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1.
Med Mycol ; 62(1)2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38126122

RESUMO

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.


Assuntos
Criptococose , Cryptococcus neoformans , Infecções por HIV , Meningite Criptocócica , Humanos , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/veterinária , Incidência , Taiwan/epidemiologia , Criptococose/tratamento farmacológico , Criptococose/epidemiologia , Criptococose/complicações , Criptococose/veterinária , Meningite Criptocócica/tratamento farmacológico , Meningite Criptocócica/epidemiologia , Meningite Criptocócica/veterinária , Antifúngicos/uso terapêutico
2.
Med Mycol ; 61(12)2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37952096

RESUMO

Cryptococcal meningitis is the second most common cause of death in people living with HIV/AIDS, yet we have a limited understanding of how cryptococcal isolates change over the course of infection. Cryptococcal infections are environmentally acquired, and the genetic diversity of these infecting isolates can also be geographically linked. Here, we employ whole genome sequences for 372 clinical Cryptococcus isolates from 341 patients with HIV-associated cryptococcal meningitis obtained via a large clinical trial, across both Malawi and Cameroon, to enable population genetic comparisons of isolates between countries. We see that isolates from Cameroon are highly clonal, when compared to those from Malawi, with differential rates of disruptive variants in genes with roles in DNA binding and energy use. For a subset of patients (22) from Cameroon, we leverage longitudinal sampling, with samples taken at days 7 and 14 post-enrollment, to interrogate the genetic changes that arise over the course of infection, and the genetic diversity of isolates within patients. We see disruptive variants arising over the course of infection in several genes, including the phagocytosis-regulating transcription factor GAT204. In addition, in 13% of patients sampled longitudinally, we see evidence for mixed infections. This approach identifies geographically linked genetic variation, signatures of microevolution, and evidence for mixed infections across a clinical cohort of patients affected by cryptococcal meningitis in Central Africa.


Cryptococcal meningitis, caused by Cryptococcus, results in approximately half a million deaths per year globally. We compare clinical Cryptococcus samples from Cameroon and Malawi to explore the genetic diversity of these isolates. We find instances of mixed-strain infections and identify genetic variants arising in Cryptococcus over disease.


Assuntos
Síndrome da Imunodeficiência Adquirida , Coinfecção , Cryptococcus neoformans , Cryptococcus , Infecções por HIV , Meningite Criptocócica , Humanos , Meningite Criptocócica/epidemiologia , Meningite Criptocócica/veterinária , Cryptococcus neoformans/genética , Cryptococcus/genética , Camarões/epidemiologia , Coinfecção/veterinária , Síndrome da Imunodeficiência Adquirida/complicações , Síndrome da Imunodeficiência Adquirida/veterinária , Variação Genética , Infecções por HIV/complicações , Infecções por HIV/veterinária
3.
Med Mycol ; 61(12)2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38031335

RESUMO

Although non-human immunodeficiency virus (HIV)-associated cryptococcal meningitis (CM) is a severe disease, there are still some non-HIV CM patients with a low risk of therapeutic failure. Recognizing clinical characteristics of low-risk non-HIV-associated CM may enable clinicians to treat non-HIV-associated CM more reasonably. According to the definition of low-risk non-HIV-associated CM in the 2010 Infectious Diseases Society of America guideline, a total of 220 non-HIV CM patients were divided into two groups (Group 1: 35 low-risk patients and Group 2: 185 non-low-risk patients). Clinical characteristics, treatment, and outcome were compared between the two groups. Compared with non-low-risk patients, low-risk patients had a lower rate of headache (82.9% vs. 95.7%, P = .012), cerebrospinal fluid (CSF) opening pressure (OP) at baseline (CSF OP < 250-mm H2O, 60.0% vs. 32.4%, P = .001), and baseline CSF cryptococcal count (median, 0 vs. 2376, P < .001), higher baseline CSF white blood cell (median, 130 vs. 90, P = .029) and CSF protein (median, 0.87 vs. 0.73, P = .011). Multivariate analysis showed that baseline CSF OP <250-mm H2O (OR: 2.545, 95% CI 1.168, 5.545, P = .019) was independently associated with low-risk for non-HIV-associated CM. The lengths of AMB-d-based induction therapy of low-risk patients (median, 20 days) were shorter (P < .001) than that of non-low-risk patients (median, 38 days). The successful outcome rate of low-risk patients was higher than non-low-risk patients (97.1% vs. 54.6%, P < .001). We demonstrated that non-HIV-associated CM patients with baseline CSF OP < 250-mm H2O were prone to the low-risk status.


This was a retrospective cohort study to find the features of low-risk non-human immunodeficiency virus (HIV)-associated cryptococcal meningitis (CM). We found that non-HIV-associated CM patients with baseline cerebrospinal fluid opening pressure <250-mm H2O were prone to low-risk status.


Assuntos
Cryptococcus , Infecções por HIV , Meningite Criptocócica , Humanos , Meningite Criptocócica/tratamento farmacológico , Meningite Criptocócica/líquido cefalorraquidiano , Meningite Criptocócica/veterinária , Estudos Retrospectivos , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/veterinária , Resultado do Tratamento
4.
Med Mycol ; 61(9)2023 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-37656871

RESUMO

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.


Assuntos
Criptococose , Cryptococcus , Infecções por HIV , Meningite Criptocócica , Adulto , Masculino , Humanos , Brasil/epidemiologia , Meningite Criptocócica/epidemiologia , Meningite Criptocócica/veterinária , Prevalência , Estudos Prospectivos , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Infecções por HIV/veterinária , Criptococose/diagnóstico , Criptococose/epidemiologia , Criptococose/veterinária , Antígenos de Fungos , Sistema Nervoso Central
5.
Med Mycol ; 61(10)2023 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-37771088

RESUMO

Host non-T cell markers to aid in the diagnosis of cryptococcal meningoencephalitis (CM) have not been identified. In this case-control study, we characterized antibody and B cell profiles in HIV-negative and HIV-positive Vietnamese individuals of the Kinh ethnicity recently diagnosed with CM and controls. The study included 60 HIV-negative with no known immunocompromising condition and 60 HIV-positive individuals, with 30 CM cases and 30 controls in each group. Participants were matched by age, sex, HIV serostatus, and CD4 count in the HIV-positive group. Plasma immunoglobulin (Ig) levels, including IgG1, IgG2, IgM, and IgA, Cryptococcus spp. glucuronoxylomannan (GXM)- and laminarin (branched ${\rm{\beta }}$-[1-3]-glucan)-binding IgG, IgM, IgA levels, and peripheral blood B cell subsets were measured. Logistic regression, principal component, and mediation analyses were conducted to assess associations between antibody, B cell levels, and CM. The results showed that GXM-IgG levels were higher and IgG1 and IgG2 were lower in CM cases than controls, regardless of HIV status. In HIV-negative individuals, IgG2 mediated an inverse association between CD19+CD27+CD43+CD5- (B-1b-like) cells and CM. In HIV-positive individuals, lower levels of IgA, laminarin-IgA, and CD19+CD27+IgM+IgD- (IgM+ memory B) cells were each associated with CM. The shared and distinct antibody and B cell profiles identified in HIV-negative and HIV-positive CM cases may inform the identification of non-T-cell markers of CM risk or unsuspected disease, particularly in HIV-negative individuals.


Unlike cryptococcal meningitis (CM) in HIV-positive individuals, there are no known biomarkers of risk in HIV-negative individuals and the diagnosis is often not suspected and delayed. This study identified non-T cells, including antibody and B cell CM-associated profiles that may guide cryptococcal antigen testing in HIV-negative individuals.


Assuntos
Cryptococcus neoformans , Infecções por HIV , Meningite Criptocócica , Meningoencefalite , Humanos , Estudos de Casos e Controles , Infecções por HIV/complicações , Infecções por HIV/veterinária , Imunoglobulina M , Imunoglobulina G , Meningoencefalite/veterinária , Imunoglobulina A , Meningite Criptocócica/veterinária
6.
Med Mycol ; 61(4)2023 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-37055372

RESUMO

Oxidative imbalances have been observed in various neurological diseases. Despite the microbiological control in cryptococcal meningitis (CM), a proportion of previously healthy patients experience a clinical deterioration known as post-infectious inflammatory response syndrome (PIIRS). However, the antioxidant status in PIIRS remains unclear. In this study, we found that the serum antioxidant status of HIV-negative immunocompetent CM patients during PIIRS episodes was lower than that of healthy controls. There was a relationship between baseline serum indirect bilirubin levels and the development of PIIRS, and serum uric acid levels may indicate the severity of the disease during PIIRS episodes. Oxidative stress may play a role in the development of PIIRS.


This retrospective study on the serum antioxidant status in HIV-negative immunocompetent CM patients suggested that during PIIRS episodes, the serum antioxidant status in CM patients may be lower. CM patients with high baseline serum Ibil levels were more likely to develop PIIRS.


Assuntos
Infecções por HIV , Meningite Criptocócica , Animais , Antioxidantes , Bilirrubina , Meningite Criptocócica/veterinária , Ácido Úrico , Infecções por HIV/veterinária , Albuminas
7.
Med Mycol ; 60(10)2022 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-36149324

RESUMO

Cryptococcal antigen (CrAg) is a capsule polysaccharide antigen that can be detected in the fluids of patients with cryptococcal infections. Cryptococcal Antigen Latex Agglutination System (CALAS), enzyme-linked immunosorbent assays (EIA), and lateral flow assay (LFA) are the main methods available. Two main commercial LFA kits are available: CryptoPS (Biosynex, Illkirch Graffenstaden, France) and CrAg LFA (IMMY, Inc. USA). In our lab, we prospectively used CryptoPS as a screening tool in serum for confirmed positive results with CALAS. We investigated the rigor of the CryptoPS test in serum in a multicentric evaluation over 3 years. To improve the specificity of CryptoPS in serum, we additionally implemented and evaluated a pretreatment protocol before CryptoPS testing. A total of 43 serum samples collected from 43 patients were investigated. We found that the CryptoPS assay is hampered by a high rate of false-positive results in serum with a high rate of CryptoPS-positive but CrAg LFA-negative and CALAS-negative sera in patients with no proof of Cryptococcus infection (n = 29). Using a simple pretreatment procedure (5 min incubation at 100°C and centrifugation) we were able to reverse false-positive results, suggesting that there could be interferent material present in the serum. Pretreatment also impacted the CryptoPS results (negative result) in two patients with the cryptococcal disease, one with isolated antigenemia and one with cryptococcal meningitis. Comparing the titers obtained with CALAS and CrAg LFA, we noticed that the titer obtained with CrAg LFA was almost 10-fold higher than those with CALAS. This study showed that Biosynex CryptoPS in serum could give false-positive results even in the absence of cryptococcal disease. These could be reduced by applying an easy pretreatment procedure to the serum before testing, with little but existing impact on the sensitivity.


Lateral flow assays are useful to detect the cryptococcal antigen in human fluids. We investigated CryptoPS-positive results and observed that true false-positive results occurred. The false-positive results can be reduced by applying an easy pretreatment procedure.


Assuntos
Criptococose , Cryptococcus , Infecções por HIV , Meningite Criptocócica , Animais , Antígenos de Fungos , Criptococose/diagnóstico , Criptococose/veterinária , Infecções por HIV/veterinária , Meningite Criptocócica/diagnóstico , Meningite Criptocócica/veterinária , Soro
8.
Med Mycol ; 60(9)2022 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-36074073

RESUMO

To explore the brain volume (BV) changes of HIV-negative and non-transplant cryptococcal meningitis (CM) in 1 year after initial therapy. Case data were collected from 78 CM patients who underwent magnetic resonance imaging (MRI) scanning at least 3 times in 1-year interval after initial therapy. The assessment of BV was measured by a non-commercial software, uAI Research Portal. Linear mixed model was used to investigate the association between clinical characteristics and the changes in BV. Longitudinal study showed a decrease in total brain volume (-4.65 cm3, P = .005), regional brain volume including white matter (-2.86 cm3, P = .031) and basal ganglia (-0.25 cm3, P = .007), and increase in cerebrospinal fluid (CSF) volume (3.58 cm3, P = .013) in CM patients in 1 year after initial therapy. Ventricular volume in patients with ventriculoperitoneal shunts (VPS) was lower than that in patients without VPS (-7.5 cm3, P < .05). Ventricular volume in patients with post-infectious inflammatory response syndrome (PIIRS) was larger than that in patients without PIIRS (7.1 cm3, P < .01). In addition, temporal lobe atrophy was associated with corticosteroid therapy (-6.8 cm3, P < .01). The present study suggested that brain atrophy, especially regional BV decrease, could happen in HIV-negative and non-transplant CM patients over a 1-year interval.


We investigated the evolution of brain volume changes in different regions among HIV-negative and non-transplant cryptococcal meningitis (CM) patients within 1 year after initial therapy. To assess whether brain atrophy occurs among HIV-negative and non-transplant CM patients.


Assuntos
Infecções por HIV , Meningite Criptocócica , Corticosteroides/uso terapêutico , Animais , Atrofia/complicações , Atrofia/patologia , Atrofia/veterinária , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Infecções por HIV/complicações , Infecções por HIV/veterinária , Estudos Longitudinais , Meningite Criptocócica/tratamento farmacológico , Meningite Criptocócica/veterinária , Estudos Retrospectivos
9.
Med Mycol ; 60(4)2022 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-35362524

RESUMO

Cryptococcus is an opportunistic pathogenic fungus and is the major cause of fungal meningitis. The cryptococcal antigen (CrAg) lateral flow assay (LFA) is an immunochromatographic test system that has simplified diagnosis as a point-of-care test. In this study, we evaluated the diagnostic performance of Cryptococcal capsular polysaccharide detection FungiXpert (Genobio Pharmaceutical, Tianjin, China) using serum and cerebrospinal fluid (CSF) samples for the diagnosis of cryptococcosis and investigated the cross-reaction of the assays to pathogenic fungi and bacterium by comparing it to the U.S. Food and Drug Administration (US FDA)-approved IMMY CrAg LFA. Eighty CSF and 119 serum/plasma samples from 158 patients were retrospectively collected to test for qualitative or semi-quantitative detection of CrAg. Cross-reaction of the assays was tested using 28 fungi and 1 bacterium. Compared to IMMY CrAg LFA, the FungiXpert LFA demonstrated 99.1% sensitivity and 98.9% specificity in the qualitative test. In the 96 semi-quantitative CrAg assay results, 39 (40.6%) test titers of FungiXpert LFA were 1-2 dilutions higher than those of IMMY CrAg LFA. The Intraclass Correlation Coefficient of the Semi-quantitative results of CrAg titer tests via the two assays was 0.976. Similar to IMMY CrAg LFA, FungiXpert LFA showed cross-reactivity with Trichosporon asahii. Compared with the IMMY CrAg LFA, the FungiXpert LFA showed an equal, yet, excellent performance. However, it is important to note that these two assays have potential cross-reactivity to T. asahii when diagnosing patients. FungiXpert LFA is a rapid screening method for the effective and practical diagnosis and treatment of cryptococcosis. LAY SUMMARY: The FungiXpert LFA was developed to diagnose fungal meningitis caused by Cryptococcus yeasts, by using serum or cerebrospinal fluid. It was compared to an existing lateral flow assay (LFA). The FungiXpert LFA performed well in qualitative and semi-quantitative tests.


Assuntos
Criptococose , Cryptococcus , Infecções por HIV , Meningite Criptocócica , Meningite Fúngica , Animais , Antígenos de Fungos , Criptococose/diagnóstico , Criptococose/veterinária , Infecções por HIV/veterinária , Meningite Criptocócica/diagnóstico , Meningite Criptocócica/veterinária , Meningite Fúngica/veterinária , Polissacarídeos , Estudos Retrospectivos
10.
Med Mycol ; 60(4)2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35353190

RESUMO

Cryptococcal antigen (CrAg) screening and pre-emptive antifungal therapy for people with CD4 cell counts <100 cells/µl are recommended by the World Health Organization and several national HIV guidelines. We sought to evaluate CrAg screening program implementation across Uganda, in relation to health center level and distance from the capital. We conducted a cross-sectional study of 22 health centers across southern Uganda from April to June 2019. We reviewed laboratory records regarding number of CD4 cell count tests performed, proportion of outpatients with CD4 counts <200 cells/µl, and number of CrAg screening tests performed. We administered surveys to health center staff to understand barriers to advanced HIV care. We observed no significant difference in health center level and performance of CrAg screening; with each subsequent health center level, there was 1.17-fold (95% CI: 0.92-1.41) higher odds of CrAg screening performed per level. CrAg screening uptake was not associated with distance from the capital city (odds ratio = 0.96, 95% CI: 0.89-1.04). Qualitative data from surveys indicated that limitations to uptake of CrAg screening were secondary to dysfunctional CD4 machines, lack of provider awareness of CrAg screening guidelines, and inadequate/intermittent supply of CrAg tests. There were no significant associations between CrAg screening uptake and level of health center or distance of health center from the capital city. We identified systemic barriers to CrAg screening related to inadequate CD4 testing, insufficient knowledge regarding national screening guidelines, and irregular laboratory testing supplies. LAY SUMMARY: The objective of this study was to evaluate cryptococcal antigen (CrAg) screening program implementation in Uganda, by type of healthcare center and by distance from the capital city. CrAg screening uptake was not associated with distance from the capital city, or the type of healthcare center.


Assuntos
Cryptococcus , Meningite Criptocócica , Animais , Antígenos de Fungos , Estudos Transversais , Humanos , Meningite Criptocócica/diagnóstico , Meningite Criptocócica/veterinária , Uganda
11.
Med Mycol ; 60(2)2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-35026017

RESUMO

Cryptococcal antigen (CrAg) screening is recommended for patients with advanced HIV to reduce AIDS-related mortality. For asymptomatic CrAg-positive persons, fluconazole pre-emptive therapy is standard, despite a ∼25% failure rate. Single-dose liposomal amphotericin B (AmBisome) is non-inferior to standard treatment for cryptococcal meningitis. We evaluate the threshold of efficacy necessary for AmBisome + fluconazole to be cost-effective as pre-emptive therapy for CrAg-positive persons.We created a decision analytic model to evaluate CrAg screening and treatment in HIV-infected persons with CD4 < 100 cells/µL. Costs were estimated for screening, pre-emptive therapy, and hospitalization for an example low-income country (Uganda) and middle-income country (South Africa). We used a discounted price range of AmBisome® at ${\$}$16.25 to ${\$}$40 per 50 mg vial for both Uganda and South Africa. We estimated AmBisome efficacy from 75 to 95%. Parameter assumptions were based on prospective CrAg screening studies and clinical trials in Africa. Disability adjusted life years (DALYs) were calculated using the age-specific life expectancy in Uganda, per WHO Global Health Observatory data. We modeled the theoretical efficacy of adjunctive AmBisome to determine cost per DALY averted.In South Africa, at ${\$}$16.25 per vial cost and a minimum efficacy of 85%, adjunctive AmBisome is cost-saving compared to fluconazole monotherapy. Compared to fluconazole pre-emptive therapy in Uganda, AmBisome + fluconazole would cost ${\$}$475, ${\$}$220, or ${\$}$136 per DALY averted if meningitis-free survival efficacy was 80, 85, or 90% at ${\$}$24 per vial cost.Investing in AmBisome may be cost-effective in low-income settings compared to using fluconazole pre-emptive therapy alone, if efficacy is 85% or greater. AmBisome pre-emptive therapy appears more cost-efficient in middle-income settings where hospitalization costs for meningitis, and GDP per capita are higher. LAY SUMMARY: We evaluate the efficacy necessary for AmBisome + fluconazole to be cost-effective to prevent cryptococcal meningitis. We found that if AmBisome pre-emptive therapy has an efficacy of 85% or greater, it is likely to be cost-effective in low-income settings.


Assuntos
Infecções por HIV , Meningite Criptocócica , Anfotericina B , Animais , Antifúngicos/uso terapêutico , Antígenos de Fungos , Contagem de Linfócito CD4/veterinária , Análise Custo-Benefício , Países em Desenvolvimento , Fluconazol , Infecções por HIV/tratamento farmacológico , Infecções por HIV/veterinária , Meningite Criptocócica/tratamento farmacológico , Meningite Criptocócica/prevenção & controle , Meningite Criptocócica/veterinária , Estudos Prospectivos , Uganda
12.
Med Mycol ; 59(10): 1041-1047, 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34169984

RESUMO

Blood cryptococcal antigen (CrAg) titers >160 are associated with concurrent subclinical cryptococcal meningitis (CM). When lumbar puncture (LP) is not immediately available in a CrAg screening program, semi-quantitative CrAg assays may provide risk stratification for CM. Two semi-quantitative assays (SQ [Immuno-Mycologics, Norman, OK, USA] and CryptoPS [Biosynex, Strasbourg, France]) were evaluated against a qualitative lateral flow assay (LFA) using 194 plasma samples from a cohort of HIV-seropositive individuals with CD4 counts <100 cells/µl. We compared SQ and CryptoPS results to titers for LFA-positive samples. Among patients with LP, we examined the association between semi-quantitative CrAg results and CM. We used a Cox proportional hazards model to determine the association between SQ score and mortality. Of 194 participants, 60 (31%) had positive LFA results, of whom 41 (68%) had a titer of ≤160 and 19 (32%) a titer >160. Fifty individuals with antigenemia had an LP; a clinically useful SQ score that identified all ten cases of subclinical CM was ≥3 (100% sensitivity, 55% specificity). Patients with an SQ score of 3 or 4 also had a 2.2-fold increased adjusted hazards of 6-month mortality (95% CI: 0.79-6.34; p = 0.13) versus those with score of <3. Nine of ten patients with subclinical CM had a strong-positive CryptoPS result versus 10/40 without subclinical CM (p < 0.001). Semi-quantitative assays offered a sensitive though not specific means of gauging the risk of concurrent CM in this patient population. LAY SUMMARY: We evaluated two single-step laboratory tests that can quantify the amount of cryptococcal antigen in plasma of patients with advanced HIV disease and could thus gauge the risk of concurrent cryptococcal meningitis and subsequent mortality. These tests are not a substitute for a lumbar puncture.


Assuntos
Cryptococcus , Infecções por HIV , Meningite Criptocócica , Animais , Antígenos de Fungos , Estudos de Coortes , Infecções por HIV/complicações , Infecções por HIV/veterinária , Meningite Criptocócica/diagnóstico , Meningite Criptocócica/veterinária
15.
BMC Vet Res ; 10: 84, 2014 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-24708822

RESUMO

BACKGROUND: Cryptococcus spp. are saprophytic and opportunistic fungal pathogens that are known to cause severe disease in immunocompromised animals. In goats there are reports of clinical cryptococcal pneumonia and mastitis but not of meningitis. CASE PRESENTATION: The following report describes a case of a five year old buck showing severe neurological signs, including paraplegia and strong pain reaction to touch of the hindquarters region. Treatment with antibiotics was unsuccessful and the animal was euthanized for humanitarian reasons. Postmortem examination revealed lumbar meningitis, lung nodules and caseous lymphadenitis lesions. Encapsulated Cryptococcus neoformans were identified from the lungs and meninges, showing that cryptococcal meningitis should be included in the differential diagnosis of goats showing paresis and hyperesthesia. The possibility of concurrent immunosuppression due to Corynebacterium pseudotuberculosis infection is raised. CONCLUSIONS: Cryptoccocal meningitis should be included in the differential diagnosis list of goat diseases with ataxia and hyperesthesia.


Assuntos
Doenças das Cabras/parasitologia , Meningite Criptocócica/veterinária , Animais , Doenças das Cabras/patologia , Cabras , Masculino , Meningite Criptocócica/patologia
16.
J Comp Pathol ; 147(2-3): 106-10, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22520822

RESUMO

Cerebral cryptococcomas are described in a 5-year-old mixed-breed cow without manifestations of systemic cryptococcosis. Two cryptococcomas were observed grossly. Microscopical examination revealed accumulations of yeast that were morphologically consistent with Cryptococcus neoformans. Immunohistochemistry characterized the organisms as C. neoformans var. grubii.


Assuntos
Doenças dos Bovinos/patologia , Criptococose/veterinária , Cryptococcus neoformans/isolamento & purificação , Meningite Criptocócica/veterinária , Animais , Antígenos de Fungos/análise , Encéfalo/microbiologia , Encéfalo/patologia , Bovinos , Doenças dos Bovinos/microbiologia , Criptococose/microbiologia , Criptococose/patologia , Cryptococcus neoformans/genética , Cryptococcus neoformans/imunologia , DNA Fúngico/análise , Feminino , Meningite Criptocócica/microbiologia , Meningite Criptocócica/patologia
17.
J Vet Diagn Invest ; 23(5): 1056-60, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21908375

RESUMO

Cryptococcal meningitis and encephalitis is reported in a 5-year-old bull. The clinical signs included multifocal neurological deficits manifested by hypermetria, ataxia, depression, circling, impaired vision, head pressing, low head carriage, wide-based stance, and falling to the side or backwards. At necropsy, 6 cavities with a gelatinous content were observed in the brain and brain stem, and the meninges were thickened and off white. Numerous yeasts, with a nonstaining capsule, and associated mild inflammatory reaction were observed histologically. Specimens for culture were not collected at necropsy, but the identity of the yeast in tissue sections as Cryptococcus neoformans var. grubii was supported by immunohistochemistry.


Assuntos
Doenças dos Bovinos/microbiologia , Meningite Criptocócica/veterinária , Animais , Encéfalo/patologia , Bovinos , Doenças dos Bovinos/diagnóstico , Doenças dos Bovinos/patologia , Cryptococcus neoformans/classificação , Cryptococcus neoformans/isolamento & purificação , Masculino , Meningite Criptocócica/diagnóstico , Meningite Criptocócica/patologia
18.
Med Mycol ; 49(7): 779-84, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21395475

RESUMO

A domestic ferret (Mustela putorius furo) was presented with lymphadenopathy and acute bilateral blindness. Cytologic evaluation and biopsy of an affected lymph node revealed pyogranulomatous lymphadenitis with intralesional yeast consistent with Cryptococcus sp. Subsequent studies demonstrated Cryptococcus gattii serotype B VGI/AFLP4 as the causative agent. The ferret was treated with fluconazole and prednisone. After one month of therapy, an improvement of the clinical symptoms was detected although blindness persisted. Seven months after presentation, the disease progressed to a severe neurologic condition, and it was euthanized. Postmortem exam revealed disseminated cryptococcosis with prominent neurologic involvement. Nasal swabs of other ferrets and humans from the same household revealed that two ferrets and two humans to be asymptomatic carriers of the same strain of cryptococcus as the necropsied ferret. These findings stress the importance of veterinary diagnostic work with pets and epidemiological investigations for disease prevention in them and in their owners.


Assuntos
Portador Sadio/microbiologia , Portador Sadio/veterinária , Criptococose/microbiologia , Criptococose/veterinária , Cryptococcus gattii/isolamento & purificação , Análise do Polimorfismo de Comprimento de Fragmentos Amplificados , Animais , Anti-Inflamatórios/administração & dosagem , Antifúngicos/administração & dosagem , Biópsia , Cegueira/microbiologia , Cegueira/veterinária , Criptococose/complicações , Criptococose/patologia , Cryptococcus gattii/classificação , Cryptococcus gattii/genética , Furões , Fluconazol/administração & dosagem , Humanos , Doenças Linfáticas/microbiologia , Doenças Linfáticas/veterinária , Meningite Criptocócica/microbiologia , Meningite Criptocócica/veterinária , Tipagem Molecular , Técnicas de Tipagem Micológica , Animais de Estimação , Prednisona/administração & dosagem
19.
Vet Radiol Ultrasound ; 52(3): 306-8, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21342308

RESUMO

A 4-year-old neutered female domestic shorthair was evaluated for mentation changes and left prosencephalic signs. This imaging report describes the imaging findings for this patient. A diagnosis of a cryptococcal mass was made based on imaging and additional diagnostics. Complete resolution of the mass was demonstrated by follow-up imaging. This report serves as a reminder that masses associated with cryptococcal infection should be included on the differential list for cats with intracranial masses. In addition, this report provides evidence that large intracranial cryptococcal masses may resolve with long-term medical therapy.


Assuntos
Doenças do Gato/diagnóstico , Criptococose/veterinária , Imageamento por Ressonância Magnética/veterinária , Meningite Criptocócica/veterinária , Animais , Gatos , Criptococose/diagnóstico , Feminino , Meningite Criptocócica/diagnóstico
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