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Background: Cryptococcosis is an invasive infection that commonly affects immunosuppressed individuals, especially patients with HIV infection. Cryptococcal infection in HIV-infected patients should be considered a major health concern because it is associated with high morbidity and mortality rates. In this study, we aimed to evaluate the clinical characteristics and prognostic factors of cryptococcal infections in human immunodeficiency virus (HIV)-infected patients to facilitate effective clinical management and improve patient outcomes., Methods: We reviewed and analyzed the clinical data and relevant laboratory test results of HIV-infected patients with positive cryptococcal cultures and reserved strains between 2013 and 2023 from Beijing Youan Hospital affiliated to Capital Medical University. The clinical characteristics and laboratory test results of the patients were compared, and the correlation between parameters and the prognoses of the patients at different observation timepoints (3, 6, 9, and 12 months) was analyzed., Results: A total of 76 patients (70 males and six females; median age, 37 years) were included in this study. The results indicated that the later the initiation of antiretroviral therapy (ART) after the diagnosis of HIV infection (> 6 months), the higher the probability of death. Analysis of the correlation between the time of ART initiation and the timing of treatment for cryptococcal infections showed that the time of ART initiation was strongly related to survival at different timepoints. Initiation of ART time within 0-4 weeks, 4-6 weeks and more than 6weeks of starting treatment for Cryptococcus infection was associated with a lower mortality rate at 12-month, the 3-month, 6- and 9-month follow-up timepoint separately., Conclusions: Although cryptococcal infection in HIV-infected patients continues to be a challenging and intricate issue, ART is a key factor that affects its prognosis. The later ART is started, the worse the prognosis of the infection. The time of ART initiation and the timing of treatment for cryptococcal infections should be further refined and balanced based on different clinical courses. Thus, clinicians should pay closer attention to cryptococcal infections in patients with HIV infection and initiate ART based on the patient's clinical condition., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Dai, Lou, Yu, Chen and Lu.)

Background: Cryptococcosis is an invasive, opportunistic fungal infection seen especially in human immunodeficiency virus (HIV) infected patients. Cryptococcal meningitis (CM) is the second leading cause of mortality in HIV patients. We report a case of disseminated cryptococcosis presenting with altered mental status in a newly diagnosed HIV infection., Methods and Results: A 50-year-old with a short history of altered mental sensorium and a history of low-grade fever and weight loss for few months presented at a tertiary care hospital in North India. He was detected positive for HIV-1. Cryptococcal antigen (CRAG) was positive in Cerebrospinal fluid (CSF), and negative in serum. The fungal culture in CSF was sterile while the fungal blood culture grew Cryptococcus neoformans. The patient was treated with single high-dose Liposomal Amphotericin B (LAmB) therapy followed by Fluconazole and Flucytosine for the next two weeks followed by fluconazole daily for consolidation and maintenance therapy. Antiretroviral therapy (ART) was started 4 weeks after induction therapy. After 6 months, the patient is doing fine., Conclusion: Single dose LAmB along with the backbone of fluconazole and flucytosine appears promising in disseminated cryptococcal infection in HIV-infected individuals., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Hepatitis B virus (HBV) infection can cause liver failure, while individuals with Acquired Immunodeficiency Virus Disease (AIDS) are highly susceptible to various opportunistic infections, which can occur concurrently. The treatment process is further complicated by the potential occurrence of immune reconstitution inflammatory syndrome (IRIS), which presents significant challenges and contributes to elevated mortality rates., Case Presentation: The 50-year-old male with a history of chronic hepatitis B and untreated human immunodeficiency virus (HIV) infection presented to the hospital with a mild cough and expectoration, revealing multi-drug resistant pulmonary tuberculosis (MDR-PTB), which was confirmed by XpertMTB/RIF PCR testing and tuberculosis culture of bronchoalveolar lavage fluid (BALF). The patient was treated with a regimen consisting of linezolid, moxifloxacin, cycloserine, pyrazinamide, and ethambutol for tuberculosis, as well as a combination of bictegravir/tenofovir alafenamide/emtricitabine (BIC/TAF/FTC) for HBV and HIV viral suppression. After three months of treatment, the patient discontinued all medications, leading to hepatitis B virus reactivation and subsequent liver failure. During the subsequent treatment for AIDS, HBV, and drug-resistant tuberculosis, the patient developed disseminated cryptococcal disease. The patient's condition worsened during treatment with liposomal amphotericin B and fluconazole, which was ultimately attributed to IRIS. Fortunately, the patient achieved successful recovery after appropriate management., Conclusion: Enhancing medical compliance is crucial for AIDS patients, particularly those co-infected with HBV, to prevent HBV reactivation and subsequent liver failure. Furthermore, conducting a comprehensive assessment of potential infections in patients before resuming antiviral therapy is essential to prevent the occurrence of IRIS. Early intervention plays a pivotal role in improving survival rates., (© 2024. The Author(s).)

Objective: Central nervous system cryptococcosis (CNSc) is an AIDS defining opportunistic infection. This retrospective study aimed to analyze the changing epidemiology of CNSc cases from the period of pre- to post-emergence of HIV epidemic in south India., Methods: Confirmed cases of CNSc from 1978 to 2015 were analyzed for demographic and clinical details with special reference to the cases diagnosed in south India during the period 1952-1977. Geographical distribution, affected age groups, clinical aspects, and comorbidities in relation to immune status were analysed RESULTS: The highest number of CNSc cases (n = 125) were recorded in 2006, with 89.6% HIV positivity. The highest HIV-positivity (93.6%) was documented in the years 2002 and 2009. CNSc cases have majorly changed after the introduction and spread of HIV in terms of predisposing factors, comorbidities, severity, affected age groups and treatment. Notably, an overall rise was observed in non-HIV associated CNSc cases from 1997 (8.1%) to 2015 (16.9%)., Conclusion: The peak of CNSc had already reached in south India during 2005-2006. However, the number of new infections has slowly decreased in last ten years. Progressive awareness and, early diagnosis of HIV and cryptococcosis, adequate availability of HAART and potential antifungal therapy has played crucial roles in changing epidemiology of the CNSc and its associated mortality., Competing Interests: Declaration of Competing Interest We declare that authors do not have any conflict of interest, (Copyright © 2023 SFMM. Published by Elsevier Masson SAS. All rights reserved.)

Background: Up to 15% of deaths of people living with HIV is attributable to meningeal cryptococcosis, with nearly 75% occuring in sub-Saharan Africa. Although rare in children, it is a major cause of morbidity and mortality in people living with HIV. A strong association between cryptococcal antigenemia and the development of meningeal cryptococcosis has been shown in adults. Thus, in 2018, the World Health Organization published an updated version of its guidelines for the diagnosis, prevention and management of cryptococcal infection in adults, adolescents and the HIV-infected child., Goal: To determine the prevalence of cryptococcal antigenemia and to identify its determinants in children infected with HIV., Methods: An analytical cross-sectional study was carried out at the approved treatment center of Laquintinie hospital in Douala over a period of 4 months. Children were recruited consecutively after informed parental consent. Cryptococcal antigenemia and CD4 assay were performed using a Cryptops® immunochromatographic rapid diagnostic test and flow cytometry, respectively. The data collected included the socio-demographic, clinical and paraclinical variables of the children, as well as their antecedents. Data analysis was performed using Epiinfo software version 3.1 and SPSS 21.0. The significance threshold was set at 5%., Results: A total of 147 children were enrolled. The mean age was 9.8 ± 4.09 years. The majority were on antiretroviral therapy (142, 96.60%). Only 13 (8.80%) were in severe immunosuppression. No child showed signs of meningeal cryptococcosis. The prevalence of cryptococcal antigenemia was 6.12%. Severe immunosuppression [OR: 10.03 (1.52-65.91), p = 0.016] and contact with pigeons [OR: 9.76 (1.14-83.65), p = 0.037] were independent factors significantly associated with the carriage of the cryptococcal antigen., Conclusion: We recommend screening for cryptococcal antigenemia and routine treatment with fluconazole of all HIV positive children with cryptococcal antigen whether symptomatic or not., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Cryptococcus neoformans is an opportunistic pathogen that causes ∼15% mortality in AIDS patients. Rio Grande City, Rio Grande do Sul (RS), Brazil, has the highest national rate of HIV/AIDS, considering cities with population more than 100,000 habitants., Objective: We aimed to evaluate the clinical and epidemiological profile of cryptococcosis in a reference service for HIV-AIDS patients in the South region of Brazil, over seven years. Material and methods A retrospective study was performed including all cryptococcosis cases diagnosed at the University Hospital, Federal University of Rio Grande (UH-FURG) between January 2010 and December 2016., Results: Seventy cases of cryptococcosis were diagnosis from 2010 to 2016 in the UH-FURG in the seven years of the study. These numbers were responsible for 2.1% to 8.1% of the hospitalizations/year for HIV patients. All were caused by C. neoformans infection (95% C. neoformans var. grubii VNI and 5% C. neoformans var. grubii VNII). Neurocryptococcosis was the major clinical manifestation and cryptococcosis was the HIV- defining condition in 40% of patients. The period of hospitalization was an average of 39.3 days (SD=31.3), and more than half of patients (53%; 37/70) died after a mean of 82 days., Discussion: The present study showed the importance of cryptococcosis as an AIDS-defining disease in HIV-AIDS patients in a tertiary hospital from Southern Brazil. More investment is necessary to reduce the impact of this opportunistic mycosis in HIV-AIDS patients from southern Brazil., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

This review summarises both the recent and relevant studies about cryptococcal infections in haematologic malignancies and haematopoietic stem cell transplantation. Although uncommon in this patient population, this infection carries a high mortality, especially if left untreated. Given the limited data, we draw some conclusions with respect to management from the solid organ transplantation and HIV-infected literature. Herein, we discuss cryptococcosis with a particular attention to its background, epidemiology, risk factors, clinical presentation, diagnosis, treatment and prevention in this group., (© 2020 Wiley-VCH GmbH.)

Early diagnosis and targeted preemptive antifungal treatment are crucial in reducing cryptococcal meningitis (CM)-related mortality in individuals living with human immunodeficiency virus (HIV). The present study was performed to determine cryptococcal antigenemia and outcomes among HIV-infected patients in Iran. This multicenter prospective study was conducted between October 2016 and December 2018. For the purpose of the study, blood samples were randomly collected from 177 profoundly immunosuppressed (CD4+ counts < 200 cells/µL) HIV-positive individuals in six major cities of Iran. The patients were antiretroviral therapy-naive or had received inadequate medication. The stored sera were screened for cryptococcal antigen (CrAg), using point-of-care lateral flow assay (IMMY® diagnostics, Norman, OK, US). Overall, out of the 174 asymptomatic patients, 3 (1.72%) cases were CrAg-positive using the LFA in serum. Accordingly, the prevalence of cryptococcal antigenemia was 7.14%, 0%, and 1.2% in the patients with the CD4+ counts of < 50, 50-100, and 100-200 cells/μL, respectively. The median age of the patients with antigenemia was 36 years (age range 8-55 years). The median CD4+ count of the cohort was 98 cells/μL (range 14-200 cells/μL). Routine screening of Iranian HIV-infected patients with CD4+ count of < 50 cells/µL before initiating antiretroviral therapy is justified. It is suggested to conduct more inclusive research throughout the whole country on more patients to recommend screening cryptococcal antigen strongly.

Background: Cryptococcus neoformans is an opportunistic fungal pathogen that causes meningitis worldwide and may be fatal in immunocompromised subjects. In Nigeria, cases have been reported with prevalence between 4 and 13.1% in Human Immunodeficiency virus (HIV) patients depending on the study subjects. This study was designed to assess the prevalence of cryptococcosis, CD4+T cell counts and possible effect on haematological parameters in HIV seropositive subject in Nnewi, South-Eastern Nigeria., Method: A total of four hundred and twenty-nine (429) subjects were recruited for the study. Of these, two hundred and ninety (290) were HIV positive and one hundred and thirty-nine (139) were HIV seronegative subjects recruited from the voluntary counseling and testing (VCT) unit and HIV care clinic at Nnamdi Azikiwe University Teaching Hospital Nnewi, Anambra State, Nigeria. Their ages were between 18-80 years. One hundred and thirty nine (139) apparently healthy HIV seronegative subjects were recruited as controls. Blood samples were taken for C. neoformans by Antigen lateral flow assay (CrAgLFA), HIV testing, CD4+T cell, platelet and Full blood count (FBC)., Results: Our results show that of the two hundred and ninety (290) who were HIV positive subjects investigated for cryptococcosis, 4 (1.4%) tested positive for CrAg of whom 1(25%) were male and 3(75%) were female. All those with cryptococcosis had their CD4 count below 200 cells/μL, three of them were on ART and one was not. There were significant differences in the CD4 counts (P<0.05) between those infected and not infected with C. neoformans. None of the control group tested positive to cryptococcosis., Conclusion: Widespread use of anti-retroviral therapy may have reduced C. neoformans infection. However, the threat remains and there may be a possibility that women may be a more vulnerable population., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Cryptococcosis has become an important infection in both immunocompromised and immunocompetent hosts. Although Cryptococcus is mainly recognized by its ability to cause meningoencephalitis, it can infect almost any organ of the human body, with pulmonary infection being the second most common disease manifestation. In cases of meningitis, symptom onset may be insidious, but headaches, fevers, or mental status changes should warrant diagnostic testing. Symptoms of pulmonary disease are nonspecific and may include fever, chills, cough, malaise, night sweats, dyspnea, weight loss, and hemoptysis. Due to protean manifestations of infection, diagnosis may be delayed or misdiagnosis may occur. Diagnosis typically is made by antigen testing of serum or cerebrospinal fluid or by culture or histopathology of infected tissues. A lumbar puncture with the measurement of opening pressure is recommended for patients with suspected or proven cryptococcosis. Treatment of cryptococcosis is based on the anatomical site of disease, severity of disease, and underlying immune status of the patient. Amphotericin B preparations plus 5-flucytosine is used as initial treatment of meningitis, disseminated infection, or moderate-to-severe pulmonary infection followed by fluconazole as a consolidation therapy. Fluconazole is effective for mild-to-moderate pulmonary infection. Important complications include elevated intracranial pressure and immune reconstitution syndrome, which may resemble active disease., Competing Interests: None., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Cryptococcosis is a life-threatening fungal infection that affects immunocompromised patients, causing predominantly meningoencephalitis and pneumonia. Lymph node involvement is rare and its identification may not be obvious. We report the case of a patient recently diagnosed with AIDS and previously treated for cryptococcal meningitis who developed multifocal cryptococcal disease despite antifungal treatment, expressed as cervical and mediastinal lymphadenitis and constitutional symptoms. The difficulty of the diagnosis was based on the fact that cryptococcal meningitis was resolved after treatment, and the new manifestations were more typical of other conditions such as tuberculosis and malignancy. Final diagnosis was established after fine-needle aspiration cytology of a lymph node with Cryptococcus identification. Such cases may be difficult to manage, and the possibility of clinical relapse versus cryptococcal immune reconstitution inflammatory syndrome is discussed. Induction therapy was restarted and maintained for a longer period, and the total duration was based on clinical response., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Cryptococcal infection is a major cause of opportunistic infection in HIV/AID-infected peoples. We determined cryptococcal antigenemia and cryptococcal meningitis among antiretroviral therapy (ART) initiated and ART-naive HIV-infected peoples. A cross-sectional study was conducted at selected health facilities in Mekelle, Ethiopia. Blood was collected to determine CD4 and plasma cryptococcal antigen (CrAg). CSF CrAg and CSF culture and urease tests were also done. Socio-demographic and clinical data were collected using a structured questionnaire and clinical chart review. From the enrolled study participants, 267 study participants had complete data, of which, 137 (51%) were females. From the study participants, 140 (52%) and 127 (48%) were ART experienced and ART naïve, respectively. The prevalence of cryptococcal antigenemia was 9 (3.4%). All the study participants, except one (CD4 = 120 cells/mm 3 ), had CD4 count less than 100 cells/mm 3 . From CrAg-positive peoples, 6 (4.7%) were ART naïve. Five CrAg-positive peoples had cryptococcal meningitis. Being male, rural residence, and being hospitalized were associated with cryptococcal antigenemia. Cryptococcal infection poses a substantial risk of HIV-positive peoples. This study provides relevant data for CrAg screening interventions in patients with low CD4 cell counts., (© 2018 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.)

Cryptococcus neoformans (C. neoformans var. grubii) is an environmentally acquired pathogen causing 181,000 HIV-associated deaths each year. We sequenced 699 isolates, primarily C. neoformans from HIV-infected patients, from 5 countries in Asia and Africa. The phylogeny of C. neoformans reveals a recent exponential population expansion, consistent with the increase in the number of susceptible hosts. In our study population, this expansion has been driven by three sub-clades of the C. neoformans VNIa lineage; VNIa-4, VNIa-5 and VNIa-93. These three sub-clades account for 91% of clinical isolates sequenced in our study. Combining the genome data with clinical information, we find that the VNIa-93 sub-clade, the most common sub-clade in Uganda and Malawi, was associated with better outcomes than VNIa-4 and VNIa-5, which predominate in Southeast Asia. This study lays the foundation for further work investigating the dominance of VNIa-4, VNIa-5 and VNIa-93 and the association between lineage and clinical phenotype.

Background: Highly active antiretroviral therapy has significantly changed the natural history of HIV infection, leading to a dramatic reduction of HIV-related morbidity and mortality. Late Presenters, Very Late Presenters and AIDS presenters still represent, also in Europe, including Italy, a huge challenge in terms of diagnostic and therapeutic management., Case Presentation: A 35-year-old male with a history of fever and back pain. HIV test resulted positive with a high HIV Viral Load and a very low T-CD4 number of cells (5 cells/mm 3 ). Imaging investigations revealed multiple vertebral and pulmonary lesions together with abdominal and thoracic lymphadenopathy. Blood cultures were positive for Cryptococcus neoformans and for Staphylococcus haemolyticus. Lymphnode biopsy resulted positive in PCR for Non-Tuberculosis Mycobacteria (Mycobacterium chelonae). A gastric biopsy also revealed a GIST. The patient also had CMV DNA positive. Although we performed antiretroviral therapy and specific-therapies for each disease, he was transferred to intensive care unit where he died due to an Acute Respiratory Distress Syndrome., Conclusion: The reported case is unusual due to the relevant number of opportunistic diseases (both infectious and tumoral) emerging not long after the HIV infection had been diagnosed. Late presenters HIV patients and AIDS presenters still represent a challenge, which is often too complex for clinicians to deal with. In spite of proper management, the risk of suboptimal results cannot be excluded.

Osteomyelitis due to Cryptococcus neoformans are described in mostly 10% of patients with disseminated cryptococcosis, being direct inoculation even more uncommon. We report the case of an HIV-infected patient with history of recurring itching on his scalp and repetitive local trauma. For eighteen months, he noticed a painful and slow growing lump on his scalp. He was submitted to an excisional biopsy of the lesion but no etiological diagnosis was identified. After this procedure, the post-surgical wound never completely healed. At admission, the patient presented nausea and headache for three days and an open orifice into his skull. Investigations confirmed meningitis and skull osteomyelitis caused by Cryptococcus neoformans. He was treated with bone debridement and combined systemic antifungals, showing good clinical and laboratorial outcome. Cryptococcal disease should be included in the differential diagnoses of chronic osteomyelitis in HIV-infected patients and trauma is a possible source of infection., (Copyright © 2018 Sociedade Brasileira de Infectologia. Published by Elsevier España, S.L.U. All rights reserved.)

Fluconazole is the most commonly used antifungal agent for both the treatment of cryptococcal meningitis, and for prophylaxis against the disease. However, its prolonged use has the potential to exert selection pressure in favour of fluconazole-resistant strains. We evaluated the prevalence of fluconazole resistance in Cryptococcus spp. clinical isolates in 29 studies from 1988 to May 2017 included in EMBASE and MEDLINE databases. A total of 4995 Cryptococcus isolates from 3210 patients constituted this study; 248 (5.0%) of the isolates from relapsed episodes of cryptococcosis were included in this analysis. Eleven (38%) of the studies used minimum inhibitory concentrations (MICs) breakpoints of ≥64 μg/mL to define fluconazole resistance, 6 (21%) used ≥32 μg/mL, 11 (38%) used ≥16 μg/mL and 1 (3%) used ≤20 μg/mL. Overall, mean prevalence of fluconazole resistance was 12.1% (95% confidence interval [CI]: 6.7-17.6) for all isolates (n = 4995). Mean fluconazole resistance was 10.6% (95% CI: 5.5-15.6) for the incident isolates (n = 4747) and 24.1% (95% CI: -3.1-51.2) for the relapse isolates (n = 248). Of the 4995 isolates, 936 (18.7%) had MICs above the ecological cut-off value. Fluconazole resistance appears to be an issue in Cryptococcus isolates from patients with relapses. It remains unclear whether relapses occur due to resistance or other factors. There is an urgent need to establish antifungal breakpoints for Cryptococcus spp., (© 2018 Blackwell Verlag GmbH.)

Cryptococcal disease, caused by Cryptococcus neoformans and Cryptococcus gattii, is associated with significant morbidity and mortality but limited data exist on its incidence and impact. A study utilizing the Nationwide Inpatient Sample from 2000 to 2007 to examine the epidemiology and impact of cryptococcal disease in the United States was undertaken. The International Classification of Diseases 9th Version code was used to identify hospital discharges with diagnosis of Cryptococcus (117.5). Our primary outcome was the incidence rate of cryptococcal admissions. The impact of AIDS, age, and sex on hospitalization rates, mortality, and costs was assessed. The results showed that a total of 10,077 hospitalizations for cryptococcosis occurred corresponding to a weighted estimate of 49,010 cases. The median age was 43 years (interquartile range 34-54), and 26% were female. Approximately 64% of cases occurred in persons with AIDS. Although rates declined overall, age-adjusted rates were significantly higher in males with AIDS than in uninfected persons (p < 0.001). The mortality rate decreased but was greater in HIV-uninfected versus infected cohorts (12% versus 10%, p < 0.001). Conversely, hospital costs were greater in persons with AIDS ($40,671 versus $40,096, p=0.02). Although cryptococcal disease rates are decreasing over time, the associated mortality and costs remain concerning.

Cryptococcosis is an invasive fungal disease caused by Cryptococcus neoformans and the closely related species C. gattii. The severe form of the disease, cryptococcal meningitis (CM), is rapidly fatal without treatment. Although typically a disease of immunocompromised (especially HIV-positive) individuals, there is growing awareness of cryptococcal disease amongst non-immunocompromised patients. Whilst substantial progress has been made in understanding the pathogenicity of C. neoformans in HIV patients, prospective data on cryptococcosis outside the context of HIV remains lacking. Below we review how innate immune responses vary between hosts depending on immunological status, and discuss risk factors and predictors of disease outcome in different groups.

BACKGROUND Cryptococcus neoformans (C. neoformans) infection is one of the most common opportunistic infections in AIDS patients. C. neoformans usually infects the central nervous system (CNS) and/or lungs with typical clinical manifestation. CASE REPORT Here, we report the case of a 52-year-old HIV-1-infected man with disseminated cryptococcosis, including subacute meningitis, pulmonary, and cutaneous cryptococcosis, but only skin lesion served as the chief complaint. Moreover, the results of cerebrospinal fluid (CSF) tests and lung computed tomography (CT) scan were atypical. CONCLUSIONS We present the clinical characteristics of this case and discuss the diagnostic procedure, which will likely help clinicians in making a timely definitive diagnosis of this disease.

Cryptococcosis is a potentially fatal fungal disease caused by the basidiomycetes yeasts Cryptococcus neoformans and C. gattii with high predilection to invade the central nervous system mainly in immunocompromised hosts. Skin can be secondarily involved in disseminated infection or be exceptionally involved as primary cutaneous infection by inoculation with contaminated materials. We report the first two Libyan cases of cryptococcal meningitis in HIV patients, in which one of them presented a secondary cutaneous involvement due to systemic dissemination. The first patient was a 17-year-old female, had fever, cough, headache and intractable vomiting as well as itchy water bumps on her skin and upper limbs. The cutaneous eruption prompted the accurate diagnosis. Cultures were positive for C. neoformans in both cerebrospinal fluid and skin specimens, as well as cryptococcal antigen was detected in serum. The isolate was identified, by molecular analysis, as C. neoformans AD-hybrid belonging to molecular type VNIII and mating type αAAα, the same genotype found for some environmental isolates recovered from olive trees in Tripoli. The second patient was a 36-years-old male with a long history of HIV on irregular treatment. Cryptococcal antigen in serum was positive and cultures yielded the growth of C. neoformans var. grubii, molecular type VNI and mating type αA. Both patients did not respond adequately to treatment and died of impaired central nervous system function and respiratory failure, respectively., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Cryptococcosis, a systemic disease caused by the fungus Cryptococcus neoformans/ Cryptococcus gattii is more severe in immunocompromised individuals. This study aimed to analyze the epidemiology of the disease, the molecular characteristics and the antifungal susceptibility of C. neoformans isolated from patients treated in a Brazilian university hospital. This retrospective study was conducted in the Clinical Hospital, Federal University of Uberlândia, and evaluated cases of cryptococcosis and strains of C. neoformans isolated from 2004 to 2013. We evaluated 41 patients, 85% of whom were diagnosed with AIDS. The fungus was isolated from the cerebrospinal fluid (CSF) of 21 patients (51%); 19.5% had fungemia and in 24% the agent was isolated from the CSF and blood, concurrently. Meningoencephalitis was the most frequent (75%) manifestation of infection. Despite adequate treatment, the mortality of the disease was 58.5%. Most isolates (97.5%) presented the VNI genotype (serotype A, var. grubii) and one isolate was genotyped as C. gattii (VGI); all the isolates were determined as mating type MATa and showed susceptibility to the tested antifungals (fluconazole, voriconazole, amphotericin B and 5-flucytosine). Although AIDS detection rates remain stable, opportunistic infections such as cryptococcosis remain as major causes of morbidity and mortality in these patients.

Cryptococcosis is an important fungal infection in immunocompromised individuals, especially those infected with HIV. In Brazil, despite the free availability of antiretroviral therapy (ART) in the public health system, the mortality rate due to Cryptococcus neoformans meningitis is still high. To obtain a more detailed picture of the population genetic structure of this species in southeast Brazil, we studied 108 clinical isolates from 101 patients and 35 environmental isolates. Among the patients, 59% had a fatal outcome mainly in HIV-positive male patients. All the isolates were found to be C. neoformans var. grubii major molecular type VNI and mating type locus alpha. Twelve were identified as diploid by flow cytometry, being homozygous (AαAα) for the mating type and by PCR screening of the STE20, GPA1, and PAK1 genes. Using the ISHAM consensus multilocus sequence typing (MLST) scheme, 13 sequence types (ST) were identified, with one being newly described. ST93 was identified from 81 (75%) of the clinical isolates, while ST77 and ST93 were identified from 19 (54%) and 10 (29%) environmental isolates, respectively. The southeastern Brazilian isolates had an overwhelming clonal population structure. When compared with populations from different continents based on data extracted from the ISHAM-MLST database (mlst.mycologylab.org) they showed less genetic variability. Two main clusters within C. neoformans var. grubii VNI were identified that diverged from VNB around 0.58 to 4.8 million years ago., Competing Interests: The authors have declared that no competing interests exist.

Cryptococcal meningitis is a severe opportunistic infection in HIV-infected patients. In Ivory Coast, despite the availability of antiretroviral treatment (ART), this infection is still prevalent. The study investigates the genetic diversity of 363 clinical isolates of Cryptococcus from 61 Ivorian HIV-positive patients, the occurrence of mixed infections and the in vitro antifungal susceptibility of the isolates. Serotyping was performed via LAC1 and CAP64 gene amplification. Genotyping was performed using the phage M13 core (GACA) 4 and (GTG) 5 primers and restriction fragment length polymorphism analysis of the URA5 gene. By PCR fingerprinting, the presence of the three serotypes were demonstrated among the 363 isolates in the population studied: A (n=318; 87.6%), AD (n=40; 11%) and B (n=4; 1.1%). Using PCR fingerprinting with primers M13 (GACA) 4 and (GTG) 5 , we grouped the isolates into 56 molecular subtypes. We observed a high frequency (39.3%) of mixed infections, with up to two different genotypes per sample. None of the isolates were resistant to amphotericin B. Only 0.3% and 1.1% of the isolates were resistant to fluconazole and flucytosine respectively. This study revealed the high genetic diversity among Cryptococcus isolates, the occurrence of mixed infections and a high antifungal susceptibility for the majority of Ivorian cryptococcal isolates., (© 2016 Blackwell Verlag GmbH.)

Cryptococcosis has been one of the most common opportunistic infections and causes of mortality among HIV-infected patients, especially in resource-limited countries. Cryptococcal meningitis is the most common form of cryptococcosis. Laboratory diagnosis of cryptococcosis includes direct microscopic examination, isolation of Cryptococcus from a clinical specimen, and detection of cryptococcal antigen. Without appropriate treatment, cryptococcosis is fatal. Early diagnosis and treatment is the key to treatment success. Treatment of cryptococcosis consists of three main aspects: antifungal therapy, intracranial pressure management for cryptococcal meningitis, and restoration of immune function with antiretroviral therapy (ART). Optimal integration of these three aspects is crucial to achieving successful treatment and reducing the mortality. Antifungal therapy consists of three phases: induction, consolidation, and maintenance. A combination of two drugs, i.e. amphotericin B plus flucytosine or fluconazole, is preferred in the induction phase. Fluconazole monotherapy is recommended during consolidation and maintenance phases. In cryptococcal meningitis, intracranial pressure rises along with CSF fungal burden and is associated with morbidity and mortality. Aggressive control of intracranial pressure should be done. Management options include therapeutic lumbar puncture, lumbar drain insertion, ventriculostomy, or ventriculoperitoneal shunt. Medical treatment such as corticosteroids, mannitol, and acetazolamide are ineffective and should not be used. ART has proven to have a great impact on survival rates among HIV-infected patients with cryptococcosis. The time to start ART in HIV-infected patients with cryptococcosis has to be deferred until 5 weeks after the start of antifungal therapy. In general, any effective ART regimen is acceptable. Potential drug interactions between antiretroviral agents and amphotericin B, flucytosine, and fluconazole are minimal. Of most potential clinical relevance is the concomitant use of fluconazole and nevirapine. Concomitant use of these two drugs should be cautious, and patients should be monitored closely for nevirapine-associated adverse events, including hepatotoxicity. Overlapping toxicities of antifungal and antiretroviral drugs and immune reconstitution inflammatory syndrome are not uncommon. Early recognition and appropriate management of these consequences can reinforce the successful integrated therapy in HIV-infected patients with cryptococcosis.

Cryptococcosis is an opportunistic invasive fungal infection that is well described and easily recognised when it occurs as meningitis in HIV-infected persons. Malignancy and its treatment may also confer a higher risk of infection with Cryptococcus neoformans, but this association has not been as well described. A case of cryptococcosis in a cancer patient is presented, and all cases of coincident C. neoformans infection and malignancy in adults published in the literature in English between 1970 and 2014 are reviewed. Data from these cases were aggregated in order to describe the demographics, type of malignancy, site of infection, clinical manifestations, treatment and outcomes of cryptococcosis in patients with cancer. Haematologic malignancies accounted for 82% of cases, with lymphomas over-represented compared to US population data (66% vs. 53% respectively). Cryptococcosis was reported rarely in patients with solid tumours. Haematologic malignancy patients were more likely to have central nervous system (P < 0.001) or disseminated disease (P < 0.001), receive Amphotericin B as part of initial therapy (P = 0.023), and had higher reported mortality rates than those with solid tumours (P = 0.222). Providers should have heightened awareness of the possibility of cryptococcosis in patients with haematologic malignancy presenting with infection., (© 2016 Blackwell Verlag GmbH.)

Cryptococcus neoformans is an important opportunistic pathogen that causes serious mortality and morbidity in AIDS patients. Although its incidence has decreased with proper antiretroviral treatment (ART), it is still a major concern in areas with low socioeconomic HIV endemic countries with poor sources of therapy. In our country, pediatric HIV infection and so, HIV-related opportunistic infections are very rare. In order to pay attention to this unusual collaboration; herein, we presented a pediatric case who was diagnosed with HIV and disseminated cryptococcus infection concomitantly. A 6.5-year-old previously healthy girl has admitted to our hospital with the complaints of prolonged fever, cough and hemoptysis. On her physical examination she had oral candidiasis, generalized lymphadenopathy and hepatosplenomegaly. Laboratory findings were as follows; white blood cell count: 3170 µL (neutrophil: 2720 µL, lymphocyte: 366 µL), hemoglobin level: 7.8 gr/dl, hematocrit: 25.5% platelets: 170.000 µL, CRP: 15.2 mg/L and serum IgG level: 1865 mg/dl. Her anti-HIV test yielde,d positive result and confirmed by Western blot assay, together with a high viral load (HIV-RNA: 3.442.000 copies/ml). She was started ART (lamivudine, zidovudine and lopinavir/ritonavir combination) with the diagnosis of stage 3 HIV infection (AIDS). Posteroanterior chest radiograph showed mediastinal extension and nodular parenchyma. Since the patient was suspected to have pulmonary tuberculosis based on the clinical and radiological findings, empirical antituberculosis therapy was started. Because of the insistance of fever, three different blood specimens, bone marrow and gastric aspirates were collected for culture, in which all of them yielded C.neoformans growth. She was then diagnosed as disseminated cryptococcosis and treated with liposomal amphotericin B and fluconazole successfully. Although pediatric HIV infection is usually diagnosed secondary to maternal disease, it can rarely be presented later in life with opportunistic infections. In the case of unusual infectious diseases, in addition to primary immune deficiency syndromes, HIV infection should also be kept in mind. Herein, we discussed a pediatric case with two rare infectious agents reported in our country and wanted to focus on secondary immune deficiency related with pediatric HIV infection.

Epidemiological cut-off values (ECVs) based on minimal inhibitory concentration (MIC) distribution have been recently proposed for some antifungal drug/Cryptococcus neoformans combinations. However, these ECVs vary according to the species studied, being serotypes and the geographical origin of strains, variables to be considered. The aims were to define the wild-type (WT) population of the C. neoformans species complex (C. neoformans) isolated from patients living in Argentina, and to propose ECVs for six antifungal drugs. A total of 707 unique C. neoformans isolates obtained from HIV patients suffering cryptococcal meningitis were studied. The MIC of amphotericin B, flucytosine, fluconazole, itraconazole, voriconazole and posaconazole was determined according to the EDef 7.2 (EUCAST) reference document. The MIC distribution, MIC50 , MIC90 and ECV for each of these drugs were calculated. The highest ECV, which included ≥95% of the WT population modelled, was observed for flucytosine and fluconazole (32 μg ml(-1) each). For amphotericin B, itraconazole, voriconazole and posaconazole, the ECVs were: 0.5, 0.5, 0.5 and 0.06 μg ml(-1) respectively. The ECVs determined in this study may aid in identifying the C. neoformans strains circulating in Argentina with decreased susceptibility to the antifungal drugs tested., (© 2016 Blackwell Verlag GmbH.)

Refractory and relapsing crytocococcosis in acquired immune deficiency syndrome (AIDS) patients have a poor prognosis. The risk factors for this complicated infection course were evaluated by comparing refractory and/or relapsing cryptococcosis in human immunodeficiency virus-coinfected patients (cohort 1) with another group of AIDS patients who adequately responded to antifungals (cohort 2). Except for one isolate of Cryptococcus gattii from a cohort 2 case, all other isolates were identified as Cryptococcus neoformans var. grubii, sex type α, genotype VNI, including Cryptococcus reisolated from the relapse or in the refractory state. No differences were observed with respect to Cryptococcus capsule size and in the melanin and phospholipase production. The cohort 1 patients presented higher prevalence of cryptococcemia, cerebral dissemination, chronic liver disease, and leucopenia, and have increased death rate. Apparently, the refractory and/or relapsing cryptococcosis in the AIDS patients were more related to the host and the extent of the infection than to the fungal characteristics., (© The American Society of Tropical Medicine and Hygiene.)

Cryptococcosis is a cosmopolitan but rare opportunistic mycosis which is usually caused by Cryptococcus neoformans. Although the most common and worrisome disease manifestation is meningoencephalitis, pulmonary cryptococcosis has the potential to be lethal. The diagnosis of cryptococcal pneumonia is challenging, given its non-specific clinical and radiographic features. Respiratory failure leading to acute respiratory distress syndrome as a consequence of cryptococcal disease has been infrequently addressed in the literature. We herein present a case of disseminated cryptococcal infection leading to acute respiratory distress syndrome, refractory shock, and multiorgan dysfunction as the initial clinical manifestation in a patient who was newly diagnosed with acquired immunodeficiency syndrome.

Cryptococcosis is a serious infection, possibly lethal, of worldwide distribution. It mainly affects immunosuppressed patients resulting with pulmonary and/or meningeal involvements or disseminated infections. Due to the rarity of visceral and osseous infections, and to the absence of specific clinical symptoms, this diagnosis is often deferred. Resulting of diagnostic errors, samples are often directed to the department of pathology and more rarely to the department of mycology. Histopathological examination appears crucial, highlighting encapsulated yeasts with alcian blue staining. Once the diagnosis is performed, an appropriate antifungal therapy must be quickly introduced because these infections are associated with a high mortality rate. The aim of our work was to report five extra-cerebral and extra-pulmonary cryptococcosis cases, to describe their histopathological features, to evoke diagnostic techniques and to discuss the differential diagnoses., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Cryptococcosis caused by the fungus Cryptococcus neoformans is an opportunistic mycosis, infecting mainly immunodepressed individuals. Molecular epidemiology studies of cryptococcosis in Europe are limited. This paper presents a retrospective study of cryptococcosis in 105 cryptococcal isolates from two hospitals in Lisbon, Portugal, among HIV/AIDS patients, from 1991 to 2007. Among these patients, the number of cases of cryptococcosis increased from 5.1 to 6.9 cases per year from the pre- to post-highly active antiretroviral therapy (HAART) era. As expected, the median age of the patients increased, from 32 (mean: 33 ± 8) to 39 (mean: 41 ± 10) years, and the ratio of male to female patients remained high (7.7 and 7.6, respectively). Strain genotyping based on restriction fragment length polymorphism of the orotidine monophosphate pyrophosphorylase (URA5-RFLP) gene showed that, in general, the relative frequencies of the genotypes VNI-IV are similar to those from other European countries. These frequencies were, respectively, for the pre- and post-HAART periods: 41.7 and 43.5 % for VNI; 2.8 and 17.4 % for VNII; 38.9 and 30.4 % for VNIII; 16.7 and 7.2 % for VNIV and 0 and 1.4 % for VGII. Some apparent although statistically insignificant differences among these values were observed between both periods. The genotypic frequencies were not also statistically different according to the patients' gender or age range. Of note are the high proportion of VNIII isolates (common in Europe) and the high increase in the frequency of the VNII genotype in the post-HAART. Ultimately, these results may have implications in disease therapy, management and control.

The HIV epidemic in Uganda has highlighted Cryptococcus and Candida infections as important opportunistic fungal infections. However, the burden of other fungal diseases is not well described. We aimed to estimate the burden of fungal infections in Uganda. All epidemiological papers of fungal diseases in Uganda were reviewed. Where there is no Ugandan data, global or East African data were used. Recurrent vaginal candidiasis is estimated to occur in 375 540 Uganda women per year; Candida in pregnant women affects up to 651,600 women per year. There are around 45,000 HIV-related oral and oesophageal candidosis cases per year. There are up to 3000 cases per year of post-TB chronic pulmonary aspergillosis. There are an estimated 40,392 people with asthma-related fungal conditions. An estimated 1,300,000 cases of tinea capitis occur in school children yearly in Uganda. There are approximately 800 HIV-positive adults with Pneumocystis jirovecii pneumonia (PJP) annually and up to 42 000 children with PJP per year. There are an estimated 4000 cryptococcal cases annually. There are an estimated 2.5 million fungal infections per year in Uganda. Cryptococcus and PJP cause around 28,000 deaths in adults and children per year. We propose replicating the model of research around cryptococcal disease to investigate and development management strategies for other fungal diseases in Uganda., (© 2015 Blackwell Verlag GmbH.)

Background: The World Health Organization (WHO) recommends screening patients living with AIDS to detect and treat early cryptococcal infection., Methods: The authors evaluated a cryptococcal antigen (CrAg) screening and treatment program at an HIV/AIDS clinic in Malawi. Eligible patients were of age >18 years, had a CD4 count <100 cells/µL or WHO clinical HIV/AIDS stage III or IV., Results: Of 552 patients who presented for care, 113 were eligible, and all (100%) agreed to CrAg screening. Of them, 2 (1.8%; 95% confidence interval [CI]: 0-4.2%) patients were CrAg positive. Among those with CD4 count <100 cells/µL or WHO stage IV, the CrAg prevalence was 3.5% (95% CI: 0-8.4%) and 5.0% (95% CI: 0-15%), respectively., Conclusion: A CrAg screening program was acceptable to new patients in a Malawian HIV/AIDS clinic. The CrAg prevalence for patients with CD4 count < 100 cells/µL and WHO stage IV was consistent with cost-effectiveness estimates. CrAg screening and treatment programs for patients living with AIDS should be expanded., (© The Author(s) 2015.)

Background: Cryptococcosis is a rare and a serious opportunistic infection that occurs primarily on the field of immunodeficiency. We report a case of disseminated cryptococcosis in acquired immunodeficiency syndrome revealed by unusual skin lesions., Observation: A 52-year-old patient consulted for two crusty ulcerative lesions situated on the left supraorbital and on the nasal tip that appeared 6 months ago. He also reported respiratory symptoms present since one year, with dry cough and dyspnea, chronic headache and vomiting with no alteration in visual acuity. The mycological study of the skin biopsy on both lesions isolated Cryptococcus neoformans as well as in the sputum and cerebrospinal fluid. Serology of human immunodeficiency virus infection was positive. Treatment with fluconazole, local care and antiretroviral triple therapy was implemented., Discussion: Skin lesions during cryptococcosis are rare and observed in 2-10% of cases. Cutaneous symptoms were the reason for consultation in our patient. This is a rare form of cutaneous cryptococcosis leading to the discovery of both pulmonary and central nervous system locations, and to diagnosis of HIV infection., (Copyright © 2015. Published by Elsevier Masson SAS.)

Aims: The utility of bone marrow aspiration and biopsy (BMAB) as a diagnostic tool in patients with HIV/AIDS and fever of unknown origin (FUO) is a subject of debate. Because highly active antiretroviral therapy has reduced incidence of opportunistic infections, it is important to reassess the efficacy of BMAB for this diagnostic purpose. To our knowledge, no such studies have been performed in Harris County which has the highest incidence of HIV in the state of Texas., Methods: We reviewed all BMABs from patients with HIV/AIDS and FUO or persistent cytopenia(s) from 2007 to 2011., Results: Of 57 evaluable patients, BMAB was positive in 24 samples by acid fast bacilli (AFB) or Gomori methenamine silver (GMS) stains (17.5%), presence of granuloma and/or lymphohistiocytic aggregates (31.6%), culture (21.0%) or a combination. Cultures demonstrated Mycobacterium avium/intracellulare (4), M tuberculosis (2), M gordonae (1), Histoplasma capsulatum (3) and Cryptococcus neoformans (2). There were three cases in which a pathogen was grown in culture but that had a negative of 'direct examination' on tissue sections (negative AFB and GMS special stains, no morphological evidence of granuloma/lymphohistiocytic infiltrates)., Conclusions: This study supports the use of diagnostic BMAB as a rapid decision-making tool in patients with HIV and FUO in the proper clinical setting. BMAB demonstrated infection-related evidence prior to positive bone marrow culture in 75% of cases. Special stains and blood cultures had similar diagnostic yield, but BMAB offers faster results. Thus, this procedure assists in clinical decision making and the refinement of treatment in a more timely manner., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

We determined the susceptibility of 102 clinical isolates Cryptococcus neoformans from Durban, South Africa, to amphotericin B, fluconazole, flucytosine, and voriconazole using broth microdilution (BMD) according to the Clinical and Laboratory Standards Institute M27-A3 document and compared these results with Etest and Vitek 2(®). Essential agreement (EA) of Etest and Vitek 2(®) compared to BMD was determined. Low MICs that were below the epidemiological cutoff values of the 4 antifungal agents tested were demonstrated by all isolates. The EA of Etests for fluconazole, amphotericin, and voriconazole was 95.1%, 83.3%, and 91.2%, respectively, and for Vitek 2(®) EA for fluconazole, amphotericin, and flucytosine was 97.1%, 95.1%, and 97.1%, respectively. The Vitek 2(®) showed good agreement with BMD and is a suitable alternative. Etests demonstrated good EA for azoles only. Clinical cryptococcal isolates from Durban remain susceptible to current recommended antifungal therapy., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Unlabelled: Cutaneous cryptococcosis is an uncommon aetiology of chronic facial ulceration but which may be associated to a potentially lethal focus of cryptococcosis., Observation: A 35-year-old AIDS patient under antiretroviral therapy, presented with a chronic facial ulceration. Histopathological examination of a biopsy of the facial ulceration showed an inflammatory granuloma and masses of yeasts. Mycological culture of the cerebrospinal fluid revealed Cryptococcus neoformans. The diagnosis of AIDS-related cutaneous cryptococcosis of the face and cryptococcal meningitis was concluded., Discussion: Cryptococcosis should be thought as a potential aetiology of a chronic facial ulceration in an AIDS patient. Screening of other foci of the cryptococcosis such as that of the central nervous system is mandatory. Mycological examinations are of great interest for the diagnosis in rare resources setting., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Cryptococcosis is a serious infection caused by an encapsulated yeast-like fungus, Cryptococcus neoformans. It is pathogenic most often in the lungs and central nervous system of immunocompromised patients. In this work we report an unusual localization of cryptococcosis in an HIV-infected patient. This rare localization was diagnosed from a stool sample sent to our laboratory for parasitological study. Direct examination of fresh stool showed the presence of many large, rounded thick-walled fungi. India ink staining of the stool showed encapsulated cryptococci, and C. neoformans was isolated by culture. Despite flucanazole treatment, the patient died.

Background: Cryptococcosis is a potentially lethal opportunistic infection among human immunodeficiency virus (HIV)-infected individuals. The mortality rate of patient with cryptococcal meningoencephalitis (CM) in Thailand is high. Studying the factors associated with treatment failure is important to improve outcome., Material and Method: A retrospective study of patients with cryptococcosis in Siriraj Hospital, Thailand, during 2005-2008 was conducted. Treatment options, outcomes, survival and factors associated with outcomes and mortality were analyzed., Results: A total of 143 patients with cryptococcosis were enrolled. Mean age was 39 years old and 58.7% were male. There were 124 HIV-infected patients (86.7%) and 116 of those had CM. Favorable clinical response in HIV-associated CM was 55.2% and 6-month survival was 67.2%. Relapse was found in 21 patients (18.1%). Factors associated with favorable clinical response included lower opening and closing pressures and a higher white blood cell in cerebrospinal fluid (CSF). Favorable mycological response was 56.8% and factors associated with favorable mycological response were a lower CD4+ T-lymphocyte count and a longer amphotericin B treatment. The median time to achieve CSF sterilization was 30 days. Factors associated with survival were a longer course of amphotericin B, a lower CSF opening pressure and a higher white blood cell in CSF., Conclusion: High mortality rate of HIV-associated CM was demonstrated and most likely linked to inadequate induction antifungal therapy resulting in inability to sterilize CSF. New strategies and/or guidelines are suggested to improve survival.

This study provides a comprehensive picture of the C. neoformans/C. gattii molecular types most often associated with human cryptococcosis in Portugal and assesses the impact of C. gattii in these infections. One hundred and twenty-two clinical isolates, from distinct patients, were identified as C. neoformans and genotyped by URA5-RFLP, with the molecular types VNI (45.5 %) and VNIII (30.9 %) being the most commonly found ones. The molecular types VNII (11.4 %) and VNIV (11.4 %) were less abundant. One patient was found to be infected with a VGII isolate. This patient exhibited unusual clinical symptoms of cryptococcosis, reinforcing the suspicion for the presence of a different genotypic pattern, as determined afterwards. This case was detected in 2007 and is the first report of a potential autochthonous C. gattii infection case in Portugal, as the patient revealed no historical record of travelling outside the country.

Cryptococcus neoformans is an important cause of morbidity in HIV-infected patients worldwide. In the northern region of Brazil, the prevalence of this infection is poorly known due to a lack of systematic investigations. This study aimed to determine the occurrence of cryptococcosis by detecting antigenaemia in HIV-infected patients in the State of Para, Brazil. A latex Cryptococcus antigen detection kit was used to test 418 serum samples from HIV-infected patients seen at two Infectious Disease Specialized Units in the State of Para. The C. neoformans antigenaemia prevalence was 2.6%, and titres reached 1:8. The cases occurred mainly in asymptomatic females, and 45% presented CD4(+) T lymphocyte counts of fewer than 200 cells/mm(3). These results show the importance of early C. neoformans antigenaemia detection to prevent fungal disease.

Unlabelled: Cryptococcus neoformans is one of the most common causes of fungal disease in HIV-infected persons, but not all of those who are infected develop cryptococcal disease (CD). Although CD4(+) T cell deficiency is a risk factor for HIV-associated CD, polymorphisms of phagocytic Fc gamma receptors (FCGRs) have been linked to CD risk in HIV-uninfected persons. To investigate associations between FCGR2A 131 H/R and FCGR3A 158 F/V polymorphisms and CD risk in HIV-infected persons, we performed PCR-based genotyping on banked samples from 164 men enrolled in the Multicenter AIDS Cohort Study (MACS): 55 who were HIV infected and developed CD and a matched control group of 54 who were HIV infected and 55 who were HIV uninfected. Using additive and allelic statistical models for analysis, the high-affinity FCGR3A 158V allele was significantly associated with CD status after adjusting for race/ethnicity (odds ratio [OR], 2.1; P = 0.005), as was the FCGR3A 158 VV homozygous genotype after adjusting for race/ethnicity, rate of CD4(+) T cell decline, and nadir CD4(+) T cell count (OR, 21; P = 0.005). No associations between CD and FCGR2A 131 H/R polymorphism were identified. In binding studies, human IgG (hIgG)-C. neoformans complexes exhibited more binding to CHO-K1 cells expressing FCGR3A 158V than to those expressing FCGR3A 158F, and in cytotoxicity assays, natural killer (NK) cells expressing FCGR3A 158V induced more C. neoformans-infected monocyte cytotoxicity than those expressing FCGR3A 158F. Together, these results show an association between the FCGR3A 158V allele and risk for HIV-associated CD and suggest that this polymorphism could promote C. neoformans pathogenesis via increased binding of C. neoformans immune complexes, resulting in increased phagocyte cargo and/or immune activation., Importance: HIV-associated CD4(+) T cell deficiency is a sine qua non for HIV-associated cryptococcal disease (CD), but not all patients with CD4(+) T cell deficiency develop CD despite serological evidence of previous infection. At present, there are no biomarkers that predict HIV-associated CD risk. The goal of our study was to understand whether Fc gamma receptor (FCGR) polymorphisms that have been shown to portend CD risk in HIV-uninfected people are associated with CD risk in HIV-infected people. Such biomarkers could identify those who would benefit most from targeted prophylaxis and/or earlier treatment, particularly in sub-Saharan Africa, where there are nearly a million cases of HIV-associated CD annually. A biomarker of risk could also identify potential candidates for immunization, should there be a vaccine for Cryptococcus neoformans.