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Li Xu, Jia Liu, Qilong Zhang, Min Li, Jingchi Liao, Weifeng Kuang, Cansheng Zhu, Huan Yi, Fuhua Peng
Objectives Amphotericin B plus flucytosine is the most widely used induction therapy regimen for non-HIV-infected and non-transplant patients; however, the therapeutic outcomes are unsatisfactory, especially when two antifungal drugs are at sub-therapeutic doses. Methods In this study of induction therapy, all non-HIV-infected, non-transplant patients with a first episode of cryptococcal meningitis were divided into two groups. In group I, the patients received amphotericin B plus 5-flucytosine. In group II, in addition to amphotericin B and 5-flucytosine, the patients also received fluconazole...
March 21, 2018: Neurological Research
Stephen Arndt, Daryl Goldman, Nicholas Kolodychuk, James Milburn
No abstract text is available yet for this article.
2018: Ochsner Journal
Síle F Molloy, Cecilia Kanyama, Robert S Heyderman, Angela Loyse, Charles Kouanfack, Duncan Chanda, Sayoki Mfinanga, Elvis Temfack, Shabir Lakhi, Sokoine Lesikari, Adrienne K Chan, Neil Stone, Newton Kalata, Natasha Karunaharan, Kate Gaskell, Mary Peirse, Jayne Ellis, Chimwemwe Chawinga, Sandrine Lontsi, Jean-Gilbert Ndong, Philip Bright, Duncan Lupiya, Tao Chen, John Bradley, Jack Adams, Charles van der Horst, Joep J van Oosterhout, Victor Sini, Yacouba N Mapoure, Peter Mwaba, Tihana Bicanic, David G Lalloo, Duolao Wang, Mina C Hosseinipour, Olivier Lortholary, Shabbar Jaffar, Thomas S Harrison
BACKGROUND: Cryptococcal meningitis accounts for more than 100,000 human immunodeficiency virus (HIV)-related deaths per year. We tested two treatment strategies that could be more sustainable in Africa than the standard of 2 weeks of amphotericin B plus flucytosine and more effective than the widely used fluconazole monotherapy. METHODS: We randomly assigned HIV-infected adults with cryptococcal meningitis to receive an oral regimen (fluconazole [1200 mg per day] plus flucytosine [100 mg per kilogram of body weight per day] for 2 weeks), 1 week of amphotericin B (1 mg per kilogram per day), or 2 weeks of amphotericin B (1 mg per kilogram per day)...
March 15, 2018: New England Journal of Medicine
Laura J Schmertmann, Kathryn Stalder, Donald Hudson, Patricia Martin, Mariano Makara, Wieland Meyer, Richard Malik, Mark B Krockenberger
Disseminated cryptococcosis caused by Cryptococcus gattii (molecular type VGI) was diagnosed in an adult free-ranging female koala (Phascolarctos cinereus). Subclinical cryptococcosis was later diagnosed in this koala's joey. In the adult koala, a pathological fracture of the tibia was associated with the bone lysis of marked focal cryptococcal osteomyelitis. Limb-sparing orthopedic intervention, in the setting of disseminated cryptococcosis, was judged to have a poor prognosis, and the adult koala was euthanized...
February 24, 2018: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
Althea Campuzano, Floyd L Wormley
Cryptococcus species, the etiological agents of cryptococcosis, are encapsulated fungal yeasts that predominantly cause disease in immunocompromised individuals, and are responsible for 15% of AIDS-related deaths worldwide. Exposure follows the inhalation of the yeast into the lung alveoli, making it incumbent upon the pattern recognition receptors (PRRs) of pulmonary phagocytes to recognize highly conserved pathogen-associated molecular patterns (PAMPS) of fungi. The main challenges impeding the ability of pulmonary phagocytes to effectively recognize Cryptococcus include the presence of the yeast's large polysaccharide capsule, as well as other cryptococcal virulence factors that mask fungal PAMPs and help Cryptococcus evade detection and subsequent activation of the immune system...
March 7, 2018: Journal of Fungi (Basel, Switzerland)
Muhammad Talha Ayub, Munnam S Jafar, Muhammad Khalid, Muhammad A Baig, Benjamin Mba
We report a case of a 45-year-old male who presented with a headache, fever, vomiting, somnolence, and difficulty walking for 10 days. His cerebrospinal fluid studies revealed cryptococcal meningitis. Chest and abdominal computed tomography (CT) scans showed splenomegaly along with mediastinal, retroperitoneal and inguinal lymphadenopathy. CD4 count turned out to be 208 μL-1 . Human immunodeficiency virus (HIV) testing, serum protein electrophoresis, serum light chains and quantitative immunoglobulins were non-diagnostic and CD4 lymphopenia was attributed to acute infection...
January 1, 2018: Curēus
Lisa Frigati, Moherdran Archary, Helena Rabie, Martina Penazzato, Nathan Ford
Early mortality and morbidity remain high in children initiating antiretroviral therapy (ART), especially in sub-Saharan Africa. Many children still present with advanced human immunodeficiency virus (HIV) disease. Tuberculosis, pneumonia, and severe bacterial infections are the main causes of hospital admission in HIV-infected children. In contrast to adults with advanced HIV disease, cryptococcal disease is not common in childhood, although there is a peak in infancy and adolescence. Interventions such as TB screening in symptomatic children, and isoniazid and cotrimoxazole prophylaxis should be implemented...
March 4, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Nathan Ford, Zara Shubber, Joseph N Jarvis, Tom Chiller, Greg Greene, Chantal Migone, Marco Vitoria, Meg Doherty, Graeme Meintjes
Background: Current guidelines recommend screening all people living with human immunodeficiency virus (PLHIV) who have a CD4 count ≤100 cells/µL for cryptococcal antigen (CrAg) to identify those patients who could benefit from preemptive fluconazole treatment prior to the onset of meningitis. We conducted a systematic review to assess the prevalence of CrAg positivity at different CD4 cell counts. Methods: We searched 4 databases and abstracts from 3 conferences up to 1 September 2017 for studies reporting prevalence of CrAg positivity according to CD4 cell count strata...
March 4, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Nathan Ford, Graeme Meintjes, Alexandra Calmy, Helen Bygrave, Chantal Migone, Marco Vitoria, Martina Penazzato, Lara Vojnov, Meg Doherty
In 2017, the World Health Organization (WHO) published guidelines for the management of advanced human immunodeficiency virus (HIV) disease within a public health approach. Recent data suggest that more than a third of people starting antiretroviral therapy (ART) do so with advanced HIV disease, and an increasing number of patients re-present to care at an advanced stage of HIV disease following a period of disengagement from care. These guidelines recommend a standardized package of care for adults, adolescents, and children, based on the leading causes of morbidity and mortality: tuberculosis, severe bacterial infections, cryptococcal meningitis, toxoplasmosis, and Pneumocystis jirovecii pneumonia...
March 4, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Ahmad Mourad, John R Perfect
Cryptococcal meningitis is the most common central nervous system infection in the world today. It occurs primarily, but not exclusively, in immunocompromised individuals and despite substantial improvement in management of clinical events like AIDS, the numbers of cases of cryptococcosis remain very high. Unfortunately, despite several antifungal agents available for treatment, morbidity and mortality rates remain high with this fungal infection. In this Review, we will describe the treatments and strategies for success, identify the failures, and provide insights into the future developments / improvements for management...
2018: Memórias do Instituto Oswaldo Cruz
Christina A Cuomo, Johanna Rhodes, Christopher A Desjardins
Cryptococcus species are the causative agents of cryptococcal meningitis, a significant source of mortality in immunocompromised individuals. Initial work on the molecular epidemiology of this fungal pathogen utilized genotyping approaches to describe the genetic diversity and biogeography of two species, Cryptococcus neoformans and Cryptococcus gattii. Whole genome sequencing of representatives of both species resulted in reference assemblies enabling a wide array of downstream studies and genomic resources...
2018: Memórias do Instituto Oswaldo Cruz
Guilhem Janbon
In Cryptococcus neoformans, nearly all genes are interrupted by small introns. In recent years, genome annotation and genetic analysis have illuminated the major roles these introns play in the biology of this pathogenic yeast. Introns are necessary for gene expression and alternative splicing can regulate gene expression in response to environmental cues. In addition, recent studies have revealed that C. neoformans introns help to prevent transposon dissemination and protect genome integrity. These characteristics of cryptococcal introns are probably not unique to Cryptococcus, and this yeast likely can be considered as a model for intron-related studies in fungi...
2018: Memórias do Instituto Oswaldo Cruz
Elizabeth Nalintya, David B Meya, Sarah Lofgren, Kathy Huppler Hullsiek, David R Boulware, Radha Rajasingham
BACKGROUND: Cryptococcus is a leading cause of AIDS-related mortality. Cryptococcal antigen (CrAg) is detectable in blood before meningitis onset, and predicts death. CrAg screening amongst those with advanced HIV, and treatment of those CrAg+ with fluconazole has demonstrated survival benefit. However, implementation and widespread uptake have been slow outside of clinical trials. METHODS: We designed a CrAg screening program for routine care that incorporated intensive education and training of clinic staff...
March 2, 2018: Journal of Acquired Immune Deficiency Syndromes: JAIDS
Leonardo Euripedes Andrade-Silva, Kennio Ferreira-Paim, Thatiana Bragine Ferreira, Anderson Vilas-Boas, Delio José Mora, Verônica Morais Manzato, Fernanda Machado Fonseca, Kelli Buosi, Juliana Andrade-Silva, Bruno da Silva Prudente, Natalia Evelyn Araujo, Helioswilton Sales-Campos, Marcus Vinicius da Silva, Virmondes Rodrigues Júnior, Wieland Meyer, Mario Léon Silva-Vergara
Cryptococcal infections are mainly caused by members of the Cryptococcus neoformans species complex (molecular types VNI, VNII, VNB, VNIV and the AD hybrid VNIII). PCR of the mating type loci and MLST typing using the ISHAM-MLST consensus scheme were used to evaluate the genetic relationship of 102 (63 clinical and 39 environmental) C. neoformans isolates from Uberaba, Brazil and to correlate the obtained genotypes with clinical, antifungal susceptibility and virulence factor data. All isolates were mating type alpha...
2018: PloS One
Yunfang Meng, Yumeng Fan, Wanqing Liao, Xiaorong Lin
Cryptococcus neoformans is a major opportunistic fungal pathogen. Like many dimorphic fungal pathogens, C. neoformans can undergo morphological transition from the yeast form to the hypha form and its morphotype is tightly linked to its virulence. Although some genetic factors controlling morphogenesis have been identified, little is known about the epigenetic regulation in this process. Proteins with the plant homeodomain (PHD) finger, a structurally conserved domain in eukaryotes, are first identified in plants and are known to be involved in reading and effecting chromatin modification...
March 2, 2018: Applied and Environmental Microbiology
Mihai Mareș, Valentina Ruxandra Moroti-Constantinescu, David W Denning
OBJECTIVE: To estimate for the first time the burden of fungal infections in Romania. METHODS: Data derived from the World Health Organization (WHO), National Institute of Statistics, Romanian public health agencies and non-profit health organizations, and published annual reports on local epidemiology were used in the present study. When no data were available, specific at-risk populations were used to calculate frequencies of serious fungal diseases, using previously published epidemiological parameters...
March 1, 2018: Journal of Fungi (Basel, Switzerland)
Jeffrey Berinstein, Alisa Likhitsup, Sai Charan Vedula, Hari Conjeevaram
Cryptococcal peritonitis is an under-recognized disease that is an important cause of mortality in end-stage liver disease. We report a 43-year old male with decompensated cirrhosis secondary to refractory autoimmune hepatitis on immunosuppression with hepatocellular carcinoma who developed cryptococcal peritonitis. The patient subsequently developed ischemic bowel and multisystem organ failure secondary to abdominal compartment syndrome, leading to rapid deterioration and death. Frequently, these patients experience delays in diagnosis and treatment, which leads to a rapid and high mortality...
December 21, 2017: Curēus
Viviana Giustini, Alessandra Sottini, Stefano Belleri, Diego Bertoli, Aldo M Roccaro, Alessandro Montanelli, Matteo Filippini, Marco Fontanella, Luisa Imberti
Cryptococcal meningoencephalitis is the most common infective complication observed in patients with CD4 lymphocytopenia, including sarcoidosis. T-cell immunity is well characterized in HIV-related infections and data regarding immunity in cryptococcosis animal models is now available; on the contrary, little is known about the immune status in non-HIV-related infections. We report on reduced production of new T cells observed in a patient with sarcoidosis, CD4 lymphocytopenia, and cryptococcal-related meningoencephalitis...
February 23, 2018: Journal of Neurosurgical Sciences
Vanessa A Barcellos, Liline M S Martins, Alide C L Fontes, Julia C V Reuwsaat, Eamim D Squizani, Glauber R de Sousa Araújo, Susana Frases, Charley C Staats, Augusto Schrank, Livia Kmetzsch, Marilene H Vainstein
The Cryptococcus gattii species complex harbors the main etiological agents of cryptococcosis in immunocompetent patients. C. gattii molecular type VGII predominates in the north and northeastern regions of Brazil, leading to high morbidity and mortality rates. C. gattii VGII isolates have a strong clinical relevance and phenotypic variations. These phenotypic variations among C. gattii species complex isolates suggest that some strains are more virulent than others, but little information is available related to the pathogenic properties of those strains...
2018: Frontiers in Microbiology
Shu Shun Li, Henry Ogbomo, Michael K Mansour, Richard F Xiang, Lian Szabo, Fay Munro, Priyanka Mukherjee, Roy A Mariuzza, Matthias Amrein, Jatin M Vyas, Stephen M Robbins, Christopher H Mody
Natural killer (NK) cells use the activating receptor NKp30 as a microbial pattern-recognition receptor to recognize, activate cytolytic pathways, and directly kill the fungi Cryptococcus neoformans and Candida albicans. However, the fungal pathogen-associated molecular pattern (PAMP) that triggers NKp30-mediated killing remains to be identified. Here we show that β-1,3-glucan, a component of the fungal cell wall, binds to NKp30. We further demonstrate that β-1,3-glucan stimulates granule convergence and polarization, as shown by live cell imaging...
February 21, 2018: Nature Communications
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