Essay: An Introduction to Aspergillosis

In the spring, when trees and plants are in full bloom, the air we breathe becomes more saturated with pollen. More and more individuals are plagued with nasal congestion, sneezing, and cough- allergies. As humans, we tend to be focused on tasks, going day by day, often not stopping to notice our surroundings until it affects us- until our allergies act up or we have a sinus infection. Fungi are a prime example of such negligence. We often ignore the fact that we are merely residents in a world of fungi. It is easy to remain neglectful, until it affects us, or someone close to us. April 8th In Houston, TX, the mold count was 3381 spores per cubic meter (huston). This spore count was classified as low. The spore count in some areas will reach over 50,000 per cubic meter. These areas of high spore saturation are prime locations for fungal infections. In the stretch of twenty-four hours, the average individual will inhale hundreds of microbes and propagules (Hohl, daeg). While fungal spore inhalation innately seems hazardous, the fact is most individuals (those whom are not immunocompromised and have healthy immune systems) are left unaffected, or minimally affected by this confrontation with fungi. However, in rare cases, healthy immunocompetent individuals exposed to propagules will develop an allergic reaction to the presence of the foreign materials, spores as a result of their hypersensitive immune systems (Hohl). This allergic response will present as a cough, shortness of breath, and wheezing- essentially upper respiratory infection symptoms. On the other end of the spectrum, when those with weakened immune systems are exposed to airborne pathogens, their weakened responses result in hazardous and deadly infections of tissues and the central nervous system, often times resulting in mortality. Individuals become immunocompromised as a result of many other risks, diseases, and infections such as: AIDS, cancers/cancer treatments, surgeries, diabetes etc.
A Description of Aspergillus
The genus Aspergillus consists of ~250 of fungi and contribute to just a fraction of the hundreds of thousands of propagules present in our environment. Being a silent resident, Aspergillus is an essential member of society, contributing a significant role in the carbon and nitrogen recycling within the environment (Dagenais).  Aspergillus terreus is used to produce a cholesterol-reducing drug Lovastatin. Aspergillus oryzae is used to ferment soybeans and make soy sauce. Though genus Aspergillus contains some useful species, a number of these fungi have negative functions in society. For example, Aspergillus flavus and Aspergillus parasiticus contaminate crops with a carcinogen that has immunosuppressive properties. Consumption of contaminated crops leads to immediate death. Some Aspergillus species cause infections and inflammation in humans.  Invasive Aspergillosis describes an Aspergillus infection in humans that has progressed to affecting different tissues of the body system. Inhalation of Aspergillus conidia leads to growth of fungi in accessible spaces, and may result in disruption of many body systems and tissues such as the sinuses, central nervous system, cardiovascular, ocular, renal, etc. (introductio mycology). Aspergillus are saprophytes, are commonly found in warm environments, such as piles of compost, soil, decaying vegetation. Aspergilli produce millions of conidia, which provide the organism with a means of transmission and proliferation (hsu). Conidia readily become airborne, thus increasing the likelihood of inhalation by unsuspecting host. Upon entry into the body, will A. fumigatus colonize the mucosae of the esophagus and the pulmonary system (fif kingdom.  For Aspergillus to colonize and cause infection, the host must have risk factors that enable the pathogen to overcome the host immune system. Risk factors include AIDS, cancers/cancer treatments, surgery, age, lung transplants, and history of asthma or chronic obstructive pulmonary disease (COPD). In lung transplant patients that develop Aspergillosis, the mortality rate is as high as 87% (hsu).  Aspergillus fumigatus is the most common species resulting in invasive aspergillosis (Espinosa, introductio mycology).
Transmission of Aspergillosis
The number of cases of Aspergillosis is not directly reported to the Center for Disease Control, making the tracking of infections much more difficult. The transmission of Aspergillosis is executed primarily through inhalation of Aspergillus conidia. Spore count is one method of predicting where cases of Aspergillosis are more likely to occur. Aspergillus propagates in warm and locations, and tends to colonize piles of compost and soil. Areas that tend to stay warm and dry tend to have higher spore count (as demonstrated in the spore count map of the U.S. found in supplemental information), and will put citizens in the area at greater danger of developing fungal infections.
In 2008, over 29,000 procedures in the United State provided patients with new organs via organ transplants (pappas). Though organ transplants save thousands of lives a year, there is risk involved with such major procedures. Even with sterile techniques and the latest technology, the risk of infection is always present.  Individuals whom receive whole organ transplant also receive immunosuppressant medications, corticosteroids, to improve chances of a successful surgery. The objective of subduing the immune system is to decrease the probability of the patient initiating an immune response, and rejecting the organ. While the immune system is suppressed, the opportunity for infections increases (Sherif, daeg). Lung transplants are extremely dangerous because of high probability of Aspergillus infections becoming invasive, and ending in mortality. The Transplant-Associated Infection Surveillance Network (TRANSNET) consists of twenty-three transplant centers in the U.S. In a survey of fifteen centers within TRANSNET from March 2001 to March 2006 observing organ transplants and invasive fungal infections, it was found that 1208 fungal infections were noted within 1063 organ transplant patients (pappas). While over fifty percent of cases were noted as Candidiasis, approximately twenty percent of the 1208 fungal infections were contributed to Aspergillus species. Infection is likely to occur in any individuals who are immunocompromised and dealing with other diseases and infections. With the immune system is preoccupied with other diseases (examples: COPD, AIDS, diabetes, cystic fibrosis), fungal pathogens have higher likelihoods of colonizing within the host patient, and developing infections.
Pathogenesis: Mechanism of damage, host and microbe
Severity of Aspergillus infections in humans is very dependent of the host’s immune system, and their ability to eliminate the infection source (Dagenais). Once A. fumigatus conidia are inhaled, the conidia will make work their way to the pulmonary alveoli. Most conidia are phagocytized and discarded by alveolar macrophages in the form of sputum that is coughed out of the body (Sherif, daeg).  Conidia that survive at this point will develop into hyphal structures, the invasive form of the disease. Motifs on the cell wall of the fungi are recognized by pathogen recognition receptors. This identification recruits neutrophils to the region of fungal infection, resulting in further degradation of the foreign pathogen. Initial presentations may appear benign, as the fungus begins to colonize within cavities. These areas of filamentous growth are often termed “fungus balls”, and can be present in the sinuses, ear, and lungs (introductio mycology). The fungus ball may penetrate the surrounding tissue and blood vessels. Once access to blood vessels is attained, the fungi spreads to other tissues and lesions are formed- typically only observed in immunocompromised patients.  Aspergillosis of the central nervous system leads to neurological deficits and seizures. When an infection progresses to this stage, there are typically no interventions that can be performed to reverse/eliminate the infection, and mortality is eminent. Aspergillosis is a common cause of mortality of lung transplant patients. With the transplant of the lung, the vasculature of the organ is not reconstructed, and as a result, ischemic changes occur with each procedure. Multiple studies have noted Aspergillus’ inclination to colonize at areas of ischemia (hsu).
Diagnosis & Laboratory Workup
Because Aspergillus conidia must typically be inhaled to initiate the infection and colonizing process, Aspergillosis occurs predominantly in the esophageal tract and pulmonary system (Sherif).  The symptoms are typical upper respiratory infection characteristics- fever, shortness of breath, and cough. As the disease progresses, and begins to invade the vasculature network, patients start to complain of chest pain. These symptoms resemble an upper respiratory infection, and make it very difficult to properly diagnose in a hospital setting. After attaining access to the vasculature, the central nervous system may become colonized with Aspergillus, resulting in seizures and possible strokes. Detection of Aspergillus hyphae in tissue serves as a marker for proven positive invasive Aspergillosis (sherif). A probable diagnosis of invasive Aspergillosis is made if the patient has risk factors- such as being immunocompromised or has had recent organ transplants, has been exposed to the fungi (being around a patient with proven Aspergillosis, has been around environment susceptible to Aspergillus growth like mounds of compost). In the medical setting, fungal infections may be isolated and cultured from the sinus tract, and serves as evidence indicating Aspergillus infection. Often only diagnosed with an autopsy and tissue study, following the death of the patient.
Treatment and Therapy
Most cases of invasive Aspergillosis will go undetected and misdiagnosed, only discovered upon the patient’s death. When Aspergillosis is diagnosed, Voriconazole is the most popular and successful treatment of mycoses. Use of Voriconazole increased the survival rates in patients from 32% to 53% (sherif). In adults, the absorption rate of Voriconazole is not linear, but rather exponential. Adults receive small doses such as 200mg every twelve hours. Increasing this dose to 300mg every 12 hours increases the absorption rate by 2.5x. Children absorb Voriconazole in a linear plane, so to achieve the same amount of absorption, as needed in adults, children must receive a higher dose. More treatments will become available in the near future, as researchers are looking at the genomic sequences of Aspergillus species. With the research already performed, the diversity of organisms within the genus Aspergillus is astonishing (sherif).