Aspergillus Fumigatus

 Aspergillus Fumigatus

In the research by Jean-Paul Liage, 1999 Aspergillus Fumigatus is a weak pathogen and one of the most ubiquitous of the airborne saprophytic fungi.” Jean also explained that humans and animals constantly inhale numerous conidia of this fungus and the conidia are normally eliminated in the immunocompetent host by innate immune mechanisms. aspergilloma and allergic bronchopulmonary aspergillosis, uncommon clinical syndromes, are the only infections observed in such hosts.

Jean-Paul 1999 said that “Aspergillus fumigatus is a saprophytic fungus that plays an essential role in recycling environmental carbon and nitrogen. Its natural ecological niche is the soil, wherein it survives and grows on organic debris. Aspergillus is not the most prevalent fungus in the world, but it is one of the most ubiquitous of those with airborne conidia. It sporulates abundantly, with every conidial head producing thousands of conidia. In the research by Jean-Paul, he stated that the conidia released into the atmosphere have a diameter of 2 to 3 μm that can reach the lung alveoli. Fumigatus does not have an elaborate mechanism for releasing its conidia into the air; dissemination simply relies on disturbances of the environment and strong air currents. Once the conidia are in the air, their small size makes them buoyant, tending to keep them airborne both indoors and outdoors. Environmental surveys indicate that all humans will inhale at least several hundred fumigatus conidia per day. For most patients, therefore, disease occurs predominantly in the lungs, although dissemination to virtually any organ occurs in the most severely predisposed.

Inhalation of conidia by immunocompetent individuals rarely has any adverse effect, since the conidia are eliminated relatively efficiently by innate immune mechanisms. Fumigatus forms of the disease are farmer’s lung, a clinical condition observed among individuals exposed repeatedly to conidia, or aspergilloma, an overgrowth of the fungus on the surface of pre-existing cavities in the lungs of patients treated successfully for tuberculosis. A. fumigatus has become the most prevalent airborne fungal pathogen, causing severe and usually fatal invasive infections in immunocompromised hosts in developed countries. In 1992, IA was responsible for approximately 30% of fungal infections in patients dying of cancer, and it is estimated that IA occurs in 10 to 25% of all leukemia patients, in whom the mortality rate is 80 to 90%, even when treated. IA is now a major cause of death at leukemia treatment centers and bone marrow transplantation (BMT) and solid-organ transplantation units.

Although A. fumigatus is the most common etiologic agent, being responsible for approximately 90% of human infections, it is not the only pathogen in this genus. A. flavus, A. terreus, A. niger, and A. nidulans can also cause human infections.

The fungus Aspergillus fumigatus causes allergic diseases, respiratory illnesses, and bloodstream infections. In an article written by Joseph Bennington-Castro and medically reviewed by Robert Jasmer, MD; they gave examples of Aspergillus disease; such as Allergic bronchopulmonary aspergillosis, or ABPA, is an allergic reaction to Aspergillus that causes inflammation of the lungs. It's most common in people with cystic fibrosis or asthma. Another is Aspergillus sinusitis, also allergic that causes inflammation of the sinuses (sinusitis). Aspergilloma, or "fungus ball," is an Aspergillus ball that grows in the lungs and sinuses. It usually affects people with lung diseases, such as tuberculosis, who have pre-existing cavities in their lungs; the fungi grow within those cavities. Chronic pulmonary aspergillosis, a long-term Aspergillus infection, causes cavities in the lungs.

In the article by Joseph Bennington, Aspergillus Fumigatus Symptoms vary depending on the type of disease. For example, chronic pulmonary aspergillosis may cause: wheezing and coughing, sometimes with mucus or blood, Fever, Chest pain, difficulty breathing, fungus balls also cause a cough (with or without blood). Allergic Aspergillus sinusitis causes typical sinusitis symptoms, including Stuffy or a runny nose, reduced sense of smell. Allergic bronchopulmonary aspergillosis (ABPA) causes symptoms like of asthma, including wheezing and shortness of breath cough, especially with brown-colored mucus. Invasive aspergillosis can cause several severe symptoms, which differ depending on the organs affected.

In Joseph’s article, the treatment for A. Fumigatus varies depending on the disease. For example, the allergic forms of A. fumigatus disease are “usually treated with the antifungal drug itraconazole.” Various corticosteroids — including prednisone, prednisolone, and methylprednisolone — may also help for allergic bronchopulmonary Aspergillosis. And surgery is often necessary to remove aspergillomas. Invasive aspergillosis is typically treated with the antifungal drug voriconazole, and occasionally with surgery, depending on the extent of the disease. Other possible antifungal medications include itraconazole, lipid amphotericin formulations, caspofungin, micafungin, posaconazole.

In the study by Chotirmall et.al., they stated that “understanding Aspergillus virulence mechanisms remains critical to the development of effective research and treatment strategies to counteract the fungi.” Further, they explained that the “major virulence factors relate to fungal structure, protease release, and allergens; however, mechanisms utilized to evade immune recognition continue to be important in establishing infection.” The Aspergillus fumigatus is “crudely divided into classical and non-classical factors, the former refers to a specific component of the pathogen permitting disease while the latter, however, relates to virulence conferred by fungal structure, capacity for growth, stress adaptation, host damage and mechanisms utilized to evade the immune system,” (pg. 3)

The last subset can be termed ‘immunoevasion’ “a major virulence mechanism employed by the fungus to establish infection. We now outline the major Aspergillus virulence factors in terms of their immunoevasive capabilities.” In the non-immunoinvasive virulence factor, Chotirmall et. al. explained that “the Aspergillus cell wall is a protective barrier, essential for survival and airway persistence, however, crucial for fungal binding and subsequent invasion of host epithelium.” Further, “although fungal surface receptors and immunogenic antigens are key components facilitating penetration, the cell wall framework is polysaccharide rich particularly in mannans, mannoproteins and b-1,3-glucans that bind chitin and galactomannan forming pathogen-associated molecular patterns (PAMPs) that activate host immune responses,” (pg.4)

With the immunoevasion, “it is a strategic virulence mechanism employed by the fungus. It enables host colonization, immunosuppression, provides pathogen nutrition, and avoids the major killing methods possessed by the host including phagocytosis and exposure to ROS. The major immunoevasive Aspergillus virulence factors include the rodlets layer, DHN-melanin, detoxifying systems for ROS and toxins.” The aspergillus conidial surfaces are enfolded by a hydrophobin coat termed the rodlet layer whose mycopathologia123 primary function is conidial dispersion and soil fixation. Upon entry to the human airway, it masks cell wall b-1,3-glucans preventing immune detection (pg.4).

In the study by Spellberg B. “Aspergillus is the second most common cause of nosocomial, invasive fungal infections, with an incidence of approximately 5 per 100,000 population in the United States. Both the potential advantages of, and barriers to, a vaccine against aspergillosis are greater than with invasive candidiasis. For example, aspergillosis infection has an extremely high mortality rate despite antifungal therapy (45% to >80%). Conversely, a barrier for the development of a vaccine is that virtually all patients with invasive aspergillosis are highly immunocompromised, which could make vaccination more problematic.” Further, “the feasibility of vaccination of mice with crude antigen preparations from an Aspergillus strain, A. fumigatus, has been demonstrated, even in animals that were subsequently immunocompromised,” (Spellberg B.). Also, “vaccination was found to improve survival against both inhaled and intravenously administered fungi. Furthermore, like the rAls3p-N vaccine against disseminated candidiasis, the efficacy of A. fumigatus crude protein vaccination required the presence of IFN-γ and was mediated by CD4+ lymphocytes in adoptive transfer studies,” (Spellberg B.)

Another research by Steven. A. D. talks about the development of vaccines for aspergillus, they explained that “recent studies in our laboratory with heat-killed Saccharomyces (HKY) have raised the possibility of development of a panfungal vaccine. This yeast may be nature's experimental reagent, to show the way to a protective protein-carbohydrate conjugate vaccine. Subcutaneous HKY is an effective vaccine against Aspergillus, Coccidioides, or Candida challenge. We have learned the protective moiety is in the cell wall, and proteins, glucan, and lipid all seem important. We have also found the cell wall glycans alone, mannan or glucan, as a vaccine each provide significant protection. This leads to consideration of the importance of glycosylated proteins and glycan polymer-protein conjugates in vaccine development.

References

Chotirmall H. S., Mirkovic B., Lavelle M. G., McElvaney G. N.; Immunoevasive Aspergillus Virulence Factors (Pgs. 1-4). Mycopathologia · June 2014 DOI: 10.1007/s11046-014-9768-y

Brad Spellberg. Vaccines for invasive fungal infections. F1000 Med Rep. 2011 July; 3: 13.

Doi: [10.3410/M3-13]

Stevens A. D., Clemons V. K., Liu M., Developing a Vaccine Against Aspergillosis 

Medical Mycology, Volume 49, Issue Supplement_1, 1 April 2011, Pages S170–S176, https://doi.org/10.3109/13693786.2010.497775

Bennington-Castro J., Medically Reviewed by Jasmer R., (MD). (Updated, 2015)

Aspergillosis; Cleveland Clinic. Jean-Paul Latgé (1999). "Aspergillus fumigatus and Aspergillosis." Clinical Microbiology Reviews. Howard et al. (2009). "Frequency and Evolution of Azole Resistance in Aspergillus fumigatus Associated with Treatment Failure." Emerging Infectious Diseases.

Retrieved from: https://www.everydayhealth.com/aspergillus/

Latgé Jean-Paul. Aspergillus fumigatus and Aspergillosis.1999 Apr; Clinical Microbiology Rev. 12(2): 310–350.