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Table of Contents
Year : 2020  |  Volume : 17  |  Issue : 2  |  Page : 120-123

Aspergillus nidulans: A rare cause of brain abscess

1 Department of Microbiology, SN Medical College, Jodhpur, Rajasthan, India
2 Department of Microbiology, Dr. RML PGIMER, New Delhi, India
3 Department of Surgery, SN Medical College, Jodhpur, Rajasthan, India

Date of Submission14-May-2020
Date of Acceptance16-May-2020
Date of Web Publication18-Jun-2020

Correspondence Address:
Satya Prakash Jindal
Department of Surgery, SN Medical College, Jodhpur - 342 003, Rajasthan
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/am.am_34_20

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Fungal infections of the central nervous system (CNS) are rarely encountered, and their development largely depends on the interplay between the virulence factors of various fungi and host's immune system. Recently, there has been an increase in the number of organ transplants, chemotherapies, and human immunodeficiency virus infections due to which the incidence of fungal brain abscess has increased. Aspergillus species is the most common cause of fungal brain abscess and generally occurs in patients with hematological malignancies and cancer chemotherapy. More than 100 Aspergillus species are known, and among these, the most virulent one is Aspergillus fumigatus, but Aspergillus niger, Aspergillus flavus, and Aspergillus terreus (which is relatively amphotericin resistant) can also cause human disease. Aspergillus nidulans is a species of Aspergillus, which is more virulent than other species and has a high mortality rate. Here, we report a case of brain abscess in a 35-year-old young female caused by A. nidulans presenting with symptoms of cerebral mass effect. On potassium hydroxide examination, thin branched septate hyphae were seen, and culture showed the growth of A. nidulans. Given the complexity of the patients at risk and the diverse array of fungal pathogens, CNS fungal infection poses a considerable diagnostic and therapeutic challenge. Although outcome is frequently fatal in patients with fungal brain abscess, early diagnosis, and appropriate antifungal therapy may reduce morbidity and mortality.

Keywords: Aspergillus nidulans, brain abscess, central nervous system fungal infection, cerebral abscess, fungal brain abscess

How to cite this article:
Gupta AK, Parihar RS, Garg S, Jindal SP. Aspergillus nidulans: A rare cause of brain abscess. Apollo Med 2020;17:120-3

How to cite this URL:
Gupta AK, Parihar RS, Garg S, Jindal SP. Aspergillus nidulans: A rare cause of brain abscess. Apollo Med [serial online] 2020 [cited 2020 Jul 8];17:120-3. Available from: http://www.apollomedicine.org/text.asp?2020/17/2/120/287091

  Introduction Top

Brain abscess is a focal, intracerebral infection that begins as a localized area of cerebritis and develops into a collection of pus surrounded by a well-vascularized capsule. It accounts for approximately 8% of intracranial masses in developing countries and 1%–2% in the Western countries.[1] Most of the brain abscesses are either pyogenic or tubercular in origin. Fungal brain abscess is very rare and generally occurs as a severe complication of hematological malignancies and cancer chemotherapy.[2]

Aspergillus spp. is the most common cause of fungal brain abscess. Aspergillus nidulans is a species of Aspergillus, which is more virulent than other species and has a high mortality rate. Given the complexity of the patients at risk and the diverse array of fungal pathogens, central nervous system (CNS) fungal infection poses a considerable diagnostic and therapeutic challenge. Diagnosis depends on heightened clinical suspicion and obtaining appropriate material for culture.

Here, we are reporting a case of 35-year-old young female presenting with symptoms of the cerebral mass lesion and diagnosed as fungal abscess due to A. nidulans. Unfortunately, the patient could not be saved despite vigorous surgical and antifungal treatment.

  Case Report Top

A 35 years old Male presented in Mahatma Gandhi Hospital with a history of recurrent episodes of seizure over 1 month. Later on, she developed a pain abdomen and diagnosed with pyoperitoneum. She underwent laparotomy, and drainage of the pus was done along with peritoneal lavage. Medical history was negative for tuberculosis, bone marrow, and solid organ transplantation and malignancy. There was no history of steroid or other immunosuppressive drug consumption. Immunological tests, including immunoglobulin (Ig) levels (IgG, IgM, and IgA) as well as complete and differential blood counts, were within normal limits. Fasting blood sugar was 110 mg/dL. A serological test for HIV was negative. The chest X-ray was normal. There was no peritoneal or intestinal lesion for histological assessment, and pus culture was negative for bacterial growth. She got relieved from abdominal symptoms after surgery in the periphery. Postoperatively, she developed right-sided hemiparesis and referred to our institute.

At the time of presentation to our institute, the patient had altered levels of consciousness, right-sided hemiparesis, and increased frequency of seizures. Computed tomography (CT) head revealed a large abscess in the left cerebral temporo-parietal region with midline shift causing mass effect [Figure 1]. The patient underwent drainage of abscess under anesthesia. Pus sample collected intraoperatively was sent to the microbiology laboratory.
Figure 1: Contrast-enhanced computed tomography scan of the brain showing a well-defined abscess in the left temporoparietal region causing midline shift

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The microscopic examination of potassium hydroxide preparation showed numerous thin branched septate fungal hyphae [Figure 2]. Gram's stain preparation showed no bacteria but showed pus cells and hyaline, septate, and branched hyphae. A part of the pus sample was cultured on Sabouraud Dextrose Agar containing chloramphenicol (0.05 g/l) and cycloheximide (0.05 g/l), blood agar, and MacConkey agar. Both aerobic and anaerobic bacterial cultures were sterile. On 3rd day of incubation, whitish growth appears at both temperatures. Colonies became powdery to granular, dark green in color with dark purplish on the reverse. Lactophenol cotton blue preparation showed radiate to loosely columnar conidial heads bearing spherical, conidia. The central vesicles were pyriform-bearing biseriate metulae and phialides. Conidia were in chains at the tip of phialides. It was identified as Aspergillus species.
Figure 2: Potassium hydroxide preparation showed numerous thin branched septate fungal hyphae

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A slide culture was put on Czapek yeast agar showed hyaline, septate, branched hyphae bearing numerous conidial heads. The stripes were smooth walled, expanding into spathulate to pear-shaped vesicles, biseriate, metulae covering the upper half of vesicles. Phialides measured 4.5–8 μm × 2–3 μm. Conidia were in chains borne at the tips of phialides and were spherical. After 2 weeks, reddish-brown cleistothecia with surrounding spherical hulle cells were observed [Figure 3]. Cleistothecia were globose, dark red containing numerous asci. Ascospores were lenticular, reddish in color with longitudinal flanges. The isolate was identified as A. nidulans. Subsequently, amplification of the DNA and sequencing of the internal transcribed spacer region of ribosomal DNA confirmed the identification as A. nidulans.
Figure 3: Reddish-brown cleistothecia with surrounding spherical hulle cells

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Postoperatively, the patient was started on intravenous antifungal drugs amphotericin B along with other supportive treatment for the reduction of intracranial pressure based on the wet mount and Gram-staining result. However, the patient progressively deteriorated and succumbed to her illness, after 4 days of surgery.

  Discussion Top

Although intracranial abscesses are rare in developed countries, it still remains a significant health-care problem in developing countries. Despite diagnostic advancements with the introduction of CT, magnetic resonance imaging as well as better antimicrobial agents and neurosurgical procedures, brain abscess continues to be a serious, life-threatening condition. Invasive fungal infection affecting the CNS is a comparatively uncommon condition. This entity is usually seen in immunocompromised individuals and considered as an opportunistic infection. Although fungal infection of the CNS has been seen in immunocompetent patients but sparsely reported.[3]

The incidence of fungal infections of the CNS has increased in the past decade because of the growing number of immunocompromised patients who survive longer periods than in the past, widespread use of immunosuppressive drugs, a large aging population with increased numbers of malignancies, and the spread of AIDS.[4]

Frequently described risk factors for fungal brain infections are HIV/AIDS, hematopoietic stem cell transplant, lymphoid malignancies, neutropenia, hereditary immune defects, immunosuppressive medications, diabetes mellitus, intravenous drug abuse, and mechanical breakdown of the blood–brain barrier through surgery or trauma. Singh and Husain reported that recipients of bone marrow transplant were far more likely to have fungal brain abscess (5.2%) than solid organ transplant recipients (0.4%).[5]

The mechanism causing invasive infection with Aspergillus in immunologically competent hosts remains unclear. It is possibly caused by qualitative cellular or subcellular immunodeficiency that is either unrecognized or poorly characterized. Aspergillus spp. is the most common fungi causing brain abscess and usually manifests as mass effect causing the sudden neurological deficit. The mass lesion of the brain due to fungi occurs by either direct extension from the adjacent organ or hematogenous spread from a distant site. Direct extension of fungal infection commonly occurs from colonized paranasal sinuses or ear canal or by direct inoculation during a neurosurgical procedure.

Nosocomial aspergillosis is a life-threatening infection in immunocompromised patients and usually caused by the presence of Aspergillus spp. in air. Significantly, the higher concentration of Aspergillus spp. including A. nidulans is reported in the bathroom, where the use of water is highest. Water storage tanks yielded a higher concentration of Aspergillus spores than tap water.[6]

To establish the underlying cause of cerebral aspergilloma in our patient, we thoroughly reviewed his medical history data and the test results. The patient was remarkably well before presenting with neurological symptoms and no history suggestive of immunosuppressed state. He had no detectable paranasal sinus, lung, or any other organ involvement at the time of the clinical presentation of brain abscess. In contrast, cerebral aspergillosis arising from immunosuppression or malignancy is invariably associated with disseminated fungal disease. Although our patient was immunocompetent, and there was not any history of any comorbidity, but she belonged to the remote village area and may be exposed to these infectious fungal infections through the environment.

Aspergillosis should be considered as differential diagnosis, in cases presenting with acute onset of focal neurologic deficits and suspected vascular or mass lesion. Single or multiple abscess formation with blood vessel invasion and/or aneurysm formation are characteristic features of cerebral aspergillosis. Aspergillus hyphae can invade directly into the vessel wall, resulting in mycotic aneurysm formation.[7]

Conventional techniques including direct microscopy, histopathology, and culture of appropriate specimens remain the standard approach for the diagnosis of disseminated aspergillosis. Sequence analyses of the internal transcribed spacer region appear to be appropriate for the identification of Aspergillus isolates to the subgenus/section level. Partial β-tubulin or calmodulin are the most promising loci for Aspergillus identification to the species level.[8]

The management of cerebral fungal abscesses is controversial. Fungal brain abscess is associated with a very poor prognosis and high mortality. Mortality is reported to reach 100% in immunocompromised and 67% in immunocompetent hosts. The optimal treatment is surgical resection combined with antifungal therapy. Walsh et al. reported a case series of 17 cases, among them, only one patient can be survived with aggressive treatment. Few case reports show a good response with early introduction of voriconazole in fungal brain abscess. Therefore, an early and precise diagnosis may prove to be lifesaving in patients with the diagnosis of brain abscess.[9]

The main reason for drug ineffectiveness in cerebral aspergillosis is that CNS is a sanctuary site, and drug penetration is often inadequate. The penetration of drugs across the blood–brain barrier is mainly limited by their molecular size and physicochemical properties as well as drug interaction with transporter systems, such as P-glycoprotein at the blood–brain barrier. Most antifungal agents are large molecules (>700 Da), which makes sufficient penetration into the cerebrospinal fluid (CSF) and brain tissue unlikely, except for fluconazole and voriconazole.[10]

A. nidulans is an airborne hyaline mold found everywhere on various types of inanimate substrate, especially soil and water systems. This Aspergillus species have been reported as the cause of diverse infections in humans, including pulmonary or cerebral infections, sinusitis, endophthalmitis, osteomyelitis, eumycotic mycetoma, nail infections, and disseminated aspergillosis. There are very few cases of cerebral abscess reported due to A. nidulans in immunocompetent persons. Chakrabarti et al. reported cerebral aspergilloma caused by A. nidulans in two adult patients. Both patients were operated on and received systemic therapy with amphotericin B, but the infection proved fatal in both.[11]

The importance of identifying an infection as aspergillosis and then confirming the species is due to the variable antifungal susceptibility patterns among different species of Aspergillus. A. nidulans is frequently resistant to amphotericin as is Aspergillus terreus, and in the absence of species identification, it is important to consider these possibilities in the event of a poor response to amphotericin.

The increasing diversity of opportunistic hyaline molds and their differences in susceptibilities to antifungal agents make identification of the infecting isolate at the species level and determination of itsin vitro antifungal susceptibility profiles mandatory. Novel systems for the detection of circulating fungal cell wall markers and/or DNA in blood and other body fluids or in affecting tissues may improve the laboratory diagnosis of disseminated aspergillosis.[12]

Our results ofin vitro resistance to amphotericin B and susceptibility to voriconazole were comparable with the published data onin vitro activities of these antifungal agents for 13 worldwide clinical A. nidulans isolates from different body sites including brain/CSF.

  Conclusion Top

Brain abscess due to A. nidulans is a very rare and uncommon clinical entity in immunocompetent persons. Although outcome is frequently fatal in patients with fungal brain abscess, delay in the diagnosis also contributes to the high mortality. Early diagnosis, aggressive surgical procedures, and antibiotic therapy for fungal brain abscess may reduce morbidity and mortality.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Muzumdar D, Jhawar S, Goel A. Brain abscess: An overview. Int J Surg 2011;9:136-44.  Back to cited text no. 1
Pfaller MA, Diekema DJ. Rare and emerging opportunistic fungal pathogens: Concern for resistance beyond Candida albicans and Aspergillus fumigatus. J Clin Microbiol 2004;42:4419-31.  Back to cited text no. 2
Kim DG, Hong SC, Kim HJ, Chi JG, Han MH, Choi KS, et al. Cerebral aspergillosis in immunologically competent patients. Surg Neurol 1993;40:326-31.  Back to cited text no. 3
Murthy JM, Sundaram C, Prasad VS, Purohit AK, Rammurti S, Laxmi V. Aspergillosis of central nervous system: A study of 21 patients seen in a university hospital in south India. J Assoc Physicians India 2000;48:677-81.  Back to cited text no. 4
Singh N, Husain S. Infections of the central nervous system in transplant recipients. Transpl Infect Dis 2000;2:101-11.  Back to cited text no. 5
Anaissie EJ, Stratton SL, Dignani CM, Summerbell RC, Rex JH, Monson TP, et al. Pathologic Aspergillus species recovered from a hospital water system; a 3-year prospective study. Clin Infect Dis 2002;34;780-9.  Back to cited text no. 6
Marinovic T, Skrlin J, Vilendecic M, Vilendecic M, Rotim K, Grahovac G. Multiple Aspergillus brain abscesses in immuno-competent patient with severe craniofacial trauma. Acta Neurochir (Wien) 2007;149:629-32.  Back to cited text no. 7
Segal BH, DeCarlo ES, Kwon-Chung KJ, Malech HL, Gallin JI, Holland SM. Aspergillus nidulans infection in chronic granulomatous disease. Medicine (Baltimore) 1998;77:345-54.  Back to cited text no. 8
Walsh TJ, Hier DB, Caplan LR. Fungal infections of the central nervous system: Comparative analysis of risk factors and clinical signs in 57 patients. Neurology 1985;35:1654-7.  Back to cited text no. 9
Schwartz S, Thiel E. Cerebral aspergillosis: Tissue penetration is the key. Med Mycol 2009;47 Suppl 1:S387-93.  Back to cited text no. 10
Chakrabarti A, Marak RS, Singhi S, Gupta S, Hurst SF, Padhye AA. Brain abscess due to Aspergillus nidulans. J Med Mycol 2006;16:100-4.  Back to cited text no. 11
Dornbusch HJ, Groll A, Walsh TJ. Diagnosis of invasive fungal infections in immunocompromised children. Clin Microbiol Infect 2010;16:1328-34.  Back to cited text no. 12


  [Figure 1], [Figure 2], [Figure 3]


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