Cryptococcosis Infection Research Articles

Machine learning-based prognostic prediction for hospitalized HIV/AIDS patients with cryptococcus infection in Guangxi, China

ObjectiveTo develop and validate a machine learning model for predicting mortality-associated prognostic factors in order to reduce in-hospital mortality rates among HIV/AIDS patients with Cryptococcus infection in Guangxi, China.MethodsThis retrospective prognostic study included HIV/AIDS patients with cryptococcosis in the Fourth People’s Hospital of Nanning from October 2011 to June 2019. Clinical features were extracted and used to train ten machine learning models, including Logistic Regression, KNN, DT, RF, Adaboost, Xgboost, LightGBM, Catboost, SVM, and NBM, to predict the outcome of HIV patients with cryptococcosis infection. The sensitivity, specificity, AUC, and F1 value were applied to assess model performance in both the testing and training sets. The optimal model was selected and interpreted.ResultsA total of 396 patients were included in the study. The average in-hospital mortality of HIV/AIDS patients with cryptococcosis was 12.9% from 2012 to 2019. After feature screening, 20 clinical features were selected for model construction, accounting for 93.8%, including ART, Electrolyte disorder, Anemia, and 17 laboratory tests. The RF model (AUC 0.9787, Sensitivity 0.9535, Specificity 0.8889, F1 0.7455) and the SVM model (AUC 0.9286, Sensitivity 0.7907, Specificity 0.9786, F1 0.8293) had excellent performance. The SHAP analysis showed that the primary risk factors for prognosis prediction were identified as BUN/CREA, Electrolyte disorder, NEUT%, Urea, and IBIL.ConclusionsRF and SVM machine learning models have shown promising predictive abilities for the prognosis of hospitalized HIV/AIDS patients with cryptococcosis, which can aid clinical assessment and treatment decisions for patient prognosis.

Chemical Identification of Purified Molecule (3-Ethyl-6,7-dihydroxy-2- phenyl-chromen-4-one) Prepared from Alpinia officinarum with Anti- Cryptococcus neoformans Potential

Background: Plants contain a large number of molecules with various potentials, including antifungal impact. Cryptococcus neoformans (C. neoformans) is a yeast that causes Cryptococcosis infection in both immunocompromised and normal individuals worldwide. Objective: This study aimed to investigate the inhibitory impact of plant extracts on C. neofor-mans and perform purification of the most bioactive product for further chemical identifica-tion. Methods: The anti-C. neoformans potential of fourteen plants extracted by using various sol-vents, including water, methanol, and benzene, was tested. The most promising compound with anti-C. neoformans was purified. The minimal inhibitory level of the purified sub-frac-tion as compared to fluconazole as a standard drug was determined. The chemical identifica-tion of the purified product was carried out using FTIR, 1HNMR, elemental analysis, and Mass spectroscopy. Results: Alpinia officinarum (A. officinarum) methanolic extract has the highest antifungal impact on C. neoformans and showed an inhibition zone of 3.2±0.2 cm. The methanolic ex-tract was separated into 14 fractions, where the fifth fraction showed the highest activity. It was further separated into four sub-fractions that were tested to characterize the most promis-ing molecule with anti-C. neoformans impact, which was further chemically identified as 3-Ethyl-6,7-dihydroxy-2-phenyl-chromen-4-one. The purified product led to significant altera-tions in the ultra-structure of C. neoformans relative to the standard drug.

Human T-Lymphotropic Virus Type 1 and Cryptococcosis Infection, an Underdiagnosed Association: Case Series and Literature Review.

Clinical and epidemiological features of 7 human immunodeficiency virus-negative Peruvian patients coinfected with human T-lymphotropic virus type 1 (HTLV-1) and cryptococcosis (2006-2017) were studied. Most cases had meningeal involvement, were male, and originated from Peru's jungle. Patients with cryptococcosis should be tested for HTLV-1 in endemic areas of this retrovirus.

Disseminated cryptococcosis in a patient with idiopathic CD4 + T lymphocytopenia presenting as prostate and adrenal nodules: diagnosis from pathology and mNGS, a case report

Disseminated Cryptococcosis infection typically occurs in immunocompromised patients, often manifested as pneumonia or meningoencephalitis. Cases with involvement of either prostate or adrenal glands are less frequent. We describe a case of an immunocompromised 62-year-old man with new-found Idiopathic CD4 + T lymphocytopenia who presented with urinary irritation symptoms followed by headache. The patient was finally diagnosed as disseminated cryptococcosis of prostate, adrenal gland involvement with the help of combining histopathology of formalin-fixed, paraffin-embedded tissue with metagenomic next-generation sequencing technique to identify C neoformans sensu stricto in prostate, adrenal gland tissues. Clinicians should be aware of atypical presentations of cryptococcal disease. In this case of cryptococcosis in immunocompromised patients, we find that cryptococcosis can affect varied organs simultaneously and should be considered in the differential of infectious diseases. And mNGS technology helps to confirm the diagnosis.

Meningeal cryptococcosis and SARS-CoV-2 infection in people living with HIV/AIDS.

Fungal infections in patients with COVID-19 was one of the most debated topics during the pandemic. 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). This is an analytical and retrospective study. We reviewed medical records of patients with meningeal cryptococcosis between April 2020 and May 2021. 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). 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.

A CT-based radiomics integrated model for discriminating pulmonary cryptococcosis granuloma from lung adenocarcinoma-a diagnostic test.

Chest computed tomography (CT) is a critical tool in the diagnosis of pulmonary cryptococcosis as approximately 30% of normal immunity individuals may not exhibit any significant symptoms or laboratory findings. Pulmonary cryptococcosis granuloma and lung adenocarcinoma can appear similar on noncontrast chest CT. This study evaluates the use of an integrated model that was developed based on radiomic features combined with demographic and radiological features to differentiate pulmonary cryptococcosis nodules from lung adenocarcinomas. Preoperative chest CT images for 215 patients with solid pulmonary nodules with histopathologically confirmed lung adenocarcinoma and cryptococcosis infection were collected from two clinical centers (108 cases in the training set and 107 cases in the test set divided by the different hospitals). Radiomics models were constructed based on nodular lesion volume (LV), 5-mm extended lesion volume (ELV), and perilesion volume (PLV). A demoradiological model was constructed using logistic regression based on demographic information (age, sex) and 12 radiological features (location, number, shape and specific imaging signs). Both models were used to build an integrated model, the performance of which was assessed using the test set. A junior and a senior radiologist evaluated the nodules. Receiver operating characteristic (ROC) curve analysis was conducted, and areas under the curve (AUCs), sensitivity (SEN), and specificity (SPE) of the models were calculated and compared. Among the radiomics models, AUCs of the LV, ELV, and PLV were 0.558, 0.757, and 0.470, respectively. Age, lesion number, and lobular sign were identified as independent discriminative features providing an AUC of 0.77 in the demoradiological model (SEN 0.815, SPE 0.642). The integrated model achieved the highest AUC of 0.801 (SEN 0.759, SPE 0.755), which was significantly higher than that obtained by a junior radiologist (AUC =0.689, P=0.024) but showed no significant difference from that of the senior radiologist (AUC =0.784, P=0.388). An integrated model with radiomics and demoradiological features improves discrimination of cryptococcosis granulomas from solid adenocarcinomas on noncontrast CT. This model may be an effective strategy for machine complementation to discrimination by radiologists, and whole-lung automated recognition methods might dominate in the future.

Cryptococcosis in non-HIV/non-transplant hematological patients: A 12-year retrospective clinical analysis in a Peruvian referral cancer center.

e19536 Background: Globally, cryptococcal infection has become a public health challenge. However, relatively little is known about cryptococcal infection in non-HIV/non-transplant oncohematological patients. Methods: We developed a retrospective cohort study that includes hematological patients who had cryptococcosis infection seen in the Instituto Nacional de Enfermedades Neoplasicas between 2007 and 2018. We exclude HIV and transplant recipients patients. Results: During the 12-year study period, among 14908 individuals with hematological malignancies (HM), a total of 21 cases of cryptococcosis were identified, representing an incidence rate of 1.41 per 1000 HM diagnosed in our center. Non-Hodgkin lymphoma (NHL) (47.6%), acute leukemias (23.8%), multiple myeloma (19.1%), and Hodgkin lymphoma (9.5%). Three cases of adult T-cell leukemia/lymphoma were identified. The sub-group analysis showed that NHL (7.35 per 1000 NHL) and Multiple myeloma (4.59 per 1000 MM) had the highest incidence rates. Regarding the clinical presentation, the time between the diagnosis of cryptococcosis and HM was 42 (18–161) days. Cryptococcal fungemia and antigenemia was the most frequent diagnosis (85.7%), followed by pulmonary (52.4%) and central nervous system (38.1%) involvement. At the time of the diagnosis of cryptococcosis, 61.5% were receiving chemotherapy, 53.9% were in the induction phase, and 7.7% were on maintenance therapy. The use of immunosuppressants and chemotherapy within a month of the diagnosis of cryptococcosis was the most common risk factor (90.5%). Regarding the subanalysis performed between the different types of malignancies (NHL versus other HM), age at admission (p = 0.02), site of cryptococcosis presentation (p = 0.01), and lymphocyte count at admission (p = 0.01) were statistically different between these groups. In the NHL subgroup, there was less involvement of the lungs and higher fungemia (p = 0.01). The overall survival (OS) of our cohort at 15 and 120 days was 70% (95%CI: 0.43-0.86) and 51% (95%CI: 0.26-0.72), respectively. OS for patients with NHL was 57% at 15 days (95% CI: 0.17-0.83) and 42% at 120 days (95%CI:0.09-0.73). OS for other HM was 90% at 15 days (95%CI:0.47-0.98) and 60% at 120 days (95%CI: 0.25-0.82). Conclusions: Our cohort characterized the distinct clinical presentation, risk factors, and outcomes of cryptococcal infection in hematologic malignancies subgroups. NHL was the HM with the worst prognosis and the highest incidence rate. [Table: see text]

Abstract 6753: Non-HIV cryptococcal patients with hematological malignancies: A retrospective analysis of a ten-year study from a Peruvian oncologic center

Abstract Background Globally, cryptococcal infection has become a public health challenge. However, relatively little is known about cryptococcal infection in people with hematological disorders. Methods We developed a retrospective cohort study that includes hematological patients who had cryptococcosis infection seen in the Instituto Nacional de Enfermedades Neoplasicas between 2007 and 2017. Results During the 11-year study period, a total of 21 cases of cryptococcosis (incidence rate of 13,4 per 1000 hematological malignancies). The time of diagnosis of cryptococcosis since hematologic malignancy diagnosis was 42 (18-161) days. Non-Hodgkin lymphoma (NHL) was the most frequent malignancy (47.6%), followed by leukemias (23.8%), multiple myeloma in (19.1%), and HL (9.5%). Three cases of adult T-cell leukemia/lymphoma associated with HTLV-1 infection were identified in the NHL. Cryptococcemia was the most frequent diagnosis (85.7%) followed by pulmonary (52.4%) and CNS (38.1%) involvement. Regarding clinical presentation, f ever was the most common symptom in meningeal cryptococcosis (76.2%) and dyspnea in pulmonary cryptococcosis (61.9%). The use of immunosuppressant chemotherapy within a month before the diagnosis of cryptococcosis was the most common risk factor. The main characteristics between patients with cryptococcosis and type of neoplasms (NHL vs other hematological neoplasms) such as age at admission, site of presentation of cryptococcosis, and lymphocyte count at admission were different significantly between these groups. In the NHL group, there was less involvement of the lungs. Overall survival (OS) in 15 and 120 days were 70% (95%CI: 0.43-0.86) and 51% (95%CI: 0.26-0.72), respectively. OS for patients with NHL was 57% at 15 days (95% CI: 0.17-0.83) and 42% at 120 days (95%CI:0.09-0.73). OS for other hematological malignancies was 90% at 15 days (95%CI:0.47-0.98) and 60% at 120 days (95%CI: 0.25-0.82). Conclusions CNS cryptococcal infection was more frequent in patients with NHL. Citation Format: Kelly Meza, Luis E. Cuellar. Non-HIV cryptococcal patients with hematological malignancies: A retrospective analysis of a ten-year study from a Peruvian oncologic center. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6753.

Horse: a potential source of Cryptococcus neoformans and Cryptococcus gattii in Egypt

BackgroundCryptococcosis is an opportunistic mycozoonosis of global significance in a wide variety of host species. In equines, cryptococcosis is uncommon, and sporadic cases have been reported with rhinitis, sinusitis, pneumonia, and meningitis. Cryptococcus spp. represents a potential risk for immunosuppressed and healthy persons. In Egypt, epidemiological data on cryptococcal infection in horses are limited. The current study was carried out to investigate the occurrence of Cryptococcus spp. in horses and its possible role in the epidemiology of such disease in Egypt.A total of 223 samples was collected from different localities in Egypt included 183 nasal swabs from horses, 28 nasal swabs from humans, and 12 soil samples. Bacteriological examination and the identification of Cryptococcus spp. were performed. Molecular serotyping of Cryptococcus spp. was determined by multiplex PCR using CNa-70S/A-CNb-49S/A. The virulence genes (LAC1, CAP59, and PLB1) of the identified isolates were detected by PCR. Moreover, sequencing and phylogenetic analysis of the C. gattii gene from horses, humans, and soil isolates found nearby were performed.ResultThe overall occurrence of Cryptococcus spp. in horses were 9.3, 25, and 10.7% in horses, the soil, and humans, respectively. Molecular serotyping of the Cryptococcus spp. isolates recovered from the nasal passages of horses proved that C. gattii (B), C. neoformans, and two hybrids between C. neoformans (A) and C. gattii (B) were identified. Meanwhile, in case of soil samples, the isolates were identified as C. gattii (B). The human isolates were serotyped as C. gattii in two isolates and C. neoformans in only one isolate. Molecular detection of some virulence genes (LAC1), (CAP59), and (PLB1) were identified in both C. gattii and C. neoformans isolates. The C. gattii gene amplicons of the isolates from horses, humans, and the soil were closely related.ConclusionThis study provides the first insights into the Egyptian horse ecology of Cryptococcus species and highlights the role of horses as asymptomatic carriers in disseminating the potentially pathogenic Cryptococcus spp. It also presents the possible risk of cryptococcosis infection in humans.

717. Susceptibility to Cryptococcosis in Bruton's Tyrosine Kinase Knockout Model

Abstract Background Patients receiving the Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib have an increased likelihood of systemic and central nervous system (CNS) fungal infections. Previous work has shown that BTK knockout (KO) mice have more severe Aspergillus infection compared to wild-type (WT) mice. We sought to determine: 1) if blocking BTK impacted Cryptococcus infection; 2) if the effect was strain-dependent; and 3) if the blood-brain barrier was impaired in BTK KO mice. Methods BTK KO C57 breeding pairs were obtained from Dr. Lionakis (NIH) and expanded in the Duke Breeding Core. We collected 4 clinical C. neoformans isolates from patients who developed cryptococcosis on ibrutinib and used virulent and avirulent control strains (H99 and A1-35-8, respectively). The following doses were used for infection: 1) 5x104 yeast for intranasal (IN); 2) 5x104 for oropharyngeal aspiration (OPA); and 3) 0.1 mL of 5x105 CFU/mL for tail vein injection. Mice were sacrificed on day 7 (IN infection, 6 infection strains; N=35 WT, 80 KO) and day 14 post-infection (OPA infection H99 only; N=15 WT, 20 KO). Lung and brain tissues were collected for yeast census. For tail vein injection, mice were sacrificed 48 hours post-infection (H99 only; N=10 WT, 8 KO). Yeast census was measured by colony forming units (CFUs) per gram of tissue weight. Survival experiments through day 28 were performed for OPA infection with H99 (N=12 WT, 17 KO) and analyzed by Kaplan Meier Curve. Results We observed no difference in infection severity as measured by lung and brain yeast census at days 7 and 14 post-infection or difference in survival between BTK KO and WT mice (Figure 1). We also did not observe a distinct pattern based on Cryptococcus strain to suggest that infection severity was strain-dependent (Figure 1A-B). For tail vein infection, there was no difference in brain yeast census at 48 hours post-infection (Figure 1F). Figure 1. Yeast Census and Survival. A) Lung yeast census day 7 post-intranasal infection with 6 clinical strains and 2 control strains; B) Brain yeast census day 7 post-intranasal infection with 6 clinical strains and 2 control strains; C) Lung yeast census day 14 post infection by oropharyngeal aspiration with H99; D) Brain yeast census day 14 post infection by oropharyngeal aspiration with H99; E) 28 day survival post-infection by oropharyngeal aspiration with H99; F) Brain yeast census 48 hours post infection by tail vein injection. Conclusion Our results in mice suggest that Ibrutinib target BTK is not a major contributing factor for controlling Cryptococcus, and that human susceptibility to cryptococcosis and CNS infection may be due to an off-target effect of ibrutinib. Future work will focus on pharmacologic inhibition of BTK with ibrutinib to determine if the off-target effects of the drug increase risk for cryptococcosis. Disclosures Julia A. Messina, MD, MHS, MS, Uptodate (Other Financial or Material Support) Julia A. Messina, MD, MHS, MS, Uptodate (Individual(s) Involved: Self): Author, Other Financial or Material Support John R. Perfect, MD, Astellas Pharma, Inc. (Consultant, Grant/Research Support, Other Financial or Material Support, Honorarium)Basilea (Consultant, Grant/Research Support)Enzon (Consultant, Grant/Research Support)F2G (Consultant, Grant/Research Support)Merck (Consultant, Research Grant or Support)MethylGene (Consultant, Grant/Research Support)Pfizer, Inc. (Consultant, Grant/Research Support)Schering-Plough Corp. (Consultant, Grant/Research Support)

GRANULOMATOUS MASTITIS IS NOT ALWAYS TUBERCULAR: ROLE OF FINE NEEDLE ASPIRATION CYTOLOGY IN EVALUATION OF GRANULOMATOUS MASTITIS

INTRODUCTION AND OBJECTIVES:
 Granulomatous mastitis is rare chronic inflammatory benign breast lesion, which clinically and radiologically resembles carcinoma breast thus creating a diagnostic dilemma. The term granulomatous mastitis includes two broad categories namely specific granulomatous mastitis for which aetiological factors can be defined such as infectious causes like Mycobacterium tuberculosis, blastomycosis, cryptococcosis, histoplasmosis, actinomycosis and filarial infection. Other factors include association with autoimmunue diseases such as Wegner’s granulomatosis and giant cell arteritis and there are other rare causes such as include duct ectasia, foreign body reaction and fat necrosis which also leads to granulomatous lesions of breast.
 Cytological features of granulomatous mastitis(GM) have not been widely discussed and described in literature, so through this study we have made an attempt to thoroughly discuss cytological spectrum of granulomatous mastitis.
 MATERIALS AND METHODS:
 A retrospective study was performed over a period of four years from 2016 to 2019. A total of 465 cases of breast lump reported to cytopathology section out of which 24 cases of GM diagnosed on FNAC were included in our study. Results of Erythrocyte sedimentation rate (ESR) and Mantoux test along with TB-PCR were recorded. FNAC slides were retrieved pertaining to study period.
 Granulomatous lesions of breast were further categorized broadly into IGM/ NGM, granulomatous mastitis without caseous necrosis and tubercular mastitis where diagnosis were made definite on basis of demonstration of AFB or positive TB-PCR .
 RESULTS:
 Patient age ranged from 23 years to 55 years with the mean age of 36.6 years with maximum of patients falling in second decade followed by third decade. Granulomatous lesions were broadly categorized into Idiopathic/ Non specific granulomatous mastitis(11 cases,45.8%), GM with caseous necrosis(8 cases, 33.3%) and tubercular mastitis(5 cases, 20.9%). Histopathology was available in 7 cases(29.2%). TB-PCR was sent in all cases of granulomatous mastitis diagnosed on cytology and was positive in 10 cases(41.7%).
 CONCLUSION:
 Idiopathic granulomatous mastitis and tubercular mastitis are rare inflammatory diseases of breast which mimic malignancy clinically and radiologically. FNAC plays important role in diagnosis of granulomatous diseases of breast and also their differentiation from malignant tumors. Tubercular mastitis needs to be differentiated from IGM since treatment options are different in both the cases. Cytopathology plays an important role in differentiationg both the diseases supplemented by radiological and microbiological investigations.
 The present study thus highlights the importance of FNAC as an infalliable tool in diagnosis of granulomatous mastitis and its differentiation from neoplastic lesions of breast thus avoiding time consuming histopathological work up of cases.

Characterization of Anti-Interferon-γ Antibodies in HIV-Negative Patients Infected With Disseminated Talaromyces marneffei and Cryptococcosis.

BackgroundFew reports of Talaromyces marneffei (TM) or cryptococcosis infections among HIV-negative patients with high-titeranti–IFN-γautoantibodies (nAIGAs) have been published. We investigated the clinical manifestations of patients with nAIGAs and TM infections.MethodsHIV-negative adults (≥18 years) were enrolled if they haddisseminated TM infection (group 1; further divided into nAIGAs positive [group 1P] and negative [group 1N]); cryptococcosis(pulmonary cryptococcosis and/or cryptococcosis of the brain)(group 2); pulmonary tuberculosis (group 3); and healthy controls (group 4) with nAIGAs detected. Complete histories, physical examinations, and routine clinical laboratory tests were obtained at baseline.ResultsOverall, 88 participants were in the four groups (20,13,23, and 32 in groups 1 to 4, respectively). Significant differences occurred between groups with higher nAIGAs titers (P < 0.001), and higher total white-cell and absolute neutrophil counts (P < 0.001) in group1. Lungs (90.0%), lymph nodes (60.0%), skin (55.0%), and bones (50.0%) were most common sites of involvement. Significant differences in total white-cell and absolute neutrophil counts occurred between groups IP and 1N.Patients with recurrent TM infections, particularly group 1P, had higher initial nAIGA titer. ConclusionsPatients with persistent infection who died tended to have positive initial nAIGA titer. It suggests that nAIGAs may play a critical role in the pathogenesis of TM infections, and may be associated with more severe, refractory infection.

Proteomics of Rat Lungs Infected by Cryptococcus gattii Reveals a Potential Warburg-like Effect.

Cryptococcus gattii is the causative agent of cryptococcosis infection that can lead to pneumonia and meningitis in immunocompetent individuals. The molecular basis of the pathogenic process and impact on the host biochemistry are poorly understood and remain largely unknown. In this context, a comparative proteomic analysis was performed to investigate the response of the host during an infection caused by C. gattii. Lungs of experimentally infected rats were analyzed by shotgun proteomics to identify differentially expressed proteins induced by C. gattii clinical strain. The proteomic results were characterized using bioinformatic tools, and subsequently, the molecular findings were validated in cell culture and lungs of infected animals. A dramatic change was observed in protein expression triggered by C. gattii infection, especially related to energy metabolism. The main pathways affected include aerobic glycolysis cycle, TCA cycle, and pyrimidine and purine metabolism. Analyses in human lung fibroblast cells confirmed the altered metabolic status found in infected lungs. Thus, it is clear that C. gattii infection triggers important changes in energy metabolism leading to the activation of glycolysis and lactate accumulation in lung cells, culminating in a cancerlike metabolic status known as the Warburg effect. The results presented here provide important insights to better understand C. gattii molecular pathogenesis.

Cryptococcosis and cryptococcal meningitis: New predictors and clinical outcomes at a United States academic medical centre.

As the diagnosis of cryptococcosis is challenging in low-prevalence settings, uncovering predictive factors can improve early diagnosis and timely treatment. The aim of the study was to relate clinical outcomes to predictive variables for the presence of cryptococcosis. A retrospective case-control study matched by collection date, age and gender at a 1:2 ratio (55 cases and 112 controls) was performed in case patients diagnosed with Cryptococcus infection at the University of Colorado Hospital between 2000 and 2017 (n=167). A bivariate and a forward, stepwise multivariable logistic regression model were performed to identify predictors of cryptococcosis infection. In an adjusted multivariable model, cryptococcal infection was significantly associated with the presence of respiratory symptoms, hyponatremia, lung disease or corticosteroids. Additionally, cryptococcal meningitis was associated with headaches, corticosteroids or increased CSF protein. Conversely, a reduced risk of cryptococcosis was associated with hypertension or peripheral monocytosis. Cryptococcal meningitis leads to subsequent hearing impairment (16% vs 4% (control), P=.013), muscle weakness (40% vs 20%, P=.021), cognitive deficits (33% vs 6%, P=.0001) or any adverse outcome (84% vs 29%, P=.0001). We uncovered novel clinical predictors for the presence of cryptococcal infection or cryptococcal meningitis. This study in patients at a low-prevalence US medical centre underscores the importance of early diagnosis in this population.

Prevalence and factors associated with cryptococcosis infection in patients with HIV and AIDS, Esperanza Hospital, Luanda, 2016

Introduction: cryptococcosis is an infectious, systemic and opportunistic mycosis in HIV and AIDS patients. To date, few studies on Cryptococcosis and HIV and AIDS have been done in Angola. Thus, this study was carried out to determine the prevalence and factors associated with cryptococcosis infection in patients with HIV and AIDS at Hospital Esperana, a tertiary hospital, in Luanda, Angola. Methods: a cross-sectional study was carried out from March 1 to June 30, 2016. The data was obtained through a semi-structured questionnaire administered to participants, and a review of clinical processes and laboratory tests. For the associated factors were using the odds ratio, Chi square test (nominal variables) or Z test (numerical variables) with 95% confidence level. Results: of the 165 samples (55%) were processed, of which 33% were positive for cryptococcus and 75% were from female patients. The median age of these patients was 38 years, and 38% of the patients were from the city of Luanda. The factors associated with cryptococcal infection were: Cough (OR = 4.00; 95% CI: 2.01-7.93; p 50 mg / dL (OR = 1.08, 95% CI: 1-175, p<0.001); Anemia (OR = 6.72, 95% CI: 1.72-25.16, p = 0.004); Pneumonia (OR = 4.21, 95% CI: 1.55-11.44, p = 0.004); Tuberculosis (OR = 3.99, 95% CI: 1.74-9.17, p = 0.001) and Malaria (OR = 6.73, 95% CI: 2.73-20.84, p < 0.001). Conclusion: the present study showed a 33% prevalence of cryptococcosis infection among the HIV and AIDS patients under follow-up in Hospital Esperana, Luanda, which might be indicative of patients presenting to care at a late stage of disease and with low CD4 cell counts. To our knowledge this is the first study that evaluated the prevalence of cryptococcosis in HIV patients in Angola and this data should inform future HIV and AIDS policies and public health strategies.

Clinicopathologic Study of Granulomatous Lesions in the Bone Marrow

Introduction: Granulomatous lesion in the bone marrowis not a common finding and can be attributed to a variety of conditions ranging from infections to malignancies to drugs. Though tuberculosis is the most common etiology, bone marrow granulomas can be associated with a number of infections and other non infective conditions. The incidence of bone marrow granulomas has been increasing over the years due to the increasing surge of HIV infection. Aims: This study basically aims to study the prevalence of bone marrow granulomas, to identify the various causes and to study the pattern of granulomas in different conditions. Materials & Methods: This is a retrospective analysis of 100 cases of bone marrow granulomas conducted in the Clinical Laboratory of Kasturba hospital for a period of four and a half years from January 2009 to May 2013.The clinical details were collected from medical records and bone marrow biopsy slides were retrieved and studied. Results: Out of the 100 cases, 66% cases were diagnosed as tuberculosis. 17% cases were due to other infections like Typhoid fever (5%), Brucellosis (4%), Scrub typhus (2%), Hansen’s disease (1%), Cryptococcosis (2%) and HIV infection itself without any other opportunistic infections (3%). Malignancies accounted for 9% cases, Sarcoidosis (1%) and in 7% cases a definitive diagnosis was not reached. Among the 66 cases of tuberculosis, 40 (60%) cases were immunodeficient due to HIV infection. HIV positive cases predominantly showed single (52%), ill defined granulomas (73%), with caseation necrosis (52%), while HIV negative cases predominantly showed single (54%), small (50%), well defined or ill defined granulomas with plump epithelioid cells (58%) and Langhans giant cells (42%). Conclusion: There can be varied etiology for bone marrow granulomas with tuberculosis being the most common cause.The morphology and pattern of granulomas can aid in the diagnosis of the condition hence study of bone marrow for granulomas should be considered as an important diagnostic tool in such conditions.

Cryptococcosis manifesting as isolated biliary infection: Case report and brief review of literature

Biliary cryptococci infection is rare, which is frequently diagnosed by exploratory laparotomy, preoperative diagnosis is difficult. A 14-year-old girl presented with intermittent jaundice for 6 years. She had no pruritus, anorexia, nausea or vomiting, fever, abdominal pain, or clay stools. Laboratory tests showed obstructive jaundice, eosinophilia, and increased IgE levels. The patient was ultimately diagnosed as Cryptococcal infection by bone marrow culture. The patient responded to antifungal therapy. Unnecessary surgical intervention was avoided by an early and accurate diagnosis. Cryptococcosis infection of bile duct should be highly suspected, when the children with obstructive jaundice have eosinophilia and increased IgE levels.

Isavuconazole for Cryptococcosis and Dimorphic Fungal Infections

Isavuconazole (ISAV) is a newly approved triazole antifungal agent with a broad spectrum of activity. Oral and intravenous formulations exist as the

Curcumin enhances the activity of fluconazole against Cryptococcus gattii-induced cryptococcosis infection in mice.

The aim of this study was to investigate the invitro and invivo activities of pure curcumin, as well as its combination with fluconazole, against Cryptococcus gattii. The minimal inhibitory concentrations (MIC) of curcumin and its interactions with fluconazole against C.gattii were assessed invitro using standard methods. This same combination was used to treat C.gattii-induced cryptococcosis in mice. The behavioural and functional assessment of the mice during treatment was also performed. The average MIC for curcumin was 19·8μgml(-1) . Its combination with fluconazole resulted in FICΣ (fractional inhibitory concentration index) values between 0·79 and 2·29. Curcumin (alone or combined with fluconazole) significantly reduced pulmonary damage and fungal burden in the brain. No colonies were found in the brain following combination treatment, which was also confirmed by the improved behaviour of mice. The combination therapy with curcumin and fluconazole was the most effective among the treatments tested, as in addition to reducing the fungal burden and damage on lung tissues, it was able to eliminate the fungal burden in the brain, enhancing the survival of mice. This study points to the possibility of using curcumin in combination with fluconazole as a clinical treatment of cryptococcosis.

The heat shock protein (Hsp) 70 of Cryptococcus neoformans is associated with the fungal cell surface and influences the interaction between yeast and host cells

The pathogenic yeast Cryptococcus neoformans secretes numerous proteins, such as heat shock proteins, by unconventional mechanisms during its interaction with host cells. Hsp70 is a conserved chaperone that plays important roles in various cellular processes, including the interaction of fungi with host immune cells. Here, we report that sera from individuals with cryptococcosis infection recognize a recombinant C. neoformans Hsp70 (Cn_rHsp70). Moreover, immunofluorescence assays using antibodies against Cn_rHsp70 revealed the localization of this protein at the cell surface mainly in association with the capsular network. We found that the addition of Cn_rHsp70 positively modulated the interaction of C. neoformans with human alveolar epithelial cells and decreased fungal killing by mouse macrophages, without affecting phagocytosis rates. Immunofluorescence analysis showed that there was a competitive association among the receptor, GXM and Cn_rHsp70, indicating that the Hsp70-binding sites in host cells appear to be shared by glucuronoxylomannan (GXM), the major capsular antigen in C. neoformans. Our observations suggest additional mechanisms by which Hsp70 influences the interaction of C. neoformans with host cells.