Last data update: Dec 09, 2024. (Total: 48320 publications since 2009)
Records 1-30 (of 63 Records) |
Query Trace: Sexton C[original query] |
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Evaluation of a multiplex real-time PCR targeting the β-tubulin gene for the detection and differentiation of Sporothrix schenckii and Sporothrix brasiliensis
López LF , Gade L , Litvintseva AP , Sexton DJ . Microbiol Spectr 2024 e0116224 Sporothrix sp. is a thermally dimorphic genus of fungi known to cause subacute or chronic subcutaneous lesions in humans and animals and is the cause of increasing public health concern due to spread of feline-associated cases. Here, we adapted and evaluated a recently described real-time PCR assay targeting the β-tubulin gene to rapidly detect and differentiate two related species, S. schenckii and S. brasiliensis. The assay was tested with 55 S. brasiliensis, 19 S. schenckii, and 85 isolates from other clinically relevant fungi, and showed 100% concordance with reference identification methods. The assay showed high analytical sensitivity with a limit of detection of 1 pg of DNA per microliter of sample for both targets. The assay was further evaluated with 11 fresh and 17 formalin-fixed, paraffin-embedded (FFPE) tissues. This multiplex real-time PCR assay successfully detected the DNA from both S. brasiliensis and S. schenckii isolates as well as S. schenckii from fresh and FFPE tissues. Our results demonstrate this assay performs well and could be a helpful molecular tool to support rapid species identification in cultures and primary specimens.IMPORTANCEHaving available molecular tools to identify and differentiate closely related species will allow clinical, veterinarians, and public health labs to provide diagnostic results with accuracy and short turnaround time for the routine and outbreak response activities. |
Subcutaneous phaeohyphomycosis due to Phaeoacremonium venezuelense: The first clinical case report in Costa Rica
Cob M , López LF , Sexton DJ , Fallas A , Muñoz JD , Gutiérrez R . Med Mycol Case Rep 2024 44 100650 Phaeoacremonium is a genus of dematiaceous fungi that rarely causes human infections. We describe a case of subcutaneous infection in a 70-year-old diabetic man with lesions on the dorsum of the one foot. The agent was isolated, and for the final identification we performed matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and DNA sequencing. After diagnosis, the patient underwent curettage of the cyst and received 100mg of Itraconazole, twice daily for 6 months. Clinical resolution of the lesion was observed after treatment. This is the first case of infection by Phaeoacremonium venezuelense reported in Costa Rica. |
Sporotrichosis cluster in domestic cats and veterinary technician, Kansas, USA, 2022
Hennessee I , Barber E , Petro E , Lindemann S , Buss B , Santos A , Gade L , Lockhart SR , Sexton DJ , Chiller T , Toda M . Emerg Infect Dis 2024 30 (5) 1053-1055 We describe a feline sporotrichosis cluster and zoonotic transmission between one of the affected cats and a technician at a veterinary clinic in Kansas, USA. Increased awareness of sporotrichosis and the potential for zoonotic transmission could help veterinary professionals manage feline cases and take precautions to prevent human acquisition. |
Field-collected ticks from Benton County, Arkansas, and prevalence of associated pathogens
Panella NA , Nicholson WL , Komar N , Burkhalter KL , Hughes HR , Theuret DP , Blocher BH , Sexton C , Connelly R , Rothfeldt L , Kenney JL . J Med Entomol 2024 The recovery of a Haemaphysalis longicornis Neumann (Acari: Ixodidae) tick from a dog in Benton County, Arkansas, in 2018 triggered a significant environmental sampling effort in Hobbs State Park Conservation Area. The objective of the investigation was to assess the tick population density and diversity, as well as identify potential tick-borne pathogens that could pose a risk to public health. During a week-long sampling period in August of 2018, a total of 6,154 ticks were collected, with the majority identified as Amblyomma americanum (L), (Acari: Ixodidae) commonly known as the lone star tick. No H. longicornis ticks were found despite the initial detection of this species in the area. This discrepancy highlights the importance of continued monitoring efforts to understand the dynamics of tick populations and their movements. The investigation also focused on pathogen detection, with ticks being pooled by species, age, and sex before being processed with various bioassays. The results revealed the presence of several tick-borne pathogens, including agents associated with ehrlichiosis (n = 12), tularemia (n = 2), and Bourbon virus (BRBV) disease (n = 1), as well as nonpathogenic rickettsial and anaplasmosis organisms. These findings emphasize the importance of public health messaging to raise awareness of the risks associated with exposure to tick-borne pathogens. Prevention measures, such as wearing protective clothing, using insect repellent, and conducting regular tick checks, should be emphasized to reduce the risk of tick-borne diseases. Continued surveillance efforts and research are also essential to improve our understanding of tick-borne disease epidemiology and develop effective control strategies. |
Emergence of zoonotic sporotrichosis in Brazil: a genomic epidemiology study
Ribeiro Dos Santos A , Misas E , Min B , Le N , Bagal UR , Parnell LA , Sexton DJ , Lockhart SR , de Souza Carvalho Melhem M , Takahashi JPF , Oliboni GM , Bonfieti LX , Cappellano P , Sampaio JLM , Araujo LS , Alves Filho HL , Venturini J , Chiller TM , Litvintseva AP , Chow NA . Lancet Microbe 2024 BACKGROUND: Zoonotic sporotrichosis is a neglected fungal disease, whereby outbreaks are primarily driven by Sporothrix brasiliensis and linked to cat-to-human transmission. To understand the emergence and spread of sporotrichosis in Brazil, the epicentre of the current epidemic in South America, we aimed to conduct whole-genome sequencing (WGS) to describe the genomic epidemiology. METHODS: In this genomic epidemiology study, we included Sporothrix spp isolates from sporotrichosis cases from Brazil, Colombia, and the USA. We conducted WGS using Illumina NovaSeq on isolates collected by three laboratories in Brazil from humans and cats with sporotrichosis between 2013 and 2022. All isolates that were confirmed to be Sporothrix genus by internal transcribed spacer or beta-tubulin PCR sequencing were included in this study. We downloaded eight Sporothrix genome sequences from the National Center for Biotechnology Information (six from Brazil, two from Colombia). Three Sporothrix spp genome sequences from the USA were generated by the US Centers for Disease Control and Prevention as part of this study. We did phylogenetic analyses and correlated geographical and temporal case distribution with genotypic features of Sporothrix spp isolates. FINDINGS: 72 Sporothrix spp isolates from 55 human and 17 animal sporotrichosis cases were included: 67 (93%) were from Brazil, two (3%) from Colombia, and three (4%) from the USA. Cases spanned from 1999 to 2022. Most (61 [85%]) isolates were S brasiliensis, and all were reported from Brazil. Ten (14%) were Sporothrix schenckii and were reported from Brazil, USA, and Colombia. For S schenckii isolates, two distinct clades were observed wherein isolates clustered by geography. For S brasiliensis isolates, five clades separated by more than 100 000 single-nucleotide polymorphisms were observed. Among the five S brasiliensis clades, clades A and C contained isolates from both human and cat cases, and clade A contained isolates from six different states in Brazil. Compared with S brasiliensis isolates, larger genetic diversity was observed among S schenckii isolates from animal and human cases within a clade. INTERPRETATION: Our results suggest that the ongoing epidemic driven by S brasiliensis in Brazil represents several, independent emergence events followed by animal-to-animal and animal-to human transmission within and between Brazilian states. These results describe how S brasiliensis can emerge and spread within a country. FUNDING: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Brazil; the São Paulo Research Foundation; Productivity in Research fellowships by the National Council for Scientific and Technological Development, and Ministry of Science and Technology of Brazil. |
Evaluation of CHROMagar Candida Plus for the detection of C. auris with a panel of 206 fungal isolates and 83 colonization screening skin-swabs
Bentz ML , Le N , Min B , Nunnally NS , Sullivan V , Tran M , Lockhart SR , Litvintseva A , Berkow EL , Sexton DJ . Microbiol Spectr 2024 e0356423 CHROMagar Candida Plus is a new formulation of chromogenic media designed for the detection and differentiation of major clinical Candida species, including Candida auris. The objective of this study is to evaluate CHROMagar Candida Plus when used according to manufacturer's instructions with a panel of 206 fungal isolates and 83 skin-swab specimens originally collected for C. auris colonization screening. Of the 68 C. auris isolates tested, 66/68 displayed the expected light-blue colony morphology and blue halo within 48 h. None of the remaining 138 non-auris isolates appeared similar to C. auris. CHROMagarCandida Plus was, therefore, inclusive to 97% of 68 C. auris isolates tested and supported visual exclusion of 100% of the 138 non-C. auris isolates tested. For the 83 colonization screening specimens, direct plating onto CHROMagarCandida Plus was 60% sensitive and 100% specific when compared to the enrichment broth gold-standard reference method. In sum, these findings demonstrate the utility of this media when working with isolates but also notable limitations when working with primary skin-swabs specimens when competing yeast species are present.IMPORTANCECandida auris is an emerging fungal pathogen of public health concern. As it continues to spread, it is important to publish evaluations of new diagnostic tools. In this study, we share our experience with a new chromogenic media which can help distinguish C. auris from related species. |
Multistate outbreak of Salmonella Oranienburg infections linked to bulb onions imported from Mexico – United States, 2021
Mitchell MR , Kirchner M , Schneider B , McClure M , Neil KP , Madad A , Jemaneh T , Tijerina M , Nolte K , Wellman A , Neises D , Pightling A , Swinford A , Piontkowski A , Sexton R , McKenna C , Cornell J , Sandoval AL , Wang H , Bell RL , Stager C , Zamora Nava MC , Lara de la Cruz JL , Sánchez Córdova LI , Galván PR , Ortiz JA , Flowers S , Grisamore A , Gieraltowski L , Bazaco M , Viazis S . Food Control 2024 160 In 2021, the U.S. Food and Drug Administration (FDA), the Centers for Disease Control and Prevention (CDC), and state and local health and regulatory partners investigated an outbreak of Salmonella enterica serovar Oranienburg infections linked to bulb onions from Mexico, resulting in 1040 illnesses and 260 hospitalizations across 39 states, the District of Columbia, and Puerto Rico. The Kansas Department of Agriculture recovered the outbreak strain of Salmonella Oranienburg from a sample of condiment collected from an ill person's home. The condiment was made with cilantro, lime, and onions, but, at the time of collection, there were no onions remaining in it. FDA conducted traceback investigations for white, yellow, and red bulb onions, cilantro, limes, tomatoes, and jalapeño peppers. Growers in the state of Chihuahua, Mexico, were identified as supplying the implicated onions that could account for exposure to onions for all illnesses included in the traceback investigation, but investigators could not determine a single source or route of contamination. FDA collected product and environmental samples across the domestic supply chain but did not recover the outbreak strain of Salmonella. Binational collaboration and information sharing supported Mexican authorities in collecting environmental samples from two packing plants and onion, water, and environmental samples from 15 farms and firms in Chihuahua, Mexico identified through FDA's traceback investigation, but did not recover the outbreak strain. Distributors of the implicated onions issued voluntary recalls of red, yellow, and white whole, fresh onions imported from the state of Chihuahua, Mexico. This outbreak showcased how investigators overcame significant traceback and epidemiologic challenges, the need for strengthening the ongoing collaboration between U.S. and Mexican authorities and highlighted the need for identifying practices across the supply chain that can help improve the safety of onions. © 2024 |
Finding Candida auris in public metagenomic repositories
Mario-Vasquez JE , Bagal UR , Lowe E , Morgulis A , Phan J , Sexton DJ , Shiryev S , Slatkevičius R , Welsh R , Litvintseva AP , Blumberg M , Agarwala R , Chow NA . PLoS One 2024 19 (1) e0291406 Candida auris is a newly emerged multidrug-resistant fungus capable of causing invasive infections with high mortality. Despite intense efforts to understand how this pathogen rapidly emerged and spread worldwide, its environmental reservoirs are poorly understood. Here, we present a collaborative effort between the U.S. Centers for Disease Control and Prevention, the National Center for Biotechnology Information, and GridRepublic (a volunteer computing platform) to identify C. auris sequences in publicly available metagenomic datasets. We developed the MetaNISH pipeline that uses SRPRISM to align sequences to a set of reference genomes and computes a score for each reference genome. We used MetaNISH to scan ~300,000 SRA metagenomic runs from 2010 onwards and identified five datasets containing C. auris reads. Finally, GridRepublic has implemented a prospective C. auris molecular monitoring system using MetaNISH and volunteer computing. |
Rapid environmental contamination with candida auris and multidrug-resistant bacterial pathogens near colonized patients
Sansom SE , Gussin GM , Schoeny M , Singh RD , Adil H , Bell P , Benson EC , Bittencourt CE , Black S , Del Mar Villanueva Guzman M , Froilan MC , Fukuda C , Barsegyan K , Gough E , Lyman M , Makhija J , Marron S , Mikhail L , Noble-Wang J , Pacilli M , Pedroza R , Saavedra R , Sexton DJ , Shimabukuro J , Thotapalli L , Zahn M , Huang SS , Hayden MK . Clin Infect Dis 2023 BACKGROUND: Environmental contamination is suspected to play an important role in Candida auris transmission. Understanding speed and risks of contamination after room disinfection could inform environmental cleaning recommendations. METHODS: We conducted a prospective multicenter study of environmental contamination associated with C. auris colonization at six ventilator-capable skilled nursing facilities and one acute-care hospital in Illinois and California. Known C. auris carriers were sampled at five body-sites followed by sampling of nearby room surfaces before disinfection and at 0, 4, 8, and 12-hours post-disinfection. Samples were cultured for C. auris and bacterial multidrug-resistant organisms (MDROs). Odds of surface contamination after disinfection were analyzed using multilevel generalized estimating equations. RESULTS: Among 41 known C. auris carriers, colonization was detected most frequently on palms/fingertips (76%) and nares (71%). C. auris contamination was detected on 32.2% (66/205) of room surfaces pre-disinfection and 20.5% (39/190) of room surfaces by 4-hours post-disinfection. A higher number of C. auris-colonized body sites was associated with higher odds of environmental contamination at every time point following disinfection, adjusting for facility of residence. In the rooms of 38 (93%) C. auris carriers co-colonized with a bacterial MDRO, 2%-24% of surfaces were additionally contaminated with the same MDRO by 4-hours post-disinfection. CONCLUSIONS: C. auris can contaminate the healthcare environment rapidly after disinfection, highlighting the challenges associated with environmental disinfection. Future research should investigate long-acting disinfectants, antimicrobial surfaces, and more effective patient skin antisepsis to reduce the environmental reservoir of C. auris and bacterial MDROs in healthcare settings. |
Persistent colonization of Candida auris among inpatients rescreened as part of a weekly surveillance program
Arenas SP , Persad PJ , Patel S , Parekh DJ , Ferreira TBD , Farinas M , Sexton DJ , Lyman M , Gershengorn HB , Shukla BS . Infect Control Hosp Epidemiol 2023 1-4 We established a surveillance program to evaluate persistence of C. auris colonization among hospitalized patients. Overall, 17 patients (34%) had ≥1 negative result followed by a positive test, and 7 (41%) of these patients had ≥2 consecutive negative tests. |
Public health research priorities for fungal diseases: A multidisciplinary approach to save lives
Smith DJ , Gold JAW , Benedict K , Wu K , Lyman M , Jordan A , Medina N , Lockhart SR , Sexton DJ , Chow NA , Jackson BR , Litvintseva AP , Toda M , Chiller T . J Fungi (Basel) 2023 9 (8) 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. |
Will invasive fungal infections be the Last of Us The importance of surveillance, public-health interventions, and antifungal stewardship
Rodriguez Stewart RM , Gold JAW , Chiller T , Sexton DJ , Lockhart SR . Expert Rev Anti Infect Ther 2023 21 (8) 1-4 The video game-turned-HBO show ‘The Last of Us’ is a fanciful representation of a zombie apocalypse caused by a fungal infection. Although Ophiocordyceps, the ‘zombie fungi’ featured in the show, do not infect vertebrates, the show serves as a reminder that many fungi can cause life-threatening invasive fungal infections (IFIs). Candida and Aspergillus species are the most common and well-known causes of IFIs, but at least 300 species of opportunistic human pathogenic yeasts and molds exist. | | Each year, IFIs are responsible for over 1.5 million deaths globally and, in the United States alone, impose health-care costs ranging from five to seven billion dollars [Citation1,Citation2]. During the COVID-19 pandemic, rates of death from fungal infections have increased [Citation3], and the burden of IFIs is poised to grow given the expanding population of patients living with immunosuppressive conditions (e.g. solid organ and stem cell transplantation), increasing antifungal resistance, and potential climate-change related expansion of the geographic ranges in which pathogenic fungi live. Despite the morbidity and mortality associated with fungal infections and their growing public health importance, we still have much to learn about their diagnosis and management. In this review, we discuss gaps and global disparities in fungal laboratory capacity including antifungal susceptibility testing, the paucity of fungal surveillance, and the importance of antifungal stewardship, all against the backdrop of increasing antifungal resistance and a limited armamentarium of antifungal therapies. |
Reductions in inpatient fluoroquinolone use and postdischarge Clostridioides difficile infection (CDI) from a systemwide antimicrobial stewardship intervention
Jones KA , Onwubiko UN , Kubes J , Albrecht B , Paciullo K , Howard-Anderson J , Suchindran S , Trible R , Jacob JT , Yi SH , Goodenough D , Fridkin SK , Sexton ME , Wiley Z . Antimicrob Steward Healthc Epidemiol 2021 1 (1) e32 OBJECTIVE: To determine the impact of an inpatient stewardship intervention targeting fluoroquinolone use on inpatient and postdischarge Clostridioides difficile infection (CDI). DESIGN: We used an interrupted time series study design to evaluate the rate of hospital-onset CDI (HO-CDI), postdischarge CDI (PD-CDI) within 12 weeks, and inpatient fluoroquinolone use from 2 years prior to 1 year after a stewardship intervention. SETTING: An academic healthcare system with 4 hospitals. PATIENTS: All inpatients hospitalized between January 2017 and September 2020, excluding those discharged from locations caring for oncology, bone marrow transplant, or solid-organ transplant patients. INTERVENTION: Introduction of electronic order sets designed to reduce inpatient fluoroquinolone prescribing. RESULTS: Among 163,117 admissions, there were 683 cases of HO-CDI and 1,104 cases of PD-CDI. In the context of a 2% month-to-month decline starting in the preintervention period (P < .01), we observed a reduction in fluoroquinolone days of therapy per 1,000 patient days of 21% after the intervention (level change, P < .05). HO-CDI rates were stable throughout the study period. In contrast, we also detected a change in the trend of PD-CDI rates from a stable monthly rate in the preintervention period to a monthly decrease of 2.5% in the postintervention period (P < .01). CONCLUSIONS: Our systemwide intervention reduced inpatient fluoroquinolone use immediately, but not HO-CDI. However, a downward trend in PD-CDI occurred. Relying on outcome measures limited to the inpatient setting may not reflect the full impact of inpatient stewardship efforts. |
Worsening spread of Candida auris in the United States, 2019 to 2021
Lyman M , Forsberg K , Sexton DJ , Chow NA , Lockhart SR , Jackson BR , Chiller T . Ann Intern Med 2023 176 (4) 489-495 BACKGROUND: Candida auris is an emerging fungal threat that has been spreading in the United States since it was first reported in 2016. OBJECTIVE: To describe recent changes in the U.S. epidemiology of C auris occurring from 2019 to 2021. DESIGN: Description of national surveillance data. SETTING: United States. PATIENTS: Persons with any specimen that was positive for C auris. MEASUREMENTS: Case counts reported to the Centers for Disease Control and Prevention by health departments, volume of colonization screening, and antifungal susceptibility results were aggregated and compared over time and by geographic region. RESULTS: A total of 3270 clinical cases and 7413 screening cases of C auris were reported in the United States through 31 December 2021. The percentage increase in clinical cases grew each year, from a 44% increase in 2019 to a 95% increase in 2021. Colonization screening volume and screening cases increased in 2021 by more than 80% and more than 200%, respectively. From 2019 to 2021, 17 states identified their first C auris case. The number of C auris cases that were resistant to echinocandins in 2021 was about 3 times that in each of the previous 2 years. LIMITATION: Identification of screening cases depends on screening that is done on the basis of need and available resources. Screening is not conducted uniformly across the United States, so the true burden of C auris cases may be underestimated. CONCLUSION: C auris cases and transmission have risen in recent years, with a dramatic increase in 2021. The rise in echinocandin-resistant cases and evidence of transmission is particularly concerning because echinocandins are first-line therapy for invasive Candida infections, including C auris. These findings highlight the need for improved detection and infection control practices to prevent spread of C auris. PRIMARY FUNDING SOURCE: None. |
Accuracy of point-of-care HIV and CD4 field testing by lay healthcare workers in the Botswana combination prevention project
Bile EC , Bachanas PJ , Jarvis JN , Maurice F , Makovore V , Chebani L , Jackson KG , Birhanu S , Maphorisa C , Mbulawa MB , Alwano MG , Sexton C , Modise S , Bapati W , Segolodi T , Moore J , Fonjungo PN . J Virol Methods 2022 311 114647 Accurate HIV and CD4 testing are critical in program implementation, with HIV misdiagnosis having serious consequences at both the client and/or community level. We implemented a comprehensive training and Quality Assurance (QA) program to ensure accuracy of point-of-care HIV and CD4 count testing by lay counsellors during the Botswana Combination Prevention Project (BCPP). We compared the performance of field testing by lay counselors to results from an accredited laboratory to ascertain accuracy of testing. All trained lay counselors passed competency assessments and performed satisfactorily in proficiency testing panel evaluations in 2013, 2014, and 2015. There was excellent agreement (99.6%) between field and laboratory-based HIV test results; of the 3002 samples tested, 960 and 2030 were concordantly positive and negative respectively, with 12 misclassifications (kappa score 0.99, p < 0.0001). Of the 149 HIV-positive samples enumerated for CD4 count in the field using PIMA at a threshold of 350 cells/L; there was 86% agreement with laboratory testing, with only 21 misclassified. The mean difference between field and lab CD4 testing was -16.16 cells/L (95% CI -5.4 - 26.9). Overall, there was excellent agreement between field and laboratory results for both HIV rapid test and PIMA CD4 results. A standard training package to train lay counselors to accurately perform HIV and CD4 point-of-care testing in field settings was feasible, with point-of-care results obtained by lay counselors comparable to laboratory-based testing. |
Tools for detecting a "superbug": updates on Candida auris testing.
Lockhart SR , Lyman MM , Sexton DJ . J Clin Microbiol 2022 60 (5) jcm0080821 Candida auris is an emerging yeast species that has the unique characteristics of patient skin colonization and rapid transmission within healthcare facilities and the ability to rapidly develop antifungal resistance. When C. auris first started appearing in clinical microbiology laboratories, it could only be identified using DNA sequencing. In the decade since its first identification outside of Japan there have been many improvements in the detection of C. auris. These include the expansion of MALDI-TOF databases to include C. auris, the development of both laboratory-developed tests and commercially available kits for its detection, and special CHROMagar for identification from laboratory specimens. Here we discuss the current tools and resources that are available for C. auris identification and detection. |
Notes from the Field: Transmission of Pan-Resistant and Echinocandin-Resistant Candida auris in Health Care Facilities - Texas and the District of Columbia, January-April 2021
Lyman M , Forsberg K , Reuben J , Dang T , Free R , Seagle EE , Sexton DJ , Soda E , Jones H , Hawkins D , Anderson A , Bassett J , Lockhart SR , Merengwa E , Iyengar P , Jackson BR , Chiller T . MMWR Morb Mortal Wkly Rep 2021 70 (29) 1022-1023 Candida auris is an emerging, often multidrug-resistant yeast that is highly transmissible, resulting in health care–associated outbreaks, especially in long-term care facilities. Skin colonization with C. auris allows spread and leads to invasive infections, including bloodstream infections, in 5%–10% of colonized patients (1). Three major classes of antifungal medications exist for treating invasive infections: azoles (e.g., fluconazole), polyenes (e.g., amphotericin B), and echinocandins. Approximately 85% of C. auris isolates in the United States are resistant to azoles, 33% to amphotericin B, and 1% to echinocandins (2), based on tentative susceptibility breakpoints.* Echinocandins are thus critical for treatment of C. auris infections and are recommended as first-line therapy for most invasive Candida infections (3). Echinocandin resistance is a concerning clinical and public health threat, particularly when coupled with resistance to azole and amphotericin B (pan-resistance). |
Integrated genomic, epidemiologic investigation of Candida auris skin colonization in a skilled nursing facility.
Proctor DM , Dangana T , Sexton DJ , Fukuda C , Yelin RD , Stanley M , Bell PB , Baskaran S , Deming C , Chen Q , Conlan S , Park M , Welsh RM , Vallabhaneni S , Chiller T , Forsberg K , Black SR , Pacilli M , Kong HH , Lin MY , Schoeny ME , Litvintseva AP , Segre JA , Hayden MK . Nat Med 2021 27 (8) 1401-1409 Candida auris is a fungal pathogen of high concern due to its ability to cause healthcare-associated infections and outbreaks, its resistance to antimicrobials and disinfectants and its persistence on human skin and in the inanimate environment. To inform surveillance and future mitigation strategies, we defined the extent of skin colonization and explored the microbiome associated with C. auris colonization. We collected swab specimens and clinical data at three times points between January and April 2019 from 57 residents (up to ten body sites each) of a ventilator-capable skilled nursing facility with endemic C. auris and routine chlorhexidine gluconate (CHG) bathing. Integrating microbial-genomic and epidemiologic data revealed occult C. auris colonization of multiple body sites not targeted commonly for screening. High concentrations of CHG were associated with suppression of C. auris growth but not with deleterious perturbation of commensal microbes. Modeling human mycobiome dynamics provided insight into underlying alterations to the skin fungal community as a possible modifiable risk factor for acquisition and persistence of C. auris. Failure to detect the extensive, disparate niches of C. auris colonization may reduce the effectiveness of infection-prevention measures that target colonized residents, highlighting the importance of universal strategies to reduce C. auris transmission. |
Human Adenovirus 11 in 2 Renal Transplant Recipients: Suspected Donor-Derived Infection.
Sherman AC , Lu X , Schneider E , Langston A , Ellis CL , Pastan S , Bhatnagar J , Reagan-Steiner S , Annambhotla P , Lindstrom S , Mehta A , Pouch SM , Sexton ME . Open Forum Infect Dis 2021 8 (3) ofab092 Background: Human adenovirus (HAdV) infections can lead to high mortality in solid organ transplant (SOT) recipients, with rare reports of donor-derived infection. Methods: Two renal transplant recipients with HAdV-11 infection who received kidneys from the same donor are described. Whole-genome sequencing (WGS) was performed. Results: WGS showed 100% nucleotide sequence identity for the 2 HAdV-11 isolates. The patients presented with distinct clinical syndromes, and both were treated with brincidofovir. Conclusions: Donor-derived HAdV infection is presumed to be low; however, disseminated HAdV in SOT recipients can be severe, and clinicians should be aware of the clinical course and treatment options. © 2021 The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America. |
Evaluating the Presence of Replication-Competent SARS-CoV-2 from Nursing Home Residents with Persistently Positive RT-PCR Results.
Lutgring JD , Tobolowsky FA , Hatfield KM , Lehnertz NB , Sullivan MM , Martin KG , Keaton A , Sexton DJ , Tamin A , Harcourt JL , Thornburg NJ , Reddy SC , Jernigan JA . Clin Infect Dis 2021 74 (3) 525-528 Replication-competent virus has not been detected in individuals with mild to moderate COVID-19 more than 10 days after symptom onset. It is unknown whether these findings apply to nursing home residents. Of 273 specimens collected from nursing home residents >10 days from the initial positive test, none were culture positive. |
Positive correlation between Candida auris skin-colonization burden and environmental contamination at a ventilator-capable skilled nursing facility in Chicago
Sexton DJ , Bentz ML , Welsh RM , Derado G , Furin W , Rose LJ , Noble-Wang J , Pacilli M , McPherson TD , Black S , Kemble SK , Herzegh O , Ahmad A , Forsberg K , Jackson B , Litvintseva AP . Clin Infect Dis 2021 73 (7) 1142-1148 BACKGROUND: Candida auris is an emerging multidrug-resistant yeast that contaminates healthcare environments causing healthcare-associated outbreaks. The mechanisms facilitating contamination are not established. METHODS: C. auris was quantified in residents' bilateral axillary/inguinal composite skin swabs and environmental samples during a point-prevalence survey at a ventilator-capable skilled-nursing facility (vSNF A) with documented high colonization prevalence. Environmental samples were collected from all doorknobs, windowsills and handrails of each bed in 12 rooms. C. auris concentrations were measured using culture and C. auris-specific qPCR. The relationship between C. auris concentrations in residents' swabs and associated environmental samples were evaluated using Kendall's tau-b (τb) correlation coefficient. RESULTS: C. auris was detected in 70 /100 tested environmental samples and 31/ 57 tested resident skin swabs. The mean C. auris concentration in skin swabs was 1.22 x 10 5 cells/mL by culture and 1.08 x 10 6 cells/mL by qPCR. C. auris was detected on all handrails of beds occupied by colonized residents, as well as 10/24 doorknobs and 9/12 windowsills. A positive correlation was identified between the concentrations of C. auris in skin swabs and associated handrail samples based on culture (τb = 0.54, p = 0.0004) and qPCR (τb = 0.66, p = 3.83e -6). Two uncolonized residents resided in beds contaminated with C. auris. CONCLUSIONS: Colonized residents can have high C. auris burdens on their skin, which was positively related with contamination of their surrounding healthcare environment. These findings underscore the importance of hand hygiene, transmission-based precautions, and particularly environmental disinfection in preventing spread in healthcare facilities. |
Finding, treating and retaining persons with HIV in a high HIV prevalence and high treatment coverage country: Results from the Botswana Combination Prevention Project.
Bachanas P , Alwano MG , Lebelonyane R , Block L , Behel S , Raizes E , Ussery G , Wang H , Ussery F , Pretorius Holme M , Sexton C , Pals S , Lasry A , Del Castillo L , Hader S , Lockman S , Bock N , Moore J . PLoS One 2021 16 (4) e0250211 INTRODUCTION: The scale-up of Universal Test and Treat has resulted in reductions in HIV morbidity, mortality and incidence. However, healthcare system and personal challenges have impacted the levels of treatment coverage achieved. We implemented interventions to improve linkage to care, retention, viral load (VL) coverage and service delivery, and describe the HIV care cascade over the course of the Botswana Combination Prevention Project (BCPP) study. METHODS: BCPP was designed to evaluate the impact of prevention interventions on HIV incidence in 30 communities in Botswana. We followed a longitudinal cohort of newly identified and known HIV-positive persons not on antiretroviral therapy (ART) identified through community-based testing activities through BCPP and referred with appointments to local HIV clinics in 15 intervention communities. Those who did not keep the first or follow-up appointments were tracked and traced through phone and home contacts. Improvements to service delivery models in the intervention clinics were also implemented. RESULTS: A total of 3,657 newly identified or HIV-positive persons not on ART were identified and referred to their local HIV clinic; 90% (3,282/3,657) linked to care and of those, 93% (3,066/3,282) initiated treatment. Near the end of the study, 221 persons remained >90 days late for appointments or missing. Tracing efforts identified 54/3,066 (2%) persons who initiated treatment but died, and 106/3,066 (3%) persons were located and returned to treatment. At study end, 61/3,066 (2%) persons remained missing and were never reached. Overall, 2,951 (98%) persons living with HIV (PLHIV) who initiated treatment were still alive, retained in care and still receiving ART out of the 3,001 persons alive at the end of the study. Of those on ART, 2,854 (97%) had current VL results and 2,784 (98%) of those were virally suppressed at study end. CONCLUSIONS: This study achieved high rates of linkage, treatment initiation, retention and VL coverage and suppression in a cohort of newly identified and known PLHIV not on ART. Tracking and tracing interventions effectively identified those persons who needed more resource intensive follow-up. The interventions implemented to improve service delivery and data quality may have also contributed to high linkage and retention rates. Clinical trial number: NCT01965470. |
Antifungal activity of nikkomycin Z against Candida auris.
Bentz ML , Nunnally N , Lockhart SR , Sexton DJ , Berkow EL . J Antimicrob Chemother 2021 76 (6) 1495-1497 BACKGROUND: Nikkomycin Z is a competitive inhibitor of chitin synthase-an enzyme needed for synthesis of the fungal cell wall. Nikkomycin Z shows promise as a treatment for coccidioidomycoses and mixed activity has been described against other fungi and yeast. To our knowledge, it has not previously been tested against the emerging fungal pathogen Candida auris. OBJECTIVES: To determine the in vitro activity of nikkomycin Z against C. auris. METHODS: Nikkomycin Z was tested by broth microdilution against a panel of 100 isolates of genetically diverse C. auris from around the world. RESULTS: Nikkomycin Z showed mixed activity against the tested isolates, with an MIC range of 0.125 to >64 mg/L. The MIC50 and MIC90 were 2 and 32 mg/L, respectively. CONCLUSIONS: These findings suggest nikkomycin Z has in vitro activity against some, but not all isolates of C. auris. |
Clinical and Laboratory Findings in Patients with Potential SARS-CoV-2 Reinfection, May-July 2020.
Lee JT , Hesse EM , Paulin HN , Datta D , Katz LS , Talwar A , Chang G , Galang RR , Harcourt JL , Tamin A , Thornburg NJ , Wong KK , Stevens V , Kim K , Tong S , Zhou B , Queen K , Drobeniuc J , Folster JM , Sexton DJ , Ramachandran S , Browne H , Iskander J , Mitruka K . Clin Infect Dis 2021 73 (12) 2217-2225 BACKGROUND: We investigated patients with potential SARS-CoV-2 reinfection in the United States during May-July 2020. METHODS: We conducted case finding for patients with potential SARS-CoV-2 reinfection through the Emerging Infections Network. Cases reported were screened for laboratory and clinical findings of potential reinfection followed by requests for medical records and laboratory specimens. Available medical records were abstracted to characterize patient demographics, comorbidities, clinical course, and laboratory test results. Submitted specimens underwent further testing, including RT-PCR, viral culture, whole genome sequencing, subgenomic RNA PCR, and testing for anti-SARS-CoV-2 total antibody. RESULTS: Among 73 potential reinfection patients with available records, 30 patients had recurrent COVID-19 symptoms explained by alternative diagnoses with concurrent SARS-CoV-2 positive RT-PCR, 24 patients remained asymptomatic after recovery but had recurrent or persistent RT-PCR, and 19 patients had recurrent COVID-19 symptoms with concurrent SARS-CoV-2 positive RT-PCR but no alternative diagnoses. These 19 patients had symptom recurrence a median of 57 days after initial symptom onset (interquartile range: 47 - 76). Six of these patients had paired specimens available for further testing, but none had laboratory findings confirming reinfections. Testing of an additional three patients with recurrent symptoms and alternative diagnoses also did not confirm reinfection. CONCLUSIONS: We did not confirm SARS-CoV-2 reinfection within 90 days of the initial infection based on the clinical and laboratory characteristics of cases in this investigation. Our findings support current CDC guidance around quarantine and testing for patients who have recovered from COVID-19. |
Isolation of Borrelia miyamotoi and other Borreliae using a modified BSK medium
Replogle AJ , Sexton C , Young J , Kingry LC , Schriefer ME , Dolan M , Johnson TL , Connally NP , Padgett KA , Petersen JM . Sci Rep 2021 11 (1) 1926 Borrelia spirochetes are the causative agents of Lyme borreliosis (LB) and relapsing fever (RF). Despite the steady rise in infections and the identification of new species causing human illness over the last decade, isolation of borreliae in culture has become increasingly rare. A modified Barbour-Stoenner-Kelly (BSK) media formulation, BSK-R, was developed for isolation of the emerging RF pathogen, Borrelia miyamotoi. BSK-R is a diluted BSK-II derivative supplemented with Lebovitz's L-15, mouse and fetal calf serum. Decreasing the concentration of CMRL 1066 and other components was essential for growth of North American B. miyamotoi. Sixteen B. miyamotoi isolates, originating from Ixodes scapularis ticks, rodent and human blood collected in the eastern and upper midwestern United States, were isolated and propagated to densities > 10(8) spirochetes/mL. Growth of five other RF and ten different LB borreliae readily occurred in BSK-R. Additionally, primary culture recovery of 20 isolates of Borrelia hermsii, Borrelia turicatae, Borrelia burgdorferi and Borrelia mayonii was achieved in BSK-R using whole blood from infected patients. These data indicate this broadly encompassing borreliae media can aid in in vitro culture recovery of RF and LB spirochetes, including the direct isolation of new and emerging human pathogens. |
Borrelia burgdorferi and Borrelia miyamotoi seroprevalence in California blood donors.
Brummitt SI , Kjemtrup AM , Harvey DJ , Petersen JM , Sexton C , Replogle A , Packham AE , Bloch EM , Barbour AG , Krause PJ , Green V , Smith WA . PLoS One 2020 15 (12) e0243950 The western blacklegged tick, Ixodes pacificus, an important vector in the western United States of two zoonotic spirochetes: Borrelia burgdorferi (also called Borreliella burgdorferi), causing Lyme disease, and Borrelia miyamotoi, causing a relapsing fever-type illness. Human cases of Lyme disease are well-documented in California, with increased risk in the north coastal areas and western slopes of the Sierra Nevada range. Despite the established presence of B. miyamotoi in the human-biting I. pacificus tick in California, clinical cases with this spirochete have not been well studied. To assess exposure to B. burgdorferi and B. miyamotoi in California, and to address the hypothesis that B. miyamotoi exposure in humans is similar in geographic range to B. burgdorferi, 1,700 blood donor sera from California were tested for antibodies to both pathogens. Sampling was from high endemic and low endemic counties for Lyme disease in California. All sera were screened using the C6 ELISA. All C6 positive and equivocal samples and nine randomly chosen C6 negative samples were further analyzed for B. burgdorferi antibody using IgG western blot and a modified two ELISA test system and for B. miyamotoi antibody using the GlpQ ELISA and B. miyamotoi whole cell sonicate western blot. Of the 1,700 samples tested in series, eight tested positive for antibodies to B. burgdorferi (0.47%, Exact 95% CI: 0.20, 0.93) and two tested positive for antibodies to B. miyamotoi (0.12%, Exact 95% CI: 0.01, 0.42). There was no statistically significant difference in seroprevalence for either pathogen between high and low Lyme disease endemic counties. Our results confirm a low frequency of Lyme disease and an even lower frequency of B. miyamotoi exposure among adult blood donors in California; however, our findings reinforce public health messaging that there is risk of infection by these emerging diseases in the state. |
The changing triad of plague in Uganda: invasive black rats (Rattus rattus), indigenous small mammals, and their fleas
Enscore RE , Babi N , Amatre G , Atiku L , Eisen RJ , Pepin KM , Vera-Tudela R , Sexton C , Gage KL . J Vector Ecol 2020 45 (2) 333-355 Rattus rattus was first reported from the West Nile Region of Uganda in 1961, an event that preceded the appearance of the first documented human plague outbreak in 1970. We investigated how invasive R. rattus and native small mammal populations, as well as their fleas, have changed in recent decades. Over an 18-month period, a total of 2,959 small mammals were captured, sampled, and examined for fleas, resulting in the identification of 20 small mammal taxa that were hosts to 5,109 fleas (nine species). Over three-fourths (75.8%) of captured mammals belonged to four taxa: R. rattus, which predominated inside huts, and Arvicanthis niloticus, Mastomys sp., and Crocidura sp., which were more common outside huts. These mammals were hosts for 85.8% of fleas collected, including the efficient plague vectors Xenopsylla cheopis and X. brasiliensis, as well as likely enzootic vectors, Dinopsyllus lypusus and Ctenophthalmus bacopus. Flea loads on small mammals were higher in certain environments in villages with a recent history of plague compared to those that lacked such a history. The significance of these results is discussed in relation to historical data, the initial spread of plague in the WNR and the continuing threat posed by the disease. |
Evaluation of nine surface disinfectants against Candida auris using a quantitative disk carrier method: EPA SOP-MB-35
Sexton DJ , Welsh RM , Bentz ML , Forsberg K , Jackson B , Berkow EL , Litvintseva AP . Infect Control Hosp Epidemiol 2020 41 (10) 1-3 We tested 9 disinfectants against Candida auris using the quantitative disk carrier method EPA-MB-35-00: 5 products with hydrogen peroxide or alcohol-based chemistries were effective and 4 quaternary ammonium compound-based products were not. This work supported a FIFRA Section 18 emergency exemption granted by the US Environmental Protection Agency to expand disinfectant guidance for C. auris. |
Performance evaluation of culture-independent SYBR Green Candida auris qPCR diagnostics on anterior nares surveillance swabs
Georgacopoulos O , Nunnally NS , Le N , Lysen C , Welsh RM , Kordalewska M , Perlin DS , Berkow EL , Sexton DJ . J Clin Microbiol 2020 58 (9) Early identification of Candida auris is important for timely implementation of infection prevention and control actions. Here, we evaluated performance of the C. auris-specific SYBR Green qPCR assay on a panel of 70 anterior nares swabs. Enrichment broth culture was used as "gold standard". After performing a receiver operating curve (ROC) to optimize signal threshold, we found perfect agreement between culture and qPCR. Additionally, we found no indication of inhibitors in the anterior nares swabs. |
Population uptake of HIV testing, treatment, viral suppression, and male circumcision following a community-based intervention in Botswana (Ya Tsie/BCPP): a cluster-randomised trial
Wirth KE , Gaolathe T , Pretorius Holme M , Mmalane M , Kadima E , Chakalisa U , Manyake K , Matildah Mbikiwa A , Simon SV , Letlhogile R , Mukokomani K , van Widenfelt E , Moyo S , Bennett K , Leidner J , Powis KM , Lebelonyane R , Alwano MG , Jarvis J , Dryden-Peterson SL , Kgathi C , Moore J , Bachanas P , Raizes E , Abrams W , Block L , Sento B , Novitsky V , El-Halabi S , Marukutira T , Mills LA , Sexton C , Pals S , Shapiro RL , Wang R , Lei Q , DeGruttola V , Makhema J , Essex M , Lockman S , Tchetgen Tchetgen EJ . Lancet HIV 2020 7 (6) e422-e433 BACKGROUND: In settings with high HIV prevalence and treatment coverage, such as Botswana, it is unknown whether uptake of HIV prevention and treatment interventions can be increased further. We sought to determine whether a community-based intervention to identify and rapidly treat people living with HIV, and support male circumcision could increase population levels of HIV diagnosis, treatment, viral suppression, and male circumcision in Botswana. METHODS: The Ya Tsie Botswana Combination Prevention Project study was a pair-matched cluster-randomised trial done in 30 communities across Botswana done from Oct 30, 2013, to June 30, 2018. 15 communities were randomly assigned to receive HIV prevention and treatment interventions, including enhanced HIV testing, earlier antiretroviral therapy (ART), and strengthened male circumcision services, and 15 received standard of care. The first primary endpoint of HIV incidence has already been reported. In this Article, we report findings for the second primary endpoint of population uptake of HIV prevention services, as measured by proportion of people known to be HIV-positive or tested HIV-negative in the preceding 12 months; proportion of people living with HIV diagnosed and on ART; proportion of people living with HIV on ART with viral suppression; and proportion of HIV-negative men circumcised. A longitudinal cohort of residents aged 16-64 years from a random, approximately 20% sample of households across the 15 communities was enrolled to assess baseline uptake of study outcomes; we also administered an end-of-study survey to all residents not previously enrolled in the longitudinal cohort to provide study end coverage estimates. Differences in intervention uptake over time by randomisation group were tested via paired Student's t test. The study has been completed and is registered with ClinicalTrials.gov (NCT01965470). FINDINGS: In the six communities participating in the end-of-study survey, 2625 residents (n=1304 from standard-of-care communities, n=1321 from intervention communities) were enrolled into the 20% longitudinal cohort at baseline from Oct 30, 2013, to Nov 24, 2015. In the same communities, 10 791 (86%) of 12 489 eligible enumerated residents not previously enrolled in the longitudinal cohort participated in the end-of-study survey from March 30, 2017, to Feb 25, 2018 (5896 in intervention and 4895 in standard-of-care communities). At study end, in intervention communities, 1228 people living with HIV (91% of 1353) were on ART; 1166 people living with HIV (88% of 1321 with available viral load) were virally suppressed, and 673 HIV-negative men (40% of 1673) were circumcised in intervention communities. After accounting for baseline differences, at study end the proportion of people living with HIV who were diagnosed was significantly higher in intervention communities (absolute increase of 9% to 93%) compared with standard-of-care communities (absolute increase of 2% to 88%; prevalence ratio [PR] 1.08 [95% CI 1.02-1.14], p=0.032). Population levels of ART, viral suppression, and male circumcision increased from baseline in both groups, with greater increases in intervention communities (ART PR 1.12 [95% CI 1.07-1.17], p=0.018; viral suppression 1.13 [1.09-1.17], p=0.017; male circumcision 1.26 [1.17-1.35], p=0.029). INTERPRETATION: It is possible to achieve very high population levels of HIV testing and treatment in a high-prevalence setting. Maintaining these coverage levels over the next decade could substantially reduce HIV transmission and potentially eliminate the epidemic in these areas. FUNDING: US President's Emergency Plan for AIDS Relief through the Centers for Disease Control and Prevention. |
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