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Aspergillosis is the name given to a wide variety of diseases caused by infection by fungi of the genus Aspergillus. Aspergillosis occurs in humans, birds and other animals.

Aspergillosis
Pulmonary aspergillosis (1) invasive type.jpg
Pulmonary invasive aspergillosis in a patient with interstitial pneumonia (autopsy material), using Grocott's methenamine silver stain
Pronunciation
SpecialtyInfectious disease

Aspergillosis occurs in chronic or acute forms which are clinically very distinct. Cases of acute aspergillosis generally occur in patients with severely compromised immune systems eg those undergoing bone marrow transplants.The majority of chronic cases in humans occur in those with underlying illnesses such as asthma and here, cystic fibrosis, tuberculosis[1] or chronic obstructive pulmonary disease.[2] Most commonly, aspergillosis occurs in the form of chronic pulmonary aspergillosis (CPA), aspergilloma or allergic bronchopulmonary aspergillosis (ABPA).[3] Some forms are intertwined; for example ABPA and simple aspergilloma can progress to CPA.

Other, noninvasive manifestations include fungal sinusitis (both allergic in nature and with established fungal balls), otomycosis (ear infection), keratitis (eye infection), and onychomycosis (nail infection). In most instances, these are less severe, and curable with effective antifungal treatment.

People with deficient immune systems—such as patients undergoing hematopoietic stem cell transplantation, chemotherapy for leukaemia, or AIDS—are at risk of more disseminated disease. Acute invasive aspergillosis occurs when the immune system fails to prevent Aspergillus spores from entering the bloodstream via the lungs. Without the body mounting an effective immune response, fungal cells are free to disseminate throughout the body and can infect major organs such as the heart and kidneys.

The most frequently identified pathogens are Aspergillus fumigatus and Aspergillus flavus, ubiquitous organisms capable of living under extensive environmental stress. Most humans are thought to inhale thousands of Aspergillus spores daily, but they do not affect most people’s health due to effective immune responses. Taken together, the major chronic, invasive, and allergic forms of aspergillosis account for around 600,000 deaths annually worldwide.[disputed ][1][4][5][6][7]

Contents

BurdenEdit

Aspergillosis is thought to affect more than 14 million people worldwide, with allergic bronchopulmonary aspergillosis (ABPA, >4 million), severe asthma with fungal sensitization (>6.5 million), and chronic pulmonary aspergillosis (CPA, ∼3 million) being considerably more prevalent than invasive aspergillosis (IA, >300000). Other common conditions include Aspergillus bronchitis, Aspergillus rhinosinusitis (many millions), otitis externa, and Aspergillus onychomycosis (10 million). Alterations in the composition and function of the lung microbiome and mycobiome have been associated with an increasing number of chronic pulmonary diseases such as COPD, cystic fibrosis, chronic rhinosinusitis and asthma.

SymptomsEdit

A fungus ball in the lungs may cause no symptoms and may be discovered only with a chest X-ray, or it may cause repeated coughing up of blood, chest pain, and occasionally severe, even fatal, bleeding. A rapidly invasive Aspergillus infection in the lungs often causes cough, fever, chest pain, and difficulty breathing.

Poorly controlled aspergillosis can disseminate through the blood stream to cause widespread organ damage. Symptoms include fever, chills, shock, delirium, seizures, and blood clots. The person may develop kidney failure, liver failure (causing jaundice), and breathing difficulties. Death can occur quickly.

Aspergillosis of the ear canal causes itching and occasionally pain. Fluid draining overnight from the ear may leave a stain on the pillow. Aspergillosis of the sinuses causes a feeling of congestion and sometimes pain or discharge. It can extend beyond the sinuses.[8]

In addition to the symptoms, an X-ray or computerised tomography (CT) scan of the infected area provides clues for making the diagnosis. Whenever possible, a doctor sends a sample of infected material to a laboratory to confirm identification of the fungus.

DiagnosisEdit

On chest X-ray and CT, pulmonary aspergillosis classically manifests as a halo sign, and later, an air crescent sign.[9] In hematologic patients with invasive aspergillosis, the galactomannan test can make the diagnosis in a noninvasive way. False-positive Aspergillus galactomannan tests have been found in patients on intravenous treatment with some antibiotics or fluids containing gluconate or citric acid such as some transfusion platelets, parenteral nutrition, or PlasmaLyte.

On microscopy, Aspergillus species are reliably demonstrated by silver stains, e.g., Gridley stain or Gomori methenamine-silver.[10] These give the fungal walls a gray-black colour. The hyphae of Aspergillus species range in diameter from 2.5 to 4.5 µm. They have septate hyphae,[11] but these are not always apparent, and in such cases they may be mistaken for Zygomycota.[10] Aspergillus hyphae tend to have dichotomous branching that is progressive and primarily at acute angles of around 45°.[10]

TreatmentEdit

The current medical treatments for aggressive invasive aspergillosis include voriconazole and liposomal amphotericin B in combination with surgical debridement.[12] For the less aggressive allergic bronchopulmonary aspergillosis, findings suggest the use of oral steroids for a prolonged period of time, preferably for 6–9 months in allergic aspergillosis of the lungs. Itraconazole is given with the steroids, as it is considered to have a "steroid-sparing" effect, causing the steroids to be more effective, allowing a lower dose.[13] Other drugs used, such as amphotericin B, caspofungin (in combination therapy only), flucytosine (in combination therapy only), or itraconazole,[14][15] are used to treat this fungal infection. However, a growing proportion of infections are resistant to the triazoles.[16] A. fumigatus, the most commonly infecting species, is intrinsically resistant to fluconazole.[17]

PreventionEdit

Prevention of aspergillosis involves a reduction of mold exposure via environmental infection-control. Antifungal prophylaxis can be given to high-risk patients. Posaconazole is often given as prophylaxis in severely immunocompromised patients.[18]

Infection of animalsEdit

While relatively rare in humans, aspergillosis is a common and dangerous infection in birds, particularly in pet parrots. Mallards and other ducks are particularly susceptible, as they often resort to poor food sources during bad weather. Captive raptors, such as falcons and hawks, are susceptible to this disease if they are kept in poor conditions and especially if they are fed pigeons, which are often carriers of "asper". It can be acute in chicks, but chronic in mature birds.

Aspergillosis has been the culprit in several rapid die-offs among waterfowl. From 8 December until 14 December 2006, over 2,000 mallards died in the Burley, Idaho, area of the USA, an agricultural community about 150 miles southeast of Boise. Mouldy waste grain from the farmland and feedlots in the area is the suspected source. A similar aspergillosis outbreak caused by mouldy grain killed 500 mallards in Iowa, USA, in 2005.

While no connection has been found between aspergillosis and the H5N1 strain of avian influenza (commonly called "bird flu"), rapid die-offs caused by aspergillosis can spark fears of bird flu outbreaks. Laboratory analysis is the only way to distinguish bird flu from aspergillosis.

In dogs, aspergillosis is an uncommon disease typically affecting only the nasal passages (nasal aspergillosis). This is much more common in dolicocephalic breeds. It can also spread to the rest of the body; this is termed disseminated aspergillosis and is rare, usually affecting individuals with underlying immune disorders.

In 2019, an outbreak of aspergillosis struck the rare kakapo, a large flightless parrot endemic to New Zealand. By June the disease had killed seven of the birds, whose total population at the time was only 142 adults and 72 chicks. One fifth of the population was infected with the disease and the entire species was considered at risk of extinction.[19]

See alsoEdit

ReferencesEdit

  1. ^ a b Denning, D. W.; Pleuvry, A.; Cole, D. C. (March 2013). "Global burden of chronic pulmonary aspergillosis complicating sarcoidosis". European Respiratory Journal. 41 (3): 621–6. doi:10.1183/09031936.00226911. PMID 22743676.
  2. ^ Smith, N; Denning, D.W. (1 April 2011). "Underlying conditions in chronic pulmonary aspergillosis including simple aspergilloma". European Respiratory Journal. 37 (4): 865–872. doi:10.1183/09031936.00054810. PMID 20595150.
  3. ^ Goel, Ayush. "Pulmonary aspergillosis". Mediconotebook. Retrieved 29 May 2015.
  4. ^ Guinea J, Torres-Narbona M, Gijón P, Muñoz P, Pozo F, Peláez T, de Miguel J, Bouza E (June 2010). "Pulmonary aspergillosis in patients with chronic obstructive pulmonary disease: incidence, risk factors, and outcome". Clin Microbiol Infect. 16 (7): 870–7. doi:10.1111/j.1469-0691.2009.03015.x. PMID 19906275.
  5. ^ Chen, J; Yang Q; Huang J; Li L (September 2013). "Risk factors for invasive pulmonary aspergillosis and hospital mortality in acute-on-chronic liver failure patients: A retrospective cohort study". Int J Med Sci. 10 (12): 1625–31. doi:10.7150/ijms.6824. PMC 3804788. PMID 24151434.
  6. ^ Garcia-Vidal, C; Upton A; Kirby KA; Marr KA (October 2008). "Epidemiology of invasive mold infections in allogeneic stem cell transplant recipients: Biological risk factors for infection according to time after transplantation". Clin Infect Dis. 47 (8): 1041–50. doi:10.1086/591969. PMC 2668264. PMID 18781877.
  7. ^ Nam, HS; Jeon K; Um SW; Suh GY; Chung MP; Kim H; Kwon OJ; Koh WJ (June 2010). "Clinical characteristics and treatment outcomes of chronic necrotizing pulmonary aspergillosis: A review of 43 cases". Int J Infect Dis. 14 (6): 479–482. doi:10.1016/j.ijid.2009.07.011. PMID 19910234.
  8. ^ Ederies A, Chen J, Aviv RI, et al. (May 2010). "Aspergillosis of the Petrous Apex and Meckel's Cave". Skull Base. 20 (3): 189–92. doi:10.1055/s-0029-1246229. PMC 3037105. PMID 21318037.
  9. ^ Curtis A, Smith G, Ravin C (1 October 1979). "Air crescent sign of invasive aspergillosis". Radiology. 133 (1): 17–21. doi:10.1148/133.1.17. PMID 472287.
  10. ^ a b c Kradin RL, Mark EJ (April 2008). "The pathology of pulmonary disorders due to Aspergillus spp". Arch. Pathol. Lab. Med. 132 (4): 606–14. doi:10.1043/1543-2165(2008)132[606:TPOPDD]2.0.CO;2 (inactive 2019-02-18). PMID 18384212.
  11. ^ "Mycoses: Aspergillosis". Mycology Online. Archived from the original on 7 December 2008. Retrieved 2008-12-10.
  12. ^ Kontoyiannis DP, Lionakis MS, Lewis RE, Chamilos G, Healy M, Perego C, Safdar A, Kantarjian H, Champlin R, Walsh TJ, Raad II (April 2005). "Zygomycosis in a tertiary-care cancer center in the era of Aspergillus-active antifungal therapy: a case-control observational study of 27 recent cases". J. Infect. Dis. 191 (8): 1350–60. doi:10.1086/428780. PMID 15776383.
  13. ^ Walsh TJ, Anaissie EJ, Denning DW, Herbrecht R, Kontoyiannis DP, Marr KA, et al. (February 2008). "Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America". Clin. Infect. Dis. 46 (3): 327–60. doi:10.1086/525258. PMID 18177225.
  14. ^ Herbrecht R, Denning D, Patterson T, Bennett J, Greene R, Oestmann J, et al. (8 August 2002). Invasive Fungal Infections Group of the European Organisation for Research and Treatment of Cancer and the Global Aspergillus Study Group. "Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis". N Engl J Med. 347 (6): 408–15. doi:10.1056/NEJMoa020191. hdl:2066/185528. PMID 12167683.
  15. ^ Cornely OA, Maertens J, Bresnik M, Ebrahimi R, Ullmann AJ, Bouza E, et al. (May 2007). "Liposomal amphotericin B as initial therapy for invasive mold infection: a randomized trial comparing a high-loading dose regimen with standard dosing (AmBiLoad trial)". Clin. Infect. Dis. 44 (10): 1289–97. doi:10.1086/514341. PMID 17443465.
  16. ^ Denning DW, Park S, Lass-Florl C, Fraczek MG, Kirwan M, Gore R, Smith J, Bueid A, Bowyer P, Perlin DS (2011). "High-frequency Triazole Resistance Found In Nonculturable Aspergillus fumigatus from Lungs of Patients with Chronic Fungal Disease". Clin Infect Dis. 52 (9): 1123–9. doi:10.1093/cid/cir179. PMC 3106268. PMID 21467016.
  17. ^ Perea S, Patterson TF (November 2002). "Antifungal resistance in pathogenic fungi". Clin. Infect. Dis. 35 (9): 1073–80. doi:10.1086/344058. PMID 12384841.
  18. ^ Cornely OA, Maertens J, Winston DJ, Perfect J, Ullmann AJ, Walsh TJ, et al. (January 2007). "Posaconazole vs. fluconazole or itraconazole prophylaxis in patients with neutropenia". N. Engl. J. Med. 356 (4): 348–59. doi:10.1056/NEJMoa061094. PMID 17251531.
  19. ^ Anderson, Charles (2019-06-13). "World's fattest parrot, the endangered kākāpō, could be wiped out by fungal infection". The Guardian. ISSN 0261-3077. Retrieved 2019-06-13.

Further readingEdit

  • Latgé JP. "Aspergillus fumigatus and aspergillosis". Clinical microbiology reviews. 12 (2): 310–350. PMID 10194462. PMC 88920 (Review).
  • Sugui JA, Kwon-Chung KJ, Juvvadi PR, Latgé JP, Steinbach WJ. "Aspergillus fumigatus and related species". Cold Spring Harbor perspectives in medicine. 5 (2): a019786. doi:10.1101/cshperspect.a019786. PMID 25377144. PMC 4315914 (Review)

External linksEdit