Last data update: May 20, 2024. (Total: 46824 publications since 2009)
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Query Trace: Wadford DA [original query] |
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Serological and metagenomic interrogation of cerebrospinal fluid implicates enteroviruses in pediatric acute flaccid myelitis (preprint)
Schubert RD , Hawes IA , Ramachandran PS , Ramesh A , Crawford ED , Pak JE , Wu W , Cheung CK , O'Donovan BD , Tato CM , Lyden A , Tan M , Sit R , Sowa GA , Sample HA , Zorn KC , Banerji D , Khan LM , Bove R , Hauser SL , Gelfand AA , Johnson-Kerner BL , Nash K , Krishnamoorthy KS , Chitnis T , Ding JZ , McMillan HJ , Chiu CY , Briggs B , Glaser CA , Yen C , Chu V , Wadford DA , Dominguez SR , Ng TFF , Marine RL , Lopez AS , Nix WA , Soldatos A , Gorman MP , Benson L , Messacar K , Konopka-Anstadt JL , Oberste MS , DeRisi JL , Wilson MR . bioRxiv 2019 666230 Background Since 2014, the United States has experienced a biennial spike in pediatric acute flaccid myelitis (AFM). Epidemiologic evidence suggests non-polio enteroviruses (EVs) are a potential etiology, yet EV RNA is rarely detected in cerebrospinal fluid (CSF) and only inconsistently identified from the respiratory tract, serum, or stool.Methods We interrogated CSF from children with AFM (n=42) and pediatric controls with other neurologic diseases (OND) (n=58). Samples were incubated with T7 bacteriophage expressing 481,966 sixty-two amino acid peptides with a fourteen amino acid overlap tiled across all known vertebrate virus and arbovirus genomes, an adaption of the VirScan method. Antibody-bound phage were deep sequenced to quantify enriched peptides with normalized counts expressed as reads per hundred thousand (rpK). EV antibody findings were confirmed with ELISA using whole viral protein 1 (VP1) from contemporary enterovirus (EV) A71 and D68 strains. Separately, metagenomic next-generation sequencing (mNGS) of CSF RNA, both unbiased and with targeted enrichment for EVs, was performed.Results The most significantly enriched viral family by VirScan of CSF in AFM versus OND controls was Picornaviridae (mean rpK 11,266 versus mean rpK 950, p-adjusted < 0.001, Wilcoxon signed-rank test with Bonferroni adjustment). Enriched Picornaviridae peptides belonged almost entirely to the genus Enterovirus. The mean EV VP1 ELISA signal in AFM (mean OD 0.51) was significantly higher than OND controls (mean OD 0.08, p-value < 0.001, Mann-Whitney test). mNGS did not detect additional enterovirus RNA in CSF.Conclusion Despite the rare detection of EV RNA in the CNS of patients with AFM, a pan-viral serologic assay identified high levels of CSF EV antibodies in AFM CSF compared to CSF from OND controls. These results provide further evidence for a causal role of non-polio enteroviruses in AFM. |
Outbreak of COVID-19 among vaccinated and unvaccinated homeless shelter residents - Sonoma County, California, July 2021 (preprint)
Bukatko A , Lobato MN , Mosites E , Stainken C , Reihl K , Deldari M , Bell JM , Morris MK , Wadford DA , Harriman K , Mase S . medRxiv 2021 08 In July 2021, the Sonoma County Health Department was alerted to three cases of COVID-19 among residents of a homeless shelter in Santa Rosa, California. Among 153 shelter residents, 83 (54%) were fully vaccinated; 71 (86%) vaccinated residents had received the Janssen COVID-19 vaccine and 12 (14%) received an mRNA (Pfizer BioNTech or Moderna) COVID-19 vaccine. Within 1 month, 116 shelter residents (76%) received positive SARS-CoV-2 test results, including 66 fully vaccinated residents and 50 not fully vaccinated. 9 fully vaccinated and 1 unvaccinated were hospitalized for COVID-19. All hospitalized cases had at least one underlying medical condition. Two deaths occurred, one in a vaccinated resident and one in a non-vaccinated resident. Specimens from 52 residents underwent whole genome sequencing; all were identified as SARS-CoV-2, Delta Variant AY.13 lineage. Additional mitigation measures are needed in medically vulnerable congregate setting where limited resources make individual quarantine and isolation not feasible. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
A Genomic Survey of SARS-CoV-2 Reveals Multiple Introductions into Northern California without a Predominant Lineage (preprint)
Deng X , Gu W , Federman S , du Plessis L , Pybus OG , Faria N , Wang C , Yu G , Pan CY , Guevara H , Sotomayor-Gonzalez A , Zorn K , Gopez A , Servellita V , Hsu E , Miller S , Bedford T , Greninger AL , Roychoudhury P , Starita LM , Famulare M , Chu HY , Shendure J , Jerome KR , Anderson C , Gangavarapu K , Zeller M , Spencer E , Andersen KG , MacCannell D , Paden CR , Li Y , Zhang J , Tong S , Armstrong G , Morrow S , Willis M , Matyas BT , Mase S , Kasirye O , Park M , Chan C , Yu AT , Chai SJ , Villarino E , Bonin B , Wadford DA , Chiu CY . medRxiv 2020 The COVID-19 pandemic caused by the novel coronavirus SARS-CoV-2 has spread globally, resulting in >300,000 reported cases worldwide as of March 21st, 2020. Here we investigate the genetic diversity and genomic epidemiology of SARS-CoV-2 in Northern California using samples from returning travelers, cruise ship passengers, and cases of community transmission with unclear infection sources. Virus genomes were sampled from 29 patients diagnosed with COVID-19 infection from Feb 3rd through Mar 15th. Phylogenetic analyses revealed at least 8 different SARS-CoV-2 lineages, suggesting multiple independent introductions of the virus into the state. Virus genomes from passengers on two consecutive excursions of the Grand Princess cruise ship clustered with those from an established epidemic in Washington State, including the WA1 genome representing the first reported case in the United States on January 19th. We also detected evidence for presumptive transmission of SARS-CoV-2 lineages from one community to another. These findings suggest that cryptic transmission of SARS-CoV-2 in Northern California to date is characterized by multiple transmission chains that originate via distinct introductions from international and interstate travel, rather than widespread community transmission of a single predominant lineage. Rapid testing and contact tracing, social distancing, and travel restrictions are measures that will help to slow SARS-CoV-2 spread in California and other regions of the USA. |
SARS-CoV-2 Delta variant genomic variation associated with breakthrough infection in Northern California: A retrospective cohort study
Skarbinski J , Nugent JR , Wood MS , Liu L , Bullick T , Schapiro JM , Arunleung P , Morales C , Amsden LB , Hsiao CA , Wadford DA , Chai SJ , Reingold A , Wyman SK . J Infect Dis 2023 228 (7) 878-888 BACKGROUND: The association between SARS-CoV-2 genomic variation and breakthrough infection is not well-defined among persons with Delta variant SARS-CoV-2 infection. METHODS: In a retrospective cohort we assessed whether individual non-lineage defining mutations and overall genomic variation (including low frequency alleles) were associated with breakthrough infection defined as SARS-CoV-2 infection after COVID-19 primary vaccine series. We identified all non-synonymous single nucleotide polymorphisms, insertions and deletions in SARS-CoV-2 genomes with ≥5% allelic frequency and population frequency of ≥5% and ≤95%. Using Poisson regression, we assessed the association with breakthrough infection for each individual mutation and a viral genomic risk score. RESULTS: Thirty-six mutations met our inclusion criteria. Among 12,744 persons infected with Delta variant SARS-CoV-2, 5,949 (47%) were vaccinated and 6,795 (53%) were unvaccinated. Viruses with a viral genomic risk score in the highest quintile were 9% more likely to be associated with breakthrough infection than viruses in the lowest quintile, but including the risk score improved overall predictive model performance (measured by c-statistic) by only +0.0006. CONCLUSIONS: Genomic variation within SARS-CoV-2 Delta variant was weakly associated with breakthrough infection, however several potential non-lineage defining mutations were identified that might contribute to immune evasion by SARS-CoV-2. |
Adeno-associated virus type 2 in US children with acute severe hepatitis.
Servellita V , Gonzalez AS , Lamson DM , Foresythe A , Huh HJ , Bazinet AL , Bergman NH , Bull RL , Garcia KY , Goodrich JS , Lovett SP , Parker K , Radune D , Hatada A , Pan CY , Rizzo K , Bertumen JB , Morales C , Oluniyi PE , Nguyen J , Tan J , Stryke D , Jaber R , Leslie MT , Lyons Z , Hedman HD , Parashar U , Sullivan M , Wroblewski K , Oberste MS , Tate JE , Baker JM , Sugerman D , Potts C , Lu X , Chhabra P , Pediatric Hepatitis of Unknown Etiology Working Group , Ingram LA , Shiau H , Britt W , Sanchez LHG , Ciric C , Rostad CA , Vinjé J , Kirking HL , Wadford DA , Raborn RT , St George K , Chiu CY . Nature 2023 As of August 2022, clusters of acute severe hepatitis of unknown etiology in children have been reported from 35 countries, including the United States(1,2). Previous studies have found human adenoviruses (HAdVs) in the blood from cases in Europe and the United States(3-7), although it is unclear whether this virus is causative. Here we used PCR testing, viral enrichment based sequencing, and agnostic metagenomic sequencing to analyze samples from 16 HAdV-positive cases from October 1, 2021 to May 22, 2022, in parallel with 113 controls. In blood from 14 cases, adeno-associated virus 2 (AAV2) sequences were detected in 93% (13 of 14), compared to 4 (3.5%) of 113 controls (P<0.001) and to 0 of 30 patients with hepatitis of defined etiology (P<0.001). In controls, HAdV-41 was detected in blood from 9 (39.1%) of the 23 patients with acute gastroenteritis (without hepatitis), including 8 of 9 patients with positive stool HAdV testing, but co-infection with AAV2 was observed in only 3 (13.0%) of these 23 patients versus 93% of cases (P<0.001). Co-infections by Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6), and/or enterovirus A71 (EV-A71) were also detected in 12 (85.7%) of 14 cases, with higher herpesvirus detection in cases versus controls (P<0.001). Our findings suggest that the severity of the disease is related to co-infections involving AAV2 and one or more helper viruses. |
Effectiveness of Abbott BinaxNOW Rapid Antigen Test for Detection of SARS-CoV-2 Infections in Outbreak among Horse Racetrack Workers, California, USA.
Surasi K , Cummings KJ , Hanson C , Morris MK , Salas M , Seftel D , Ortiz L , Thilakaratne R , Stainken C , Wadford DA . Emerg Infect Dis 2021 27 (11) 2761-2767 The Abbott BinaxNOW rapid antigen test is cheaper and faster than real-time reverse transcription PCR (rRT-PCR) for detecting severe acute respiratory syndrome coronavirus 2. We compared BinaxNOW with rRT-PCR in 769 paired specimens from 342 persons during a coronavirus disease outbreak among horse racetrack workers in California, USA. We found positive percent agreement was 43.3% (95% CI 34.6%-52.4%), negative percent agreement 100% (95% CI 99.4%-100%), positive predictive value 100% (95% CI 93.5%-100%), and negative predictive value 89.9% (95% CI 87.5%-92.0%). Among 127 rRT-PCR-positive specimens, the 55 with paired BinaxNOW-positive results had a lower mean cycle threshold than the 72 with paired BinaxNOW-negative results (17.8 vs. 28.5; p<0.001). Of 100 specimens with cycle threshold <30, a total of 51 resulted in positive virus isolation; 45 (88.2%) of those were BinaxNOW-positive. Our comparison supports immediate isolation for BinaxNOW-positive persons and confirmatory testing for negative persons. |
Introduction, Transmission Dynamics, and Fate of Early SARS-CoV-2 Lineages in Santa Clara County, California.
Villarino E , Deng X , Kemper CA , Jorden MA , Bonin B , Rudman SL , Han GS , Yu G , Wang C , Federman S , Bushnell B , Wadford DA , Lin W , Tao Y , Paden CR , Bhatnagar J , MacCannell T , Tong S , Batson J , Chiu CY . J Infect Dis 2021 224 (2) 207-217 We combined viral genome sequencing with contact tracing to investigate introduction and evolution of SARS-CoV-2 lineages in Santa Clara County, California from January 27 to March 21, 2020. Of 558 persons with COVID-19, 101 genomes from 143 available clinical samples comprised 17 different lineages including SCC1 (n=41), WA1 (n=9, including the first 2 reported deaths in the United States, diagnosed post-mortem), D614G (n=4), ancestral Wuhan Hu-1 (n=21), and 13 others (n=26). Public health intervention may have curtailed the persistence of lineages that appeared transiently during February-March. By August, only D614G lineages introduced after March 21 were circulating in SCC. |
Timely Intervention and Control of a Novel Coronavirus (COVID-19) Outbreak at a Large Skilled Nursing Facility - San Francisco, California, 2020.
Karmarkar E , Blanco I , Amornkul P , DuBois A , Deng X , Moonan PK , Rubenstein BL , Miller DA , Kennedy I , Yu J , Dauterman J , Ongpin M , Hathaway W , Hoo L , Trammell S , Ememu E , Yu G , Khwaja Z , Lu W , Talai N , Jain S , Louie J , Philip S , Federman S , Masinde G , Wadford DA , Bobba N , Stoltey J , Smith A , Epson E , Chiu C , Bennett A , Vasquez AM , Williams T . Infect Control Hosp Epidemiol 2020 42 (10) 1-20 OBJECTIVE: To describe epidemiologic and genomic characteristics of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak in a large skilled nursing facility (SNF), and the strategies that controlled transmission. DESIGN, SETTING, AND PARTICIPANTS: Cohort study during March 22-May 4, 2020 of all staff and residents at a 780-bed SNF in San Francisco, California. METHODS: Contact tracing and symptom screening guided targeted testing of staff and residents; respiratory specimens were also collected through serial point prevalence surveys (PPS) in units with confirmed cases. Cases were confirmed by real-time reverse transcription-polymerase chain reaction testing for SARS-CoV-2; whole genome sequencing (WGS) characterized viral isolate lineages and relatedness. Infection prevention and control (IPC) interventions included restricting from work any staff who had close contact to a confirmed case; restricting movements between units; implementing surgical face masking facility-wide; and recommended PPE (isolation gown, gloves, N95 respirator and eye protection) for clinical interactions in units with confirmed cases. RESULTS: Of 725 staff and residents tested through targeted testing and serial PPS, twenty-one (3%) were SARS-CoV-2-positive; sixteen (76%) staff and 5 (24%) residents. Fifteen (71%) were linked to a single unit. Targeted testing identified 17 (81%) cases; PPS identified 4 (19%). Most (71%) cases were identified prior to IPC intervention. WGS was performed on SARS-CoV-2 isolates from four staff and four residents; five were of Santa Clara County lineage and the three others were distinct lineages. CONCLUSIONS: Early implementation of targeted testing, serial PPS, and multimodal IPC interventions limited SARS-CoV-2 transmission within the SNF. |
Acute fulminant cerebral edema: A newly recognized phenotype in children with suspected encephalitis
Krishnan P , Glenn OA , Samuel MC , Sheriff H , Foster-Barber A , Sejvar JJ , Roy-Burman A , Wadford DA , Preas CP , Tureen JH , Glaser CA . J Pediatric Infect Dis Soc 2020 10 (3) 289-294 BACKGROUND: Encephalitis is a severe neurological syndrome associated with significant morbidity and mortality. The California Encephalitis Project (CEP) enrolled patients for more than a decade. A subset of patients with acute and fulminant cerebral edema was noted. METHODS: All pediatric encephalitis patients with cerebral edema referred to the CEP between 1998 and 2012 were reviewed. A case definition was developed for acute fulminant cerebral edema (AFCE) that included the CEP case definition for encephalitis and progression to diffuse cerebral edema on neuroimaging and/or autopsy, and no other recognized etiology for cerebral edema (eg, organic, metabolic, toxin). Prodromic features, demographic and laboratory data, neuroimaging, and outcomes were compared with non-AFCE encephalitis cases. RESULTS: Of 1955 pediatric cases referred to the CEP, 30 (1.5%) patients met the AFCE case definition. The median age for AFCE and non-AFCE cases was similar: 8.2 years (1-18 years) and 8.0 years (0.5-18 years), respectively. Asian-Pacific Islanders comprised a larger proportion of AFCE cases (44%) compared with non-AFCE cases (14%, P < .01). AFCE cases often had a prodrome of high fever, vomiting, and profound headache. Mortality among AFCE patients was significantly higher than among non-AFCE patients (80% vs 13%, P < .01). A confirmed etiology was identified in only 2 cases (enterovirus, human herpes virus type 6), while 10 others had evidence of a respiratory pathogen.Thirty pediatric patients referred to the California Encephalitis Project with a unique, and often fatal, form of encephalitis are reported. Demographic and clinical characteristics, possible etiologies and a proposed case definition for acute fulminant cerebral edema (AFCE) are described. CONCLUSIONS: AFCE is a recently recognized phenotype of encephalitis with a high mortality. AFCE may be triggered by common pediatric infections. Here, we propose a case definition. |
Genomic surveillance reveals multiple introductions of SARS-CoV-2 into Northern California.
Deng X , Gu W , Federman S , du Plessis L , Pybus OG , Faria N , Wang C , Yu G , Bushnell B , Pan CY , Guevara H , Sotomayor-Gonzalez A , Zorn K , Gopez A , Servellita V , Hsu E , Miller S , Bedford T , Greninger AL , Roychoudhury P , Starita LM , Famulare M , Chu HY , Shendure J , Jerome KR , Anderson C , Gangavarapu K , Zeller M , Spencer E , Andersen KG , MacCannell D , Paden CR , Li Y , Zhang J , Tong S , Armstrong G , Morrow S , Willis M , Matyas BT , Mase S , Kasirye O , Park M , Masinde G , Chan C , Yu AT , Chai SJ , Villarino E , Bonin B , Wadford DA , Chiu CY . Science 2020 369 (6503) 582-587 The COVID-19 pandemic caused by the novel coronavirus SARS-CoV-2 has spread globally, with >52,000 cases in California as of May 4, 2020. Here we investigate the genomic epidemiology of SARS-CoV-2 in Northern California from late January to mid-March 2020, using samples from 36 patients spanning 9 counties and the Grand Princess cruise ship. Phylogenetic analyses revealed the cryptic introduction of at least 7 different SARS-CoV-2 lineages into California, including epidemic WA1 strains associated with Washington State, with lack of a predominant lineage and limited transmission between communities. Lineages associated with outbreak clusters in 2 counties were defined by a single base substitution in the viral genome. These findings support contact tracing, social distancing, and travel restrictions to contain SARS-CoV-2 spread in California and other states. |
Public Health Responses to COVID-19 Outbreaks on Cruise Ships - Worldwide, February-March 2020.
Moriarty LF , Plucinski MM , Marston BJ , Kurbatova EV , Knust B , Murray EL , Pesik N , Rose D , Fitter D , Kobayashi M , Toda M , Canty PT , Scheuer T , Halsey ES , Cohen NJ , Stockman L , Wadford DA , Medley AM , Green G , Regan JJ , Tardivel K , White S , Brown C , Morales C , Yen C , Wittry B , Freeland A , Naramore S , Novak RT , Daigle D , Weinberg M , Acosta A , Herzig C , Kapella BK , Jacobson KR , Lamba K , Ishizumi A , Sarisky J , Svendsen E , Blocher T , Wu C , Charles J , Wagner R , Stewart A , Mead PS , Kurylo E , Campbell S , Murray R , Weidle P , Cetron M , Friedman CR . MMWR Morb Mortal Wkly Rep 2020 69 (12) 347-352 An estimated 30 million passengers are transported on 272 cruise ships worldwide each year* (1). Cruise ships bring diverse populations into proximity for many days, facilitating transmission of respiratory illness (2). SARS-CoV-2, the virus that causes coronavirus disease (COVID-19) was first identified in Wuhan, China, in December 2019 and has since spread worldwide to at least 187 countries and territories. Widespread COVID-19 transmission on cruise ships has been reported as well (3). Passengers on certain cruise ship voyages might be aged >/=65 years, which places them at greater risk for severe consequences of SARS-CoV-2 infection (4). During February-March 2020, COVID-19 outbreaks associated with three cruise ship voyages have caused more than 800 laboratory-confirmed cases among passengers and crew, including 10 deaths. Transmission occurred across multiple voyages of several ships. This report describes public health responses to COVID-19 outbreaks on these ships. COVID-19 on cruise ships poses a risk for rapid spread of disease, causing outbreaks in a vulnerable population, and aggressive efforts are required to contain spread. All persons should defer all cruise travel worldwide during the COVID-19 pandemic. |
Nearly Complete Genome Sequence of an Echovirus 30 Strain from a Cluster of Aseptic Meningitis Cases in California, September 2017.
Pan CY , Huynh T , Padilla T , Chen A , Ng TFF , Marine RL , Castro CJ , Nix WA , Wadford DA . Microbiol Resour Announc 2019 8 (44) We report the nearly complete genome sequence of a human enterovirus, a strain of echovirus 30, obtained from a cerebrospinal fluid specimen from a teenaged patient with aseptic meningitis in September 2017. |
Pan-viral serology implicates enteroviruses in acute flaccid myelitis.
Schubert RD , Hawes IA , Ramachandran PS , Ramesh A , Crawford ED , Pak JE , Wu W , Cheung CK , O'Donovan BD , Tato CM , Lyden A , Tan M , Sit R , Sowa GA , Sample HA , Zorn KC , Banerji D , Khan LM , Bove R , Hauser SL , Gelfand AA , Johnson-Kerner BL , Nash K , Krishnamoorthy KS , Chitnis T , Ding JZ , McMillan HJ , Chiu CY , Briggs B , Glaser CA , Yen C , Chu V , Wadford DA , Dominguez SR , Ng TFF , Marine RL , Lopez AS , Nix WA , Soldatos A , Gorman MP , Benson L , Messacar K , Konopka-Anstadt JL , Oberste MS , DeRisi JL , Wilson MR . Nat Med 2019 25 (11) 1748-1752 Since 2012, the United States of America has experienced a biennial spike in pediatric acute flaccid myelitis (AFM)(1-6). Epidemiologic evidence suggests non-polio enteroviruses (EVs) are a potential etiology, yet EV RNA is rarely detected in cerebrospinal fluid (CSF)(2). CSF from children with AFM (n = 42) and other pediatric neurologic disease controls (n = 58) were investigated for intrathecal antiviral antibodies, using a phage display library expressing 481,966 overlapping peptides derived from all known vertebrate and arboviruses (VirScan). Metagenomic next-generation sequencing (mNGS) of AFM CSF RNA (n = 20 cases) was also performed, both unbiased sequencing and with targeted enrichment for EVs. Using VirScan, the viral family significantly enriched by the CSF of AFM cases relative to controls was Picornaviridae, with the most enriched Picornaviridae peptides belonging to the genus Enterovirus (n = 29/42 cases versus 4/58 controls). EV VP1 ELISA confirmed this finding (n = 22/26 cases versus 7/50 controls). mNGS did not detect additional EV RNA. Despite rare detection of EV RNA, pan-viral serology frequently identified high levels of CSF EV-specific antibodies in AFM compared with controls, providing further evidence for a causal role of non-polio EVs in AFM. |
Rotavirus vaccination coverage during a rotavirus outbreak resulting in a fatality at a subacute care facility
Burke RM , Tate JE , Han GS , Quenelle R , Gautam R , Wadford DA , Bowen MD , Parashar UD . J Pediatric Infect Dis Soc 2019 9 (3) 287-292 BACKGROUND: The introduction of rotavirus vaccine in the United States has reduced rotavirus disease burden, but outbreaks still occur. Complete-series rotavirus vaccination coverage is <75% in the United States, and it might be lower among vulnerable populations. We describe here the clinical characteristics and vaccination status of children during a rotavirus outbreak in a pediatric subacute care facility in 2017. METHODS: Clinical history, signs and symptoms, and vaccination history were abstracted for the 26 patients residing in the facility during the time of the outbreak. A case-patient was defined as one who experienced 3 or more loose stools in a period of 24 hours with onset between April 17 and May 17, 2017. Stool samples from 14 resident patients were tested for rotavirus with reverse-transcription polymerase chain reaction. RESULTS: The median patient age at the facility was 2.9 years. Of the 26 resident patients, 22 (85%) met the case definition. One child died. Stool samples from 11 case-patients were positive according to reverse-transcription polymerase chain reaction for rotavirus. Fifteen case-patients were unvaccinated against rotavirus; 3 were partially vaccinated, and 2 were fully vaccinated. Vaccination status could not be completely determined in 2 cases. CONCLUSIONS: An outbreak of rotavirus affected nearly all resident patients of a subacute care facility and caused 1 death. Because of recommendations against giving rotavirus vaccine in an intensive care setting, infants who require a prolonged intensive care stay might age out of rotavirus vaccine eligibility (the first dose must be given before 15 weeks of age according to Advisory Committee on Immunization Practices recommendations). The result is a vulnerable population of unvaccinated infants who might later congregate in another care setting. |
Outbreak of epidemic keratoconjunctivitis caused by human adenovirus type D53 in an eye care clinic - Los Angeles County, 2017
OYong K , Killerby M , Pan CY , Huynh T , Green NM , Wadford DA , Terashita D . MMWR Morb Mortal Wkly Rep 2018 67 (48) 1347-1349 On June 22, 2017, the Los Angeles County Department of Public Health (LAC DPH) was notified of seven patients who were seen at an eye care clinic on June 8, 2017, and later developed symptoms of epidemic keratoconjunctivitis (EKC). EKC is a contagious, severe form of viral conjunctivitis that can cause pain and blurred vision for up to 4 weeks (1). LAC DPH conducted an investigation, which identified 17 patients with EKC, including 15 who had visited the optometry clinic and two who were household contacts of clinic patients. Observations in the clinic found deficiencies in disinfection of tonometers (an instrument connected to a slit lamp and used to test for glaucoma by measuring intraocular pressure) and multiuse eye drop administration. Staff member education and revision of disinfection practices interrupted further transmission. Patient specimens tested positive for human adenovirus (HAdV) type D53 (HAdV-53). As the first documented EKC outbreak associated with HAdV-D53 in the United States, this outbreak highlights the need for rigorous implementation of recommended infection prevention practices in eye care settings. |
Genome Sequences of Rhinovirus Genotype C56 Detected in Three Patients with Acute Respiratory Illness, California, 2016 to 2017.
Pan CY , Yagi S , Padilla T , Fei Fan Ng T , Marine RL , Nix WA , Wadford DA . Microbiol Resour Announc 2018 7 (7) We report here two genome sequences of a newly designated rhinovirus genotype, RV-C56, which were obtained from respiratory specimens of three patients with acute respiratory illness in 2016 and 2017. To our knowledge, these sequences represent the first near-complete genomes for RV-C56 strains. |
Whole-Genome Sequence of Human Rhinovirus C47, Isolated from an Adult Respiratory Illness Outbreak in Butte County, California, 2017.
Pan CY , Padilla T , Yagi S , Lewis LS , Ng TFF , Marine RL , Nix WA , Wadford DA . Genome Announc 2018 6 (5) Here, we report the full coding sequence of rhinovirus C47 (RV-C47), obtained from a patient respiratory sample collected during an acute respiratory illness investigation in Butte County, California, in January 2017. This is the first whole-genome sequence of RV-C47 to be reported. |
Acute flaccid myelitis of unknown etiology in California, 2012-2015
Van Haren K , Ayscue P , Waubant E , Clayton A , Sheriff H , Yagi S , Glenn-Finer R , Padilla T , Strober JB , Aldrovandi G , Wadford DA , Chiu CY , Xia D , Harriman K , Watt JP , Glaser CA . JAMA 2015 314 (24) 2663-2671 IMPORTANCE: There has been limited surveillance for acute flaccid paralysis in North America since the regional eradication of poliovirus. In 2012, the California Department of Public Health received several reports of acute flaccid paralysis cases of unknown etiology. OBJECTIVE: To quantify disease incidence and identify potential etiologies of acute flaccid paralysis cases with evidence of spinal motor neuron injury. DESIGN, SETTING, AND PARTICIPANTS: Case series of acute flaccid paralysis in patients with radiological or neurophysiological findings suggestive of spinal motor neuron involvement reported to the California Department of Public Health with symptom onset between June 2012 and July 2015. Patients meeting diagnostic criteria for other acute flaccid paralysis etiologies were excluded. Cerebrospinal fluid, serum samples, nasopharyngeal swab specimens, and stool specimens were submitted to the state laboratory for infectious agent testing. MAIN OUTCOMES AND MEASURES: Case incidence and infectious agent association. RESULTS: Fifty-nine cases were identified. Median age was 9 years (interquartile range [IQR], 4-14 years; 50 of the cases were younger than 21 years). Symptoms that preceded or were concurrent included respiratory or gastrointestinal illness (n = 54), fever (n = 47), and limb myalgia (n = 41). Fifty-six patients had T2 hyperintensity of spinal gray matter on magnetic resonance imaging and 43 patients had cerebrospinal fluid pleocytosis. During the course of the initial hospitalization, 42 patients received intravenous steroids; 43, intravenous immunoglobulin; and 13, plasma exchange; or a combination of these treatments. Among 45 patients with follow-up data, 38 had persistent weakness at a median follow-up of 9 months (IQR, 3-12 months). Two patients, both immunocompromised adults, died within 60 days of symptom onset. Enteroviruses were the most frequently detected pathogen in either nasopharynx swab specimens, stool specimens, serum samples (15 of 45 patients tested). No pathogens were isolated from the cerebrospinal fluid. The incidence of reported cases was significantly higher during a national enterovirus D68 outbreak occurring from August 2014 through January 2015 (0.16 cases per 100000 person-years) compared with other monitoring periods (0.028 cases per 100000 person-years; P <.001). CONCLUSIONS AND RELEVANCE: In this series of patients identified in California from June 2012 through July 2015, clinical manifestations indicated a rare but distinct syndrome of acute flaccid paralysis with evidence of spinal motor neuron involvement. The etiology remains undetermined, most patients were children and young adults, and motor weakness was prolonged. |
Inducible nitric oxide contributes to viral pathogenesis following highly pathogenic influenza virus infection in mice
Perrone LA , Belser JA , Wadford DA , Katz JM , Tumpey TM . J Infect Dis 2013 207 (10) 1576-84 Highly pathogenic influenza A viruses including avian H5N1 viruses and the 1918 pandemic virus cause severe respiratory disease in humans and animals. Virus infection is followed by intense pulmonary congestion due to an extensive influx of macrophages and neutrophils which can release large quantities of reactive oxygen species potentially contributing to the pathogenesis of lung disease. Here the role of nitric oxide (NO), a potent signaling molecule in inflammation was evaluated following highly pathogenic influenza virus challenge in mice. We observed higher levels of NO in mice infected with H5N1 and 1918 viruses compared to a seasonal H1N1 virus. Mice deficient in inducible nitric oxide synthase (NOS2(-/-)) exhibited reduced morbidity, mortality and diminished cytokine production in lung tissue following H5N1 and 1918-virus challenge compared with wild-type control mice. Furthermore, systemic treatment of mice with the NOS inhibitor NG-monomethyl-L-arginine (L-NMMA) delayed weight loss and death among 1918 virus infected mice compared to untreated control animals. This study demonstrates that NO contributes to the pathogenic outcome of H5N1 and 1918 viral infections in the mouse model. |
Human pulmonary microvascular endothelial cells support productive replication of highly pathogenic avian influenza viruses: possible involvement in the pathogenesis of human H5N1 virus infection
Zeng H , Pappas C , Belser JA , Houser KV , Zhong W , Wadford DA , Stevens T , Balczon R , Katz JM , Tumpey TM . J Virol 2011 86 (2) 667-78 Highly pathogenic avian influenza (HPAI) H5N1 viruses continue to cause sporadic human infections with a high fatality rate. Respiratory failure due to acute respiratory distress syndrome (ARDS) is a complication among hospitalized patients. Since progressive pulmonary endothelial damage is the hallmark of ARDS, we investigated host responses following HPAI virus infection of human pulmonary microvascular endothelial cells. Evaluation of these cells for the presence of receptors preferred by influenza virus demonstrated that avian-like (alpha2-3 linked) receptors were more abundant than human-like (alpha2-6 linked) receptors. To test the permissiveness of pulmonary endothelial cells to virus infection, we compared the replication of selected seasonal, pandemic (2009 H1N1 and 1918), and potentially pandemic (H5N1) influenza strains. We observed that these cells only support productive replication of HPAI H5N1 viruses which preferentially enter through and are released from the apical surface of polarized human endothelial monolayers. Furthermore, A/Thailand/16/2004 and A/Vietnam/1203/2004 (VN/1203) H5N1 viruses, which exhibit heightened virulence in mammalian models, replicated to higher titers than less virulent H5N1 strains. VN/1203 infection caused a significant decrease in endothelial cell proliferation compared to other subtype viruses. VN/1203 virus was also found to be a potent inducer of cytokines and adhesion molecules known to regulate inflammation during acute lung injury. Deletion of the H5 hemagglutinin (HA) multi-basic cleavage site did not impact virus infectivity but resulted in decreased virus replication in endothelial cells. Our results highlight remarkable tropism and infectivity of the H5N1 viruses for human pulmonary endothelial cells resulting in the potent induction of host inflammatory responses. |
Influenza virus aerosol exposure and analytical system for ferrets
Gustin KM , Belser JA , Wadford DA , Pearce MB , Katz JM , Tumpey TM , Maines TR . Proc Natl Acad Sci U S A 2011 108 (20) 8432-7 Understanding the transmission ability of newly emerging influenza viruses is central to the development of public health preparedness and prevention strategies. Animals are used to model influenza virus infection and transmission, but the routinely used intranasal inoculation of a liquid virus suspension does not reflect natural infection. We report the development of an inoculation method that delivers an influenza virus aerosol inoculum to ferrets and the characterization of size distribution and viable virus present in aerosols shed from infected ferrets during normal breathing and sneezing. By comparing virus deposition, infectivity, virulence, and transmissibility among animals inoculated intranasally or by aerosols with a human (H3N2) or avian (H5N1) influenza virus, we demonstrate that aerosol inoculations more closely resemble a natural, airborne influenza virus infection and that viable virus is measurable in droplets and droplet nuclei exhaled by infected ferrets. These methods will provide improved risk assessment of emerging influenza viruses that pose a threat to public health. |
2009 pandemic influenza A (H1N1) and vaccine failure in pregnancy
Louie JK , Wadford DA , Norman A , Jamieson DJ . Obstet Gynecol 2011 117 470-2 BACKGROUND: Emerging data suggest that pregnancy conveys high risk for severe complications from the 2009 pandemic influenza A virus (2009 H1N1) infection. CASE: We describe an infected pregnant woman with critical illness owing to acute respiratory distress syndrome despite previous vaccination. Early serologic testing indicated absent immunity, followed 11 days later by a robust immune response. The patient required mechanical ventilation for 11 days, but ultimately improved, and was discharged home on hospital day 14. CONCLUSION: With the expectation that 2009 H1N1 will continue to cause disease in the immediate future, the virus has been included as a component of the 2010-2011 seasonal influenza vaccine. Vaccination of pregnant women is strongly encouraged. However, regardless of vaccination history, clinicians should remain vigilant for 2009 H1N1 infection when the virus is in circulation, and should not delay antiviral treatment of pregnant women with suspected influenza. |
Pathogenesis of pandemic influenza A (H1N1) and triple-reassortant swine influenza A (H1) viruses in mice
Belser JA , Wadford DA , Pappas C , Gustin KM , Maines TR , Pearce MB , Zeng H , Swayne DE , Pantin-Jackwood M , Katz JM , Tumpey TM . J Virol 2010 84 (9) 4194-203 The pandemic H1N1 virus of 2009 (2009 H1N1) continues to cause illness worldwide, primarily in younger age groups. To better understand the pathogenesis of these viruses in mammals, we used a mouse model to evaluate the relative virulence of selected 2009 H1N1 viruses and compared them to a representative human triple-reassortant swine influenza virus that has circulated in pigs in the United States for over a decade preceding the current pandemic. Additional comparisons were made with the reconstructed 1918 virus, a 1976 H1N1 swine influenza virus, and a highly pathogenic H5N1 virus. Mice were inoculated intranasally with each virus and monitored for morbidity, mortality, viral replication, hemostatic parameters, cytokine production and lung histology. All 2009 H1N1 viruses replicated efficiently in the lungs of mice and possessed a high degree of infectivity, but did not cause lethal disease or exhibit extrapulmonary virus spread. Transient weight loss, lymphopenia, and proinflammatory cytokine and chemokine production were present following 2009 H1N1 virus infection, but these levels were generally muted compared with a triple-reassortant swine virus and the 1918 virus. 2009 H1N1 viruses isolated from fatal cases did not demonstrate enhanced virulence in this model compared with isolates from mild human cases. Histologically, infection with the 2009 viruses resulted in lesions in the lung varying from mild to moderate bronchiolitis with occasional necrosis of bronchiolar epithelium, and mild to moderate peribronchiolar alveolitis. Taken together, these studies demonstrate that the 2009 H1N1 viruses exhibited mild to moderate virulence in mice compared with highly pathogenic viruses. |
Ocular infection of mice with influenza A (H7) viruses: a site of primary replication and spread to the respiratory tract
Belser JA , Wadford DA , Xu J , Katz JM , Tumpey TM . J Virol 2009 83 (14) 7075-84 Avian H7 influenza viruses have been responsible for poultry outbreaks worldwide and have resulted in numerous cases of human infection in recent years. The high rate of conjunctivitis associated with avian H7 subtype virus infections may represent a portal of entry for avian influenza viruses and highlights the need to better understand the apparent ocular tropism observed in humans. To study this, mice were inoculated by the ocular route with viruses of multiple subtypes and degrees of virulence. We found that in contrast to human (H3N2 and H1N1) viruses, H7N7 viruses isolated from The Netherlands in 2003 and H7N3 viruses isolated from British Columbia, Canada, in 2004, two subtypes that were highly virulent for poultry, replicated to a significant titer in the mouse eye. Remarkably, an H7N7 virus, as well as some avian H5N1 viruses, spread systemically following ocular inoculation, including to the brain, resulting in morbidity and mortality of mice. This correlated with efficient replication of highly pathogenic H7 and H5 subtypes in murine corneal epithelial sheets (ex vivo) and primary human corneal epithelial cells (in vitro). Influenza viruses were labeled to identify the virus attachment site in the mouse cornea. Although we found abundant H7 virus attachment to corneal epithelial tissue, this did not account for the differences in virus replication as multiple subtypes were able to attach to these cells. These findings demonstrate that avian influenza viruses within H7 and H5 subtypes are capable of using the eye as a portal of entry. |
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