Invasive aspergillosis usually only occurs in severely immunocompromised patients and has a high mortality rate (25-90%). Chances of living are improved the earlier a diagnosis is made, but unfortunately there is no good single diagnostic test. Often treatment must be administered when the condition is only suspected. Invasive disease is most commonly seen in the lungs, which is called pulmonary aspergillosis. Although less common, dissemination of Aspergillus to other tissues has been reported.
Presentation:
Invasive aspergillosis is usually clinically diagnosed in a person with low defences, such as bone marrow transplant, low white cells after cancer treatment, AIDS or major burns. There is also a rare inherited condition called chronic granulomatous disease (CGD) which causes low immunity and puts affected people at moderate risk. People with invasive aspergillosis usually have a fever and symptoms from the lungs (cough, breathlessness, chest pain or discomfort); these do not respond to standard antibiotics. X-rays and scans are usually abnormal and help to localise the disease. Bronchoscopy (inspection of the inside of the lung with a small tube inserted via the nose) is often used to help to confirm the diagnosis. Cultures and blood tests (especially antigen detection) are usually necessary to confirm the disease.
In people with particularly poor immune systems, the fungus can transfer from the lung into the blood stream, and infect the brain or other organs (including the eye, the heart, the kidneys and the skin). Usually this is a bad sign, as the condition has grown more severe and the patient will be sicker, with a higher risk of death. However, sometimes infection of the skin enables the diagnosis to be made earlier and treatment to be commenced sooner.
Treatment:
Treatment is with antifungal drugs, such as voriconazole, caspofungin, micafungin, itraconazole, amphotericin B, posaconazole or itraconazole. Voriconazole can be given orally or intravenously and is usually better than amphotericin B. It may require dose modification to maximise success, especially in children, those with liver disease or cirrhosis, and possibly the elderly. Some other drugs used for the treatment of tuberculosis or epilepsy can reduce the blood levels of voriconazole. Caspofungin and micafungin can only be given intravenously, and are also partially effective, especially in those with normal white cell counts. Caspofungin has been used as rescue therapy in combination with other antifungals, with reasonable success.
Amphotericin B must to be given intravenously in large doses. In some patients the treatment can damage the kidneys and other organs. Newer forms of amphotericin B (Amphotec or Amphocil, Abelcet or AmBisome) are useful, especially when the patient experiences side effects. These forms usually cause fewer adverse effects, especially less renal dysfunction. Posaconazole is a new potent oral antifungal drug given as a liquid; it is useful for preventing aspergillosis and in treatment. Itraconazole is generally given orally, although an intravenous preparation is now available. Itraconazole is often used for follow on therapy after intravenous treatment or to prevent infection. Resistance to itraconazole has become more frequent since 2004.
The earlier treatment is commenced, the better the chances of survival. In patients with low numbers of white blood cells (infection fighters), recovery of these cells can be important in preventing the growth of the fungus. Sometimes surgery is also required. Overall, more than half of patients survive invasive aspergillosis if treated; on the other hand, no one survives without treatment. All of these conditions can affect children and should be diagnosed and treated in the same way.
A lot of encouraging research is being performed at the moment to speed up the diagnosis of invasive aspergillosis and to improve its treatment.