Emergence of a Resistant Form of Aspergillus
Triazole Resistance in A.fumigatus, Cause of Invasive Aspergillosis
Nov 16, 2008
Aspergillus is a fungus whose spores are present in the air we breathe, but do not normally cause illness. However, an individual with a weakened immune status may be susceptible to Aspergillus infection. Aspergillus fumigatus (A. fumigatus) is one of the most common Aspergillus species to cause disease, such as aspergillosis in immunocompromised individuals.
Aspergillus Causes Invasive Aspergillosis
Aspergillus fumigatus can cause a large spectrum of disease, from allergic syndromes to invasive aspergillosis. Invasive aspergillosis causes lung lesions associated with symptoms such as shortness of breath, wheezing, fever, and brown color sputum. For more details on aspergillus and aspergillosis see the aspergillus web site.
Aspergillosis normally only occurs in severely immune-compromised patients and is associated with a high mortality rate, as much as 80% in high risk patients. Four percent of all patients dying in tertiary care hospitals in Europe have invasive aspergillosis.
Treatment Resistance in Aspergillus Fumigatus
The mortality rate seemed to be decreasing with the use of azole compounds, a group of effective antifungal agents. However, since 1998, Dr Paul Verweij from the Rabdoud University Nijmegen Medical Center (Nijmejen, the Netherlands) has observed an emergence of azole resistance in A. fumigatus, the principal strain causing of aspergillosis.
The frequency and the spread of the resistance to azole drugs in A. fumigatus is unknown but may have a strong impact on the clinical use of azole compounds and mortality rate due to aspergillosis.
Increase Prevalence of Azole Resistance in Aspergillus Fumigatus
In November 2008, Dr Paul Verweij reported, in a new study titled 'Emergence of azole resistance in A. fumigatus and spread of a single resistance mechanism' (PLOS Medicine, vol.5, 11, e219, 2008), an increased prevalence of azole resistance in A. fumigatus.
The team of researchers collected A. fumigatus isolates from 1219 patients in The Netherlands over a period of 14 yrs (from 1994 to 2007). They found 32 patients with a resistant form of A. fumigatus, representing an increasing frequency of 1.7% to 6% per year.
The resistant form of A. fumigatus was due to a genetic mutation in the cyp51A gene, causing a substitution of one amino acid encoded by this gene. The cause of the development of resistant mutants is unknown but the scientists suspect the use of azole fungicides. Indeed azole compounds are widely used for plant protection.
A Resistant Aspergillus Fumigatus Is Spreading in Europe
They also analyzed isolates from 20 different cities in the Netherlands and 6 other European countries (France, Belgium, UK, Sweden, Norway and Greece) and were able to observe similar resistant strains of A. fumigatus in these countries.
Even if the researchers were not able to determine an accurate estimate of the spread of resistance, their study indicates that the genetic mutant A. fumigatus has spread in several European countries and might begin to globally spread in the environment. International surveillance studies as needed, since this will be a determinant factor for selecting the drug of choice in fisrt-line treatment of patients with invasive aspergillosis.
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