Fungal colonization of the brain: anatomopathological aspects of neurological cryptococcosis

Colombo, Ana Caroline; Rodrigues, Márcio L.

doi:10.1590/0001-3765201520140704

Cited by 39 publications

(42 citation statements)

References 135 publications

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“…For example, meningitis caused by the genus Cryptococcus is (after tuberculosis) the second leading cause of death in people living with HIV [13]. Importantly, cryptococcal meningitis is a brain infection that, if left untreated, results in an agonizing death for people living with HIV [17].…”

Section: Aids and Opportunistic Fungal Diseases: Problem Solved Or Cumentioning

confidence: 99%

Fungal diseases as neglected pathogens: A wake-up call to public health officials

2020

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Fungal diseases: A real threat to public healthHuman fungal diseases differ fundamentally from other infections in diverse ways. As eukaryotic pathogens, fungi share many similarities with their host cells, which impairs the development of antifungal compounds. Fungal tropism is highly variable, as pathogens infect a wide range of cell types. A single fungal pathogen can infect multiple tissues in the same patient (depending on the host's immunological status) and can undergo morphogenic shifts during infection. Fungi are still underappreciated as major pathogens by both the public and public health officials. Diseases caused by protozoa, bacteria, and viruses have been recognized as important public health issues for centuries. For instance, syphilis, influenza, and Chagas disease have been documented for over 100 years [1], while invasive mycoses were only widely acknowledged as medically important pathogens in the 1980s [2]. Viral diseases of major population impact (such as smallpox, influenza and-more recentlydengue, Zika, Chikungunya, and coronavirus) have affected millions of people with significant effects on human health in developed, developing, and less developed nations [3,4]. These conditions have boosted the generation of knowledge, which has led to the eradication of smallpox [5], the wide availability of effective vaccines [6], and the development of diagnostic and preventive tools against influenza [7] and, more recently, Zika [8]. Bacterial diseases have profoundly impacted human health at different times in history, and although the phenomenon of antimicrobial resistance is a matter of extreme concern, there are several effective tools for the prevention, treatment, and diagnosis of bacterial infections [9]. Human parasitosis have been recognized to negatively impact public health in different parts of the globe for decades, which has stimulated the ongoing development of vaccines, new drugs, and diagnostic tests for malaria, sleeping sickness, leishmaniasis, filariasis, and Chagas disease [10]. Fungal infections, however, are part of a different scenario. These diseases, for most of recorded history as well as the majority of the last century, have been rare or had a low impact on human health.The increase in the number of immunocompromised patients, some of whom are highly susceptible to fungal infections, has totally changed this picture. The invasive diseases caused by fungi, the so-called systemic mycoses, profoundly impact human health. Moreover, the Global Action Fund for Fungal Infections (GAFFI) also highlights the devastating impact of focal fungal diseases in individuals who often have intact immune systems. GAFFI estimates that more than 1 million eyes go blind each year due to fungal keratitis [11]. Nearly one billion people have skin mycoses, which makes this disease only slightly less common on the planet than headaches and dental caries. Fungal spores contribute to significant reactive airway diseases in over 10 million individuals. In total, the GAFFI estimates that over 300 mi...

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Section: Aids and Opportunistic Fungal Diseases: Problem Solved Or Cumentioning

confidence: 99%

Fungal diseases as neglected pathogens: A wake-up call to public health officials

2020

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“…Cryptococcus neoformans is a yeast-like pathogen that causes expressive brain damage in immunosuppressed individuals (Colombo and Rodrigues, 2015). The fungus reaches the lungs of humans after inhalation of environmental cells.…”

Section: Introductionmentioning

confidence: 99%

The Anti-helminthic Compound Mebendazole Has Multiple Antifungal Effects against Cryptococcus neoformans

et al. 2017

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Cryptococcus neoformans is the most lethal pathogen of the central nervous system. The gold standard treatment of cryptococcosis, a combination of amphotericin B with 5-fluorocytosine, involves broad toxicity, high costs, low efficacy, and limited worldwide availability. Although the need for new antifungals is clear, drug research and development (R&D) is costly and time-consuming. Thus, drug repurposing is an alternative to R&D and to the currently available tools for treating fungal diseases. Here we screened a collection of compounds approved for use in humans seeking for those with anti-cryptococcal activity. We found that benzimidazoles consist of a broad class of chemicals inhibiting C. neoformans growth. Mebendazole and fenbendazole were the most efficient antifungals showing in vitro fungicidal activity. Since previous studies showed that mebendazole reaches the brain in biologically active concentrations, this compound was selected for further studies. Mebendazole showed antifungal activity against phagocytized C. neoformans, affected cryptococcal biofilms profoundly and caused marked morphological alterations in C. neoformans, including reduction of capsular dimensions. Amphotericin B and mebendazole had additive anti-cryptococcal effects. Mebendazole was also active against the C. neoformans sibling species, C. gattii. To further characterize the effects of the drug a random C. gattii mutant library was screened and indicated that the antifungal activity of mebendazole requires previously unknown cryptococcal targets. Our results indicate that mebendazole is as a promising prototype for the future development of anti-cryptococcal drugs.

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“…The most common fungal pathogen infecting the brain is Cryptococcus neoformans , a yeast-like pathogen that is highly efficient in causing damage to immunosuppressed human hosts [ 3 ]. The fungus, which is widespread in the environment, primarily reaches the lung after inhalation of environmental cells and disseminates to the brain in the immunosuppressed host.…”

Section: Introductionmentioning

confidence: 99%

“…The fungus, which is widespread in the environment, primarily reaches the lung after inhalation of environmental cells and disseminates to the brain in the immunosuppressed host. Clinical studies in humans in combination with animal models of neurological cryptococcosis enabled the classification of the disease into different syndromes, including meningitis, encephalitis, meningoencephalitis, ventriculitis, increased intracranial pressure, and space-occupying lesions [ 3 ]. According to the Centers for Disease Control and Prevention (CDC) of the United States, cryptococcal meningitis is a global problem.…”

Section: Introductionmentioning

confidence: 99%

Fungal colonization of the brain: anatomopathological aspects of neurological cryptococcosis

Cited by 39 publications

References 135 publications

Fungal diseases as neglected pathogens: A wake-up call to public health officials

Fungal diseases as neglected pathogens: A wake-up call to public health officials

The Anti-helminthic Compound Mebendazole Has Multiple Antifungal Effects against Cryptococcus neoformans

Funding and Innovation in Diseases of Neglected Populations: The Paradox of Cryptococcal Meningitis

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