Cerebral Aspergillosis caused by Neosartorya hiratsukae, Brazil - Dispatches

Emerging Infectious Diseases, Sept, 2002 by Josep Guarro, Esper G. Kallas, Patricio Godoy, Anna Karenina, Josepa Gene, Alberto Stchigel, Arnaldo Lopes Colombo

We report the first case of infection by Neosartorya hiratsukae, an ascomycete in which the conidial state resembles Aspergillus fumigatus. The fungus caused a brain infection in a Brazilian woman, who died despite itraconazole treatment. Diagnosis was established by direct microscopic examination, computed tomographic scan, and magnetic resonance imaging of the brain, and repeated cultures from the lesions. The in vitro antifungal susceptibility of the isolate is provided.

**********

Aspergillus fumigatus is the most common filamentous fungus to cause opportunistic infections in humans. Two close relatives of A. fumigatus, classified in the ascomycetous genus Neosartorya, have been documented to cause occasional opportunistic infections (1). These species are N. fischeri and N. pseudofischeri. The former has been reported on two occasions as causing systemic infection in transplant recipients (2, 3), as well as a mixed pulmonary infection in a patient with myeloma (4). N. pseudofischeri has been reported to cause different localized and invasive infections (5-9). The conidial states of these species are morphologically very similar to that of A. fumigatus.

We describe the first cerebral infection caused by another species of Neosartorya, N. hiratsukae. This taxon has been described only in Japan, where it was isolated from air and from pasteurized aloe juice (10).

Case Report

A 75-year-old Brazilian woman was admitted to the Hospital do Servidor Publico Estadual de Sao Paulo on May 5, 1999, with progressive memory loss, confusion, and involuntary movements in the upper right arm after a fall 1 year earlier. She had also developed gait disorder, with short steps and constant loss of balance that led to a diagnosis of Parkinson's disease in a neurology consultation in March 1999; however, the condition did not respond to the usual treatment. On April 30, a computed tomographic (CT) scan of the brain showed multiple lesions in both brain hemispheres, after which the patient was referred to the hospital. Past clinical history showed an evaluation of productive cough in 1996, with bloody sputum, night sweats, and intermittent fever; she underwent bronchoscopy with pathologic examination, which showed vascular congestion and focal intra-alveolar edema, but no specific pathogen was identified.

On examination, the patient appeared chronically ill, mildly pale, disoriented, and confused, although she was able to follow simple commands. The lungs had decreased sounds in both lower thirds, with rales. The upper arms moved slowly and repetitively, with a loss of strength. Tendon reflexes were normal. The patient underwent surgical exploration, with drainage of the frontal and occipital lesions. Four samples of a yellowish, dense liquid were collected. Laboratory examination did not show neoplastic cells or neutrophils in the liquid. Direct microscopic examination showed septate hyphae in all the samples. Cultures were negative for aerobic and anaerobic bacteria and mycobacteria, and two samples were positive for a fungus, tentatively identified as Aspergillus sp. The patient was initially treated for 21 days with ceftriaxone, oxacillin, and metronidazole without major improvement. When the fungus was isolated, she was treated with amphotericin B and underwent postdrainage magnetic resonance imaging (MRI) of the brain, which showed multifocal brain abscesses, including subtentorial and supratentorial lesions (Figure 1). A chest x-ray and a CT scan of the thorax showed a small, bilateral pleural effusion and a left pulmonary cavitary lesion. Left pleural drainage obtained 80 mL of a clear yellow pleural effusion with pH 7.5, 19,870 leukocytes/mL and 970 erythrocytes/mL, with negative cultures for mycobacteria, aerobic and anaerobic bacteria, and fungi. Refractory hypokalemia developed after the patient received a total dose of 1 g of amphotericin B, which led to discontinuation of this drug. A course of itraconazole (400 mg/day) was initiated.

[FIGURE 1 OMITTED]

On the first day of itraconazole therapy, another MRI of the brain was performed, which showed an increase in the volume of the abscesses. During the next few days, the patient's mental state worsened, and she had another cerebral drainage 8 days later. A yellowish opaque liquid, with a white granular deposit, was obtained from the frontal and parietal abscesses. A cerebral fragment was obtained for analysis, which showed only reactional brain tissue. All cultures were negative for bacteria but positive for the same fungus that had been isolated previously. Her clinical and neurologic status improved, and she was discharged to a nursing home on July 20, 1999; itraconazole (400 mg/day) treatment was continued.

The patient was again admitted to the hospital on August 8, and she stayed for 21 days after being diagnosed with urinary sepsis caused by Escherichia coli. She was successfully treated with intravenous ceftriaxone. Her neurologic condition had been stable since her previous hospital discharge. She was last seen at the outpatient clinic on September 29, with an unchanged neurologic condition. During the hospital stay, another MRI of the brain showed a decrease in the size of all lesions, which was interpreted as a good response to the itraconazole therapy. Because of the difficulties of maintaining home care, she was admitted to another nursing hospital. Her clinical state deteriorated, and she died in November 1999 from multiple organ failure. Clinical information on this last hospital admission is very limited, and a postmortem examination was not performed.