Last data update: Apr 22, 2024. (Total: 46599 publications since 2009)
Records 1-30 (of 58 Records) |
Query Trace: Moreno A [original query] |
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Author Correction: Multiplexed CRISPR-based microfluidic platform for clinical testing of respiratory viruses and identification of SARS-CoV-2 variants
Welch NL , Zhu M , Hua C , Weller J , Mirhashemi ME , Nguyen TG , Mantena S , Bauer MR , Shaw BM , Ackerman CM , Thakku SG , Tse MW , Kehe J , Uwera MM , Eversley JS , Bielwaski DA , McGrath G , Braidt J , Johnson J , Cerrato F , Moreno GK , Krasilnikova LA , Petros BA , Gionet GL , King E , Huard RC , Jalbert SK , Cleary ML , Fitzgerald NA , Gabriel SB , Gallagher GR , Smole SC , Madoff LC , Brown CM , Keller MW , Wilson MM , Kirby MK , Barnes JR , Park DJ , Siddle KJ , Happi CT , Hung DT , Springer M , MacInnis BL , Lemieux JE , Rosenberg E , Branda JA , Blainey PC , Sabeti PC , Myhrvold C . Nat Med 2023 In the version of the article originally published, some of the oligonucleotide sequences in Supplementary Table 4, on the “21 viruses” and “RVP” tabs, were mislabeled. The Supplementary Tables file has now been corrected. |
Proteomic and genetic analyses of influenza A viruses identify pan-viral host targets
Haas KM , McGregor MJ , Bouhaddou M , Polacco BJ , Kim EY , Nguyen TT , Newton BW , Urbanowski M , Kim H , Williams MAP , Rezelj VV , Hardy A , Fossati A , Stevenson EJ , Sukerman E , Kim T , Penugonda S , Moreno E , Braberg H , Zhou Y , Metreveli G , Harjai B , Tummino TA , Melnyk JE , Soucheray M , Batra J , Pache L , Martin-Sancho L , Carlson-Stevermer J , Jureka AS , Basler CF , Shokat KM , Shoichet BK , Shriver LP , Johnson JR , Shaw ML , Chanda SK , Roden DM , Carter TC , Kottyan LC , Chisholm RL , Pacheco JA , Smith ME , Schrodi SJ , Albrecht RA , Vignuzzi M , Zuliani-Alvarez L , Swaney DL , Eckhardt M , Wolinsky SM , White KM , Hultquist JF , Kaake RM , García-Sastre A , Krogan NJ . Nat Commun 2023 14 (1) 6030 Influenza A Virus (IAV) is a recurring respiratory virus with limited availability of antiviral therapies. Understanding host proteins essential for IAV infection can identify targets for alternative host-directed therapies (HDTs). Using affinity purification-mass spectrometry and global phosphoproteomic and protein abundance analyses using three IAV strains (pH1N1, H3N2, H5N1) in three human cell types (A549, NHBE, THP-1), we map 332 IAV-human protein-protein interactions and identify 13 IAV-modulated kinases. Whole exome sequencing of patients who experienced severe influenza reveals several genes, including scaffold protein AHNAK, with predicted loss-of-function variants that are also identified in our proteomic analyses. Of our identified host factors, 54 significantly alter IAV infection upon siRNA knockdown, and two factors, AHNAK and coatomer subunit COPB1, are also essential for productive infection by SARS-CoV-2. Finally, 16 compounds targeting our identified host factors suppress IAV replication, with two targeting CDK2 and FLT3 showing pan-antiviral activity across influenza and coronavirus families. This study provides a comprehensive network model of IAV infection in human cells, identifying functional host targets for pan-viral HDT. |
Description of a University COVID-19 Outbreak and Interventions to Disrupt Transmission, Wisconsin, August – October 2020 (preprint)
Currie DW , Moreno GK , Delahoy MJ , Pray IW , Jovaag A , Braun KM , Cole D , Shechter T , Fajardo GC , Griggs C , Yandell BS , Goldstein S , Bushman D , Segaloff HE , Kelly GP , Pitts C , Lee C , Grande KM , Kita-Yarbro A , Grogan B , Mader S , Baggott J , Bateman AC , Westergaard RP , Tate JE , Friedrich TC , Kirking HL , O'Connor DH , Killerby ME . medRxiv 2021 2021.05.07.21256834 University settings have demonstrated potential for COVID-19 outbreaks, as they can combine congregate living, substantial social activity, and a young population predisposed to mild illness. Using genomic and epidemiologic data, we describe a COVID-19 outbreak at the University of Wisconsin (UW)–Madison. During August – October 2020, 3,485 students tested positive, including 856/6,162 students living in residence halls. Case counts began rising during move-in week for on-campus students (August 25-31, 2020), then rose rapidly during September 1-11, 2020. UW-Madison initiated multiple prevention efforts, including quarantining two residence halls; a subsequent decline in cases was observed. Genomic surveillance of cases from Dane County, where UW-Madison is located, did not find evidence of transmission from a large cluster of cases in the two residence halls quarantined during the outbreak. Coordinated implementation of prevention measures can effectively reduce SARS-CoV-2 spread in university settings and may limit spillover to the community surrounding the university.Competing Interest StatementThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. Use of trade names is for identification only and does not imply endorsement by the Centers for Disease Control and Prevention.Clinical TrialN/A.Funding StatementG.K.M. is supported by an NLM training grant to the Computation and Informatics in Biology and Medicine Training Program (NLM 5T15LM007359). This work was funded in part by the U.S. Centers for Disease Control and Prevention Contract #75D30120C09870: Defining the Role of College Students in SARS-CoV-2 Spread in the Upper Midwest.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:A waiver of HIPAA Authorization was obtained by the Western Institutional Review Board (WIRB #1-1290953-1) to obtain the clinical specimens for whole genome sequencing. This analysis was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy. These activities were determined to be non-research public health surveillance by the Institutional Review Board at UW-Madison.All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesAll sequencing data is available on www.gisaid.org. Scripts for sequence data analysis is available at https://github.com/gagekmoreno/SARS-CoV-2-at-UW_Madison. https://github.com/gagekmoreno/SARS-CoV-2-at-UW_Madison |
SARS-CoV-2 transmission in intercollegiate athletics not fully mitigated with daily antigen testing (preprint)
Moreno GK , Braun KM , Pray IW , Segaloff HE , Lim A , Poulson K , Meiman J , Borcher J , Westergaard RP , Moll MK , Friedrich TC , O'Connor DH . medRxiv 2021 BACKGROUND: High frequency, rapid turnaround SARS-CoV-2 testing continues to be proposed as a way of efficiently identifying and mitigating transmission in congregate settings. However, two SARS-CoV-2 outbreaks occurred among intercollegiate university athletic programs during the fall 2020 semester despite mandatory directly observed daily antigen testing. METHODS: During the fall 2020 semester, athletes and staff in both programs were tested daily using Quidel's Sofia SARS Antigen Fluorescent Immunoassay (FIA), with positive antigen results requiring confirmatory testing with real-time reverse transcription polymerase chain reaction (RT-PCR). We used genomic sequencing to investigate transmission dynamics in these two outbreaks. RESULTS: In Outbreak 1, 32 confirmed cases occurred within a university athletics program after the index patient attended a meeting while infectious despite a negative antigen test on the day of the meeting. Among isolates sequenced from Outbreak 1, 24 (92%) of 26 were closely related, suggesting sustained transmission following an initial introduction event. In Outbreak 2, 12 confirmed cases occurred among athletes from two university programs that faced each other in an athletic competition despite receiving negative antigen test results on the day of the competition. Sequences from both teams were closely related and unique from strains circulating in the community, suggesting transmission during intercollegiate competition. CONCLUSIONS: These findings suggest that antigen testing alone, even when mandated and directly observed, may not be sufficient as an intervention to prevent SARS-CoV-2 outbreaks in congregate settings, and highlights the importance of supplementing serial antigen testing with appropriate mitigation strategies to prevent SARS-CoV-2 outbreak in congregate settings. SUMMARY: High frequency, rapid turnaround SARS-CoV-2 testing continues to be proposed as a way of efficiently identifying and mitigating transmission in congregate settings. However, here we describe two SARS-CoV-2 outbreaks occurred among intercollegiate university athletic programs during the fall 2020 semester. |
Deep dive into gaps and barriers to implementation of antimicrobial stewardship programs in hospitals in Latin America
Fabre V , Secaira C , Cosgrove SE , Lessa FC , Patel TS , Alvarez AA , Anchiraico LM , Del Carmen Bangher M , Barberis MF , Burokas MS , Castañeda X , Colque AM , De Ascencao G , Esquivel C , Ezcurra C , Falleroni LA , Frassone N , Garzón MI , Gomez C , Gonzalez JA , Hernandez D , Laplume D , Lemir CG , Maldonado Briones H , Melgar M , Mesplet F , Martinez G , Pertuz CM , Moreno C , Nemirovsky C , Nuccetelli Y , Palacio B , Sandoval N , Vergara H , Videla H , Villamandos S , Villareal O , Viteri A , Quiros R . Clin Infect Dis 2023 77 S53-s61 BACKGROUND: Antimicrobial resistance has worsened in Latin America. There is an urgent need to understand the development of antimicrobial stewardship programs (ASPs) and the barriers to implementing effective ASPs in light of limited national action plans or policies to promote ASPs in the region. METHODS: We performed a descriptive mixed-methods study of ASPs in 5 Latin American countries in March-July 2022. An electronic questionnaire with an associated scoring system (hospital ASP self-assessment) was used, and ASP development was classified based on the scores (inadequate, 0-25; basic, 26-50; intermediate, 51-75; or advanced, 76-100). Interviews among healthcare workers (HCWs) involved in antimicrobial stewardship (AS) inquired about behavioral and organizational factors that influence AS activities. Interview data were coded into themes. Results from the ASP self-assessment and interviews were integrated to create an explanatory framework. RESULTS: Twenty hospitals completed the self-assessment, and 46 AS stakeholders from these hospitals were interviewed. ASP development was inadequate/basic in 35% of hospitals, intermediate in 50%, and advanced in 15%. For-profit hospitals had higher scores than not-for-profit hospitals. Interview data validated the self-assessment findings and provided further insight into ASP implementation challenges, which included limited formal hospital leadership support, inadequate staffing and tools to perform AS work more efficiently, limited awareness of AS principles by HCWs, and limited training opportunities. CONCLUSIONS: We identified several barriers to ASP development in Latin America, suggesting the need to create accurate business cases for ASPs to obtain the necessary funding for their effective implementation and sustainability. |
Contribution of PEPFAR-supported HIV and TB molecular diagnostic networks to COVID-19 testing preparedness in 16 countries
Romano ER , Sleeman K , Hall-Eidson P , Zeh C , Bhairavabhotla R , Zhang G , Adhikari A , Alemnji G , Cardo YR , Pinheiro A , Pocongo B , Eno LT , Shang JD , Ndongmo CB , Rosario H , Moreno O , DeLen LAC , Fonjungo P , Kabwe C , Ahuke-Mundeke S , Gama D , Dlamini S , Maphalala G , Abreha T , Purfield A , Gebrehiwot YT , Desalegn DM , Basiye F , Mwangi J , Bowen N , Mengistu Y , Lecher S , Kampira E , Kaba M , Bitilinyu-Bangoh J , Masamha G , Viegas SO , Beard RS , vanRooyen G , Shiningavamwe AN , I JM , Iriemenam NC , Mba N , Okoi C , Katoro J , Kenyi DL , Bior BK , Mwangi C , Nabadda S , Kaleebu P , Yingst SL , Chikwanda P , Veri L , Simbi R , Alexander H . Emerg Infect Dis 2022 28 (13) S59-s68 The US President's Emergency Plan for AIDS Relief (PEPFAR) supports molecular HIV and tuberculosis diagnostic networks and information management systems in low- and middle-income countries. We describe how national programs leveraged these PEPFAR-supported laboratory resources for SARS-CoV-2 testing during the COVID-19 pandemic. We sent a spreadsheet template consisting of 46 indicators for assessing the use of PEPFAR-supported diagnostic networks for COVID-19 pandemic response activities during April 1, 2020, to March 31, 2021, to 27 PEPFAR-supported countries or regions. A total of 109 PEPFAR-supported centralized HIV viral load and early infant diagnosis laboratories and 138 decentralized HIV and TB sites reported performing SARS-CoV-2 testing in 16 countries. Together, these sites contributed to >3.4 million SARS-CoV-2 tests during the 1-year period. Our findings illustrate that PEPFAR-supported diagnostic networks provided a wide range of resources to respond to emergency COVID-19 diagnostic testing in 16 low- and middle-income countries. |
Diel activity patterns of vector mosquito species in the urban environment: Implications for vector control strategies
Wilke ABB , Mhlanga A , Kummer AG , Vasquez C , Moreno M , Petrie WD , Rodriguez A , Vitek C , Hamer GL , Mutebi JP , Ajelli M . PLoS Negl Trop Dis 2023 17 (1) e0011074 Mathematical models have been widely used to study the population dynamics of mosquitoes as well as to test and validate the effectiveness of arbovirus outbreak responses and mosquito control strategies. The objective of this study is to assess the diel activity of mosquitoes in Miami-Dade, Florida, and Brownsville, Texas, the most affected areas during the Zika outbreak in 2016-2017, and to evaluate the effectiveness of simulated adulticide treatments on local mosquito populations. To assess variations in the diel activity patterns, mosquitoes were collected hourly for 96 hours once a month from May through November 2019 in Miami-Dade County, Florida, and Brownsville, Texas. We then performed a PERMANOVA followed by a SIMPER analysis to assess whether the abundance and species richness significantly varies at different hours of the day. Finally, we used a mathematical model to simulate the population dynamics of 5 mosquito vector species and evaluate the effectiveness of the simulated adulticide applications. A total of 14,502 mosquitoes comprising 17 species were collected in Brownsville and 10,948 mosquitoes comprising 19 species were collected in Miami-Dade County. Aedes aegypti was the most common mosquito species collected every hour in both cities and peaking in abundance in the morning and the evening. Our modeling results indicate that the effectiveness of adulticide applications varied greatly depending on the hour of the treatment. In both study locations, 9 PM was the best time for adulticide applications targeting all mosquito vector species; mornings/afternoons (9 AM- 5 PM) yielded low effectiveness, especially for Culex species, while at night (12 AM- 6 AM) the effectiveness was particularly low for Aedes species. Our results indicate that the timing of adulticide spraying interventions should be carefully considered by local authorities based on the ecology of the target mosquito species in the focus area. |
Household transmission of influenza A viruses in 2021-2022
Rolfes MA , Talbot HK , McLean HQ , Stockwell MS , Ellingson KD , Lutrick K , Bowman NM , Bendall EE , Bullock A , Chappell JD , Deyoe JE , Gilbert J , Halasa NB , Hart KE , Johnson S , Kim A , Lauring AS , Lin JT , Lindsell CJ , McLaren SH , Meece JK , Mellis AM , Moreno Zivanovich M , Ogokeh CE , Rodriguez M , Sano E , Silverio Francisco RA , Schmitz JE , Vargas CY , Yang A , Zhu Y , Belongia EA , Reed C , Grijalva CG . JAMA 2023 329 (6) 482-489 IMPORTANCE: Influenza virus infections declined globally during the COVID-19 pandemic. Loss of natural immunity from lower rates of influenza infection and documented antigenic changes in circulating viruses may have resulted in increased susceptibility to influenza virus infection during the 2021-2022 influenza season. OBJECTIVE: To compare the risk of influenza virus infection among household contacts of patients with influenza during the 2021-2022 influenza season with risk of influenza virus infection among household contacts during influenza seasons before the COVID-19 pandemic in the US. DESIGN, SETTING, AND PARTICIPANTS: This prospective study of influenza transmission enrolled households in 2 states before the COVID-19 pandemic (2017-2020) and in 4 US states during the 2021-2022 influenza season. Primary cases were individuals with the earliest laboratory-confirmed influenza A(H3N2) virus infection in a household. Household contacts were people living with the primary cases who self-collected nasal swabs daily for influenza molecular testing and completed symptom diaries daily for 5 to 10 days after enrollment. EXPOSURES: Household contacts living with a primary case. MAIN OUTCOMES AND MEASURES: Relative risk of laboratory-confirmed influenza A(H3N2) virus infection in household contacts during the 2021-2022 season compared with prepandemic seasons. Risk estimates were adjusted for age, vaccination status, frequency of interaction with the primary case, and household density. Subgroup analyses by age, vaccination status, and frequency of interaction with the primary case were also conducted. RESULTS: During the prepandemic seasons, 152 primary cases (median age, 13 years; 3.9% Black; 52.0% female) and 353 household contacts (median age, 33 years; 2.8% Black; 54.1% female) were included and during the 2021-2022 influenza season, 84 primary cases (median age, 10 years; 13.1% Black; 52.4% female) and 186 household contacts (median age, 28.5 years; 14.0% Black; 63.4% female) were included in the analysis. During the prepandemic influenza seasons, 20.1% (71/353) of household contacts were infected with influenza A(H3N2) viruses compared with 50.0% (93/186) of household contacts in 2021-2022. The adjusted relative risk of A(H3N2) virus infection in 2021-2022 was 2.31 (95% CI, 1.86-2.86) compared with prepandemic seasons. CONCLUSIONS AND RELEVANCE: Among cohorts in 5 US states, there was a significantly increased risk of household transmission of influenza A(H3N2) in 2021-2022 compared with prepandemic seasons. Additional research is needed to understand reasons for this association. |
Multiple introductions and recombination events underlie the emergence of a hyper-transmissible Cryptosporidium hominis subtype in the USA.
Huang W , Guo Y , Lysen C , Wang Y , Tang K , Seabolt MH , Yang F , Cebelinski E , Gonzalez-Moreno O , Hou T , Chen C , Chen M , Wan M , Li N , Hlavsa MC , Roellig DM , Feng Y , Xiao L . Cell Host Microbe 2022 31 (1) 112-123 e4 The parasite Cryptosporidium hominis is a leading cause of the diarrheal disease cryptosporidiosis, whose incidence in the United States has increased since 2005. Here, we show that the newly emerged and hyper-transmissible subtype IfA12G1R5 is now dominant in the United States. In a comparative analysis of 127 newly sequenced and 95 published C. hominis genomes, IfA12G1R5 isolates from the United States place into three of the 14 clusters (Pop6, Pop13, and Pop14), indicating that this subtype has multiple ancestral origins. Pop6 (IfA12G1R5a) has an East Africa origin and has recombined with autochthonous subtypes after its arrival. Pop13 (IfA12G1R5b) is imported from Europe, where it has recombined with the prevalent local subtype, whereas Pop14 (IfA12G1R5c) is a progeny of secondary recombination between Pop6 and Pop13. Selective sweeps in invasion-associated genes have accompanied the emergence of the dominant Pop14. These observations offer insights into the emergence and evolution of hyper-transmissible pathogens. |
MaHPIC malaria systems biology data from Plasmodium cynomolgi sporozoite longitudinal infections in macaques.
DeBarry JD , Nural MV , Pakala SB , Nayak V , Warrenfeltz S , Humphrey J , Lapp SA , Cabrera-Mora M , Brito CFA , Jiang J , Saney CL , Hankus A , Stealey HM , DeBarry MB , Lackman N , Legall N , Lee K , Tang Y , Gupta A , Trippe ED , Bridger RR , Weatherly DB , Peterson MS , Jiang X , Tran V , Uppal K , Fonseca LL , Joyner CJ , Karpuzoglu E , Cordy RJ , Meyer EVS , Wells LL , Ory DS , Lee FE , Tirouvanziam R , Gutiérrez JB , Ibegbu C , Lamb TJ , Pohl J , Pruett ST , Jones DP , Styczynski MP , Voit EO , Moreno A , Galinski MR , Kissinger JC . Sci Data 2022 9 (1) 722 Plasmodium cynomolgi causes zoonotic malarial infections in Southeast Asia and this parasite species is important as a model for Plasmodium vivax and Plasmodium ovale. Each of these species produces hypnozoites in the liver, which can cause relapsing infections in the blood. Here we present methods and data generated from iterative longitudinal systems biology infection experiments designed and performed by the Malaria Host-Pathogen Interaction Center (MaHPIC) to delve deeper into the biology, pathogenesis, and immune responses of P. cynomolgi in the Macaca mulatta host. Infections were initiated by sporozoite inoculation. Blood and bone marrow samples were collected at defined timepoints for biological and computational experiments and integrative analyses revolving around primary illness, relapse illness, and subsequent disease and immune response patterns. Parasitological, clinical, haematological, immune response, and -omic datasets (transcriptomics, proteomics, metabolomics, and lipidomics) including metadata and computational results have been deposited in public repositories. The scope and depth of these datasets are unprecedented in studies of malaria, and they are projected to be a F.A.I.R., reliable data resource for decades. |
Assessing costs of a hypertension program in primary care: evidence from the HEARTS program in Mexico
Chivardi C , Hutchinson B , Molina V , Moreno E , Fajardo I , Giraldo-Arcila GP , Malo HM , Ordunez P , Rodrguez-Franco R , Moran AE , Kostova D . Rev Panam Salud Publica 2022 46 e144 OBJECTIVE: In 2021, Mexico launched the HEARTS program to improve the prevention and control of cardiovascular disease (CVD) risk factors in 20 primary care facilities in the states of Chiapas and Yucatn. This study projects the annual cost of program implementation and discusses budgetary implications for scaling up the program. METHODS: We obtained district-level data on treatment protocols, medication costs, and other resources required to prevent and treat CVD. We used the HEARTS Costing Tool to estimate total and per-patient costs. A "partial implementation" scenario calculated the costs of implementing HEARTS if existing pharmacological treatment protocols are left in place. The second scenario, "full implementation," examined costs if programs use HEARTS pharmacological protocol. RESULTS: Respectively in the partial and full implementation scenarios, total annual costs to implement and operate HEARTS were $260 023 ($32.1 per patient/year) and $255 046 ($31.5 per patient/year) in Chiapas, and $1 000 059 ($41.3 per patient/year) and $1 013 835 ($43.3 per patient/year) in Yucatn. In Chiapas, adopting HEARTS standardized treatment protocols resulted in a 9.7 % reduction in annual medication expenditures relative to maintaining status-quo treatment approaches. In Yucatn, adoption was $12 875 more expensive, in part because HEARTS hypertension treatment regimens were more intensive than status quo regimens. CONCLUSION: HEARTS in the Americas offers a standardized strategy to treating and controlling CVD risk factors. In Mexico, approaches that may lead to improved program affordability include adoption of the recommended HEARTS treatment protocols with preferred medications and task shifting of services from physicians to nurses and other providers. |
The use of readily available laboratory tests for the identification of the emerging yeast Candida auris in Mexico
González-Durán E , Contreras-Pérez CU , Caceres DH , Ríos-Rosas C , Piñón-Ortega JJ , Téllez-Saucedo MD , Marín-Suro ES , Wong-Arámbula CE , Moreno-Escobar EA , Ramírez-González JE , Ramírez-Barrios JG , Montes-Colima NA , Lockhart SR , Martínez-Montiel N , Martínez-Contreras RD , García-Ruíz P , Salazar-Sánchez MI , Hernández-Rivas L , López-Martínez I . Arch Microbiol 2022 204 (9) 592 Identification of the emerging multidrug-resistant yeast Candida auris is challenging. Here, we describe the role of the Mexico national reference laboratory Instituto de Diagnóstico y Referencia Epidemiológicos Dr. Manuel Martínez Báez (InDRE) and the Mexican national laboratory network in the identification of C. auris. Reference identification of six suspected isolates was done based on phenotypic and molecular laboratory methods, including growth in special media, evaluation of isolate micromorphology, and species-specific PCR and pan-fungal PCR and sequencing. The four C. auris isolates identified were able to grow on modified Sabouraud agar with 10% NaCl incubated at 42 °C. With one exception, isolates of C. auris were spherical to ovoid yeast-like cells and blastoconidia, with no hyphae or pseudohyphae on cornmeal agar. C. auris isolates were resistant to fluconazole. Species-specific and pan-fungal PCR confirmed isolates as C. auris. Sequence analysis revealed the presence of two different C. auris clades in Mexico, clade I (South Asia) and clade IV (South America). |
Self-medication and ILI etiologies among individuals presenting at pharmacies with influenza-like illness: Guatemala City, 2018 influenza season
Ramay BM , Jara J , Moreno MP , Lupo P , Serrano C , Alvis JP , Arriola CS , Veguilla V , Kaydos-Daniels SC . BMC Public Health 2022 22 (1) 1541 OBJECTIVES: We aimed to characterize the proportion of clients presenting to community pharmacies with influenza-like illness (ILI) and the severity of their illness; the proportion with detectable influenza A, influenza B, and other pathogens (i.e., parainfluenza I, II, and III, adenovirus, respiratory syncytial virus, human metapneumovirus); and to describe their self-medication practices. METHODS: A cross-sectional study was conducted in six pharmacies in Guatemala City. Study personnel collected nasopharyngeal and oropharyngeal swabs from participants who met the ILI case definition and who were self-medicating for the current episode. Participants were tested for influenza A and B and other pathogens using real-time RT-PCR. Participants' ILI-associated self-medication practices were documented using a questionnaire. RESULTS: Of all patients entering the pharmacy during peak hours who responded to a screening survey (n = 18,016) 6% (n = 1029) self-reported ILI symptoms, of which 45% (n = 470/1029) met the study case definition of ILI. Thirty-one percent (148/470) met inclusion criteria, of which 87% (130/148) accepted participation and were enrolled in the study. Among 130 participants, nearly half tested positive for viral infection (n = 55, 42.3%) and belonged to groups at low risk for complications from influenza. The prevalence of influenza A was 29% (n = 35). Thirteen percent of the study population (n = 17) tested positive for a respiratory virus other than influenza. Sixty-four percent of participants (n = 83) reported interest in receiving influenza vaccination if it were to become available in the pharmacy. Medications purchased included symptom-relieving multi-ingredient cold medications (n = 43/100, 43%), nonsteroidal anti-inflammatory drugs (n = 23, 23%), and antibiotics (n = 16, 16%). Antibiotic use was essentially equal among antibiotic users regardless of viral status. The broad-spectrum antibiotics ceftriaxone and azithromycin were the most common antibiotics purchased. CONCLUSIONS: During a typical influenza season, a relatively low proportion of all pharmacy visitors were experiencing influenza symptoms. A high proportion of clients presenting to pharmacies with ILI tested positive for a respiratory virus. Programs that guide appropriate use of antibiotics in this population are needed and become increasingly important during pandemics caused by respiratory viral pathogens. |
The use of a chimeric antigen for Plasmodium falciparum and P. vivax seroprevalence estimates from community surveys in Ethiopia and Costa Rica.
McCaffery JN , Singh B , Nace D , Assefa A , Hwang J , Plucinski M , Calvo N , Moreno A , Udhayakumar V , Rogier E . PLoS One 2022 17 (5) e0263485 BACKGROUND: In low-transmission settings, accurate estimates of malaria transmission are needed to inform elimination targets. Detection of antimalarial antibodies provides exposure history, but previous studies have mainly relied on species-specific antigens. The use of chimeric antigens that include epitopes from multiple species of malaria parasites in population-based serological surveys could provide data for exposure to multiple Plasmodium species circulating in an area. Here, the utility of P. vivax/P. falciparum chimeric antigen for assessing serological responses was evaluated in Ethiopia, an endemic country for all four human malarias, and Costa Rica, where P. falciparum has been eliminated with reports of sporadic P. vivax cases. METHODS: A multiplex bead-based assay was used to determine the seroprevalence of IgG antibodies against a chimeric malaria antigen (PvRMC-MSP1) from blood samples collected from household surveys in Ethiopia in 2015 (n = 7,077) and Costa Rica in 2015 (n = 851). Targets specific for P. falciparum (PfMSP1) and P. vivax (PvMSP1) were also included in the serological panel. Seroprevalence in the population and seroconversion rates were compared among the three IgG targets. RESULTS: Seroprevalence in Costa Rica was 3.6% for PfMSP1, 41.5% for PvMSP1 and 46.7% for PvRMC-MSP1. In Ethiopia, seroprevalence was 27.6% for PfMSP1, 21.4% for PvMSP1, and 32.6% for PvRMC-MSP1. IgG levels in seropositive individuals were consistently higher for PvRMC-MSP1 when compared to PvMSP1 in both studies. Seroconversion rates were 0.023 for PvMSP1 and 0.03 for PvRMC-MSP1 in Costa Rica. In Ethiopia, seroconversion rates were 0.050 for PfMSP1, 0.044 for PvMSP1 and 0.106 for PvRMC-MSP1. CONCLUSIONS: Our data indicate that chimeric antigen PvRMC-MSP1 is able to capture antibodies to multiple epitopes from both prior P. falciparum and P. vivax infections, and suitable chimeric antigens can be considered for use in serosurveys with appropriate validation. |
Diel activity patterns of two distinct populations of Aedes aegypti in Miami, FL and Brownsville, TX
Mutebi JP , Wilke ABB , Ostrum E , Vasquez C , Cardenas G , Carvajal A , Moreno M , Petrie WD , Rodriguez A , Presas H , Rodriguez J , Barnes F , Hamer GL , Juarez JG , Carbajal E , Vitek CJ , Estrada X , Rios T , Marshall J , Beier JC . Sci Rep 2022 12 (1) 5315 The diel biting activity of Aedes (Stegomyia) aegypti (L) populations was extensively investigated in the early 1900s to gain more information on the biology of Ae. aegypti, and this information was used to devise effective approaches to controlling populations of this species and protect the human population from widespread arbovirus outbreaks. However, few contemporary studies are available regarding the diel activity patterns of Ae. aegypti. To assess the diel activity patterns of Ae. aegypti in southern Florida and Texas, we conducted 96-h uninterrupted mosquito collections once each month from May through November 2019 in Miami, Florida, and Brownsville, Texas, using BG-Sentinel 2 Traps. The overall diel activity pattern in both cities was bimodal with morning and evening peak activity between 7:00 and 8:00 and between 19:00 and 20:00. There were significant daily, monthly, seasonal, and site-specific differences in activity patterns, but these differences did not affect the overall peak activity times. These differences suggest daily, monthly, seasonal, and site-specific variations in human exposure to Ae. aegypti. Our observations can be used in planning and executing Ae. aegypti vector control activities in southern Florida and southern Texas, specifically those targeting the adult mosquito populations. |
HIV surveillance and research for migrant populations: Protocol integrating respondent-driven sampling, case finding, and medicolegal services for Venezuelans living in Colombia
Wirtz AL , Page KR , Stevenson M , Guillén JR , Ortíz J , López JJ , Ramírez JF , Quijano C , Vela A , Moreno Y , Rigual F , Case J , Hakim AJ , Hladik W , Spiegel PB . JMIR Res Protoc 2022 11 (3) e36026 BACKGROUND: Epidemiologic research among migrant populations is limited by logistical, methodological, and ethical challenges, but it is necessary for informing public health and humanitarian programming. OBJECTIVE: We describe a methodology to estimate HIV prevalence among Venezuelan migrants in Colombia. METHODS: Respondent-driven sampling, a nonprobability sampling method, was selected for attributes of reaching highly networked populations without sampling frames and analytic methods that permit estimation of population parameters. Respondent-driven sampling was modified to permit electronic referral of peers via SMS text messaging and WhatsApp. Participants complete sociobehavioral surveys and rapid HIV and syphilis screening tests with confirmatory testing. HIV treatment is not available for migrants who have entered Colombia through irregular pathways; thus, medicolegal services integrated into posttest counseling provide staff lawyers and legal assistance to participants diagnosed with HIV or syphilis for sustained access to treatment through the national health system. Case finding is integrated into respondent-driven sampling to allow partner referral. This study is implemented by a local community-based organization providing HIV support services and related legal services for Venezuelans in Colombia. RESULTS: Data collection was launched in 4 cities in July and August 2021. As of November 2021, 3105 of the target 6100 participants were enrolled, with enrollment expected to end by February/March 2022. CONCLUSIONS: Tailored methods that combine community-led efforts with innovations in sampling and linkage to care can aid in advancing health research for migrant and displaced populations. Worldwide trends in displacement and migration underscore the value of improved methods for translation to humanitarian and public health programming. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/36026. |
Multiplexed CRISPR-based microfluidic platform for clinical testing of respiratory viruses and identification of SARS-CoV-2 variants.
Welch NL , Zhu M , Hua C , Weller J , Mirhashemi ME , Nguyen TG , Mantena S , Bauer MR , Shaw BM , Ackerman CM , Thakku SG , Tse MW , Kehe J , Uwera MM , Eversley JS , Bielwaski DA , McGrath G , Braidt J , Johnson J , Cerrato F , Moreno GK , Krasilnikova LA , Petros BA , Gionet GL , King E , Huard RC , Jalbert SK , Cleary ML , Fitzgerald NA , Gabriel SB , Gallagher GR , Smole SC , Madoff LC , Brown CM , Keller MW , Wilson MM , Kirby MK , Barnes JR , Park DJ , Siddle KJ , Happi CT , Hung DT , Springer M , MacInnis BL , Lemieux JE , Rosenberg E , Branda JA , Blainey PC , Sabeti PC , Myhrvold C . Nat Med 2022 28 (5) 1083-1094 The COVID-19 pandemic has demonstrated a clear need for high-throughput, multiplexed, and sensitive assays for detecting SARS-CoV-2 and other respiratory viruses as well as their emerging variants. Here, we present a cost-effective virus and variant detection platform, called microfluidic CARMEN (mCARMEN), that combines CRISPR-based diagnostics and microfluidics with a streamlined workflow for clinical use. We developed the mCARMEN respiratory virus panel (RVP) to test for up to 21 viruses, including SARS-CoV-2, other coronaviruses and both influenza strains, and demonstrated its diagnostic-grade performance on 525 patient specimens in an academic setting and 166 specimens in a clinical setting. We further developed an mCARMEN panel to enable identification of 6 SARS-CoV-2 variant lineages, including Delta and Omicron, and evaluated it on 2,088 patient specimens, with near-perfect concordance to sequencing-based variant classification. Lastly, we implemented a combined Cas13 and Cas12 approach that enables quantitative measurement of SARS-CoV-2 and influenza A viral copies in samples. The mCARMEN platform enables high-throughput surveillance of multiple viruses and variants simultaneously, enabling rapid detection of SARS-CoV-2 variants. |
Zika-associated birth defects reported in pregnancies with laboratory evidence of confirmed or possible Zika virus infection - U.S. Zika Pregnancy and Infant Registry, December 1, 2015-March 31, 2018
Roth NM , Reynolds MR , Lewis EL , Woodworth KR , Godfred-Cato S , Delaney A , Akosa A , Valencia-Prado M , Lash M , Elmore A , Langlois P , Khuwaja S , Tufa A , Ellis EM , Nestoridi E , Lyu C , Longcore ND , Piccardi M , Lind L , Starr S , Johnson L , Browne SE , Gosciminski M , Velasco PE , Johnson-Clarke F , Locklear A , Chan M , Fornoff J , Toews KE , Tonzel J , Marzec NS , Hale S , Nance AE , Willabus T , Contreras D , Adibhatla SN , Iguchi L , Potts E , Schiffman E , Lolley K , Stricklin B , Ludwig E , Garstang H , Marx M , Ferrell E , Moreno-Gorrin C , Signs K , Romitti P , Leedom V , Martin B , Castrodale L , Cook A , Fredette C , Denson L , Cronquist L , Nahabedian JF3rd , Shinde N , Polen K , Gilboa SM , Martin SW , Cragan JD , Meaney-Delman D , Honein MA , Tong VT , Moore CA . MMWR Morb Mortal Wkly Rep 2022 71 (3) 73-79 Zika virus infection during pregnancy can cause serious birth defects of the brain and eyes, including intracranial calcifications, cerebral or cortical atrophy, chorioretinal abnormalities, and optic nerve abnormalities (1,2). The frequency of these Zika-associated brain and eye defects, based on data from the U.S. Zika Pregnancy and Infant Registry (USZPIR), has been previously reported in aggregate (3,4). This report describes the frequency of individual Zika-associated brain and eye defects among infants from pregnancies with laboratory evidence of confirmed or possible Zika virus infection. Among 6,799 live-born infants in USZPIR born during December 1, 2015-March 31, 2018, 4.6% had any Zika-associated birth defect; in a subgroup of pregnancies with a positive nucleic acid amplification test (NAAT) for Zika virus infection, the percentage was 6.1% of live-born infants. The brain and eye defects most frequently reported included microcephaly, corpus callosum abnormalities, intracranial calcification, abnormal cortical gyral patterns, ventriculomegaly, cerebral or cortical atrophy, chorioretinal abnormalities, and optic nerve abnormalities. Among infants with any Zika-associated birth defect, one third had more than one defect reported. Certain brain and eye defects in an infant might prompt suspicion of prenatal Zika virus infection. These findings can help target surveillance efforts to the most common brain and eye defects associated with Zika virus infection during pregnancy should a Zika virus outbreak reemerge, and might provide a signal to the reemergence of Zika virus, particularly in geographic regions without ongoing comprehensive Zika virus surveillance. |
Interventions to Disrupt Coronavirus Disease Transmission at a University, Wisconsin, USA, August-October 2020.
Currie DW , Moreno GK , Delahoy MJ , Pray IW , Jovaag A , Braun KM , Cole D , Shechter T , Fajardo GC , Griggs C , Yandell BS , Goldstein S , Bushman D , Segaloff HE , Kelly GP , Pitts C , Lee C , Grande KM , Kita-Yarbro A , Grogan B , Mader S , Baggott J , Bateman AC , Westergaard RP , Tate JE , Friedrich TC , Kirking HL , O'Connor DH , Killerby ME . Emerg Infect Dis 2021 27 (11) 2776-2785 University settings have demonstrated potential for coronavirus disease (COVID-19) outbreaks; they combine congregate living, substantial social activity, and a young population predisposed to mild illness. Using genomic and epidemiologic data, we describe a COVID-19 outbreak at the University of Wisconsin-Madison, Madison, Wisconsin, USA. During August-October 2020, a total of 3,485 students, including 856/6,162 students living in dormitories, tested positive. Case counts began rising during move-in week, August 25-31, 2020, then rose rapidly during September 1-11, 2020. The university initiated multiple prevention efforts, including quarantining 2 dormitories; a subsequent decline in cases was observed. Genomic surveillance of cases from Dane County, in which the university is located, did not find evidence of transmission from a large cluster of cases in the 2 quarantined dorms during the outbreak. Coordinated implementation of prevention measures can reduce COVID-19 spread in university settings and may limit spillover to the surrounding community. |
Severe Acute Respiratory Syndrome Coronavirus 2 Transmission in Intercollegiate Athletics Not Fully Mitigated With Daily Antigen Testing.
Moreno GK , Braun KM , Pray IW , Segaloff HE , Lim A , Poulsen K , Meiman J , Borcher J , Westergaard RP , Moll MK , Friedrich TC , O'Connor DH . Clin Infect Dis 2021 73 S45-S53 BACKGROUND: High-frequency, rapid-turnaround SARS-CoV-2 testing continues to be proposed as a way of efficiently identifying and mitigating transmission in congregate settings. However, two SARS-CoV-2 outbreaks occurred among intercollegiate university athletic programs during the fall 2020 semester despite mandatory directly observed daily antigen testing. METHODS: During the fall 2020 semester, athletes and staff in both programs were tested daily using Quidel's Sofia SARS Antigen Fluorescent Immunoassay (FIA), with positive antigen results requiring confirmatory testing with real-time reverse transcription polymerase chain reaction (RT-PCR). We used genomic sequencing to investigate transmission dynamics in these two outbreaks. RESULTS: In Outbreak 1, 32 confirmed cases occurred within a university athletics program after the index patient attended a meeting while infectious despite a negative antigen test on the day of the meeting. Among isolates sequenced from Outbreak 1, 24 (92%) of 26 were closely related, suggesting sustained transmission following an initial introduction event. In Outbreak 2, 12 confirmed cases occurred among athletes from two university programs that faced each other in an athletic competition despite receiving negative antigen test results on the day of the competition. Sequences from both teams were closely related and distinct from viruses circulating in Team 1's community, suggesting transmission during intercollegiate competition in Team 2's community. CONCLUSIONS: These findings suggest that antigen testing alone, even when mandated and directly observed, may not be sufficient as an intervention to prevent SARS-CoV-2 outbreaks in congregate settings, and highlight the importance of supplementing serial antigen testing with appropriate mitigation strategies to prevent SARS-CoV-2 outbreak in congregate settings. |
Natural infections with different Plasmodium species induce antibodies reactive to a chimeric Plasmodium vivax recombinant protein
McCaffery JN , Singh B , Nace D , Moreno A , Udhayakumar V , Rogier E . Malar J 2021 20 (1) 86 BACKGROUND: As malaria incidence and transmission in a region decreases, it becomes increasingly difficult to identify areas of active transmission. Improved methods for identifying and monitoring foci of active malaria transmission are needed in areas of low parasite prevalence in order to achieve malaria elimination. Serological assays can provide population-level infection history to inform elimination campaigns. METHODS: A bead-based multiplex antibody detection assay was used to evaluate a chimeric Plasmodium vivax MSP1 protein (PvRMC-MSP1), designed to be broadly immunogenic for use in vaccine studies, to act as a pan-malaria serological tool based on its ability to capture IgG in plasma samples obtained from naturally exposed individuals. Samples from 236 US travellers with PCR confirmed infection status from all four major Plasmodium species infecting humans, Plasmodium falciparum (n = 181), Plasmodium vivax (n = 38), Plasmodium malariae (n = 4), and Plasmodium ovale (n = 13) were tested for IgG capture using PvRMC-MSP1 as well as the four recombinant MSP1-19 kD isoforms representative of these Plasmodium species. RESULTS: Regardless of infecting Plasmodium species, a large proportion of plasma samples from infected US travellers provided a high assay signal to the PvRMC-MSP1 chimeric protein, with 115 high responders out of 236 samples assessed (48.7%). When grouped by active infection, 38.7% P. falciparum-, 92.1% of P. vivax-, 75.0% P. malariae-, and 53.4% of P. ovale-infected individuals displayed high assay signals in response to PvRMC-MSP1. It was also determined that plasma from P. vivax-infected individuals produced increased assay signals in response to the PvRMC-MSP1 chimera as compared to the recombinant PvMSP1 for 89.5% (34 out of 38) of individuals. PvRMC-MSP1 also showed improved ability to capture IgG antibodies from P. falciparum-infected individuals when compared to the capture by recombinant PvMSP1, with high assay signals observed for 38.7% of P. falciparum-infected travellers in response to PvRMC-MSP1 IgG capture compared to just 1.1% who were high responders to capture by the recombinant PvMSP1 protein. CONCLUSIONS: These results support further study of designed antigens as an approach for increasing sensitivity or broadening binding capacity to improve existing serological tools for determining population-level exposure to Plasmodium species. Including both broad-reacting and Plasmodium species-specific antigen-coated beads in an assay panel could provide a nuanced view of population-level exposure histories, an extensive IgG profile, and detailed seroestimates. A more sensitive serological tool for detection of P. vivax exposure would aid malaria elimination campaigns in co-endemic areas and regions where P. vivax is the dominant parasite. |
Genomic Diversity of Burkholderia pseudomallei Isolates, Colombia.
Duarte C , Montufar F , Moreno J , Sánchez D , Rodríguez JY , Torres AG , Morales S , Bautista A , Huertas MG , Myers JN , Gulvik CA , Elrod MG , Blaney DD , Gee JE . Emerg Infect Dis 2021 27 (2) 655-658 We report an analysis of the genomic diversity of isolates of Burkholderia pseudomallei, the cause of melioidosis, recovered in Colombia from routine surveillance during 2016-2017. B. pseudomallei appears genetically diverse, suggesting it is well established and has spread across the region. |
Final program data and factors associated with long-acting reversible contraception removal: The Zika Contraception Access Network
Lathrop E , Hurst S , Mendoza Z , Zapata LB , Cordero P , Powell R , Green C , Moreno N , Jamieson DJ , Romero L . Obstet Gynecol 2020 135 (5) 1095-1103 OBJECTIVE: To describe characteristics of the full population of women who participated in the Zika Contraception Access Network program in Puerto Rico during the virus outbreak and to examine factors associated with removal of a long-acting reversible contraception (LARC) method by a Zika Contraception Access Network provider during the program's duration (May 2016-September 2017). METHODS: We conducted an observational cohort study. The Zika Contraception Access Network program was designed to increase access to contraception services in Puerto Rico for women who chose to prevent pregnancy during the Zika virus outbreak as a primary strategy to reduce adverse Zika virus-related pregnancy and birth outcomes. Among program participants, an observational cohort of women served by the Zika Contraception Access Network Program, we describe their demographic and program-specific characteristics, including contraceptive method mix before and after the program. We also report on LARC removals by Zika Contraception Access Network providers during the program. We examined factors associated with LARC removal using multivariable logistic regression. RESULTS: A total of 29,221 women received an initial Zika Contraception Access Network visit during the program. Ninety-six percent (27,985) of women received same-day provision of a contraceptive method and 70% (20,381) chose a LARC method. While the program was active, 719 (4%) women who chose a LARC at the initial visit had it removed. Women with a college degree or higher were more likely to have their LARC removed (adjusted prevalence ratio [aPR] 1.24); breastfeeding women (aPR 0.67) and those using a LARC method before Zika Contraception Access Network (aPR 0.55) were less likely to have their LARC removed. CONCLUSION: The Zika Contraception Access Network program was designed as a short-term response for rapid implementation of contraceptive services in a complex emergency setting in Puerto Rico and served more than 29,000 women. The Zika Contraception Access Network program had high LARC uptake and a low proportion of removals by a Zika Contraception Access Network provider during the program. A removal-inclusive design, with access to removals well beyond the program period, maximizes women's reproductive autonomy to access LARC removal when desired. This model could be replicated in other settings where the goal is to increase contraception access. |
Having a sexual photo shared without permission and associated health risks: A snapshot of nonconsensual sexting
Pampati S , Lowry R , Moreno MA , Rasberry CN , Steiner RJ . JAMA Pediatr 2020 174 (6) 618-619 This study examines the prevalence of adolescents who have had sexual photos shared without permission, including variation by demographics, and associations with interpersonal violence experiences, mental health and suicidality, and sexual risk behaviors. |
Autochthonous Chagas disease - Missouri, 2018
Turabelidze G , Vasudevan A , Rojas-Moreno C , Montgomery SP , Baker M , Pratt D , Enyeart S . MMWR Morb Mortal Wkly Rep 2020 69 (7) 193-195 On December 13, 2017, the Missouri Department of Health and Senior Services (MDHSS) was notified of a suspected case of Chagas disease in a Missouri woman. The patient had donated blood, and laboratory screening revealed antibodies to Trypanosoma cruzi, the parasite that causes Chagas disease. Evaluation by physicians found no clinical symptoms consistent with Chagas disease. The patient had no travel history that would have suggested a significant risk for Chagas disease risk and had no occupational exposure to the disease agent. She had never received a blood transfusion or organ transplant. Confirmatory testing of the patient's serum at CDC for T. cruzi antibody was consistent with infection. These findings raise the possibility that the exposure to T. cruzi occurred locally (autochthonously) in Missouri. Although the insect vector for the parasite T. cruzi, triatomines (commonly known as "kissing bugs"), has been identified previously in Missouri, no locally acquired human cases of Chagas disease have been identified in the state. Health care providers and public health professionals should be aware of the possibility of locally acquired Chagas disease in the southern United States. |
An Isothermal, Multiplex Amplification Assay for Detection and Genotyping of Human Papillomaviruses in Formalin-Fixed, Paraffin-Embedded Tissues.
Tang YW , Lozano L , Chen X , Querec TD , Katabi N , Moreno-Docon A , Wang H , Fix D , De Brot L , McMillen TA , Yoon JY , Torroba A , Wang Y , Unger ER , Park KJ . J Mol Diagn 2020 22 (3) 419-428 Rapid and accurate identification of human papillomavirus (HPV) is important for both clinical management and population screening. We performed analytic validation of Atila AmpFire Multiplex HPV assays on formalin-fixed, paraffin-embedded (FFPE) cervix/vulva and oropharynx diagnostic tissue samples. The AmpFire assay incorporates a novel isothermal multiplex amplification coupled with real-time fluorescent detection to detect and genotype 15 high-risk (HR) HPV genotypes. Limits of detection determined by plasmids cloned with HPV genotype-specific sequences were 2 copies/reaction for HPV16, HPV18, and some HR HPV genotypes, and 20 copies/reaction for the remaining HR HPV genotypes. The performance of the AmpFire assays in clinical samples was evaluated using 214 FFPE specimens. The AmpFire assay failed in one clinical specimen for an invalid rate of 0.5%. The AmpFire assay detected HPV in clinical samples with positive percent agreements of 100.0% for HPV16, 100.0% for HPV18, and 94.7% for non-16/18 HR-HPV, and 100% negative percent agreements for HPV16, HPV18, and non-16/18 HR-HPV. Qualitative detection agreement was obtained in the reproducibility study. In summary, the Atila AmpFire HPV assay demonstrated excellent analytic sensitivity and specificity for detection and genotyping of 15 HR HPV genotypes. Assay parameters of simple specimen processing, small sample size requirement, rapid turnaround time, and being near instrument-free render it well suited for HPV detection and genotyping in FFPE specimens. |
Nonparticipation reasons in a randomized international trial of a new latent tuberculosis infection regimen
Hedges KNC , Borisov AS , Saukkonen JJ , Scott NA , Hecker EJ , Bozeman L , Dukes Hamilton C , Kerrigan A , Bessler P , Moreno-Martinez A , Arevalo B , Goldberg SV . Clin Trials 2019 17 (1) 1740774519885380 BACKGROUND/AIMS: Efficient recruitment of eligible participants, optimizing time and sample size, is a crucial component in conducting a successful clinical trial. Inefficient participant recruitment can impede study progress, consume staff time and resources, and limit quality and generalizability or the power to assess outcomes. Recruitment for disease prevention trials poses additional challenges because patients are asymptomatic. We evaluated candidates for a disease prevention trial to determine reasons for nonparticipation and to identify factors that can be addressed to improve recruitment efficiency. METHODS: During 2001-2009, the Tuberculosis Trials Consortium conducted Study 26 (PREVENT TB), a randomized clinical trial at 26 sites in four countries, among persons with latent tuberculosis infection at high risk for tuberculosis disease progression, comparing 3 months of directly observed once-weekly rifapentine plus isoniazid with 9 months of self-administered daily isoniazid. During March 2005-February 2008, non-identifying demographic information, risk factors for experiencing active tuberculosis disease, and reasons for not enrolling were collected from screened patients to facilitate interpretation of trial data, to meet Consolidated Standards of Reporting Trials standards, and to evaluate reasons for nonparticipation. RESULTS: Of the 7452 candidates screened in Brazil, Canada, Spain, and the United States, 3584 (48%) were not enrolled, because of ineligibility (41%), site decision (10%), or patient choice (49%). Among those who did not enroll by own choice, and for whom responses were recorded on whether they would accept treatment outside of the study (n = 1430), 68% reported that they planned to accept non-study latent tuberculosis infection treatment. Among 1305 patients with one or more reported reasons for nonparticipation, study staff recorded a total of 1886 individual reasons (reason count: median = 1/patient; range = 1-9) for why patients chose not to enroll, including grouped concerns about research (24% of 1886), work or school conflicts (20%), medication or health beliefs (16%), latent tuberculosis infection beliefs (11%), and patient lifestyle and family concerns (10%). CONCLUSION: Educational efforts addressing clinical research concerns and beliefs about medication and health, as well as study protocols that accommodate patient-related concerns (e.g. work, school, and lifestyle) might increase willingness to enter clinical trials. Findings from this evaluation can support development of communication and education materials for clinical trial sites at the beginning of a trial to allow study staff to address potential participant concerns during study screening. |
Distinct amino acid and lipid perturbations characterize acute versus chronic malaria.
Cordy RJ , Patrapuvich R , Lili LN , Cabrera-Mora M , Chien JT , Tharp GK , Khadka M , Meyer EV , Lapp SA , Joyner CJ , Garcia A , Banton S , Tran V , Luvira V , Rungin S , Saeseu T , Rachaphaew N , Pakala SB , DeBarry JD , Kissinger JC , Ortlund EA , Bosinger SE , Barnwell JW , Jones DP , Uppal K , Li S , Sattabongkot J , Moreno A , Galinski MR . JCI Insight 2019 4 (9) Chronic malaria is a major public health problem and significant challenge for disease eradication efforts. Despite its importance, the biological factors underpinning chronic malaria are not fully understood. Recent studies have shown that host metabolic state can influence malaria pathogenesis and transmission, but its role in chronicity is not known. Here, with the goal of identifying distinct modifications in the metabolite profiles of acute versus chronic malaria, metabolomics was performed on plasma from Plasmodium-infected humans and nonhuman primates with a range of parasitemias and clinical signs. In rhesus macaques infected with Plasmodium coatneyi, significant alterations in amines, carnitines, and lipids were detected during a high parasitemic acute phase and many of these reverted to baseline levels once a low parasitemic chronic phase was established. Plasmodium gene expression, studied in parallel in the macaques, revealed transcriptional changes in amine, fatty acid, lipid and energy metabolism genes, as well as variant antigen genes. Furthermore, a common set of amines, carnitines, and lipids distinguished acute from chronic malaria in plasma from human Plasmodium falciparum cases. In summary, distinct host-parasite metabolic environments have been uncovered that characterize acute versus chronic malaria, providing insights into the underlying host-parasite biology of malaria disease progression. |
Taxonomy of the order Mononegavirales: update 2019.
Amarasinghe GK , Ayllon MA , Bao Y , Basler CF , Bavari S , Blasdell KR , Briese T , Brown PA , Bukreyev A , Balkema-Buschmann A , Buchholz UJ , Chabi-Jesus C , Chandran K , Chiapponi C , Crozier I , de Swart RL , Dietzgen RG , Dolnik O , Drexler JF , Durrwald R , Dundon WG , Duprex WP , Dye JM , Easton AJ , Fooks AR , Formenty PBH , Fouchier RAM , Freitas-Astua J , Griffiths A , Hewson R , Horie M , Hyndman TH , Jiang D , Kitajima EW , Kobinger GP , Kondo H , Kurath G , Kuzmin IV , Lamb RA , Lavazza A , Lee B , Lelli D , Leroy EM , Li J , Maes P , Marzano SL , Moreno A , Muhlberger E , Netesov SV , Nowotny N , Nylund A , Okland AL , Palacios G , Palyi B , Paweska JT , Payne SL , Prosperi A , Ramos-Gonzalez PL , Rima BK , Rota P , Rubbenstroth D , Shi M , Simmonds P , Smither SJ , Sozzi E , Spann K , Stenglein MD , Stone DM , Takada A , Tesh RB , Tomonaga K , Tordo N , Towner JS , van den Hoogen B , Vasilakis N , Wahl V , Walker PJ , Wang LF , Whitfield AE , Williams JV , Zerbini FM , Zhang T , Zhang YZ , Kuhn JH . Arch Virol 2019 164 (7) 1967-1980 In February 2019, following the annual taxon ratification vote, the order Mononegavirales was amended by the addition of four new subfamilies and 12 new genera and the creation of 28 novel species. This article presents the updated taxonomy of the order Mononegavirales as now accepted by the International Committee on Taxonomy of Viruses (ICTV). |
Multi-walled carbon nanotubes inhibit estrogen receptor expression in vivo and in vitro through transforming growth factor beta1
Smith LC , Moreno S , Robinson S , Orandle M , Porter DW , Das D , Saleh NB , Sabo-Attwood T . NanoImpact 2019 14 Exposure to multi-walled carbon nanotubes (MWCNTs) is suspected to contribute to pulmonary fibrosis through modulation of transforming growth factor beta1 (TGF-1). There is growing evidence that estrogen signaling is important in pulmonary function and modulates pro-fibrogenic signaling in multiple models of pulmonary fibrosis, however an interaction between MWCNT exposure and estrogen signaling in the lung is not known. The purpose of this work was to determine whether estrogen signaling in the lung is a target for MWCNTs and to identify potential signaling mechanisms mediating MWCNT-induced responses using a whole-body inhalation mouse model and an in vitro human lung cell model. Mice exposed to MWCNTs had reduced mRNA expression of estrogen receptor alpha and beta (Esr1 and Esr2, respectively) in lung tissue at multiple time-points post exposure, whereas expression of G-protein coupled estrogen receptor 1 (Gper1) was more variable. We localized ESR1 protein expression as primarily associated with bronchioles and within inflammatory macrophages. The reduction in estrogen receptor expression was concomitant to an increase in TGF-1 levels in the bronchoalveolar lavage fluid (BALF) of MWCNT-exposed animals. We confirmed a role for TGF-1 in mediating MWCNT-induced repression of ESR1 mRNA expression using a TGF- type-I receptor inhibitor in bronchial epithelial cells in vitro. Overall these results highlight a novel mechanism of MWCNT-induced signaling where MWCNT-induced regulation of TGF-1 represses estrogen receptor expression. Dysregulated estrogen signaling through altered receptor expression may have potential consequences on lung function. |
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