Fatal Cerebral Phaeohyphomycosis in an Immunocompetent Individual Due to Thielavia subthermophila

Abstract

We report the first case of fatal brain infection in an Indian farmer caused by Thielavia subthermophila, a dematiaceous thermophilic fungus in the order Sordariales, and present a review of previous infections from this order. The patient failed amphotericin B therapy combined with surgical excision despite the drug's low MICs in vitro. CASE REPORTA 39-year-old male presented in the Emergency Department of Government Medical College Hospital (GMCH), Chandigarh, India, with complaints of multiple episodes of generalized tonic-clonic seizures for the previous 10 days. He experienced, in addition to the seizures, uncontrolled movements of his limbs and rolling of his eyes, incontinence of urine, and production of foam from his mouth. There was a history of fever for 2 days, associated with an attack of seizures. He was a resident of Ambala (Haryana State, northern India) and a farmer by occupation, with a low socioeconomic status. He was first admitted to a local hospital in Ambala and was subsequently transported to the GMCH. In the past, he never had headaches or any other significant complaints. There was no history of any trauma, roadside accidents, near-drowning, or similar predisposing factors.On examination, the patient was having an altered sensorium and was disoriented, with a Glasgow coma score of E2V2M4. On the basis of generalized tonic-clonic seizures, a presumptive diagnosis of meningioma was made. His chest X ray and electrocardiogram (ECG) were normal. A lumbar puncture was done, and cerebrospinal fluid (CSF) was sent for cytological, biochemical, and microbiological examination. Gram staining, Ziehl-Neelsen (ZN) staining, and fungal smears of CSF were negative, and there was no growth of either bacteria or fungi. The cytological and biochemical examination of CSF was noncontributory. The other laboratory investigations revealed that his hemogram, white blood cells, serum electrolytes, liver function, and glucose concentration were within normal ranges.A magnetic resonance image (MRI) of his brain showed a large, supratentorial, intracranial, right-frontotemporal, spaceoccupying lesion (7.0 by 7.5 by 8.6 cm) and also small components devoid of frank edema alongside the frontal part of the falx cerebri, suggestive of meningioma in the right sphenoidal wing (Fig. 1A and B). Therefore, right-frontotemporal craniotomy was done for excision of the intracranial mass, which intraoperatively showed a white, cheesy, and gelatinous substance, suggestive of infective pathology rather than of meningioma. The excised intracranial mass was sent for histopathological and microbiological examination. Direct microscopy revealed neither Mycobacterium nor other bacteria with ZiehlNeelsen (ZN) staining or Gram staining, respectively, but KOH preparations showed septate, branched fungal hyphae ( Fig. 2A). Histopathological examination with periodic acidSchiff (PAS) staining showed fungal granulomas in the brain parenchyma centered around blood vessels. Granulomas were made up of epithelioid cells with giant cells and c...

Phylogenetic Findings Suggest Possible New Habitat and Routes of Infection of Human Eumyctoma

“…Fatal, disseminated and cerebral infections by Chaetomiaceae have also been reported. In the literature about 20 deep and disseminated cases were described, nearly all in immunocompromised and severely debilitated patients [21], [22]. Several Chaetomium -like fungi thus show rather pronounced pathology, sometimes with species-specific predilections.…”

Chaetomium-like fungi causing opportunistic infections in humans: a possible role for extremotolerance

“…Apparently also immunocompetent individuals are at risk of deep infections by Chaetomium or related fungi. As an example, a case of fatal cerebral phaeohyphomycosis caused by Thielavia subthermophila was reported in immunocompetent individuals (Badali et al 2011). Chaetomium atrobrunneum, C. perlucidum, and C. strumarium were now regarded as neurotropic species causing serious and lifethreatening infections (Abbott et al 1995;Barron et al 2003;Guppy et al 1998).…”

“…Members of Pleosporales are preponderantly found as degraders of plants debris or as mild opportunistic pathogens; human infections mostly comprise traumatic inoculation of contaminated materials (Revankar and Sutton 2010). Recently, the significance of Sordariales was underlined (Badali et al 2011;de Hoog et al 2013b), particularly the Chaetomiaceae whose prevalence has been underestimated because of diagnostic problems.…”

First fatal cerebral phaeohyphomycosis due to Rhinocladiella mackenziei in Iran, based on ITS rDNA

“…DNA was extracted from obtained materials by using an Ultra Clean microbial DNA isolation kit (MO BIO, Carlsbad, CA) according to the manufacturer's instructions and PCR amplification and sequencing were carried out as previously described [7]. Briefly, the universal fungal primer pairs ITS1 (5-TCCGTAGGTGAACCTGCGG-3) and ITS4 (5-TCCTCCGCTT-ATTGATATGC-3) were used for amplification of internal Amplicons were purified using GFX PCR DNA and a gel band purification kit (GE Healthcare, Ltd., Buckinghamshire, United Kingdom).…”

“…The infection is recognized as a disease associated with high mortality and ultimately a poor prognosis despite the application of surgery and antifungal therapy [16,17]. The majority of species involved are members of the order Chaetothyriales which contain the black yeasts and relatives such as Cladophialophora bantiana, Fonsecaea monophora, and R. mackenziei [6,9], however, members of the Pleosporales (Alternaria, Bipolaris, Exserohilum), Xylariales (Nodulisporium), Sordariales (Thielavia) and Botryosphaeriales (Neoscytalidium) might be concerned [7,10,17]. The present paper reports a severe case of brain infection due to R. mackenziei in a 54-year-old immunocompetent male at Iran where this infection has not been previously reported.…”