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Infectious Disease Clinics of North... Mar 2016Cryptococcosis is an invasive mycosis caused by pathogenic encapsulated yeasts in the genus Cryptococcus. Cryptococcus gained prominence as a pathogen capable of... (Review)
Review
Cryptococcosis is an invasive mycosis caused by pathogenic encapsulated yeasts in the genus Cryptococcus. Cryptococcus gained prominence as a pathogen capable of widespread disease outbreaks in vulnerable populations. We have gained insight into the pathobiology of Cryptococcus, including the yeast' s capacity to adapt to environmental pressures, exploit new geographic environments, and cause disease in both immunocompromised and apparently immunocompetent hosts. Inexpensive, point-of-care testing makes diagnosis more feasible than ever. The associated worldwide burden and mortality remains unacceptably high. Novel screening strategies and preemptive therapy offer promise at making a sustained and much needed impact on this sugar-coated opportunistic mycosis.
Topics: Antifungal Agents; Cryptococcosis; Cryptococcus; Humans
PubMed: 26897067
DOI: 10.1016/j.idc.2015.10.006 -
Fungal Genetics and Biology : FG & B May 2015The human fungal pathogen Cryptococcus neoformans is able to rapidly and effectively adapt to varying conditions, favoring its survival in the environment and in the... (Review)
Review
The human fungal pathogen Cryptococcus neoformans is able to rapidly and effectively adapt to varying conditions, favoring its survival in the environment and in the infected host. Many microbial phenotypes have been specifically correlated with virulence in this opportunistic pathogen, such as capsule production, melanin formation, and the secretion of various proteins. Additionally, cellular features such as the cell wall and morphogenesis play important roles in the interaction of this fungus with host immune recognition and response pathways. Survival in the face of host stress also requires maintaining RNA/DNA integrity. Additionally, aging and senescence of the fungal cells determines resistance to host-derived stresses. New mechanisms regulating the expression of these virulence-associated phenotypes have been recently explored. Importantly, human clinical studies are now confirming the roles of specific microbial factors in human infections.
Topics: Cryptococcosis; Cryptococcus neoformans; Host-Pathogen Interactions; Humans; Virulence; Virulence Factors
PubMed: 25256589
DOI: 10.1016/j.fgb.2014.09.004 -
Nature Reviews. Microbiology Jul 2021Cryptococcus spp., in particular Cryptococcus neoformans and Cryptococcus gattii, have an enormous impact on human health worldwide. The global burden of cryptococcal... (Review)
Review
Cryptococcus spp., in particular Cryptococcus neoformans and Cryptococcus gattii, have an enormous impact on human health worldwide. The global burden of cryptococcal meningitis is almost a quarter of a million cases and 181,000 deaths annually, with mortality rates of 100% if infections remain untreated. Despite these alarming statistics, treatment options for cryptococcosis remain limited, with only three major classes of drugs approved for clinical use. Exacerbating the public health burden is the fact that the only new class of antifungal drugs developed in decades, the echinocandins, displays negligible antifungal activity against Cryptococcus spp., and the efficacy of the remaining therapeutics is hampered by host toxicity and pathogen resistance. Here, we describe the current arsenal of antifungal agents and the treatment strategies employed to manage cryptococcal disease. We further elaborate on the recent advances in our understanding of the intrinsic and adaptive resistance mechanisms that are utilized by Cryptococcus spp. to evade therapeutic treatments. Finally, we review potential therapeutic strategies, including combination therapy, the targeting of virulence traits, impairing stress response pathways and modulating host immunity, to effectively treat infections caused by Cryptococcus spp. Overall, understanding of the mechanisms that regulate anti-cryptococcal drug resistance, coupled with advances in genomics technologies and high-throughput screening methodologies, will catalyse innovation and accelerate antifungal drug discovery.
Topics: Antifungal Agents; Cell Wall; Cryptococcosis; Cryptococcus; Drug Resistance, Fungal; Echinocandins; Fungal Capsules; Fungal Polysaccharides; Virulence Factors
PubMed: 33558691
DOI: 10.1038/s41579-021-00511-0 -
Journal of Feline Medicine and Surgery Jul 2013Cryptococcosis is worldwide the most common systemic fungal disease in cats; it is caused by the Cryptococcus neoformans- Cryptococcus gattii species complex, which... (Review)
Review
OVERVIEW
Cryptococcosis is worldwide the most common systemic fungal disease in cats; it is caused by the Cryptococcus neoformans- Cryptococcus gattii species complex, which includes eight genotypes and some subtypes (strains) with varying geographical distribution, pathogenicity and antimicrobial susceptibility. Cats acquire the infection from a contaminated environment. The prognosis is favourable in most cases, provided a diagnosis is obtained sufficiently early and prolonged treatment is maintained.
INFECTION
Basidiospores are the infectious propagules of Cryptococcus species as they penetrate the respiratory system and induce primary infection. Asymptomatic colonisation of the respiratory tract is more common than clinical disease. Avian guanos, particularly pigeon droppings, offer favourable conditions for the reproduction of C neoformans. Both Cryptococcus species are associated with decaying vegetation.
DISEASE SIGNS
Cryptococcosis caused by C neoformans or C gattii is indistinguishable clinically. The disease can present in nasal, central nervous system (which can derive from the nasal form or occur independently), cutaneous and systemic forms.
DIAGNOSIS
An easy and reliable test for cryptococcosis diagnosis is antigen detection in body fluids. Only isolation and polymerase chain reaction allow identification of the species genotype.
DISEASE MANAGEMENT
Amphotericin B, ketoconazole, fluconazole and itraconazole have all been used to treat cats. Surgical excision of any nodules in the skin, nasal or oral mucosa assists recovery. Continued treatment is recommended until the antigen test is negative.
PREVENTION
Efficient preventive measures have not been demonstrated. Vaccines are not available.
Topics: Animals; Antifungal Agents; Cat Diseases; Cats; Cryptococcosis
PubMed: 23813826
DOI: 10.1177/1098612X13489224 -
Nature Reviews. Microbiology Feb 2016Cryptococcosis is a globally distributed invasive fungal infection that is caused by species within the genus Cryptococcus which presents substantial therapeutic... (Review)
Review
Cryptococcosis is a globally distributed invasive fungal infection that is caused by species within the genus Cryptococcus which presents substantial therapeutic challenges. Although natural human-to-human transmission has never been observed, recent work has identified multiple virulence mechanisms that enable cryptococci to infect, disseminate within and ultimately kill their human host. In this Review, we describe these recent discoveries that illustrate the intricacy of host-pathogen interactions and reveal new details about the host immune responses that either help to protect against disease or increase host susceptibility. In addition, we discuss how this improved understanding of both the host and the pathogen informs potential new avenues for therapeutic development.
Topics: Antifungal Agents; Cryptococcosis; Cryptococcus; Host-Pathogen Interactions; Humans; Virulence
PubMed: 26685750
DOI: 10.1038/nrmicro.2015.6 -
Clinical Infectious Diseases : An... Feb 2010Cryptococcosis is a global invasive mycosis associated with significant morbidity and mortality. These guidelines for its management have been built on the previous...
Cryptococcosis is a global invasive mycosis associated with significant morbidity and mortality. These guidelines for its management have been built on the previous Infectious Diseases Society of America guidelines from 2000 and include new sections. There is a discussion of the management of cryptococcal meningoencephalitis in 3 risk groups: (1) human immunodeficiency virus (HIV)-infected individuals, (2) organ transplant recipients, and (3) non-HIV-infected and nontransplant hosts. There are specific recommendations for other unique risk populations, such as children, pregnant women, persons in resource-limited environments, and those with Cryptococcus gattii infection. Recommendations for management also include other sites of infection, including strategies for pulmonary cryptococcosis. Emphasis has been placed on potential complications in management of cryptococcal infection, including increased intracranial pressure, immune reconstitution inflammatory syndrome (IRIS), drug resistance, and cryptococcomas. Three key management principles have been articulated: (1) induction therapy for meningoencephalitis using fungicidal regimens, such as a polyene and flucytosine, followed by suppressive regimens using fluconazole; (2) importance of early recognition and treatment of increased intracranial pressure and/or IRIS; and (3) the use of lipid formulations of amphotericin B regimens in patients with renal impairment. Cryptococcosis remains a challenging management issue, with little new drug development or recent definitive studies. However, if the diagnosis is made early, if clinicians adhere to the basic principles of these guidelines, and if the underlying disease is controlled, then cryptococcosis can be managed successfully in the vast majority of patients.
Topics: Antifungal Agents; Case Management; Child; Child, Preschool; Cryptococcosis; Female; Humans; Intracranial Hypertension; Pregnancy; United States
PubMed: 20047480
DOI: 10.1086/649858 -
Medical Mycology Journal 2019Cutaneous cryptococcosis is classified either as primary or secondary based on the route of infection. The disease can also be classified either as localized cutaneous... (Review)
Review
Cutaneous cryptococcosis is classified either as primary or secondary based on the route of infection. The disease can also be classified either as localized cutaneous cryptococcosis or cutaneous manifestations of disseminated cryptococcosis. However, from a physician's point of view, whether lesions are localized to the skin or are disseminated/systemic is more important than the route of infection. The Clinical Practice Guidelines for Diagnosis and Treatment of Cryptococcosis, which was established in 2019 by the Japanese Society for Medical Mycology, adopted the latter classification. Localized cutaneous cryptococcosis is defined as a condition in which lesions are confined within a limited part of the skin, not systemically disseminated at the same time, and are associated with neither cryptococcal fungemia nor antigenemia. This type of cutaneous cryptococcosis is uncommon in Japan. Only 65 cases were reported during the 50-year study period from 1968 to August 2018, with the patients divided into two groups: immunocompromised patients (n=44, 68%) and immunocompetent patients (n=21, 32%). None of the patients were infected with the human immunodeficiency virus (HIV). Localized cutaneous cryptococcosis can also occur in non-HIV-infected patients and well-appearing individuals, therefore, it is considered an important infection in routine dermatology practice. Here, we outline the classification, diagnosis, and treatment of cutaneous cryptococcosis and present a summary of cutaneous cryptococcosis cases reported in Japan.
Topics: Adult; Aged; Aged, 80 and over; Child; Cryptococcosis; Dermatomycoses; Female; Humans; Immunocompetence; Immunocompromised Host; Male; Middle Aged
PubMed: 31787730
DOI: 10.3314/mmj.19.008 -
Mycopathologia Oct 2021
Topics: Cryptococcosis; Cryptococcus gattii; Cryptococcus neoformans; Humans
PubMed: 34224075
DOI: 10.1007/s11046-021-00577-7 -
Journal of Veterinary Diagnostic... Nov 2020We review herein infections by spp., spp., and spp. in sheep and goats. spp. are common causes of rhinitis in sheep and are less frequent in goats, in which spp.... (Review)
Review
We review herein infections by spp., spp., and spp. in sheep and goats. spp. are common causes of rhinitis in sheep and are less frequent in goats, in which spp. also cause skin lesions. spp. cause rhinitis, meningitis, encephalitis, and pneumonia in goats, and are rarely observed in sheep. spp. may cause rhinitis in goats, and pneumonia and mastitis in sheep and goats. Gross and microscopic lesions caused by these 3 fungal infections may be similar to each other. The diagnosis of these diseases must be based on gross and microscopic lesions, coupled with detection of the agent by immunohistochemical, molecular, and/or culture-based methods.
Topics: Animals; Aspergillosis; Conidiobolus; Cryptococcosis; Female; Goat Diseases; Goats; Sheep; Sheep Diseases; Zygomycosis
PubMed: 32921278
DOI: 10.1177/1040638720958338 -
BMC Pulmonary Medicine Jul 2023Cryptococcosis is an invasive fungal disease with increased morbidity in China over the past two decades. Cryptococci can infect immunocompromised hosts as well as... (Review)
Review
Cryptococcosis is an invasive fungal disease with increased morbidity in China over the past two decades. Cryptococci can infect immunocompromised hosts as well as immunocompetent ones. In this study, we reviewed data of 71 inpatients with cryptococcosis at Ningbo First Hospital from May 2010 to May 2020 and compared the clinical profiles of pulmonary cryptococcosis (PC) and extrapulmonary cryptococcosis (EPC). Of 71 patients (38 males, 33 females), 70 were non-HIV. The annual inpatient population increased dramatically, especially in the PC group. PC was confirmed in 77.46% (55/71) of cases by pathology. The rest were EPC including intracranial infection (15.49%, 11/71) and cryptococcemia (7.04%, 5/71). Compared with PC, a larger proportion of EPC patients were found to have immunocompromised conditions judged by predisposing factors (p < 0.01), or detectable humoral or cellular immunodeficiency. Fever and headache were more common in EPC patients (p < 0.001). Patients with EPC had lower serum sodium level (p = 0.041), lower monocyte counts (p = 0.025) and higher C-reactive protein (p = 0.012). In our study, the sensitivity of cryptococcus antigen detection for EPC was 100% regardless of sample type, while serum lateral flow assay (LFA) tested negative in 25% (5/20) of PC. Immunocompromised hosts are more likely to suffer from EPC than PC.
Topics: Male; Female; Humans; Retrospective Studies; Tertiary Care Centers; East Asian People; Cryptococcosis; China; Antigens, Fungal
PubMed: 37501136
DOI: 10.1186/s12890-023-02578-2