288 results on '"Tom, Chiller"'
Search Results
2. Tracing histoplasmosis genomic epidemiology and species occurrence across the USA
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Bernardo Guerra Tenório, Daniel R. Kollath, Lalitha Gade, Anastasia P. Litvintseva, Tom Chiller, Jeff S. Jenness, Jason E. Stajich, Daniel R. Matute, Andrew S. Hanzlicek, Bridget M. Barker, and Marcus de Melo Teixeira
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Histoplasmosis ,molecular epidemiology ,Histoplasma ohiense ,Histoplasma mississippiense ,genomics ,species distribution modelling ,Infectious and parasitic diseases ,RC109-216 ,Microbiology ,QR1-502 - Abstract
ABSTRACTHistoplasmosis is an endemic mycosis in North America frequently reported along the Ohio and Mississippi River Valleys, although autochthonous cases occur in non-endemic areas. In the United States, the disease is provoked by two genetically distinct clades of Histoplasma capsulatum sensu lato, Histoplasma mississippiense (Nam1) and H. ohiense (Nam2). To bridge the molecular epidemiological gap, we genotyped 93 Histoplasma isolates (62 novel genomes) including clinical, environmental, and veterinarian samples from a broader geographical range by whole-genome sequencing, followed by evolutionary and species niche modelling analyses. We show that histoplasmosis is caused by two major lineages, H. ohiense and H. mississippiense; with sporadic cases caused by H. suramericanum in California and Texas. While H. ohiense is prevalent in eastern states, H. mississipiense was found to be prevalent in the central and western portions of the United States, but also geographically overlapping in some areas suggesting that these species might co-occur. Species Niche Modelling revealed that H. ohiense thrives in places with warmer and drier conditions, while H. mississippiense is endemic to areas with cooler temperatures and more precipitation. In addition, we predicted multiple areas of secondary contact zones where the two species co-occur, potentially facilitating gene exchange and hybridization. This study provides the most comprehensive understanding of the genomic epidemiology of histoplasmosis in the USA and lays a blueprint for the study of invasive fungal diseases.
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- 2024
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3. Effects of climate change on fungal infections.
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Samantha L Williams, Mitsuru Toda, Tom Chiller, Joan M Brunkard, and Anastasia P Litvintseva
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Immunologic diseases. Allergy ,RC581-607 ,Biology (General) ,QH301-705.5 - Published
- 2024
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4. Understanding the exposure risk of aerosolized Coccidioides in a Valley fever endemic metropolis
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W. Tanner Porter, Lalitha Gade, Parker Montfort, Joseph R. Mihaljevic, Jolene R. Bowers, Andrew Willman, Brian A. Klimowski, Bonnie J. LaFleur, Rebecca H. Sunenshine, Jennifer Collins, Guillermo Adame, Shane Brady, Kenneth K. Komatsu, Samantha Williams, Mitsuru Toda, Tom Chiller, Anastasia P. Litvintseva, and David M. Engelthaler
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Medicine ,Science - Abstract
Abstract Coccidioides is the fungal causative agent of Valley fever, a primarily pulmonary disease caused by inhalation of fungal arthroconidia, or spores. Although Coccidioides has been an established pathogen for 120 years and is responsible for hundreds of thousands of infections per year, little is known about when and where infectious Coccidioides arthroconidia are present within the ambient air in endemic regions. Long-term air sampling programs provide a means to investigate these characteristics across space and time. Here we present data from > 18 months of collections from 11 air sampling sites across the Phoenix, Arizona, metropolitan area. Overall, prevalence was highly variable across space and time with no obvious spatial or temporal correlations. Several high prevalence periods were identified at select sites, with no obvious spatial or temporal associations. Comparing these data with weather and environmental factor data, wind gusts and temperature were positively associated with Coccidioides detection, while soil moisture was negatively associated with Coccidioides detection. These results provide critical insights into the frequency and distribution of airborne arthroconidia and the associated risk of inhalation and potential disease that is present across space and time in a highly endemic locale.
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- 2024
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5. Increased Hospitalizations Involving Fungal Infections during COVID-19 Pandemic, United States, January 2020–December 2021
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Jeremy A.W. Gold, Stacey Adjei, Adi V. Gundlapalli, Ya-Lin A. Huang, Tom Chiller, Kaitlin Benedict, and Mitsuru Toda
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fungi ,invasive fungal infections ,mycoses ,hospitalizations ,aspergillosis ,candidiasis ,Medicine ,Infectious and parasitic diseases ,RC109-216 - Abstract
Hospitalizations involving fungal infections increased 8.5% each year in the United States during 2019–2021. During 2020–2021, patients hospitalized with COVID-19–associated fungal infections had higher (48.5%) in-hospital mortality rates than those with non–COVID-19–associated fungal infections (12.3%). Improved fungal disease surveillance is needed, particularly during respiratory virus pandemics.
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- 2023
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6. Prevalence of Histoplasmosis among Persons with Advanced HIV Disease, Nigeria
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Rita O. Oladele, Iriagbonse I. Osaigbovo, Alani S. Akanmu, Olukemi A. Adekanmbi, Bassey E. Ekeng, Yahaya Mohammed, Mary A. Alex-Wele, Mark O. Okolo, Stephen T. Ayanbeku, Uchechukwu S. Unigwe, Iorhen E. Akase, Alali Dan-Jumbo, Dennis Isralski, David W. Denning, Alessandro C. Pasqualotto, and Tom Chiller
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HIV/AIDS and other retroviruses ,histoplasmosis ,histoplasma ,fungi ,tuberculosis and other mycobacteria ,infections ,Medicine ,Infectious and parasitic diseases ,RC109-216 - Abstract
We sought to determine the prevalence of probable disseminated histoplasmosis among advanced HIV disease (AHD) patients in Nigeria. We conducted a cross-sectional study in 10 sites across 5 of 6 geopolitical zones in Nigeria. We identified patients with urinary samples containing CD4 cell counts 2 clinical features of disseminated histoplasmosis, and we tested them for Histoplasma antigen using a Histoplasma enzyme immune assay. Of 988 participants we recruited, 76 (7.7%) were antigen-positive. The 76 Histoplasma antigen–positive participants had significantly lower (p = 0.03) CD4 counts; 9 (11.8%) were also co-infected with tuberculosis. Most antigen-positive participants (50/76; 65.8%; p = 0.015) had previously received antiretroviral treatment; 26/76 (34.2%) had not. Because histoplasmosis is often a hidden disease among AHD patients in Nigeria, Histoplasma antigen testing should be required in the AHD package of care.
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- 2022
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7. The importance of antimicrobial resistance in medical mycology
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Neil A. R. Gow, Carolyn Johnson, Judith Berman, Alix T. Coste, Christina A. Cuomo, David S. Perlin, Tihana Bicanic, Thomas S. Harrison, Nathan Wiederhold, Mike Bromley, Tom Chiller, and Keegan Edgar
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Science - Abstract
The impact of fungal infections on human health has been exacerbated by the rise of antifungal drug resistance. In this Review, the authors outline the problem of antifungal resistance and suggest how this growing threat might be mitigated.
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- 2022
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8. Modelling the impact of CD4 testing on mortality from TB and cryptococcal meningitis among patients with advanced HIV disease in nine countries
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Ikwo Kitefre Oboho, Heather Paulin, Carl Corcoran, Matt Hamilton, Alex Jordan, Hannah L. Kirking, Elfriede Agyemang, Laura Jean Podewils, Carel Pretorius, Greg Greene, Tom Chiller, Mitesh Desai, Roma Bhatkoti, Ray W. Shiraishi, and N. Sarita Shah
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advanced HIV disease ,CD4 testing ,cryptococcal meningitis ,deaths averted ,mortality ,TB mortality ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Abstract Introduction Despite antiretroviral therapy (ART) scale‐up among people living with HIV (PLHIV), those with advanced HIV disease (AHD) (defined in adults as CD4 count
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- 2023
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9. Public Health Research Priorities for Fungal Diseases: A Multidisciplinary Approach to Save Lives
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Dallas J. Smith, Jeremy A. W. Gold, Kaitlin Benedict, Karen Wu, Meghan Lyman, Alexander Jordan, Narda Medina, Shawn R. Lockhart, D. Joseph Sexton, Nancy A. Chow, Brendan R. Jackson, Anastasia P. Litvintseva, Mitsuru Toda, and Tom Chiller
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fungal diseases ,research priorities ,fungal disease surveillance ,fungal disease diagnostic tests ,fungal disease treatment ,Biology (General) ,QH301-705.5 - Abstract
Fungal infections can cause severe disease and death and impose a substantial economic burden on healthcare systems. Public health research requires a multidisciplinary approach and is essential to help save lives and prevent disability from fungal diseases. In this manuscript, we outline the main public health research priorities for fungal diseases, including the measurement of the fungal disease burden and distribution and the need for improved diagnostics, therapeutics, and vaccines. Characterizing the public health, economic, health system, and individual burden caused by fungal diseases can provide critical insights to promote better prevention and treatment. The development and validation of fungal diagnostic tests that are rapid, accurate, and cost-effective can improve testing practices. Understanding best practices for antifungal prophylaxis can optimize prevention in at-risk populations, while research on antifungal resistance can improve patient outcomes. Investment in vaccines may eliminate certain fungal diseases or lower incidence and mortality. Public health research priorities and approaches may vary by fungal pathogen.
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- 2023
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10. Six months survival and risk factors for attrition for patients detected with cryptococcal antigenemia through screening in Malawi.
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Master R O Chisale, Alex Jordan, Pocha S Kamudumuli, Bernard Mvula, Michael Odo, Alice Maida, James Kandulu, Ben Chilima, Frank W Sinyiza, Pauline Katundu, Hsin-Yi Lee, Rebecca Mtegha, Tsung-Shu Joseph Wu, Joseph Bitirinyo, Rose Nyirenda, Thoko Kalua, Greg Greene, and Tom Chiller
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Medicine ,Science - Abstract
Main objectiveA cohort of adult Malawian people living with HIV (PLHIV) testing positive for cryptococcal antigenemia was observed and followed to determine the outcomes and risk factors for attrition.Methods conceptEligible PLHIV were enrolled at 5 health facilities in Malawi, representing different levels of health care. ART naïve patients, ART defaulters returning to care, and patients with suspected or confirmed ART treatment failure with CD4 ResultsA total of 2146 patients were screened and 112 (5.2%) had cryptococcal antigenemia. Prevalence ranged from 3.8% (Mzuzu Central Hospital) to 25.8% (Jenda Rural Hospital). Of the 112 patients with antigenemia, 33 (29.5%) were diagnosed with concurrent CM at the time of enrollment. Six-month crude survival of all patients with antigenemia (regardless of CM status) ranged from 52.3% (assuming lost-to-follow-up (LTFU) patients died) to 64.9% (if LTFU survived). Patients who were diagnosed with concurrent CM by CSF test had poor survival (27.3-39.4%). Patients with antigenemia who were not diagnosed with concurrent CM had 71.4% (if LTFU died)- 89.8% (if LTFU survived) survival at six months. In adjusted analyses, patients with cryptococcal antigenemia detected after admission to inpatient care (aHR: 2.56, 1.07-6.15) and patients with concurrent CM at the time of positive antigenemia result (aHR: 2.48, 1.04-5.92) had significantly higher hazard of attrition at six months.ConclusionsOverall, our findings indicate a need for routine access to CrAg screening and pre-emptive fluconazole treatment as a way to detect cryptococcal antigenemia and prevent CM in outpatient and inpatient settings. Rapid access to diagnosis and treatment for cryptococcal meningitis (CM) with gold-standard antifungals is needed to improve survival of patients with advanced HIV in Malawi.
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- 2023
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11. The 'Histoplasmosis Porto Alegre manifesto'-Addressing disseminated histoplasmosis in AIDS.
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Alessandro C Pasqualotto, Flavio Queiroz-Telles, Alberto Chebabo, Terezinha M J S Leitao, Diego R Falci, Melissa O Xavier, Monica B Bay, Eduardo Sprinz, Daiane Dalla Lana, Adriana P Vincentini, Lisandra Serra Damasceno, Alexandre V Schwarzbold, Paulo Abrão Ferreira, Cassia Miranda Godoy, Jose Ernesto Vidal, Rossana Basso, Candida Driemeyer, Valerio R Aquino, Cecilia B Severo, Marcelo Simão Ferreira, Claudilson Bastos, Filipe Prohaska, Marineide Melo, Francelise Bridi Cavassin, Marcus Lacerda, Renata Soares, Rosely Zancope-Oliveira, Marcus Teixeira, Freddy Perez, Diego H Caceres, Juan Luis Rodriguez-Tudela, Tom Chiller, and Arnaldo L Colombo
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Arctic medicine. Tropical medicine ,RC955-962 ,Public aspects of medicine ,RA1-1270 - Published
- 2023
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12. Epidemiology, Clinical Features, and Outcomes of Coccidioidomycosis, Utah, 2006–2015
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Adrienne Carey, Morgan E. Gorris, Tom Chiller, Brendan Jackson, Wei Beadles, and Brandon J. Webb
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antifungal agents ,Coccidioides ,Coccidioides immitis ,Coccidioides posadasii ,coccidioidomycosis ,epidemiology ,Medicine ,Infectious and parasitic diseases ,RC109-216 - Abstract
On the basis of a 1957 geographic Coccidioides seropositivity survey, 3 counties in southwestern Utah, USA, were considered coccidioidomycosis-endemic, but there has been a paucity of information on the disease burden in Utah since. We report findings from a recent clinical and epidemiologic study of coccidioidomycosis in Utah. To describe clinical characteristics, we identified all coccidioidomycosis cases in an integrated health system in the state during 2006–2015. For epidemiologic analysis, we used cases reported to the Utah Department of Health during 2009–2015. Mean state incidence was 1.83 cases/100,000 population/year. Washington County, in southwestern Utah, had the highest incidence, 17.2 cases/100,000 population/year. In a generalized linear model with time as a fixed effect, mean annual temperature, population, and new construction were associated with regional variations in incidence. Using these variables in a spatiotemporal model, we estimated the adjusted regional variation by county to predict areas where Coccidioides infections might increase.
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- 2021
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13. Application of Real-Time PCR Assays for the Diagnosis of Histoplasmosis in Human FFPE Tissues Using Three Molecular Targets
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Luisa F. López, Ángela M. Tobón, Diego H. Cáceres, Tom Chiller, Anastasia P. Litvintseva, Lalitha Gade, Ángel González, and Beatriz L. Gómez
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histoplasmosis ,Histoplasma capsulatum ,diagnosis ,real time PCR ,FFPE tissues ,Biology (General) ,QH301-705.5 - Abstract
Histoplasmosis is a fungal infection caused by the thermally dimorphic fungus Histoplasma capsulatum. This infection causes significant morbidity and mortality in people living with HIV/AIDS, especially in countries with limited resources. Currently used diagnostic tests rely on culture and serology but with some limitations. No molecular assays are commercially available and the results from different reports have been variable. We aimed to evaluate quantitative real-time PCR (qPCR) targeting three protein-coding genes of Histoplasma capsulatum (100-kDa, H and M antigens) for detection of this fungus in formalin-fixed paraffin-embedded (FFPE) samples from patients with proven histoplasmosis. The sensitivity of 100-kDa, H and M qPCR assays were 93.9%, 91% and 57%, respectively. The specificity of 100-kDa qPCR was 93% when compared against samples from patients with other mycoses and other infections, and 100% when samples from patients with non-infectious diseases were used as controls. Our findings demonstrate that real-time PCR assays targeting 100-kDa and H antigen showed the most reliable results and can be successfully used for diagnosing this mycosis when testing FFPE samples.
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- 2023
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14. Tackling Histoplasmosis Infection in People Living with HIV from Latin America: From Diagnostic Strategy to Public Health Solutions
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Diego H. Cáceres, Beatriz L. Gómez, Ángela M. Tobón, Ángela Restrepo, Tom Chiller, Mark D. Lindsley, Jacques F. Meis, and Paul E. Verweij
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Histoplasma ,histoplasmosis ,VIH ,Latin America ,diagnostic ,public health ,Biology (General) ,QH301-705.5 - Abstract
Histoplasmosis, caused by the thermally dimorphic fungus Histoplasma spp., is a disease with a broad clinical spectrum, presenting from asymptomatic/flu-like symptoms to progressive disseminated disease in people with immunosuppression. In recent years, the concept of histoplasmosis as a disease restricted to the American continent has changed, as now histoplasmosis is reported in many regions around the world. In Latin America, histoplasmosis represents a threat, especially in people with advanced HIV disease (AHD). Diagnosis of histoplasmosis in people living with HIV (PLHIV) is challenging due to the low index of suspicion of the disease, non-specificity of signs and symptoms, and limited access to specific laboratory testing, while the diagnostic delay is significantly associated with mortality. In the last decade, novel diagnostic tests have been developed for the rapid detection of histoplasmosis, such as commercial kits for antigen detection. Furthermore, advocacy groups were created that presented histoplasmosis as a public health problem, with emphasis on patients at risk of progressive disseminated disease. This review aims to discuss the impact of histoplasmosis associated with AHD in Latin America and the strategies employed to tackle histoplasmosis, from the implementation of laboratory testing to disease advocacy and public health interventions.
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- 2023
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15. Fatal Fungicide-Associated Triazole-Resistant Aspergillus fumigatus Infection, Pennsylvania, USA
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Kennedy Bradley, Audrey Le-Mahajan, Beth Morris, Tiina Peritz, Tom Chiller, Kaitlin Forsberg, Natalie S. Nunnally, Shawn R. Lockhart, Jeremy A.W. Gold, and Jane M. Gould
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Fungi ,antimicrobial resistance ,respiratory infections ,Aspergillus fumigatus ,antifungal drug resistance ,invasive mold infection ,Medicine ,Infectious and parasitic diseases ,RC109-216 - Abstract
We report a fatal infection in a 65-year-old immunocompromised male patient caused by pan-triazole–resistant Aspergillus fumigatus containing a TR34/L98H genetic mutation linked to agricultural fungicide use. Clinical and environmental surveillance of triazole-resistant A. fumigatus is needed in the United States to prevent spread and guide healthcare and agricultural practices.
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- 2022
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16. Rhizopus microsporus Infections Associated with Surgical Procedures, Argentina, 2006–2014
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Jolene R. Bowers, Juan Monroy-Nieto, Lalitha Gade, Jason Travis, Nicolás Refojo, Ruben Abrantes, Jorge Santander, Chris French, María Cecilia Dignani, Alejandra Ines Hevia, Chandler C. Roe, Darrin Lemmer, Shawn R. Lockhart, Tom Chiller, Anastasia P. Litvintseva, Liliana Clara, and David M. Engelthaler
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Rhizopus microsporus ,outbreak ,whole-genome sequencing ,surgical infections ,surgical procedures ,fungi ,Medicine ,Infectious and parasitic diseases ,RC109-216 - Abstract
Rhizopus spp. fungi are ubiquitous in the environment and a rare but substantial cause of infection in immunosuppressed persons and surgery patients. During 2005–2017, an abnormally high number of Rhizopus infections in surgery patients, with no apparent epidemiologic links, were reported in Argentina. To determine the likelihood of a common source of the cluster, we performed whole-genome sequencing on samples collected during 2006–2014. Most isolates were separated by >60 single-nucleotide polymorphisms, and we found no evidence for recombination or nonneutral mutation accumulation; these findings do not support common source or patient-to-patient transmission. Assembled genomes of most isolates were ≈25 Mbp, and multiple isolates had substantially larger assembled genomes (43–51 Mbp), indicative of infections with strain types that underwent genome expansion. Whole-genome sequencing has become an essential tool for studying epidemiology of fungal infections. Less discriminatory techniques may miss true relationships, possibly resulting in inappropriate attribution of point source.
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- 2020
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17. Influenza associated pulmonary aspergillosis in california: A case series
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John Z. Deng, Karlyn D. Beer, Mitsuru Toda, Brendan Jackson, Tiffany Lin, Marjan Javanbakht, Chrysovalantis Stafylis, Tom Chiller, and Jeffrey D. Klausner
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Aspergillus ,Aspergillosis ,Influenza ,Influenza associated pulmonary aspergillosis ,Infectious and parasitic diseases ,RC109-216 - Abstract
Introduction: Invasive pulmonary aspergillosis has been reported to occur in patients who are critically ill with severe influenza. The mortality rate is high. Methods: We reviewed electronic medical records from University of California at Los Angeles Health Hospitals for patients who had a positive influenza and Aspergillus test from September 1st, 2019 to May 6th, 2020. We classified cases using definitions from the European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG), Aspergillus Intensive Care Unit (AspICU), and Influenza Associated Pulmonary Aspergillosis (IAPA) definition. Results: We identified 8 cases where the patient had both a positive influenza and Aspergillus test. Four (50%) of the 8 patients did not have underlying conditions that were considered typical risk factors for aspergillosis. Seven (87.5%) of the 8 patients were admitted to the intensive care unit and four (50%) of the 8 patients died. One patient met the diagnostic criteria by the EORTC/MSG guidelines, six by the AspICU, and seven by the IAPA definition. Conclusion: We found cases of influenza-associated pulmonary aspergillosis in a Los Angeles hospital population. Typical underlying conditions for aspergillosis were absent in four of the 8 cases. The ability to categorize the cases as influenza associated pulmonary aspergillosis varied. Further research and development of more sensitive guidelines to establish a diagnosis of invasive pulmonary aspergillosis in patients critically ill with influenza may be warranted.
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- 2022
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18. Cost-effectiveness of cryptococcal antigen screening at CD4 counts of 101–200 cells/µL in Botswana [version 2; peer review: 2 approved]
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Ponego Ponatshego, Charles Muthoga, Greg Greene, Mark W. Tenforde, Joseph N. Jarvis, Bruce A. Larson, Madisa Mine, Julia Ngidi, Tom Chiller, and Alexander Jordan
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Cryptococcal antigen ,CrAg ,fluconazole ,pre-emptive treatment ,cryptococcal meningitis ,HIV ,eng ,Medicine ,Science - Abstract
Background: Cryptococcal antigen (CrAg) screening in individuals with advanced HIV reduces cryptococcal meningitis (CM) cases and deaths. The World Health Organization recently recommended increasing screening thresholds from CD4 ≤100 cells/µL to ≤200 cells/µL. CrAg screening at CD4 ≤100 cells/µL is cost-effective; however, the cost-effectiveness of screening patients with CD4 101–200 cells/µL requires evaluation. Methods: Using a decision analytic model with Botswana-specific cost and clinical estimates, we evaluated CrAg screening and treatment among individuals with CD4 counts of 101–200 cells/µL. We estimated the number of CM cases and deaths nationally and treatment costs without screening. For screening we modeled the number of CrAg tests performed, number of CrAg-positive patients identified, proportion started on pre-emptive fluconazole, CM cases and deaths. Screening and treatment costs were estimated and cost per death averted or disability-adjusted life year (DALY) saved compared with no screening. Results: Without screening, we estimated 142 CM cases and 85 deaths annually among individuals with CD4 101–200 cells/µL, with treatment costs of $368,982. With CrAg screening, an estimated 33,036 CrAg tests are performed, and 48 deaths avoided (1,017 DALYs saved). While CrAg screening costs an additional $155,601, overall treatment costs fall by $39,600 (preemptive and hospital-based CM treatment), yielding a net increase of $116,001. Compared to no screening, high coverage of CrAg screening and pre-emptive treatment for CrAg-positive individuals in this population avoids one death for $2440 and $114 per DALY saved. In sensitivity analyses assuming a higher proportion of antiretroviral therapy (ART)-naïve patients (75% versus 15%), cost per death averted was $1472; $69 per DALY saved. Conclusions: CrAg screening for individuals with CD4 101–200 cells/µL was estimated to have a modest impact, involve additional costs, and be less cost-effective than screening populations with CD4 counts ≤100 cells/µL. Additional CrAg screening costs must be considered against other health system priorities.
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- 2021
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19. A global call for talaromycosis to be recognised as a neglected tropical disease
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Shanti Narayanasamy, MBBS, Vu Quoc Dat, MD, Nguyen Tat Thanh, MD, Vo Trieu Ly, MD, Jasper Fuk-Woo Chan, MD, Kwok-Yung Yuen, MD, Chuanyi Ning, MD, Hao Liang, MD, Linghua Li, MD, Anuradha Chowdhary, MD, Sirida Youngchim, PhD, Khuanchai Supparatpinyo, MD, Ne Myo Aung, MD, Josh Hanson, MBBS, Alex Andrianopoulos, PhD, John Dougherty, MD, Nelesh P Govender, ProfMBBCh, David W Denning, ProfFRCP, Tom Chiller, MD, Guy Thwaites, ProfMD, H Rogier van Doorn, ProfMD, John Perfect, ProfMD, and Thuy Le, MD
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Public aspects of medicine ,RA1-1270 - Abstract
Summary: Talaromycosis (penicilliosis) is an invasive mycosis that is endemic in tropical and subtropical Asia. Talaromycosis primarily affects individuals with advanced HIV disease and other immunosuppressive conditions, and the disease disproportionally affects people in low-income and middle-income countries, particularly agricultural workers in rural areas during their most economically productive years. Approximately 17 300 talaromycosis cases and 4900 associated deaths occur annually. Talaromycosis is highly associated with the tropical monsoon season, when flooding and cyclones can exacerbate the poverty-inducing potential of the disease. Talaromycosis can present as localised or disseminated disease, the latter causing cutaneous lesions that are disfiguring and stigmatising. Despite up to a third of diagnosed cases resulting in death, talaromycosis has received little attention and investment from regional and global funders, policy makers, researchers, and industry. Diagnostic and treatment modalities remain extremely insufficient, however control of talaromycosis is feasible with known public health strategies. This Viewpoint is a global call for talaromycosis to be recognised as a neglected tropical disease to alleviate its impact on susceptible populations.
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- 2021
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20. Skin Metagenomic Sequence Analysis of Early Candida auris Outbreaks in U.S. Nursing Homes
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Xin Huang, Rory M. Welsh, Clay Deming, Diana M. Proctor, Pamela J. Thomas, Gabrielle M. Gussin, Susan S. Huang, Heidi H. Kong, Meghan L. Bentz, Snigdha Vallabhaneni, Tom Chiller, Brendan R. Jackson, Kaitlin Forsberg, Sean Conlan, Anastasia P. Litvintseva, and Julia A. Segre
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Microbiology ,QR1-502 - Abstract
Candida aurisCandida auris
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- 2021
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21. Update on the Epidemiology, Diagnosis, and Treatment of Coccidioidomycosis
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Samantha L. Williams and Tom Chiller
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coccidioidomycosis ,Coccidioides ,Valley fever ,endemic mycoses ,fungal diseases ,Biology (General) ,QH301-705.5 - Abstract
Coccidioidomycosis is a fungal infection caused by Coccidioides immitis and Coccidioides posadasii. The dimorphic fungi live in the soils of arid and semi-arid regions of the western United States, as well as parts of Mexico, Central America, and South America. Incidence of disease has risen consistently in recent years, and the geographic distribution of Coccidioides spp. appears to be expanding beyond previously known areas of endemicity. Climate factors are predicted to further extend the range of environments suitable for the growth and dispersal of Coccidioides species. Most infections are asymptomatic, though a small proportion result in severe or life-threatening forms of disease. Primary pulmonary coccidioidomycosis is commonly mistaken for community-acquired pneumonia, often leading to inappropriate antibacterial treatment and unnecessary healthcare costs. Diagnosis of coccidioidomycosis is challenging and often relies on clinician suspicion to pursue laboratory testing. Advancements in diagnostic tools and antifungal therapy developments seek to improve the early detection and effective management of infection. This review will highlight recent updates and summarize the current understanding of the epidemiology, diagnosis, and treatment of coccidioidomycosis.
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- 2022
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22. Worsening Spread of Candida auris in the United States, 2019 to 2021
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Meghan Lyman, Kaitlin Forsberg, D. Joseph Sexton, Nancy A. Chow, Shawn R. Lockhart, Brendan R. Jackson, and Tom Chiller
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Internal Medicine ,General Medicine - Published
- 2023
23. Prevalence of cryptococcal antigen (CrAg) among HIV-positive patients in Eswatini, 2014–2015
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Samson M. Haumba, Mitsuru Toda, Rossana Jeffries, Peter Ehrenkranz, Munyaradzi Pasipamire, Trong Ao, Nomthandazo Lukhele, Sikhathele Mazibuko, Mandzisi Mkhontfo, Rachel M. Smith, and Tom Chiller
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cryptococcal antigenaemia screening ,prevalence ,people living with hiv ,cryptococcal meningitis ,advanced hiv disease package ,eswatini ,Public aspects of medicine ,RA1-1270 ,Medicine (General) ,R5-920 - Abstract
Background: Cryptococcal meningitis is a leading cause of death amongst people living with HIV. However, routine cryptococcal antigen (CrAg) screening was not in the national guidelines in Eswatini. Objectives: A cross-sectional study was conducted between August 2014 and March 2015 to examine CrAg prevalence at Mbabane Government Hospital in Eswatini. Methods: We collected urine and whole blood from antiretroviral-therapy-naïve patients with HIV and a cluster of differentiation 4 (CD4) counts 200 cells/mm3 for plasma and urine CrAg lateral flow assay (LFA) screening at the national HIV reference laboratory. Two CD4 cut-off points were used to estimate CrAg prevalence: CD4 100 and 200 cells/mm3. Sensitivity and specificity of urine CrAg LFA was compared to plasma CrAg LFA. Results: Plasma CrAg prevalence was 4% (8/182, 95% confidence interval [CI]: 2–8) amongst patients with CD4 counts of 200 cells/mm3, and 8% (8/102, 95% CI: 3–15) amongst patients with CD4 counts of 100 cells/mm3. Urine CrAg LFA had a sensitivity of 100% (95% CI: 59–100) and a specificity of 80% (95% CI: 72–86) compared with plasma CrAg LFA tests for patients with CD4 200 cells/mm3. Forty-three per cent of 99 patients with CD4 100 were at World Health Organization clinical stages I or II. Conclusion: The prevalence of CrAg in Eswatini was higher than the current global estimate of 6% amongst HIV-positive people with CD4 100 cell/mm3, indicating the importance of initiating a national screening programme. Mechanisms for CrAg testing, training, reporting, and drug and commodity supply issues are important considerations before national implementation.
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- 2020
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24. Cost-effectiveness of reflex laboratory-based cryptococcal antigen screening for the prevention and treatment of cryptococcal meningitis in Botswana [version 2; peer review: 2 approved]
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Mark W. Tenforde, Charles Muthoga, Andrew Callaghan, Ponego Ponatshego, Julia Ngidi, Madisa Mine, Alexander Jordan, Tom Chiller, Bruce A. Larson, and Joseph N. Jarvis
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Medicine ,Science - Abstract
Background: Cryptococcal antigen (CrAg) screening for antiretroviral therapy (ART)-naïve adults with advanced HIV/AIDS can reduce the incidence of cryptococcal meningitis (CM) and all-cause mortality. We modeled the cost-effectiveness of laboratory-based “reflex” CrAg screening for ART-naïve CrAg-positive patients with CD4
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- 2020
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25. Tackling cryptococcal meningitis in Nigeria, one-step at a time; the impact of training.
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Rita O Oladele, Alexander Jordan, Patrick Akande, Sulaimon A Akanmu, Iorhen E Akase, Sani Aliyu, David W Denning, and Tom Chiller
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Medicine ,Science - Abstract
BACKGROUND:Nigeria is estimated to have 25,000 cases of cryptococcal antigenemia (CrAg) annually. CrAg screening with pre-emptive fluconazole treatment is recommended but not yet implemented in Nigeria. Trainings were conducted to improve health-care provider (HCP) awareness and clinical skills in the management and prevention of cryptococcal meningitis (CM). METHODS:HCPs providing care for people living with HIV were targeted for training at 13 sites from April to November 2018 Course content was adapted from CDC Cryptococcal Screening Program Training Manual and LIFE-website. "Hands-on" training on CrAg testing and lumbar puncture was included. A 14-point pre and post-test assessment instrument was designed to capture the impact of the training and focus group discussions (FGDs) were conducted. RESULTS:A total of 761 HCPs were trained. 519 HCPs completed the pre-test evaluation while 470 (90.6%) took part in the post-test evaluation. Post-training, HCPs were significantly more likely to respond correctly to all 14 assessment items, with the mean percentage score rising to 91.0% from a pre-training value of 60.0%. FGDs revealed that many of the HCPs were not aware of the CrAg screening and pre-emptive treatment recommendations in Nigerian guidelines, and reported not having seen or managed a case of CM. Also, they highlighted challenges with routine CrAg screening due to a lack of access to CD4 testing, CrAg test kits, antifungal drugs, as well as the need for similar trainings across all tiers of care in Nigeria. CONCLUSION:Training significantly improved HCPs' understanding of Nigerian policy on CrAg screening, CM diagnosis and best management practices. This training could be included in routine capacity building efforts for HCPs involved in HIV care in Nigeria.
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- 2020
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26. Southern African HIV Clinicians Society guideline for the prevention, diagnosis and management of cryptococcal disease among HIV-infected persons: 2019 update
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Nelesh P. Govender, Graeme Meintjes, Phetho Mangena, Jeremy Nel, Samantha Potgieter, Denasha Reddy, Helena Rabie, Douglas Wilson, John Black, David Boulware, Tom Boyles, Tom Chiller, Halima Dawood, Sipho Dlamini, Thomas S. Harrison, Prudence Ive, Joseph Jarvis, Alan Karstaedt, Matamela C. Madua, Colin Menezes, Mahomed-Yunus S. Moosa, Zaaheera Motlekar, Amir Shroufi, Sarah L. Stacey, Merika Tsitsi, Gilles van Cutsem, Ebrahim Variava, Michelle Venter, and Rachel Wake
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Public aspects of medicine ,RA1-1270 ,Infectious and parasitic diseases ,RC109-216 - Abstract
No abstract available.
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- 2019
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27. The important role of co-infections in patients with AIDS and progressive disseminated histoplasmosis (PDH): A cohort from Colombia
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Diego H. Caceres, Ángela M. Tobón, Ángela Restrepo, Tom Chiller, and Beatriz L. Gómez
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AIDS ,Histoplasmosis ,Histoplasma ,Co-infection ,Medicine (General) ,R5-920 ,Biology (General) ,QH301-705.5 - Abstract
A total of 23/45 (51%) patients with AIDS and histoplasmosis from Medellín, Colombia had other infections. Tuberculosis was the most common (n = 16/23, 70%). Pneumocystosis and cryptococcosis were found in three patients each (13%), bacterial infection and cytomegalovirus occurred each in two patients (9%) while toxoplasmosis, herpes virus and esophageal candidiasis were recorded in one patient each (4%). Of all co-infected patients, 18/23 (78%) had one, four (17%) had two and one (4%) had three additional opportunistic infections.
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- 2018
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28. Emerging Fungal Infections: from the Fields to the Clinic, Resistant Aspergillus fumigatus and Dermatophyte Species: a One Health Perspective on an Urgent Public Health Problem
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Antonia Langfeldt, Jeremy A. W. Gold, and Tom Chiller
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Microbiology (medical) ,Infectious Diseases - Published
- 2022
29. Current situation of endemic mycosis in the Americas and the Caribbean: Proceedings of the first international meeting on endemic mycoses of the Americas ( <scp>IMEMA</scp> )
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Diego H. Caceres, Laura C. Echeverri Tirado, Alexandro Bonifaz, Antoine Adenis, Beatriz L. Gomez, Claudia Lizette Banda Flores, Cristina E. Canteros, Daniel Wagner Santos, Eduardo Arathoon, Elia Ramirez Soto, Flavio Queiroz‐Telles, Ilan S. Schwartz, Jeannete Zurita, Lisandra Serra Damasceno, Nataly Garcia, Norma B. Fernandez, Omayra Chincha, Patricia Araujo, Ricardo Rabagliati, Tom Chiller, and Gustavo Giusiano
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Antifungal Agents ,Histoplasma ,Dermatology ,General Medicine ,blastomyces ,paracoccidioides ,coccidioides ,histoplasma ,Infectious Diseases ,Mycoses ,Humans ,Itraconazole ,Americas ,Histoplasmosis - Abstract
Background The Americas are home to biologically and clinically diverse endemic fungi, including Blastomyces, Coccidioides, Emergomyces, Histoplasma, Paracoccidioides and Sporothrix. In endemic areas with high risk of infection, these fungal pathogens represent an important public health problem. Objectives This report aims to summarise the main findings of the regional analysis carried out on the status of the endemic mycoses of the Americas, done at the first International Meeting on Endemic Mycoses of the Americas (IMEMA). Methods A regional analysis for the Americas was done, the 27 territories were grouped into nine regions. A SWOT analysis was done. Results All territories reported availability of microscopy. Seventy percent of territories reported antibody testing, 67% of territories reported availability of Histoplasma antigen testing. None of the territories reported the use of (1-3)-beta-d-glucan. Fifty two percent of territories reported the availability of PCR testing in reference centres (mostly for histoplasmosis). Most of the territories reported access to medications such as trimethoprim-sulfamethoxazole, itraconazole, voriconazole and amphotericin B (AMB) deoxycholate. Many countries had limited access to liposomal formulation of AMB and newer azoles, such as posaconazole and isavuconazole. Surveillance of these fungal diseases was minimal. Conclusions A consensus emerged among meeting participants, this group concluded that endemic mycoses are neglected diseases, and due to their severity and lack of resources, the improvement of diagnosis, treatment and surveillance is needed.
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- 2022
30. Validation and Concordance Analysis of a New Lateral Flow Assay for Detection of Histoplasma Antigen in Urine
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Diego H. Cáceres, Beatriz L. Gómez, Ángela M. Tobón, Melissa Minderman, Nicole Bridges, Tom Chiller, and Mark D. Lindsley
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histoplasmosis ,Histoplasma ,antigen ,HIV ,AIDS ,Biology (General) ,QH301-705.5 - Abstract
Histoplasmosis is a major cause of mortality in people living with HIV (PLHIV). Rapid methods to diagnose Histoplasma capsulatum disease could dramatically decrease the time to initiate treatment, resulting in reduced mortality. The aim of this study was to validate a MiraVista® Diagnostics (MVD) Histoplasma urine antigen lateral flow assay (MVD LFA) for the detection of H. capsulatum antigen (Ag) in urine and compare this LFA against the MVista® Histoplasma Ag quantitative enzyme immunoassays (MVD EIA). We assessed the MVD LFA using a standardized reference panel of urine specimens from Colombia. We tested 100 urine specimens, 26 from PLHIV diagnosed with histoplasmosis, 42 from PLHIV with other infectious diseases, and 32 from non-HIV infected persons without histoplasmosis. Sensitivity and specificity of the MVD LFA was 96%, compared with 96% sensitivity and 77% specificity of the MVD EIA. Concordance analysis between MVD LFA and the MVD EIA displayed an 84% agreement, and a Kappa of 0.656. The MVD LFA evaluated in this study has several advantages, including a turnaround time for results of approximately 40 min, no need for complex laboratory infrastructure or highly trained laboratory personnel, use of urine specimens, and ease of performing.
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- 2021
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31. Single High-dose of Liposomal Amphotericin B in HIV/AIDS-related Disseminated Histoplasmosis: a Randomized Trial
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Alessandro C Pasqualotto, Daiane Dalla Lana, Cassia S M Godoy, Terezinha do Menino Jesus Silva Leitão, Monica B Bay, Lisandra Serra Damasceno, Renata B A Soares, Roger Kist, Larissa R Silva, Denusa Wiltgen, Marineide Melo, Taiguara F Guimarães, Marilia R Guimarães, Hareton T Vechi, Jacó R L de Mesquita, Gloria Regina de G Monteiro, Antoine Adenis, Nathan C Bahr, Andrej Spec, David R Boulware, Dennis Israelski, Tom Chiller, and Diego R Falci
- Subjects
Microbiology (medical) ,Infectious Diseases - Abstract
Background Histoplasmosis is a major AIDS-defining illness in Latin America. Liposomal amphotericin B (L-AmB) is the drug of choice for treatment, but access is restricted due to the high drug and hospitalization costs of the conventional long regimens. Methods Prospective randomized multicenter open-label trial of one or two-dose induction therapy with L-AmB versus control for disseminated histoplasmosis in AIDS, followed by oral itraconazole therapy. We randomized subjects to: (i) Single dose 10 mg/kg of L-AmB; (ii) 10 mg/kg of L-AmB on D1, and 5 mg/kg of L-AmB on D3; (iii) 3 mg/kg of L-AmB daily for 2 weeks (control). The primary outcome was clinical response (resolution of fever and signs/symptoms attributable to histoplasmosis) at day 14. Results A total of 118 subjects were randomizedMedian CD4+ counts and clinical presentations were similar between arms. Infusion-related toxicity, kidney toxicity at multiple time-points and frequency of anemia, hypokalemia, hypomagnesemia, and liver toxicity were similar. Day 14 clinical response was 84% for Single-dose L-AmB, 69% Two-dose L-AmB, and 74% Control arm (p=0.69). Overall survival on D14 was 89.0% (34/38) for Single-dose L-AmB, 78.0% (29/37) for Two-dose L-AmB, and 92.1% (35/38) for Control arm (p=0.82). Conclusions One day induction therapy with 10 mg/kg of L-AmB in AIDS-related histoplasmosis was safe. Although clinical response may be non-inferior to standard L-AmB therapy, a confirmatory phase III clinical trial is needed. A single induction dose would markedly reduce drug-acquisition costs (>4-fold) and markedly shorten and simplify treatment, which are key points in terms of increased access.
- Published
- 2023
32. Cost-effectiveness of reflex laboratory-based cryptococcal antigen screening for the prevention and treatment of cryptococcal meningitis in Botswana [version 1; peer review: 2 approved]
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Mark W. Tenforde, Charles Muthoga, Andrew Callaghan, Ponego Ponetshego, Julia Ngidi, Madisa Mine, Alexander Jordan, Tom Chiller, Bruce A. Larson, and Joseph N. Jarvis
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Medicine ,Science - Abstract
Background: Cryptococcal antigen (CrAg) screening for antiretroviral therapy (ART)-naïve adults with advanced HIV/AIDS can reduce the incidence of cryptococcal meningitis (CM) and all-cause mortality. We modeled the cost-effectiveness of laboratory-based “reflex” CrAg screening for ART-naïve CrAg-positive patients with CD4
- Published
- 2019
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33. The NDV-3A vaccine protects mice from multidrug resistant Candida auris infection.
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Shakti Singh, Priya Uppuluri, Zeinab Mamouei, Abdullah Alqarihi, Hana Elhassan, Samuel French, Shawn R Lockhart, Tom Chiller, John E Edwards, and Ashraf S Ibrahim
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Immunologic diseases. Allergy ,RC581-607 ,Biology (General) ,QH301-705.5 - Abstract
Candida auris is an emerging, multi-drug resistant, health care-associated fungal pathogen. Its predominant prevalence in hospitals and nursing homes indicates its ability to adhere to and colonize the skin, or persist in an environment outside the host-a trait unique from other Candida species. Besides being associated globally with life-threatening disseminated infections, C. auris also poses significant clinical challenges due to its ability to adhere to polymeric surfaces and form highly drug-resistant biofilms. Here, we performed bioinformatic studies to identify the presence of adhesin proteins in C. auris, with sequence as well as 3-D structural homologies to the major adhesin/invasin of C. albicans, Als3. Anti-Als3p antibodies generated by vaccinating mice with NDV-3A (a vaccine based on the N-terminus of Als3 protein formulated with alum) recognized C. auris in vitro, blocked its ability to form biofilms and enhanced macrophage-mediated killing of the fungus. Furthermore, NDV-3A vaccination induced significant levels of C. auris cross-reactive humoral and cellular immune responses, and protected immunosuppressed mice from lethal C. auris disseminated infection, compared to the control alum-vaccinated mice. The mechanism of protection is attributed to anti-Als3p antibodies and CD4+ T helper cells activating tissue macrophages. Finally, NDV-3A potentiated the protective efficacy of the antifungal drug micafungin, against C. auris candidemia. Identification of Als3-like adhesins in C. auris makes it a target for immunotherapeutic strategies using NDV-3A, a vaccine with known efficacy against other Candida species and safety as well as efficacy in clinical trials. Considering that C. auris can be resistant to almost all classes of antifungal drugs, such an approach has profound clinical relevance.
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- 2019
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34. Food and Drug Administration Public Workshop Summary—Development Considerations of Antifungal Drugs to Address Unmet Medical Need
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Yuliya Yasinskaya, Shukal Bala, Ursula Waack, Cheryl Dixon, Karen Higgins, Jason N Moore, Caroline J Jjingo, Elizabeth O'Shaughnessy, Philip Colangelo, Radu Botgros, Sumathi Nambiar, David Angulo, Aaron Dane, Tom Chiller, Michael R Hodges, Taylor Sandison, William Hope, Thomas J Walsh, Peter Pappas, Aspasia Katragkou, Laura Kovanda, John H Rex, Kieren A Marr, Luis Ostrosky-Zeichner, Shohko Sekine, Monika Deshpande, Sunita J Shukla, and John Farley
- Subjects
Microbiology (medical) ,Infectious Diseases - Abstract
Pressing challenges in the treatment of invasive fungal infections (IFIs) include emerging and rare pathogens, resistant/refractory infections, and antifungal armamentarium limited by toxicity, drug-drug interactions, and lack of oral formulations. Development of new antifungal drugs is hampered by the limitations of the available diagnostics, clinical trial endpoints, prolonged trial duration, difficulties in patient recruitment, including subpopulations (eg, pediatrics), and heterogeneity of the IFIs. On 4 August 2020, the US Food and Drug Administration convened a workshop that included IFI experts from academia, industry, and other government agencies to discuss the IFI landscape, unmet need, and potential strategies to facilitate the development of antifungal drugs for treatment and prophylaxis. This article summarizes the key topics presented and discussed during the workshop, such as incentives and research support for drug developers, nonclinical development, clinical trial design challenges, lessons learned from industry, and potential collaborations to facilitate antifungal drug development.
- Published
- 2023
35. Summary of Guidelines for Managing Histoplasmosis among People Living with HIV
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Freddy Perez, Diego H. Caceres, Nathan Ford, Giovanni Ravasi, Beatriz L. Gomez, Alessandro C. Pasqualotto, Paul Hine, Antoine A. Adenis, Mathieu Nacher, Tom Chiller, John Baddley, and for the Guideline Development Group for diagnosing and managing disseminated histoplasmosis among people living with HIV
- Subjects
advanced HIV disease ,diagnosis ,histoplasmosis ,Histoplasma ,guidelines ,World Health Organization (WHO) ,Biology (General) ,QH301-705.5 - Abstract
Histoplasmosis is a frequent fungal opportunistic infection in people living with HIV (PLHIV), associated every year to a total of 5% to 15% of AIDS-related deaths among this population. In 2020, the first global guidelines for diagnosing and managing disseminated histoplasmosis among PLHIV was published. This document recommends (1) detection of circulating Histoplasma antigens as the recommended laboratory assay to diagnose histoplasmosis among PLHIV; (2) the use of liposomal amphotericin for induction therapy in severe or moderately severe disease, followed by a maintenance therapy with itraconazole for 12 months; a shorter maintenance therapy could be considered if the patient is clinically stable and if immune status has improved; (3) antiretroviral therapy initiation as soon as possible among patients with histoplasmosis without involvement of central nervous system; and (4) that for the treatment of co-infection with histoplasmosis and tuberculosis (TB), treatment of TB should be initiated according to the World Health Organization treatment guidelines. Appropriate health education of providers, supportive supervision, and policy guidance for the care of PLHIV are required.
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- 2021
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36. Notes from the Field: First Reported U.S. Cases of Tinea Caused by Trichophyton indotineae — New York City, December 2021–March 2023
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Avrom S. Caplan, Sudha Chaturvedi, YanChun Zhu, Gabrielle C. Todd, Lu Yin, Adriana Lopez, Lisa Travis, Dallas J. Smith, Tom Chiller, Shawn R. Lockhart, Karen A. Alroy, William G. Greendyke, and Jeremy A. W. Gold
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Health (social science) ,Health Information Management ,Epidemiology ,Health, Toxicology and Mutagenesis ,General Medicine - Published
- 2023
37. Validation of a Lateral Flow Assay for Rapid Diagnosis of Histoplasmosis in Advanced HIV Disease, Buenos Aires, Argentina
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Mariana Andreani, Claudia E. Frola, Diego H. Caceres, Cristina E. Canteros, María J. Rolón, Tom Chiller, and Liliana Guelfand
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General Earth and Planetary Sciences ,histoplasmosis ,HIV ,rapid diagnosis ,lateral flow assay ,General Environmental Science - Abstract
Histoplasmosis is a major cause of mortality in individuals with advanced human immunodeficiency virus (HIV) disease (AHD). We evaluated in patients with AHD a lateral flow assay (LFA) developed by MiraVista® Diagnostics (MVD LFA). Histoplasmosis was defined based on the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) case definitions. We also compared the results of this LFA with those obtained using a commercial enzyme immunoassay (EIA) developed by IMMY, Clarus Histoplasma GM EIA, IMMY (HGM EIA). A retrospective observational study was conducted at Hospital Juan A. Fernández, located in Buenos Aires, Argentina. The study included 48 urine specimens from patients aged >18 years with AHD. Urine specimens included 17 patients with disseminated histoplasmosis and 31 specimens from patients without evidence of histoplasmosis. Specimens were tested using the MVD LFA and the HGM EIA. The MVD LFA and the HGM EIA had similar analytical performance, with a sensitivity of 94%, specificity of 100%, positive predictive value of 100%, negative predictive value of 97%, and an accuracy of 98%. Comparison of the MVD LFA with the HGM EIA demonstrated a Kappa agreement index of 0.906. The LFA evaluated in this study had high analytical performance; it provided rapid diagnosis of histoplasmosis with minimal requirements for laboratory training, equipment, and laboratory infrastructure.
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- 2022
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38. Dating the Cryptococcus gattii Dispersal to the North American Pacific Northwest
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Chandler C. Roe, Jolene Bowers, Hanna Oltean, Emilio DeBess, Philippe J. Dufresne, Scott McBurney, David P. Overy, Bodo Wanke, Colleen Lysen, Tom Chiller, Wieland Meyer, George R. Thompson, Shawn R. Lockhart, Crystal M. Hepp, and David M. Engelthaler
- Subjects
Cryptococcus ,genomics ,molecular epidemiology ,mycology ,Microbiology ,QR1-502 - Abstract
ABSTRACT The emergence of Cryptococcus gattii, previously regarded as a predominantly tropical pathogen, in the temperate climate of the North American Pacific Northwest (PNW) in 1999 prompted several questions. The most prevalent among these was the timing of the introduction of this pathogen to this novel environment. Here, we infer tip-dated timing estimates for the three clonal C. gattii populations observed in the PNW, VGIIa, VGIIb, and VGIIc, based on whole-genome sequencing of 134 C. gattii isolates and using Bayesian evolutionary analysis by sampling trees (BEAST). We estimated the nucleotide substitution rate for each lineage (1.59 × 10−8, 1.59 × 10−8, and 2.70 × 10−8, respectively) to be an order of magnitude higher than common neutral fungal mutation rates (2.0 × 10−9), indicating a microevolutionary rate (e.g., successive clonal generations in a laboratory) in comparison to a species’ slower, macroevolutionary rate (e.g., when using fossil records). The clonal nature of the PNW C. gattii emergence over a narrow number of years would therefore possibly explain our higher mutation rates. Our results suggest that the mean time to most recent common ancestor for all three sublineages occurred within the last 60 to 100 years. While the cause of C. gattii dispersal to the PNW is still unclear, our research estimates that the arrival is neither ancient nor very recent (i.e.,
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- 2018
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39. Evaluation of a Cryptococcal antigen Lateral Flow Assay in serum and cerebrospinal fluid for rapid diagnosis of cryptococcosis in Colombia
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Diego H. Cáceres, Alejandra Zuluaga, Ángela M. Tabares, Tom Chiller, Ángel González, and Beatriz L. Gómez
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Cryptococcosis ,Cryptococcus ,Antigen ,Diagnosis ,Point-of-care ,Lateral Flow Assay ,Immunochromatographic assay ,Latex agglutination system ,Arctic medicine. Tropical medicine ,RC955-962 ,Infectious and parasitic diseases ,RC109-216 - Abstract
ABSTRACT A Lateral Flow Assay to detect cryptococcal antigen (CrAg® LFA) in serum and cerebrospinal fluid for the rapid diagnosis of cryptococcosis was evaluated. A retrospective validation was performed. Sensitivity and specificity of the CrAg® LFA was 100%. High concordance (kappa index=1.0) between Cryptococcal Antigen Latex Agglutination System (CALAS®) and CrAg® LFA was observed. CrAg® LFA showed higher analytical sensitivity for detecting low concentrations of cryptococcal antigen.
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- 2017
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40. Diagnosis of fungal opportunistic infections in people living with HIV from Guatemala and El Salvador
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Tom Chiller, Jose Rodas, Diego H. Caceres, Eduardo Arathoon, Carlos Mejía, Remei Gordillo, Angela A. Cleveland, Blanca Samayoa, Rolando A. Cedillos, Diana Forno, and Narda Medina
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medicine.medical_specialty ,Tuberculosis ,cryptococcosis ,diagnosis ,Human immunodeficiency virus (HIV) ,HIV Infections ,Dermatology ,medicine.disease_cause ,Article ,Histoplasmosis ,Internal medicine ,El Salvador ,medicine ,Humans ,Cd4 cell count ,rapid tests ,AIDS-Related Opportunistic Infections ,histoplasmosis ,business.industry ,Public health ,HIV ,General Medicine ,opportunistic infections ,Guatemala ,medicine.disease ,Antiretroviral therapy ,CD4 Lymphocyte Count ,Cross-Sectional Studies ,Infectious Diseases ,Cryptococcosis ,business ,Hiv disease - Abstract
OBJECTIVES Histoplasmosis and cryptococcosis are important public health problems in people living with HIV (PLHIV) in Central America. Conventional laboratory tests, such as culture and microscopy, are not optimal; however, antigen (Ag) tests are rapid, highly sensitive, and specific for diagnosis of fungal opportunistic infections (OI). The aim of this study was to describe the results of a laboratory-based surveillance system for histoplasmosis and cryptococcosis. METHODS An observational cross-sectional study based on laboratory surveillance, was carried out in two hospitals in Guatemala and one hospital in El Salvador, between July 2012 and December 2014. Diagnosis of histoplasmosis and cryptococcosis in PLHIV were performed by culture and Ag test. RESULTS A total of 160 PLHIV were diagnosed with fungal OI, of which, 96 (60%) were diagnosed with histoplasmosis, 62 (39%) were with cryptococcosis, and two patients (1%) were diagnosed with both fungal diseases. Of the 160 patients analysed in this study, 94 (59%) were diagnosed using only an Ag assay. CD4 cell count data were available for 136 (85%) patients; 127 (93%) patients had a CD4 count
- Published
- 2021
41. P258 Incidence of Histoplasmosis, Cryptococcosis, and TB Among People Living with HIV in Paraguay-Preliminary Report
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Tania Samudio, Gloria Aguilar, Omar Sued, Gladys López, Alexander Jordan, Diego H. Cáceres, Patricia Ovelar, Miguel Cardozo, Cristina Vicenti, Virgilio Lezcano, José Pereira, Carlos Rios-Gonzalez, Sergio Munoz, Juan Figueredo, Aurelia Taboada, Tom Chiller, and Gustavo Benítez
- Subjects
Infectious Diseases ,General Medicine - Abstract
Poster session 2, September 22, 2022, 12:30 PM - 1:30 PM Objectives Endemic fungal infections such as Histoplasmosis and Cryptococcosis as well as tuberculosis (TB) are important causes of mortality among people living with HIV (PLHIV) in Latin America. Rapid diagnostic assays (RDAs) could decrease the time to diagnosis and treatment of these infections, resulting in a reduction in mortality. The objectives of this study were to determine the incidence of Histoplasmosis, Cryptococcosis, and TB using RDAs in PLHIV with advanced HIV disease (AHD) and calculate 30-day mortality. Methods PLHIV 18 years and older, treated at the Institute of Tropical Medicine hospital in Asuncion, Paraguay, not receiving ART and presenting CD4 count ≤ 200 cells/μL or clinical symptoms suggestive of WHO stage 3 or 4 diseases were enrolled and followed for 30 days. Detection of Histoplasma Ag (HisAg) in urine was performed by enzyme immunoassay (EIA), Cryptococcus Ag (CrAg) detection in serum and cerebrospinal fluid specimens by lateral flow assay (LFA), and liparabinomannan (LAM) detection in urine by LFA (TB LAM) (limited to those patients with CD4 counts ≤ 100 cells/μL) and by GeneXpert (limited to patients with respiratory symptoms). Results From August 2021 to 25 March 2022, a total of 335 PLHIV were enrolled. Patient median age was 37 years [Interquartile Range (IQR) 16 years], median CD4 count at enrollment was 91 cells/μL (IQR 147 cell/μL). A total of 80% (n = 269) of patients were symptomatic for one or more of the three diseases being screened for. Ag positivity rate was 20% (40/196) for TB-LAM, 10% (32/314) for HisAg, and 11% (35/329) for CrAg (15 diagnosed with cryptococcal meningitis). GeneXpert testing showed a positivity of 14% (15/108), and six of these patients with positive GeneXpert also tested positive for TB-LAM. In total, 100/335 (30%) of patients tested had a positive result and coinfections were observed among 14/335 (4.2%) patients (Table 1). Histoplasmosis + TB was the most frequent co-infection observed 12/335 (3.6%). Mortality among those who completed 30-day follow-up was 12.6% (32/254) and 11% among those with an OI (11/102) Conclusions Preliminary results show that TB and fungal opportunistic infections, including co-infection were common in people with advanced HIV. Longitudinal follow-up will help to evaluate the feasibility and cost of implementing RDAs for the early detection of opportunistic infections in PLHIV with AHD in Paraguay. Early diagnosis could impact mortality reduction.
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- 2022
42. S5.5a Standing up FungiNet: Genomic epidemiology and surveillance of fungal diseases
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Nancy Chow, Lindsay Parnell, Patricia Escandon, Nelesh Govender, and Tom Chiller
- Subjects
Infectious Diseases ,General Medicine - Abstract
S5.5 Genomic Epidemiology of Fungal Infections, September 22, 2022, 3:00 PM - 4:30 PM Objectives With the advent of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing, the public health landscape for genomic epidemiology and surveillance has transformed for a variety of pathogens. For fungal diseases, the U.S. Centers for Disease Control and Prevention (CDC) is working with global partners to stand up FungiNet, a network that aims to equip scientists with laboratory, bioinformatics, and informatics resources to harness genomic data. FungiNet partners will use genomic and epidemiologic data to detect outbreaks, identify introductions, and characterize transmission of fungal infections. In 2022, FungiNet aims to onboard nine state and local health departments in the United States and two global partners, the Instituto Nacional de Salud in Colombia and the National Institute for Communicable Diseases in South Africa, with a focus on Candida auris. Methods To streamline the onboarding process, CDC generated standardized operating procedures (SOPs) specific to C. auris. For DNA extraction, SOPs were created for workflows using the Zymo Research Quick-DNA™ (ZR) Fungal/Bacterial Miniprep, Qiagen Dneasy Blood and Tissue, and Epicentre (Illumina) MasterPure Yeast DNA Purification kits. For library preparation and Illumina sequencing, PulseNet methods used for foodborne pathogens were validated for C. auris. For NCBI data submissions, required data elements were defined. For SNP and phylogenetic analyses, the bioinformatics workflow MycoSNP was adapted to use Nextflow software and the Terra platform. For visualization with epidemiologic data, guidance documents and tutorials for Microreact were created. Finally, for data reporting, processes are being designed in REDCap and in laboratory information management systems to rapidly share genomic-related data. Results To date, 11 partners have committed to building capacity for C. auris genomic sequencing and analysis as a FungiNet partner. Of these, seven have validated methods for DNA extraction, and nine have generated high-quality sequencing data. Only one partner has installed and locally run MycoSNP, and none have submitted raw sequence data to NCBI. Conclusions Currently, 11 FungiNet partners are working to onboard C. auris genomic sequencing and bioinformatics analysis in 2022. This process is complex, requiring several laboratories, bioinformatics, and informatics workflows. For many partners, bioinformatics analysis and NCBI submission are the most challenging activities with the installation of MycoSNP and the ability to batch upload data to NCBI as the main barriers. Next steps will focus on the validation of informatics methods to link genomic and epidemiologic data.
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- 2022
43. S10.2d Fungal beta-glucans and mannan performances in HIV-associated histoplasmosis
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Aurore Moussiegt, Sigrid Mac Donald, Marie-Elisabeth Bougnoux, Marja van Eer, Stephen Vreden, Tom Chiller, Mathieu Nacher, Olivier Lortholary, and Antoine Adenis
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Infectious Diseases ,General Medicine - Abstract
S10.2 Fungal Infections in Transplant Patients, September 24, 2022, 10:30 AM - 12:00 PM Objectives Diagnosis of histoplasmosis in people living with HIV (PLWHIV) remains challenging despite developments in Histoplasma antigen and molecular detection tools. Fungal markers such as Beta-(1,3)-D-glucan (BDG) and galactomannan Aspergillus antigen (GM) are widely available, but the experience is limited during PLWHIV workup for suspicion of histoplasmosis. Our objective was to evaluate and compare BDG and GM performances for the diagnosis of HIV-associated histoplasmosis. Methods We performed a diagnostic accuracy study using primary serum samples stored frozen in a certified biorepository (CRB Amazonie-DC-2021-4649). Samples consisted of consecutive hospitalized PLWHIV unexposed to oral antifungals during the previous month (EDIRAPHIS study-NCT01884779). All patients gave consent for biobanking and ancillary studies on fungal markers. Histoplasmosis cases, proven (EORTC/MSG criteria) and probable (polyclonal or monoclonal Histoplasma antigen detections in urines or serum), as well as negative controls, were randomly selected. Patients with a proven or suspected Pneumocystis jirovecii infection were excluded. Following manufacturers’ instructions, samples were blindly tested for BDG and GM using Fungitell® and PlateliaTM Aspergillus Ag assays, respectively. Gold standard definition used three scenarios: EORTC scenario (cases and controls defined according to the EORTC/MSG 2020 criteria for endemic mycoses); strict scenario with proven cases restricted to those positives to all three previous Histoplasma antigen detections, and controls conversely negatives for all methods; and a large scenario with proven or probable cases and controls negatives for all methods. Results We included 121 samples, 92 HIV-associated histoplasmosis cases (34 proven and 58 probable), and 29 negative controls. Compared with controls, histoplasmosis cases were significantly younger and advanced in the course of HIV disease [median CD4 count level 33/mm3 (15-87) vs 116 (62-245)]. BDG and GM median detection levels were significantly higher among histoplasmosis cases compared with controls across all scenarios [368 (176-441) pg/ml vs 142 (89-211) for BDG and 2.5 (1.3-4.8) vs 0.19 (0.14-0.36) for GM, in cases vs controls of the strict scenario, respectively]. In the strict scenario, at 150 pg/ml and 0.5 for BDG and GM respectively, sensitivity, specificity, positive and negative likelihood ratios were respectively: 95% [95%confidence interval (CI), 85-100] vs 90% [77-100], 52% [34-70] vs 83% [69-97], 2 [1.4-3.0] vs 5.3 [2.4-12.0], and 0.1 [0.01-0.7] vs 0.12 [0.03-0.45]. ROC curves found AUCs of 0.82 [0.68-0.91] vs 0.92 [0.80-0.98], and optimal thresholds at 288 pg/ml and 1.29, for BDG and GM, respectively (Fig. 1). Post-test probabilities showed best performances at the lowest thresholds for negative testing of both BDG and GM, and at the 0.7 thresholds for a positive GM test (Fig. 2). Conclusion BDG and GM may not be used for the same objective when searching for HIV-associated histoplasmosis. Although a negative BDG test at the lowest thresholds should rule out histoplasmosis in a screening context, limitations of a positive BDG test, even at the highest thresholds, call for a consecutive positive GM test before starting patients on antifungal therapy targeting histoplasmosis. Still, when considering the highest costs of BDG testing, higher balanced diagnostic performances, and lower costs of GM testing alone, one may favor the use of GM, notably in resources-limited settings.
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- 2022
44. P033 Genomic epidemiology of the antifungal-resistant dermatophytosis epidemic, India, 2017-2019
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Ujwal Bagal, Lalitha Gade, Ngoc Le, Meghan Bentz, Elizabeth Berkow, Steven Hurst, Shawn Lockhart, Anastasia Litvintseva, Brian Min, Joseph Sexton, Silke Uhrlaß, Brendan Jackson, Nancy Chow, Tom Chiller, Pietro Nenoff, and Shyam Verma
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Infectious Diseases ,General Medicine - Abstract
Poster session 1, September 21, 2022, 12:30 PM - 1:30 PM Objective The epidemic of antifungal-resistant dermatophytosis in India has been reported. These infections are associated with severe morbidity, resistance to oral itraconazole and terbinafine, and the widespread misuse of topical steroids. Trichophyton indotineae has emerged as the predominant causative agent. In this study, we investigated 162 dermatophytosis infections from eight Indian states using genomic sequencing. The primary objective was to determine whether a clonal outbreak strain is responsible for the current epidemic. Methods A total of 161 T. indotineae and one T. rubrum isolates from skin scrapings collected from India in 2017-2019 and previously reported were sent to the U.S. Centers for Disease Control and Prevention (CDC) for genomic analysis. After species identification, genomic DNA was extracted and sequenced using Illumina NovaSeq. Single-nucleotide (SNP) analysis was performed using the portable workflow MycoSNP (v0.21). Briefly, MycoSNP prepared the reference genome, performed pre-processing, aligned sample reads to the reference using the BWA (v 0.7.17) alignment algorithm, and called variants using GATK (v4.1.4.1). High-quality SNPs were used for constructing phylogenetic trees using neighbor-joining (NJ) and maximum likelihood (ML) methods. Further, to understand if infections are genetically clustered by state or region, multi-dimensional scaling (MDS) was applied using the ML tree in R. Result SNP analysis identified 1259 450 variant sites which were used to construct an NJ and ML tree. The tree topology from both NJ and ML methods showed consensus. All 161 T. indotineae isolates from India clustered together forming a large, well-supported clade. SNP differences between the samples varied from 0-160 SNPs. Historical isolates available at CDC were included as controls and clustered over 40 000 SNPs from the clade comprising isolates from India. The MDS plot revealed that isolates did not cluster by state or region. Conclusion Antifungal-resistant dermatophytosis is an emerging threat with cases of chronic, recurrent infection reported from several countries including India. Additionally, the rapid spread of infections involves person-to-person spread. Our results suggest that a clonal outbreak of a T. indotineae strain is circulating in multiple states in India. Current plans are to expand the geographic scope of the study by including over 10 countries from Europe, Middle East, and the Americas. This work will allow the public health community to better understand the emergence and transmission of antifungal-resistant dermatophytosis worldwide.
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- 2022
45. Incidence of Invasive Fungal Infections in Patients Initiating Ibrutinib and Other Small Molecule Kinase Inhibitors—United States, July 2016–June 2019
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Jeremy A W Gold, Seda S Tolu, Tom Chiller, Kaitlin Benedict, and Brendan R Jackson
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Microbiology (medical) ,Infectious Diseases ,Piperidines ,Adenine ,Incidence ,Humans ,Article ,Invasive Fungal Infections ,United States - Abstract
We analyzed administrative data to determine the 1-year incidence of invasive fungal infections (IFIs) in patients beginning small molecule kinase inhibitor (SMKI) therapy. The incidence of IFIs by small molecule kinase inhibitor ranged from 0.0% to 10.6%, with patients taking midostaurin having the highest incidence. An IFI developed in 38 of 1286 patients taking ibrutinib (3.0%).
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- 2022
46. Taskforce report on the diagnosis and clinical management of COVID-19 associated pulmonary aspergillosis
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Cornelius J. Clancy, Philipp Koehler, Jeroen Schouten, Stijn Blot, Roger J. M. Brüggemann, Elie Azoulay, Oliver A. Cornely, Paul E. Verweij, Matteo Bassetti, Peter Wei Lun Liu, Frank L. van de Veerdonk, Alejandro Rodriguez, Thomas R. Rogers, Olivier Lortholary, Ignacio Martin-Loeches, Cornelia Lass-Flörl, Pieter Depuydt, Russell E. Lewis, Joost Wauters, Katrien Lagrou, Jochem B. Buil, Thierry Calandra, Dylan W. de Lange, Thomas F. Patterson, Tom Chiller, Bart J. A. Rijnders, Johan Maertens, M. Hong Nguyen, Verweij P.E., Bruggemann R.J.M., Azoulay E., Bassetti M., Blot S., Buil J.B., Calandra T., Chiller T., Clancy C.J., Cornely O.A., Depuydt P., Koehler P., Lagrou K., de Lange D., Lass-Florl C., Lewis R.E., Lortholary O., Liu P.-W.L., Maertens J., Nguyen M.H., Patterson T.F., Rijnders B.J.A., Rodriguez A., Rogers T.R., Schouten J.A., Wauters J., van de Veerdonk F.L., Martin-Loeches I., and Internal Medicine
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INVASIVE ASPERGILLOSIS ,Conference Reports and Expert Panel ,lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] ,COVID-19 ,Humans ,Intensive Care Units ,Invasive Pulmonary Aspergillosis/diagnosis ,Pulmonary Aspergillosis/diagnosis ,Pulmonary Aspergillosis/drug therapy ,Pulmonary Aspergillosis/epidemiology ,SARS-CoV-2 ,ICU ,Invasive aspergillosis ,Viral pneumonia ,Disease ,GUIDELINES ,Critical Care and Intensive Care Medicine ,POSACONAZOLE ,law.invention ,Invasive aspergillosi ,0302 clinical medicine ,Bronchoscopy ,law ,Epidemiology ,Medicine and Health Sciences ,Invasive Pulmonary Aspergillosis ,medicine.diagnostic_test ,Incidence (epidemiology) ,Intensive care unit ,VORICONAZOLE PHARMACOKINETICS ,DIFFERENTIATION ,Life Sciences & Biomedicine ,CRITICALLY-ILL PATIENTS ,Human ,medicine.medical_specialty ,Intensive Care Unit ,Invasive Pulmonary Aspergillosi ,SOCIETY ,BETA ,03 medical and health sciences ,Critical Care Medicine ,General & Internal Medicine ,Anesthesiology ,medicine ,Intensive care medicine ,Science & Technology ,business.industry ,030208 emergency & critical care medicine ,medicine.disease ,lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4] ,Bronchoalveolar lavage ,030228 respiratory system ,Pulmonary Aspergillosis ,business - Abstract
Purpose Invasive pulmonary aspergillosis (IPA) is increasingly reported in patients with severe coronavirus disease 2019 (COVID-19) admitted to the intensive care unit (ICU). Diagnosis and management of COVID-19 associated pulmonary aspergillosis (CAPA) are challenging and our aim was to develop practical guidance. Methods A group of 28 international experts reviewed current insights in the epidemiology, diagnosis and management of CAPA and developed recommendations using GRADE methodology. Results The prevalence of CAPA varied between 0 and 33%, which may be partly due to variable case definitions, but likely represents true variation. Bronchoscopy and bronchoalveolar lavage (BAL) remain the cornerstone of CAPA diagnosis, allowing for diagnosis of invasive Aspergillus tracheobronchitis and collection of the best validated specimen for Aspergillus diagnostics. Most patients diagnosed with CAPA lack traditional host factors, but pre-existing structural lung disease and immunomodulating therapy may predispose to CAPA risk. Computed tomography seems to be of limited value to rule CAPA in or out, and serum biomarkers are negative in 85% of patients. As the mortality of CAPA is around 50%, antifungal therapy is recommended for BAL positive patients, but the decision to treat depends on the patients’ clinical condition and the institutional incidence of CAPA. We recommend against routinely stopping concomitant corticosteroid or IL-6 blocking therapy in CAPA patients. Conclusion CAPA is a complex disease involving a continuum of respiratory colonization, tissue invasion and angioinvasive disease. Knowledge gaps including true epidemiology, optimal diagnostic work-up, management strategies and role of host-directed therapy require further study. Supplementary Information The online version contains supplementary material available at 10.1007/s00134-021-06449-4.
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- 2021
47. Patient notification about suspected hospital-associated outbreaks of invasive mold infections: Considerations for public health and hospital personnel
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Brendan R Jackson, Kaitlin Benedict, Mitsuru Toda, Pooja Gandhi, Tom Chiller, and Karlyn D. Beer
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0301 basic medicine ,Microbiology (medical) ,medicine.medical_specialty ,Epidemiology ,030106 microbiology ,Disease ,Disease Outbreaks ,Course of action ,03 medical and health sciences ,0302 clinical medicine ,Health care ,Humans ,Medicine ,030212 general & internal medicine ,business.industry ,Public health ,Fungi ,Outbreak ,medicine.disease ,Hospitals ,Personnel, Hospital ,Fungal disease ,Infectious Diseases ,Public Health ,Medical emergency ,business - Abstract
A common type of fungal disease investigation involves hospital-associated clusters of invasive mold infections (IMIs), which typically occur among immunocompromised patients. Responding to IMI clusters can be challenging for public health and hospital personnel for several reasons such as difficulty of confirming the existence of an outbreak, difficulty of determining source. Although many resources exist to guide patient notification about healthcare incidents (eg, bloodborne exposures, disease outbreaks), IMI clusters involve special considerations related to the complex diseases, uncertain exposures, and differential benefits and risks of notification. Early, nuanced communication about hospital-associated IMI clusters is almost always the best course of action to help reduce risks to patients’ health and foster trust between patients and hospitals.
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- 2021
48. Implementation of rapid diagnostics assays for detection of histoplasmosis and cryptococcosis in central american people living with HIV
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Julio C Zuniga-Moya, Diego H. Cáceres, Carlos Saenz, Diana Forno, Ana Belén Araúz, Isis Zohar Lainez Arteaga, Felipe A Torres-Meneses, Arturo Garcia, Jose Abdo, Carlos Flores, Tom Chiller, Sandra Montoya, Paul E. Verweij, Erika Santiago, and Hortencia Peralta
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Adult ,Male ,0301 basic medicine ,Antigens, Fungal ,cryptococcosis ,Panama ,Histoplasma ,030106 microbiology ,Human immunodeficiency virus (HIV) ,Cryptococcus ,HIV Infections ,Nicaragua ,Dermatology ,medicine.disease_cause ,Histoplasmosis ,Immunoenzyme Techniques ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Antigen ,Acquired immunodeficiency syndrome (AIDS) ,medicine ,Humans ,medicine.diagnostic_test ,biology ,histoplasmosis ,business.industry ,HIV ,Original Articles ,General Medicine ,Flow Cytometry ,medicine.disease ,biology.organism_classification ,Virology ,AIDS ,Infectious Diseases ,Honduras ,Immunoassay ,Cryptococcosis ,Original Article ,Female ,business - Abstract
Objectives Histoplasmosis and cryptococcosis are important public health problems in people living with HIV (PLHIV) in Central America. Conventional laboratory assays, based on microscopy and culture, are not optimal for the diagnosis of either disease. However, antigen (Ag) assays are rapid and highly accurate for the diagnosis of these infections. Methods Laboratory surveillance of PLHIV was carried out in four hospitals in Panama, Honduras and Nicaragua, between 2015 and 2019. Detection of Histoplasma antigens in urine was performed by enzyme immunoassay (EIA), and Cryptococcus antigen detection in sera and cerebrospinal fluid specimens was performed by lateral flow assay (LFA). Results A total of 4,453 PLHIV with clinical suspicion of histoplasmosis (n = 1,343) or cryptococcosis (n = 3,110; 2,721 sera and 389 CSF) were tested. Of 1,343 patients suspected of having histoplasmosis, 269 (20%) were Histoplasma Ag positive. Of 3,110 patients tested using the Cryptococcus Ag assay, 329 (11%) were positive. Honduras reported the highest positivity rates (32% for Histoplasma Ag, and 16% for Cryptococcus Ag); Panama reported the largest number of patients testing positive using the Histoplasma Ag assay (n = 201); and Nicaragua reported the largest number of patients testing positive using the Cryptococcus Ag assay (n = 170). Conclusion Here, we show how the implementation of rapid diagnostics assays impacted case detection and was useful for the care of people with advanced HIV. Rapid and accurate diagnosis could reduce mortality associated with histoplasmosis and cryptococcosis in PLHIV.
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- 2021
49. Cryptococcal meningitis: A neglected NTD?
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Síle F Molloy, Tom Chiller, Gregory S Greene, Jessica Burry, Nelesh P Govender, Cecilia Kanyama, Sayoki Mfinanga, Sokoine Lesikari, Yacouba N Mapoure, Charles Kouanfack, Victor Sini, Elvis Temfack, David R Boulware, Francoise Dromer, David W Denning, Jeremy Day, Neil R H Stone, Tihana Bicanic, Joseph N Jarvis, Olivier Lortholary, Thomas S Harrison, Shabbar Jaffar, and Angela Loyse
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Arctic medicine. Tropical medicine ,RC955-962 ,Public aspects of medicine ,RA1-1270 - Published
- 2017
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50. Standardization and validation of real time PCR assays for the diagnosis of histoplasmosis using three molecular targets in an animal model.
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Luisa F López, César O Muñoz, Diego H Cáceres, Ángela M Tobón, Vladimir Loparev, Oliver Clay, Tom Chiller, Anastasia Litvintseva, Lalitha Gade, Ángel González, and Beatriz L Gómez
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Medicine ,Science - Abstract
Histoplasmosis is considered one of the most important endemic and systemic mycoses worldwide. Until now few molecular techniques have been developed for its diagnosis. The aim of this study was to develop and evaluate three real time PCR (qPCR) protocols for different protein-coding genes (100-kDa, H and M antigens) using an animal model. Fresh and formalin-fixed and paraffin-embedded (FFPE) lung tissues from BALB/c mice inoculated i.n. with 2.5x106 Histoplasma capsulatum yeast or PBS were obtained at 1, 2, 3, 4, 8, 12 and 16 weeks post-infection. A collection of DNA from cultures representing different clades of H. capsulatum (30 strains) and other medically relevant pathogens (36 strains of related fungi and Mycobacterium tuberculosis) were used to analyze sensitivity and specificity. Analytical sensitivity and specificity were 100% when DNAs from the different strains were tested. The highest fungal burden occurred at first week post-infection and complete fungal clearance was observed after the third week; similar results were obtained when the presence of H. capsulatum yeast cells was demonstrated in histopathological analysis. In the first week post-infection, all fresh and FFPE lung tissues from H. capsulatum-infected animals were positive for the qPCR protocols tested except for the M antigen protocol, which gave variable results when fresh lung tissue samples were analyzed. In the second week, all qPCR protocols showed variable results for both fresh and FFPE tissues. Samples from the infected mice at the remaining times post-infection and uninfected mice (controls) were negative for all protocols. Good agreement was observed between CFUs, histopathological analysis and qPCR results for the 100-kDa and H antigen protocols. We successfully standardized and validated three qPCR assays for detecting H. capsulatum DNA in fresh and FFPE tissues, and conclude that the 100-kDa and H antigen molecular assays are promising tests for diagnosing this mycosis.
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- 2017
- Full Text
- View/download PDF
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