Exposure to Aspergillus is universal, but aspergillosis is uncommon unless drugs, infection, or malignancy have altered the host immune defenses. The disease usually occurs in transplant recipients or in patients with hematologic malignancies, when phagocytic host defenses by granulocytes and macrophages are quantitatively or functionally suppressed.
Despite the severe immunosuppression that results from advanced HIV infection, there are relatively few cases of aspergillosis in patients with HIV disease.(1) Data analyzed from the Adult and Adolescent Spectrum of HIV Disease (ASD) project revealed 228 cases of aspergillosis among 35,252 HIV-infected persons, yielding an overall incidence of 3.5 cases per 1,000 person-years.(2) The incidence of aspergillosis was significantly higher among people >=35 years old, men who have sex with men (MSM), and in the setting of white blood count <2,500 cells/µL, CD4 count <100 cells/µL, prior history of an opportunistic infection, and prescribed medications associated with neutropenia.
In patients with AIDS, aspergillosis most commonly affects the lungs with a variety of distinct manifestations, including thick-walled cavitary disease of the upper lobes, diffuse unilateral or bilateral infiltrates, ulcerative tracheobronchial disease, and obstructive bronchitis. Other sites affected much less commonly are the blood, sinuses, skin, ear, bone, brain, and heart. The diagnosis often is made only postmortem and relies on the histologic or microbiologic identification of the fungus in infected tissue. Pulmonary involvement in patients with a compatible clinical presentation can be documented most reliably by bronchoalveolar lavage. Patients with advanced HIV disease and Aspergillus infections generally are treated with amphotericin B, caspofungin, voriconazole, or itraconazole. The relative effectiveness of these drugs has not been established, and despite antifungal therapy, the median survival in AIDS patients with invasive aspergillosis (IA) is 3 months, with only 26% surviving >1 year.(2)
Aspergillus species are ubiquitous throughout the world. The fungus commonly grows in decaying vegetation and soil. Exposure to the fungus occurs through the inhalation of spores. Although more than 300 species of Aspergillus exist, the literature implicates only a few as causes of human disease. A fumigatus causes the most severe disease in humans and is found in >90% of infections.(3) Other important pathogens include A niger and A flavus.
The major portal of entry for infection is the respiratory tract. The small, airborne spores of Aspergillus reach the bronchial tree, including the alveoli, where the fungus establishes colonization, and, in the immunocompromised patient, can initiate invasive disease. Hyphae may invade blood vessels, resulting in vascular inflammation with thrombosis, necrosis, and hemorrhage--histopathologic hallmarks of invasive disease. Aspergillus may colonize and grow in bronchi, cysts, or cavities caused by previous infections such as tuberculosis. In patients with invasive disease, epithelioid cells and, in areas of abscess formation, multinucleated giant cells surround hyphae.
Host defense against infection depends primarily on phagocytic cells--granulocytes and alveolar macrophages. As with other invasive fungi, severe immunosuppression with prolonged neutropenia, high-dose corticosteroid use, and possibly broad-spectrum antibiotic therapy constitute the major risk factors for Aspergillus infection. Previous episodes of pneumonia due to other opportunistic pathogens, particularly Pneumocystis jiroveci, Streptococcus pneumoniae, cytomegalovirus, and mycobacteria are risk factors for pulmonary aspergillosis in patients with advanced HIV disease.(1,4-6)
The relative paucity of Aspergillus infection in the setting of HIV disease is probably because relatively intact phagocytic cell function accompanies the T-cell dysfunction in these patients. In keeping with this hypothesis, more than half of the patients with AIDS who develop IA have either neutropenia, usually secondary to ganciclovir, or corticosteroid treatment as additional risk factors.(6) Nevertheless, some patients with IA have no such risk factors, and this observation, combined with the fact that aspergillosis typically occurs in the setting of advanced HIV infection with <50 CD4 cells/µL, indicates that HIV infection may represent an independent risk factor for IA.(2,5,6)
| Clinical Presentation|
| Pulmonary Aspergillosis Syndromes|
Aspergillus species produce a spectrum of pulmonary disease, which can be grouped into 3 clinical syndromes--allergic bronchopulmonary aspergillosis, Aspergillus mycetoma or fungal ball, and IA. The immune status of the infected host largely determines the particular presentation.(7)
| Allergic Bronchopulmonary Aspergillosis|
Allergic bronchopulmonary aspergillosis (ABPA) occurs in persons with a history of asthma and atopy and is characterized by the allergic response of the host to the fungus, which colonizes the tracheobronchial tree without evidence of invasion. Wheezing, eosinophilia, pulmonary infiltrates, and bronchial plugging are all manifestations of ABPA. The disease responds to treatment with corticosteroids and itraconazole.
| Mycetoma or Fungal Ball|
This infection usually is a result of fungal colonization of a preexisting cavity. Infection is localized to the cavity and rarely disseminates. Complications are caused mainly by the underlying disease process responsible for the pulmonary cavity formation (eg, tuberculosis), and are limited largely to bleeding and secondary bacterial infection.(7)
| Invasive Aspergillosis|
IA usually occurs in the setting of severe immunosuppression and presents as a fulminant disease with high fevers, pulmonary consolidation, and hematogenous dissemination. Four types of IA have been described: 1) acute or chronic pulmonary aspergillosis; 2) tracheobronchitis and obstructive bronchial disease with various degrees of invasion of the mucosa and cartilage as well as pseudomembrane formation, seen predominantly in patients with AIDS; 3) acute invasive rhinosinusitis; and 4) disseminated disease frequently invading the brain (more common in bone marrow transplant patients) and other organs.(3) Uncommon manifestations of Aspergillus infection include endocarditis, sinusitis, endophthalmitis, osteomyelitis, esophagitis, necrotizing skin ulcers, meningitis, and brain abscesses.(8) These extrapulmonary forms of infection are seen almost exclusively in the severely neutropenic patient.
| Aspergillosis in Patients with Advanced HIV Disease|
Aspergillus infections are relatively uncommon in patients with advanced HIV disease.(2,9,10) Most Aspergillus infections occur in patients with preexisting or coexisting opportunistic infections rather than as isolated fungal infections. Aspergillosis does not fulfill the U.S. Centers for Disease Control and Prevention (CDC) criteria for being an AIDS-defining illness. Furthermore, as stated previously, the majority of patients with advanced HIV disease and aspergillosis have neutropenia or other risk factors.(11)
| Pulmonary Involvement|
The lung is the most common site of IA in patients with advanced HIV disease.(6,11) Reports have described several forms of invasive pulmonary aspergillosis and a syndrome of bronchial obstructing aspergillosis, whereas the ABPA and intracavitary aspergillomas described in non-HIV-infected patients do not appear to play an important role in patients with advanced HIV disease.(9,11-13)
In invasive pulmonary disease, symptoms include fever, dyspnea, cough, chest pain, and hemoptysis. In approximately one third of patients, chest radiographic findings include thick-walled cavities, most commonly in the upper lobes.(6,14) These cavities represent pulmonary infarcts or abscesses.(14) Approximately 20% of patients have either unilateral or bilateral diffuse or nodular infiltrates.(5,14,15) Involvement of the bronchial tree can be invasive, leading to a pseudomembranous tracheobronchitis associated with extensive bronchial hemorrhage and invasion of the bronchial walls and vessels.
A syndrome of noninvasive, obstructing bronchial aspergillosis, in which fungus plugs obstruct the bronchi, can lead to breathlessness, cough, and chest pain.(6,9) The symptoms in these patients resemble ABPA (see previous discussion). Chest radiographs show hazy infiltrates reflecting segmental or lobar atelectasis, and bronchoscopy or postmortem examination reveal extensive plugging of bronchi and smaller airways by large mucoid casts containing fungal masses. Empyema or pleural masses are rare.(6)
In a small observational cohort study conducted in Spain, investigators identified 19 of 1,605 HIV-infected individuals with invasive pulmonary aspergillosis, yielding an incidence rate of 1.12%.(16) Ninety-five percent of the subjects had AIDS. Unilateral cavitary disease was present radiographically in 37%. Median survival was 148 days with 37% surviving >1 year. Median survival was 906 days in patients on potent antiretroviral therapy (ART) or in those for whom this therapy was modified after diagnosis of aspergillosis, which is a marked increase when compared with the median survival of 86 days for those who never initiated ART. At the time this study was published in 2000, 16% of the patients were still alive after a mean time of 36 months. This suggests that antifungal therapy in conjunction with combination ART may improve the outcomes of aspergillosis associated with HIV.(16)
| Extrapulmonary Involvement|
Extrapulmonary aspergillosis involving the central nervous system (CNS) is quite uncommon. CNS aspergillosis may present as focal abscesses or hemorrhagic or mycotic aneurysms.(1,6) CNS involvement may manifest with focal neurologic deficits and other signs attributed to an intracranial mass lesion.(3) In a review of 33 cases, the most common presenting symptoms were nonspecific, including headache, cranial or somatic nerve weakness or paresthesia, altered mental status, and seizures.(17) The most common sites of additional involvement with Aspergillus were the lung, sinuses, ears, eyes, and orbits. Of note, most of the CNS cases were a result of direct extension from the sinuses, ears, or eyes rather than hematogenous spread from the lung as more commonly seen among individuals with hematologic malignancies.(17) The CNS site was the only site infected with Aspergillus in one fourth of the cases reviewed. The final diagnosis of aspergillosis was made at autopsy in more than half of the cases, and antifungal therapy was ineffective for all cases. Eighty percent of sinusitis secondary to fungal infections is due to Aspergillus. Other unusual manifestations in patients with advanced HIV disease include endocarditis and myocarditis, esophagitis, lymphadenitis, musculoskeletal and skin abscess, liver and spleen involvement, and renal and pancreatic abscesses.(6,8,15,18,19)
IA, despite its rarity, should be included in the differential diagnosis of patients with advanced HIV disease and pulmonary or systemic signs of illness. Clinicians should collect appropriate specimens (sputum, blood, bone marrow, organ tissue) based on the patient's symptoms. Specimens should be examined by microscopy and cultured for fungi. The fungus can be difficult to detect by both microscopy and culture, however, and in most cases, the diagnosis is not made before death.(6)
The definitive diagnosis of Aspergillus infection requires both microscopic invasion seen in tissue and isolation of the organism by culture. Microscopy alone cannot distinguish Aspergillus species from Fusarium species or Pseudallescheria species.
Because Aspergillus species are ubiquitous, growth of aspergilli in a specimen culture may not reflect actual disease. Whereas a positive sputum culture from a normal host may have no clinical significance, a positive culture of sputum or nasal secretion from a neutropenic, febrile patient must be treated as indicating invasive disease. For the same reason, invasive infection should be suspected if Aspergillus grows in a culture of sputum from patients with advanced HIV disease and consistent respiratory symptoms, especially if the culture grows A fumigatus.(3,20)
In one study, Aspergillus was cultured from the sputum of 45 patients with advanced HIV disease, but only 5 had invasive disease.(21) In a separate study of 40 AIDS patients with cultures of Aspergillus species, 24 of the cultures represented colonization.(22) This finding suggests that detection of Aspergillus by sputum culture, even in patients with advanced HIV disease, is not equivalent to documenting invasive disease requiring antifungal therapy.
To complicate matters further, only 10-30% of patients with invasive pulmonary aspergillosis have positive findings on sputum culture. Cultures of bronchoalveolar lavage fluid, however, are positive in most patients with advanced HIV disease with pathologically proved invasive pulmonary aspergillosis.(5,9) Hyphae in a transbronchial biopsy specimen indicate invasive disease. The fungus is rarely cultured from blood, cerebrospinal fluid, bone marrow, or other organs (brain, kidneys, liver). Isolation of Aspergillus from blood must be considered indicative of invasive disease if the patient has a clinical history and presentation compatible with IA or if the fungus is isolated from another site. Laboratory contamination has become less common with the introduction of closed blood culture collection systems.
Much controversy, however, surrounds the methods for diagnosing most invasive fungal infections, as there are often shades of uncertainty in disease definition. As a result, an international consensus was reached in 2002 whereby a combination of host factor, mycological evidence, and clinical features are used to express disease certainty on a spectrum from proven to probable or possible. Currently, the agreement applies to clinical research involving patients with cancer and hematologic stem cell transplants, but is expected to affect the stratification of patients with HIV who are included in clinical trials.(23)
As stated above, it is difficult to distinguish aspergilli from other fungi. The implications of this are mainly clinical in that Fusarium and Pseudallescheria may not respond as well to amphotericin B. Therefore, there has been much interest in developing improved molecular or immunohistochemical techniques to assist in the diagnosis. Both monoclonal and polyclonal antibodies have been of limited use due to their cross-reactivity among various fungal species; however, there has been preliminary evidence that monoclonal antibodies may be more specific.(24,25) Another possible technique under investigation is the enzyme-linked immunosorbent assay (ELISA) for detecting galactomannan polysaccharides, a component of the fungal cell wall that is released into the circulation during fungal growth. The ELISA was approved by the U.S. Food and Drug Administration (FDA) in 2003 to allow earlier detection of Aspergillus infection in patients with malignancy or "immune systems compromised by illness."(26) In a study comparing DNA polymerase chain reaction (PCR) for Aspergillus with the ELISA for galactomannan among 44 patients with pulmonary aspergillosis, the PCR was positive in 31 of 33 patients with aspergilloma, all 4 patients with invasive pulmonary aspergillosis, 3 of 4 patients with Aspergillus pyothorax, and 1 of 4 with ABPA, compared with the ELISA, which was positive in only 21 of 33 aspergilloma patients and in none of the pyothorax or ABPA patients.(26) All 4 of the patients with invasive pulmonary aspergillosis had a positive ELISA. All samples from 39 patients without aspergillosis showed negative results in both the PCR and ELISA tests, suggesting that both assays may be useful for their negative predictive value. A subsequent study performed on cancer patients revealed similar findings with the PCR assay, suggesting a high negative predictive value and high specificity but poor sensitivity and positive predictive value.(27) All data available about the performance of PCR and ELISA have been obtained from patients with hematologic malignancy, bone marrow transplant, or solid organ transplant. A recent metaanalysis indicates that the performance of the ELISA varies widely across populations.(28) In a recent study comparing DNA PCR for Aspergillus with the ELISA for galactomannan among 5 patients with hematological malignancies and proven or probable IA by international consensus criteria, sensitivity for PCR and ELISA were 100% and 60%, respectively, with specificities of 85% and 95%, respectively. The negative predictive values for PCR and ELISA were 100% and 80%, respectively.(29) Many other studies conducted among patients with hematological malignancies also suggest that PCR has better sensitivity, whereas ELISA has better specificity. In this sense, using both assays may be helpful in improving negative predictive value. However, there are insufficient data at this time regarding the utility of these molecular techniques on samples obtained from HIV-infected subjects with aspergillosis.
Because experience in treating Aspergillus infections in patients with HIV disease is minimal, treatment generally follows recommendations for invasive disease in other immunosuppressed patients. The length of therapy is not fixed and depends on the clinical response.
| Amphotericin B|
Amphotericin B at a dosage of 1 mg/kg daily has been the treatment of choice for most forms of IA, regardless of the cause of the underlying immunosuppression. Overall, therapeutic responses have been less than optimal, particularly in patients with advanced HIV disease.(9) Amphotericin B in combination with flucytosine has been used in non-HIV-infected patients.(10) No study, however, has carefully compared amphotericin B with amphotericin B plus flucytosine in HIV-infected patients. There are 3 commercially available lipid-based formulations of amphotericin B: amphotericin B lipid complex, amphotericin B colloidal dispersion, and liposomal amphotericin B.(30) It is beyond the scope of this chapter to discuss in depth the differences among the 3 preparations. Extensive studies have been performed in the oncology field but very little data are available on the use of these formulations in HIV patients with aspergillosis. There have been conflicting data about which formulation appears to be the least nephrotoxic, although there is a trend favoring liposomal amphotericin B.(31-33) In addition, there has been one study demonstrating less toxicity and improved survival in HIV-infected patients with histoplasmosis treated with liposomal amphotericin B compared with those treated with conventional amphotericin B.(34) The applicability of these results to HIV-infected patients with aspergillosis is unclear.
Caspofungin inhibits the synthesis of beta-(1,3)-D-glucan, which is an essential component of the cell wall in Aspergillus species. Beta-(1,3)-D-glucan is not present in mammalian cell walls. Therefore, the toxicity that is associated with amphotericin B (which binds to sterols) is not seen with caspofungin in humans. Caspofungin is well tolerated with infrequent reports of histamine-mediated symptoms.
Caspofungin is given intravenously as a single 70-mg loading dose followed by 50 mg intravenously daily. In patients not clinically responding to caspofungin, the dosage may be increased to 70 mg daily, provided there are no contraindicating factors such as liver disease or concurrent administration of cyclosporine A. Dosage reduction to 35 mg is recommended in patients with moderate liver dysfunction. Caspofungin is not a substrate for P-glycoprotein and is a poor substrate for cytochrome P450 enzymes. Significant effects of caspofungin on antiretroviral drug concentrations therefore are not expected. However, when caspofungin is coadministered with inducers of hepatic metabolism, such as efavirenz and nevirapine, an increase in the daily dosage of caspofungin to 70 mg should be considered.(35)
Caspofungin was approved by the FDA for the treatment of IA in patients who are intolerant of or refractory to other antifungal agents. Caspofungin is not approved as first-line therapy for aspergillosis. There are no published studies on the effectiveness of caspofungin as a primary therapy in aspergillosis; however, preliminary data presented to the FDA indicated that clinical improvement or complete response occurred in 41% of patients with IA who were either intolerant of or refractory to amphotericin B or lipid preparations of amphotericin B.(36-38) In a randomized, double-blind trial comparing amphotericin B with caspofungin in the treatment of oral and esophageal candidiasis (98% of participants were HIV infected), the efficacy between the 2 arms was similar, with a trend favoring improved clinical response and significantly less toxicity in the caspofungin arm.(39)
Other echinocandins currently being investigated include micafungin and anidulafungin. One of the potential uses of these echinocandins is the ability to combine them with an azole antifungal (either voriconazole or itraconazole) or with amphotericin B to target 2 different aspects of fungal metabolism: caspofungin echinocandins inhibiting synthesis of the cell wall, and the azole or amphotericin B inhibiting synthesis of the cell membrane.(40) Studies evaluating triazoles in concert with echinocandins in neutropenic animal models have shown reduced mortality rates and decreased fungal burden when compared with either drug alone.(41,42)
The azoles are attractive in comparison with amphotericin B because they can be administered orally and have fewer adverse effects. Among the azoles, itraconazole and voriconazole appear to have the best activity against Aspergillus.
A multicenter open-label prospective study with strict entry criteria for IA enrolled and evaluated 76 patients with various underlying conditions.(21) Of the 76 individuals, 16 had AIDS. Patients were evaluated at 12 weeks, and at the end of treatment with itraconazole 600 mg daily for 4 days, followed by 400 mg daily. Duration of therapy for all patients varied from 0.3 to 97 weeks with a median of 46 weeks. Responses were categorized as "complete," "partial," "stable," or "failure." Thirty patients (39%) had a complete or partial response. At 12 weeks, however, none of the 16 patients with AIDS had a complete response; only 2 had a partial response and 7 were considered stable. At the end of treatment, none of the 16 had a partial or complete response or were considered stable.
The "failure" category was further categorized as "itraconazole failure" (defined as progressive disease necessitating a change in antifungal therapy, or death due to aspergillosis) and "failure for other reasons" (defined as toxicity terminating therapy, inability to take oral medication, and death due to other causes, but with persistent aspergillosis). Overall, 26% (20 of 76) were itraconazole failures, and 40% (30 of 76) failed for other reasons. Of the 16 patients with AIDS evaluated at 12 weeks, 4 were itraconazole failures, and 3 failed for other reasons. At the end of treatment, 44% (7 of 16) were itraconazole failures, and 56% (9 of 16) failed for other reasons. The authors of the report suggest that the overall failure and response rates are similar to those reported for amphotericin B.
No comparative trials of itraconazole with amphotericin B have been performed. A critical factor with itraconazole is the need for adequate serum concentrations, and it appears that serum concentrations below 7 mmol/L are not effective.(10) Relatively low serum levels of itraconazole are found in patients with advanced HIV disease compared with patients without HIV infection. Both decreased stomach acidity and drugs inducing the P450 enzyme systems (eg, rifampin) lead to substantially lowered serum levels, and in these patients, itraconazole levels should be monitored.(6) Bioavailability of itraconazole may be improved by using the liquid or intravenous formulation.
Voriconazole is structurally similar to fluconazole, but includes an additional fluoropyrimidine group and a methyl group that broaden its antifungal activity to include Aspergillus and Fusarium species but not the Zygomycetes. Voriconazole is well absorbed and has a high bioavailability of 96%. This allows switching between the intravenous and oral formulations. The clinical studies used a 2-dose loading regimen of either 400 mg or 6 mg/kg intravenously twice on the first day followed by a maintenance dosage of 200 mg orally twice daily. Voriconazole was FDA approved and available for use in July 2002. The FDA only recommends voriconazole for use in disseminated aspergillosis based primarily on the results of a trial evaluating the efficacy of voriconazole compared with conventional amphotericin B in the treatment of definite or probable IA in immunocompromised subjects, including a few subjects with HIV.(43) A total of 391 patients were enrolled but 114 did not fulfill the criteria of definitive or probable IA, and in the final analysis a total of 277 subjects were evaluated (144 on voriconazole, and 133 on amphotericin B). Most subjects had pulmonary aspergillosis. Twenty-one subjects on voriconazole and 16 subjects on amphotericin B had extrapulmonary aspergillosis. At 12 weeks, 52.8% of the patients on voriconazole had clinical success compared with 31.6% of the patients randomized to amphotericin B (intention-to-treat analysis). Seventy-one percent of subjects on the voriconazole arm survived through day 84 compared with 58% of subjects on the amphotericin B arm.
There are insufficient data at this time to routinely recommend the use of voriconazole over itraconazole. Voriconazole may be preferred over itraconazole when it is difficult to achieve therapeutic itraconazole levels by oral administration and voriconazole may have fewer potential drug interactions. Although there were no significant interactions reported between voriconazole and indinavir, other protease inhibitors and nonnucleoside reverse transcriptase inhibitors are known inhibitors and/or inducers of CYP3A4, and the clinical significance of an in vivo interaction with voriconazole currently is unknown. Therefore, the potential for significant drug interactions with voriconazole poses a challenge for the pharmacist and clinician. The most common adverse effects observed were increase in liver function tests and reversible visual disturbances. Another potential application for voriconazole is use in combination with caspofungin for the treatment of life-threatening infections such as IA. Although there is a theoretical concern of antagonism between azoles and amphotericin B based on potentially competitive mechanisms of action, there is no such concern regarding the combination of voriconazole and caspofungin. The new triazoles posaconazole and ravuconazole, currently in phase III and phase II clinical trials, respectively, may have a broader spectrum and greater clinical efficacy. Ongoing studies are evaluating this combination and it may ultimately displace amphotericin B as the "default" antifungal.
| Granulocyte-Macrophage Colony-Stimulating Factor|
Anecdotal reports suggest that granulocyte-macrophage colony-stimulating factor (GM-CSF) may have an adjuvant role in the treatment of systemic mycoses.(44) GM-CSF is a polypeptide hormone that reduces the duration of neutropenia by promoting the proliferation and differentiation of myeloid-committed progenitors. Tissue macrophages may be the sole defense against fungal infection in neutropenic patients. GM-CSF not only increases the absolute number of macrophages capable of ingesting organisms but also increases the number of organisms that each macrophage can ingest. However, no formal study of the adjunctive use of GM-CSF in combination with antifungal agents for the therapy of aspergillosis in AIDS patients has been published.
| Other Treatment Options|
Other investigational therapeutic options for aspergillosis include pradimicin,(45,46) echinocandins and pneumocandins.(47) Intranasal and aerosolized amphotericin B may be of prophylactic benefit to reduce nasal carriage in patients with prolonged neutropenia,(48) but have not been shown to decrease mortality in patients with hematologic malignancies who are at risk for IA.(49)
IA usually occurs in patients with advanced HIV disease and it is difficult to diagnose and treat. Even when the diagnosis is made antemortem and appropriate therapy is instituted, the long-term prognosis is poor, with a mean survival of 2 to 4 months. Death occurs either from uncontrolled aspergillosis and its complications or from other complications of AIDS. In the cavitary form of invasive pulmonary aspergillosis, fatal hemoptysis is responsible for the death of a substantial proportion of patients.(4) It remains unclear whether ART will have a major impact on the morbidity and mortality of aspergillosis; however, it would appear prudent to treat all HIV-infected patients aggressively with both ART and appropriate antifungal therapy. Liposomal amphotericin B or the combination of caspofungin and voriconazole should be considered, given the lower risk of adverse effects and less potential for drug interactions in patients with refractory IA.
Construction sites in hospitals and contaminated air-conditioning systems can increase the risk for nosocomial infection with Aspergillus.(50,51) A nosocomial outbreak affecting 5 AIDS patients has been reported in which false ceilings in a hospital ward were handled during their hospitalization.(52) Given the widespread distribution of Aspergillus species, it is impossible to prevent HIV-infected patients from being exposed to the organism; however, precautions should be taken on hospital wards to limit the exposure of AIDS patients to Aspergillus. Active prophylaxis of the infection appears an elusive goal. Whether surveillance cultures of nasal secretion are useful in prospectively predicting future development of invasive disease in HIV-infected patients, as suggested for leukemic patients, is unknown.(53)
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