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. 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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23. 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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24. 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.
- Published
- 2020
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25. Southern African HIV Clinicians Society guideline for the prevention, diagnosis and management of cryptococcal disease among HIV-infected persons: 2019 update
- Author
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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
- Subjects
Public aspects of medicine ,RA1-1270 ,Infectious and parasitic diseases ,RC109-216 - Abstract
No abstract available.
- Published
- 2019
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26. The important role of co-infections in patients with AIDS and progressive disseminated histoplasmosis (PDH): A cohort from Colombia
- Author
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Diego H. Caceres, Ángela M. Tobón, Ángela Restrepo, Tom Chiller, and Beatriz L. Gómez
- Subjects
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.
- Published
- 2018
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27. Validation and Concordance Analysis of a New Lateral Flow Assay for Detection of Histoplasma Antigen in Urine
- Author
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Diego H. Cáceres, Beatriz L. Gómez, Ángela M. Tobón, Melissa Minderman, Nicole Bridges, Tom Chiller, and Mark D. Lindsley
- Subjects
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.
- Published
- 2021
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28. 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]
- Author
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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
- Subjects
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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29. The NDV-3A vaccine protects mice from multidrug resistant Candida auris infection.
- Author
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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
- Subjects
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.
- Published
- 2019
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30. 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.
- Published
- 2021
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31. 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.,
- Published
- 2018
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32. 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
- Subjects
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.
- Published
- 2017
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33. 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
- Subjects
Arctic medicine. Tropical medicine ,RC955-962 ,Public aspects of medicine ,RA1-1270 - Published
- 2017
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34. 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
- Subjects
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.
- Published
- 2017
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35. Cryptococcal antigen screening by lay cadres using a rapid test at the point of care: A feasibility study in rural Lesotho.
- Author
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Fernanda Rick, Aline Aurore Niyibizi, Amir Shroufi, Kazumi Onami, Sarah-Jane Steele, Malehlohonolo Kuleile, Innocent Muleya, Tom Chiller, Tiffany Walker, and Gilles Van Cutsem
- Subjects
Medicine ,Science - Abstract
Cryptococcal meningitis is one of the leading causes of death among people with HIV in Africa, primarily due to delayed presentation, poor availability and high cost of treatment. Routine cryptococcal antigen (CrAg) screening of patients with a CD4 count less than 100 cells/mm3, followed by pre-emptive therapy if positive, might reduce mortality in high prevalence settings. Using the cryptococcal antigen (CrAg) lateral flow assay (LFA), screening is possible at the point of care (POC). However, critical shortages of health staff may limit adoption. This study investigates the feasibility of lay counsellors conducting CrAg LFA screening in rural primary care clinics in Lesotho.From May 2014 to June 2015, individuals who tested positive for HIV were tested for CD4 count and those with CD4
- Published
- 2017
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36. The Diagnosis of Fungal Neglected Tropical Diseases (Fungal NTDs) and the Role of Investigation and Laboratory Tests: An Expert Consensus Report
- Author
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Roderick Hay, David W Denning, Alexandro Bonifaz, Flavio Queiroz-Telles, Karlyn Beer, Beatriz Bustamante, Arunaloke Chakrabarti, Maria de Guadalupe Chavez-Lopez, Tom Chiller, Muriel Cornet, Roberto Estrada, Guadalupe Estrada-Chavez, Ahmed Fahal, Beatriz L Gomez, Ruoyu Li, Yesholata Mahabeer, Anisa Mosam, Lala Soavina Ramarozatovo, Mala Rakoto Andrianarivelo, Fahafahantsoa Rapelanoro Rabenja, Wendy van de Sande, and Eduard E Zijlstra
- Subjects
fungal NTDs ,laboratory diagnosis ,mycetoma ,sporotrichosis ,chromoblastomycosis ,integrated approaches ,Medicine - Abstract
The diagnosis of fungal Neglected Tropical Diseases (NTD) is primarily based on initial visual recognition of a suspected case followed by confirmatory laboratory testing, which is often limited to specialized facilities. Although molecular and serodiagnostic tools have advanced, a substantial gap remains between the desirable and the practical in endemic settings. To explore this issue further, we conducted a survey of subject matter experts on the optimal diagnostic methods sufficient to initiate treatment in well-equipped versus basic healthcare settings, as well as optimal sampling methods, for three fungal NTDs: mycetoma, chromoblastomycosis, and sporotrichosis. A survey of 23 centres found consensus on the key role of semi-invasive sampling methods such as biopsy diagnosis as compared with swabs or impression smears, and on the importance of histopathology, direct microscopy, and culture for mycetoma and chromoblastomycosis confirmation in well-equipped laboratories. In basic healthcare settings, direct microscopy combined with clinical signs were reported to be the most useful diagnostic indicators to prompt referral for treatment. The survey identified that the diagnosis of sporotrichosis is the most problematic with poor sensitivity across the most widely available laboratory tests except fungal culture, highlighting the need to improve mycological diagnostic capacity and to develop innovative diagnostic solutions. Fungal microscopy and culture are now recognized as WHO essential diagnostic tests and better training in their application will help improve the situation. For mycetoma and sporotrichosis, in particular, advances in identifying specific marker antigens or genomic sequences may pave the way for new laboratory-based or point-of-care tests, although this is a formidable task given the large number of different organisms that can cause fungal NTDs.
- Published
- 2019
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37. On the Origins of a Species: What Might Explain the Rise of Candida auris?
- Author
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Brendan R. Jackson, Nancy Chow, Kaitlin Forsberg, Anastasia P. Litvintseva, Shawn R. Lockhart, Rory Welsh, Snigdha Vallabhaneni, and Tom Chiller
- Subjects
Candida auris ,yeast ,ecological niche ,fungal infection ,emerging infections ,Biology (General) ,QH301-705.5 - Abstract
Candida auris is an emerging multidrug-resistant yeast first described in 2009 that has since caused healthcare-associated outbreaks of severe human infections around the world. In some hospitals, it has become a leading cause of invasive candidiasis. C. auris is markedly different from most other pathogenic Candida species in its genetics, antifungal resistance, and ability to spread between patients. The reasons why this fungus began spreading widely in the last decade remain a mystery. We examine available data on C. auris and related species, including genomic epidemiology, phenotypic characteristics, and sites of detection, to put forth hypotheses on its possible origins. C. auris has not been detected in the natural environment; related species have been detected in in plants, insects, and aquatic environments, as well as from human body sites. It can tolerate hypersaline environments and higher temperatures than most Candida species. We explore hypotheses about the pre-emergence niche of C. auris, whether in the environmental or human microbiome, and speculate on factors that might have led to its spread, including the possible roles of healthcare, antifungal use, and environmental changes, including human activities that might have expanded its presence in the environment or caused increased human contact.
- Published
- 2019
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38. Cryptococcus gattii Infections in Multiple States Outside the US Pacific Northwest
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Julie R. Harris, Shawn R. Lockhart, Gail Sondermeyer, Duc J. Vugia, Matthew B. Crist, Melissa Tobin D’Angelo, Brenda Sellers, Carlos Franco-Paredes, Monear Makvandi, Chad Smelser, John Greene, Danielle Stanek, Kimberly Signs, Randall J. Nett, Tom Chiller, and Benjamin J. Park
- Subjects
Cryptococcus ,gattii ,meningitis ,pneumonia ,fungal ,fungi ,Medicine ,Infectious and parasitic diseases ,RC109-216 - Abstract
Clonal VGII subtypes (outbreak strains) of Cryptococcus gattii have caused an outbreak in the US Pacific Northwest since 2004. Outbreak-associated infections occur equally in male and female patients (median age 56 years) and usually cause pulmonary disease in persons with underlying medical conditions. Since 2009, a total of 25 C. gattii infections, 23 (92%) caused by non–outbreak strain C. gattii, have been reported from 8 non–Pacific Northwest states. Sixteen (64%) patients were previously healthy, and 21 (84%) were male; median age was 43 years (range 15–83 years). Ten patients who provided information reported no past-year travel to areas where C. gattii is known to be endemic. Nineteen (76%) patients had central nervous system infections; 6 (24%) died. C. gattii infection in persons without exposure to known disease-endemic areas suggests possible endemicity in the United States outside the outbreak-affected region; these infections appear to differ in clinical and demographic characteristics from outbreak-associated C. gattii. Clinicians outside the outbreak-affected areas should be aware of locally acquired C. gattii infection and its varied signs and symptoms.
- Published
- 2013
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39. Local Population Structure and Patterns of Western Hemisphere Dispersal for Coccidioides spp., the Fungal Cause of Valley Fever
- Author
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David M. Engelthaler, Chandler C. Roe, Crystal M. Hepp, Marcus Teixeira, Elizabeth M. Driebe, James M. Schupp, Lalitha Gade, Victor Waddell, Kenneth Komatsu, Eduardo Arathoon, Heidi Logemann, George R. Thompson, Tom Chiller, Bridget Barker, Paul Keim, and Anastasia P. Litvintseva
- Subjects
Microbiology ,QR1-502 - Abstract
ABSTRACT Coccidioidomycosis (or valley fever) is a fungal disease with high morbidity and mortality that affects tens of thousands of people each year. This infection is caused by two sibling species, Coccidioides immitis and C. posadasii, which are endemic to specific arid locales throughout the Western Hemisphere, particularly the desert southwest of the United States. Recent epidemiological and population genetic data suggest that the geographic range of coccidioidomycosis is expanding, as new endemic clusters have been identified in the state of Washington, well outside the established endemic range. The genetic mechanisms and epidemiological consequences of this expansion are unknown and require better understanding of the population structure and evolutionary history of these pathogens. Here we performed multiple phylogenetic inference and population genomics analyses of 68 new and 18 previously published genomes. The results provide evidence of substantial population structure in C. posadasii and demonstrate the presence of distinct geographic clades in central and southern Arizona as well as dispersed populations in Texas, Mexico, South America, and Central America. Although a smaller number of C. immitis strains were included in the analyses, some evidence of phylogeographic structure was also detected in this species, which has been historically limited to California and Baja, Mexico. Bayesian analyses indicated that C. posadasii is the more ancient of the two species and that Arizona contains the most diverse subpopulations. We propose a southern Arizona-northern Mexico origin for C. posadasii and describe a pathway for dispersal and distribution out of this region. IMPORTANCE Coccidioidomycosis, or valley fever, is caused by the pathogenic fungi Coccidioides posadasii and C. immitis. The fungal species and disease are primarily found in the American desert southwest, with spotted distribution throughout the Western Hemisphere. Initial molecular studies suggested a likely anthropogenic movement of C. posadasii from North America to South America. Here we comparatively analyze eighty-six genomes of the two Coccidioides species and establish local and species-wide population structures to not only clarify the earlier dispersal hypothesis but also provide evidence of likely ancestral populations and patterns of dispersal for the known subpopulations of C. posadasii.
- Published
- 2016
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40. Recognition and Diagnosis of Cryptococcus gattii Infections in the United States
- Author
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Sally Ann Iverson, Tom Chiller, Susan Beekmann, Philip M. Polgreen, and Julie Harris
- Subjects
Cryptococcus gattii ,physicians ,survey ,EIN ,United States ,bacteria ,Medicine ,Infectious and parasitic diseases ,RC109-216 - Published
- 2012
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41. Disseminated histoplasmosis in HIV-infected patients in South America: a neglected killer continues on its rampage.
- Author
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Mathieu Nacher, Antoine Adenis, Sigrid Mc Donald, Margarete Do Socorro Mendonca Gomes, Shanti Singh, Ivina Lopes Lima, Rosilene Malcher Leite, Sandra Hermelijn, Merril Wongsokarijo, Marja Van Eer, Silvia Marques Da Silva, Maurimelia Mesquita Da Costa, Marizette Silva, Maria Calvacante, Terezinha do Menino Jesus Silva Leitao, Beatriz L Gómez, Angela Restrepo, Angela Tobon, Cristina E Canteros, Christine Aznar, Denis Blanchet, Vincent Vantilcke, Cyrille Vautrin, Rachida Boukhari, Tom Chiller, Christina Scheel, Angela Ahlquist, Monika Roy, Olivier Lortholary, Bernard Carme, Pierre Couppié, and Stephen Vreden
- Subjects
Arctic medicine. Tropical medicine ,RC955-962 ,Public aspects of medicine ,RA1-1270 - Published
- 2013
- Full Text
- View/download PDF
42. Guidelines for the prevention, diagnosis and management of cryptococcal meningitis and disseminated cryptococcosis in HIV-infected patients
- Author
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Kerrigan McCarthy, Graeme Meintjes, Beth Arthington-Skaggs, Tihana Bicanic, Mark Cotton, Tom Chiller, Nelesh Govender, Tom Harrison, Alan Karstaed, Gary Maartens, Ebrahim Varavia, Francois Venter, and Hester Vismer
- Subjects
Public aspects of medicine ,RA1-1270 ,Infectious and parasitic diseases ,RC109-216 - Abstract
No abstract available.
- Published
- 2007
- Full Text
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43. Tracking Resistant Organisms: Workshop for Improving State-based Surveillance Programs
- Author
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Brendan Noggle, Martha Iwamoto, Tom Chiller, Monina Klevens, Matthew R. Moore, Jennifer Wright, and Cynthia G. Whitney
- Subjects
Drug Resistance ,Bacterial ,Multiple ,Streptococcus pneumonia ,Staphylococcus aureus ,Neisseria meningitides ,Medicine ,Infectious and parasitic diseases ,RC109-216 - Published
- 2006
- Full Text
- View/download PDF
44. Worsening Spread of Candida auris in the United States, 2019 to 2021
- Author
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Meghan Lyman, Kaitlin Forsberg, D. Joseph Sexton, Nancy A. Chow, Shawn R. Lockhart, Brendan R. Jackson, and Tom Chiller
- Subjects
Internal Medicine ,General Medicine - Published
- 2023
45. 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
- Author
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Antonia Langfeldt, Jeremy A. W. Gold, and Tom Chiller
- Subjects
Microbiology (medical) ,Infectious Diseases - Published
- 2022
46. 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> )
- Author
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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
- Subjects
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.
- Published
- 2022
47. Single High-dose of Liposomal Amphotericin B in HIV/AIDS-related Disseminated Histoplasmosis: a Randomized Trial
- Author
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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
48. Food and Drug Administration Public Workshop Summary—Development Considerations of Antifungal Drugs to Address Unmet Medical Need
- Author
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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
49. 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
50. Validation of a Lateral Flow Assay for Rapid Diagnosis of Histoplasmosis in Advanced HIV Disease, Buenos Aires, Argentina
- Author
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Mariana Andreani, Claudia E. Frola, Diego H. Caceres, Cristina E. Canteros, María J. Rolón, Tom Chiller, and Liliana Guelfand
- Subjects
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.
- Published
- 2022
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