RESUMO
BACKGROUND: Cryptococcosis is a global invasive mycosis associated with significant morbidity and mortality. Cryptococcal antigen (CrAg) testing from serum and cerebrospinal fluid (CSF) has been regarded as a gold standard for early diagnosis. This study aimed to develop and validate a rapid and sensitive sandwich chemiluminescent magnetic microparticle immunoassay (CMIA) for quantitative detection of CrAg in sera. RESEARCH DESIGN AND METHODS: CMIA is based on magnetic beads modified with capture antibodies and biotinylated antibodies and Streptavidin-polyHRP, where biotinylated antibodies functioned as the recognition element and Streptavidin-polyHRP as the signal component. Assay parameters were first optimized, and then assay performances were evaluated. RESULTS: Under optimized conditions, the total runtime of the CMIA was 22 min. The assay had a wide linear range (2 -10,000 ng/mL) and high analytical sensitivity (0.24 ng/mL), together with acceptable reproducibility, accuracy, and stability. Besides, it exhibited no cross-reactivity with other pathogens. Importantly, the assay showed 92.91% (95% CI, 80.97-93.02%) overall qualitative agreement with a commercial ELISA kit in a retrospective cohort of 55 cases with confirmed cryptococcal infection, and 72 controls without evidence of invasive fungal disease (IFD). CONCLUSION: These results demonstrated that the present study paved a novel strategy for reliable quantitative detection of CrAg in sera.
Assuntos
Antígenos de Fungos , Criptococose , Medições Luminescentes , Humanos , Antígenos de Fungos/sangue , Antígenos de Fungos/imunologia , Medições Luminescentes/métodos , Imunoensaio/métodos , Criptococose/diagnóstico , Criptococose/sangue , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Cryptococcus/imunologia , Estudos RetrospectivosRESUMO
A 31-year-old Japanese man presented with cerebral and pulmonary cryptococcosis. Cryptococcus gattii (C. gattii) genotype VGIIb was detected in the patient's sputum and cerebrospinal fluid specimens. The serum levels of anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) antibodies were elevated in this patient, which has been associated with pulmonary alveolar proteinosis and is considered a risk factor for C. gattii infection. After undergoing >12 months of antifungal treatments, the patient showed improvements in symptoms and findings on brain and lung imaging. Several Japanese patients who develop C. gattii infection have also been reported; however, most of these patients have been infected outside Japan, as C. gattii infection is rare in Japan. Only one patient with C. gattii genotype VGIIb infection has been reported in Japan, and it is believed that this patient contracted the infection in China. In the present case, our patient has never been outside Japan, indicating that the infection originated in Japan. Our findings suggest that C. gattii might be spreading in Japan. Therefore, patients with positive serum anti-GM-CSF antibodies should be thoroughly monitored for C. gattii infection, even those living in Japan.
Assuntos
Criptococose , Cryptococcus gattii , Genótipo , Fator Estimulador de Colônias de Granulócitos e Macrófagos , Humanos , Masculino , Adulto , Fator Estimulador de Colônias de Granulócitos e Macrófagos/imunologia , Cryptococcus gattii/genética , Cryptococcus gattii/imunologia , Cryptococcus gattii/isolamento & purificação , Criptococose/microbiologia , Criptococose/imunologia , Criptococose/diagnóstico , Criptococose/tratamento farmacológico , Criptococose/sangue , Japão , Antifúngicos/uso terapêutico , Pneumopatias Fúngicas/microbiologia , Pneumopatias Fúngicas/imunologia , Pneumopatias Fúngicas/diagnóstico , População do Leste AsiáticoRESUMO
There is limited research into Invasive fungal disease (IFD) in children with no underlying disease. We undertook a retrospective study of children with IFD who did not suffer from another underlying disease, from June 2010 to March 2018 in Changsha, China. Nine children were identified. Eosinophil counts were elevated in six cases. The level of procalcitonin (PCT) was elevated in six cases. Fungal culture was positive in all patients, including eight cases of Cryptococcus neoformans and one case of Candida parapsilosis. 8.33 days following antifungal treatment, the body temperature of the eight patients affected by cryptococcal disease had returned to normal. Our study indicates that the primary pathogen in IFD was Cryptococcus neoformans in children who had no other underlying disease. Eosinophils can be considered to be indicators of cryptococcal infection. IFD in children with no other underlying disease has a satisfactory prognosis.
Assuntos
Candida parapsilosis/isolamento & purificação , Candidíase/microbiologia , Criptococose/microbiologia , Cryptococcus neoformans/isolamento & purificação , Infecções Fúngicas Invasivas/microbiologia , Adolescente , Antifúngicos/uso terapêutico , Biomarcadores/sangue , Candida parapsilosis/efeitos dos fármacos , Candidíase/sangue , Candidíase/diagnóstico , Candidíase/tratamento farmacológico , Criança , Pré-Escolar , China , Criptococose/sangue , Criptococose/diagnóstico , Criptococose/tratamento farmacológico , Cryptococcus neoformans/efeitos dos fármacos , Eosinófilos/microbiologia , Feminino , Humanos , Infecções Fúngicas Invasivas/sangue , Infecções Fúngicas Invasivas/diagnóstico , Infecções Fúngicas Invasivas/tratamento farmacológico , Contagem de Leucócitos , Masculino , Valor Preditivo dos Testes , Pró-Calcitonina/sangue , Estudos Retrospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Up to 15% of deaths of people living with HIV is attributable to meningeal cryptococcosis, with nearly 75% occuring in sub-Saharan Africa. Although rare in children, it is a major cause of morbidity and mortality in people living with HIV. A strong association between cryptococcal antigenemia and the development of meningeal cryptococcosis has been shown in adults. Thus, in 2018, the World Health Organization published an updated version of its guidelines for the diagnosis, prevention and management of cryptococcal infection in adults, adolescents and the HIV-infected child. GOAL: To determine the prevalence of cryptococcal antigenemia and to identify its determinants in children infected with HIV. METHODS: An analytical cross-sectional study was carried out at the approved treatment center of Laquintinie hospital in Douala over a period of 4 months. Children were recruited consecutively after informed parental consent. Cryptococcal antigenemia and CD4 assay were performed using a Cryptops® immunochromatographic rapid diagnostic test and flow cytometry, respectively. The data collected included the socio-demographic, clinical and paraclinical variables of the children, as well as their antecedents. Data analysis was performed using Epiinfo software version 3.1 and SPSS 21.0. The significance threshold was set at 5%. RESULTS: A total of 147 children were enrolled. The mean age was 9.8 ± 4.09 years. The majority were on antiretroviral therapy (142, 96.60%). Only 13 (8.80%) were in severe immunosuppression. No child showed signs of meningeal cryptococcosis. The prevalence of cryptococcal antigenemia was 6.12%. Severe immunosuppression [OR: 10.03 (1.52-65.91), p = 0.016] and contact with pigeons [OR: 9.76 (1.14-83.65), p = 0.037] were independent factors significantly associated with the carriage of the cryptococcal antigen. CONCLUSION: We recommend screening for cryptococcal antigenemia and routine treatment with fluconazole of all HIV positive children with cryptococcal antigen whether symptomatic or not.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Antígenos de Fungos/sangue , Portador Sadio/epidemiologia , Criptococose/epidemiologia , Cryptococcus/isolamento & purificação , Infecções Oportunistas Relacionadas com a AIDS/sangue , Infecções Oportunistas Relacionadas com a AIDS/imunologia , Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Adolescente , Antígenos de Fungos/imunologia , Camarões/epidemiologia , Portador Sadio/sangue , Portador Sadio/imunologia , Portador Sadio/microbiologia , Criança , Pré-Escolar , Estudos Transversais , Criptococose/sangue , Criptococose/imunologia , Criptococose/microbiologia , Cryptococcus/imunologia , Feminino , Humanos , Lactente , Masculino , PrevalênciaRESUMO
There is scarce information about HIV-related cryptococcosis in the Brazilian Amazon basin where laboratory infrastructure is limited. The serum cryptococcal antigen (CrAg) lateral flow assay (LFA) has simplified diagnosis of cryptococcosis and is recommended for screening in advanced HIV disease. We evaluated the prevalence of cryptococcal antigenemia using finger-prick CrAg LFA in the Brazilian Amazon basin. We enrolled a prospective cohort of outpatients and hospitalized individuals with advanced HIV disease at two centers in Santarém Municipality, Northern Brazil. All individuals were > 18 years old with advanced HIV disease, regardless of antiretroviral therapy (ART) status and with no prior or current history of confirmed cryptococcal meningitis. We tested CrAg LFA on finger-prick whole blood using an exact volume transfer pipette. From August 2018 to October 2019, 104 individuals were enrolled (outpatients 62 [60%] and hospitalized 42 [40%]). Median age was 38 years (interquartile range [IQR] 30-46), and 84 (81%) were male. Sixty-five (63%) individuals were ART-naïve. Prevalence of finger-prick CrAg LFA-positive was 10.6%; 95% CI, 5.4 to 18.1%. Prevalence of finger-prick CrAg LFA-positive among individuals without neurological symptoms was 6.0%; 95% CI, 1.7-14.6%. The number needed to test to detect one CrAg-positive individual was 9.4 persons (95% CI, 5.5-18.5). Prevalence of cryptococcal antigenemia using finger-prick whole blood CrAg LFA was high. Point-of-care approach was important for the diagnosis and screening of cryptococcosis in resource-limited settings. Screening and preemptive therapy strategy should be urgently implemented in individuals with advanced HIV disease in the Brazilian Amazon basin.
This prospective cohort study was carried-out in the Brazilian Amazon basin. We used a cryptococcal rapid test in patients with AIDS. We included 104 participants, and 11 (10.6%) of them had positive results showing a high prevalence of cryptococcal antigenemia.
Assuntos
Antígenos de Fungos/sangue , Criptococose/sangue , Criptococose/diagnóstico , Infecções por HIV/complicações , Manejo de Espécimes/métodos , Adulto , Brasil/epidemiologia , Estudos de Coortes , Criptococose/epidemiologia , Criptococose/etiologia , Feminino , Infecções por HIV/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Fatores de RiscoRESUMO
BACKGROUND: The effects of cryptococcemia on patient outcomes in those with or without HIV remain unclear. METHODS: One hundred and seventy-nine cryptococcemia patients were enrolled in this retrospective study. Demographic characteristics, blood test results and outcome were compared between the two groups. RESULTS: The diagnosis time of Cryptococcus infection was 2.0(0-6.0) days for HIV-infected patients, 5.0 (1.5-8.0) days for HIV-uninfected patients (p = .008), 2.0 (1.0-6.0) days for cryptococcal meningitis (CM) patients and 6.0 (5.0-8.0) days for non-CM patients (p < .001). HIV infection [adjusted odds ratio (AOR) (95% confidence interval): 6.0(2.3-15.9)], CRP < 15 mg/L [AOR:3.7(1.7-8.1)) and haemoglobin > 110 g/L [AOR:2.5(1.2-5.4)] were risk factors for CM development. Forty-six (25.7%) patients died within 90 days. ICU stay [AOR:2.8(1.1-7.1)], hypoalbuminemia [AOR:2.7(1.4-5.3)], no anti-cryptococcal treatment [AOR:4.7(1.9-11.7)] and altered consciousness [AOR:2.4(1.0-5.5)] were independent risk factors for 90-day mortality in all patients. HIV infection did not increase the 90-day mortality of cryptococcemia patients when anti-Cryptococcus treatment was available. Non-Amphotericin B treatment [AOR:3.4(1.0-11.2)] was associated with 90-day mortality in HIV-infected patients, but age ≥ 50.0 years old [AOR:2.7(1.0-2.9)], predisposing disease [AOR:4.1(1.2-14.2)] and altered consciousness [AOR:3.7(1.1-12.9)] were associated with 90-day mortality in HIV-uninfected patients who accepted anti-Cryptococcus treatment. CONCLUSION: HIV infection increased the incidence of CM rather than mortality in cryptococcemia patients. The predictive model was completely divergent in HIV-infected and HIV-uninfected patients, suggesting that novel strategies for diagnosis and treatment algorithms are urgently needed.
Assuntos
Criptococose , Infecções por HIV/complicações , Resultado do Tratamento , Adulto , Idoso , Antifúngicos/uso terapêutico , Criptococose/sangue , Criptococose/tratamento farmacológico , Criptococose/epidemiologia , Cryptococcus/efeitos dos fármacos , Cryptococcus/patogenicidade , Feminino , Humanos , Incidência , Masculino , Meningite Criptocócica/tratamento farmacológico , Meningite Criptocócica/epidemiologia , Pessoa de Meia-Idade , Mortalidade , Estudos Retrospectivos , Fatores de RiscoRESUMO
Cryptococcus neoformans is a human-pathogenic fungal pathogen that causes life-threatening meningoencephalitis in immunocompromised individuals. To investigate the roles of N-glycan core structure in cryptococcal pathogenicity, we constructed mutant strains of C. neoformans with defects in the assembly of lipid-linked N-glycans in the luminal side of the endoplasmic reticulum (ER). Deletion of ALG3 (alg3Δ), which encodes dolichyl-phosphate-mannose (Dol-P-Man)-dependent α-1,3-mannosyltransferase, resulted in the production of truncated neutral N-glycans carrying five mannose residues as a major species. Despite moderate or nondetectable defects in virulence-associated phenotypes in vitro, the alg3Δ mutant was avirulent in a mouse model of systemic cryptococcosis. Notably, the mutant did not show defects in early stages of host cell interaction during infection, including attachment to lung epithelial cells, opsonic/nonopsonic phagocytosis, and manipulation of phagosome acidification. However, the ability to drive macrophage cell death was greatly decreased in this mutant, without loss of cell wall remodeling capacity. Furthermore, deletion of ALG9 and ALG12, encoding Dol-P-Man-dependent α-1,2-mannosyltransferases and α-1,6-mannosyltransferases, generating truncated core N-glycans with six and seven mannose residues, respectively, also displayed remarkably reduced macrophage cell death and in vivo virulence. However, secretion levels of interleukin-1ß (IL-1ß) were not reduced in the bone marrow-derived dendritic cells obtained from Asc- and Gsdmd-deficient mice infected with the alg3Δ mutant strain, excluding the possibility that pyroptosis is a main host cell death pathway dependent on intact core N-glycans. Our results demonstrated N-glycan structures as a critical feature in modulating death of host cells, which is exploited by as a strategy for host cell escape for dissemination of C. neoformansIMPORTANCE We previously reported that the outer mannose chains of N-glycans are dispensable for the virulence of C. neoformans, which is in stark contrast to findings for the other human-pathogenic yeast, Candida albicans Here, we present evidence that an intact core N-glycan structure is required for C. neoformans pathogenicity by systematically analyzing alg3Δ, alg9Δ, and alg12Δ strains that have defects in lipid-linked N-glycan assembly and in in vivo virulence. The alg null mutants producing truncated core N-glycans were defective in inducing host cell death after phagocytosis, which is triggered as a mechanism of pulmonary escape and dissemination of C. neoformans, thus becoming inactive in causing fatal infection. The results clearly demonstrated the critical features of the N-glycan structure in mediating the interaction with host cells during fungal infection. The delineation of the roles of protein glycosylation in fungal pathogenesis not only provides insight into the glycan-based fungal infection mechanism but also will aid in the development of novel antifungal agents.
Assuntos
Morte Celular , Cryptococcus neoformans/genética , Cryptococcus neoformans/patogenicidade , Interações Hospedeiro-Patógeno , Polissacarídeos/química , Células A549 , Animais , Criptococose/sangue , Cryptococcus neoformans/química , Modelos Animais de Doenças , Feminino , Glicosilação , Humanos , Macrófagos/microbiologia , Macrófagos/patologia , Manose/química , Camundongos , Mutação , VirulênciaRESUMO
The basidiomycete yeast Cryptococcus neoformans causes disease in immunocompromized patients. Whole genome sequencing (WGS) technology provides insights into the molecular epidemiology of C. neoformans. However, the number of such studies is limited. Here we used WGS and multilocus sequence typing (MLST) to determine the genetic diversity of C. neoformans isolates and genetic structures of their populations among patients admitted to a single hospital in Bangkok, Thailand. Seven isolates from six patients collected during 1 year were identified as C. neoformans sensu stricto according to colony morphology, microscopy, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and nucleotide sequence analysis of internal transcribed sequences. These isolates were sensitive to the antifungal drugs amphotericin B, fluconazole, 5-flucytosine, voriconazole, itraconazole and posaconazole and were mating type α and molecular type VNI. MLST analysis identified ST4, ST5 and ST6. We further employed WGS to determine the genetic diversity and relationships of C. neoformans isolated here combined with C. neoformans sequences data acquired from a public database (n = 42). We used the data to construct a phylogenetic tree. WGS provided additional genomics data and achieved high discriminatory power for identifying C. neoformans isolates isolated in Thailand. This report further demonstrates the applicability of WGS analysis for conducting molecular epidemiology and provides insight into the genetic diversity of C. neoformans isolates from one hospital in Thailand.
Assuntos
Criptococose/microbiologia , Cryptococcus neoformans/classificação , Variação Genética , Antifúngicos/farmacologia , Criptococose/sangue , Criptococose/líquido cefalorraquidiano , Cryptococcus neoformans/efeitos dos fármacos , Cryptococcus neoformans/genética , Cryptococcus neoformans/isolamento & purificação , Genótipo , Humanos , Tipagem de Sequências Multilocus , Tailândia , Sequenciamento Completo do GenomaAssuntos
Antígenos de Fungos/sangue , Criptococose/microbiologia , Infecções por HIV/complicações , Pneumopatias Fúngicas/microbiologia , Meningite Criptocócica/complicações , Pneumonia/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/sangue , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Adulto , Antígenos de Fungos/imunologia , Brasil/epidemiologia , Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/microbiologia , Criptococose/sangue , Criptococose/diagnóstico , Cryptococcus neoformans/isolamento & purificação , Feminino , Humanos , Pneumopatias Fúngicas/diagnóstico , Masculino , Meningite Criptocócica/diagnóstico , Pessoa de Meia-Idade , Pneumonia/complicações , Pneumonia/diagnóstico , Prevalência , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Cryptococcus species are associated with invasive fungal infections in immunosuppressed individuals. The clinical significance of low-titer cryptococcal antigen (CrAg) by lateral flow assay is frequently uncertain. We investigated the correlation of low CrAg titers with disease in an immunocompromised patient population. Patients with first-time positive CrAg results with low serum titers (≤1:10) at two medical centers (Los Angeles, CA) from April 2014 to July 2018 were included. Age-matched controls with high (≥1:20) and negative titers were selected. We extracted medical records for pertinent clinical, radiologic, and laboratory data for cryptococcal disease. From 2,196 serum samples submitted for CrAg testing, 96 cases were included (32 each in low-titer, high-titer, and negative-titer groups). One or more immunocompromising condition was identified in 95% of patients, including HIV infection (45%), solid organ transplant (26%), and cirrhosis (22%). Pulmonary cryptococcosis was diagnosed in 9 (28%) low-titer and 8 (25%) high-titer patients (P = 1.00). Disseminated cryptococcosis occurred in 7 (22%) low-titer and 15 (47%) high-titers cases (P = 0.064). Titers ≤1:10 more frequently represented isolated antigenemia in HIV-positive than non-HIV, immunocompromised patients (P < 0.001). Follow-up testing in patients with ≤1:5 titers (n = 21) showed persistently low titers in 6 of 12 instances and increased titers in 2 cases. Twenty-seven patients with low CrAg titers were treated with antifungal therapy and 22 (81%) responded well clinically. Low-serum CrAg titers (≤1:10) correlated with cryptococcal disease in a substantial proportion of non-HIV immunocompromised patients and should prompt careful clinical workup for cryptococcal infection.
Assuntos
Antígenos de Fungos/sangue , Criptococose/diagnóstico , Hospedeiro Imunocomprometido , Antifúngicos/uso terapêutico , Bioensaio/estatística & dados numéricos , Estudos de Casos e Controles , Criptococose/sangue , Criptococose/tratamento farmacológico , Feminino , Infecções por HIV/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
The benefits of screening for cryptococcal antigenemia and of preemptive antifungal treatment in HIV-infected patients have been proven. Liver cirrhosis is an important risk factor for cryptococcal infections. Cryptococcal infections are rapidly fatal in patients with liver cirrhosis, especially when diagnosis is delayed. However, screening for cryptococcal antigenemia has not been investigated in these patients. The aim of this study was to investigate the prevalence of cryptococcal antigenemia in hospitalized patients with liver cirrhosis. This prospective study was conducted at Seoul National University Hospital from July 2017 to January 2018. We included patients with liver cirrhosis who were admitted regardless of symptoms or signs suggesting cryptococcal infections. The severity of cirrhosis was evaluated from Child-Pugh and model for end-stage liver disease (MELD) scores. Serum cryptococcal antigenemia was determined using a latex agglutination test. A total of 294 patients were included in the analysis, comprising 104 (35.4%), 100 (34.0%), and 90 (30.6%) patients in Child-Pugh classes A, B, and C, respectively. There were 21 cases of spontaneous bacterial peritonitis, and 14 of hepatic encephalopathy, but none of cryptococcal peritonitis or meningitis. In addition, none of the patient specimens tested positive in the serum cryptococcal latex agglutination test (one-sided 97.5% confidence interval, 0% â¼ 1.2%). Liver cirrhosis is a major risk factor for cryptococcal infections, but the prevalence of serum cryptococcal antigen positivity in patients with liver cirrhosis is very low. Therefore, screening for cryptococcal antigenemia and preemptive antifungal treatment in cirrhotic patients might not be beneficial.
Assuntos
Antígenos de Fungos/sangue , Criptococose/sangue , Cirrose Hepática/epidemiologia , Cirrose Hepática/microbiologia , Idoso , Antígenos de Fungos/imunologia , Criptococose/complicações , Criptococose/imunologia , Cryptococcus , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Testes de Fixação do Látex , Cirrose Hepática/complicações , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Fatores de Risco , Soro/imunologia , Índice de Gravidade de DoençaRESUMO
Although the point-of-care cryptococcal antigen lateral flow assay (LFA) has revolutionized the diagnosis of cryptococcosis in human patients, to date there has been no large-scale examination of this test in animals. We therefore assessed the LFA in cats, dogs and koalas suspected of having cryptococcosis. In sum, 528 serum specimens (129 from cats, 108 from dogs, 291 from koalas) were tested using the LFA and one of two commercially available latex cryptococcal antigen agglutination test (LCAT) kits. The LCAT is a proven and well-accepted method in veterinary patients and therefore taken as the "gold standard" against which the LFA was compared. The LFA achieved a sensitivity of 92%, 100%, and 98% in cats, dogs, and koalas, respectively, with corresponding negative predictive values of 94%, 100%, and 98%. The specificity of the LFA was 81%, 84%, and 62% for cats, dogs, and koalas, respectively, with corresponding positive predictive values of 76%, 48%, and 69%. These findings suggest the most appropriate role for the LFA is as a screening test to rule out a diagnosis of cryptococcosis in cats, dogs, and koalas. Point-of-care accessibility makes it equally suited for use in the field and as a cage-side test in veterinary hospitals. The suboptimal specificity of the LFA makes it less suited to definitive confirmation of cryptococcosis in animals; therefore, all LFA-positive test results should be confirmed by LCAT testing. The discrepancy between these observations and the high specificity of the LFA in humans may reflect differences in the host-pathogen interactions amongst the species.
Assuntos
Doenças do Gato/diagnóstico , Cromatografia de Afinidade/veterinária , Criptococose/veterinária , Doenças do Cão/diagnóstico , Testes de Fixação do Látex/veterinária , Phascolarctidae/microbiologia , Animais , Antígenos de Fungos/sangue , Doenças do Gato/sangue , Doenças do Gato/microbiologia , Gatos , Criptococose/sangue , Criptococose/diagnóstico , Cryptococcus , Doenças do Cão/sangue , Doenças do Cão/microbiologia , Cães , Masculino , Sistemas Automatizados de Assistência Junto ao Leito , Valor Preditivo dos Testes , Fitas Reagentes , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Cryptococcus is encapsulated opportunistic yeast that causes life threatening meningoencephalitis of patients with human immunodeficiency virus (HIV). The magnitude of Cryptococcosis among HIV patients varies from 1-10% in Western countries as opposed to almost a one third of HIV-infected individuals in sub-Saharan Africa where it is associated with high mortality. METHODOLOGY: By using key terms "Cryptococcosis among HIV patients in sub-saharan Africa countries", articles that published in different journals from 2010-2017 searched on Pub-Med and Google scholar database. Those freely accessible and included the prevalence of Cryptococcosis in the result section, their PDF file was downloaded and the result extracted manually and presented in table. Articles that did not report the prevalence of Cryptococcosis, with a study design otherthan cross sectional, or a sample size less than 100, and those duplicated in the same study area and period by the same authors were excluded. The article selection followed the PRISMA guidelines and meta- analysis was performed using OpenMeta(analyst). RESULTS: The overall pooled magnitude of Cryptococcosis among HIV patients in sub saharan African countries was 8.3% (95%CI 6.1-10.5%). The highest prevalence was from Uganda (19%) and the least was from Ethiopia at 1.6%. There was 87.2 % of substantial heterogeneity among the studies with p-value<0.001. The symmetry ofthe forest plot showed that there was little publication bias. The most commonly used method for diagnosis of Cryptococcosis was lateral flow assay and latex agglutination test and culture was the least method employed. CONCLUSION: The overall pooled magnitude of Cryptococcosisis high among HIV patients in sub-Saharan African countries. The studies showed substantial heterogeneity, and little publication bias. Most of the studies relied on LFA & LA that showed the scarcity of facilities for fungal culture. Therefore, paying attention to screening HIV patients; those with signs and symptoms of meningitis may help to reduce the loss of HIV patients.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Criptococose/epidemiologia , Infecções por HIV/complicações , Meningoencefalite/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/sangue , África/epidemiologia , Fármacos Anti-HIV/uso terapêutico , Criptococose/sangue , Criptococose/complicações , Etiópia/epidemiologia , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Infecções por HIV/imunologia , Humanos , Masculino , Meningoencefalite/sangue , Meningoencefalite/complicações , Prevalência , Uganda/epidemiologiaRESUMO
BACKGROUND: The indications for lumbar puncture in non-HIV-infected, non-transplant (NHNT) patients with cryptococcosis without meningeal signs need to be more fully defined. OBJECTIVES: This study was designed to determine the optimal predictors of central nervous system (CNS) involvement in adult NHNT patients with cryptococcosis. METHODS: The study population consisted of adult NHNT patients with culture-confirmed cryptococcosis who sought care at a university hospital in Taiwan from 2002 to 2016. We used a case-control method to identify the clinical characteristics and laboratory findings associated with CNS involvement in patients who underwent a diagnostic lumbar puncture. In the sensitivity analysis, we included additional control patients who did not undergo lumbar puncture, but were followed beyond 12 months without the development of CNS involvement in the absence of exposure to any fungicidal agents. RESULTS: We entered 270 NHNT adult patients into the study during the 15-year period. CNS involvement was confirmed in 66 (71.0%) of 93 patients who underwent lumbar puncture. A multivariable analysis revealed that presence of neurological manifestations and elevated serum CRAG titers were independently associated with a 23.97-fold (95% confidence interval [CI], 4.37-182.23) and 1.53-fold (per 2-fold increment, 95% CI 1.26-1.92) increased odds ratio for CNS involvement, respectively. Headache and focal neurologic signs were independently associated with CNS involvement. A cut-off serum CRAG titer of ≥1:64 provided the highest diagnostic performance by Youden index (sensitivity 83% and specificity 65%). Similar findings were noted in the sensitivity analysis including 198 (73%) patients. CONCLUSION: Lumbar puncture is indicated for NHNT patients with cryptococcosis who have neurologic manifestations or a serum CRAG titer of ≥1:64.
Assuntos
Criptococose/complicações , Infecções por HIV/complicações , Vértebras Lombares/patologia , Punção Espinal , Transplante , Adulto , Idoso , Antígenos de Bactérias/sangue , Sistema Nervoso Central/patologia , Criptococose/sangue , Criptococose/imunologia , Humanos , Pessoa de Meia-Idade , Curva ROCRESUMO
BACKGROUND: Point-of-care (POC) Cryptococcus antigen assays may provide veterinarians with a more rapid, patient-side diagnosis when compared with traditional laboratory-based latex agglutination tests. OBJECTIVE: To determine the sensitivity and specificity of 2 POC lateral flow cryptococcal serum antigen tests, CrAg LFA (Immy, Norman, OK) and the CryptoPS (Biosynex, Strasbourg, France) for diagnosis of cryptococcosis in dogs and cats, using the cryptococcal antigen latex agglutination system (CALAS) as the reference standard. ANIMALS: 102 serum samples from 51 dogs and 40 cats. METHODS: Specimens were classified as CALAS-positive (n = 25) or CALAS-negative (n = 77). The sensitivity and specificity of each POC assay was calculated by comparing the results to the serologic reference standard results. RESULTS: The CrAg LFA assay correctly classified 23/25 CALAS-positive specimens and 69/74 CALAS-negative specimens resulting in a sensitivity of 92.0% (confidence interval [CI], 75.0%-98.6%) and specificity of 93.2% (CI, 85.1%-97.1%). The CryptoPS assay correctly classified 8/10 tested CALAS-positive specimens and 56/59 tested CALAS-negative specimens resulting in a sensitivity of 80.0% (CI, 49.0%-96.5%) and specificity of 94.9% (CI, 86.1%-98.6%). CONCLUSION AND CLINICAL IMPORTANCE: The POC assays appear to be a sensitive and specific alternative to the traditional CALAS assay with more rapid turnaround times, which may result in earlier diagnosis and treatment.
Assuntos
Antígenos de Fungos/sangue , Doenças do Gato/diagnóstico , Criptococose/veterinária , Cryptococcus/imunologia , Doenças do Cão/diagnóstico , Animais , Doenças do Gato/imunologia , Doenças do Gato/microbiologia , Gatos , Criptococose/sangue , Criptococose/diagnóstico , Criptococose/imunologia , Doenças do Cão/imunologia , Doenças do Cão/microbiologia , Cães , Testes Imediatos , Sensibilidade e EspecificidadeAssuntos
Celulite (Flegmão)/diagnóstico , Criptococose/diagnóstico , Cryptococcus neoformans/isolamento & purificação , Idoso , Antifúngicos/uso terapêutico , Criptococose/sangue , Criptococose/tratamento farmacológico , Criptococose/microbiologia , Diagnóstico Diferencial , Feminino , Fluconazol/uso terapêutico , Humanos , Hospedeiro Imunocomprometido , Pele/microbiologia , Pele/patologia , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Coxa da Perna , Resultado do TratamentoRESUMO
Concomitant influenza and cryptococcal infections are rare. Herein, we describe an unusual case of an avian influenza A (H7N9) infection with several severe mixed bacterial infections and systemic super-infection with Cryptococcus neoformans presenting as ventilator-associated pneumonia (VAP) and bloodstream infection in a previously immunocompetent man during hospitalization.A 58-year-old man was admitted to our hospital complaining of hyperpyrexia, dyspnoea, cough, and phlegm with blood. A chest computed tomography scan revealed multiple ground-glass opacities and consolidation in both lungs with right pleural effusion. An initial sputum test was positive for influenza A (H7N9) virus. After antiviral treatment and other supportive measures, the patient's condition improved. However, the patient's condition deteriorated again approximately 2 weeks after admission, and bronchoalveolar lavage fluid (BALF) and blood cultures were positive for C. neoformans. Therapy with intravenous liposomal amphotericin B and fluconazole was started. After a 2-week antifungal treatment, BALF and blood cultures were negative for C. neoformans. However, the patient had persistent lung infiltrates with severe pulmonary fibrosis with a prolonged course of disease. On hospital day 40, BALF and blood cultures were both positive for multidrug-resistant Stenotrophomonas maltophilia. Finally, the patient developed septic shock, disseminated intravascular coagulation and multi-organ failure and succumbed to treatment failure.Cryptococcal infection can occur in patients with severe influenza during hospitalization with a more severe condition, and the clinician should be aware of this infection.
Assuntos
Coinfecção , Criptococose/complicações , Cryptococcus neoformans , Influenza Humana/complicações , Coinfecção/sangue , Coinfecção/diagnóstico , Coinfecção/tratamento farmacológico , Criptococose/sangue , Criptococose/diagnóstico , Criptococose/tratamento farmacológico , Diagnóstico Diferencial , Evolução Fatal , Humanos , Influenza Humana/sangue , Influenza Humana/diagnóstico , Influenza Humana/tratamento farmacológico , Masculino , Pessoa de Meia-IdadeRESUMO
Cryptococcal infection is a major cause of opportunistic infection in HIV/AID-infected peoples. We determined cryptococcal antigenemia and cryptococcal meningitis among antiretroviral therapy (ART) initiated and ART-naive HIV-infected peoples. A cross-sectional study was conducted at selected health facilities in Mekelle, Ethiopia. Blood was collected to determine CD4 and plasma cryptococcal antigen (CrAg). CSF CrAg and CSF culture and urease tests were also done. Socio-demographic and clinical data were collected using a structured questionnaire and clinical chart review. From the enrolled study participants, 267 study participants had complete data, of which, 137 (51%) were females. From the study participants, 140 (52%) and 127 (48%) were ART experienced and ART naïve, respectively. The prevalence of cryptococcal antigenemia was 9 (3.4%). All the study participants, except one (CD4 = 120 cells/mm3 ), had CD4 count less than 100 cells/mm3 . From CrAg-positive peoples, 6 (4.7%) were ART naïve. Five CrAg-positive peoples had cryptococcal meningitis. Being male, rural residence, and being hospitalized were associated with cryptococcal antigenemia. Cryptococcal infection poses a substantial risk of HIV-positive peoples. This study provides relevant data for CrAg screening interventions in patients with low CD4 cell counts.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Fármacos Anti-HIV/administração & dosagem , Criptococose/microbiologia , Cryptococcus/fisiologia , Infecções por HIV/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/sangue , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/imunologia , Adulto , Fármacos Anti-HIV/efeitos adversos , Antígenos de Fungos/sangue , Contagem de Linfócito CD4 , Estudos Transversais , Criptococose/sangue , Criptococose/epidemiologia , Criptococose/imunologia , Cryptococcus/classificação , Cryptococcus/genética , Cryptococcus/isolamento & purificação , Etiópia/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
OBJECTIVES: Pentraxin 3 (PTX3) contributes to resistance to Aspergillus infections. This study aimed to evaluate the presence of PTX3 in bronchoalveolar lavage fluid (BALF) and plasma in non-neutropenic patients with pulmonary aspergillosis. METHODS: BALF (n = 211) and plasma samples (n = 307) were collected from patients initially suspected of having pulmonary aspergillosis. Among these, 112 cases (51 BALF samples and 89 plasma samples) were proven to be pulmonary aspergillosis. These cases were classified as invasive pulmonary aspergillosis (IPA), subacute invasive aspergillosis (SAIA) and chronic pulmonary aspergillosis (CPA). The remaining cases were non-aspergillosis controls and were diagnosed with community-acquired pneumonia (CAP), lung cancer and pulmonary cryptococcosis. Plasma samples from healthy controls (n = 30) were also collected. RESULTS: The median (interquartile range, IQR) BALF PTX3 for aspergillosis cases was significantly higher than for non-aspergillosis cases: 6.97 (2.91-13.51) ng/mL versus 1.26 (0.76-1.76) ng/mL. When the PTX3 threshold was set at 1.9 ng/mL, sensitivity and specificity of BALF PTX3 for aspergillosis were 86.3% (95%CI 83.8-88.4%) and 82.5% (95%CI 79.7-85.0%), respectively. The median (IQR) plasma PTX3 for aspergillosis cases was significantly higher than for non-aspergillosis cases and healthy controls: 7.10 (3.36-9.53) ng/mL versus 1.57 (0.86-2.35) ng/mL versus 1.10 (0.49-1.51) ng/mL. With a PTX3 threshold of 2.3 ng/mL, sensitivity and specificity were 79.8% (95%CI 70.1-81.2%) and 72.1% (95%CI 69.5-74.5%) respectively. CONCLUSIONS: BALF and plasma PTX3 may be biomarkers for differentiating aspergillosis from other conditions such as CAP, lung cancer, and pulmonary cryptococcosis in non-neutropenic patients.