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ABSTRACT: Background. Defining dispersal of influenza virus via aerosol is essential for the development of prevention measures.Methods. During the 2010-2011 influenza season, subjects with influenza-like illness were enrolled in an emergency department and throughout a tertiary care hospital, nasopharyngeal swab specimens were obtained, and symptom severity, treatment, and medical history were recorded. Quantitative impaction air samples were taken not ≤0.305 m (1 foot), 0.914 m (3 feet), and 1.829 m (6 feet) from the patient's head during routine care. Influenza virus was detected by rapid test and polymerase chain reaction.Results. Sixty-one of 94 subjects (65%) tested positive for influenza virus. Twenty-six patients (43%) released influenza virus into room air, with 5 (19%) emitting up to 32 times more virus than others. Emitters surpassed the airborne 50% human infectious dose of influenza virus at all sample locations. Healthcare professionals (HCPs) were exposed to mainly small influenza virus particles (diameter, <4.7 µm), with concentrations decreasing with increasing distance from the patient's head (P < .05). Influenza virus release was associated with high viral loads in nasopharyngeal samples (shedding), coughing, and sneezing (P < .05). Patients who reported severe illness and major interference with daily life also emitted more influenza virus (P < .05).Conclusions. HCPs within 1.829 m of patients with influenza could be exposed to infectious doses of influenza virus, primarily in small-particle aerosols. This finding questions the current paradigm of localized droplet transmission during non-aerosol-generating procedures.
The Journal of Infectious Diseases 01/2013; · 6.41 Impact Factor
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ABSTRACT: We evaluated the limits of detection of 3 rapid influenza diagnostic tests-BD Veritor(TM) System for Flu A+B, Binax NOW® Influenza A+B, and QuickVue® Influenza-for influenza strains circulating in 2010-2012. Limits of detection varied by influenza strain, with Veritor(TM) Flu A+B test showing the lowest limit of detection for all strains.
Diagnostic microbiology and infectious disease 12/2012; · 2.45 Impact Factor
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ABSTRACT: We estimated the potential impact of parental Tdap immunization before delivery, at delivery and at the 2-week newborn visit on U.S. infant pertussis hospitalizations. We used published data for pertussis hospitalization rates among U.S. infants aged 0-4 months, the Tdap vaccine efficacy in adults, and the proportion of infants with pertussis <6 months of age in which either parent was the source (16-40% from mothers and 16-20% from fathers). Immunizing parents before pregnancy or ≥ 2 weeks prior to delivery should reduce pertussis hospitalizations among infants 0-4 months by 2694-9314 if both parents are vaccinated, and by 1347-6909 if only mothers are vaccinated. Greater reductions in pertussis hospitalizations would be achieved if parents are immunized ≥ 2 weeks prior to delivery than after delivery or the 2-week newborn visit. Although immunizing parents prior to pregnancy or delivery is best, immunizing parents in the postpartum period should provide protection to that newborn and to infants of subsequent pregnancies.
Vaccine 06/2012; 30(37):5527-32. · 3.77 Impact Factor
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ABSTRACT: We estimated the potential impact of administering the first dose of rotavirus vaccine at 6 weeks (42 days of life) instead of 2 months of age, which is permissible for all U.S. vaccines recommended at 2 months of age, on rotavirus hospitalization rates. We used published data for hospitalization rates, vaccine coverage, and vaccine efficacy after one dose and assumed a two-week delay in seroconversion after vaccine administration in the United States. Administering the first dose of rotavirus vaccine at 6 weeks instead of 8 weeks of age should have prevented 1110, 1660, and 2210 rotavirus hospitalizations among U.S. infants <3 months of age in 2006 when the vaccine was first introduced. This estimated benefit represents a 2-4% reduction in rotavirus hospitalizations among children <5 years of age.
Vaccine 02/2012; 30(17):2738-41. · 3.77 Impact Factor
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The Journal of Infectious Diseases 11/2011; · 6.41 Impact Factor
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The Journal of Infectious Diseases 11/2011; · 6.41 Impact Factor
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ABSTRACT: The efficacy of barrier precautions to prevent influenza transmission is unknown.
Twenty-eight participants were exposed to monodispersed live attenuated influenza vaccine (LAIV) particles (4.9 μm) in 6 groups: group 1, no precautions; group 2, ocular exposure only; group 3, surgical mask without eye protection; group 4, surgical mask with eye protection; group 5, fit-tested N95 respirator without eye protection; and group 6, fit-tested N95 respirator with eye protection. Influenza was detected by reverse-transcription polymerase chain reaction (RT-PCR) and culture in nasal washes. Exact 95% confidence intervals (CIs) were calculated.
Influenza was detected in 4 of 4 participants in group 1 (95% CI, 0-.60), 3 of 4 in group 2 (95% CI, .006-.806]), 5 of 5 in group 3 (95% CI, 0-.522), 5 of 5 in group 4, (95% CI, 0-.522), 3 of 5 in group 5 (95% CI, .053-.853), and 1 of 5 in group 6 (95% CI, .05-.72). RT-PCR revealed significant differences between group 1 and all other groups except group 3.
Transocular transmission of LAIV occured in most participants suggesting the necessity of eye protection. An N95 respirator provided the best guard further enhanced by eye protection.
The Journal of Infectious Diseases 07/2011; 204(2):193-9. · 6.41 Impact Factor
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ABSTRACT: To estimate the potential effect of the acceleration of administration of the first dose of pneumococcal conjugate vaccine from 2 months to 6 weeks of age.
Prediction model using data from a retrospective cohort study.
Published data from 8 states that participated in Active Bacterial Core Surveillance of the Emerging Infections Program Network for pneumococcus before pneumococcal conjugate vaccine introduction (July 1, 1997- June 30, 2000).
A total of 759 739 live births under surveillance. Intervention Estimating the potential benefit of administration of the first dose of the pneumococcal conjugate vaccine at 6 weeks of age instead of 2 months of age.
Estimation of reduction in the rate of invasive pneumococcal disease in infants 61 to 90 days of age.
The estimated direct effect of the acceleration of administration of the first dose of pneumococcal conjugate vaccine from 2 months to 6 weeks of age when this vaccine was first introduced could have reduced the burden of invasive pneumococcal disease in infants 61 to 90 days of age by 39.9%, 56.0%, and 72.1% for respective vaccine efficacies of 50%, 70%, and 90%. This translates into preventing an estimated 73, 103, and 133 cases of invasive pneumococcal disease per year among approximately 4 112 052 live births in the United States.
The acceleration of administration of the pneumococcal conjugate vaccine from 2 months to 6 weeks of age could reduce the burden of invasive pneumococcal disease among infants. This observation may be important when a new conjugate vaccine becomes available, particularly among populations with prevalent invasive pneumococcal disease from a serotype included in the new vaccine.
Archives of pediatrics & adolescent medicine 06/2009; 163(5):422-5. · 3.73 Impact Factor
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ABSTRACT: Human metapneumovirus (HMPV) is a recently discovered paramyxovirus of the subfamily Pneumovirinae, which also includes avian pneumovirus and human respiratory syncytial virus (HRSV). HMPV is an important cause of respiratory disease worldwide. To understand early events in HMPV replication, cDNAs encoding the HMPV nucleoprotein (N), phosphoprotein (P), matrix protein (M), M2-1 protein and M2-2 protein were cloned from cells infected with the genotype A1 HMPV wild-type strain TN/96-12. HMPV N and P were shown to interact using a variety of techniques: yeast two-hybrid assays, co-immunoprecipitation and fluorescence resonance energy transfer (FRET). Confocal microscopy studies showed that, when expressed individually, fluorescently tagged HMPV N and P exhibited a diffuse expression pattern in the host-cell cytoplasm of uninfected cells but were recruited to cytoplasmic viral inclusion bodies in HMPV-infected cells. Furthermore, when HMPV N and P were expressed together, they also formed cytoplasmic inclusion-like complexes, even in the absence of viral infection. FRET microscopy revealed that HMPV N and P interacted directly within cytoplasmic inclusion-like complexes. Moreover, it was shown by yeast two-hybrid analysis that the N-terminal 28 aa are required for the recruitment to and formation of cytoplasmic inclusions, but are dispensable for binding to HMPV P. This work showed that HMPV N and P proteins provide the minimal viral requirements for HMPV inclusion body formation, which may be a distinguishing characteristic of members of the subfamily Pneumovirinae.
Journal of General Virology 12/2008; 89(Pt 11):2698-708. · 3.36 Impact Factor
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ABSTRACT: This study estimates the potential impact, on rates of pertussis infections, hospitalizations, and deaths among infants in the United States, of administering the first dose of diphtheria and tetanus toxoids and acellular pertussis vaccine at 6 weeks rather than 2 months of age.
We used existing data to estimate current US rates of pertussis infections, hospitalizations, and deaths according to age and infant population in 2004. We then estimated the potential impact of accelerating the administration of the first dose of diphtheria and tetanus toxoids and acellular pertussis vaccine from 2 months to 6 weeks of age, an alternative schedule consistent with current vaccination guidelines. We used Poisson distribution analysis to determine 95% confidence intervals for projected rates of pertussis disease.
Acceleration of administration of the first dose of diphtheria and tetanus toxoids and acellular pertussis vaccine from 2 months to 6 weeks of age is expected to prevent 1236 cases of pertussis, 898 hospitalizations, and 7 deaths attributable to pertussis per year in the United States. These decreases represent 9% reduction in cases, 9% reduction in hospitalizations, and 6% reduction in deaths attributable to pertussis among infants <3 months of age. Acceleration of the second and third doses by 2 weeks is expected to prevent an additional 923 cases, 520 hospitalizations, and 2 deaths attributable to pertussis each year.
Acceleration of administration of diphtheria and tetanus toxoids and acellular pertussis vaccine from 2 months to 6 weeks should reduce the burden of pertussis among young infants.
PEDIATRICS 11/2008; 122(5):1021-6. · 4.47 Impact Factor
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JAMA The Journal of the American Medical Association 05/2007; 297(16):1825-6. · 30.03 Impact Factor
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Xinhong Dong,
Hua Li,
Aaron Derdowski,
Lingmei Ding,
Atuhani Burnett,
Xuemin Chen, Timothy R Peters,
Terence S Dermody,
Elvin Woodruff,
Jaang-Jiun Wang,
Paul Spearman
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ABSTRACT: Gag proteins direct the process of retroviral particle assembly and form the major protein constituents of the viral core. The matrix region of the HIV-1 Gag polyprotein plays a critical role in the transport of Gag to the plasma membrane assembly site. Recent evidence indicates that Gag trafficking to late endosomal compartments, including multivesicular bodies, occurs prior to viral particle budding from the plasma membrane. Here we demonstrate that the matrix region of HIV-1 Gag interacts directly with the delta subunit of the AP-3 complex, and that this interaction plays an important functional role in particle assembly. Disruption of this interaction eliminated Gag trafficking to multivesicular bodies and diminished HIV particle formation. These studies illuminate an early step in retroviral particle assembly and provide evidence that the trafficking of Gag to late endosomes is part of a productive particle assembly pathway.
Cell 04/2005; 120(5):663-74. · 32.40 Impact Factor
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ABSTRACT: Coronaviruses encode the largest replicase polyprotein of any known positive-strand RNA virus. Replicase protein precursors and mature products are thought to mediate the formation and function of viral replication complexes on the surfaces of intracellular double-membrane vesicles. However, the functions of only a few of these proteins are known. For the coronavirus mouse hepatitis virus (MHV), the first proteolytic processing event of the replicase polyprotein liberates an amino-terminal 28-kDa product (p28). While previous biochemical studies have suggested that p28 is associated with viral replication complexes, the intracellular localization and interactions of p28 with other proteins during the course of MHV replication have not been defined. We used immunofluorescence confocal microscopy to show that p28 localizes to viral replication complexes in the cytoplasm during early times postinfection. However, at late times postinfection, p28 localizes to sites of M accumulation distinct from the replication complex. Furthermore, by yeast two-hybrid and coimmunoprecipitation analyses, we demonstrate that p28 specifically binds to p10 and p15, two coronavirus replicase proteins of unknown function. Deletion mutagenesis experiments determined that the carboxy terminus of p28 is not required for its interactions with p10 and p15. These results suggest that p28 may play a part at the replication complex by interacting with p10 and p15. Moreover, our findings highlight a potential role for p28 at virion assembly sites.
Journal of Virology 12/2004; 78(21):11551-62. · 5.40 Impact Factor
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ABSTRACT: Reovirus replication occurs in the cytoplasm of infected cells and culminates in the formation of crystalline arrays of progeny virions within viral inclusions. Two viral nonstructural proteins, sigma NS and micro NS, and structural protein sigma 3 form protein-RNA complexes early in reovirus infection. To better understand the minimal requirements of viral inclusion formation, we expressed sigma NS, mu NS, and sigma 3 alone and in combination in the absence of viral infection. In contrast to its concentration in inclusion structures during reovirus replication, sigma NS expressed in cells in the absence of infection is distributed diffusely throughout the cytoplasm and does not form structures that resemble viral inclusions. Expressed sigma NS is functional as it complements the defect in temperature-sensitive, sigma NS-mutant virus tsE320. In both transfected and infected cells, mu NS is found in punctate cytoplasmic structures and sigma 3 is distributed diffusely in the cytoplasm and the nucleus. The subcellular localization of mu NS and sigma 3 is not altered when the proteins are expressed together or with sigma NS. However, when expressed with micro NS, sigma NS colocalizes with mu NS to punctate structures similar in morphology to inclusion structures observed early in viral replication. During reovirus infection, both sigma NS and mu NS are detectable 4 h after adsorption and colocalize to punctate structures throughout the viral life cycle. In concordance with these results, sigma NS interacts with mu NS in a yeast two-hybrid assay and by coimmunoprecipitation analysis. These data suggest that sigma NS and mu NS are the minimal viral components required to form inclusions, which then recruit other reovirus proteins and RNA to initiate viral genome replication.
Journal of Virology 06/2003; 77(10):5948-63. · 5.40 Impact Factor
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ABSTRACT: Reovirus attachment to cells is mediated by the binding of viral attachment protein sigma 1 to junctional adhesion molecule 1 (JAM1). The crystal structure of the extracellular region of human JAM1 (hJAM1) reveals two concatenated Ig-type domains with a pronounced bend at the domain interface. Two hJAM1 molecules form a dimer that is stabilized by extensive ionic and hydrophobic contacts between the N-terminal domains. This dimeric arrangement is similar to that observed previously in the murine homolog of JAM1, indicating physiologic relevance. However, differences in the dimeric structures of hJAM1 and murine JAM1 suggest that the interface is dynamic, perhaps as a result of its ionic nature. We demonstrate that hJAM1, but not the related proteins hJAM2 and hJAM3, serves as a reovirus receptor, which provides insight into sites in hJAM1 that likely interact with sigma 1. In addition, we present evidence that the previously reported structural homology between sigma 1 and the adenovirus attachment protein, fiber, also extends to their respective receptors, which form similar dimeric structures. Because both receptors are located at regions of cell-cell contact, this similarity suggests that reovirus and adenovirus use conserved mechanisms of entry and pathways of infection.
Proceedings of the National Academy of Sciences 05/2003; 100(9):5366-71. · 9.68 Impact Factor
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Pediatric Annals 05/2002; 31(4):261-8. · 0.48 Impact Factor
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ABSTRACT: A 7-year-old girl with a midbrain glioma contracted Pneumocystis carinii pneumonia (PCP) in the absence of cytotoxic or corticosteroid therapy. Gliomas are known to cause immunosuppression, and PCP prophylaxis should be considered for patients with these tumors.
Pediatric Hematology and Oncology 04/2002; 19(2):141-3. · 0.89 Impact Factor
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ABSTRACT: 14-year-old white male with a past medical history of congenital bicuspid aortic valve, Streptococcus viridans endocarditis, and pulmonary valve homograft presented with culture-negative endocarditis. Molecular studies identified the causative organism as Bartonella henselae and subsequent serologic studies supported this diagnosis. This rare cause of endocarditis may be under recognized in children. Bartonella henselae endocarditis should be considered in all children with culture-negative endocarditis, and molecular studies using a polymerase chain reaction-based assay should be routinely utilized in the evaluation of all endocarditis cases that are culture negative to rapidly diagnosis this treatable cause of endocarditis.
Pediatric Cardiology 27(6):769-71. · 1.30 Impact Factor
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ABSTRACT: To assess the validity of parental report for seasonal and monovalent H1N1 influenza vaccinations among children 6 months to <18 years who were recommended to receive both vaccines in 2009-2010.
Children with fever or respiratory symptoms were prospectively enrolled in both emergency departments in Forsyth County, North Carolina, and the only pediatric hospital in the region. Enrollment occurred from September 1, 2009, through April 12, 2010, during the H1N1 influenza pandemic. A parental questionnaire was administered by trained interviewers to ascertain the status of seasonal and monovalent H1N1 influenza vaccines. Parental report was compared with that documented in the medical record and/or the North Carolina immunization registry.
Among 297 enrolled children 6 months to <18 years of age, 174 (59%) were 6 months to 4 years, 67 (23%) were 5-8 years, and 56 (19%) were 9 to <18 years. Parents reported that 140 (47%) children had received ≥1 dose of 2009-2010 influenza vaccine-128 (43%) for seasonal vaccine and 63 (21%) for H1N1 vaccine. Confirmed vaccination data indicated that 156 (53%) children had received ≥1 dose of any 2009-2010 vaccine-120 (40%) for seasonal vaccine and 53 (18%) for H1N1 vaccine. Parental report of any seasonal influenza vaccination was 92% sensitive and 86% specific and had a kappa of 0.76. Parental report for any H1N1 influenza vaccination was 88% sensitive and 92% specific with a kappa of 0.71.
Parental report of 2009-2010 seasonal and monovalent H1N1 influenza vaccinations was sensitive and specific and had reasonable agreement with the medical record and/or immunization registry.
Academic pediatrics 12(1):36-42.
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ABSTRACT: The heptavalent pneumococcal conjugate vaccine (PCV7) that has been recommended since the year 2000 for all US children younger than 2 years has been a towering success. Childhood PCV7 vaccination has resulted in much greater reductions in invasive disease in young children, as well as older children and adults through herd immunity, than had been anticipated.1- 4 From 2001 through 2005, Active Bacterial Core surveillance of the Centers for Disease Control and Prevention showed that the US burden of invasive pneumococcal disease decreased by more than 100 000 cases, including about 2000 cases of meningitis and 25 000 cases of pneumonia with bacteremia. Invasive disease occurred in 188 per 100 000 US children younger than 2 years before PCV7 licensure. In 2005, 5 years after PCV7 licensure, rates of invasive disease decreased 81% to 36 per 100 000 children.5 The success of this vaccine is underscored by the recent recommendation of the World Health Organization to include PCV7 in national immunization programs worldwide.6
JAMA The Journal of the American Medical Association 297(16):1825-1826. · 30.03 Impact Factor
