| Aspergillosis | |
|---|---|
_invasive_type.jpg) | |
| Pulmonary invasive aspergillosis in a person withinterstitial pneumonia (autopsy material), usingGrocott's methenamine silver stain | |
| Pronunciation | |
| Specialty | Infectious disease |
| Complications | Bleeding, systemic infection[1] |
| Causes | Aspergillusfungal infection |
| Frequency | 14 million |
Aspergillosis is afungal infection of usually the lungs,[2] caused by the genusAspergillus, a commonmold that is breathed in frequently from the air, but does not usually affect most people.[3][4] It generally occurs in people withlung diseases such asasthma,cystic fibrosis ortuberculosis, or those who areimmunocompromised such as those who have had astem cell ororgan transplant or those who take medications such assteroids and somecancer treatments which suppress the immune system.[2][5] Rarely, it can affect skin.[5][6]
Aspergillosis occurs in humans, birds and other animals. Aspergillosis occurs in chronic or acute forms which are clinically very distinct. Most cases of acute aspergillosis occur in people with severely compromised immune systems such as those undergoingbone marrow transplantation.[7] Chronic colonization or infection can cause complications in people with underlying respiratory illnesses, such asasthma,[8]cystic fibrosis,[9]sarcoidosis,[10]tuberculosis, orchronic obstructive pulmonary disease.[11] Most commonly, aspergillosis occurs in the form ofchronic pulmonary aspergillosis (CPA),aspergilloma, orallergic bronchopulmonary aspergillosis (ABPA).[12] Some forms are intertwined; for example ABPA and simple aspergilloma can progress to CPA.
Other, noninvasive manifestations include fungalsinusitis (bothallergic in nature and with established fungal balls),otomycosis (ear infection),keratitis (eye infection), andonychomycosis (nail infection). In most instances, these are less severe, and curable with effectiveantifungal treatment.
The most frequently identified pathogens areAspergillus fumigatus andAspergillus flavus, ubiquitous organisms capable of living under extensive environmental stress. Most people are thought to inhale thousands ofAspergillus spores daily but without effect due to an efficient immune response. Invasive aspergillosis has a 20% mortality at 6 months.[13] The major chronic, invasive, and allergic forms of aspergillosis account for around 600,000 deaths annually worldwide.[10][14][15][16][17]
Afungus ball in the lungs may cause no symptoms and may be discovered only with a chest X-ray, or it may cause repeatedcoughing up of blood, chest pain, and occasionally severe, even fatal, bleeding.[2] A rapidly invasiveAspergillus infection in the lungs often causes cough, fever, chest pain, and difficulty breathing.[citation needed]
Poorly controlled aspergillosis can disseminate through the blood to cause widespread organ damage.[2] Symptoms include fever, chills, shock, delirium, seizures, and blood clots. The person may developkidney failure,liver failure (causingjaundice), and breathing difficulties.[2] 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.[18]
Aspergillosis is caused byAspergillus, a commonmold, which tends to affect people who already have a lung disease such ascystic fibrosis orasthma, or whocannot fight infection themselves.[3] The most common causative species isAspergillus fumigatus.[19]
People who areimmunocompromised—such as patients undergoinghematopoietic stem cell transplantation,chemotherapy forleukaemia, orAIDS—are at an increased risk for invasive aspergillosis infections. These people may have neutropenia or corticosteroid-induced immunosuppression as a result of medical treatments.Neutropenia is often caused by extremelycytotoxic medications such as cyclophosphamide.Cyclophosphamide interferes with cellular replication including that of white blood cells such asneutrophils. A decreased neutrophil count inhibits the ability of the body to mountimmune responses againstpathogens. Althoughtumor necrosis factor alpha (TNF-α)—a signaling molecule related to acute inflammation responses—is produced, the abnormally low number of neutrophils present in neutropenic patients leads to a depressed inflammatory response.If the underlying neutropenia is not fixed, rapid and uncontrolledhyphal growth of the invasive fungi will occur and result in negative health outcomes.[20] In addition to decreased neutrophil degranulation, the antiviral response againstFlu andSARS-CoV-2 viruses, mediated by type I and type IIinterferon, is diminished jointly with the local antifungal immune response measured in the lungs of patients with IAPA (Influenza-Associated Pulmonary Aspergillosis) and CAPA (COVID-19-Associated Pulmonary Aspergillosis).[21] COVID-19 patients with preexisting or newly diagnosed bronchiectasis are at particular risk of developing pulmonary aspergillosis.[22]
Normally themucociliary clearance mechanism of the airways of the lungs removes inhaled particles. However, in those with underlying lung diseases, such ascystic fibrosis orbronchiectasis, this mucociliary clearance mechanism is impaired and aspergillus spores (which are 2–5 μm in diameter) are able to colonize the airways and sinuses.[13]
Onchest X-ray and CT, pulmonary aspergillosis classically manifests as ahalo sign, and later, anair crescent sign.[24]In hematologic patients with invasive aspergillosis, thegalactomannan test can make the diagnosis in a noninvasive way. Galactomannan is a component of the fungal wall.[13] False-positiveAspergillus 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.[25][26]
Onmicroscopy,Aspergillus species are reliably demonstrated bysilver stains, e.g., Gridley stain orGomori methenamine-silver.[27] These give the fungal walls a gray-black colour. Thehyphae ofAspergillus species range in diameter from 2.5 to 4.5 μm. They have septatehyphae,[28] but these are not always apparent, and in such cases they may be mistaken forZygomycota.[27]Aspergillus hyphae tend to havedichotomous branching that is progressive and primarily atacute angles of around 45°.[27]
In those with suspected pulmonary aspergillosis,bronchoalveolar lavage can be done to collect fluid from the airways of the lungs for analysis. This involves exploration of the airway with abronchoscope, then the introduction of a small amount of fluid into the airway which is then collected for analysis. This analysis can include assessment of cells, galactomannan testing, staining and fungal culture as well aspolymerase chain reaction (PCR) assessment.[13] PCR has an 85% sensitivity and 76% specificity for the diagnosis of aspergillosis, sensitivity is increased when the test is combined with galactomannan testing.[13]
Allergic bronchopulmonary aspergillosis (ABPA) is diagnosed by establishing an immune sensitization to aspergillosis, which can be done by measuring totaleosinophils, totalimmunoglobulin E (IgE) and aspergillus specific IgE andIgG levels. Elevations of these markers, combined with clinical and radiologic findings suggesting infection are used to confirm ABPA.[13]
_invasive_type.jpg)
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.[29]N95 respirators are also effective at reducing mold inhalation.[30]
A systematic review has evaluated the diagnostic accuracy ofpolymerase chain reaction (PCR) tests in people with defective immune systems from medical treatment such as chemotherapy.[31] Evidence suggests PCR tests have moderate diagnostic accuracy when used for screening for invasive aspergillosis in high risk groups.[31] CT and MRI are vital to diagnosis, however it is always highly recommended to undergo a biopsy of the area to confirm a diagnosis.[32][33][34]
The current medical treatments for aggressive invasive aspergillosis includevoriconazole andliposomal amphotericin B in combination with surgicaldebridement.[35]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.[36]Other drugs used, such asamphotericin B,caspofungin (in combination therapy only),flucytosine (in combination therapy only), or itraconazole,[37][38]are used to treat thisfungal infection. However, a growing proportion of infections areresistant to the triazoles.[39]A. fumigatus, the most commonly infecting species, is intrinsically resistant tofluconazole.[40]
Aspergillosis is thought to affect more than 14 million people worldwide, with allergic bronchopulmonary aspergillosis (ABPA) infecting about 4 million, severe asthma with fungal sensitization affecting about 6.5 million, andchronic pulmonary aspergillosis (CPA) infecting about 3 million people, considerably more than invasive aspergillosis which affects about 300,000 people.[41] Other common conditions includeAspergillus bronchitis,Aspergillusrhinosinusitis, orotitis externa.[42][43]
During theCOVID-19 pandemic 2020/21,COVID-19-associated pulmonary aspergillosis was reported in some people who had been admitted to hospital and received longterm steroid treatment.[44]
While relatively rare in humans, aspergillosis is a common and dangerous infection in birds, particularly in petparrots.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.[citation needed]
In the United States, aspergillosis has been the culprit in several rapid die-offs among waterfowl. From 8 December until 14 December 2006, over 2,000 mallards died nearBurley, Idaho, an agricultural community about 150 miles southeast ofBoise. Mouldy waste grain from the farmland andfeedlots in the area is the suspected source. A similar aspergillosis outbreak caused by mouldy grain killed 500 mallards inIowa in 2005.[citation needed]
While no connection has been found between aspergillosis and the H5N1 strain ofavian 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.[citation needed]
In dogs, aspergillosis is an uncommon disease typically affecting only the nasal passages (nasal aspergillosis). This is much more common indolicocephalic 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.[citation needed]
In 2019, an outbreak of aspergillosis struck the rarekākāpō, 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.[45]
