Last data update: Apr 22, 2024. (Total: 46599 publications since 2009)
Records 1-30 (of 103 Records) |
Query Trace: Pappas C [original query] |
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Pathogenesis and transmission assessment of three swine-origin influenza A(H3N2) viruses with zoonotic risk to humans isolated in the U.S from 2017-2020
Sun X , Belser JA , Pulit-Penaloza JA , Brock N , Pappas C , Zanders N , Jang Y , Jones J , Tumpey TM , Davis CT , Maines TR . J Infect Dis 2024 229 (4) 1107-1111 The sporadic occurrence of human infections with swine-origin influenza A(H3N2) viruses and the continual emergence of novel A(H3N2) viruses in swine herds underscore the necessity for ongoing assessment of the pandemic risk posed by these viruses. Here, we selected 3 recent novel swine-origin A(H3N2) viruses isolated between 2017 to 2020, bearing hemagglutinins from the 1990.1, 2010.1, or 2010.2 clades, and evaluated their ability to cause disease and transmit in a ferret model. We conclude that despite considerable genetic variances, all 3 contemporary swine-origin A(H3N2) viruses displayed a capacity for robust replication in the ferret respiratory tract and were also capable of limited airborne transmission. These findings highlight the continued public health risk of swine-origin A(H3N2) strains, especially in human populations with low cross-reactive immunity. |
Improving antifungal stewardship in dermatology in an era of emerging dermatophyte resistance
Caplan AS , Gold JAW , Smith DJ , Lipner SR , Pappas PG , Elewski B . JAAD Int 2024 15 168-169 |
Highly pathogenic avian influenza A(H5N1) virus of clade 2.3.4.4b isolated from a human case in Chile causes fatal disease and transmits between co-housed ferrets
Pulit-Penaloza JA , Brock N , Belser JA , Sun X , Pappas C , Kieran TJ , Thakur PB , Zeng H , Cui D , Frederick J , Fasce R , Tumpey TM , Maines TR . Emerg Microbes Infect 2024 2332667 Clade 2.3.4.4b highly pathogenic avian influenza A(H5N1) viruses have caused large outbreaks within avian populations on five continents, with concurrent spillover into a variety of mammalian species. Mutations associated with mammalian adaptation have been sporadically identified in avian isolates, and more frequently among mammalian isolates following infection. Reports of human infection with A(H5N1) viruses following contact with infected wildlife have been reported on multiple continents, highlighting the need for pandemic risk assessment of these viruses. In this study, the pathogenicity and transmissibility of A/Chile/25945/2023 HPAI A(H5N1) virus, a novel reassortment with four gene segments (PB1, PB2, NP, MP) from North America lineage, isolated from a severe human case in Chile, was evaluated in vitro and using the ferret model. This virus possessed a high capacity to cause fatal disease, characterized by high morbidity and extrapulmonary spread in virus-inoculated ferrets. The virus was capable of transmission to naïve contacts in a direct contact setting, with contact animals similarly exhibiting severe disease, but did not exhibit productive transmission in respiratory droplet or fomite transmission models. Our results indicate that the virus would need to acquire an airborne transmissible phenotype in mammals to potentially cause a pandemic. Nonetheless, this work warrants continuous monitoring of mammalian adaptations in avian viruses, especially in strains isolated from humans, to aid pandemic preparedness efforts. |
Lactic acid salts of nicotine potentiate the transfer of toxic metals into electronic cigarette aerosols
Pappas RS , Gray N , Halstead M , Watson CH . Toxics 2024 12 (1) The designs and liquid formulations of Electronic Nicotine Delivery System (ENDS) devices continue to rapidly evolve. Thus, it is important to monitor and characterize ENDS aerosols for changes in toxic constituents. Many ENDS liquid formulations now include the addition of organic acids in a 1 to 1 molar ratio with nicotine. Metal concentrations in aerosols produced by ENDS devices with different nicotine salt formulations were analyzed. Aerosols from devices containing lactic acid had higher nickel, zinc, copper, and chromium concentrations than aerosols produced by devices containing benzoic acid or levulinic acid. Our scanning electron microscope with energy dispersive X-ray analytical findings showed that the metals determined in the inductively coupled plasma-mass spectrometry analytical results were consistent with the metal compositions of the ENDS device components that were exposed to the liquids and that nickel is a major constituent in many ENDS internal components. As a result of the exposure of the nickel-containing components to the ENDS liquids, resulting aerosol nickel concentrations per puff were higher from devices that contained lactic acid in comparison to devices with benzoic or levulinic acid. The aerosol nickel concentrations in 10 puffs from ENDS-containing lactic acid were, in some cases, hundreds of times higher than cigarette mainstream smoke nickel deliveries. Thus, the design of an ENDS device in terms of both physical construction components and the liquid chemical formulations could directly impact potential exposures to toxic constituents such as metals. |
A naturally occurring HA-stabilizing amino acid (HA1-Y17) in an A(H9N2) low-pathogenic influenza virus contributes to airborne transmission
Sun X , Belser JA , Pulit-Penaloza JA , Brock N , Kieran TJ , Zeng H , Pappas C , Tumpey TM , Maines TR . mBio 2023 e0295723 Despite the accumulation of evidence showing that airborne transmissible influenza A virus (IAV) typically has a lower pH threshold for hemagglutinin (HA) fusion activation, the underlying mechanism for such a link remains unclear. In our study, by using a pair of isogenic recombinant A(H9N2) viruses with a phenotypical difference in virus airborne transmission in a ferret model due to an acid-destabilizing mutation (HA1-Y17H) in the HA, we demonstrate that an acid-stable A(H9N2) virus possesses a multitude of advantages over its less stable counterpart, including better fitness in the ferret respiratory tract, more effective aerosol emission from infected animals, and improved host susceptibility. Our study provides supporting evidence for the requirement of acid stability in efficient airborne transmission of IAV and sheds light on fundamental mechanisms for virus airborne transmission. |
Concerning rates of laboratory-confirmed antifungal-resistant onychomycosis and tinea pedis: An online survey of podiatrists, United States
Benedict K , Gold JAW , Jones CT , Tushla LA , Lipner SR , Joseph WS , Tower DE , Elewski B , Pappas PG . Health Sci Rep 2023 6 (11) e1694 Onychomycosis (tinea unguium) and tinea pedis are common, frequently concomitant infections of the nails and feet, respectively, and are often caused by dermatophyte fungi (Trichophyton, Microsporum, and Epidermophyton spp.). 1 Antifungal‐resistant tinea is an emerging global public health problem. 2 A recent, large analysis of toenail samples from US patients with suspected onychomycosis found that nearly 4% of Trichophyton spp samples had squalene epoxidase gene mutations, which are associated with terbinafine resistance. 3 Clinicians may be increasingly likely to encounter resistant tinea infections. Therefore, we aimed to assess diagnostic approaches, antifungal resistance testing practices, and treatment practices for treatment‐resistant onychomycosis and tinea pedis. |
A conceptual framework for nomenclatural stability and validity of medically important fungi: a proposed global consensus guideline for fungal name changes supported by ABP, ASM, CLSI, ECMM, ESCMID-EFISG, EUCAST-AFST, FDLC, IDSA, ISHAM, MMSA, and MSGERC
de Hoog S , Walsh TJ , Ahmed SA , Alastruey-Izquierdo A , Alexander BD , Arendrup MC , Babady E , Bai FY , Balada-Llasat JM , Borman A , Chowdhary A , Clark A , Colgrove RC , Cornely OA , Dingle TC , Dufresne PJ , Fuller J , Gangneux JP , Gibas C , Glasgow H , Gräser Y , Guillot J , Groll AH , Haase G , Hanson K , Harrington A , Hawksworth DL , Hayden RT , Hoenigl M , Hubka V , Johnson K , Kus JV , Li R , Meis JF , Lackner M , Lanternier F , Leal SM Jr , Lee F , Lockhart SR , Luethy P , Martin I , Kwon-Chung KJ , Meyer W , Nguyen MH , Ostrosky-Zeichner L , Palavecino E , Pancholi P , Pappas PG , Procop GW , Redhead SA , Rhoads DD , Riedel S , Stevens B , Sullivan KO , Vergidis P , Roilides E , Seyedmousavi A , Tao L , Vicente VA , Vitale RG , Wang QM , Wengenack NL , Westblade L , Wiederhold N , White L , Wojewoda CM , Zhang SX . J Clin Microbiol 2023 61 (11) e0087323 The rapid pace of name changes of medically important fungi is creating challenges for clinical laboratories and clinicians involved in patient care. We describe two sources of name change which have different drivers, at the species versus the genus level. Some suggestions are made here to reduce the number of name changes. We urge taxonomists to provide diagnostic markers of taxonomic novelties. Given the instability of phylogenetic trees due to variable taxon sampling, we advocate to maintain genera at the largest possible size. Reporting of identified species in complexes or series should where possible comprise both the name of the overarching species and that of the molecular sibling, often cryptic species. Because the use of different names for the same species will be unavoidable for many years to come, an open access online database of the names of all medically important fungi, with proper nomenclatural designation and synonymy, is essential. We further recommend that while taxonomic discovery continues, the adaptation of new name changes by clinical laboratories and clinicians be reviewed routinely by a standing committee for validation and stability over time, with reference to an open access database, wherein reasons for changes are listed in a transparent way. |
Clinical testing guidance for coccidioidomycosis, histoplasmosis, and blastomycosis in patients with community-acquired pneumonia for primary and urgent care providers
Smith DJ , Free RJ , Thompson Iii GR , Baddley JW , Pappas PG , Benedict K , Gold JAW , Tushla LA , Chiller T , Jackson BR , Toda M . Clin Infect Dis 2023 Coccidioidomycosis, histoplasmosis, and blastomycosis are underrecognized and frequently misdiagnosed fungal infections that can clinically resemble bacterial and viral community-acquired pneumonia (CAP). This guidance is intended to help clinicians in outpatient settings test for these fungal diseases in patients with CAP to reduce misdiagnoses, unnecessary antibacterial use, and poor outcomes. |
Update on outbreak of fungal meningitis among U.S. residents who received epidural anesthesia at two clinics in Matamoros, Mexico
Smith DJ , Gold JAW , Chiller T , Bustamante ND , Marinissen MJ , Rodriquez GG , Cortes VBG , Molina CD , Williams S , Vazquez Deida AA , Byrd K , Pappas PG , Patterson TF , Wiederhold NP , Thompson Iii GR , Ostrosky-Zeichner L . Clin Infect Dis 2023 BACKGROUND: Public health officials are responding to an outbreak of fungal meningitis among patients who received procedures under epidural anesthesia at two clinics (River Side Surgical Center and Clinica K-3) in Matamoros, Mexico, during January 1-May 13, 2023. This report describes outbreak epidemiology and outlines interim diagnostic and treatment recommendations. METHODS: Interim recommendations for diagnosis and management were developed by the Mycoses Study Group Research Education and Consortium (MSGERC) based on the clinical experience of clinicians caring for patients during the current outbreak or during previous outbreaks of healthcare-associated fungal meningitis in Durango, Mexico, and the United States. RESULTS: As of July 7, 2023, the situation has evolved into a multistate and multinational fungal meningitis outbreak. A total of 185 residents in 22 U.S. states and jurisdictions have been identified who might be at risk of fungal meningitis because they received epidural anesthesia at the clinics of interest in 2023. Among these patients, 11 suspected, 10 probable, and 10 confirmed U.S. cases have been diagnosed, with severe vascular complications and eight deaths occurring. Fusarium solani species complex has been identified as the causative agent, with antifungal susceptibility testing of a single isolate demonstrating poor in vitro activity for most available antifungals. Currently, triple therapy with intravenous voriconazole, liposomal amphotericin B, and fosmanogepix is recommended. CONCLUSIONS: Efforts to understand the source of this outbreak and optimal treatment approaches are ongoing, but infectious diseases physicians should be aware of available treatment recommendations. New information will be available on CDC's website. |
Contamination control during sample preparation for trace element analysis of electronic cigarette aerosol with inductively coupled plasma-mass spectrometry, Part 2
Pappas RS , Gray N . Spectroscopy (Santa Monica) 2023 38 (7) 6-13 Part 1 of this tutorial addressed how environmental contamination may be minimized by using proper personal analytical practices, sample preparation environmental suggestions, avoidance of glass and low purity quartz contact with samples and standards during sample collection and preparation, and appropriate choices of high purity solvents during sample collection and preparation. Part 2 continues the discussion in terms of minimizing sample contamination issues by using high purity polymer materials for sample collection and preparation, as well as discuss the differences between instrument and method limits of detection (LODs). Accepted and appropriate procedures for calculating method LODs are related to variability in instrument response and unavoidable environmental contamination during even the cleanest sample preparation. Adherence to such practices will help analysts avoid false positives and report results with a high level of confidence. © 2023 Advanstar Communications Inc.. All rights reserved. |
COVID-19 cases and hospitalizations averted by case investigation and contact tracing in the United States (preprint)
Rainisch G , Jeon S , Pappas D , Spencer KD , Fischer LS , Adhikari BB , Taylor MM , Greening B , Moonan PK , Oeltmann JE , Kahn EB , Washington ML , Meltzer MI . medRxiv 2021 21 Importance: Evidence of the impact of COVID-19 Case Investigation and Contact Tracing (CICT) programs is lacking. Policymakers need this evidence to assess its value. Objective(s): Estimate COVID-19 cases and hospitalizations averted nationwide by US states' CICT programs. Design(s): We combined data from US CICT programs (e.g., proportion of cases interviewed, contacts notified or monitored, and days to case and contact notification) with incidence data to model CICT impacts over 60 days period (November 25, 2020 to January 23, 2021) during the height of the pandemic. We estimated a range of impacts by varying assumed compliance with isolation and quarantine recommendations. Setting(s): US States and Territories Participants: Fifty-nine state and territorial health departments that received federal funding supporting COVID-19 pandemic response activities were eligible for inclusion. Of these, 22 states and 1 territory reported all measures necessary for the analysis. These 23 jurisdictions covered 42.5% of the US population (140 million persons), spanned all 4 census regions, and reported data that reflected all 59 federally funded CICT programs. Intervention(s): Public health case investigation and contact tracing Main Outcomes and Measures: Cases and hospitalizations averted; percent of cases averted among cases not prevented by vaccination and other non-pharmaceutical interventions (other NPIs). Result(s): We estimated 1.11 million cases and 27,231 hospitalizations were averted by CICT programs under a scenario where 80% of interviewed cases and monitored contacts, and 30% of notified contacts fully complied with isolation and quarantine guidance, eliminating their contributions to future transmission. As many as 1.36 million cases and 33,527 hospitalizations could have been prevented if all interviewed cases and monitored contacts had entered into and fully complied with isolation and quarantine guidelines upon being interviewed or notified. Across all scenarios and jurisdictions, CICT averted a median of 21.2% (range: 1.3% - 65.8%) of the cases not prevented by vaccination and other NPIs. Conclusions and Relevance: CICT programs likely had a substantial role in curtailing the pandemic in most jurisdictions during the winter 2020-2021 peak. Differences in impact across jurisdictions indicate an opportunity to further improve CICT effectiveness. These estimates demonstrate the potential benefits from sustaining and improving these programs. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license. |
Influenza A virus multicycle replication yields comparable viral population emergence in human respiratory and ocular cell types
Kieran TJ , DaSilva J , Stark TJ , York IA , Pappas C , Barnes JR , Maines TR , Belser JA . Microbiol Spectr 2023 11 (4) e0116623 While primarily considered a respiratory pathogen, influenza A virus (IAV) is nonetheless capable of spreading to, and replicating in, numerous extrapulmonary tissues in humans. However, within-host assessments of genetic diversity during multicycle replication have been largely limited to respiratory tract tissues and specimens. As selective pressures can vary greatly between anatomical sites, there is a need to examine how measures of viral diversity may vary between influenza viruses exhibiting different tropisms in humans, as well as following influenza virus infection of cells derived from different organ systems. Here, we employed human primary tissue constructs emulative of the human airway or corneal surface, and we infected both with a panel of human- and avian-origin IAV, inclusive of H1 and H3 subtype human viruses and highly pathogenic H5 and H7 subtype viruses, which are associated with both respiratory disease and conjunctivitis following human infection. While both cell types supported productive replication of all viruses, airway-derived tissue constructs elicited greater induction of genes associated with antiviral responses than did corneal-derived constructs. We used next-generation sequencing to examine viral mutations and population diversity, utilizing several metrics. With few exceptions, generally comparable measures of viral diversity and mutational frequency were detected following homologous virus infection of both respiratory-origin and ocular-origin tissue constructs. Expansion of within-host assessments of genetic diversity to include IAV with atypical clinical presentations in humans or in extrapulmonary cell types can provide greater insight into understanding those features most prone to modulation in the context of viral tropism. IMPORTANCE Influenza A virus (IAV) can infect tissues both within and beyond the respiratory tract, leading to extrapulmonary complications, such as conjunctivitis or gastrointestinal disease. Selective pressures governing virus replication and induction of host responses can vary based on the anatomical site of infection, yet studies examining within-host assessments of genetic diversity are typically only conducted in cells derived from the respiratory tract. We examined the contribution of influenza virus tropism on these properties two different ways: by using IAV associated with different tropisms in humans, and by infecting human cell types from two different organ systems susceptible to IAV infection. Despite the diversity of cell types and viruses employed, we observed generally similar measures of viral diversity postinfection across all conditions tested; these findings nonetheless contribute to a greater understanding of the role tissue type contributes to the dynamics of virus evolution within a human host. |
Analysis of Toxic Metals in Aerosols from Devices Associated with Electronic Cigarette, or Vaping, Product Use Associated Lung Injury
Gonzalez-Jimenez N , Gray N , Pappas RS , Halstead M , Lewis E , Valentin-Blasini L , Watson C , Blount B . Toxics 2021 9 (10) Research gaps exist in toxic metals characterization in e-cigarette, or vaping, products (EVPs) as these analytes typically have low concentrations and most standard aerosol trapping techniques have high metals background. An additional complication arises from differences in the EVP liquid formulations with nicotine products having polar properties and non-nicotine products often being non-polar. Differences in polar and non-polar matrices and the subsequent aerosol chemistries from various EVPs required modifications of our previously reported nicotine-based EVP aerosol method. Validation and application of the expanded method, suitable for both hydrophobic and hydrophilic aerosols, are reported here. The metals analyzed for this study were Al, Cr, Fe, Co, Ni, Cu, Cd, Sn, Ba, and Pb. The method limits of detection for the modified method ranged from 0.120 ng/10 puffs for Cd to 29.3 ng/10 puffs for Al and were higher than reported for the previous method. Results of the analyses for metals in aerosols obtained from 50 EVP products are reported. Cannabinoid based EVP aerosols were below reportable levels, except for one sample with 16.08 ng/10 puffs for Cu. Nicotine-based EVP results ranged from 6.72 ng/10 puffs for Pb to 203 ng/10 puffs for Sn. Results of the analyses for these metals showed that aerosols from only 5 of the 50 devices tested had detectable metal concentrations. Concentrations of toxic elements in the aerosols for nicotine-based EVP aerosol metal concentration ranges were consistent with previously published results of aerosol analyses from this class of devices. |
Food and Drug Administration public workshop summary-development considerations of antifungal drugs to address unmet medical need
Yasinskaya Y , Bala S , Waack U , Dixon C , Higgins K , Moore JN , Jjingo CJ , O'Shaughnessy E , Colangelo P , Botgros R , Nambiar S , Angulo D , Dane A , Chiller T , Hodges MR , Sandison T , Hope W , Walsh TJ , Pappas P , Katragkou A , Kovanda L , Rex JH , Marr KA , Ostrosky-Zeichner L , Sekine S , Deshpande M , Shukla SJ , Farley J . Clin Infect Dis 2023 77 (3) 380-387 Pressing challenges in the treatment of invasive fungal infections (IFI) 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 (e.g., pediatrics); and heterogeneity of the IFIs. On August 4, 2020, the U.S. 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 paper 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. |
Enhanced fitness of SARS-CoV-2 B.1.617.2 Delta variant in ferrets.
Sun X , Belser JA , Kieran TJ , Brock N , Pulit-Penaloza JA , Pappas C , Basu Thakur P , Jones J , Wentworth DE , Zhou B , Tumpey TM , Maines TR . Virology 2023 582 57-61 Competition assays were conducted in vitro and in vivo to examine how the Delta (B.1.617.2) variant displaced the prototype Washington/1/2020 (WA/1) strain. While WA/1 virus exhibited a moderately increased proportion compared to that in the inoculum following co-infection in human respiratory cells, Delta variant possessed a substantial in vivo fitness advantage as this virus becoming predominant in both inoculated and contact animals. This work identifies critical traits of the Delta variant that likely played a role in it becoming a dominant variant and highlights the necessities of employing multiple model systems to assess the fitness of newly emerged SARS-CoV-2 variants. |
Fatal Human Rabies Infection with Suspected Host-mediated Failure of Post-Exposure Prophylaxis Following a Recognized Zoonotic Exposure-Minnesota, 2021.
Holzbauer SM , Schrodt CA , Prabhu RM , Asch-Kendrick RJ , Ireland M , Klumb C , Firestone MJ , Liu G , Harry K , Ritter JM , Levine MZ , Orciari LA , Wilkins K , Yager P , Gigante CM , Ellison JA , Zhao H , Niezgoda M , Li Y , Levis R , Scott D , Satheshkumar PS , Petersen BW , Rao AK , Bell WR , Bjerk SM , Forrest S , Gao W , Dasheiff R , Russell K , Pappas M , Kiefer J , Bickler W , Wiseman A , Jurantee J , Reichard RR , Smith KE , Lynfield R , Scheftel J , Wallace RM , Bonwitt J . Clin Infect Dis 2023 77 (8) 1201-1208 BACKGROUND: No rabies post-exposure prophylaxis (PEP) failure has been documented in humans in the United States using modern cell-culture vaccines. In January 2021, an 84-year-old male died from rabies six months after being bitten by a rabid bat despite receiving timely rabies post-exposure prophylaxis (PEP). We investigated the cause of breakthrough infection. METHODS: We reviewed medical records, laboratory results, and autopsy findings, and performed whole genome sequencing (WGS) to compare patient and bat virus sequences. Storage, administration, and integrity of PEP biologics administered to the patient were assessed; samples from leftover rabies immunoglobulin were evaluated for potency. We conducted risk assessments for persons potentially exposed to the bat and for close contacts of the patient. RESULTS: Rabies virus antibodies present in serum and cerebrospinal fluid were non-neutralizing. Antemortem blood testing revealed the patient had unrecognized monoclonal gammopathy of unknown significance. Autopsy findings showed rabies meningoencephalitis and metastatic prostatic adenocarcinoma. Rabies virus sequences from the patient and the offending bat were identical by WGS. No deviations were identified in potency, quality control, administration, or storage of administered PEP. Of 332 persons assessed for potential rabies exposure to the case patient, three (0.9%) warranted PEP. CONCLUSION: This is the first reported failure of rabies PEP in the Western Hemisphere using a cell culture vaccine. Host-mediated primary vaccine failure attributed to previously unrecognized impaired immunity is the most likely explanation for this breakthrough infection. Clinicians should consider measuring rabies neutralizing antibody titers after completion of PEP if there is any suspicion for immunocompromise. |
Global responses to the COVID-19 pandemic
Cassell CH , Raghunathan PL , Henao O , Pappas-DeLuca KA , Rémy WL , Dokubo EK , Merrill RD , Marston BJ . Emerg Infect Dis 2022 28 (13) S4-s7 Confronted with a novel coronavirus, countries worldwide were forced to rapidly adjust their public health systems, platforms, and tools to respond to COVID-19. The US Centers for Disease Control and Prevention (CDC) and its global partners adapted health systems and programs originally developed for other purposes, such as controlling the HIV/AIDS pandemic through the US President’s Emergency Plan for AIDS Relief (PEPFAR), Global Health Security Agenda implementation, influenza surveillance, and vaccine-preventable disease elimination and eradication. This special supplement of Emerging Infectious Diseases highlights responses to the early phases of the COVID-19 pandemic from >80 countries, spanning 6 continents and representing >130 organizations. This article summarizes global adaptations of core public health functions during COVID-19: surveillance, information, and laboratory systems; workforce, institutional, and public health capacity; and clinical and health services delivery. |
Relapsing Fever Caused by Borrelia lonestari after Tick Bite in Alabama, USA.
Vazquez Guillamet LJ , Marx GE , Benjamin W , Pappas P , Lieberman NAP , Bachiashvili K , Leal S , Lieberman JA . Emerg Infect Dis 2023 29 (2) 441-444 We report an immunocompromised patient in Alabama, USA, 75 years of age, with relapsing fevers and pancytopenia who had spirochetemia after a tick bite. We identified Borrelia lonestari by using PCR, sequencing, and phylogenetic analysis. Increasing clinical availability of molecular diagnostics might identify B. lonestari as an emerging tickborne pathogen. |
Kinetics and magnitude of viral RNA shedding as indicators for Influenza A virus transmissibility in ferrets
Pulit-Penaloza JA , Brock N , Belser JA , Sun X , Pappas C , Tumpey TM , Maines TR . Commun Biol 2023 6 (1) 90 The ferret transmission model is routinely used to evaluate the pandemic potential of newly emerging influenza A viruses. However, concurrent measurement of viral load in the air is typically not a component of such studies. To address this knowledge gap, we measured the levels of virus in ferret nasal washes as well as viral RNA emitted into the air for 14 diverse influenza viruses, encompassing human-, swine-, and avian-origin strains. Here we show that transmissible viruses display robust replication and fast release into the air. In contrast, poorly- and non-transmissible viruses show significantly reduced or delayed replication along with lower detection of airborne viral RNA at early time points post inoculation. These findings indicate that efficient ferret-to-ferret transmission via the air is directly associated with fast emission of virus-laden particles; as such, quantification of viral RNA in the air represents a useful addition to established assessments of new influenza virus strains. |
Detection of Airborne Influenza A and SARS-CoV-2 Virus Shedding following Ocular Inoculation of Ferrets.
Belser JA , Sun X , Kieran TJ , Brock N , Pulit-Penaloza JA , Pappas C , BasuThakur P , Jones J , Wentworth DE , Zhou B , Tumpey TM , Maines TR . J Virol 2022 96 (24) e0140322 Despite reports of confirmed human infection following ocular exposure with both influenza A virus (IAV) and SARS-CoV-2, the dynamics of virus spread throughout oculonasal tissues and the relative capacity of virus transmission following ocular inoculation remain poorly understood. Furthermore, the impact of exposure route on subsequent release of airborne viral particles into the air has not been examined previously. To assess this, ferrets were inoculated by the ocular route with A(H1N1)pdm09 and A(H7N9) IAVs and two SARS-CoV-2 (early pandemic Washington/1 and Delta variant) viruses. Virus replication was assessed in both respiratory and ocular specimens, and transmission was evaluated in direct contact or respiratory droplet settings. Viral RNA in aerosols shed by inoculated ferrets was quantified with a two-stage cyclone aerosol sampler (National Institute for Occupational Safety and Health [NIOSH]). All IAV and SARS-CoV-2 viruses mounted a productive and transmissible infection in ferrets following ocular inoculation, with peak viral titers and release of virus-laden aerosols from ferrets indistinguishable from those from ferrets inoculated by previously characterized intranasal inoculation methods. Viral RNA was detected in ferret conjunctival washes from all viruses examined, though infectious virus in this specimen was recovered only following IAV inoculation. Low-dose ocular-only aerosol exposure or inhalation aerosol exposure of ferrets to IAV similarly led to productive infection of ferrets and shedding of aerosolized virus. Viral evolution during infection was comparable between all inoculation routes examined. These data support that both IAV and SARS-CoV-2 can establish a high-titer mammalian infection following ocular exposure that is associated with rapid detection of virus-laden aerosols shed by inoculated animals. IMPORTANCE Documented human infection with influenza viruses and SARS-CoV-2 has been reported among individuals wearing respiratory protection in the absence of eye protection, highlighting the capacity of these respiratory tract-tropic viruses to exploit nonrespiratory routes of exposure to initiate productive infection. However, comprehensive evaluations of how ocular exposure may modulate virus pathogenicity and transmissibility in mammals relative to respiratory exposure are limited and have not investigated multiple virus families side by side. Using the ferret model, we show that ocular exposure with multiple strains of either coronaviruses or influenza A viruses leads to an infection that results in shedding of detectable aerosolized virus from inoculated animals, contributing toward onward transmission of both viruses to susceptible contacts. Collectively, these studies support that the ocular surface represents a susceptible mucosal surface that, if exposed to a sufficient quantity of either virus, permits establishment of an infection which is similarly transmissible as that following respiratory exposure. |
Comparative Assessment of Severe Acute Respiratory Syndrome Coronavirus 2 Variants in the Ferret Model.
Pulit-Penaloza JA , Belser JA , Sun X , Pappas C , Brock N , Kieran TJ , Ritter JM , Seixas JN , Jones J , BasuThakur P , Pusch E , Wang L , Tumpey TM , Wentworth DE , Zhou B , Maines TR . mBio 2022 13 (5) e0242122 The continued spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in humans necessitates evaluation of variants for enhanced virulence and transmission. We used the ferret model to perform a comparative analysis of four SARS-CoV-2 strains, including an early pandemic isolate from the United States (WA1), and representatives of the Alpha, Beta, and Delta lineages. While Beta virus was not capable of pronounced replication in ferrets, WA1, Alpha, and Delta viruses productively replicated in the ferret upper respiratory tract, despite causing only mild disease with no overt histopathological changes. Strain-specific transmissibility was observed; WA1 and Delta viruses transmitted in a direct contact setting, whereas Delta virus was also capable of limited airborne transmission. Viral RNA was shed in exhaled air particles from all inoculated animals but was highest for Delta virus. Prior infection with SARS-CoV-2 offered varied protection against reinfection with either homologous or heterologous variants. Notable genomic variants in the spike protein were most frequently detected following WA1 and Delta virus infection. IMPORTANCE Continued surveillance and risk assessment of emerging SARS-CoV-2 variants are critical for pandemic response and preparedness. As such, in vivo evaluations are indispensable for early detection of variants with enhanced virulence and transmission. Here, we used the ferret model to compare the pathogenicity and transmissibility of an original SARS-CoV-2 isolate (USA-WA1/2020 [WA1]) to those of a panel of Alpha, Beta, and Delta variants, as well as to evaluate protection from homologous and heterologous reinfection. We observed strain-specific differences in replication kinetics in the ferret respiratory tract and virus load emitted into the air, revealing enhanced transmissibility of the Delta virus relative to previously detected strains. Prior infection with SARS-CoV-2 provided varied levels of protection from reinfection, with the Beta strain eliciting the lowest level of protection. Overall, we found that ferrets represent a useful model for comparative assessments of SARS-CoV-2 infection, transmission, and reinfection. |
A Care Step Pathway for the Diagnosis and Treatment of COVID-19-Associated Invasive Fungal Infections in the Intensive Care Unit.
Jones CT , Kopf RS , Tushla L , Tran S , Hamilton C , Lyman M , McMullen R , Shah D , Stroman A , Wilkinson E , Kelmenson D , Vazquez J , Pappas PG . Crit Care Nurse 2022 42 (6) e1-e11 BACKGROUND: In March 2020, the World Health Organization declared COVID-19, caused by the SARS-CoV-2 virus, a pandemic. Patients with severe cases resulting in hospitalization and mechanical ventilation are at risk for COVID-19-associated pulmonary aspergillosis, an invasive fungal infection, and should be screened for aspergillosis if they have persistent hemodynamic instability and fever. Early detection and treatment of this fungal infection can significantly reduce morbidity and mortality in this population. OBJECTIVE: To develop an evidence-based care step pathway tool to help intensive care unit clinicians assess, diagnose, and treat COVID-19-associated pulmonary aspergillosis. METHODS: A panel of 18 infectious disease experts, advanced practice registered nurses, pharmacists, and clinical researchers convened in a series of meetings to develop the Care Step Pathway tool, which was modeled on a tool developed by advanced practice nurses to evaluate and manage side effects of therapies for melanoma. The Care Step Pathway tool addresses various aspects of disease management, including assessment, screening, diagnosis, antifungal treatment, pharmacological considerations, and exclusion of other invasive fungal coinfections. RESULTS: The Care Step Pathway tool was applied in the care of a patient with COVID-19-associated aspergillosis. The patient was successfully treated. CONCLUSION: The Care Step Pathway is an effective educational tool to help intensive care unit clinicians consider fungal infection when caring for COVID-19 patients receiving mechanical ventilation in the intensive care unit, especially when the clinical course is deteriorating and antibiotics are ineffective. |
Pathogenesis and Transmission of Human Seasonal and Swine-origin A(H1) Influenza Viruses in the Ferret Model.
Pulit-Penaloza JA , Brock N , Jones J , Belser JA , Jang Y , Sun X , Thor S , Pappas C , Zanders N , Tumpey TM , Todd Davis C , Maines TR . Emerg Microbes Infect 2022 11 (1) 1-20 Influenza A viruses (IAVs) in the swine reservoir constantly evolve, resulting in expanding genetic and antigenic diversity of strains that occasionally cause infections in humans and pose threat of emerging as a strain capable of human-to-human transmission. For these reasons, there is an ongoing need for surveillance and characterization of newly emerging strains to aid pandemic preparedness efforts, particularly for the selection of candidate vaccine viruses and conducting risk assessments. Here, we performed a parallel comparison of the pathogenesis and transmission of genetically and antigenically diverse swine-origin A(H1N1) variant (v) and A(H1N2)v, and human seasonal A(H1N1)pdm09 IAVs using the ferret model. Both groups of viruses were capable of replication in the ferret upper respiratory tract; however, variant viruses were more frequently isolated from the lower respiratory tract as compared to the human-adapted viruses. Regardless of virus origin, observed clinical signs of infection differed greatly between strains, with some viruses causing nasal discharge, sneezing and, in some instances, diarrhea in ferrets. The most striking difference between the viruses was the ability to transmit through the air. Human-adapted viruses were capable of airborne transmission between all ferret pairs. In contrast, only one out of the four tested variant viruses was able to transmit via the air as efficiently as the human-adapted viruses. Overall, this work highlights the need for sustained monitoring of emerging swine IAVs to identify strains of concern such as those that are antigenically different from vaccine strains and that possess adaptations required for efficient respiratory droplet transmission in mammals. |
Estimated COVID-19 Cases and Hospitalizations Averted by Case Investigation and Contact Tracing in the US.
Rainisch G , Jeon S , Pappas D , Spencer KD , Fischer LS , Adhikari BB , Taylor MM , Greening BJr , Moonan PK , Oeltmann JE , Kahn EB , Washington ML , Meltzer MI . JAMA Netw Open 2022 5 (3) e224042 IMPORTANCE: Evidence of the impact of COVID-19 case investigation and contact tracing (CICT) programs is lacking, but policy makers need this evidence to assess the value of such programs. OBJECTIVE: To estimate COVID-19 cases and hospitalizations averted nationwide by US states' CICT programs. DESIGN, SETTING, AND PARTICIPANTS: This decision analytical model study used combined data from US CICT programs (eg, proportion of cases interviewed, contacts notified or monitored, and days to case and contact notification) with incidence data to model outcomes of CICT over a 60-day period (November 25, 2020, to January 23, 2021). The study estimated a range of outcomes by varying assumed compliance with isolation and quarantine recommendations. Fifty-nine state and territorial health departments that received federal funding supporting COVID-19 pandemic response activities were eligible for inclusion. Data analysis was performed from July to September 2021. EXPOSURE: Public health case investigation and contact tracing. MAIN OUTCOMES AND MEASURES: The primary outcomes were numbers of cases and hospitalizations averted and the percentage of cases averted among cases not prevented by vaccination and other nonpharmaceutical interventions. RESULTS: In total, 22 states and 1 territory reported all measures necessary for the analysis. These 23 jurisdictions covered 42.5% of the US population (approximately 140 million persons), spanned all 4 US Census regions, and reported data that reflected all 59 federally funded CICT programs. This study estimated that 1.11 million cases and 27 231 hospitalizations were averted by CICT programs under a scenario where 80% of interviewed cases and monitored contacts and 30% of notified contacts fully complied with isolation and quarantine guidance, eliminating their contributions to future transmission. As many as 1.36 million cases and 33 527 hospitalizations could have been prevented if all interviewed cases and monitored contacts had entered into and fully complied with isolation and quarantine guidelines upon being interviewed or notified. Across both scenarios and all jurisdictions, CICT averted an estimated median of 21.2% (range, 1.3%-65.8%) of the cases not prevented by vaccination and other nonpharmaceutical interventions. CONCLUSIONS AND RELEVANCE: These findings suggest that CICT programs likely had a substantial role in curtailing the pandemic in most jurisdictions during the 2020 to 2021 winter peak. Differences in outcomes across jurisdictions indicate an opportunity to further improve CICT effectiveness. These estimates demonstrate the potential benefits from sustaining and improving these programs. |
Coronavirus Disease 2019-Associated Invasive Fungal Infection.
Baddley JW , Thompson GR3rd , Chen SC , White PL , Johnson MD , Nguyen MH , Schwartz IS , Spec A , Ostrosky-Zeichner L , Jackson BR , Patterson TF , Pappas PG . Open Forum Infect Dis 2021 8 (12) ofab510 Coronavirus disease 2019 (COVID-19) can become complicated by secondary invasive fungal infections (IFIs), stemming primarily from severe lung damage and immunologic deficits associated with the virus or immunomodulatory therapy. Other risk factors include poorly controlled diabetes, structural lung disease and/or other comorbidities, and fungal colonization. Opportunistic IFI following severe respiratory viral illness has been increasingly recognized, most notably with severe influenza. There have been many reports of fungal infections associated with COVID-19, initially predominated by pulmonary aspergillosis, but with recent emergence of mucormycosis, candidiasis, and endemic mycoses. These infections can be challenging to diagnose and are associated with poor outcomes. The reported incidence of IFI has varied, often related to heterogeneity in patient populations, surveillance protocols, and definitions used for classification of fungal infections. Herein, we review IFI complicating COVID-19 and address knowledge gaps related to epidemiology, diagnosis, and management of COVID-19-associated fungal infections. |
Characterizing the transport of aluminum-, silicon- and titanium-containing particles and nanoparticles in mainstream tobacco smoke
Fresquez MR , Watson CH , Valentin-Blasini L , Steven Pappas R . J Anal Toxicol 2021 45 (7) 722-729 The most commonly observed forms of aluminum, silicon and titanium in tobacco products are aluminum silicates (e.g., kaolin), silica and titanium(IV) oxide. These compounds are neither water soluble nor volatile at cigarette combustion temperatures. Rather, they are transported in mainstream tobacco smoke as particles after being freed by combustion from the tobacco filler and can induce pulmonary inflammation when inhaled. Aluminum silicate particles are the most frequently observed particles in the pulmonary macrophages of smokers and have become known as 'smokers' inclusions'. A relatively new technique, single particle triple quadrupole inductively coupled plasma-mass spectrometry was used to analyze aluminum-, silicon- and titanium-containing particle deliveries in cigarette and little cigar mainstream tobacco smoke, and to collect information on solid inorganic particles. The mass concentration of aluminum-containing particles transmitted in mainstream smoke was low (0.89-0.56 ng/cigarette), which was not surprising because aluminum silicates are not volatile. Although the collective masses (ng/cigarette) of aluminum-, silicon- and titanium-containing particles under 100 nm diameter transported in mainstream smoke were low, an abundance of 'ultrafine' particles (particles < 100 nm or nanoparticles) was observed. Limitations of the particle background equivalent diameter (the smallest detectable particle size (MassHunter 4.5 Software) due to the environmentally ubiquitous silicon background restricted the determination of silica nanoparticles, but silica particles slightly below 200 nm diameter were consistently detected. Aluminum- and titanium-containing nanoparticles were observed in all cigarette and little cigar samples, with titanium(IV) oxide particle deliveries consistently fewer in number and smaller in diameter than the other two types of particles. The highest concentrations of aluminum-containing particles (as kaolin) were in the nanoparticle range with much lower concentrations extending to the larger particle sizes (>100 nm). The number and range of particle sizes determined in mainstream smoke is consistent with pulmonary deposition of aluminum silicates described by other researchers as contributing to the 'smokers' inclusions' observed in pulmonary macrophages. |
MSG07: An International Cohort Study Comparing Epidemiology and Outcomes of Patients with Cryptococcus neoformans or Cryptococcus gattii infections
Baddley JW , Chen SC , Huisingh C , Benedict K , DeBess EE , Galanis E , Jackson BR , MacDougall L , Marsden-Haug N , Oltean H , Perfect JR , Phillips P , Sorrell TC , Pappas PG . Clin Infect Dis 2021 73 (7) 1133-1141 BACKGROUND: Cryptococcosis due to Cryptococcus neoformans and Cryptococcus gattii varies with geographic region, populations affected, disease manifestations and severity of infection, which impact treatment. METHODS: We developed a retrospective cohort of patients diagnosed with culture-proven cryptococcosis during 1995-2013 from five centers in North America and Australia. We compared underlying diseases, clinical manifestations, treatment and outcomes in patients with C. gattii or C. neoformans infection. RESULTS: A total of 709 patients (452 C. neoformans; 257 C. gattii) were identified. Mean age was 50.2 years; 61.4% were male; and 52.3% were Caucasian. Time to diagnosis was prolonged in C. gattii patients compared with C. neoformans (mean 52.2 vs 36.0 days; p<0.003) and there was a higher proportion of C. gattii patients without underlying disease (40.5% vs 10.2%; p<0.0001). Overall, 59% had central nervous system (CNS) infection, with lung (42.5%) and blood (24.5%) being common sites. Pulmonary infection was more common in patients with C. gattii than those with C. neoformans (60.7% vs 32.1%; p<0.0001). CNS or blood infections were more common in C. neoformans-infected patients (p≤0.0001 for both). Treatment of CNS disease with induction therapy of amphotericin B and flucytosine occurred in 76.4% of patients. Crude 12-month mortality was higher in patients with C neoformans (28.4% vs 20.2%; Odds Ratio 1.56; 95% CI 1.08, 2.26). CONCLUSIONS: This study emphasizes differences in species-specific epidemiology and outcomes of patients with cryptococcosis, including underlying diseases, site of infection and mortality. Species identification in patients with cryptococcosis is necessary to discern epidemiologic patterns, guide treatment regimens and predict clinical progression and outcomes. |
A review of data for quantifying human exposures to micro and nanoplastics and potential health risks
Zarus GM , Muianga C , Hunter CM , Pappas RS . Sci Total Environ 2020 756 144010 Plastic debris have been shown to degenerate to particle sizes that can be transported in air, water, and food. Small particles are documented to enter and exit our bodies and translocate to and from some internal organs. Health effects on respiratory, hepatic, immune, and gastrointestinal systems have been reported in humans and other mammals in response to elevated particle or fiber exposures. These health effects differed by plastic type and size, and there was evidence of dose response for a few health endpoints. We conducted a systematic word search and reviewed published literature to identify microplastic and nanoplastic studies that quantified exposure via the ingestion, inhalation, and subcutaneous absorption (not dermal) exposure pathways; identified translocation, internal dose, and associations with health effects and markers related to exposures to specific sizes and types of plastics. We identified the data gaps in relating exposure data to health effects and biomarkers, most notably the lack of characterization of plastic particles and fibers smaller than 10 μm in most media. |
Toxic metals in liquid and aerosol from pod-type electronic cigarettes
Gray N , Halstead M , Valentin-Blasini L , Watson C , Pappas RS . J Anal Toxicol 2020 46 (1) 69-75 High quality, accurate data on liquid contents and aerosol emissions from electronic nicotine delivery systems (ENDS, e.g. e-cigarettes) are crucial to address potential health concerns as these devices evolve and mature. Metals are an important class of ENDS constituents that merit attention as they have various health implications. Proper sampling, handling, and aerosol trapping materials are essential to generate accurate quantitative metals data and to reduce the likelihood of inaccurate results originating from inappropriate collection vessels and materials that contribute to high background levels. Published methods that meet these criteria were applied to the analyses of chromium, nickel, copper, zinc, cadmium, tin, and lead in liquid and aerosol from mint/menthol and tobacco flavors of currently popular pod-based devices from 3 manufacturers. Metal concentrations from pods that had not been used for generating aerosol ranged from below our lowest reportable level to 0.164 µg/g for Cr, 61.3 µg/g for Ni, 927 µg/g for Cu, 14.9 µg/g for Zn, 58.2 µg/g for Sn, and 2.56 µg/g for Pb. Cadmium was included in our analyte panel and was not present above detection limits in liquid or aerosol. Aerosol metal concentrations (using a 55 mL puff) ranged from below our lowest reportable level to 29.9 ng/10 puffs for Cr, 373 ng/10 puffs for Ni, 209 ng/10 puffs for Cu, 4,580 ng/10 puffs for Zn, 127 ng/10 puffs for Sn, and 463 ng/10 puffs for Pb. Our results showed some metals delivery from all the products examined and highly variable metal levels between manufacturer, brand, and package. |
Toxicological analysis of aerosols derived from three electronic nicotine delivery systems using Normal human bronchial epithelial cells
Pearce K , Gray N , Gaur P , Jeon J , Suarez A , Shannahan J , Pappas RS , Wright C . Toxicol In Vitro 2020 69 104997 Electronic nicotine delivery systems (ENDS) are a rapidly growing global market advertised as a safer alternative to combustible cigarettes. However, comprehensive investigations of END aerosol physicochemical and toxicological properties have not been fully explored across brands to assess relative safety. In this study, we evaluated aerosols collected from three ENDS - Juul Fruit Medley (5% nicotine), Logic Power (2.4% nicotine), and Mistic (1.8% nicotine). ENDS aerosols were generated using standard machine puffing regimen and collected with a novel fluoropolymer condensation trap. Triple quadrupole-inductively coupled plasma-mass determined the presence of heavy metals in collected aerosols. The toxicological effects of ENDS aerosols on normal human bronchial epithelial cells (NHBE) were investigated using cellular viability, reactive oxygen species, oxidative stress assays, along with DNA damage assessments using the CometChip©. Results indicated the total metal concentrations within collected ENDS aerosols were higher for Mistic and Logic compared to Juul. Logic Power aerosols elicited higher reactive oxygen species levels than Mistic and Juul in NHBE after 24-h exposure. Similar dose-dependent reductions of cellular viability and total glutathione were found for each exposure. However, Logic and Juul aerosols caused greater single stranded DNA damage compared to Mistic. Our study indicates that regardless of brand, ENDS aerosols are toxic to upper airway epithelial cells and may pose a potential respiratory hazard to occasional and frequent users. |
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