Last data update: Jun 17, 2024. (Total: 47034 publications since 2009)
Records 1-24 (of 24 Records) |
Query Trace: Villanueva JM [original query] |
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Travel history among persons infected with SARS-CoV-2 variants of concern in the United States, December 2020-February 2021.
Dunajcik A , Haire K , Thomas JD , Moriarty LF , Springer Y , Villanueva JM , MacNeil A , Silk B , Nemhauser JB , Byrkit R , Taylor M , Queen K , Tong S , Lee J , Batra D , Paden C , Henderson T , Kunkes A , Ojo M , Firestone M , Martin Webb L , Freeland M , Brown CM , Williams T , Allen K , Kauerauf J , Wilson E , Jain S , McDonald E , Silver E , Stous S , Wadford D , Radcliffe R , Marriott C , Owes JP , Bart SM , Sosa LE , Oakeson K , Wodniak N , Shaffner J , Brown Q , Westergaard R , Salinas A , Hallyburton S , Ogale Y , Offutt-Powell T , Bonner K , Tubach S , Van Houten C , Hughes V , Reeb V , Galeazzi C , Khuntia S , McGee S , Hicks JT , Dinesh Patel D , Krueger A , Hughes S , Jeanty F , Wang JC , Lee EH , Assanah-Deane T , Tompkins M , Dougherty K , Naqvi O , Donahue M , Frederick J , Abdalhamid B , Powers AM , Anderson M . PLOS Glob Public Health 2023 3 (3) e0001252 ![]() The first three SARS-CoV-2 phylogenetic lineages classified as variants of concern (VOCs) in the United States (U.S.) from December 15, 2020 to February 28, 2021, Alpha (B.1.1.7), Beta (B.1.351), and Gamma (P.1) lineages, were initially detected internationally. This investigation examined available travel history of coronavirus disease 2019 (COVID-19) cases reported in the U.S. in whom laboratory testing showed one of these initial VOCs. Travel history, demographics, and health outcomes for a convenience sample of persons infected with a SARS-CoV-2 VOC from December 15, 2020 through February 28, 2021 were provided by 35 state and city health departments, and proportion reporting travel was calculated. Of 1,761 confirmed VOC cases analyzed, 1,368 had available data on travel history. Of those with data on travel history, 1,168 (85%) reported no travel preceding laboratory confirmation of SARS-CoV-2 and only 105 (8%) reported international travel during the 30 days preceding a positive SARS-CoV-2 test or symptom onset. International travel was reported by 92/1,304 (7%) of persons infected with the Alpha variant, 7/55 (22%) with Beta, and 5/9 (56%) with Gamma. Of the first three SARS-CoV-2 lineages designated as VOCs in the U.S., international travel was common only among the few Gamma cases. Most persons infected with Alpha and Beta variant reported no travel history, therefore, community transmission of these VOCs was likely common in the U.S. by March 2021. These findings underscore the importance of global surveillance using whole genome sequencing to detect and inform mitigation strategies for emerging SARS-CoV-2 VOCs. |
Rapid diagnostic testing for response to the monkeypox outbreak - Laboratory Response Network, United States, May 17-June 30, 2022
Aden TA , Blevins P , York SW , Rager S , Balachandran D , Hutson CL , Lowe D , Mangal CN , Wolford T , Matheny A , Davidson W , Wilkins K , Cook R , Roulo RM , White MK , Berman L , Murray J , Laurance J , Francis D , Green NM , Berumen RA3rd , Gonzalez A , Evans S , Hudziec M , Noel D , Adjei M , Hovan G , Lee P , Tate L , Gose RB , Voermans R , Crew J , Adam PR , Haydel D , Lukula S , Matluk N , Shah S , Featherston J , Ware D , Pettit D , McCutchen E , Acheampong E , Buttery E , Gorzalski A , Perry M , Fowler R , Lee RB , Nickla R , Huard R , Moore A , Jones K , Johnson R , Swaney E , Jaramillo J , Reinoso Webb C , Guin B , Yost J , Atkinson A , Griffin-Thomas L , Chenette J , Gant J , Sterkel A , Ghuman HK , Lute J , Smole SC , Arora V , Demontigny CK , Bielby M , Geeter E , Newman KAM , Glazier M , Lutkemeier W , Nelson M , Martinez R , Chaitram J , Honein MA , Villanueva JM . MMWR Morb Mortal Wkly Rep 2022 71 (28) 904-907 As part of public health preparedness for infectious disease threats, CDC collaborates with other U.S. public health officials to ensure that the Laboratory Response Network (LRN) has diagnostic tools to detect Orthopoxviruses, the genus that includes Variola virus, the causative agent of smallpox. LRN is a network of state and local public health, federal, U.S. Department of Defense (DOD), veterinary, food, and environmental testing laboratories. CDC developed, and the Food and Drug Administration (FDA) granted 510(k) clearance* for the Non-variola Orthopoxvirus Real-time PCR Primer and Probe Set (non-variola Orthopoxvirus [NVO] assay), a polymerase chain reaction (PCR) diagnostic test to detect NVO. On May 17, 2022, CDC was contacted by the Massachusetts Department of Public Health (DPH) regarding a suspected case of monkeypox, a disease caused by the Orthopoxvirus Monkeypox virus. Specimens were collected and tested by the Massachusetts DPH public health laboratory with LRN testing capability using the NVO assay. Nationwide, 68 LRN laboratories had capacity to test approximately 8,000 NVO tests per week during June. During May 17-June 30, LRN laboratories tested 2,009 specimens from suspected monkeypox cases. Among those, 730 (36.3%) specimens from 395 patients were positive for NVO. NVO-positive specimens from 159 persons were confirmed by CDC to be monkeypox; final characterization is pending for 236. Prompt identification of persons with infection allowed rapid response to the outbreak, including isolation and treatment of patients, administration of vaccines, and other public health action. To further facilitate access to testing and increase convenience for providers and patients by using existing provider-laboratory relationships, CDC and LRN are supporting five large commercial laboratories with a national footprint (Aegis Science, LabCorp, Mayo Clinic Laboratories, Quest Diagnostics, and Sonic Healthcare) to establish NVO testing capacity of 10,000 specimens per week per laboratory. On July 6, 2022, the first commercial laboratory began accepting specimens for NVO testing based on clinician orders. |
Use of Ebola vaccine: Expansion of recommendations of the Advisory Committee on Immunization Practices to include two additional populations - United States, 2021
Malenfant JH , Joyce A , Choi MJ , Cossaboom CM , Whitesell AN , Harcourt BH , Atmar RL , Villanueva JM , Bell BP , Hahn C , Loehr J , Davey RT , Sprecher A , Kraft CS , Shoemaker T , Montgomery JM , Helfand R , Damon IK , Frey SE , Chen WH . MMWR Morb Mortal Wkly Rep 2022 71 (8) 290-292 On December 19, 2019, the Food and Drug Administration (FDA) approved rVSVΔG-ZEBOV-GP Ebola vaccine (ERVEBO, Merck) for the prevention of Ebola virus disease (EVD) caused by infection with Ebola virus, species Zaire ebolavirus, in adults aged ≥18 years. In February 2020, the Advisory Committee on Immunization Practices (ACIP) recommended preexposure vaccination with ERVEBO for adults aged ≥18 years in the United States who are at highest risk for potential occupational exposure to Ebola virus because they are responding to an outbreak of EVD, work as health care personnel at federally designated Ebola treatment centers in the United States, or work as laboratorians or other staff members at biosafety level 4 facilities in the United States (1). |
Multistate Outbreak of SARS-CoV-2 Infections, Including Vaccine Breakthrough Infections, Associated with Large Public Gatherings, United States.
Gharpure R , Sami S , Vostok J , Johnson H , Hall N , Foreman A , Sabo RT , Schubert PL , Shephard H , Brown VR , Brumfield B , Ricaldi JN , Conley AB , Zielinski L , Malec L , Newman AP , Chang M , Finn LE , Stainken C , Mangla AT , Eteme P , Wieck M , Green A , Edmundson A , Reichbind D , Brown VJr , Quiñones L , Longenberger A , Hess E , Gumke M , Manion A , Thomas H , Barrios CA , Koczwara A , Williams TW , Pearlowitz M , Assoumou M , Senisse Pajares AF , Dishman H , Schardin C , Wang X , Stephens K , Moss NS , Singh G , Feaster C , Webb LM , Krueger A , Dickerson K , Dewart C , Barbeau B , Salmanson A , Madoff LC , Villanueva JM , Brown CM , Laney AS . Emerg Infect Dis 2022 28 (1) 35-43 During July 2021, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.617.2 variant infections, including vaccine breakthrough infections, occurred after large public gatherings in Provincetown, Massachusetts, USA, prompting a multistate investigation. Public health departments identified primary and secondary cases by using coronavirus disease surveillance data, case investigations, and contact tracing. A primary case was defined as SARS-CoV-2 detected <14 days after travel to or residence in Provincetown during July 3-17. A secondary case was defined as SARS-CoV-2 detected <14 days after close contact with a person who had a primary case but without travel to or residence in Provincetown during July 3-August 10. We identified 1,098 primary cases and 30 secondary cases associated with 26 primary cases among fully and non-fully vaccinated persons. Large gatherings can have widespread effects on SARS-CoV-2 transmission, and fully vaccinated persons should take precautions, such as masking, to prevent SARS-CoV-2 transmission, particularly during substantial or high transmission. |
Pregnancy, Birth, Infant, and Early Childhood Neurodevelopmental Outcomes among a Cohort of Women with Symptoms of Zika Virus Disease during Pregnancy in Three Surveillance Sites, Project Vigilancia de Embarazadas con Zika (VEZ), Colombia, 2016-2018
Mercado-Reyes M , Gilboa SM , Valencia D , Daza M , Tong VT , Galang RR , Winfield CM , Godfred-Cato S , Benavides M , Villanueva JM , Thomas JD , Daniels J , Zaki S , Reagan-Steiner S , Bhatnagar J , Schiffer J , Steward-Clark E , Ricaldi JN , Osorio J , Sancken CL , Pardo L , Tinker SC , Anderson KN , Rico A , Burkel VK , Hojnacki J , Delahoy MJ , González M , Osorio MB , Moore CA , Honein MA , Ospina Martinez ML . Trop Med Infect Dis 2021 6 (4) Project Vigilancia de Embarazadas con Zika (VEZ), an intensified surveillance of pregnant women with symptoms of the Zika virus disease (ZVD) in Colombia, aimed to evaluate the relationship between symptoms of ZVD during pregnancy and adverse pregnancy, birth, and infant outcomes and early childhood neurodevelopmental outcomes. During May-November 2016, pregnant women in three Colombian cities who were reported with symptoms of ZVD to the national surveillance system, or with symptoms of ZVD visiting participating clinics, were enrolled in Project VEZ. Data from maternal and pediatric (up to two years of age) medical records were abstracted. Available maternal specimens were tested for the presence of the Zika virus ribonucleic acid and/or anti-Zika virus immunoglobulin antibodies. Of 1213 enrolled pregnant women with symptoms of ZVD, 1180 had a known pregnancy outcome. Results of the Zika virus laboratory testing were available for 569 (48.2%) pregnancies with a known pregnancy outcome though testing timing varied and was often distal to the timing of symptoms; 254 (21.5% of the whole cohort; 44.6% of those with testing results) were confirmed or presumptive positive for the Zika virus infection. Of pregnancies with a known outcome, 50 (4.2%) fetuses/infants had Zika-associated brain or eye defects, which included microcephaly at birth. Early childhood adverse neurodevelopmental outcomes were more common among those with Zika-associated birth defects than among those without and more common among those with laboratory evidence of a Zika virus infection compared with the full cohort. The proportion of fetuses/infants with any Zika-associated brain or eye defect was consistent with the proportion seen in other studies. Enhancements to Colombia's existing national surveillance enabled the assessment of adverse outcomes associated with ZVD in pregnancy. |
Performance characteristics of the Abbott BinaxNOW SARS-CoV-2 antigen test in comparison to real-time RT-PCR and viral culture in community testing sites during November 2020.
Almendares O , Prince-Guerra JL , Nolen LD , Gunn JKL , Dale AP , Buono SA , Deutsch-Feldman M , Suppiah S , Hao L , Zeng Y , Stevens VA , Knipe K , Pompey J , Atherstone C , Bui DP , Powell T , Tamin A , Harcourt JL , Petway M , Bohannon C , Folster JM , MacNeil A , Salerno R , Kuhnert-Tallman W , Tate JE , Thornburg N , Kirking HL , Villanueva JM , Rose DA , Neatherlin JC , Anderson M , Rota PA , Honein MA , Bower WA . J Clin Microbiol 2021 60 (1) Jcm0174221 Point-of-care antigen tests are an important tool for SARS-CoV-2 detection. Antigen tests are less sensitive than real-time reverse-transcriptase PCR (rRT-PCR). Data on the performance of the BinaxNOW antigen test compared to rRT-PCR and viral culture by symptom and known exposure status, timing during disease or exposure period and demographic variables are limited. During November 3(rd)-17(th), 2020, we collected paired upper respiratory swab specimens to test for SARS-CoV-2 by rRT-PCR and Abbott BinaxNOW (BinaxNOW) antigen test at two community testing sites in Pima County, Arizona. We administered a questionnaire to capture symptoms, known exposure status and previous SARS-CoV-2 test results. Specimens positive by either test were analyzed by viral culture. Previously we showed overall BinaxNOW sensitivity was 52.5%. Here we showed BinaxNOW sensitivity increased to 65.7% among currently symptomatic individuals reporting a known exposure. BinaxNOW sensitivity was lower among participants with a known exposure and previously symptomatic (32.4%) or never symptomatic (47.1%) within 14 days of testing. Sensitivity was 71.1% in participants within a week of symptom onset. In participants with a known exposure, sensitivity was highest 8-10 days post-exposure (75%). The positive predictive value for recovery of virus in cell culture was 56.7% for BinaxNOW-positive and 35.4% for rRT-PCR-positive specimens. Result reporting time was 2.5 hours for BinaxNOW and 26 hours for rRT-PCR. Point-of-care antigen tests have a shorter turn-around time compared to laboratory-based nucleic acid amplification tests, which allows for more rapid identification of infected individuals. Antigen test sensitivity limitations are important to consider when developing a testing program. |
Evaluation of Abbott BinaxNOW Rapid Antigen Test for SARS-CoV-2 Infection at Two Community-Based Testing Sites - Pima County, Arizona, November 3-17, 2020.
Prince-Guerra JL , Almendares O , Nolen LD , Gunn JKL , Dale AP , Buono SA , Deutsch-Feldman M , Suppiah S , Hao L , Zeng Y , Stevens VA , Knipe K , Pompey J , Atherstone C , Bui DP , Powell T , Tamin A , Harcourt JL , Shewmaker PL , Medrzycki M , Wong P , Jain S , Tejada-Strop A , Rogers S , Emery B , Wang H , Petway M , Bohannon C , Folster JM , MacNeil A , Salerno R , Kuhnert-Tallman W , Tate JE , Thornburg NJ , Kirking HL , Sheiban K , Kudrna J , Cullen T , Komatsu KK , Villanueva JM , Rose DA , Neatherlin JC , Anderson M , Rota PA , Honein MA , Bower WA . MMWR Morb Mortal Wkly Rep 2021 70 (3) 100-105 Rapid antigen tests, such as the Abbott BinaxNOW COVID-19 Ag Card (BinaxNOW), offer results more rapidly (approximately 15-30 minutes) and at a lower cost than do highly sensitive nucleic acid amplification tests (NAATs) (1). Rapid antigen tests have received Food and Drug Administration (FDA) Emergency Use Authorization (EUA) for use in symptomatic persons (2), but data are lacking on test performance in asymptomatic persons to inform expanded screening testing to rapidly identify and isolate infected persons (3). To evaluate the performance of the BinaxNOW rapid antigen test, it was used along with real-time reverse transcription-polymerase chain reaction (RT-PCR) testing to analyze 3,419 paired specimens collected from persons aged ≥10 years at two community testing sites in Pima County, Arizona, during November 3-17, 2020. Viral culture was performed on 274 of 303 residual real-time RT-PCR specimens with positive results by either test (29 were not available for culture). Compared with real-time RT-PCR testing, the BinaxNOW antigen test had a sensitivity of 64.2% for specimens from symptomatic persons and 35.8% for specimens from asymptomatic persons, with near 100% specificity in specimens from both groups. Virus was cultured from 96 of 274 (35.0%) specimens, including 85 (57.8%) of 147 with concordant antigen and real-time RT-PCR positive results, 11 (8.9%) of 124 with false-negative antigen test results, and none of three with false-positive antigen test results. Among specimens positive for viral culture, sensitivity was 92.6% for symptomatic and 78.6% for asymptomatic individuals. When the pretest probability for receiving positive test results for SARS-CoV-2 is elevated (e.g., in symptomatic persons or in persons with a known COVID-19 exposure), a negative antigen test result should be confirmed by NAAT (1). Despite a lower sensitivity to detect infection, rapid antigen tests can be an important tool for screening because of their quick turnaround time, lower costs and resource needs, high specificity, and high positive predictive value (PPV) in settings of high pretest probability. The faster turnaround time of the antigen test can help limit transmission by more rapidly identifying infectious persons for isolation, particularly when used as a component of serial testing strategies. |
Mitigating a COVID-19 Outbreak Among Major League Baseball Players - United States, 2020.
Murray MT , Riggs MA , Engelthaler DM , Johnson C , Watkins S , Longenberger A , Brett-Major DM , Lowe J , Broadhurst MJ , Ladva CN , Villanueva JM , MacNeil A , Qari S , Kirking HL , Cherry M , Khan AS . MMWR Morb Mortal Wkly Rep 2020 69 (42) 1542-1546 Mass gatherings have been implicated in higher rates of transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), and many sporting events have been restricted or canceled to limit disease spread (1). Based on current CDC COVID-19 mitigation recommendations related to events and gatherings (2), Major League Baseball (MLB) developed new health and safety protocols before the July 24 start of the 2020 season. In addition, MLB made the decision that games would be played without spectators. Before a three-game series between teams A and B, the Philadelphia Department of Public Health was notified of a team A player with laboratory-confirmed COVID-19; the player was isolated as recommended (2). During the series and the week after, laboratory-confirmed COVID-19 was diagnosed among 19 additional team A players and staff members and one team B staff member. Throughout their potentially infectious periods, some asymptomatic team A players and coaches, who subsequently received positive SARS-CoV-2 test results, engaged in on-field play with teams B and C. No on-field team B or team C players or staff members subsequently received a clinical diagnosis of COVID-19. Certain MLB health and safety protocols, which include frequent diagnostic testing for rapid case identification, isolation of persons with positive test results, quarantine for close contacts, mask wearing, and social distancing, might have limited COVID-19 transmission between teams. |
Zika virus disease and pregnancy outcomes in Colombia
Ospina ML , Tong VT , Gonzalez M , Valencia D , Mercado M , Gilboa SM , Rodriguez AJ , Tinker SC , Rico A , Winfield CM , Pardo L , Thomas JD , Avila G , Villanueva JM , Gomez S , Jamieson DJ , Prieto F , Meaney-Delman D , Pacheco O , Honein MA . N Engl J Med 2020 383 (6) 537-545 BACKGROUND: In 2015 and 2016, Colombia had a widespread outbreak of Zika virus. Data from two national population-based surveillance systems for symptomatic Zika virus disease (ZVD) and birth defects provided complementary information on the effect of the Zika virus outbreak on pregnancies and infant outcomes. METHODS: We collected national surveillance data regarding cases of pregnant women with ZVD that were reported during the period from June 2015 through July 2016. The presence of Zika virus RNA was identified in a subgroup of these women on real-time reverse-transcriptase-polymerase-chain-reaction (rRT-PCR) assay. Brain or eye defects in infants and fetuses and other adverse pregnancy outcomes were identified among the women who had laboratory-confirmed ZVD and for whom data were available regarding pregnancy outcomes. We compared the nationwide prevalence of brain and eye defects during the outbreak with the prevalence both before and after the outbreak period. RESULTS: Of 18,117 pregnant women with ZVD, the presence of Zika virus was confirmed in 5926 (33%) on rRT-PCR. Of the 5673 pregnancies with laboratory-confirmed ZVD for which outcomes had been reported, 93 infants or fetuses (2%) had brain or eye defects. The incidence of brain or eye defects was higher among pregnancies in which the mother had an onset of ZVD symptoms in the first trimester than in those with an onset during the second or third trimester (3% vs. 1%). A total of 172 of 5673 pregnancies (3%) resulted in pregnancy loss; after the exclusion of pregnancies affected by birth defects, 409 of 5426 (8%) resulted in preterm birth and 333 of 5426 (6%) in low birth weight. The prevalence of brain or eye defects during the outbreak was 13 per 10,000 live births, as compared with a prevalence of 8 per 10,000 live births before the outbreak and 11 per 10,000 live births after the outbreak. CONCLUSIONS: In pregnant women with laboratory-confirmed ZVD, brain or eye defects in infants or fetuses were more common during the Zika virus outbreak than during the periods immediately before and after the outbreak. The frequency of such defects was increased among women with a symptom onset early in pregnancy. (Funded by the Colombian Instituto Nacional de Salud and the Centers for Disease Control and Prevention.). |
US CDC Real-Time Reverse Transcription PCR Panel for Detection of Severe Acute Respiratory Syndrome Coronavirus 2.
Lu X , Wang L , Sakthivel SK , Whitaker B , Murray J , Kamili S , Lynch B , Malapati L , Burke SA , Harcourt J , Tamin A , Thornburg NJ , Villanueva JM , Lindstrom S . Emerg Infect Dis 2020 26 (8) 1654-65 ![]() ![]() Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified as the etiologic agent associated with coronavirus disease, which emerged in late 2019. In response, we developed a diagnostic panel consisting of 3 real-time reverse transcription PCR assays targeting the nucleocapsid gene and evaluated use of these assays for detecting SARS-CoV-2 infection. All assays demonstrated a linear dynamic range of 8 orders of magnitude and an analytical limit of detection of 5 copies/reaction of quantified RNA transcripts and 1 x 10(-1.5) 50% tissue culture infectious dose/mL of cell-cultured SARS-CoV-2. All assays performed comparably with nasopharyngeal and oropharyngeal secretions, serum, and fecal specimens spiked with cultured virus. We obtained no false-positive amplifications with other human coronaviruses or common respiratory pathogens. Results from all 3 assays were highly correlated during clinical specimen testing. On February 4, 2020, the Food and Drug Administration issued an Emergency Use Authorization to enable emergency use of this panel. |
Performance of the Trioplex real-time RT-PCR assay for detection of Zika, dengue, and chikungunya viruses.
Santiago GA , Vazquez J , Courtney S , Matias KY , Andersen LE , Colon C , Butler AE , Roulo R , Bowzard J , Villanueva JM , Munoz-Jordan JL . Nat Commun 2018 9 (1) 1391 ![]() ![]() The emergence and spread of Zika virus (ZIKV) presented a challenge to the diagnosis of ZIKV infections in areas with transmission of dengue (DENV) and chikungunya (CHIKV) viruses. To facilitate detection of ZIKV infections, and differentiate these infections from DENV and CHIKV, we developed the Trioplex real-time RT-PCR assay (Trioplex assay). Here, we describe the optimization of multiplex and singleplex formats of the assay for a variety of chemistries and instruments to facilitate global standardization and implementation. We evaluated the analytical performance of all Trioplex modalities for detection of these three pathogens in serum and whole blood, and for ZIKV in urine. The limit of detection for the three viruses and in different RNA-extraction modalities is near 10(3) genome copy equivalents per milliliter (GCE/mL). Simultaneous testing of more than one specimen type from each patient provides a 6.4% additional diagnostic sensitivity. Overall, the high sensitivity of the Trioplex assay demonstrates the utility of this assay ascertaining Zika cases. |
Update: interim guidance for health care providers caring for pregnant women with possible Zika virus exposure - United States, July 2016
Oduyebo T , Igbinosa I , Petersen EE , Polen KN , Pillai SK , Ailes EC , Villanueva JM , Newsome K , Fischer M , Gupta PM , Powers AM , Lampe M , Hills S , Arnold KE , Rose LE , Shapiro-Mendoza CK , Beard CB , Munoz JL , Rao CY , Meaney-Delman D , Jamieson DJ , Honein MA . MMWR Morb Mortal Wkly Rep 2016 65 (29) 739-44 CDC has updated its interim guidance for U.S. health care providers caring for pregnant women with possible Zika virus exposure, to include the emerging data indicating that Zika virus RNA can be detected for prolonged periods in some pregnant women. To increase the proportion of pregnant women with Zika virus infection who receive a definitive diagnosis, CDC recommends expanding real-time reverse transcription-polymerase chain reaction (rRT-PCR) testing. Possible exposures to Zika virus include travel to or residence in an area with active Zika virus transmission, or sex* with a partner who has traveled to or resides in an area with active Zika virus transmission without using condoms or other barrier methods to prevent infection.(dagger) Testing recommendations for pregnant women with possible Zika virus exposure who report clinical illness consistent with Zika virus disease( section sign) (symptomatic pregnant women) are the same, regardless of their level of exposure (i.e., women with ongoing risk for possible exposure, including residence in or frequent travel to an area with active Zika virus transmission, as well as women living in areas without Zika virus transmission who travel to an area with active Zika virus transmission, or have unprotected sex with a partner who traveled to or resides in an area with active Zika virus transmission). Symptomatic pregnant women who are evaluated <2 weeks after symptom onset should receive serum and urine Zika virus rRT-PCR testing. Symptomatic pregnant women who are evaluated 2-12 weeks after symptom onset should first receive a Zika virus immunoglobulin (IgM) antibody test; if the IgM antibody test result is positive or equivocal, serum and urine rRT-PCR testing should be performed. Testing recommendations for pregnant women with possible Zika virus exposure who do not report clinical illness consistent with Zika virus disease (asymptomatic pregnant women) differ based on the circumstances of possible exposure. For asymptomatic pregnant women who live in areas without active Zika virus transmission and who are evaluated <2 weeks after last possible exposure, rRT-PCR testing should be performed. If the rRT-PCR result is negative, a Zika virus IgM antibody test should be performed 2-12 weeks after the exposure. Asymptomatic pregnant women who do not live in an area with active Zika virus transmission, who are first evaluated 2-12 weeks after their last possible exposure should first receive a Zika virus IgM antibody test; if the IgM antibody test result is positive or equivocal, serum and urine rRT-PCR should be performed. Asymptomatic pregnant women with ongoing risk for exposure to Zika virus should receive Zika virus IgM antibody testing as part of routine obstetric care during the first and second trimesters; immediate rRT-PCR testing should be performed when IgM antibody test results are positive or equivocal. This guidance also provides updated recommendations for the clinical management of pregnant women with confirmed or possible Zika virus infection. These recommendations will be updated when additional data become available. |
Structure and receptor binding preferences of recombinant hemagglutinins from avian and human h6 and h10 influenza A virus subtypes
Yang H , Carney PJ , Chang JC , Villanueva JM , Stevens J . J Virol 2015 89 (8) 4612-23 During 2013, three new avian influenza A virus subtypes, A(H7N9), A(H6N1), and A(H10N8), resulted in human infections. While the A(H7N9) virus resulted in a significant epidemic in China across 19 provinces and municipalities, both A(H6N1) and A(H10N8) viruses resulted in only a few human infections. This study focuses on the major surface glycoprotein hemagglutinins from both of these novel human viruses. The detailed structural and glycan microarray analyses presented here highlight the idea that both A(H6N1) and A(H10N8) virus hemagglutinins retain a strong avian receptor binding preference and thus currently pose a low risk for sustained human infections. IMPORTANCE: Human infections with zoonotic influenza virus subtypes continue to be a great public health concern. We report detailed structural analysis and glycan microarray data for recombinant hemagglutinins from A(H6N1) and A(H10N8) viruses, isolated from human infections in 2013, and compare them with hemagglutinins of avian origin. This is the first structural report of an H6 hemagglutinin, and our results should further the understanding of these viruses and provide useful information to aid in the continuous surveillance of these zoonotic influenza viruses. |
Neuraminidase mutations conferring resistance to oseltamivir in influenza A(H7N9) viruses
Marjuki H , Mishin VP , Chesnokov AP , De La Cruz JA , Davis CT , Villanueva JM , Fry AM , Gubareva LV . J Virol 2015 89 (10) 5419-26 Human infections by avian influenza A(H7N9) virus entail substantial morbidity and mortality. Treatment of infected patients with the neuraminidase (NA) inhibitor oseltamivir was associated with emergence of viruses carrying NA substitutions. In the NA inhibition (NI) assay, R292K conferred highly reduced inhibition by oseltamivir, while E119V and I222K each caused reduced inhibition. To facilitate establishment of laboratory correlates of clinically relevant resistance, experiments were conducted in ferrets infected with virus carrying wild-type or variant NA genes recovered from the A/Taiwan/1/2013 isolate. Oseltamivir treatment (5 or 25 mg/kg/dose) was given 4 hours post-infection followed by twice daily treatment for 5 days. Treatment of ferrets infected with wild-type virus resulted in a modest dose-dependent reduction (0.7-1.5 log10TCID50) in nasal wash viral titers and inflammation response. Conversely, treatment failed to significantly inhibit the replication of R292K or E119V viruses. A small reduction of viral titers was detected on day 5 in ferrets infected with the I222K virus. Propensity for oseltamivir resistance emergence was assessed in oseltamivir-treated animals infected with wild-type virus; emergence of R292K virus was detected in 3 of 6 ferrets within 5-7 days post-infection. Collectively, we demonstrate that R292K, E119V and I222K reduced the inhibitory activity of oseltamivir not only in the NI assay, but also in infected ferrets, judged particularly by viral loads in nasal washes, and may signal the need for alternative therapeutics. Thus, these clinical outcomes measured in the ferret model may correlate with clinically relevant oseltamivir resistance in humans. IMPORTANCE: This report provides more evidence for using the ferret model to assess susceptibility of influenza A(H7N9) viruses to oseltamivir, the most prescribed anti-influenza drug. The information gained can be used to assist in the establishment of laboratory correlates of human disease and drug therapy. The rapid emergence of viruses with R292K in treated ferrets correlates well with the multiple reports on this NA variant in treated human patients. Our findings highlight the importance for discovery and characterization of new antiviral drugs with different mechanism of action and the use of combination treatment strategies against emerging viruses with pandemic potential such as avian H7N9 virus, particularly against those carrying drug resistance markers. |
Structure and receptor binding preferences of recombinant human A(H3N2) virus hemagglutinins
Yang H , Carney PJ , Chang JC , Guo Z , Villanueva JM , Stevens J . Virology 2015 477c 18-31 A(H3N2) influenza viruses have circulated in humans since 1968, and antigenic drift of the hemagglutinin (HA) protein continues to be a driving force that allows the virus to escape the human immune response. Since the major antigenic sites of the HA overlap into the receptor binding site (RBS) of the molecule, the virus constantly struggles to effectively adapt to host immune responses, without compromising its functionality. Here, we have structurally assessed the evolution of the A(H3N2) virus HA RBS, using an established recombinant expression system. Glycan binding specificities of nineteen A(H3N2) influenza virus HAs, each a component of the seasonal influenza vaccine between 1968 and 2012, were analyzed. Results suggest that while its receptor-binding site has evolved from one that can bind a broad range of human receptor analogs to one with a more restricted binding profile for longer glycans, the virus continues to circulate and transmit efficiently among humans. |
Oseltamivir-resistant influenza A(H1N1)pdm09 viruses, United States, 2013-14.
Okomo-Adhiambo M , Fry AM , Su S , Nguyen HT , Elal AA , Negron E , Hand J , Garten RJ , Barnes J , Xiyan X , Villanueva JM , Gubareva LV . Emerg Infect Dis 2015 21 (1) 136-41 ![]() We report characteristics of oseltamivir-resistant influenza A(H1N1)pdm09 viruses and patients infected with these viruses in the United States. During 2013-14, fifty-nine (1.2%) of 4,968 analyzed US influenza A(H1N1)pdm09 viruses had the H275Y oseltamivir resistance-conferring neuraminidase substitution. Our results emphasize the need for local surveillance for neuraminidase inhibitor susceptibility among circulating influenza viruses. |
Structural and functional analysis of surface proteins from an A(H3N8) influenza virus isolated from New England harbor seals
Yang H , Nguyen HT , Carney PJ , Guo Z , Chang JC , Jones J , Davis CT , Villanueva JM , Gubareva LV , Stevens J . J Virol 2014 89 (5) 2801-12 In late 2011, an A(H3N8) influenza virus infection resulted in the deaths of 162 New England harbor seals. Virus sequence analysis and virus receptor binding studies highlighted potential markers responsible for mammalian adaptation and a mixed receptor binding preference (Anthony et al. ; MBio 3: e00166-00112). Here we present a detailed structural and biochemical analysis of the surface antigens of this virus. Results obtained with recombinant proteins for both the hemagglutinin and neuraminidase, indicate a true avian receptor binding preference. Although the detection of this virus in new species highlights an increased potential for cross-species transmission with these viruses, our results indicate that the A(H3N8) virus currently poses a low risk to humans. IMPORTANCE: Cross-species transmission of zoonotic influenza viruses increases public health concerns. Here we report a molecular and structural study of the major surface proteins from an A(H3N8) influenza virus isolated from New England harbor seals. Results improve our understanding of these viruses as they evolve and provide important information to aid ongoing risk assessment analyses, as these zoonotic influenza viruses continue to circulate and adapt to new hosts. |
Use of highly pathogenic avian influenza A(H5N1) gain-of-function studies for molecular-based surveillance and pandemic preparedness.
Davis CT , Chen LM , Pappas C , Stevens J , Tumpey TM , Gubareva LV , Katz JM , Villanueva JM , Donis RO , Cox NJ . mBio 2014 5 (6) ![]() Zoonotic influenza viruses circulating in poultry and swine pose an ever present threat to human health. In particular, the rapid geographical expansion of highly pathogenic avian influenza (HPAI) A(H5N1) throughout Asia and then into Europe, the Middle East, and Africa during the 2000s galvanized the global community in an attempt to control this rapidly growing threat. Despite successful control efforts in some countries, the virus remains endemic in poultry in at least six countries and continues to cause human illness and deaths as well as countless outbreaks in birds. During the past decade, 668 cases and 393 deaths were detected and reported to the World Health Organization (WHO) (1). During the 17 years since human infections with HPAI A(H5N1) were first identified in Hong Kong, Special Administrative Region, People’s Republic of China, in 1997, these viruses have evolved substantially through mutation and reassortment, resulting in multiple divergent genotypes and clades (2). | Ongoing H5N1 circulation has appropriately resulted in a focus on sequencing viral genomes to understand the evolution of these viruses and the significance of observed genetic changes. Expanded laboratory capacity for high-throughput Sanger sequencing and recent technological advances, such as next-generation sequencing and parallel computing, have revolutionized the quantity, quality, and availability of gene sequences and our ability to quickly and accurately analyze these data (3). Consequently, the number of animal and human influenza virus sequences available in publically accessible databases has dramatically increased over the years, as have the bioinformatics tools required for efficient investigation (4, 5). These advances in laboratory and analytical methods provide strong incentives to utilize molecular data for pandemic risk assessment of zoonotic influenza viruses at the animal-human interface (6). |
Characterization of drug-resistant influenza A(H7N9) variant viruses isolated from an oseltamivir-treated patient in Taiwan
Marjuki H , Mishin VP , Chesnokov AP , Jones J , De La Cruz JA , Sleeman K , Tamura D , Nguyen HT , Wu HS , Chang FY , Liu MT , Fry AM , Cox NJ , Villanueva JM , Davis CT , Gubareva LV . J Infect Dis 2014 211 (2) 249-57 BACKGROUND: Patients contracting influenza A(H7N9) often developed severe disease causing respiratory failure. Neuraminidase (NA) inhibitors (NAIs) are the primary option for treatment, but information on drug-resistance markers for A(H7N9) is limited. METHODS: Four NA variants of A/Taiwan/1/2013 (H7N9) virus containing a single substitution (NA-E119 V, NA-I222 K, NA-I222R or NA-R292 K), recovered from an oseltamivir-treated patient, were tested for NAI susceptibility in vitro; their replicative fitness was evaluated in cell culture, mice and ferrets. RESULTS: NA-R292 K led to highly reduced inhibition by oseltamivir and peramivir, while NA-E119 V, NA-I222 K and NA-I222R caused reduced inhibition by oseltamivir. Mice infected with any virus showed severe clinical signs with high mortality rates. NA-I222 K virus was the most virulent in mice, whereas virus lacking NA change (NA-WT) and NA-R292 K virus seemed the least virulent. Sequence analysis suggests that PB2-S714N increased virulence of the NA-I222 K virus in mice; NS1-K126R, alone or in combination with PB2-V227M, produced contrasting effects in NA-WT and NA-R292 K viruses. In ferrets, all viruses replicated to high titers in the upper respiratory tract, but produced only mild illness. NA-R292 K virus, showed reduced replicative fitness in this animal model. CONCLUSIONS: Our data highlight challenges in assessment of replicative fitness of H7N9 NA variants emerged in NAI-treated patients. |
Rapid strategy for screening by pyrosequencing of influenza virus reassortants--candidates for live attenuated vaccines.
Shcherbik SV , Pearce NC , Levine ML , Klimov AI , Villanueva JM , Bousse TL . PLoS One 2014 9 (3) e92580 ![]() BACKGROUND: Live attenuated influenza vaccine viruses (LAIVs) can be generated by classical reassortment of gene segments between a cold adapted, temperature sensitive and attenuated Master Donor Virus (MDV) and a seasonal wild-type (wt) virus. The vaccine candidates contain hemagglutinin (HA) and neuraminidase (NA) genes derived from the circulating wt viruses and the remaining six genes derived from the MDV strains. Rapid, efficient selection of the viruses with 6ratio2 genome compositions from the large number of genetically different viruses generated during reassortment is essential for the biannual production schedule of vaccine viruses. METHODOLOGY/PRINCIPAL FINDINGS: This manuscript describes a new approach for the genotypic analysis of LAIV reassortant virus clones based on pyrosequencing. LAIV candidate viruses were created by classical reassortment of seasonal influenza A (H3N2) (A/Victoria/361/2011, A/Ohio/02/2012, A/Texas/50/2012) or influenza A (H7N9) (A/Anhui/1/2013) wt viruses with the MDV A/Leningrad/134/17/57(H2N2). Using strain-specific pyrosequencing assays, mixed gene variations were detected in the allantoic progenies during the cloning procedure. The pyrosequencing analysis also allowed for estimation of the relative abundance of segment variants in mixed populations. This semi-quantitative approach was used for selecting specific clones for the subsequent cloning procedures. CONCLUSIONS/SIGNIFICANCE: The present study demonstrates that pyrosequencing analysis is a useful technique for rapid and reliable genotyping of reassortants and intermediate clones during the preparation of LAIV candidates, and can expedite the selection of vaccine virus candidates. |
Structural stability of influenza A(H1N1)pdm09 virus hemagglutinins
Yang H , Chang JC , Guo Z , Carney PJ , Shore DA , Donis RO , Cox NJ , Villanueva JM , Klimov AI , Stevens J . J Virol 2014 88 (9) 4828-38 The non-covalent interactions that mediate trimerization of the influenza hemagglutinin (HA) are important determinants of its biological activities. Recent studies have demonstrated that mutations in the HA trimer interface affect the thermal and pH sensitivities of HA, suggesting a possible impact on vaccine stability (Farnsworth et al. 2011. Vaccine 29:: 1529-1533). We used size exclusion chromatography analysis of recombinant HA ectodomain to compare the differences among recombinant trimeric HA proteins from early 2009 pandemic H1N1 viruses, which dissociate to monomers, with those of more recent virus HAs that can be expressed as trimers. We analyzed differences amongst the HA sequences and identified inter-molecular interactions mediated by the residue at position 374 (HA0 numbering) of the HA2 sub-domain as critical for HA trimer stability. Crystallographic analyses of HA from the recent H1N1 virus A/Washington/5/2011 highlight the structural basis for this observed phenotype. It remains to be seen whether more recent viruses with this mutation will yield more stable vaccines in the future. IMPORTANCE: Hemagglutinins from the early 2009 H1N1 pandemic viruses are unable to maintain a trimeric complex when expressed in a recombinant system. However HAs from 2010 and 2011 strains are more stable and our work highlights the improvement in stability can be attributed to an E47K substitution in the HA2 subunit of the stalk that emerged naturally in the circulating viruses. |
Pathogenesis and transmission of avian influenza A (H7N9) virus in ferrets and mice
Belser JA , Gustin KM , Pearce MB , Maines TR , Zeng H , Pappas C , Sun X , Carney PJ , Villanueva JM , Stevens J , Katz JM , Tumpey TM . Nature 2013 501 (7468) 556-9 On 29 March 2013, the Chinese Center for Disease Control and Prevention confirmed the first reported case of human infection with an avian influenza A(H7N9) virus. The recent human infections with H7N9 virus, totalling over 130 cases with 39 fatalities to date, have been characterized by severe pulmonary disease and acute respiratory distress syndrome (ARDS). This is concerning because H7 viruses have typically been associated with ocular disease in humans, rather than severe respiratory disease. This recent outbreak underscores the need to better understand the pathogenesis and transmission of these viruses in mammals. Here we assess the ability of A/Anhui/1/2013 and A/Shanghai/1/2013 (H7N9) viruses, isolated from fatal human cases, to cause disease in mice and ferrets and to transmit to naive animals. Both H7N9 viruses replicated to higher titre in human airway epithelial cells and in the respiratory tract of ferrets compared to a seasonal H3N2 virus. Moreover, the H7N9 viruses showed greater infectivity and lethality in mice compared to genetically related H7N9 and H9N2 viruses. The H7N9 viruses were readily transmitted to naive ferrets through direct contact but, unlike the seasonal H3N2 virus, did not transmit readily by respiratory droplets. The lack of efficient respiratory droplet transmission was corroborated by low receptor-binding specificity for human-like alpha2,6-linked sialosides. Our results indicate that H7N9 viruses have the capacity for efficient replication in mammals and human airway cells and highlight the need for continued public health surveillance of this emerging virus. |
Detecting 2009 pandemic influenza A (H1N1) virus infection: availability of diagnostic testing led to rapid pandemic response
Jernigan DB , Lindstrom SL , Johnson JR , Miller JD , Hoelscher M , Humes R , Shively R , Brammer L , Burke SA , Villanueva JM , Balish A , Uyeki T , Mustaquim D , Bishop A , Handsfield JH , Astles R , Xu X , Klimov AI , Cox NJ , Shaw MW . Clin Infect Dis 2011 52 S36-S43 Diagnostic tests for detecting emerging influenza virus strains with pandemic potential are critical for directing global influenza prevention and control activities. In 2008, the Centers for Disease Control and Prevention received US Food and Drug Administration approval for a highly sensitive influenza polymerase chain reaction (PCR) assay. Devices were deployed to public health laboratories in the United States and globally. Within 2 weeks of the first recognition of 2009 pandemic influenza H1N1, the Centers for Disease Control and Prevention developed and began distributing a new approved pandemic influenza H1N1 PCR assay, which used the previously deployed device platform to meet a >8-fold increase in specimen submissions. Rapid antigen tests were widely used by clinicians at the point of care; however, test sensitivity was low (40%-69%). Many clinical laboratories developed their own pandemic influenza H1N1 PCR assays to meet clinician demand. Future planning efforts should identify ways to improve availability of reliable testing to manage patient care and approaches for optimal use of molecular testing for detecting and controlling emerging influenza virus strains. |
Validation of a method for preparing influenza H5N1 simulated samples
Lednicky JA , Villanueva JM , Burke SA , Shively R , Shaw MW , Daniels DE , Hamilton SB , Donis RO . J Virol Methods 2010 167 (2) 125-131 ![]() Avian influenza virus type A subtype H5N1 and potentially other novel influenza A viruses continue to pose a concern with mutation into a form easily transmitted between humans. The ability to rapidly detect and characterize influenza viruses, and distinguish seasonal and novel influenza A viruses such as H5N1, remains important to minimize morbidity and mortality in humans. As with other rare and emerging viral pathogens, clinical specimens from persons with H5N1 infections are extremely rare. Consequently, development of standardized methods and accepted criteria are necessary for both ensuring the validity of available diagnostic methods and for assessing the potential of new diagnostic tests that can detect and differentiate H5N1 and other novel influenza A viruses. Additionally, genotypic and antigenic evolution of H5N1 poses a challenge with maintaining updated reference virus strains. In this report, a method for preparing simulated samples using defined procedures and carefully selected H5N1 virus strains is described, and the reliability for using these samples in an evaluation protocol with a laboratory test for differentiating H5N1 virus from other influenza A viruses is evaluated. |
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