergillus fumigatus is the most virulent species within the
Aspergillus genus, and causes invasive infections with high mortality
rates. The exopolysaccharide galactosaminogalactan (GAG) contributes to
the virulence of A. fumigatus. A co-regulated five-gene cluster has been
identified and proposed to encode the proteins required for GAG
biosynthesis. One of these genes, sph3, is predicted to encode a protein
belonging to the spherulin 4 family, a protein family with no known
function. Construction of an sph3-deficient mutant demonstrated that the
gene is necessary for GAG production. To determine the role of Sph3 in
GAG biosynthesis Bamford et al.(2015) determined the structure of Aspergillus clavatus Sph3 to 1.25 Å. The structure revealed a (β/α)8 fold, with
similarities to glycoside hydrolase families 18, 27, and 84. Recombinant
Sph3 displayed hydrolytic activity against both purified and cell
wall-associated GAG. Structural and sequence alignments identified three
conserved acidic residues, D166, E167, and E222, which are located
within the putative active site groove. In vitro and in vivo mutagenesis
analysis demonstrated that all three residues are important for
activity. Variants of D166 yielded the greatest decrease in activity
suggesting a role in catalysis. This work shows that Sph3 is a glycoside
hydrolase essential for GAG production and defines a new glycoside
hydrolase family, GHXXX.
Invasive aspergillosis (IA) is the most common life-threatening
opportunistic invasive mould infection in immunocompromised people.
Early diagnosis of IA and prompt administration of appropriate
antifungal treatment are critical to the survival of people with IA.
Antifungal drugs can be given as prophylaxis or empirical therapy,
instigated on the basis of a diagnostic strategy (the pre-emptive
approach) or for treating established disease. Consequently there is an
urgent need for research into both new diagnostic tools and drug
treatment strategies. Newer methods such as polymerase chain reaction
(PCR) to detect fungal nucleic acids are increasingly being
OBJECTIVES: Cruciani et al.(2015) provide an overall summary of the diagnostic accuracy of PCR-based
tests on blood specimens for the diagnosis of IA in immunocompromised
Although in textbooks asthma and chronic obstructive pulmonary disease
(COPD) are viewed as distinct disorders, there is increasing awareness
that many patients have features of both. This article by Postma & Rabe (2015) reviews the
asthma-COPD overlap syndrome.
organisms of various size ranges present in air are called airborne
particles or bioaerosol which mainly includes live or dead fungi and
bacteria, their secondary metabolites, viruses, pollens, etc. which have
been related to health issues of human beings and other life stocks.
Characterization i.e. identification and
quantification of different airborne microorganisms in various indoor
environments is necessary to identify the associated risks and to
establish exposure threshold.
Along with the bioaerosol sampling and their analytical techniques,
various literatures revealing the concentration levels of bioaerosol
have been mentioned in this review by Ghosh, Lil & Srivastava (2015) thereby contributing to the knowledge
of identification and quantification of bioaerosols and their different
constituents in various indoor environments (both occupational and
Apart from recognition of bioaerosol, developments of their control
mechanisms also play an important role. Hence several control methods
have also been briefly reviewed. However, several individual levels of
efforts such as periodic cleaning operations, maintenance activities and
proper ventilation system also serve in their best way to improve
indoor air quality.
The importance of aspergillosis in humans and various animal species has
increased over the last decades. Aspergillus species are found
worldwide in humans and in almost all domestic animals and birds as well
as in many wild species, causing a wide range of diseases from
localized infections to fatal disseminated diseases, as well as allergic
responses to inhaled conidia. Some prevalent forms of animal
aspergillosis are invasive fatal infections in sea fan corals,
stonebrood mummification in honey bees, pulmonary and air sac infection
in birds, mycotic abortion and mammary gland infections in cattle,
guttural pouch mycoses in horses, sinonasal infections in dogs and cats,
and invasive pulmonary and cerebral infections in marine mammals and
nonhuman primates. This article by Seyedmousavi et.al. (2015) represents a comprehensive overview of
the most common infections reported by Aspergillus species and the
corresponding diseases in various types of animals.
Nominate fungal (incl. non-pathogenic) genomes for sequencing at the Joint Genome Institute (JGI) here.
Contribute to clinical data on rare infections:
Aspergillosis Community (National Aspergillosis Centre) meets on the first friday of every 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 broadcast
Dedicated newsletter available at the Patients Website