Article
Microbiology
Andrew J. Jezewski, Laura C. Ristow, Damian J. Krysan
Summary: Flucytosine-based combination therapy has been successful in treating cryptococcal infections globally. However, there are limitations in determining the susceptibility of clinical isolates, as flucytosine susceptibility varies widely. This study found that simulating host-like carbon dioxide conditions enhances flucytosine susceptibility in clinical isolates, suggesting that the activity of flucytosine is highly dependent on the host environment and may not be well represented by standard in vitro testing.
MICROBIOLOGY SPECTRUM
(2023)
Review
Immunology
Herdson Renney de Sousa, Stefania de Frazao, Getulio Pereira de Oliveira Junior, Patricia Albuquerque, Andre Moraes Nicola
Summary: Cryptococcosis, caused by Cryptococcus spp, has a high mortality rate and lacks effective prevention and treatment methods. Understanding fungal virulence and host responses could lead to improved therapies. Studies using clinical isolates to correlate laboratory and patient data have provided valuable insights into the pathophysiology of cryptococcosis.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Immunology
Chunxi Yang, Zeyuan Bian, Oliver Blechert, Fengyi Deng, Hui Chen, Yueting Li, Yunhong Yang, Min Chen, Ping Zhan
Summary: This study conducted in hospitals in Jiangxi Province, South Central China, recruited 230 clinically suspected cryptococcosis cases and found Cryptococcus neoformans to be the predominant species causing the disease in the region. A large proportion of strains were not sensitive to fluconazole, and a high percentage of HIV-related infections were reported, highlighting the importance of continuous monitoring of species distribution and antifungal sensitivity in the investigation of this severe disease.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Microbiology
Priscilla Belbir Atim, David B. Meya, Elliot S. Gerlach, Dennis Muhanguzi, Allan Male, Benedict Kanamwanji, Kirsten Nielsen
Summary: This study investigated the SNPs of the ERG11 gene in clinical isolates of C. neoformans in Uganda and found two missense mutations, but these mutations were not associated with fluconazole susceptibility.
Article
Microbiology
Christopher J. Winski, Yuanyuan Qian, Shahriar Mobashery, Felipe H. Santiago-Tirado
Summary: This study demonstrates a novel dual role for PDR transporters in C. neoformans, which could represent a potential target for antifungal therapeutics. Furthermore, the atypical half-size transporter encoded by PDR6 is conserved in many fungal pathogens, but absent in model nonpathogenic fungi. This study provides insights into the function of this unique group of fungal half-size PDR transporters that, although conserved, remain largely understudied.
Editorial Material
Microbiology
Nicolas Papon, Gustavo H. Goldman
Summary: Cryptococcus neoformans poses a significant threat to immunocompromised patients, with limited treatment options available. The newly discovered echinocandins were initially promising, but the natural resistance of C. neoformans to these drugs has hindered their effectiveness. Recent research by the Panepinto group sheds light on a new mechanism through which C. neoformans regulates caspofungin resistance.
Review
Microbiology
Katrina M. Jackson, Minna Ding, Kirsten Nielsen
Summary: The human pathogenic fungus Cryptococcus neoformans is a global health concern. Previous research has primarily focused on using reference strains to study the fungus, but studying clinical isolates has expanded our knowledge of its pathogenesis and the host-pathogen interaction during infection.
Article
Immunology
Elliot S. Gerlach, Sophie Altamirano, J. Marina Yoder, Tony S. Luggya, Andrew Akampurira, David B. Meya, David R. Boulware, Joshua Rhein, Kirsten Nielsen
Summary: In this study, ATI-2307 showed promising antifungal activity against clinical isolates of Cryptococcus neoformans with high fluconazole IC50 values, with no correlation between fluconazole resistance and ATI-2307 or amphotericin B susceptibility observed. This suggests that ATI-2307 could be a potential new antifungal drug for use in cases of high fluconazole MICs or in combination therapy.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Review
Infectious Diseases
Youbao Zhao, Leixin Ye, Fujie Zhao, Lanyue Zhang, Zhenguo Lu, Tianxin Chu, Siyu Wang, Zhanxiang Liu, Yukai Sun, Min Chen, Guojian Liao, Chen Ding, Yingchun Xu, Wanqing Liao, Linqi Wang
Summary: The study reviews progress made in the past two decades on Cryptococcus neoformans, the highest-ranked fungal pathogen in the World Health Organization's Fungal Priority Pathogens List. It examines its global burden, clinical manifestation and management, and antifungal resistance. The purpose of the study is to drive research efforts to improve future diagnoses, therapies, and interventions associated with fungal infections.
INFECTIOUS DISEASES OF POVERTY
(2023)
Article
Microbiology
Norida Velez, Nelson Vega-Vela, Marina Munoz, Paola Gomez, Patricia Escandon, Juan David Ramirez, Oscar Zaragoza, Lucia Monteoliva Diaz, Claudia-Marcela Parra-Giraldo
Summary: In this study, the relationship between phenotypes and genotypes of clinical isolates of Cryptococcus neoformans from different cities in Colombia was investigated. The study found that isolates showed variations in pigmentation, capsule size, and pathogenicity. Polymorphism analysis revealed genetic variants associated with capsule size change, melanin production, or pathogenicity. However, no clear patterns were found in the analysis of phenotype and genotype for Cryptococcus.
Article
Infectious Diseases
Lanyu Zhang, Saisai Wang, Nan Hong, Muyuan Li, Yiting Liu, Tao Zhou, Yan Peng, Changhua Hu, Xiaoxu Li, Zhen Zhang, Mengzhu Guo, Massimo Cogliati, Megan Hitchcock, Jianping Xu, Min Chen, Guojian Liao
Summary: Genotypic diversity and antifungal susceptibility of Cryptococcus neoformans species complex isolates from HIV-infected patients in China were investigated. The study found novel genotypes, ST15 and ST632/ST636, and an increasing trend of drug resistance in this region.
Review
Biochemistry & Molecular Biology
Stephanie Nguyen, Jia Q. Truong, John B. Bruning
Summary: Invasive fungal infections pose a serious threat to human health, necessitating the development of novel antifungal drugs. Targeted interruption of essential metabolic pathways in fungi shows promise as a strategy to disrupt fungal survival and virulence.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Microbiology
Yang Zhang, Liyan Zhou, Yan Liu, Xi Zhao, Xianqiang Lian, Jie Zhang, De Zhao, Yujuan Wang, Jin Zhong, Junfeng Wang, Hongli Wang, Linqi Wang, Yu Fu
Summary: SP1, a peptide derived from yeast GAPDH, has the potential to be developed as a treatment option for cryptococcosis by efficiently killing Cryptococcus neoformans and Cryptococcus gattii.
MICROBIOLOGY SPECTRUM
(2022)
Article
Microbiology
Brenda Moreira-Walsh, Abigail Ragsdale, Woei Lam, Rajendra Upadhya, Evan Xu, Jennifer K. Lodge, Maureen J. Donlin
Summary: The intrinsic resistance of Cryptococcus neoformans to caspofungin limits the available therapies for treating cryptococcal infections. By screening gene deletion strains, researchers identified biological processes associated with altered membrane permeability that could render the cell more susceptible to caspofungin. Targeting these genes or other genes affecting membrane permeability may provide potential for novel therapies against this global fungal pathogen.
Article
Microbiology
Zena M. Birkenfeld, Nikita Dittel, Thomas Harrer, Christoph Stephan, Albrecht F. Kiderlen, Volker Rickerts
Summary: The clinical isolates of Cryptococcus neoformans var. neoformans exhibit substantial phenotypic variability, with isolates from disseminated infections showing stronger melanization and larger capsules. These isolates also demonstrate increased cytotoxicity for amoeba in coincubation, indicating a potential difference in virulence potential among strains from localized and disseminated infections.
Article
Oncology
Tomohiro Tanaka, Charles F. Lynch, Kelly J. Yu, Bozena M. Morawski, Mei-Chin Hsieh, Georgetta Alverson, April A. Austin, Yun Zeng, Eric A. Engels
Summary: The incidence of pancreatic cancer is higher in solid organ transplant recipients, particularly in liver transplant recipients. Compared with the general population, pancreatic cancer is more commonly diagnosed in transplant recipients, especially in cases arising in the head of the pancreas and those diagnosed at localized stage. Risk factors for pancreatic cancer in transplant recipients are consistent with those in the general population, including male sex, older age, non-O blood type, and history of diabetes.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2023)
Article
Immunology
Nathan C. Bahr, Caleb P. Skipper, Kathy Huppler-Hullsiek, Kenneth Ssebambulidde, Bozena M. Morawski, Nicole W. Engen, Edwin Nuwagira, Carson M. Quinn, Prashanth S. Ramachandran, Emily E. Evans, Sarah M. Lofgren, Mahsa Abassi, Conrad Muzoora, Michael R. Wilson, David B. Meya, Joshua Rhein, David R. Boulware
Summary: Recurrent symptoms in individuals with prior cryptococcal meningitis are common and difficult to diagnose using current methods. This study aimed to summarize the characteristics, causes, and outcomes of second-episode symptomatic recurrence, providing valuable insights for treatment.
CLINICAL INFECTIOUS DISEASES
(2023)
Article
Plant Sciences
Abigail R. Meyer, Maria Valentin, Laima Liulevicius, Tami R. McDonald, Matthew P. Nelsen, Jean Pengra, Robert J. Smith, Daniel Stanton
Summary: The long-term potential for acclimation by lichens to changing climates is poorly known. A previous study showed that the mass and physiological function of lichens were severely lost after a 2 degrees C increase in temperature, mainly due to the decrease in activity of their symbiotic partners. This finding is important for understanding the response mechanisms of lichens to climate change.
AMERICAN JOURNAL OF BOTANY
(2023)
Article
Surgery
Allyson Hart, Ruth M. Pfeiffer, Bozena M. Morawski, Charles F. Lynch, Yun Zeng, Karen Pawlish, Deborah Hurley, Kelly J. Yu, Eric A. Engels
Summary: This study examined the outcomes of solid organ transplant recipients with a pretransplant cancer diagnosis. It found that pretransplant cancer was associated with increased overall mortality, cancer-specific mortality, and risk of developing posttransplant cancer. Improved candidate selection and cancer screening and prevention may help reduce mortality in this population.
AMERICAN JOURNAL OF TRANSPLANTATION
(2023)
Article
Public, Environmental & Occupational Health
Fergal P. Mills, Gilmar Reis, Lindsay A. Wilson, Kristian Thorlund, Jamie I. Forrest, Christina M. Guo, David R. Boulware, Edward J. Mills, TOGETHER Investigators
Summary: According to two published randomized trials, early treatment with fluvoxamine has shown clinical benefits for symptomatic adults with COVID-19 compared to placebo. A cost-consequence analysis was conducted using the largest trial, TOGETHER trial, to assess the health system benefits of preventing progression to severe COVID-19 in outpatient populations in the United States. The analysis showed that fluvoxamine administration to high-risk symptomatic outpatients was cost-saving and resulted in fewer hospitalization days compared to standard of care. Nirmatrelvir-ritonavir also demonstrated cost savings despite its higher acquisition cost.
AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
(2023)
Editorial Material
Medicine, General & Internal
Todd C. Lee, David R. Boulware
ANNALS OF INTERNAL MEDICINE
(2023)
Article
Medicine, Research & Experimental
Oriol Mitja, Gilmar Reis, David R. Boulware, Adam M. Spivak, Ammar Sarwar, Christine Johnston, Brandon Webb, Michael D. Hill, Davey Smith, Peter Kremsner, Marla Curran, David Carter, Jim Alexander, Marc Corbacho, Todd C. Lee, Katherine Huppler Hullsiek, Emily G. McDonald, Rachel Hess, Michael Hughes, Jared M. Baeten, Ilan Schwartz, Luanne Metz, Lawrence Richer, Kara W. Chew, Eric Daar, David Wohl, Michael Dunne
Summary: This study conducted a pooled analysis of individual participant data from 11 randomized controlled trials to evaluate the efficacy of hydroxychloroquine (HCQ) in outpatients with mild COVID-19. The results suggest that HCQ does not show significant effects on viral clearance and hospitalization rate, and therefore, the use of HCQ in mild COVID-19 outpatients should be discontinued to reduce the risk of disease progression.
CTS-CLINICAL AND TRANSLATIONAL SCIENCE
(2023)
Article
Medicine, General & Internal
Matthew W. McCarthy, Susanna Naggie, David R. Boulware, Christopher J. Lindsell, Thomas G. Stewart, G. Michael Felker, Dushyantha Jayaweera, Mark Sulkowski, Nina Gentile, Carolyn Bramante, Upinder Singh, Rowena J. Dolor, Juan Ruiz-Unger, Sybil Wilson, Allison DeLong, April Remaly, Rhonda Wilder, Sean Collins, Sarah E. Dunsmore, Stacey J. Adam, Florence Thicklin, George Hanna, Adit A. Ginde, Mario Castro, Kathleen McTigue, Elizabeth Shenkman, Adrian F. Hernandez
Summary: This study aimed to evaluate the efficacy of low-dose fluvoxamine (50 mg twice daily for 10 days) compared with placebo for the treatment of mild to moderate COVID-19. The results showed that treatment with fluvoxamine did not improve the time to sustained recovery compared with placebo. These findings do not support the use of fluvoxamine at this dose and duration in patients with mild to moderate COVID-19.
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
(2023)
Article
Immunology
Alessandro C. Pasqualotto, Daiane Dalla Lana, Cassia S. M. Godoy, Terezinha do Menino Jesus Silva Leitao, Monica B. Bay, Lisandra Serra Damasceno, Renata B. A. Soares, Roger Kist, Larissa R. Silva, Denusa Wiltgen, Marineide Melo, Taiguara F. Guimaraes, Marilia R. Guimaraes, Hareton T. Vechi, Jaco R. L. de Mesquita, Gloria Regina de G. Monteiro, Antoine Adenis, Nathan C. Bahr, Andrej Spec, David R. Boulware, Dennis Israelski, Tom Chiller, Diego R. Falci
Summary: This is the first trial to show that AIDS patients with disseminated histoplasmosis can be safely and effectively treated with a single high dose of liposomal amphotericin B (10 mg/kg).
CLINICAL INFECTIOUS DISEASES
(2023)
Editorial Material
Immunology
David R. Boulware, Joseph N. Jarvis
CLINICAL INFECTIOUS DISEASES
(2023)
Article
Medicine, General & Internal
Susanna Naggie, David R. Boulware, Christopher J. Lindsell, Thomas G. Stewart, Alex J. Slandzicki, Stephen C. Lim, Jonathan Cohen, David Kavtaradze, Arch P. Amon, Ahab Gabriel, Nina Gentile, G. Michael Felker, Dushyantha Jayaweera, Matthew W. McCarthy, Mark Sulkowski, Russell L. Rothman, Sybil Wilson, Allison DeLong, April Remaly, Rhonda Wilder, Sean Collins, Sarah E. Dunsmore, Stacey J. Adam, Florence Thicklin, George J. Hanna, Adit A. Ginde, Mario Castro, Kathleen McTigue, Elizabeth Shenkman, Adrian F. Hernandez
Summary: The study evaluated the effectiveness of ivermectin at a maximum targeted dose of 600 μg/kg daily for 6 days in the treatment of early mild to moderate COVID-19. The results showed that compared to placebo, ivermectin treatment did not improve the time to sustained recovery, suggesting no benefits of ivermectin for patients with mild to moderate COVID-19.
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
(2023)
Article
Infectious Diseases
Carolyn T. Bramante, John B. Buse, David M. Liebovitz, Jacinda M. Nicklas, Michael A. Puskarich, Ken Cohen, Hrishikesh K. Belani, Blake J. Anderson, Jared D. Huling, Christopher J. Tignanelli, Jennifer L. Thompson, Matthew Pullen, Esteban Lemus Wirtz, Lianne K. Siegel, Jennifer L. Proper, David J. Odde, Nichole R. Klatt, Nancy E. Sherwood, Sarah M. Lindberg, Amy B. Karger, Kenneth B. Beckman, Spencer M. Erickson, Sarah L. Fenno, Katrina M. Hartman, Michael R. Rose, Tanvi Mehta, Barkha Patel, Gwendolyn Griffiths, Neeta S. Bhat, Thomas A. Murray
Summary: This study aimed to evaluate the potential of outpatient COVID-19 treatment with metformin, ivermectin, or fluvoxamine to reduce the risk of long COVID. The findings showed that metformin treatment was associated with a 41% reduction in the incidence of long COVID compared to placebo, while ivermectin and fluvoxamine did not have the same effect.
LANCET INFECTIOUS DISEASES
(2023)
Article
Multidisciplinary Sciences
Olivie C. Namuju, Proscovia M. Namuwenge, Richard Kwizera, Emmanuel Obuya, Paul Kirumira, Rose Naluyima, Cynthia Ahimbisibwe, JaneFrancis Ndyetukira, Hawa Nakato, Robert Kirungi, Jane Gakuru, Samuel Junju, Edwin Nuwagira, Morris Rutakagirwa, Sara Nsibirwa, Vennie Nabitaka, Elizabeth Nalintya, Edward Mpoza, Conrad K. Muzoora, Abdu K. Musubire, David R. Boulware, David B. Meya
Summary: This study aimed to assess adherence to HIV-associated cryptococcal meningitis (CM) guidelines and stock management of CM supplies in selected public health facilities in Uganda. The findings showed low adherence to CM screening and management guidelines by health workers, highlighting the need for training and support.
Article
Medicine, Research & Experimental
Kristian Thorlund, Davey Smith, Christopher Linsell, Nicholas White, Christopher Butler, David Boulware, Judith Currier, Ofir Harari, Edouard Lhomme, Nathalie Strub-Wourgaft, Stacey Adam, Edward Mills
Summary: Clinical trial endpoints should be carefully selected to inform policy- and decision-making, considering the preferences of different stakeholders. The selection of endpoints for COVID-19 clinical trials has been problematic, as they did not always match the usual efficacy endpoints required by guideline panels. This has made it difficult to compare and evaluate interventions timely. Selecting appropriate endpoints is crucial for researchers to provide reliable, valid, and interpretable results.
COMMUNICATIONS MEDICINE
(2023)
Article
Medicine, General & Internal
Lillian Tugume, Kenneth Ssebambulidde, John Kasibante, Jayne Ellis, Rachel M. Wake, Jane Gakuru, David S. Lawrence, Mahsa Abassi, Radha Rajasingham, David B. Meya, David R. Boulware
Summary: Cryptococcus neoformans and Cryptococcus gattii species complexes cause life-threatening meningoencephalitis, particularly in individuals with compromised immune system, such as those with HIV. Although the global incidence of HIV-associated cryptococcal meningitis has decreased, it still remains a significant cause of AIDS-related deaths worldwide. Strategies to decrease mortality associated with cryptococcosis include antigen screening and preemptive therapy, while new combination treatment regimens are being evaluated in clinical trials. Short courses of amphotericin-based therapy combined with flucytosine are currently recommended for induction therapy. The long-term effects of short-course induction regimens on morbidity are yet to be studied. In this article, the authors discuss the immunology, changing epidemiology, and management updates of cryptococcal meningitis, with a focus on HIV-associated disease.
NATURE REVIEWS DISEASE PRIMERS
(2023)