Aspergillus: Introduction, Medical Importance, Pathogenecity, Laboratory Diagnosis, Treatment, Prevention and Prophylaxis

Aspergillus niger on sda

Introduction of Aspergillus 

Aspergillus niger is widespread in soil and on plants and is common in food. Colonies are initially white but quickly become black with the production of the fruiting structures. This species grows rapidly with a pale yellow reverse. Like other Aspergillus species, hyphae are hyaline and septate. Conidial heads are biseriate and cover the entire vesicle. Conidia are brown to black and are very rough (4–5 µm) This species, which is commonly associated with colonization and otic infections, produces oxalate crystals in clinical specimens.

Scientific Classification

  • Kingdom: Fungi
  • Division: Ascomycota
  • Class:  Eurotiomycetes
  • Order: Eurotiales
  • Family: Trichocomaceae
  • Genus: Aspergillus

Species

  • Aspergillus fumigatus
  • Aspergillus flavus
  • Aspergillus niger
  • Aspergillus terreus
  • Aspergillus versicolor
  • Aspergillus nidulans
  • Aspergillus oryzae
  • Aspergillus glaucus
  • Note: From top to down is according to medical importance

Medical importance

Micheli in Florence first recognized Aspergillus in 1729 (Micheli, 1729). He gave the name  Aspergillus and an aspergillum used to sprinkle holy water (with the name derived from the Latin aspergo, to sprinkle) Later first detailed microscopic descriptions of this organism were provided by Virchow in 1856. Initial descriptions of clinical cases were first detailed in workers that had been occupationally exposed to the organism and the association was made with infection and certain occupations—such as pigeon feeders, wig combers, farmers, feed-mill workers, and others exposed to dust or grains (Denning, 1998). Others noted the potential for mold to colonize or invade cavities that formed following other diseases such as tuberculosis. Deve described fungus balls due to Aspergillus (aspergilloma) in 1938 (Deve, 1938). The potential for allergic reactions to the organisms in the form of allergic bronchopulmonary aspergillosis was described in 1952 (Hinson et al, 1952). It was not until the mid-1950s with the introduction of immunosuppressive agents such as corticosteroids and cytotoxic chemotherapy that the first occurrences of invasive aspergillosis in immunocompromised hosts were recognized (Rankin, 1953). In recent decades the use of immunosuppressive therapies in increasing numbers of patients has resulted in a dramatic global increase in cases of invasive infections due to Aspergillus (Groll et al, 1996).

Pathogenicity of Aspergillus

It causes a disease called aspergillosis. The opportunistic mold Aspergillus is the etiologic agent responsible for a variety of infections and conditions referred to as aspergillosis. These manifestations include allergic responses following exposure to the organisms (allergic bronchopulmonary aspergillosis), colonization with Aspergillus spp. (aspergilloma or fungus ball due to this organism  and other conditions such as external ear colonization) and invasive infection (invasive pulmonary aspergillosis and other clinical syndromes of tissue invasion). Invasive aspergillosis is a significant cause of morbidity and mortality in high-risk patients A major factor associated with the increased number of cases of invasive aspergillosis is the increase in patients at risk for this disease, such as patients undergoing bone marrow or organ transplantation and patients with other immunodeficiencies.

Laboratory Diagnosis 

  • Specimens

sputum

Bronchoalveolar lavage (BAL)

Biopsy

  • Direct microscopy:  Potassium hydroxide (KOH) preparation of the specimens reveals non-pigmented septate hyphae (3-5 µm in diameter) with characteristics dichotomous branching ( at an angle of approximately 45°). Biopsy sections can be stained with hematoxylin and eosin (H& E) stain and  Periodic acid–Schiff stain (PAS)  staining and examined for the characteristic hyphae.
  • Culture: The clinical sample is inoculated on SDA without cycloheximide and incubated at 25 °C.
  • Colonies appear within 1-2 days due to being a fast grower and show a velvety to the powdery surface, Colonies are colorful as shown above image.

Treatment 

Useful antifungal agents are-

Polyenes group

  • Amphotericin B
  • Liposomal amphotericin
  • Amphotericin B lipid complex
  • Amphotericin B colloidal dispersion

Azoles group

  • Itraconazole

Echinocandins group

  • Caspofungin
  • micafungin,
  • and anidulafungin

triazoles

  • voriconazole,
  • posaconazole,
  • and ravuconazole

Prevention and Prophylaxis

Outbreaks of Aspergillus infections have been linked to hospital construction, contaminated ventilation systems, and operating rooms, and more recently to contaminated water. Nevertheless, it is important to recognize that high-risk immunosuppressed patients now spend much of their treatment course in the outpatient setting; consequently, community-acquired infection is also common. Prevention of nosocomial aspergillosis in the highest risk populations is difficult even using state-of-the-art air control systems including point-of-use HEPA filters, frequent air exchanges, and positive pressure ventilation. Unfortunately, these high-risk patients have exposures in the hospital setting outside of their protective environment. Antifungal prophylaxis using agents with activity against molds has been attempted, usually, in the setting of an outbreak, this infection involves multiple other interventions to control the outbreak. Efficacy in that setting is usually compared to the incidence of infection during a prior historical setting. Agents evaluated in this setting include low-dose amphotericin B, low doses of lipid formulations of amphotericin B, and nasal and aerosolized forms of amphotericin B. None of these have been conclusively demonstrated to have benefits in large, randomized clinical trials. Itraconazole has been suggested to have benefits in preventing mold infections but poor tolerance of itraconazole by high-risk patients has limited its use.  Thus, no agents are currently recommended for the prevention of mold infections.

Bibliography

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