Cryptococcal Infection Research Articles

Crazy-Paving Pattern: A Rare Case of Autoimmune Pulmonary Alveolar Proteinosis (PAP) with Positive Anti-GM-CSF Antibody Following Cryptococcal Infection in an otherwise Healthy Individual and Review of Literature

Crazy-Paving Pattern: A Rare Case of Autoimmune Pulmonary Alveolar Proteinosis (PAP) with Positive Anti-GM-CSF Antibody Following Cryptococcal Infection in an otherwise Healthy Individual and Review of Literature

Immune Reconstitution Inflammatory Syndrome and Hodgkin’s Lymphoma

Immune reconstitution inflammatory syndrome (IRIS) is defined as a clinically significant exacerbation of known oligosymptomatic serious, more often infectious, diseases with considerably increased CD4+ T-lymphocyte count in response to highly active anti-retroviral therapy (HAART) of HIV infection. The review comprehensively discusses tuberculosis issues in HIV-positive HAART recipients. Related recommendations contain strict guidelines on compulsory treatment of tuberculosis prior to HAART assignment. Similar recommendations for specific therapy preceding HAART are provided for other opportunistic infections (mycotic and cryptococcal infections, parasitosis, molluscum contagiosum, toxoplasmosis, herpes-zoster virus, leishmaniasis, syphilis, and lepra). Without prior specific therapy of an opportunistic infection its exacerbation with pronounced symptoms and signs on HAART can be fatal for the patient. Lymphomas including Hodgkin’s lymphoma (HL) are dealt with in the context of the same challenge. However, what remains unclear is the specificity of targeted T-lymphocytes in the microenvironment to hitherto unclarified cause-specific antigens of the tumor. As opposed to other malignant lymphoid tumors arising with low level of CD4+ T-lymphocytes, HL develops when the level of CD4+ T-lymphocytes is increased in response to HAART in HIV-positive patients during the first months of anti-retroviral therapy. HL is diagnosed in 8 % of HIV-positive off-HAART subjects. After HAART assignment the HL incidence goes up to 17 %. Therefore, IRIS can be considered the main challenge in the study of etiology and pathogenesis of HL in HIV-positive patients. In this context, the demand to extend the research in this field becomes not only obvious but crucial for practical applications.

Cryptococcosis complicating diabetes mellitus: a scoping review.

Background:A better understanding of the epidemiology of cryptococcal infection in HIV-negative individuals is an international research interest. Immune dysfunction in diabetes mellitus (DM) significantly increases the risk of acquiring and reactivation of infection due to Cryptococcus neoformans. Risk factors and outcomes of cryptococcosis in DM are not well documented.Objective:The objective of this study was to determine the clinical characteristics and outcomes of cryptococcal infections in persons living with DM.Methods:MEDLINE (via PubMed), EMBASE, and the Cochrane Library databases were searched in November 2020. The searches covered the period between 1980 and 2020.We included studies that reported confirmed cryptococcosis in patients with DM. Reference lists of included articles were also searched, and additional studies were included if appropriate. No language restriction was applied. Single case reports, case series and original articles were included whereas review articles were excluded.Results:A total of 28 studies (24 single case reports, 4 retrospectives) were included involving 47 unique patients from Asia (17 cases), North America (six cases), South America (three cases) and Africa (two cases). Men constituted 75% (n = 18) of the cases. Median age was 60.5 (range: 27–79) years. The majority of the patients had cryptococcal meningitis (68.1%, n = 32) followed by disseminated cryptococcosis (6.4%, n = 7), and others (isolated cutaneous disease one, peritonitis one, pleural one, thyroid one, adrenal one). Diagnosis was achieved through either culture and microscopy (38/47), cryptococcal antigen tests (9/47) or histopathology (9/47) singly or in a combination. All-cause mortality was 38.3% (n = 18). Among those with meningitis mortality was 36.2%.Conclusion:A wide spectrum of cryptococcal infections with varying severity occurs in DM. Mortality remains unacceptably high. There is a need for more studies to characterize better cryptococcal disease in DM.

Clinical Usefulness of Lateral Flow Antigen Detection Assay and PCR for Laboratory Diagnosis of Cryptococcal Infections

Clinical Usefulness of Lateral Flow Antigen Detection Assay and PCR for Laboratory Diagnosis of Cryptococcal Infections

Primary Cutaneous Cryptococcosis: A Rare Masquerading Presentation of Cryptococcus Infection

The yeast, Cryptococcus is widely present in the environment. Its main portal of entry is the respiratory tract. Clinical and experimental evidences indicate that cryptococcosis is usually a reactivation of a dormant infection. They have been recovered from soil contaminated with avian excreta, especially pigeon droppings and from decaying wood, fruits, vegetables and dust. Cryptococcusmay be found on skin of healthy subjects without causing any manifestation but it is known to cause life threatening infection in immunocompromised hosts. Primary Cutaneous Cryptococcosis (PCC) is an uncommon condition which is characterised by localised cryptococcal skin eruptions without dissemination to internal organs. Clinicians are aware of the typical presentation of cryptococcal infections occurring mostly in immunocompromised patients. Rare manifestations like PCC may go unnoticed leading to prolonged morbidity and health care cost. The present article is a case report of PCC in a 39-year-old immunocompetent male who presented with two months history of scattered erythematous indurated papules and plaques on his right foot, arm and abdominal region developed after having suffered minor injury at the cement factory. The patient was started on fluconazole to which he responded well.

CryptoCEST: A promising tool for spatially resolved identification of fungal brain lesions and their differentiation from brain tumors with MRI

Infectious brain lesions caused by the pathogenic fungi Cryptococcus neoformans and C. gattii, also referred to as cryptococcomas, could be diagnosed incorrectly as cystic brain tumors if only based on conventional magnetic resonance (MR) images. Previous MR spectroscopy (MRS) studies showed high local concentrations of the fungal disaccharide trehalose in cryptococcomas. The aim of this study was to detect and localize fungal brain lesions caused by Cryptococcus species based on Chemical Exchange Saturation Transfer (CEST) MR imaging of endogenous trehalose, and hereby to distinguish cryptococcomas from gliomas. In phantoms, trehalose and cryptococcal cells generated a concentration-dependent CEST contrast in the 0.2 – 2 ppm chemical shift range, similar to glucose, but approximately twice as strong. In vivo single voxel MRS of a murine cryptococcoma model confirmed the presence of trehalose in cryptococcomas, but mainly for lesions that were large enough compared to the size of the MRS voxel. With CEST MRI, combining the more specific CEST signal at 0.7 ppm with the higher signal-to-noise ratio signal at 4 ppm in the CryptoCEST contrast enabled localization and distinction of cryptococcomas from the normal brain and from gliomas, even for lesions smaller than 1 mm3. Thanks to the high endogenous concentration of the fungal biomarker trehalose in cryptococcal cells, the CryptoCEST contrast allowed identification of cryptococcomas with high spatial resolution and differentiation from gliomas in mice. Furthermore, the CryptoCEST contrast was tested to follow up antifungal treatment of cryptococcomas. Translation of this non-invasive method to the clinic holds potential for improving the differential diagnosis and follow-up of cryptococcal infections in the brain.

An Unusual Presentation of Cryptococcal Infection in a Post Renal Transplant Patient: A Case Report

Background: Cryptococcus neoformans is opportunistic yeast commonly found in soil contaminated by bird feces throughout the world. Cryptococcosis is a severe fungal infection in a with a high mortality rate among solid organ transplant recipients. The infection usually involves the lungs, central nervous system, skin, bones, and the urinary tract. Cryptococcosis continues to cause significant mortality and morbidity in immunocompromised patients.

A Rare Presentation of Cryptococcal Meningitis in a Treatment-Naive Patient with Sarcoidosis.

Cryptococcus is an opportunistic fungal infection commonly diagnosed in immunocompromised patients.Sarcoidosis is a multi-systemic disease characterized by the formation of granulomas in various organs, most commonly found in the lungs and mediastinal lymph nodes.

Increased mortality associated with uncontrolled diabetes mellitus in patients with pulmonary cryptococcosis: a single US cohort study.

Background:Diabetes mellitus is an established risk factor for bacterial infections, but its role in cryptococcosis is unclear. The study aimed to determine whether uncontrolled diabetes (HbA1c >7%) was an independent risk factor for mortality in cryptococcosis.Methods:A retrospective case–control study partially matched by age and gender was performed in patients tested for Cryptococcus infection at the University of Colorado Hospital from 2000 to 2019. A multivariable logistic regression model was used to identify mortality predictors. Cox proportional hazard model was used for survival analysis.Results:We identified 96 cases of cryptococcosis and 125 controls. Among cases, cryptococcal meningitis (49.0%) and pneumonia (36.5%) constituted most infections. Cases with pulmonary cryptococcosis with uncontrolled diabetes had a higher mortality at 10 weeks (50% versus 7%, p = 0.006) and 1 year (66.7% versus 13.8%, p = 0.005) compared to pulmonary cases with controlled or no diabetes. Unadjusted Cox proportional hazard model found an increased rate of death for uncontrolled diabetes at 10 weeks [hazard ratio 8.4, confidence interval (CI): 1.4–50.8, p = 0.02] and 1 year (hazard ratio 7.0, CI: 1.7–28.4, p = 0.007) among pulmonary cryptococcosis cases. Multivariable analysis showed a significantly increased odds of 10 weeks [odds ratio (OR) = 4.3, CI: 1.1–16.5, p = 0.035] and 1 year (OR = 5.0, CI: 1.4–18.3, p = 0.014) mortality for uncontrolled diabetes among pulmonary cryptococcosis cases. After adjustment for gender, age, and case/control, for every 1% increase in HbA1c levels, the odds of pulmonary cryptococcosis mortality at 1 year increased by 11% (OR = 1.6, CI 95%: 1.1–2.3, p = 0.006).Conclusion:Uncontrolled diabetes is associated with worse outcomes in pulmonary cryptococcosis, including a 4-fold and 6-fold increased odds of death at 10 weeks and 1 year, respectively. Glucose control interventions should be explored to improve clinical outcomes in patients with pulmonary cryptococcosis.

1168. Higher Glycosylated Hemoglobin (A1c) Levels are Associated with Increased Mortality from Cryptococcus Infection

BackgroundDiabetes mellitus is a well-established risk factor for the development of bacterial infections. However, the role of diabetes mellitus as a risk factor in the occurrence of Cryptococcosis is unknown. The aim of the study was to determine whether diabetes and A1c levels were independent risk factors for infection and mortality in Cryptococcus infection.MethodsA retrospective hospital-based case-control study matched by age and gender (96 cases and 125 controls) was performed in patients tested for Cryptococcus infection at University of Colorado Hospital from 2001-2019 (n=221). Data was extracted through RedCap. A multivariable logistic regression model was used to identify predictors of infection and mortality.ResultsDiabetes mellitus was present in 24 cases (25.0%) and 24 controls (19.2%). In cases, the mean age was 54 years, 79% were men, and diabetes was the only known risk factor in 6 cases (6.3%) and accompanied additional risk factor in 18 cases (18.8%). Other common risk factors included: HIV (39.9%), steroid use (24.7%), malignancy (23.2%), solid organ transplant recipients (18.1%), and cirrhosis (5.2%). Cryptococcal meningitis (49.0%) followed by pulmonary infection (36.5%) were the most common sites of infection. The mean A1c value for cases vs. controls was 6.5 ± 1.5 vs. 6.2 ± 1.8 mmol/L, p=0.43. Overall mortality was 27.3% vs. 26.9% among cases and controls, respectively. Among cases, the risk of death was higher for patients with diabetes, although not significantly (39.1% vs 23.1%, p= 0.137). Adjusted for gender, age and case/control; for every 1-point increase in A1c levels, the odds of mortality increased by 40% (OR = 1.4, CI: 1.0-1.9, p= 0.045).ConclusionDiabetes mellitus alone is an uncommon risk factor for acquiring Cryptococcus infection. However, uncontrolled diabetes in Cryptococcosis may worsen outcomes from infection, including increased mortality. Glucose control interventions may improve clinical outcomes in patients with cryptococcal infection.Disclosures All Authors: No reported disclosures

1099. Opportunistic Infections Among Long Term Survivors of Kidney Transplantation: Defining Risk Factors

BackgroundOpportunistic infections (OIs) in kidney transplant recipients (KTR) most commonly occur in the early post-transplant period or with increased immunosuppression, largely as a result of impaired T-cell function. Additionally, age confers susceptibility to infection independent of time post-transplant. The combined impact of cumulative immunosuppression and immunosenescence on infection risk of long-term KT survivors has not been well described.MethodsWe performed a retrospective chart review of patients age ≥ 18 years who underwent KT between 2003 to 2009 and who survived ≥ 10 years post-KT, in order to evaluate the risk factors for OIs. Demographics, comorbidities, immunosuppression, and clinical data for OIs occurring ≥ 10 years of KT were collected. AST ID Working Group on Infectious Disease Monitoring definitions for OIs was used. Risk factors for OIs were assessed by simple logistic regression.ResultsOf 332 KTR, 16 (4.8%) had an OI with 18 total episodes. Of 16 KTR, half were white, 10 (62.5%) were male, median age at time of transplant was 43 (range 25-72) and the median post-transplant follow-up was 14.2 years (range 10.3-37.6). The mean Charlson Comorbidity Index (CCI) at diagnosis was 5.6 (S.D. 3.6). Ten patients (62.5%) were on mycophenolate-based regimens. The mean absolute lymphocyte count (ALC) at the time of OI was 0.78 x 103/µL (S.D. 0.43). Two (12.5%) had acute rejection within 1 year of OI. Of 18 OI episodes, there were 6 PJP, 2 candida esophagitis, 3 CMV (2 viremia, 1 colitis), 2 cryptococcal infections (1 meningitis, 1 myositis/disseminated), 2 adenovirus (pneumonia, colitis), 2 VZV (herpes zoster) and 1 HSV (esophagitis). Two patients had 2 concurrent OIs (1 had PJP and cryptococcus and 1 had HSV and candida esophagitis). Three died within 30-days of OI diagnosis. OI incidence was associated with years from date of transplant [OR 1.3, p=0.002], cerebrovascular disease [OR 4.45, p=0.02], and lower ALC [OR 5.9, p < 0.05]. CCI also trended towards association [OR 1.24, p=0.09].Table 1: Demographics, comorbidities, immunosuppression, and clinical data for patients with OIs Table 2: Detailed characteristics of each patient with opportunistic infections ConclusionOIs were infrequently observed beyond 10 years of transplant among long-term survivors of KT. However, OI incidence was associated with poor outcome. Low ALC and a higher burden of comorbidities were risk factors for very late occurrence of OIs in this population.Disclosures All Authors: No reported disclosures

Lymphnode cytopathology and CD4 count in HIV positive patients

Introduction: CD4 is an important prognostic as well as therapeutic marker in the management of HIV and this study identifies the correlation between CD4 counts and FNAC lymphnode (LN) patterns in these patients. Study Design: The study was conducted in the rural areas at Nalgonda district by Kamineni Institute of Medical Sciences, Telangana. Eventhough Fine Needle Aspiration Cytology (FNAC) was done on total 56 selected patients who had lymphadenopathy and were tested HIV positive, only 50 of them have CD4 counts and were selected as final study group. Suspected cytosmears have acid fast staining done by Ziehl Nelson technique. The final cytopathological findings were correlated with CD4 counts. Results: In our study, high CD4 counts were associated with reactive lymphadenitis (26%;13/50) most and Low CD4 counts were associated with less frequent suppurative lymphadenitis and particulary TB lymphadenitis was noticed in 56% (28/50) and morphologically exhibited 4 different patterns– caseous with epitheloid granuloma, only caseous necrosis, only epitheloid granuloma and suppurative. Conclusion: CD4 count correlated well with the different stages of immunosuppression in HIV patients. The patients with reactive lymphadenitis demonstrated high CD4 counts suggesting good immunological response. The low CD4 counts seen in patients with suppurative lymphadenitis and cryptococcal infection suggests severe immuno-compromised state. Keywords: Cytopathology, CD4 count, Granuloma, HIV, Lymphnode, Tuberculosis.

Glucuronoxylomannan in the Cryptococcus species capsule as a target for Chimeric Antigen Receptor T-cell therapy

Background aimsThe genus Cryptococcus comprises two major fungal species that cause clinical infections in humans: Cryptococcus gattii and Cryptococcus neoformans. To establish invasive human disease, inhaled cryptococci must penetrate the lung tissue and reproduce. Each year, about 1 million cases of Cryptococcus infection are reported worldwide, and the infection's mortality rate ranges from 20% to 70%. Many HIV+/AIDS patients are affected by Cryptococcus infections, with 220,000 cases of cryptococcal meningitis reported worldwide in this population every year (C. neoformans infection statistics, via the Centers for Disease Control and Prevention, https://www.cdc.gov/fungal/diseases/cryptococcosis-neoformans/statistics.html). To escape from host immune cell attack, Cryptococcus covers itself in a sugar-based capsule composed primarily of glucuronoxylomannan (GXM). To evade phagocytosis, yeast cells increase to a >45-µm perimeter and become titan, or giant, cells. Cryptococci virulence is directly proportional to the percentage of titan/giant cells present during Cryptococcus infection. To combat cryptococcosis, the authors propose the redirection of CD8+ T cells to target the GXM in the capsule via expression of a GXM-specific chimeric antigen receptor (GXMR-CAR). ResultsGXMR-CAR has an anti-GXM single-chain variable fragment followed by an IgG4 stalk in the extracellular domain, a CD28 transmembrane domain and CD28 and CD3-ς signaling domains. After lentiviral transduction of human T cells with the GXMR-CAR construct, flow cytometry demonstrated that 82.4% of the cells expressed GXMR-CAR on their surface. To determine whether the GXMR-CAR+ T cells exhibited GXM-specific recognition, these cells were incubated with GXM for 24 h and examined with the use of brightfield microscopy. Large clusters of proliferating GXMR-CAR+ T cells were observed in GXM-treated cells, whereas no clusters were observed in control cells. Moreover, the interaction of GXM with GXMR-CAR+ T cells was detected via flow cytometry by using a GXM-specific antibody, and the recognition of GXM by GXMR-CAR T cells triggered the secretion of granzyme and interferon gamma (IFN-γ). The ability of GXMR-CAR T cells to bind to the yeast form of C. neoformans was detected by fluorescent microscopy, but no binding was detected in mock-transduced control T cells (NoDNA T cells). Moreover, lung tissue sections were stained with Gomori Methenamine Silver and evaluated by NanoZoomer (Hamamatsu), revealing a significantly lower number of titan cells, with perimeters ranging from 50 to 130 µm and giant cells >130 µm in the CAR T-cell treated group when compared with other groups. Therefore, the authors validated the study's hypothesis by the redirection of GXMR-CAR+ T cells to target GXM, which induces the secretion of cytotoxic granules and IFN-γ that will aid in the control of cryptococcosis ConclusionsThus, these findings reveal that GXMR-CAR+ T cells can target C. neoformans. Future studies will be focused on determining the therapeutic efficacy of GXMR-CAR+ T cells in an animal model of cryptococcosis.

Cryptococcus neoformans Secretes Small Molecules That Inhibit IL-1β Inflammasome-Dependent Secretion.

Cryptococcus neoformans is an encapsulated yeast that causes disease mainly in immunosuppressed hosts. It is considered a facultative intracellular pathogen because of its capacity to survive and replicate inside phagocytes, especially macrophages. This ability is heavily dependent on various virulence factors, particularly the glucuronoxylomannan (GXM) component of the polysaccharide capsule. Inflammasome activation in phagocytes is usually protective against fungal infections, including cryptococcosis. Nevertheless, recognition of C. neoformans by inflammasome receptors requires specific changes in morphology or the opsonization of the yeast, impairing proper inflammasome function. In this context, we analyzed the impact of molecules secreted by C. neoformans B3501 strain and its acapsular mutant Δcap67 in inflammasome activation in an in vitro model. Our results showed that conditioned media derived from B3501 was capable of inhibiting inflammasome-dependent events (i.e., IL-1β secretion and LDH release via pyroptosis) more strongly than conditioned media from Δcap67, regardless of GXM presence. We also demonstrated that macrophages treated with conditioned media were less responsive against infection with the virulent strain H99, exhibiting lower rates of phagocytosis, increased fungal burdens, and enhanced vomocytosis. Moreover, we showed that the aromatic metabolite DL-Indole-3-lactic acid (ILA) and DL-p-Hydroxyphenyllactic acid (HPLA) were present in B3501's conditioned media and that ILA alone or with HPLA is involved in the regulation of inflammasome activation by C. neoformans. These results were confirmed by in vivo experiments, where exposure to conditioned media led to higher fungal burdens in Acanthamoeba castellanii culture as well as in higher fungal loads in the lungs of infected mice. Overall, the results presented show that conditioned media from a wild-type strain can inhibit a vital recognition pathway and subsequent fungicidal functions of macrophages, contributing to fungal survival in vitro and in vivo and suggesting that secretion of aromatic metabolites, such as ILA, during cryptococcal infections fundamentally impacts pathogenesis.

A case of disseminated Cryptococcus neoformans in a non HIV patient

Background: Cryptococcus neoformans predominantly causes significant infections in immunocompromised individuals, of which 80–90% occur in people infected with human immunodeficiency virus (HIV). The clinical manifestations can vary from asymptomatic colonization of the respiratory airways to dissemination of infection into any part of the human body. Disseminated cryptococcal infection especially noncutaneous cryptococcal abscess in immunocompetent host is uncommon. We report a case of disseminated Cryptococcus neoformans with soft tissue and pulmonary involvement in an otherwise healthy immunocompetent patient diagnosed by culture of the abscess. Case Description: Mr S, 72 y old Malay man, no known medical illness, a farmer at palm oil plantation in Benut, Johor, presented with progressive anterior chest wall swelling for 1 week duration associated with fever. CECT thorax showed left upper lobe and right chest wall abscess complicated with septic arthritis and osteomyelitis. The swelling was incised and pus was drained. Histopathological examination showed numerous encapsulated yeast like organism with thick capsule. Culture from tissue and pus of this patient grew Cryptococcus neoformans var grubii. Patient was treated as disseminated Cryptococcus neoformans and responding well to Amphotericin B. Discussion: Cryptococcal infections are common in immunosuppressed and relatively rare among immunocompetent population. In this case, the culture of the pus grew Cryptococcus neoformans serotype A (var. grubii) identified by Malditof. This variant of Cryptococcus is most commonly isolated from AIDS patient. The pathogenesis of cryptococcosis is rely on status of host defences, virulence strain and size of the inoculums. The mode of transmission in this case as he is a farmer, most likely from inhalation and direct of inoculation of the pathogen. Conclusion: Absence of immunosuppression should not be a reason to exclude cryptococcosis from the differential diagnosis when patient presents with an abscess.

Cryptococcal antigenemia and susceptibility of Cryptococcuss neoformans to antifungal agents in HIV infection

Background: Cryptococcus neoformans is a ubiquitous, environmental encapsulated fungus commonly found in soil and pigeon faecal samples. Transmitted C. neoformans via aerosols threatens HIV patients’ survival with ‘subtle’ meningitis, particularly in patients whose CD4+ counts declines below 200 cells/mm3 and causes early mortality in HIV-infected cohorts in resource-limited countries in sub-Saharan Africa. Early detection of C. neoformans in HIV patients is very crucial to their survival. Hence, this study investigated strategic cultural and serological diagnostics favourable for early detection of Cryptococossis in HIV patients and susceptibility to antifungal agents on clinical and environmental isolates of C. neoformans. Case description: A total of 665 blood samples were obtained from 615 seropositive HIV-infected patients and 60 seronegative patients across three referral health facilities in Abeokuta, Ogun, Nigeria. Following ethical approval, voluntary and informed consents were obtained from the study population. Structured questionnaires were administered to obtain the demographic data of the patients. Lateral flow serological methods were employed to determine Cryptococcal antigen (CrAg) in the serum of the patients. The cerebrospinal fluid (CSF) samples of HIV patients and pigeon droppings in soil were aseptically collected and cultured on five different culture media in order to isolate and identify C. neoformans. Agar-well-dilution and micro-tube dilution methods were used to determine the susceptible isolates’ to ketoconazole and fluconazole antifungal agents. Discussion: The results showed HIV prevalence among ages 21–40 years and female to male ratio of 2:1. Lateral flow CrAg detected C. neoformans antigenemia in HIV seropositive patients whose CD4 counts were less than 200 cells/mm3. The detection capacity of the five different media used revealed no significant association between isolates obtained from CSF and soil contaminated with pigeon droppings (P > X2 = 1.27, P = 0.115). The clinical, environmental and control isolates showed similar susceptibility rate (P value > 0.05) to ketoconazole and fluconazole. Conclusion: Lateral flow assay offered early detection of sub-clinical cryptococcal infection in HIV patients, while prompt therapeutic intervention using ketoconazole and fluconazole were effective antifungal agents as combination therapy with anti-retroviral agents. Minimising exposure of HIV patients to contaminated soil could reduce associated risks of cryptococcosis in HIV seropositive people.

Protective Immunity Against Cryptococcus Neoformans Infection

Cryptococcus neoformans, the etiological agent of cryptococcosis, is an occasional opportunistic fungal pathogen of immune competent individuals. However, it is a relatively frequent cause of life-threatening meningoencephalitis and pulmonary infections in immunosuppressed hosts and is a leading mycological cause of morbidity and mortality among patients with AIDS in most parts of the world. The lack of an effective fungicidal regimen and the development of antifungal resistant strains suggest that continued investigation is necessary to devise immunotherapeutic strategies, drug targets and/or vaccines to combat C. neoformans infections. Until recently, cryptococcal virulence factors such as its polysaccharide capsule, macrophage parasitism, and its ability to induce an ineffective antibody mediated immune (AMI) response along with a non-protective type II (Th2) cell-mediated immune response have thwarted efforts to induce complete protective immunity against a lethal cryptococcal strain in murine models. The presence of C. neoformans antibodies in adult human serum suggests that immune competent individuals have difficulty resolving an early cryptococcal infection allowing for the establishment of a subclinical chronic infection. Recent studies have shown that pro-inflammatory cytokines, specifically interferon-g (IFN-gamma), associated with type I (Th1) cell-mediated immunity can successfully drive cell-mediated immune (CMI) responses to produce protective immunity to a second experimental C. neoformans infection in mice. This review will evaluate the intricacies of the host-cryptococcal interaction and discuss recent developments in C. neoformans research and the potential for human vaccines and/or drug therapies.

Epidemiology of Cryptococcal antigenemia among HIV infected patients in South-western Nigeria

Background: Cryptococcosis is a life-threatening fungal infection that presents diversely with no specific pathognomonic features. Cryptococcal disease is one of the most important opportunistic infections, and a major contributor to early mortality in HIV infected subjects. Cryptococcal antigenemia occurs in Nigeria, but the magnitude of this disease remains unclear. This study was carried out to determine the prevalence of CrAg among HIV seropositive and seronegative individuals attending Adeoyo Maternity Teaching Hospital (AMTH), Yemetu, Ibadan. Methods and materials: This was a case-control study in which 114 cases and 228 controls were recruited. Cases were HIV seropositive individuals while controls were HIV seronegative individuals receiving care at AMTH. Adult male and female (age range: 18–65 years) who agree to participate in the study were recruited. Simple random sampling was used to select subjects. Semi-structured interviewer administered questionnaire was used to collect data from subjects and retrospective review of CD4 count records in HIV infected subjects. Five millilitres venous blood was collected from each participant. Serum Cryptococcal antigen testing was done using CrAg Lateral Flow Assay. Data was analyzed using descriptive statistics and bivariate analysis at 5% level of significance. Results: Mean age of cases was 41.2 ± 10.0 years and 85 (74.6%) were females while mean age of control subjects was 38.9 ± 13.7 years 156 (68.4%) were females. The cumulative prevalence of CrAg was 8.5%. However, the prevalence of CrAg among cases was 11.4% and 7.0% among controls. Age groups 41-50 years and 21-30 years were the most affected among cases and controls respectively. HIV positive subjects were about two times more likely to test positive for CrAg. Individuals with CD4 counts of ≤100cells/μl were 20 times more likely to have positive serum cryptococcal antigen than individuals with CD4 counts >100 cells/μl (OR: 20.3, 95%CI: 5.23-78.9). Conclusion: Cryptococcal antigen was present among both cases and controls; however, the prevalence was higher among cases. Since asymptomatic cryptococcal antigenemia predicts impending cryptococcal infection (pneumonia and meningitis) with probable mortality, screening for CrAg should be part of the routine tests amongst all confirmed HIV seropositive cases

15672 A cutaneous crypt for cryptococcosis: The skin as a marker for disseminated disease

Cutaneous cryptococcosis is caused by Cryptococcus neoformans, an opportunistic, encapsulated yeast that can cause significant morbidity and mortality. Cutaneous cryptococcosis can affect both immunocompromised and immunocompetent individuals, and can result from direct inoculation or hematogenous spread to skin. In primary cutaneous cryptococcosis, localized infection is subsequent to direct inoculation. In contrast, the more common, secondary skin involvement is due to hematogenous dissemination, which can be accompanied by spread to other organs such as the lungs and central nervous system. Here, we present a case of a 66-year-old man with a history of deceased-donor renal transplant secondary to polycystic kidney disease on chronic immunosuppression. He presented with a 2-month history of an enlarging, deep tender ulceration with heaped up borders and yellow purulent crust on the left eyelid. HSV and VZV PCR, bacterial culture and blood culture were negative. Lumbar puncture results were consistent with cryptococcal meningitis. Similarly, a biopsy of the periphery of the lesion demonstrated granulomatous and suppurative inflammation and refractile yeast forms, findings compatible with cryptococcosis. Gomori methenamine silver stain highlighted many fungi and mucicarmine stain highlighted their capsules. The patient was treated with intravenous amphotericin B and flucytosine for disseminated cryptococcal infection with cutaneous involvement. In immunocompromised patients, the diagnosis can be challenging, as cutaneous findings are nonspecific and can often mimic other conditions. Cutaneous involvement can serve as a helpful clue of underlying disseminated disease, and dermatologists play a crucial role in the diagnosis and early treatment of this opportunistic, often life threatening disease.

Clinical Evaluation a New Treatment for Infection After Ventriculoperitoneal Shunt.

To explore a new surgical treatment for infection and obstruction of ventriculoperitoneal shunt in hydrocephalus. Two cases of post-operative infection of ventriculoperitoneal shunt were analyzed retrospectively. One case was cryptococcal infection, the other case was Acinetobacter lwoffii. The number of cerebrospinal fluid cells was high, the infection of ventriculoperitoneal shunt was generally complicated with abdominal obstruction, and the hydrocephalus was aggravated again, The authors try to pull out the drainage tube at the end of abdominal cavity for external drainage, combined with intravenous antibiotics, completely control of infection, and then use the original shunt device for intraventricular jugular shunt. The authors explore that this method is simple, safe and effective, and it is an effective and feasible method for the treatment of infection after ventriculoperitoneal shunt.