Cryptococcal Infection Research Articles

Cryptococcal Meningitis in an Apparently Immunocompetent Individual: A Case Report

Cryptococcus neoformans, a saprophyte, is commonly found in soil contaminated with pigeon droppings but has also been isolated from the wood of several tree species in South America and India, including the flowers and bark of eucalyptus trees. Inhalation of small, encapsulated yeasts may lead to an initial pulmonary infection. However, this is usually short-lived and frequently silent, especially in immunocompetent individuals. Immunocompromised patients are usually tested for Cryptococcus as a causative agent when presenting with features of meningitis, but when dealing with immunocompetent patients, it is seldom considered. This report presented a case of a 39-year-old male who was apparently immunocompetent, yet developed cryptococcal meningitis. He had no prior history of any chronic illness, malignancy, immunosuppressive medication, or steroid use. Routine blood investigations were within normal limits. Autoimmune workup and viral markers were negative. He had raised Intracranial Pressure (ICP), Cerebrospinal Fluid (CSF) leukocytosis, and encapsulated yeast forms consistent with cryptococcal meningitis initially demonstrated by CSF cytology examination with Papanicolaou stain and May-Grunwald-Giemsa, and further confirmed by special stains. This case highlights the role of initial cytological workup in detecting cryptococcal infection through morphological and special stain studies in an immunocompetent host.

LAMinar Flow: Sterol Transport in a Pathogenic Yeast.

Cryptococcus neoformans is an important fungal pathogen, responsible for over 140,000 deaths per year worldwide. Like other yeasts, C. neoformans relies on ergosterol as its major membrane sterol and carefully regulates its synthesis and distribution. Ergosterol is also targeted by two of the three compound classes currently used to treat cryptococcal infection. We recently reported the discovery and characterization in C. neoformans of a single retrograde ergosterol transporter of the LAM family, Ysp2. Here we review these findings and discuss directions for future research, including the connections between processes that are perturbed by the absence of Ysp2 (which also abrogates cryptococcal virulence) and possible roles for Ysp2 and other, as yet unknown, lipid transport proteins in this organism.

Vaccine Strategies for Cryptococcus neoformans.

Cryptococcus neoformans infections are a major worldwide concern as current treatment strategies are becoming less effective in alleviating the infection. The most extreme and fatal cases are those of immunocompromised individuals. Clinical treatments for cryptococcosis are limited to a few classes of approved drugs, and due to a rise in drug resistance, these drugs are becoming less effective. Therefore, it is essential to develop innovative ways to control this infection. Vaccinations have emerged as a safe, viable, and cost-effective solution to treat a number of diseases over the years. Currently, there are no clinically available vaccines to treat cryptococcal infections, but a number of studies have shown promising results in animal models. Here, we present step-by-step experimental protocols using live-attenuated or heat-killed C. neoformans cells as a vaccination strategy in a preventive or in a therapeutic murine model of cryptococcosis.

Metastatic Cryptococcosis as a manifestation of immune reconstitution inflammatory syndrome in a patient with COVID-19 infection

Disseminated cryptococcosis is an infrequent fungal illness primarily observed in immunocompromised individuals, particularly among those with human immunodeficiency virus (HIV). In this report, a case where the initiation of antiretroviral therapy revealed a previously hidden Cryptococcus infection in an HIV-positive male who also had COVID-19 is presented. A 30-year-old male with a medical history of HIV sought medical attention at the Emergency Department due to the presence of a widespread, non-itchy skin rash along with severe difficulty breathing. Diagnosis of unmasking immune reconstitution inflammatory syndrome (IRIS) associated with disseminated cryptococcosis, all while testing positive for COVID-19 was made based on clinical presentation and performed analyses. COVID-19 management guidelines were strictly adhered to and treatment included the administration of steroids, amphotericin B and fluconazole. Additionally, empirical coverage for Pneumocystis carinii pneumonia (PCP) was initiated. Regrettably, the patient's clinical condition deteriorated in the following days, ultimately resulting in his passing. The ongoing pandemic has understandably prioritised the diagnosis of COVID-19 by healthcare providers, sometimes overshadowing the exploration of alternative diagnoses. It is crucial to maintain a heightened clinical suspicion for opportunistic infections, especially among immunocompromised individuals, particularly those with HIV.

Neutron Scattering Analysis of Cryptococcus neoformans Polysaccharide Reveals Solution Rigidity and Repeating Fractal-like Structural Patterns.

Cryptococcus neoformans is a fungal pathogen that can cause life-threatening brain infections in immunocompromised individuals. Unlike other fungal pathogens, it possesses a protective polysaccharide capsule that is crucial for its virulence. During infections, Cryptococcus cells release copious amounts of extracellular polysaccharides (exo-PS) that interfere with host immune responses. Both exo-PS and capsular-PS play pivotal roles in Cryptococcus infections and serve as essential targets for disease diagnosis and vaccine development strategies. However, understanding their structure is complicated by their polydispersity, complexity, sensitivity to sample isolation and processing, and scarcity of methods capable of isolating and analyzing them while preserving their native structure. In this study, we employ small-angle neutron scattering (SANS) and ultra-small-angle neutron scattering (USANS) for the first time to investigate both fungal cell suspensions and extracellular polysaccharides in solution. Our data suggests that exo-PS in solution exhibits collapsed chain-like behavior and demonstrates mass fractal properties that indicate a relatively condensed pore structure in aqueous environments. This observation is also supported by scanning electron microscopy (SEM). The local structure of the polysaccharide is characterized as a rigid rod, with a length scale corresponding to 3-4 repeating units. This research not only unveils insights into exo-PS and capsular-PS structures but also demonstrates the potential of USANS for studying changes in cell dimensions and the promise of contrast variation in future neutron scattering studies.

Frequency of cryptococcal antigenemia in hiv treatment naïve patients with CD4 count below 200/ml

Background: Cryptococcosis is a dangerous opportunistic fungal infection that poses a significant threat to individuals with advanced HIV/AIDS and compromised cellular immunity. The objective was to determine the frequency of asymptomatic cryptococcal antigenemia in treatment naïve HIV patients. Material and Methods: This cross-sectional study was conducted at The Indus Hospital and Health Network, Karachi from July to December 2022. We included all consecutive HIV patients of age > 18 years, either gender, who were treatment naïve, with CD4 counts ≤200/μL, and did not have any symptoms of cryptococcal infection. Cryptococcal antigen (CrAg) was tested in blood based on the Direct Agglutination test. Results: A total of 100 HIV patients were enrolled. The mean age was 35.12 ± 10.93 years. The majority (78%) of the subjects were males, and 2/3rd were sexually active; exposure to birds was identified in 31% of patients. Most of the patients enrolled belonged to WHO HIV stage 1 (61%), followed by stage 4 (30%). The median CD4 count was 103.5 (IQR: 56.5 – 126.5) /μL. 48 patients had CD4 count between 101 to 200/μL, while 51 patients had CD4 count ≤100/μL. Only 2 patients were found to have CrAg positive making an overall prevalence of 2%. Both patients had a CD4 count ≤ 100/μL (n = 2/51, 3.9%). 30% of patients had other opportunistic co-infections (n = 30). Conclusion: The prevalence of asymptomatic cryptococcosis in the treatment naïve HIV is low in the Pakistani population. A routine CrAg screening can be individualized and avoided in selected patients with CD4 count >100/μL in a resource-limited country like Pakistan. Keywords: AIDS, HIV stages, Asymptomatic, Opportunistic infection.

Identification of risk factors for disseminated cryptococcosis in non-hiv patients: a retrospective analysis

ObjectiveThis study aimed to investigate the potential risk factors associated with disseminated cryptococcosis in HIV-negative individuals.MethodsA total of 106 HIV-negative patients with cryptococcal disease were enrolled. The observation group consisted of patients with disseminated cryptococcosis (DC), whereas the control groups included patients with pulmonary cryptococcosis (PC) and cryptococcal meningitis (CM). Univariate and multivariate logistic regression algorithms were used to explore the significant clinical and laboratory characteristics that affect the progression of cryptococcal infections. Finally, receiver operating characteristics (ROC) curves are applied to assess the diagnostic value of identified risk factors.LE: Kindly check the edit made in the title.I agreeResultsOf the 106 patients, 57 were diagnosed with pulmonary cryptococcosis, 22 with cryptococcal meningitis, and 27 with disseminated cryptococcosis. The logistic regression equation included five variables: diabetes, decompensated liver cirrhosis, long-term use of immunosuppressive agents, decreased serum albumin level, and elevated plasma cytokine IL-10 level. The ROC curves showed that albumin (AUC > 0.7), IL-10 (AUC > 0.7) and decompensated liver cirrhosis (AUC > 0.6) have relatively high diagnostic capacity in predicting the progression of Cryptococcus.ConclusionThis study identified elevated IL-10 levels as an independent risk factor for developing disseminated cryptococcosis in the control groups. Furthermore, decompensated liver cirrhosis and decreased serum albumin independently affected the progression of cryptococcosis in the CM and PC groups, respectively.

CLINICAL AND TYPICAL IMAGING CHARACTERISTICS OF CRYPTOCOCCAL MENINGITIS IN HIV INFECTED PATIENT: A CASE REPORT

Although Cryptococcal infection is worldwide distribution, it is more seen in the immunocompromised patients. Cryptococcus neoformans is the most common central neurvous system fungal pathogen in HIV infected patients. Besides clinical features and laboratory tests, imaging findings play an important role in the evaluation of cryptococcal infection. In this paper we present an immunocompromised HIV infected case of C. neoformans meningitis with clinical features and imaging characteristics by MR image.

Cryptococcal proteases exhibit the potential to activate the latent SARS-CoV-2 spike protein

BackgroundThe COVID-19 pandemic has affected more than 650 million people and resulted in over 6.8 million deaths. Notably, the disease could co-manifest with microbial infections, like cryptococcosis, which also presents as a primary lung infection. ObjectiveIn this contribution, we sought to determine if cryptococcal supernatant (which contains secreted furin-like proteases) could activate the SARS-CoV-2 spike protein. MethodsMolecular docking of the crystal structures of the SARS-CoV-2 spike protein (target) and selected cryptococcal proteases (ligands) was executed using the high ambiguity driven protein-protein docking (HADDOCK) server, with the furin protease serving as a reference ligand. The furin protease is found in human cells and typically activates the SARS-CoV-2 spike protein.Importantly, in order to provide experimental evidence for enzymatic activity, we also assessed the biochemical efficiency of cryptococcal proteases to initiate viral entry into HEK-293 T cells by SARS-CoV-2 spike pseudotyped Lentivirus. ResultsWe show that the selected cryptococcal proteases could interact with the spike protein, and some had a better or comparable binding affinity for the spike protein than furin protease following an in silico comparative analysis of the molecular docking parameters. Furthermore, it was noted that the biochemical efficiency of the cryptococcal supernatant to transduce HEK-293 T cells with SARS-CoV-2 pseudovirions was comparable (p > 0.05) to that of recombinant furin. ConclusionsTaken together, these data show that cryptococcal proteases could activate the SARS-CoV-2 spike protein. In practice, it may be critical to determine if patients have an underlying cryptococcal infection, as this microbe could secrete proteases that may further activate the SARS-CoV-2 viral particles, thus undermining COVID-19 intervention measures.

Cryptococcal Infection Presenting as a Pleural Effusion in a Liver Transplant Recipient

Abstract We report a rare case of a liver transplant recipient who experienced acute respiratory failure early posttransplantation because of cryptococcal pleural effusion. Although cryptococcal disease presenting solely as pleural effusion has been reported in the literature, it is not widely described in liver transplant recipients. Cryptococcal disease usually manifests late in the posttransplant period, whereas our patient was diagnosed with the infection early posttransplant. Diagnosis was made by pleural fluid culture. The initial serum cryptococcal antigen testing was negative. This case demonstrates the potential of subclinical or latent infections in patients with cirrhosis and liver transplant recipients and the importance of considering pleural fluid culture in the diagnostic evaluation of pleural effusions in cirrhotic patients.

A Case of Generalized Cryptococcal Infection in an HIV-Infected Patient with Coinfections of Cytomegalovirus and Tuberculosis

This case report presents the observation of a patient with HIV infection diagnosed with a combination of several opportunistic infections, including cryptococcosis, cytomegalovirus infection and tuberculosis. The patient underwent treatment at the National Institute of Phthisiology and Pulmonology named after F.G. Yanovsky NAMS of Ukraine and the Institute of Epidemiology and Infectious Diseases named after L.V. Gromashevsky NAMS of Ukraine.HIV infection was detected at the Institute of Phthisiology and Pulmonology during an examination for exudative pleuritis. Initial evaluation raised suspicion of tuberculous exudative pleuritis. Mycobacterium tuberculosis was not detected in the biopsy material using the Xpert MTB/RIF method. Morphological analysis indicated a rare variant of cryptococcal infection involving intrathoracic lymph nodes and pleura. Additional testing revealed a positive cryptococcal antigen. Cryptococci were also identified in the cerebrospinal fluid. Cytomegalovirus chorioretinitis was diagnosed. The patient was treated according to the opportunistic infection management protocol. Antiretroviral therapy (TDF, FTC, DTG — tenofovir, emtricitabine, dolutegravir) was initiated after six weeks. The patient received prophylaxis for Pneum­cystis pneumonia with cotrimoxazole and for tuberculosis with isoniazid. One month after starting antiretroviral therapy, the patient developed a febrile illness. Further examination revealed infiltrative pulmonary tuberculosis. Repeat bacteriological testing detected rifampicin-susceptible Mycobacterium tuberculosis. The patient received standard tuberculosis treatment (2HRZE/4HR) and achieved a cure.This case highlights the diagnosis and treatment of a patient with acquired immunodeficiency syndrome and multiple secondary infections. Despite advanced immunodeficiency, timely and adequate medical interventions resulted in high treatment efficacy, contributing to increased life expectancy and improved quality of life in individuals living with HIV.

Orthotopic Heart Transplantation Followed By Autologous Stem Cell Transplantation in Patients with Cardiac AL Amyloidosis: Results from a Single Centre Prospective Study

Background: Patients with advanced cardiac AL amyloidosis have a dismal prognosis, with an overall survival (OS) of only 5 months for Stage IIIb patients (Palladini et al, 2023). Induction chemotherapy followed by high dose chemotherapy and autologous stem cell transplantation (HDT and ASCT) has been widely used as treatment for AL amyloidosis. However, patients with advanced cardiac AL amyloidosis are often not suitable for HDT and ASCT due to high transplant related mortality (TRM). Orthotopic cardiac transplantation (OHT) following induction treatment may improve patient fitness and thus allow HDT and ASCT to deepen and prolong responses. We present our single centre, prospective study of patients with Stage IIIa and Stage IIIb cardiac AL amyloidosis who received OHT followed by sequential HDT and ASCT. Aims: The primary outcomes were 3 year OS and progression-free survival (PFS). Efficacy and safety were assessed as secondary outcomes. Efficacy was evaluated by light chain and cardiac response after ASCT. Safety was assessed by rate of TRM, cardiac rejection, opportunistic infections, and cytopenia related complications. Methods: During 2015 to 2021, patients with Stage IIIa or Stage IIIb AL amyloidosis aged under 65 years underwent OHT followed by HDT and ASCT. Patients with multiple myeloma were excluded. At approximately 6 months following OHT, patients underwent stem cell mobilization with granulocyte colony-stimulating factor alone followed by peripheral blood apheresis stem cell collection. Mycophenolate immunosuppression was temporarily withheld during stem cell mobilization and collection. Patients then received a high dose melphalan ASCT followed by 3-6 monthly assessments. Results: Nine patients (median age of 53 years, range 47-60 years) completed both OHT and ASCT. Seven other patients were screened but did not proceed with OHT. The cohort included both stage IIIa (55%) and stage IIIb (44%) patients. Most patients received cyclophosphamide-bortezomib-dexamethasone induction therapy (89%) and one patient received lenalidomide-bortezomib-dexamethasone. The median time from diagnosis of AL amyloidosis to OHT was 11 months (range 5-57 months) and median time from OHT to ASCT was 7 months (range 5-8 months). 3 year OS was 83% and PFS was 56% (Figure 1). At a median follow up of 37 months (range 17-69 months), 89% of patients remain alive. One patient with Stage IIIa disease who underwent HDT and ASCT with progressive disease (PD) died 28 months following ASCT due to PD. Subgroup analysis demonstrated 3 year OS in Stage IIIa patients of 75% compared to 100% in Stage IIIb (p=0.48). 3 year PFS was 53% in Stage IIIa patients and 66% in Stage IIIb (p=0.8). Patients in complete remission (CR) prior to ASCT had an improved 3 year OS of 100% compared to 66% for those in partial remission (PR) or with PD (p=0.32). 3 year PFS was significantly improved at 100% when ASCT occurred in CR compared to 0% in those in PR or with PD (p=0.01) (Figure 2). All patients either maintained a CR or achieved an improved haematological response following HDT and ASCT, with 89% of patients in CR at 6 months post ASCT. At the median follow up of 37 months, 78% were in CR and 22% had PD. At last follow up, there has been no documented amyloid recurrence in a cardiac allograft. There was no TRM noted in this study. All patients had cardiac rejection with 66% developing Grade 3A/2R rejection requiring methylprednisone. The most common infective complication was CMV reactivation (44%). Other infective complications included cryptococcal infection (11%), aspergillus and MAC infection (11%) and HSV reactivation requiring hospitalization (11%). During admission for HDT and ASCT, 89% had febrile neutropenia and there were no bleeding complications. Conclusions: We have demonstrated, in a prospective design, that sequential OHT/ASCT following induction therapy is safe in patients with Stage IIIa/b cardiac AL amyloidosis without an increase in TRM. This approach was associated with excellent survival outcomes compared with historical cohorts. Given the deep and prolonged responses seen with daratumumab based induction, a risk adapted strategy may be more appropriate moving forward, with only those not achieving a haematological CR undergoing consolidation ASCT following OHT.

Macrophages-derived exo-miR-4449 induced by Cryptococcus affects HUVEC permeability and promotes pyroptosis in BEAS-2B via the HIC1 pathway

Macrophages have recently been discovered to assume a significant role in the progression of cryptococcosis. However, the potential involvement of macrophage-derived exosomes in the pathogenesis of cryptococcosis remains uncertain. In this study, we investigated the changes of microRNAs in macrophage exosomes (exo-miRNAs) in cryptococcal infections and the role of markedly altered exo-miRNAs in the modulation of Human Umbilical Vein Endothelial Cells (HUVEC) permeability and ROS accumulation and pyroptosis in Human Bronchial Epithelioid Cells (BEAS-2B). Techniques such as microarray analysis and real-time quantitative PCR were used to detect different exo-miRNAs and to screen for the most highly expressed exo-miRNAs. Then its mimics were transfected into HUVEC to study its effect on the monolayer permeability of HUVEC. Finally, the relationship between this exo-miRNAs and the ROS accumulation and pyroptosis was verified by bioinformatics analysis. The results showed that five exo-miRNAs were overexpressed and two exo-miRNAs were reduced, among which, exo-miR-4449 was expressed at the highest level. Exo-miR-4449 could be internalized by HUVEC and enhanced its monolayer permeability. Moreover, exo-miR-4449 was found to promote ROS accumulation and pyroptosis in BEAS-2B through HIC1 pathway. Thus, exo-miR-4449 plays an important role in the pathogenesis of cryptococcosis and holds promise as a significant biomarker for treatment.

Genetic diversity and microevolution in clinical Cryptococcus isolates from Cameroon.

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

Asymptomatic Pulmonary Cryptococcosis And Tuberculosis Co-infection in an immunocompetent Host: A case report

Pulmonary Cryptococcosis is a rare fungal infection that mostly occurs in immunocompromised host. However, with advancement in diagnostic approach like tissue biopsy, cryptococcal infections are now increasingly being recognised.In immunocompetent host, cryptococcal infection is often asymptomatic and rarely becomes disseminated.
 Symptom development in immunocompetent host largely depends on burden and virulence of pathogen. Due to similarities in clinical, radiological and pathological findings in Cryptococcosis, Tuberculosis and other fungal infections like Blastomycocosis, it is important to have a tissue biospy to confirm the diagnosis.
 The aim of this case report is to highlight the investigation necessary to diagnose both fungal infection and Tuberculosis due to similar clinical, radiological features in both. We report a case of Gene Xpert positive Tuberculosis and histopathology proven Pulmonary Cryptococcos in same patient.

CNS Cryptococcoma in an Immunocompetent Adult from a Low Resource Setting: An Illustrative Case Report

Purpose: Cryptococcal infection in the Central Nervous System (CNS) is frequently seen in human immunodeficiency virus (HIV) patients and others with low immunity. CNS cryptococcoma in immunocompetent patients is rare. We present a case of CNS cryptococcoma in an immunocompetent patient and review literature.
 Methodology: A 62-year-old, HIV negative, immunocompetent female patient with no known chronic illness, presented with 5 months’ history of a progressive headache, associated with on and off episodic generalized convulsions. She had been to several hospitals before referral to our center with a diagnosis of a brain tumor on CT scan imaging. Before this and despite a negative CSF analysis result, she had received treatment for bacterial meningitis with no success.
 Findings: At Mbarara Regional Referral Hospital (MRRH), she had surgery with excision biopsy which showed features consistent with cryptococcosis on histology. The patient had a successful adjuvant treatment with antifungal drugs following surgery.
 Unique Contribution to Theory, Practice and Policy: The diagnosis of a CNS cryptococcal infection in an immunocompetent patient and its successful treatment by including surgery, were both unusual. Fatal postsurgical outcomes have been reported by other authors who favor a totally conservative approach to the treatment of this lesion.

Dendritic Cells: Multifunctional Roles in Host Defenses to Cryptococcus Infections.

Fungal infections are an increasingly growing public health concern, and Cryptococcus is one of the most problematic fungal organisms causing substantial mortality and morbidity worldwide. Clinically, this high incidence of cryptococcosis is most commonly seen in immunocompromised patients, especially those who lack an adaptive T cell response, such as HIV/AIDS patients. However, patients with other underlying immunodeficiencies are also at an increased risk for cryptococcosis. The adaptive immune response, in particular the Th1/Th17 T-cell-mediated responses, to pulmonary Cryptococcus infections are required for host protection. Dendritic cells (DCs), encompassing multiple subsets identified to date, are recognized as the major professional antigen-presenting cell (APC) subset essential for the initiation and execution of T-cell immunity. Apart from their prominent role in orchestration of the adaptive arm of the immune defenses, DCs are fully armed cells from the innate immune system capable of the recognition, uptake, and killing of the fungal cells. Thus, DCs serve as a critical point for the endpoint outcomes of either fungal control or unrestrained fungal infection. Multiple studies have shown that DCs are required for anti-cryptococcal defense in the lungs. In addition, the role of DCs in Cryptococcus gattii infections is just starting to be elucidated. C. gattii has recently risen to prominence with multiple outbreaks in the US and Canada, demonstrating increased virulence in non-immunocompromised individuals. C. gattii infection fails to generate an inflammatory immune response or a protective Th1/Th17 T cell response, at least in part, through a lack of proper DC function. Here we summarize the multiple roles of DCs, including subsets of DCs in both mouse and human models, the roles of DCs during cryptococcal infection, and mechanisms by cryptococcal cells to attempt to undermine these host defenses.

Characteristics and risk factors for readmission in HIV-infected patients with Talaromyces marneffei infection.

Talaromyces marneffei (T. marneffei) is an opportunistic fungal infection (talaromycosis), which is common in subtropical regions and is a leading cause of death in HIV-1-infected patients. This study aimed to determine the characteristics and risk factors associated with hospital readmissions in HIV patients with T. marneffei infection in order to reduce readmissions. We conducted a retrospective study of admitted HIV-infected individuals at the Fourth People's Hospital of Nanning, Guangxi, China, from 2012 to 2019. Kaplan-Meier analyses and Principal component analysis (PCA) were used to evaluate the effects of T. marneffei infection on patient readmissions. Additionally, univariate and multifactorial analyses, as well as Propensity score matching (PSM) were used to analyze the factors associated with patient readmissions. HIV/AIDS patients with T. marneffei-infected had shorter intervals between admissions and longer lengths of stay than non-T. marneffei-infected patients, despite lower readmission rates. Compared with non-T. marneffei-infected patients, the mortality rate for talaromycosis patients was higher at the first admission. Among HIV/AIDS patients with opportunistic infections, the mortality rate was highest for T. marneffei at 16.2%, followed by cryptococcus at 12.5%. However, the readmission rate was highest for cryptococcus infection (37.5%) and lowest for T. marneffei (10.8%). PSM and Logistic regression analysis identified leukopenia and elevated low-density lipoprotein (LDL) as key factors in T.marneffei-infected patients hospital readmissions. The first admission represents a critical window to intervene in the prognosis of patients with T. marneffei infection. Leukopenia and elevated LDL may be potential risk factors impacting readmissions. Our findings provide scientific evidence to improve the long-term outcomes of HIV patients with T. marneffei infection.

Invasive fungal infection in ANCA-associated vasculitis: Between the Devil and Deep blue sea. Case series and review of the literature.

Patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV) are susceptible to opportunistic infections, including invasive fungal infections (IFI). This is due to many factors, including prolonged immunosuppressive therapy. The treatment of AAV with such IFIs is challenging. A descriptive analysis of 5 patients with AAV complicated by concomitant invasive fungal infections was performed. We also have done a comprehensive literature review of IFIs in AAV using PubMed and Google Scholar databases. All 5 patients initially received immunosuppressive medication but subsequently acquired IFI. One patient had sphenoid sinus involvement, and four had lung parenchymal involvement. Aspergillus infection was diagnosed in three patients, Cryptococcus infection in one patient and mixed infection with Aspergillus and Mucor infection in one patient. All our patients were on low doses of corticosteroids for several months to years or had received high-dose pulse steroids with cyclophosphamide in the last few weeks before being diagnosed with IFI. It was difficult to distinguish disease activity from IFI in all the cases. Two of the five patients died despite antifungal therapy. The literature review revealed a prevalence of IFIs ranging from 1 to 9.6% (excluding pneumocystis pneumonia). Aspergillosis was the predominant type of IFI, affecting 46 of 86 patients. Most of these patients (40/46) had pulmonary involvement. The prognosis for patients with IFI was consistently poor, as evidenced by 19 deaths out of 29 reported outcomes. Overall, IFIs have a poor prognosis in patients with AAV. Differentiating disease activity from IFI is difficult because of similar organ distribution, imaging lesions, and histopathological characteristics. A high suspicion index and good-quality microbiology are needed for early treatment and prevention of mortality.

Inbred SJL mice recapitulate human resistance to Cryptococcus infection due to differential immune activation.

Cryptococcosis studies often utilize the common C57BL/6J mouse model. Unfortunately, infection in these mice fails to replicate the basic course of human disease, particularly hampering immunological studies. This work demonstrates that SJL/J mice can recapitulate human infection better than other mouse strains. The immunological response to Cryptococcus infection in SJL/J mice was markedly different from C57BL/6J and much more productive in combating this infection. Characterization of infected mice demonstrated strain-specific genetic linkage and differential regulation of multiple important immune-relevant genes in response to Cryptococcus infection. While our results validate many of the previously identified immunological features of cryptococcosis, we also demonstrate limitations from previous mouse models as they may be less translatable to human disease. We concluded that SJL/J mice more faithfully recapitulate human cryptococcosis serving as an exciting new animal model for immunological and genetic studies.