TreatmentUpdate61; Volume 7, No. 7 - July 1995
Sean Hosein

The "most common life-threatening mould infection worldwide" is aspergillosis. It is a relatively serious complication seen in people with AIDS and others receiving:

+ chemotherapy for cancer + transplanted cells/tissues + corticosteroids (more than 10 mg/day)

* WHO GETS IT?

Although the mould tends to cause infections and complications in people with less than 100 CD4+ cells, cases have occurred in people with CD4+ cell counts greater. Among people with AIDS, there are a number of reports of people first having bacterial pneumonia or PCP followed by aspergillosis. It may be that these other infections weaken or damage the lungs and make it easier for the mould to infect and spread there (in the lungs).

* SYMPTOMS

Over 70% of cases of aspergillosis reported have occurred in the lungs, thus causing symptoms like:

+ cough + fever + [shortness of breath] + chest pain + [coughing up blood]

Chest X-ray pictures of the lungs usually suggest that there is an infection of some kind.

* DETECTING THE MOULD

In most cases, laboratories use fluid samples from patients to try and grow or culture the mould. Several teams are developing various detection kits to measure antibodies against the mould. To date, results from testing antibody kits have not been very useful. So other teams are working on developing tests that detect the fungus (or antigen) in blood samples. In some cases the results from these antigen tests have not been accurate. Thus diagnosis of pulmonary aspergillosis "can be difficult." As the mould is found worldwide, it can be detected in fluid samples from the lungs of healthy people. As one group of doctors cautioned, ``the "detection] of Aspergillus species from fluid samples in the lungs] does not automatically imply [that the mould is the cause of serious complications]." The mould can also infect other parts of the body such as the brain, heart and other organs. In the CNS (central nervous system) people can have a variety of problems such as bleeding, "fever and seizures or symptoms mimicking those with a stroke."

* TREATMENT

Recovery from aspergillosis in people with AIDS is not as rapid as in non-HIV-infected people.

- Amphotericin B

One research team suggests beginning with iv AmB, "starting with 0.8 to 1 mg/kg/day and [adjusting] the dose according to the [patient's] response or [symptoms of] toxicity." In cases of invasive aspergillosis, they suggest higher doses be used, between 1 and 4 mg/kg/day.

- Itraconazole

Treatment with itraconazole--600 mg/day for the first 4 days followed by "at least 400 mg/day [taken] with food." They recommend therapy for the rest of the person's life. As well, they also warn that absorption of itraconazole could be reduced if taken with drugs such as rifampin and Zantac.

- Itraconazole plus

In a more recent study, among 16 HIV-infected subjects with invasive aspergillosis, half did not improve despite use of itraconazole (in the dose and schedule used above). In a study in Japan, researchers have been performing laboratory experiments with the mould and antifungal drugs. They found that a combination of Aura, ketoconazole or fluconazole or itraconazole either had the same effect as AmB alone or had weaker antifungal effects. Treating the mould with alternating drugs (AmB followed by itraconazole) had greater antifungal effect than combination therapy. Clearly, better treatment regimens need to be developed.

REFERENCES:

1. Patterson TF, Miniter P. Patterson JE, et al. Aspergillus antigen detection in the diagnosis of invasive aspergillosis. Journal of Infectious Diseases 1995;171:1553-1558.

2. Denning DW, Lee JY, Hostetler JS, et al. NIAID Mycoses study group multicentre trial of oral itraconazole therapy for invasive aspergillosis. American Journal of Medicine 1994;97:135-144.

3. Khoo SH and Denning DW Invasive aspergillosis in patients with AIDS. Clinical Infectious Diseases 1994;19 (supplement 1):s41-s48.

4. Maesaki S, Kohno S, Kaku M, et al. Effects of antifungal agent combinations administered simultaneously and sequentially against aspergillosis fumigatus. Antimicrobial Agents and Chemotherapy 1994;38(12):2843-2845.

950701
CATE6109

Copyright © 1995 - TreatmentUpdate. Reproduced with permission. Reproduction of this article (other than one copy for personal reference) must be cleared through the Editor, The Canadian AIDS Treatment Information Exchange, 555 Richmond St. West, Suite 505, Box 1104, Toronto, ON, M5V 3B1 • Phone: 416-203-7122 • Toll Free: 1-800-263-1638 • Fax: 416-203-8284  http://www.catie.ca