Case Of Cryptococcosis Research Articles

A rare case of disseminated pulmonary cryptococcosis in an immunocompetent patient

Pulmonary cryptococcosis is an uncommon invasive fungal infection of the lungs seen in immunocompromised individuals but increasingly reported among the immunocompetent. We report a rare case of pulmonary cryptococcosis in an immunocompetent host highlighting its unique clinical and radiological presentation.Clinical trial number: Not applicable.

SEROUS RETINAL DETACHMENT DUE TO CRYPTOCOCCOSIS IN AN IMMUNOCOMPETENT PATIENT

Purpose: To report a case of bilateral ocular cryptococcosis in an immunocompetent patient without neurologic findings. Methods: Case report. Results: A 30-year-old healthy Caucasian man presented with painless blurred vision in the left eye. Examination showed bilateral serous detachments and white retinal lesions. The visual acuity (VA) was 20/40 in the right eye and hand motions in the left eye. Neurologic workup and serologies were negative, and a computer tomography-positron emission tomography scan showed diffuse lymph node enlargement with metabolic activity and a suspected lymphoproliferative disorder. The myelogram and immunohistochemistry were normal. A biopsy of the cervical lymph nodes was positive for Cryptococcus neoformans. He was treated with antifungal medications and had complete resolution of the subretinal fluid and VA improvement. Conclusion: Cryptococcosis is a rare entity in an immunocompetent person. A systemic workup is necessary to diagnose cryptococcosis and initiate prompt treatment.

Cryptococcosis at the university hospital of Marseille: A case series

Cryptococcosis is a fungal infection burdened by a high case-fatality rate in immunocompromised patients. Once limited to human immunodeficiency virus (HIV)-infected patients, the epidemiology of cryptococcosis has evolved in recent years and new risk factors have emerged. It is therefore essential to identify these risk factors in order to improve prevention and therapeutic efficacy. We conducted a retrospective observational study including all cases of cryptococcosis between January 2016 and December 2022, diagnosed at the University Hospital of Marseille. During the study period 15 cases of cryptococcosis were diagnosed. Six patients were HIV-infected. Nine patients had one or more comorbidities including liver cirrhosis, type 2 diabetes mellitus, primary immunodeficiency disorder, chronic lymphocytic leukemia and solid organ transplantation. Ten patients had central nervous system cryptococcosis, four had pulmonary cryptococcosis and one patient had extra-pulmonary disseminated cryptococcosis. Of the three patients with liver cirrhosis, two patients died with a post-mortem diagnosis. Our data suggest that emerging risk factors are probably underestimated by clinicians. It emphasizes the need for cryptococcal antigenemia as part of syndromic investigation of any unexplained fever or neurological symptoms in an at-risk patient. Early diagnosis and treatment are essential for patient's survival.

Association between neuroimaging and clinical outcomes in individuals with central nervous system cryptococcosis.

The radiological manifestations of central nervous system (CNS) cryptococcosis are diverse and often subtle. There is heterogeneity on how different neuroimaging patterns impact prognosis. This study aims to assess the association between the neuroimaging and clinical outcomes of CNS cryptococcosis. All patients with CNS cryptococcosis between July 2017 and April 2023 who underwent brain magnetic resonance imaging (MRI) were included. The primary outcome was mortality during hospitalisation. Secondary outcomes were readmission, ventricular shunting, duration of hospitalisation and time to the first negative cerebrospinal fluid culture. We compared the outcomes for each of the five main radiological findings on the brain MRI scan. We included 46 proven CNS cryptococcosis cases. The two main comorbidity groups were HIV infection (20, 43%) and solid organ transplantation (10, 22%), respectively. Thirty-nine patients exhibited at least one radiological abnormality (85%), with the most common being meningeal enhancement (34, 74%). The mortality rates occurred at 11% (5/46) during hospitalisation. We found no significant disparities in mortality related to distinct radiological patterns. The presence of pseudocysts was significantly associated with the need for readmission (p = .027). The ventricular shunting was significantly associated with the presence of pseudocysts (p = .005) and hydrocephalus (p = .044). In this study, there is no association between brain MRI findings and mortality. Larger studies are needed to evaluate this important issue.

A Case of Disseminated Cryptococcus in an HIV-Positive Patient

A 69-year-old male with a history of untreated Human Immunodeficiency Virus (HIV) was admitted to the emergency department for symptoms such as cough, shortness of breath, lethargy, and weight loss. His physical examination revealed severe wasting, oral thrush, and hypoxia. Chest imaging revealed cavitary lesions and blood work showed an absolute CD4 count of 23 cells/mm3. An IR-guided biopsy revealed abundant necrosis and scattered narrow-based fungal organisms consistent with Cryptococcus neoformans infection. The patient was treated with liposomal amphotericin B and flucytosine. Due to the increased risk of Immune Reconstitution Inflammatory Syndrome (IRIS), HIV treatment was deferred. The patient deteriorated, transitioned to comfort care, and unfortunately expired. INTRODUCTION Cryptococcus neoformans is a ubiquitous environmental yeast and a leading cause of invasive fungal infection in humans with significant morbidity and mortality that affects both immunocompetent and immune-compromised hosts.1,2 Globally, there are approximately 1 million cases of AIDS-related cryptococcosis each year, leading to over 600,000 deaths. This represents a prevalence of 6.0% (95% CI 5.8–6.2) among people with a CD4 cell count of less than 100 cells per uL.2 The transmission mode is by inhalation of microscopic fungus (desiccated yeast or spores). Immunosuppression is the strongest risk factor for disease development, including HIV infection, stem cell and solid organ transplantation, prolonged immunosuppressive therapy, invasive medical procedures, hematological malignancies, advanced age, and prematurity.1,2,3 Treatment usually involves a fungicidal regimen of IV liposomal amphotericin B, plus flucytosine followed by oral fluconazole.4,5 Overall, 90-day all-cause mortality in patients with cryptococcal infection is 19.4%. Mortality rates are significantly higher in HIV/transplant patients at 90 days (41.7% versus 8.3%, p = 0.017) and one year (41.7% versus 12.5%, p = 0.047).6,7 This case describes a 69-year-old HIV-positive patient who presented with multisystemic manifestations and cavitary lung lesions with blood and cerebrospinal fluid (CSF) findings of cryptococcal antigen and positive fungal culture and lung biopsy confirmation of Cryptococcus.

Semisynthetic Glycoconjugate Vaccine Candidates against Cryptococcus neoformans.

Cryptococcus neoformans is a fungus classified by the World Health Organization as a critically important pathogen, which poses a significant threat to immunocompromised individuals. In this study, we present the chemical synthesis and evaluation of two semisynthetic vaccine candidates targeting the capsular polysaccharide glucuronoxylomannan (GXM) of C. neoformans. These semisynthetic glycoconjugate vaccines contain an identical synthetic decasaccharide (M2 motif) antigen. This antigen is present in serotype A strains, which constitute 95% of the clinical cryptococcosis cases. This synthetic oligosaccharide was conjugated to two proteins (CRM197 and Anthrax 63 kDa PA) and tested for immunogenicity in mice. The conjugates elicited a specific antibody response that bound to the M2 motif but also exhibited additional cross-reactivity toward M1 and M4 GXM motifs. Both glycoconjugates produced antibodies that bound to GXM in ELISA assays and to live fungal cells. Mice immunized with the CRM197 glycoconjugate produced weakly opsonic antibodies and displayed trends toward increased median survival relative to mice given a mock PBS injection (18 vs 15 days, p = 0.06). These findings indicate promise, achieving a successful vaccine demands further optimization of the glycoconjugate. This antigen could serve as a component in a multivalent GXM motif vaccine.

Less Is More? Two Cases of Cryptococcosis Treated Using Single-dose Liposomal Amphotericin B as Part of Induction Therapy in Solid Organ Transplant Recipients.

Less Is More? Two Cases of Cryptococcosis Treated Using Single-dose Liposomal Amphotericin B as Part of Induction Therapy in Solid Organ Transplant Recipients.

A Case of Miliary Pulmonary Cryptococcosis Showing Different Changes in Computed Tomography Images of the Left and Right Lungs

A Case of Miliary Pulmonary Cryptococcosis Showing Different Changes in Computed Tomography Images of the Left and Right Lungs

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

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

Epidemiological trends and clinical outcomes of cryptococcosis in a medically insured population in the United States: a claims-based analysis from 2017 to 2019.

Emerging risk factors highlight the need for an updated understanding of cryptococcosis in the United States. Describe the epidemiological trends and clinical outcomes of cryptococcosis in three patient groups: people with HIV (PWH), non-HIV-infected and non-transplant (NHNT) patients, and patients with a history of solid organ transplantation. We utilized data from the Merative Medicaid Database to identify individuals aged 18 and above with cryptococcosis based on the International Classification of Diseases, Tenth Revision diagnosis codes from January 2017 to December 2019. Patients were stratified into PWH, NHNT patients, and transplant recipients according to Infectious Diseases Society of America guidelines. Baseline characteristics, types of cryptococcosis, hospitalization details, and in-hospital mortality rates were compared across groups. Among 703 patients, 59.7% were PWH, 35.6% were NHNT, and 4.7% were transplant recipients. PWH were more likely to be younger, male, identify as Black, and have fewer comorbidities than patients in the NHNT and transplant groups. Notably, 24% of NHNT patients lacked comorbidities. Central nervous system, pulmonary, and disseminated cryptococcosis were most common overall (60%, 14%, and 11%, respectively). The incidence of cryptococcosis fluctuated throughout the study period. PWH accounted for over 50% of cases from June 2017 to June 2019, but this proportion decreased to 47% from July to December 2019. Among the 52% of patients requiring hospitalization, 61% were PWH and 35% were NHNT patients. PWH had longer hospital stays. In-hospital mortality at 90 days was significantly higher in NHNT patients (22%) compared to PWH (7%) and transplant recipients (0%). One-year mortality remained lowest among PWH (8%) compared to NHNT patients (22%) and transplant recipients (13%). In this study, most cases of cryptococcosis were PWH. Interestingly, while the incidence remained relatively stable in PWH, it slightly increased in those without HIV by the end of the study period. Mortality was highest in NHNT patients.

Epidemiological approach to Cryptococcus meningitis and related species in northeast Brazil: a scoping review

Introduction: Cryptococcosis is a fungal infection associated with yeast of the Cryptococcus genus. It is an opportunistic infection, more prevalent in individuals with AIDS, primarily manifesting as meningitis. Although there are numerous cases of cryptococcosis in northeastern Brazil, little is reported in the literature regarding meningitis cases. Objective: This study aimed to conduct a scoping review of meningitis cases associated with the Cryptococcus genus reported in the northeastern region of Brazil. Methodology: Four databases were utilized. Twenty-one studies were selected, totaling 492 cases. All states had publications on cryptococcal meningitis cases. RESULTS: The results revealed few studies on Cryptococcus meningitis in the region, with 492 identified cases. The majority were caused by Cryptococcus neoformans (356 cases), followed by C. gattii (98 cases), and other related species. AIDS was the primary underlying condition, associated with high mortality. Genetic research was underutilized. Conclusion: There is a need to enhance diagnostic methods in conjunction with increased case reporting to obtain a more detailed and comprehensive understanding of the epidemiology of neurocryptococcosis in northeastern Brazil.

Usefulness of minimally invasive autopsy in the diagnosis of arboviruses to increase the sensitivity of the Epidemiological Surveillance System in Ceará, Brazil.

To create a protocol for performing minimally invasive autopsies (MIA) in detecting deaths from arboviruses and report preliminary data from its application in Ceará state, Brazil. Training was provided to medical pathologists on MIA. A protocol was established for performing MIA, defining criteria for sample collection, storage methods, and diagnoses to be carried out according to the type of biological sample; 43 MIAs were performed in three months. Of these, 21 (48.8%) arrived at the Death Verification Service (SVO) with arboviruses as a diagnostic hypothesis, and seven (16.3%) were confirmed (six chikungunya cases and one dengue case); cases of COVID-19 (n = 9), tuberculosis (n = 5), meningitis (n = 4), cryptococcosis (n = 1), Creutzfeldt-Jakob disease (n = 1), breast cancer (n = 1), and human rabies (n = 1) were also confirmed. The protocol implemented enabled identification of a larger number of suspected arbovirus-related deaths, as well as confirmation of other diseases of interest for surveillance. A protocol was developed to perform minimally invasive autopsies (MIAs) in Death Verification Services (SVO), capable of expanding the system's capacity to identify a greater number of deaths suspected to be due to arboviruses. The experience suggests that in-service trained health professionals are able to perform MIA, and that use of this technique in SVOs has been shown to be capable of increasing the system's sensitivity in detecting deaths of interest to public health. Trained professionals will be able to collect biological material in hospitals, through MIA, in cases of interest for health surveillance and when family members do not allow a complete conventional autopsy to be performed.

Estudo retrospectivo e espacial de diagnósticos anatomopatológicos da criptococose canina e felina em municípios do estado de São Paulo

ABSTRACT Cryptococcosis is a systemic mycosis caused by the genus Cryptococcus that affects humans and animals. The present study aimed to describe the epidemiological and anatomopathological profiles, occurrence, and distribution of the infection by Cryptococcus spp. in 30 dogs and 110 cats residing in the State of São Paulo, from 2014 to 2020. The study evaluated the results from 140 necropsies and histopathology and cytopathology tests provided by Veterinary Pathology services. A higher occurrence of positive diagnosis was observed in females of both cats and dogs, adults, and mixed breeds of both species. The main diagnostic method used was histopathology, with a predominance of integumentary lesions in dogs and cats (skin pattern), with no significant difference between species and lesion location (p≤ 0.827). The time-spatial distribution showed a significant increase in the diagnoses in dogs and cats over the seven years, the identification of areas with a higher rate of diagnosis of cryptococcosis such as Campinas and São José do Rio Preto, and the positive correlation of a diagnosis with climatic data. Retrospective studies of anatomopathological data help to identify suspected cases of cryptococcosis and demonstrate the importance of monitoring and surveillance of cryptococcosis.

Cryptococcus neoformans Infections Differ Among Human Immunodeficiency Virus (HIV)-Seropositive and HIV-Seronegative Individuals: Results From a Nationwide Surveillance Program in France.

Among 1107 cryptococcosis cases from the French surveillance network (2005-2020), the proportion of HIV-seronegative individuals has recently surpassed that of HIV-seropositive individuals. We observed marked differences in patient characteristics, disease presentations, cryptococcal antigen results, infecting species, and mortality according to HIV serostatus.

Cryptococcal Meningoencephalitis in Phenotypically Normal Patients.

Cryptococcosis is an invasive fungal infection found worldwide that causes significant morbidity and mortality among a broad range of hosts. There are approximately 223,000 new cases of cryptococcosis annually throughout the world, and at least 180,000 deaths are attributed to this infection each year. Most of these are due to complications of cryptococcal meningoencephalitis among HIV-infected patients in resource-limited environments. The majority of individuals diagnosed with cryptococcosis have underlying conditions associated with immune dysfunction such as HIV, solid organ transplant, hematologic malignancy, organ failure syndromes, and/or the use of immunosuppressive agents such as glucocorticosteroids and biologic agents. In most clinical series, there is a small proportion of patients with cryptococcosis who are phenotypically normal; that is, they have no clinically obvious predisposition to disease. Cryptococcal meningoencephalitis (CME) presentation and management differ substantially between these normal individuals and their immunocompromised counterparts. In this review, we will focus on CME in the phenotypically normal host and underscore differences in the clinical presentation, management, outcome, and potential risk factors for these patients compared to immunocompromised persons who develop this potential devastating invasive fungal infection.

Meningoencefalomielite e pneumonia causada por Cryptococcus spp. em um gato - relato de caso

ABSTRACT Cryptococcosis is an important systemic mycosis with worldwide distribution that affects men and also domestic and wild animals. The infection is acquired by inhalation of the fungus or basidiospores present in the environment and may manifest as localized nasal or ocular injury, pulmonary illness or, less commonly, as meningoencephalomyelitis. Long-term treatment is necessary, and the prognosis is reserved. This paper aims to report a case of invasive cryptococcosis in a domestic cat that was presented with neurological signs. It is intended to emphasize the systemic nature of the infection and its possible routes of infection, reinforcing the importance of investigating this disease as a differential diagnosis of clinical manifestations with neurological involvement in cats.

Primary Cutaneous Cryptococcosis Caused by Cryptococcus Neoformans in an Immunocompetent Patient

Cryptococcosis is a fungal infection caused by Cryptococcus species, most commonly affecting immunocompromised individuals, while very few cases of the infection in immunocompetent hosts are available in the literature. In this manuscript, we present a case of primary cutaneous cryptococcosis caused by Cryptococcus neoformans in an immunocompetent patient. While cutaneous manifestation is usually a secondary sign of the disseminated disease, our patient presented with primary cutaneous cryptococcosis. Additionally, reports on cryptococcosis cases suggest that immunocompetent hosts are typically infected by C. gattii. However, culture of the discharge from our immunocompetent patient showed heavy growth of C. neoformans. This case highlights the importance of considering cutaneous cryptococcosis as differential diagnosis of ulcerated skin lesions in patients with an exposure to bird droppings, regardless of their immune status and systemic manifestations.

Disseminated Cryptococcosis Is a Common Finding among Human Immunodeficiency Virus-Infected Patients with Suspected Sepsis and Is Associated with Higher Mortality Rates.

Cryptococcosis is the leading cause of death among people with HIV in Sub-Saharan Africa. The lack of optimum diagnoses and medications significantly impair the management of the disease. We investigated the burden of cryptococcosis and related mortality among people with HIV and suspected sepsis in Ethiopia. We conducted a prospective study at (1) Adama Hospital Medical College and (2) Asella Referral and Teaching Hospital from September 2019 to November 2020. We enrolled adult, HIV-infected patients presenting with suspected sepsis and assessed their 28-day survival rates. We performed blood cultures and cryptococcal antigen (CrAg) testing. In total, 82 participants were enrolled with a median age of 35 years, and 61% were female. Overall, eleven (13%) had positive CrAg tests, of which five grew Cryptococcus in blood cultures. Despite high-dose fluconazole (1200 mg/d) monotherapy being given to those with positive CrAg tests, the 28-day mortality was 64% (7/11), with mortality being significantly higher than among the CrAg-negative patients (9% (6/71); p < 0.001). Cryptococcosis was the leading cause of mortality among HIV-infected sepsis patients in this Ethiopian cohort. The CrAg screening of HIV-infected patients attending an emergency department can minimize the number of missed cryptococcosis cases irrespective of the CD4 T cell count and viral load. These findings warrant the need for a bundle approach for the diagnosis of HIV-infected persons presenting with sepsis in low- and middle-income countries.

The management and outcome of cryptococcosis in patients with different immune statuses and treatment protocols: A multicenter real-world study in Jiangsu Province - China.

The incidence of cryptococcosis is increasing in non-immunocompromised patients. However, the evidence on proper management is inadequate in this population. We conducted this multi-center real-world study in pulmonary cryptococcosis patients with different immune statuses, so as to provide practical evidence for optimized clinical management of cryptococcosis, especially for mild-to-moderate immunodeficient diseases patients. This is a prospective observational study. The clinical data of patients with proven cryptococcosis were collected and analyzed from 7 tertiary teaching hospitals in Jiangsu Province, China from January, 2013 to December, 2018. Proven cases include pulmonary cryptococcosis, cryptococcal meningitis, cryptococcemia and cutaneous cryptococcosis. Patients were followed up over 24 months. According to their immune status, patients with cryptococcosis were divided into three groups, namely immunocompetent group (IC), mild-to-moderate immunodeficient diseases group (MID), severe immunodeficient diseases group (SID). Meanwhile, pulmonary crypotococcosis (PC) and extrapulmonary crypotococcosis (EPC) were also classified and analyzed. 255 proven cases of cryptococcosis were enrolled. Finally, 220 cases completed the follow-up. 143 proven cases (65.0%) were immunocompetent (IC), 41 cases (18.6%) were MID, and 36 cases (16.4%) were SID. 174 cases (79.1%) were PC and 46 cases (20.9%) were EPC. The mortality was significantly higher in SID and MID patients [47.2% (SID) vs. 12.2% (MID) vs. 0.0% (IC), p<0.001]. The mortality was also significantly higher in EPC patients [45.7% vs. 0.6% (PC), p<0.001]. Patients with alternative initial antifungal treatment had higher mortality than patients with guideline recommended initial treatment [23.1% vs. 9.5%, p=0.041]. In MID group, the mortality of receiving alternative initial antifungal treatment was significantly higher than recommended initial treatment [2/3 vs. 3/34(8.8%), p=0.043]. In pulmonary cryptococcosis patients with MID, the mortality was very similar to IC group [0.0% vs. 0.0% (IC)], lower than SID group [0.0% vs. 11.1% (SID), p=0.555]. However, in extrapulmonary cryptococcosis patients with MID, the mortality was significantly higher than that in IC [62.5% vs. 0.0% (IC)], and similar to SID patients [62.5% vs. 59.3% (SID)]. The immune status exert a significant influence on the management and prognosis of cryptococcosis patients. The mortality of cryptococcosis patients with MID is higher than that of immunocompetent patients. For MID patients with pure pulmonary cryptococcosis, it is acceptable to take the treatment recommended as IC patients. For the MID patients with extrapulmonary cryptococcosis, the mortality is high and the initial treatment should follow the regimen for SID patients. Following the recommended treatment regimen in the IDSA guideline can reduce mortality in patients with cryptococcosis. Starting on alternative initial antifungal treatment may bring worse outcomes.

Diversity of potencial pathogenic Cryptococcus species isolated from environment in country side São Paulo state, Brazil

Cryptococcosis is a systemic disease caused by two species. C. neoformans species complexes are associated with cases of cryptococcosis in immunosuppressed patients, being commonly isolated from the soil and birds feces. C. gattii species complexes affects mainly immunocompetent individuals and is often isolated in native or exotic tree species in state of biodegradation. This study aimed to perform the environmental mapping of pathogenic species of the genus Cryptococcus in tree samples of public places of the city of Birigui, São Paulo. The samples were collected from regions with greater traffic in this city. After processing, morphophysiological, biochemical, carbon and nitrogen assimilation, URA5 PCR and RFLP with double enzymatic digestion tests were performed to characterize the Cryptococcus species/species complexes. The percentage of tree colonization by the C. gattii VGII was 5%, for C. neoformans VNIV was 1%, and was found 6% of C. laurentii and 3% of C. albidus species. These results suggest that there are a micro-foci and diversity of pathogenic Cryptococcus species in arboreal environment locations investigated in this study.