Cryptococcosis-a systematic review to inform the World Health Organization Fungal Priority Pathogens List.

Cryptococcosis causes a high burden of disease worldwide. This systematic review summarizes the literature on Cryptococcus neoformans and C. gattii infections to inform the World Health Organization's first Fungal Priority Pathogen List. PubMed and Web of Science were used to identify studies reporting on annual incidence, mortality, morbidity, antifungal resistance, preventability, and distribution/emergence in the past 10 years. Mortality rates due to C. neoformans were 41%-61%. Complications included acute renal impairment, raised intracranial pressure needing shunts, and blindness. There was moderate evidence of reduced susceptibility (MIC range 16-32 mg/l) of C. neoformans to fluconazole, itraconazole, ketoconazole, voriconazole, and amphotericin B. Cryptococcus gattii infections comprised 11%-33% of all cases of invasive cryptococcosis globally. The mortality rates were 10%-23% for central nervous system (CNS) and pulmonary infections, and ∼43% for bloodstream infections. Complications described included neurological sequelae (17%-27% in C. gattii infections) and immune reconstitution inflammatory syndrome. MICs were generally low for amphotericin B (MICs: 0.25-0.5 mg/l), 5-flucytosine (MIC range: 0.5-2 mg/l), itraconazole, posaconazole, and voriconazole (MIC range: 0.06-0.5 mg/l). There is a need for increased surveillance of disease phenotype and outcome, long-term disability, and drug susceptibility to inform robust estimates of disease burden.

Outcomes and factors associated with cryptococcal disease among cirrhotics: A study of the national inpatient sample 2005 to 2014.

BACKGROUND: Cryptococcal disease (CD) confers a higher mortality in cirrhotic patients compared to non-cirrhotic patients. Factor association for CD in cirrhotic patients is poorly understood. Our aim was to determine the incidence, demographic, and comorbidities associated with CD among cirrhotic patients in the United States (US). METHOD: Retrospective analysis of admissions of cirrhotic patients, with or without CD, using the National Inpatient Sample (NIS) database from 2005 to 2014. The number of admissions were reported in raw and weighted frequencies. The trends of CD among cirrhotic patients and overall CD were evaluated. Rao-Scott chi-square, t-tests, and multivariate logistic regressions were performed to evaluate variables and CD among cirrhotic patients. RESULTS: There were 886,962 admissions for cirrhosis, and 164 of these with CD. By adjusted odds ratio (AOR), CD was more often associated with cirrhosis in Southern (2.95; 95 % CI 1.24, 7.02) and Western regions (4.45; 95 % CI 1.91, 10.37), Hispanic patients (1.80; 95 % CI 1.01, 3.20), and patients with chronic kidney disease (CKD) (3.13; 95 % CI 2.09, 4.69). Of note, CD in cirrhotic patients was associated with higher inpatient mortality (AOR of 3.89, 95 % CI 2.53, 5.99), longer length of stay (9.87 vs. 4.88 days), and a higher total charge ($76,880 vs. $ 37,227) when compared to cirrhotic patients without CD. DISCUSSION: Patients with cirrhosis admitted with CD have a high inpatient mortality. The geographical location and CKD were important factors associated with CD among cirrhotic patients. Autoimmune liver diseases and immunosuppression did not appear to increase the risk of CD.

Molecular characterization of clinical and environmental isolates from the Cryptococcus neoformans/C. Gattii species complexes of Maceió, Alagoas, Brazil.

Cryptococcosis is one of the major life-threatening opportunistic/systemic fungal diseases of worldwide occurrence, which can be asymptomatic or establish pneumonia and meningoencephalitis mainly in immunosuppressed patients, caused by the Cryptococcus neoformans and C. gattii species complexes. Acquisition is by inhaling fungal propagules from avian droppings, tree hollows and decaying wood, and the association of the molecular types with geographic origin, virulence and antifungal resistance have epidemiological importance. Since data on cryptococcosis in Alagoas are limited, we sought to determine the molecular types of etiological agents collected from clinical and environmental sources. We evaluated 21 isolates previously collected from cerebrospinal fluid and from environment sources (pigeon droppings and tree hollows) in Maceió-Alagoas (Brazil). Restriction fragment length polymorphism of URA5 gene was performed to characterize among the eight standard molecular types (VNI-VNIV and VGI-VGIV). Among isolates, 66.67% (14) were assigned to C. neoformans VNI - 12 of them (12/14) recovered from liquor and 2 from a tree hollow (2/14). One isolate from pigeon droppings (4.76%) corresponded to C. neoformans VNIV, while five strains from tree hollows and one from pigeon droppings (6, 28.57%) to C. gattii VGII. VNI-type was present in clinical and environmental samples and most C. neoformans infections were observed in HIV-positive patients, while types VNIV and VGII were prevalent in environmental sources in Alagoas. This is the first molecular characterization of Cryptococcus spp. in Alagoas, our study provides additional information on the ecoepidemiology of Cryptococcus spp. in Brazil, contributing to a closer view of the endemic species.

Implementation of a rapid diagnostic assay package for cryptococcosis, histoplasmosis and tuberculosis in people living with HIV in Paraguay.

BACKGROUND: Opportunistic infections (OIs) are common causes of mortality among people living with HIV (PLHIV). We determined prevalence and 30-day mortality due to histoplasmosis, cryptococcosis, and TB in PLHIV with advanced HIV disease (AHD). METHODS: PLHIV 18 years and older, with a CD4 + T-cell count of less than 350 cells/mm3 newly diagnosed with HIV infection or re-engaged in care after being without ART for more than 90 days (Group A). The second group included symptomatic PLHIV regardless of ART status or CD4 + T-cell count (Group B); all followed for 30 days. Detection of Histoplasma Ag (HisAg) in urine was done by enzyme immunoassay (EIA), Cryptococcus antigen (CrAg) was detected in serum and cerebrospinal fluid (CSF) specimens by lateral flow assay (LFA), and lipoarabinomannan (LAM) detection in urine was by LFA (TB LAM) and in sputum by GeneXpert for diagnosis of Mycobacterium infections. RESULTS: From August 2021 to June 2022, 491 PLHIV were enrolled; 482 (98%) had a CD4 + T-cell result, and 381 patients (79%) were classified with AHD according to CD4 + T-cell count (< 200 CD4/mm3). Frequency of an OI was 38% (n = 145/381). Antigen test positivity rate was 16% (72/467) for TB-LAM, 9% (43/464) for HisAg, and 11% (51/484) for CrAg. Twenty-one of 34 (62%) patients receiving CSF CrAg tests were positive, confirming meningitis. Significant differences in 30-day mortality were observed in patients with an OI (16%) vs. no OI (7%) (p = 0.002). Mortality was highest in patients with histoplasmosis (25%), co-infection (22%), cryptococcosis (18% overall; 19% for cryptococcal meningitis), and TB (10%). CONCLUSIONS: TB and fungal OIs, including co-infection, were common in PLHIV in Paraguay and had high associated mortality. Laboratories and health facilities need access to CD4 + T-cell testing and rapid diagnostic assays.

Features of cryptococcosis among 652 HIV-seronegative individuals in France: a cross-sectional observational study (2005-2020).

OBJECTIVES: We aimed to describe features and outcomes of cryptococcosis among HIV-seronegative individuals in a large surveillance network for cryptococcosis in France. METHODS: We included incident cases of cryptococcosis in HIV-seronegative individuals from 2005 to 2020. We compared patient characteristics, disease presentations, cryptococcal antigen results, and induction antifungal treatments according to underlying disease. We examined factors associated with 90-day mortality. Among patients with disseminated infections, we investigated whether receipt of flucytosine and polyene combination was associated with lower mortality. RESULTS: Among 652 individuals, 209 (32.1%) had malignancy, 130 (19.9%) were solid-organ transplant recipients, 204 (31.3%) had other immunocompromising conditions, and 109 (16.7%) had no reported underlying factor. The commonest presentations were disseminated infections (63.3%, 413/652) and isolated pulmonary infections (25.3%, 165/652). Solid-organ transplant patients were most likely to have disseminated infections and a positive serum cryptococcal antigen result. Patients with malignancy were older and less likely to receive a flucytosine-containing regimen for disseminated infections than others (58.7%, 78/133 vs. 73.2%, 194/265; p 0.029). The crude 90-day case-fatality ratio was 27.2% (95% CI, 23.5%-31.1%). Age ≥60 years (aOR: 2.75 [1.78-4.26]; p < 0.001), meningitis/fungaemia (aOR: 4.79 [1.80-12.7]; p 0.002), and malignancy (aOR: 2.4 [1.14-5.07]; p 0.02) were associated with higher 90-day mortality. Receipt of flucytosine and polyene combination was associated with lower 90-day mortality (aOR: 0.40 [0.23-0.71]; p 0.002) in multivariable analysis and inverse probability of treatment weighted analysis (aOR: 0.45 [0.25-0.80]; p 0.006). DISCUSSION: HIV-seronegative individuals with cryptococcosis comprise a wide range of underlying conditions with different presentations and outcomes, requiring a tailored approach to diagnosis and management.

Molecular epidemiological investigation of Cryptococcus spp. carried by captive koalas (Phascolarctos cinereus) in Japan.

Cryptococcus neoformans and Cryptococcus gattii cause cryptococcosis, a systemic mycosis that infects a wide range of species. Recent molecular biological investigations have allowed for the genotyping of these species, providing more detailed information on their pathogenicity and infection routes. Koalas (Phascolarctos cinereus) are frequently colonized by Cryptococcus spp., but molecular epidemiological studies have yet to be conducted in Japan. Here, we conducted multi-locus sequence typing (MLST) analysis on Cryptococcus spp. colonization isolates obtained from all koalas kept in seven parks across Japan. Out of 46 koalas examined, 10 (22%) were positive for C. gattii and 3 (6.5%) were positive for C. neoformans. All C. gattii isolates belonged to molecular type VGI and were either sequence type (ST) 51 or a novel ST, and all C. neoformans isolates belonged to molecular type VNI and ST23. Despite the frequent movement of koalas between parks, the STs were relatively park-specific, suggesting that the floor of the rearing barns is a source of infection and may act as a reservoir. MLST analysis confirmed that C. gattii was transported, established, and spread by koalas in areas where C. gattii was not originally present. MLST analysis is considered useful in assessing the pathogenicity and tracing the transmission routes of Cryptococcus spp. carried by koalas.IMPORTANCEThis is the first study to conduct a multi-locus sequence typing analysis on Cryptococcus spp. carried by captive koalas in Japan. Cryptococcosis remains a globally high-fatality fungal infection in humans, and captive koalas are known to carry a high percentage of Cryptococcus spp. Through this research, the molecular types and transmission routes of Cryptococcus spp. carried by koalas have been elucidated, revealing the potential role of enclosure flooring as a reservoir. It has been confirmed that Cryptococcus gattii, which is not endemic in Japan, has become established through koalas and is spreading to new individuals in Japan. This study is believed to provide valuable insights into koala conservation and contribute to the One Health approach for Cryptococcosis, a zoonotic infection.

Survival after cryptococcosis in Germany: A retrospective multicenter cohort study of patients diagnosed between 2004 and 2021.

Cryptococcosis is the most prevalent fungal infection of the central nervous system worldwide. We performed a retrospective multicenter cohort study to gain insights into the epidemiology of cryptococcosis in Germany. We describe the use of diagnostic tests, clinical management and patient outcome. We included 64 patients with underlying HIV infection (55%) or other predispositions. Molecular typing by MLST documented 20 individual sequence types among 42 typed isolates. A fatal outcome was documented in 14% of patients in the first two months after diagnosis.

Pediatric Cryptococcosis.

BACKGROUND: Seroprevalence studies have shown that 70% of children are exposed to Cryptococcus , the most common cause of meningitis in people living with human immunodeficiency virus (HIV), but reported pediatric disease prevalence is much lower than in adults. METHODS: PubMed and Ovid Global Health databases were searched with the terms "cryptococcosis," "cryptococcal meningitis," " Cryptococcus neoformans " or " Cryptococcus gattii ." All studies reporting pediatric specific data in the English language from 1980 up until December 2022 were included. RESULTS: One hundred sixty-eight publications were reviewed totaling 1469 children, with the majority reported from Africa (54.2%). Sixty-five percent (961) were HIV positive, 10% (147) were non-HIV immunocompromised and 19% (281) were immunocompetent. Clinical signs and symptoms were only reported for 458 children, with fever (64%), headache (55%) and vomiting (39%) being the most common. Most children (80%) suffered from meningoencephalitis. Lung involvement was rarely described in HIV-positive children (1%), but significantly more common in the non-HIV immunocompromised (36%) and immunocompetent (40%) groups ( P < 0.0001). Only 22% received the recommended antifungal combination therapy, which was significantly higher in immunocompetent children than those with HIV (39% vs. 6.8%; P < 0.0001). Overall mortality was 23%. A significant higher mortality was observed in children with HIV compared with immunocompetent children (32% vs. 16%; P < 0.001), but not compared with children with non-HIV immunosuppression (25). CONCLUSIONS: This is the largest review of pediatric cryptococcosis with new observations on differences in clinical presentation and outcome depending on the underlying condition. The lack of granular clinical data urges prospective clinical epidemiological studies for improved insight in the epidemiology, management and outcome of cryptococcosis in children.

Trends in the Incidence of Disseminated Cryptococcosis in Japan: A Nationwide Observational Study, 2015-2021.

BACKGROUND: Cryptococcus species can cause severe disseminated infections in immunocompromised hosts. This study investigated the epidemiological features and trends in disseminated cryptococcosis in Japan. METHODS: We used publicly available Infectious Diseases Weekly Reports to obtain data on the incidence of disseminated cryptococcosis in Japan from 2015 to 2021. Patient information, including age, sex, and regional and seasonal data, were extracted. The Joinpoint regression program was used to determine the age-adjusted incidence rate (AAR) per 100,000 population, annual percentage change (APC), and average APC (AAPC). RESULTS: A total of 1047 cases of disseminated cryptococcosis were reported, of which those aged ≥ 70 years accounted for 68.8%. The AAR in men was significantly higher than that in women (median: 0.13 vs. 0.09: p = 0.0024). APC for the overall cases increased by 9.9% (95% confidence interval [95% CI] - 5.4-27.7) from 2015 to 2018 and then decreased by 3.3% (95% CI - 15.5-10.7) from 2018 to 2021. AAPC for the entire study period was 3.1% (95% CI - 1.5-8.0), indicating a possible increase in its number, although not statistically significant. In terms of regional distribution, the average AAR was highest in Shikoku District (0.17) and lowest in Hokkaido District (0.04). Northern Japan exhibited a significantly lower median AAR (median [interquartile range]: 0.06 [0.05, 0.08]) than the Eastern (0.12 [0.12, 0.13]), Western (0.11 [0.10, 0.13]), and Southern (0.14 [0.12, 0.15]) regions. No seasonal variation in incidence was observed. CONCLUSION: The prevalence of disseminated cryptococcosis has not increased in Japan. Geographically, the incidence is lower in Northern Japan. Further investigations that incorporate detailed clinical data are required.

Temporal trends in antifungal susceptibility of Cryptococcus neoformans isolates from a reference laboratory in the United States, 2011-2021.

BACKGROUND: There are no established clinical breakpoints for antifungal agents against Cryptococcus species; however, epidemiological cut-off values can help distinguish wild-type (WT) isolates without any acquired resistance from non-WT strains, which may harbour resistance mechanisms. PATIENTS/METHODS: We describe the trends of antifungal MICs and percentages of WT C. neoformans species complex (CNSC) isolates processed in our reference laboratory from November 2011 to June 2021. There were only nine isolates in 2011, thus, we included them in the year 2012 for data analysis. Clinical data is also described when available. RESULTS: We identified 632 CNSC, the majority collected from blood (n = 301), cerebrospinal fluid (n = 230), and respiratory (n = 71) sources. The overall percentage of WT isolates for amphotericin B (AMB), 5-flucytosine, and fluconazole was 77%, 98%, and 91%, respectively. We noticed a statistically significant change in the percentage of AMB WT isolates over the years, with 98% of isolates being WT in 2012 compared to 79% in 2021 (p < .01). A similar change was not observed for other antifungal agents. Clinical data was available for 36 patients, primarily non-HIV immunocompromised patients with disseminated cryptococcosis. There were no statistically significant differences in the clinical characteristics and outcomes between patients with WT (58.3%) versus non-WT (41.7%) isolates, but we noticed higher mortality in patients infected with an AMB non-WT CNSC isolate. CONCLUSIONS: We observed an increase in the percentage of AMB non-WT CNSC isolates in the past decade. The clinical implications of this finding warrant further evaluation in larger studies.

The incidences and clinical outcomes of cryptococcosis in Taiwan: A nationwide, population-based study, 2002-2015.

Large-scale epidemiological data on cryptococcosis other than cryptococcal meningitis (CM), human immunodeficiency virus (HIV)- or solid organ transplantation (SOT)-associated cryptococcosis are limited. This study investigated the disease burden of cryptococcosis in Taiwan over 14 years. Incident episodes of cryptococcosis, comorbidities, treatment, and outcomes were captured from Taiwan's National Health Insurance Research Database and National Death Registry between 2002 and 2015. Of 6647 episodes analyzed, the crude incidence rate per 100 000 population increased from 1.48 in 2002 to 2.76 in 2015, which was driven by the growing trend in the non-CM group (0.86-2.12) but not in the CM group (0.62-0.64). The leading three comorbidities were diabetes mellitus (23.62%), malignancy (22.81%), and liver disease (17.42%). HIV accounted for 6.14% of all episodes and was associated with the highest disease-specific incidence rate (269/100 000 population), but the value dropped 16.20% biennially. Within 90 days prior to cohort entry, 30.22% of episodes had systemic corticosteroid use. The in-hospital mortality of all episodes was 10.80%, which varied from 32.64% for cirrhosis and 13.22% for HIV to 6.90% for SOT. CM was associated with a higher in-hospital mortality rate than non-CM (19.15% vs. 6.33%). At diagnosis, only 48.53% of CM episodes were prescribed an amphotericin-based regimen. The incidence rate of cryptococcosis was increasing, especially that other than meningitis and in the non-HIV population. A high index of clinical suspicion is paramount to promptly diagnose, treat, and improve cryptococcosis-related mortality in populations other than those with HIV infection or SOT.

This nationwide study showed that the incidence rate of cryptococcosis doubled from 2002 to 2015. Non-meningeal cryptococcosis and non-HIV/nontransplant (NHNT)-associated cryptococcosis contributed to this increase. Our study highlighted the underestimated burden of cryptococcosis in the NHNT hosts.

Diabetes Mellitus Type 2 as a Risk Factor and Outcome Modifier for Cryptococcosis in HIV Negative, Non-transplant Patients, a Propensity Score Match Analysis.

Cryptococcosis is an opportunistic fungal infection of worldwide distribution with significant associated morbidity and mortality. HIV, organ transplantation, malignancy, cirrhosis, sarcoidosis, and immunosuppressive medications are established risk factors for cryptococcosis. Type 2 diabetes mellitus (DM2) has been hypothesized as a risk factor and an outcome modifier for cryptococcosis. We aimed to compare outcomes among HIV-negative, non-transplant (NHNT) patients with and without DM2. We queried a global research network to identify NHNT patients (n = 3280). We performed a propensity score-matched (PSM) analysis comparing clinical outcomes among cryptococcosis patients by DM status. We also characterize adults with cryptococcosis and DM2 as the only risk factor. After PSM, NHNT patients with DM2 were more likely to develop cognitive dysfunction [9% vs. 6%, OR 1.6; 95% CI (1.1-2.3); P = 0.01] but had similar mortality, hospitalization, ICU, and stroke risk after acquiring cryptococcosis when compared to NHNT patients without DM2. Pulmonary cryptococcosis was the most common site of infection. Among 44 cryptococcosis patients with DM2 as the only identifiable risk factor for disease, the annual incidence of cryptococcosis was 0.001%, with a prevalence of 0.002%. DM2 is associated with increased cognitive dysfunction risk in NHNT patients with cryptococcosis. It is rare for DM2 to be the only identified risk factor for developing cryptococcosis. Kidney disease, hyperglycemia, and immune dysfunction can increase the risk of cryptococcosis in patients with DM2.

High prevalence of central nervous system cryptococcosis using a fingerprick whole-blood lateral flow assay in individuals with neurological symptoms and advanced HIV disease in a Brazilian emergency department.

Timely diagnosis is key in managing central nervous system (CNS) cryptococcosis in people living with HIV/AIDS (PLWHA). There are few data on implementing fingerprick whole-blood cryptococcal antigen (CrAg) lateral flow assay (LFA) as the first test for diagnosing CNS cryptococcosis. We evaluated the prevalence of CNS cryptococcosis and cryptococcal antigenemia using fingerprick whole-blood in a referral emergency department (ED) in São Paulo, Brazil. This was a prospective cohort study of consecutive adult PLWHA with advanced HIV disease and neurological symptoms. Fingerprick whole-blood CrAg LFA was performed at bedside. Seventy-four individuals were enrolled (median age = 40 years; males = 62%). Prevalence of CNS cryptococcosis was 17.6% (13/74); 95% confidence interval (CI), 9.4-30.0%, and prevalence of positive fingerprick whole-blood CrAg LFA was 25.7% (19/74); 95% CI, 15.5-40.1%. Among the six (8.1%) patients with positive fingerprick whole-blood CrAg LFA and negative CSF CrAg LFA, four (5.4%) had isolated asymptomatic cryptococcal antigenemia, one (1.3%) had symptomatic cryptococcal antigenemia, and one (1.3%) had cryptococcemia. Prevalence of CNS cryptococcosis and cryptococcal antigenemia using fingerprick whole-blood CrAg LFA was high. Point-of-care testing was important for diagnosing CNS cryptococcosis in an ED from a middle-income country.

Meningeal cryptococcosis and SARS-CoV-2 infection in people living with HIV/AIDS. / Criptococosis meníngea e infección por SARS-CoV-2 en personas con VIH/SIDA

INTRODUCTION: Fungal infections in patients with COVID-19 was one of the most debated topics during the pandemic. OBJECTIVES: To analyze the clinical characteristics and evolution of people living with HIV/AIDS and coinfection with cryptococcus and COVID-19 (group A) or without it (group B). MATERIALS AND METHODS: This is an analytical and retrospective study. We reviewed medical records of patients with meningeal cryptococcosis between April 2020 and May 2021. RESULTS: We studied 65 people living with HIV/AIDS and with cryptococcosis infection diagnosed from April 2020 to May 2021. Fifteen patients with HIV/AIDS suffered from cryptococcosis and COVID-19, and out of these, 14 presented meningitis (group A), while 28 suffered from meningeal cryptococcosis, but did not have COVID-19 (group B). CONCLUSIONS: No statistically significant differences were observed between the two groups (A and B) considering: intracranial hypertension, presence of Cryptococcus antigens in cerebrospinal fluid, sensorium deterioration or mortality. The detection of Cryptococcus antigens in serum by lateral flow assay was highly effective to rapidly diagnose cryptococcosis in patients with HIV/AIDS who also developed COVID-19. Patients of both groups consulted for cryptoccocosis sometime after, in comparison with the pre-pandemic cases related to this infection.

Introducción: Las infecciones fúngicas en pacientes con COVID-19 fue uno de los temas más debatidos durante la pandemia. Objetivo: Analizar las características clínicas y la evolución de personas con VIH/SIDA que presentaron la asociación de criptococosis meníngea y COVID-19 (grupo A), y compararlas con aquellas personas con VIH/SIDA que padecieron criptococosis meníngea, pero sin infección de COVID-19 (grupo B). Materiales y métodos: Se realizó un estudio analítico y retrospectivo en el que se revisaron las historias clínicas de pacientes que padecieron criptococosis meníngea entre abril de 2020 y mayo de 2021. Resultados: Se estudiaron 65 pacientes con HIV/SIDA y con criptococosis, diagnosticados entre abril de 2020 y mayo de 2021 (63 habían desarrollado sida y 2 eran negativos para VIH). De estos, 15 de los pacientes con sida padecían criptococosis y COVID-19, y 14 presentaban meningitis (grupo A), mientras que 28 pacientes padecieron criptococosis meníngea, pero no tuvieron COVID-19 (grupo B). Conclusiones: No se observaron diferencias estadísticamente significativas, entre los dos grupos, respecto a la hipertensión intracraneal, la presencia de antígenos de criptoccoco en líquido cefalorraquídeo, el deterioro del sensorio o la mortalidad. La detección de antígenos de Cryptococcus en suero por ensayo de flujo lateral fue efectiva para diagnosticar rápidamente criptococosis en personas con VIH/sida y con infección de COVID-19. Se observó que los pacientes de ambos grupos consultaron tarde por criptococosis en comparación con los casos prepandémicos de esta infección.

Forest Disturbance and Disease: Exploring the Effects of Tree Harvesting Area on Cryptococcus gattii sensu lato Infection Risk, Vancouver Island, Canada, 1998-2014.

BACKGROUND: The disturbance of colonized trees and soil, such as through forestry activities, has been proposed to disperse soil- and tree-inhabiting fungal pathogens. Cryptococcus gattii sensu lato is one such pathogen that was detected on Vancouver Island, British Columbia, Canada, beginning in 1999 and caused human and animal illness. OBJECTIVES: Our aim was to determine if C. gattii s.l. human case incidence on Vancouver Island was correlated with the intensity of landscape-level tree harvesting occurring near human settlement areas. METHODS: We created buffers around human settlement areas with radii increments of 2.5km, from 2.5 to 20km, and summed the area of annual tree harvests occurring within each buffer zone. We then performed Spearman rank-order correlation to measure the association between case incidence and annual tree harvest intensity at each radius from 1998 through 2014. RESULTS: The incidence of C. gattii was positively correlated with tree harvesting intensity only at distances of 7.5km (r=0.66, p=0.004) and 10km (r=0.64, p=0.005) from human settlement areas. As annual tree harvesting area increased between 1999 and 2003, so did annual C. gattii incidence in humans, before both plateaued around 2002 and decreased after 2007. DISCUSSION: Our findings suggest that tree harvesting plays a role in the spread of C. gattii on Vancouver Island. This may be due to tree cutting or soil disturbance facilitating the aerosolization of spores to increase infection risk. This research also illustrates the contribution that geographic information systems can make to public health research on environmental disturbance and disease outbreaks. https://doi.org/10.1289/EHP12396.

CRYPTOCOCCOSIS: A bibliographic narrative review on antifungal resistance.

Cryptococcosis is an infectious fungal disease widely studied for its epidemiological importance in the context of public health, given the high morbidity and mortality associated with this invasive fungal infection. Many cases of the disease present clinical resistance and progress to death, even in the presence of antifungal therapy. The prolonged use of triazole drugs to maintain the treatment of cryptococcosis in AIDS patients, can lead to selective pressure from mutant strains, among other resistance mechanisms, justifying the poor clinical evolution of some cases. In this study, a narrative review of the literature on the occurrence of antifungal resistance in cryptococcosis agents was performed. Publications from 2010 to 2022 that address this topic were selected using Google Scholars and Scopus website. Data from the studies were analyzed for the values of minimum inhibitory concentration (MIC) of drugs used in the management of cryptococcosis. The review showed that the highest MIC values occurred for voriconazole, especially against C. neoformans. It is concluded that there is a lack of studies with statistical analysis of the data obtained, in order to provide a better dimensioning of the resistance rates of cryptococcosis agents to different antifungal agents, both in geographical and temporal context.

Retrospective analysis of pulmonary cryptococcosis and extrapulmonary cryptococcosis in a chinese tertiary hospital.

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.

Molecular typing and antifungal susceptibility of clinical isolates of Cryptococcus neoformans and Cryptococcus gattii species complexes from the National Invasive Fungal Surveillance Network of Uruguay.

Cryptococcus neoformans and C. gattii species complexes (phylum: Basidiomycota) are environmental yeasts and are the main cause of human cryptococcosis worldwide. The most recent molecular typing studies in Latin America have focused on the intertropical region. Thus, this study aimed to update the knowledge of human cryptococcosis in the South American temperate region. We obtained and analyzed 116 C. neoformans/C. gattii species complexes isolates from the Public Health Surveillance Laboratory between 2008-2013 and 2017-2021 (C. gattii species complex = 1 and C. neoformans species complex = 115). The average patient age was 45 years, with an overall male:female ratio of 3.1:1. The proportion of HIV-negative patients was significantly higher in the second study period. Restriction fragment length polymorphism typing of URA5 gene revealed that the C. neoformans species complex comprised 75.7% VNI, 2.6% VNII, 0.9% VNIII, 1.7% VNIV, 17.4% VNII/VNIV hybrids, and one C. neoformans isolate (0.9%) misidentified as VGI; the C. gattii species complex isolates comprised one VGII. The overall case fatality rate was 49.5%, with no differences in lethality between VNI and hybrid isolates. Of the four isolates responsible for episodes of reoccurrence, only one had a genotype different from the first episode. Antifungal susceptibility testing revealed that most isolates fell below the local epidemiological cut-off value. This study provides additional information for the analysis of C. neoformans/C. gattii species complexes dynamics in the South American temperate region.

This study describes the epidemiological and molecular trends of human cryptococcosis according to the public health Uruguayan surveillance network. The findings provide additional information for analyzing the Cryptococcusneoformans/C. gattii species complexes in the South American temperate region.

Cryptococcal meningoencephalitis: Risk factors associated to death in a hospital in Northeastern Brazil.

INTRODUCTION: Cryptococcosis is an opportunistic systemic mycosis caused by pathogenic encapsulated yeasts of the genus Cryptococcus. The objective of the present study was to evaluate the risk factors associated with death of patients diagnosed with meningitis due to Cryptococcus spp. METHODS: This retrospective cohort study included patients admitted to the São José Hospital (SJH) with Cryptococcal Meningoencephalitis (CM) who were diagnosed between 2010 and 2018. Data collection was carried out by reviewing the patients' medical records. Death during hospitalization was considered the primary outcome. RESULTS: From 2010 to 2018, 21,519 patients were admitted to the HSJ, 124 of whom were hospitalized due to CM. The CM incidence rate was 5.8 cases/103 hospitalizations. We included 112 patients in the study. Male patients were the most affected (82.1%), and the median age was 37 years [IQR: 29-45]. HIV coinfection occurred in 79.4% of the patients. Fever (65.2%) and headache (88.4%) were the most frequent symptoms. Greater cellularity in the CSF was the most related factor to CM in non-HIV individuals (p < 0.05). Death during hospitalization occurred in 28.6% (n = 32) of the patients. The independent risk factors associated with death during the hospitalization were women (p = 0.009), age > 35 years (p = 0.046), focal neurological deficits (p = 0.013), altered mental status (p = 0.018) and HIV infection (p = 0.040). The twelve-month survival was lower in HIV-positive patients (p < 0.05). CONCLUSION: Early diagnosis, optimal treatment, and clinical follow-up strategies, especially in HIV patients, should be prioritized.