Pathobiology of fungal infections of the central nervous system with special reference to the Indian scenario

Abstract

Ubiquitously present fungi in the environment find a nidus in the human body and adopt its metabolic machinery to be in symbiosis or become pathogenic. Immunocompromised states like human immunodeficiency virus (HIV) / acquired immunodeficiency syndrome (AIDS), systemic neoplasia and organ transplantation have enhanced the frequency of fungal infections. High-risk behavior, IV drug abuse and air travel have led to the emergence of new fungal infections hitherto geographically localized. The pathology in the central nervous system (CNS) is dictated largely by the size of the fungus - the yeast forms, by virtue of their small size enter the microcirculation to cause meningitis and microabscesses, while hyphal forms invade the vasculature to manifest as large pale or hemorrhagic infarcts. The growth kinetics of fungi, the antigenic character of the capsule. the proteases secreted by the mycelial forms and the biochemical milieu in the host also determine clinical manifestations. A hospital-based analysis of the available information from India suggests that in the non-HIV patient population, hyphal forms like Aspergillosis and Zygomycosis are the most common pathogens, while yeast forms like Cryptococcus and Candida are the prime pathogens in cases of HIV/AIDS, the altered macrophage function acting in synergy with suppressed cell-mediated immunity. In Northeastern states, systemic infection by Penicillium marneffei is reported in association with HIV though CNS involvement is not recorded. Although fungal infections of the CNS are reported from various hospitals in India, studies are limited by non-availability of relevant microbiological studies and the reported prevalence data is biased by the surgical practices, availability of postmortem and microbiology and laboratory support. Detailed clinical and mycological investigations related to the interaction between the fungus and host environment is a fertile area of research to understand the basic pathogenetic mechanisms.

Cerebral Phaeohyphomycosis Due to Cladophialophora bantiana – A Case Report and Review of Literature from India

“…High mortality is mainly due to delay in surgical resection and treatment with less effective antifungal agents like amphotericin B [25]. In the present review an overall mortality rate of 48% was observed in those patients where outcome was reported (12 out of 25).…”

Rhinocerebral mucormycosis: Pathology revisited with emphasis on perineural spread

“…The broad hyphae invade and occlude intermediate/large-sized arteries/veins resulting in pale/hemorrhagic infarcts. [18] The morphology of the fungus was delineated on H and E, GMS, and PAS in all our samples, and co-infection by Candida species was identified in one biopsy. Histopathiogical examination of tissue allows differentiation of Mucorales species from other angioinvasive fungi such as Aspergillus spp., Scedosporidium spp., and Fusarium spp.…”

Cerebral Aspergillosis on autopsy; masquerading clinically as Brain tumor in a young female

“…Its germination into filamentous forms results in tissue destruction and disease. [8] Aspergillus spores are commensal in the respiratory tract and external auditory canal. Maxillary sinusitis of dental origin or the lungs are the most common sites of primary aspergillus infection.…”

“…The infection in the nervous system can be found in the cerebral parenchyma, meninges or the vascular system. [8] Aspergillus tends to invade arteries and veins because of its angiotropism, leading to necrotizing vasculitis, secondary thrombosis and hemorrhage. [11] Extension of fungal invasion in the neighbouring neuronal tissues and in blood vessels provoke hemorrhage, thrombosis, infarcts, necrosis, meningitis and ventriculitis.…”

“…[5][6] [7][8] Compromised sinus aeration, altered immune status could facilitate growth of the organism and eventual contiguous spread into the cranial cavity. [8] We report a case of cerebral aspergillosis diagnosed on post-mortem histopathological examination. Antemortem the patient was suspected of brain tumor and was IJBAR (2015) 6 (01) www.ssjournals.com investigated accordingly and died due to lack of appropriate diagnosis and treatment.…”