I hope you're doing well and enjoying summer. I also hope that you'll find the following
article about Aspergillosis by Fernando Fernandez both interesting and useful.
With best wishes,
By Fernando A. Fernandez, Ph.D., EMLab P&K Mycologist
The genus Aspergillus is an extremely important fungal group and possibly the one with the
greatest overall impact in human affairs and civilization. This fungus was first recognized by the
botanist P. A. Micheli, who described it in his Nova Plantarum Genera publication in 1729.
Throughout human history, members of this fungal genus have gained particular notoriety because
of their uncanny ability to produce enzymes, acids, and mycotoxins. An indication of the
biochemical importance of this group is the fact that 147 US patents involving Aspergillus
metabolites were filed between 1971 and 1991, and many more have been filed since then (Klich 2002).
Aspergillosis is generally defined as a spectrum of diseases of humans and animals caused by
members of the genus Aspergillus. In 1863, the German physician/botanist Georg Fresenius
is credited with first describing the most notorious disease-causing species in the genus,
A. fumigatus, from an infection in a great bustard (a bird), and thereby coined the term
aspergillosis to describe the condition (Bennett 2009). Prior to 1863, reports of suspect
Aspergillus infections in birds were made by Reaumur in 1749 in describing 'moulding' of
eggs, infections of the thoracic air sacs of a duck by Montagu in 1803, and those of a jay by
Mayer in 1815 (Bennett 2009). It comes as no surprise that A. fumigatus is predominant
in causing animal mycoses, specifically avian aspergillosis, which once accounted for 10% of
losses of broiler chicks (Klich 2002), and mycotic abortion in cattle, sometimes affecting up
to 10% of the pregnant cows in a herd (Pier & Richard 1992). Other animals involved in
agriculture, such as horses and bees, companion animals, particularly dogs and parrots, and
zoological or wildlife animals, such as dolphins, raptors and waterfowl, are also at risk
Rudolf Virchow was the first to accurately describe human aspergillosis in 1856, with a less
definite report made by Sluyter in 1847. The first known occupational mycoses were cases of
aspergillosis reported in 1897 among squab feeders and wig cleaners; all presumed to have been
repeatedly exposed to heavy amounts of A. fumigatus spores (Bennett 2009). It should be
pointed out that irrespective of occupations, it is common for spores of Aspergillus to
enter our bodies continuously through the respiratory system, at rates of hundreds per day without
creating any complications in healthy individuals (Hospenthal et al. 1998). However, those
individuals with compromised immune systems, especially those recipients of stem-cell and solid
organ transplants, those undergoing chemotherapy and those with advanced HIV infection, are
particularly at risk in developing the disease when exposed to the fungus. Healthcare-associated
aspergillosis is most commonly acquired via inhalation of airborne spores resulting in pulmonary
aspergillosis and subsequently the fungus may disseminate via the bloodstream to involve other
organs (Weber et al. 2009).
In the clinical setting, aspergillosis has been subdivided into different subtypes, to reflect
the spectrum of diseases it encompasses. These general types are: aspergilloma ('fungus ball'),
allergic bronchopulmonary aspergillosis (ABPA) and invasive (systemic) aspergillosis (IA).
Aspergilloma is the saprobic colonization of a preexisting cavity in the lungs by an
Aspergillus species. The fungus characteristically forms a compact mycelial ball which
does not invade adjacent tissues. In ABPA, airway infections with Aspergillus exacerbate
asthma symptoms in patients with chronic asthma and cystic fibrosis. Aspergillus fumigatus
is the most commonly implicated species, although other species can also be involved
(Goldman & Huffnagle 2009). In contrast, IA is characterized by mycelium of the fungus
growing between epithelial cells, becoming primarily localized in the lungs, and disseminating
through the circulatory system with severe immunosuppression as an essential precondition
(Hoog et al. 2002).
Invasive aspergillosis has become particularly serious and has increased during the past two
decades, primarily due to the broad use of chemotherapies and immunosuppressive therapies in
many different patient groups (Mascheyer et al. 2009). Risk groups include recipients of
hematopoietic stem cell transplants (HSCT), solid-organ transplants, patients undergoing
chemotherapy and patients with advanced HIV infections (Weber et al. 2009). In 2002, a cooperative
effort named TRANSNET was created among academic institutions and the Centers for Disease
Control (CDC). This multi-institutional collaboration serves as a surveillance network of 25
transplant centers in hospitals that perform stem cell and/or solid organ transplants in the
U.S., to monitor the incidence of invasive fungal infections in transplant recipients (Morgan
et al. 2005). The network has provided important information on the epidemiology of IA infections
in the United States (Weber et al. 2009), including details of which species of Aspergillus
have been involved in infections. Aspergillus fumigatus is still prevalent (56-60%),
followed by A. flavus (9-19%), A. terreus (12-16%), A. niger (8-18%), and
A. versicolor (1%) (Baddley et al. 2003, Morgan et al. 2005). These data contrast with
earlier epidemiologic data from a decade earlier when the vast majority of cases (90%) were
secondary to A. fumigatus (Marr et al. 2002). Other species such as A. glaucus,
A. nidulans, A. oryzae and A. ustus have also been involved in
healthcare-associated aspergillosis outbreaks (Weber et al. 2009).
Early diagnosis is critical for a favorable outcome in patients with systemic fungal infections,
and particularly with aspergillosis. However, diagnosis remains challenging due to the low
sensitivity of microbiological culture techniques and the low specificity of radiological
procedures (Maschmeyer et al. 2009). More sensitive diagnostic tests have been developed based
on detecting Aspergillus-specific molecules with immunosorbent techniques (ELISA) and
DNA techniques by using PCR; the latter are not yet commercially available and are not standardized
(Maschmeyer et al. 2009).
Powerful antifungal agents are currently used to treat patients with aspergillosis. Those include
amphotericin B, triazoles (itraconazole, voriconazole and posaconazole) and echinocandins
(caspofungin, micafungin, anidulafungin) (Stevens 2009). Problems with these drugs include the
development of resistance, toxicity, and harmful interactions with other drugs. A good example
of drug resistance is shown by A. terreus which consistently show decreased susceptibility
to amphotericin B in vitro and in vivo (Baddley et al. 2003). On the preventative front, there is
research work in progress to develop a vaccine that could provide protection against
A. fumigatus, with promising results in laboratory mice (Ito et al. 2009).
In the indoor environment, Aspergillus can be found in household dust, building materials,
ornamental plants, flower arrangements, tobacco, food and water (Warris & Verwej 2005).
Dispersal of fungal structures (spores, hyphal fragments) is impacted by activities such as
construction, demolition, excavation, disturbance of dust accumulations during routine cleaning,
water intrusion and moisture accumulation. In addition, aspergillosis outbreaks in healthcare
facilities have been associated with contaminated air conditioners, air filters, particle board
frames of air filters, air duct systems, ceiling tiles and fireproofing materials (Haiduven 2009).
However, concentrations of Aspergillus spores have not been found to be correlated to any
seasonal pattern or the occurrence of invasive aspergillosis (Hospenthal et al. 1998). Also, the
relationship between airborne spore counts and infection risk has been difficult to assess because
it has been impossible to relate a specific number of airborne spores to a quantifiable infection
risk among patients, including highly immunocompromised patients. For this reason, the CDC has not
provided recommendations regarding routine microbiologic air sampling before, during, or after
facility construction or renovation, or before or during occupancy of areas housing
immunocompromised patients (Weber 2009).
The CDC provides excellent on-line resources, including several publications with guidelines to
managing infectious agents (http://www.cdc.gov/hicpac/pubs.html). Also, the mycotic disease branch
of the CDC has a web page with relevant and updated information on fungal diseases
It is important to keep in mind that members of the genus Aspergillus are all free-living,
saprobic species that can potentially become opportunistic pathogens (Bennett 2009). There is no
evidence that these fungi derive obvious benefits from parasitizing humans, other animals, or that
they have evolved to take advantage of living hosts. It is then reasonable to conclude that their
ability to cause disease stems from their overall ability to survive under a wide array of living
conditions. Then it is also reasonable to conclude that management of Aspergillus and the
disease-casuing members of this genus will remain an important issue in the management of
environmental and clinical health in the future.
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