Last data update: May 06, 2024. (Total: 46732 publications since 2009)
Records 1-22 (of 22 Records) |
Query Trace: Radford K[original query] |
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Fatal human alphaherpesvirus 1 infection in free-ranging black-tufted marmosets in anthropized environments, Brazil, 2012-2019
Wilson TM , Ritter JM , Martines RB , Bullock HA , Fair P , Radford KW , Macedo IL , Sousa DER , Goncalves AAB , Romano AP , Passsos PHO , Ramos DG , Costa GRT , Cavalcante KRLJ , de Melo CB , Zaki SR , Castro MB . Emerg Infect Dis 2022 28(4) (4) 802-811 Human alphaherpesvirus 1 (HuAHV1) causes fatal neurologic infections in captive New World primates. To determine risks for interspecies transmission, we examined data for 13 free-ranging, black-tufted marmosets (Callithrix penicillata) that died of HuAHV1 infection and had been in close contact with humans in anthropized areas in Brazil during 2012-2019. We evaluated pathologic changes in the marmosets, localized virus and antigen, and assessed epidemiologic features. The main clinical findings were neurologic signs, necrotizing meningoencephalitis, and ulcerative glossitis; 1 animal had necrotizing hepatitis. Transmission electron microscopy revealed intranuclear herpetic inclusions, and immunostaining revealed HuAHV1 and herpesvirus particles in neurons, glial cells, tongue mucosal epithelium, and hepatocytes. PCR confirmed HuAHV1 infection. These findings illustrate how disruption of the One Health equilibrium in anthropized environments poses risks for interspecies virus transmission with potential spillover not only from animals to humans but also from humans to free-ranging nonhuman primates or other animals. Copyright © 2022 Centers for Disease Control and Prevention (CDC). All rights reserved. |
Performance Evaluation of Serial SARS-CoV-2 Rapid Antigen Testing During a Nursing Home Outbreak.
McKay SL , Tobolowsky FA , Moritz ED , Hatfield KM , Bhatnagar A , LaVoie SP , Jackson DA , Lecy KD , Bryant-Genevier J , Campbell D , Freeman B , Gilbert SE , Folster JM , Medrzycki M , Shewmaker PL , Bankamp B , Radford KW , Anderson R , Bowen MD , Negley J , Reddy SC , Jernigan JA , Brown AC , McDonald LC , Kutty PK . Ann Intern Med 2021 174 (7) 945-951 BACKGROUND: To address high COVID-19 burden in U.S. nursing homes, rapid SARS-CoV-2 antigen tests have been widely distributed in those facilities. However, performance data are lacking, especially in asymptomatic people. OBJECTIVE: To evaluate the performance of SARS-CoV-2 antigen testing when used for facility-wide testing during a nursing home outbreak. DESIGN: A prospective evaluation involving 3 facility-wide rounds of testing where paired respiratory specimens were collected to evaluate the performance of the BinaxNOW antigen test compared with virus culture and real-time reverse transcription polymerase chain reaction (RT-PCR). Early and late infection were defined using changes in RT-PCR cycle threshold values and prior test results. SETTING: A nursing home with an ongoing SARS-CoV-2 outbreak. PARTICIPANTS: 532 paired specimens collected from 234 available residents and staff. MEASUREMENTS: Percentage of positive agreement (PPA) and percentage of negative agreement (PNA) for BinaxNOW compared with RT-PCR and virus culture. RESULTS: BinaxNOW PPA with virus culture, used for detection of replication-competent virus, was 95%. However, the overall PPA of antigen testing with RT-PCR was 69%, and PNA was 98%. When only the first positive test result was analyzed for each participant, PPA of antigen testing with RT-PCR was 82% among 45 symptomatic people and 52% among 343 asymptomatic people. Compared with RT-PCR and virus culture, the BinaxNOW test performed well in early infection (86% and 95%, respectively) and poorly in late infection (51% and no recovered virus, respectively). LIMITATION: Accurate symptom ascertainment was challenging in nursing home residents; test performance may not be representative of testing done by nonlaboratory staff. CONCLUSION: Despite lower positive agreement compared with RT-PCR, antigen test positivity had higher agreement with shedding of replication-competent virus. These results suggest that antigen testing could be a useful tool to rapidly identify contagious people at risk for transmitting SARS-CoV-2 during nascent outbreaks and help reduce COVID-19 burden in nursing homes. PRIMARY FUNDING SOURCE: None. |
Clinical and epidemiologic findings from enhanced monkeypox surveillance in Tshuapa Province, Democratic Republic of the Congo during 2011-2015
Whitehouse ER , Bonwitt J , Hughes CM , Lushima RS , Likafi T , Nguete B , Kabamba J , Monroe B , Doty JB , Nakazawa Y , Damon I , Malekani J , Davidson W , Wilkins K , Li Y , Radford KW , Schmid DS , Pukuta E , Muyamuna E , Karhemere S , Tamfum JM , Okitolonda EW , McCollum AM , Reynolds MG . J Infect Dis 2021 223 (11) 1870-1878 BACKGROUND: Monkeypox is a poorly described emerging zoonosis endemic to Central and Western Africa. METHODS: Using surveillance data from Tshuapa Province, Democratic Republic of the Congo during 2011-2015, we evaluated differences in incidence, exposures, and clinical presentation of PCR-confirmed cases by sex and age. RESULTS: We report 1,057 confirmed cases. Average annual incidence was 14·1 per 100,000 (95% CI: 13·3-15·0). Incidence was higher in males (incidence rate ratio [IRR] males: females: 1·21, 95% CI 1·07-1·37), except among 20-29-year-old (IRR: 0·70, 95% CI: 0·51-0·95). Females aged 20-29 years also reported a high frequency of exposures (26·2%) to people with monkeypox-like symptoms. Highest incidence was among 10-19-year-old males, the cohort reporting the highest proportion of animal exposures (37·5%). Incidence was lower among those presumed to have received smallpox vaccination versus those presumed unvaccinated. No differences were observed by age group in lesion count or lesion severity score. CONCLUSIONS: Monkeypox incidence was twice that reported during 1980-1985, an increase possibly linked to declining immunity provided by smallpox vaccination. The high proportion of cases attributed to human exposures suggests changing exposure patterns. Cases were distributed across age and sex, suggesting frequent exposures that follow socio-cultural norms. |
A tale of two viruses: Coinfections of monkeypox and varicella zoster virus in the Democratic Republic of Congo
Hughes CM , Liu L , Davidson WB , Radford KW , Wilkins K , Monroe B , Metcalfe MG , Likafi T , Lushima RS , Kabamba J , Nguete B , Malekani J , Pukuta E , Karhemere S , Muyembe Tamfum JJ , Wemakoy EO , Reynolds MG , Schmid DS , McCollum AM . Am J Trop Med Hyg 2020 104 (2) 604-611 Recent enhanced monkeypox (MPX) surveillance in the Democratic Republic of Congo, where MPX is endemic, has uncovered multiple cases of MPX and varicella zoster virus (VZV) coinfections. The purpose of this study was to verify if coinfections occur and to characterize the clinical nature of these cases. Clinical, epidemiological, and laboratory results were used to investigate MPX/VZV coinfections. A coinfection was defined as a patient with at least one Orthopoxvirus/MPX-positive sample and at least one VZV-positive sample within the same disease event. Between September 2009 and April 2014, 134 of the 1,107 (12.1%) suspected MPX cases were confirmed as MPX/VZV coinfections. Coinfections were more likely to report symptoms than VZV-alone cases and less likely than MPX-alone cases. Significantly higher lesion counts were observed for coinfection cases than for VZV-alone but less than MPX-alone cases. Discernible differences in symptom and rash severity were detected for coinfection cases compared with those with MPX or VZV alone. Findings indicate infection with both MPX and VZV could modulate infection severity. Collection of multiple lesion samples allows for the opportunity to detect coinfections. As this program continues, it will be important to continue these procedures to assess variations in the proportion of coinfected cases over time. |
Detection and Genetic Characterization of Community-Based SARS-CoV-2 Infections - New York City, March 2020.
Greene SK , Keating P , Wahnich A , Weiss D , Pathela P , Harrison C , Rakeman J , Langley G , Tong S , Tao Y , Uehara A , Queen K , Paden CR , Szymczak W , Orner EP , Nori P , Lai PA , Jacobson JL , Singh HK , Calfee DP , Westblade LF , Vasovic LV , Rand JH , Liu D , Singh V , Burns J , Prasad N , Sell J , CDC COVID-19 Surge Laboratory Group , Abernathy Emily , Anderson Raydel , Bankamp Bettina , Bell Melissa , Galloway Renee , Graziano James , Kim Gimin , Kondas Ashley , Lee Christopher , Radford Kay , Rogers Shannon , Smith Peyton , Tiller Rebekah , Weiner Zachary , Wharton Adam , Whitaker Brett . MMWR Morb Mortal Wkly Rep 2020 69 (28) 918-922 To limit introduction of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), the United States restricted travel from China on February 2, 2020, and from Europe on March 13. To determine whether local transmission of SARS-CoV-2 could be detected, the New York City (NYC) Department of Health and Mental Hygiene (DOHMH) conducted deidentified sentinel surveillance at six NYC hospital emergency departments (EDs) during March 1-20. On March 8, while testing availability for SARS-CoV-2 was still limited, DOHMH announced sustained community transmission of SARS-CoV-2 (1). At this time, twenty-six NYC residents had confirmed COVID-19, and ED visits for influenza-like illness* increased, despite decreased influenza virus circulation.(†) The following week, on March 15, when only seven of the 56 (13%) patients with known exposure histories had exposure outside of NYC, the level of community SARS-CoV-2 transmission status was elevated from sustained community transmission to widespread community transmission (2). Through sentinel surveillance during March 1-20, DOHMH collected 544 specimens from patients with influenza-like symptoms (ILS)(§) who had negative test results for influenza and, in some instances, other respiratory pathogens.(¶) All 544 specimens were tested for SARS-CoV-2 at CDC; 36 (6.6%) tested positive. Using genetic sequencing, CDC determined that the sequences of most SARS-CoV-2-positive specimens resembled those circulating in Europe, suggesting probable introductions of SARS-CoV-2 from Europe, from other U.S. locations, and local introductions from within New York. These findings demonstrate that partnering with health care facilities and developing the systems needed for rapid implementation of sentinel surveillance, coupled with capacity for genetic sequencing before an outbreak, can help inform timely containment and mitigation strategies. |
Analysis of the reiteration regions (R1 to R5) of varicella-zoster virus.
Jensen NJ , Depledge DP , Ng TFF , Leung J , Quinlivan M , Radford KW , Folster J , Tseng HF , LaRussa P , Jacobsen SJ , Breuer J , Schmid DS . Virology 2020 546 38-50 The varicella-zoster virus (VZV) genome, comprises both unique and repeated regions. The genome also includes reiteration regions, designated R1 to R5, which are tandemly repeating sequences termed elements. These regions represent an understudied feature of the VZV genome. The R4 region is duplicated, with one copy in the internal repeat short (IRs) which we designated R4A and a second copy in the terminal repeat short (TRs) termed R4B. We developed primers to amplify and Sanger sequence these regions, including independent amplification of both R4 regions. Reiteration regions from >80 cases of PCR-confirmed shingles were sequenced and analyzed. Complete genome sequences for the remaining portions of these viruses were determined using Illumina MiSeq. We identified 28 elements not previously reported, including at least one element for each R region. Length heterogeneity was substantial in R3, R4A and R4B. Length heterogeneity between the two copies of R4 was common. |
Varicella in Tshuapa Province, Democratic Republic of Congo, 2009-2014
Leung J , McCollum AM , Radford K , Hughes C , Lopez AS , Guagliardo SAJ , Nguete B , Likafi T , Kabamba J , Malekani J , Lushima RS , Pukuta E , Karhemere S , Tamfum JJM , Reynolds MG , Okitolonda EW , Schmid DS , Marin M . Trop Med Int Health 2019 24 (7) 839-848 OBJECTIVE: To describe varicella cases in Tshuapa Province of the Democratic Republic of the Congo identified during monkeypox surveillance. METHODS: Demographic, clinical, and epidemiological data were collected from each suspected monkeypox case 2009-2014. Samples were tested by PCR for both Orthopoxviruses and varicella-zoster virus (VZV); a subset of VZV positive samples were genotyped. We defined a varicella case as a rash illness with laboratory-confirmed VZV. RESULTS: 366 varicella cases were identified; 66% were </=19 years old. Most patients had non-typical varicella rash with lesions reported as the same size and stage of evolution (86%), deep and profound (91%), on palms of hands and/or soles of feet (86%), and not itchy (49%). Many had non-typical signs and symptoms, such as lymphadenopathy (70%) and sensitivity to light (23%). A higher proportion of persons aged >/=20 years than persons aged </=19 years had >/=50 lesions (79% versus 65%, p = 0.007) and were bedridden (15% versus 9%, p = 0.056). All VZV isolates genotyped from 79 varicella cases were clade 5. During the surveillance period, one possible VZV-related death occurred in a 7 year-old child. CONCLUSIONS: A large proportion of patients presented with nontypical varicella rash and clinical signs and symptoms, highlighting challenges identifying varicella in an area with endemic monkeypox. Continued surveillance and laboratory diagnosis will help in rapid identification and control of both monkeypox and varicella and improve our understanding of varicella epidemiology in Africa. This article is protected by copyright. All rights reserved. |
Non-mumps viral parotitis during the 2014-2015 influenza season in the United States
Elbadawi LI , Talley P , Rolfes MA , Millman AJ , Reisdorf E , Kramer NA , Barnes JR , Blanton L , Christensen J , Cole S , Danz T , Dreisig JJ , Garten R , Haupt T , Isaac BM , Jackson MA , Kocharian A , Leifer D , Martin K , McHugh L , McNall RJ , Palm J , Radford KW , Robinson S , Rosen JB , Sakthivel SK , Shult P , Strain AK , Turabelidze G , Webber LA , Weinberg MP , Wentworth DE , Whitaker BL , Finelli L , Jhung MA , Lynfield R , Davis JP . Clin Infect Dis 2018 67 (4) 493-501 Background: During the 2014-2015 US influenza season, 320 cases of non-mumps parotitis (NMP) among residents of 21 states were reported to the Centers for Disease Control and Prevention (CDC). We conducted an epidemiologic and laboratory investigation to determine viral etiologies and clinical features of NMP during this unusually large occurrence. Methods: NMP was defined as acute parotitis or other salivary gland swelling of >2 days duration in a person with a mumps- negative laboratory result. Using a standardized questionnaire, we collected demographic and clinical information. Buccal samples were tested at the CDC for selected viruses, including mumps, influenza, human parainfluenza viruses (HPIVs) 1-4, adenoviruses, cytomegalovirus, Epstein-Barr virus (EBV), herpes simplex viruses (HSVs) 1 and 2, and human herpes viruses (HHVs) 6A and 6B. Results: Among the 320 patients, 65% were male, median age was 14.5 years (range, 0-90), and 67% reported unilateral parotitis. Commonly reported symptoms included sore throat (55%) and fever (48%). Viruses were detected in 210 (71%) of 294 NMP patients with adequate samples for testing, >/=2 viruses were detected in 37 samples, and 248 total virus detections were made among all samples. These included 156 influenza A(H3N2), 42 HHV6B, 32 EBV, 8 HPIV2, 2 HPIV3, 3 adenovirus, 4 HSV-1, and 1 HSV-2. Influenza A(H3N2), HHV6B, and EBV were the most frequently codetected viruses. Conclusions: Our findings suggest that, in addition to mumps, clinicians should consider respiratory viral (influenza) and herpes viral etiologies for parotitis, particularly among patients without epidemiologic links to mumps cases or outbreaks. |
Revisiting the genotyping scheme for varicella-zoster viruses based on whole-genome comparisons.
Jensen NJ , Rivailler P , Tseng HF , Quinlivan ML , Radford K , Folster J , Harpaz R , LaRussa P , Jacobsen S , Schmid DS . J Gen Virol 2017 98 (6) 1434-1438 We report whole-genome sequences (WGSs) for four varicella-zoster virus (VZV) samples from a shingles study conducted by Kaiser Permanente of Southern California. Comparative genomics and phylogenetic analysis of all published VZV WGSs revealed that strain KY037798 is in clade IX, which shall henceforth be designated clade 9. Previously published single nucleotide polymorphisms (SNP)-based genotyping schemes fail to discriminate between clades 6 and VIII and employ positions that are not clade-specific. We provide an updated list of clade-specific positions that supersedes the list determined at the 2008 VZV nomenclature meeting. Finally, we propose a new targeted genotyping scheme that will discriminate the circulating VZV clades with at least a twofold redundancy. Genotyping strategies using a limited set of targeted SNPs will continue to provide an efficient 'first pass' method for VZV strain surveillance as vaccination programmes for varicella and zoster influence the dynamics of VZV transmission. |
Evaluation of TaqMan Array Card (TAC) for the Detection of Central Nervous System Infections in Kenya.
Onyango CO , Loparev V , Lidechi S , Bhullar V , Schmid DS , Radford K , Lo MK , Rota P , Johnson BW , Munoz J , Oneko M , Burton D , Black CM , Neatherlin J , Montgomery JM , Fields B . J Clin Microbiol 2017 55 (7) 2035-2044 Infections of the central nervous system (CNS) are often acute with significant morbidity and mortality. Routine diagnosis of such infections is limited in developing countries and requires modern equipment in advanced laboratories that may be unavailable to a number of patients in sub-Saharan Africa. We developed a TaqMan Array Card (TAC) that detects multiple pathogens simultaneously from cerebrospinal fluid (CSF). The 21-pathogen TAC assays include two parasites (Balamuthia mandrillaris and Acanthamoeba), six bacterial pathogens (Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, Mycoplasma pneumoniae, Mycobacterium tuberculosis, and Bartonella) and 13 viruses (parechovirus, dengue, nipah, varicella zoster, mumps, measles, lyssa, herpes simplex virus 1 and 2, Epstein Barr virus, enterovirus, cytomegalovirus and chikungunya). The card also includes human RNAse P as a nucleic acid extraction control and an internal manufacturer control (glyceraldehyde 3-phosphate dehydrogenase (GAPDH)). This CNS-TAC can test up to eight samples for all 21 agents within 2.5 hours following nucleic acid extraction. The assay was validated for linearity, limit of detection, sensitivity and specificity by either using live viruses (dengue, mumps and measles) or nucleic acid material (nipah and chikungunya). Of the 120 samples tested by individual real-time PCR (IRTP), 35 were positive for eight different targets while CNS-TAC detected 37 positive samples across nine different targets. The TAC assays showed 85.6% sensitivity and 96.7% specificity across the assays. This assay may be useful for outbreak investigation and surveillance of suspected neurological disease. |
Biological matrix effects in quantitative tandem mass spectrometry-based analytical methods: advancing biomonitoring
Panuwet P , Hunter RE Jr , D'Souza PE , Chen X , Radford SA , Cohen JR , Marder ME , Kartavenka K , Ryan PB , Barr DB . Crit Rev Anal Chem 2016 46 (2) 93-105 The ability to quantify levels of target analytes in biological samples accurately and precisely in biomonitoring involves the use of highly sensitive and selective instrumentation such as tandem mass spectrometers and a thorough understanding of highly variable matrix effects. Typically, matrix effects are caused by co-eluting matrix components that alter the ionization of target analytes as well as the chromatographic response of target analytes, leading to reduced or increased sensitivity of the analysis. Thus, before the desired accuracy and precision standards of laboratory data are achieved, these effects must be characterized and controlled. Here we present our review and observations of matrix effects encountered during the validation and implementation of tandem mass spectrometry-based analytical methods. We also provide systematic, comprehensive laboratory strategies needed to control challenges posed by matrix effects in order to ensure delivery of the most accurate data for biomonitoring studies assessing exposure to environmental toxicants. |
Cytomegalovirus viral and antibody correlates in young children
Dollard SC , Keyserling H , Radford K , Amin MM , Stowell J , Winter J , Schmid DS , Cannon MJ , Hyde TB . BMC Res Notes 2014 7 776 BACKGROUND: Young, healthy children shedding cytomegalovirus (CMV) in urine and saliva appear to be the leading source of CMV in primary infection of pregnant women. FINDINGS: We screened 48 children 6 months - 5 years old for CMV IgG and measured levels of CMV IgG, IgM and IgG avidity antibodies, frequency of CMV shedding, and viral loads in blood, urine, and saliva. Thirteen of the 48 children (27%) were CMV IgG positive, among whom 3 were also CMV IgM positive with evidence of recent primary infection. Nine of the 13 seropositive children (69%) were shedding 102-105 copies/ml of CMV DNA in one or more bodily fluid. Among seropositive children, low IgG antibody titer (1:20-1:80) was associated with the absence of shedding (p = 0.014), and enrollment in daycare was associated with the presence of CMV shedding (p = 0.037). CONCLUSIONS: CMV antibody profiles correlated with CMV shedding. The presence of CMV IgM more often represents primary infection in children than in adults. Correlating antibodies with primary infection and viral shedding in healthy children adds to the understanding of CMV infection in children that can inform the prevention of CMV transmission to pregnant women. |
Non dermatomal rash and pancytopenia in a 5 year old child
Khandelwal P , Marsh R , Schmid DS , Folster J , Radford KW , Davies SM , Filipovich A . J Clin Virol 2014 60 (2) 81-3 Immune deficiency patients can have unusual presentations to vaccines. | Vaccine strain varicella can cause a non-dermatomal rash. | Hemophagocytic lymphohistiocytosis may be triggered by vaccine strain varicella. |
Herpes zoster caused by vaccine-strain varicella zoster virus in an immunocompetent recipient of zoster vaccine
Tseng HF , Schmid DS , Harpaz R , Larussa P , Jensen NJ , Rivailler P , Radford K , Folster J , Jacobsen SJ . Clin Infect Dis 2014 58 (8) 1125-8 We report the first laboratory-documented case of herpes zoster caused by the attenuated varicella zoster virus (VZV) contained in Zostavax in a 68-year-old immunocompetent adult with strong evidence of prior wild-type VZV infection. The complete genome sequence of the isolate revealed that the strain carried 15 of 42 (36%) recognized varicella vaccine-associated single-nucleotide polymorphisms, including all 5 of the fixed vaccine markers present in nearly all of the strains in the vaccine. The case of herpes zoster was relatively mild and resolved without complications. |
Cytomegalovirus survival and transferability and the effectiveness of common hand-washing agents against cytomegalovirus on live human hands
Stowell JD , Forlin-Passoni D , Radford K , Bate SL , Dollard SC , Bialek SR , Cannon MJ , Schmid DS . Appl Environ Microbiol 2014 80 (2) 455-61 Congenital cytomegalovirus (CMV) transmission can occur when women acquire CMV while pregnant. Infection control guidelines may reduce risk for transmission. We studied the duration of CMV survival after application of bacteria to the hands and after transfer from the hands to surfaces and the effectiveness of cleansing with water, regular and antibacterial soaps, sanitizer, and diaper wipes. Experiments used CMV AD169 in saliva at initial titers of 1 x 10(5) infectious particles/ml. Samples from hands or surfaces (points between 0 and 15 min) were placed in culture and observed for at least 2 weeks. Samples were also tested using CMV real-time PCR. After application of bacteria to the hands, viable CMV was recovered from 17/20 swabs at 0 min, 18/20 swabs at 1 min, 5/20 swabs at 5 min, and 4/20 swabs at 15 min. After transfer, duration of survival was at least 15 min on plastic (1/2 swabs), 5 min on crackers and glass (3/4 swabs), and 1 min or less on metal and cloth (3/4 swabs); no viable virus was collected from wood, rubber, or hands. After cleansing, no viable virus was recovered using water (0/22), plain soap (0/20), antibacterial soap (0/20), or sanitizer (0/22). Viable CMV was recovered from 4/20 hands 10 min after diaper wipe cleansing. CMV remains viable on hands for sufficient times to allow transmission. CMV may be transferred to surfaces with reduced viability. Hand-cleansing methods were effective at eliminating viable CMV from hands. |
Viruses detected among sporadic cases of parotitis, United States, 2009-2011
Barskey AE , Juieng P , Whitaker BL , Erdman DD , Oberste MS , Chern SW , Schmid DS , Radford KW , McNall RJ , Rota PA , Hickman CJ , Bellini WJ , Wallace GS . J Infect Dis 2013 208 (12) 1979-86 BACKGROUND: Sporadic cases of parotitis are generally assumed to be mumps, which often requires a resource-intensive public health response. This project surveyed the frequency of viruses detected among such cases. METHODS: During 2009-2011, 8 jurisdictions throughout the United States investigated sporadic cases of parotitis. Epidemiologic information, serum, and buccal and oropharyngeal swabs were collected. Polymerase chain reaction methods were used to detect a panel of viruses. Anti-mumps virus immunoglobulin M (IgM) antibodies were detected using a variety of methods. RESULTS: Of 101 specimens, 38 were positive for a single virus: Epstein-Barr virus (23), human herpesvirus (HHV)-6B (10), human parainfluenza virus (HPIV)-2 (3), HPIV-3 (1), and human bocavirus (1). Mumps virus, enteroviruses (including human parechovirus), HHV-6A, HPIV-1, and adenoviruses were not detected. Early specimen collection did not improve viral detection rate. Mumps IgM was detected in 17% of available specimens. Patients in whom a virus was detected were younger, but no difference was seen by sex or vaccination profile. No seasonal patterns were identified. CONCLUSIONS: Considering the timing of specimen collection, serology results, patient vaccination status, and time of year may be helpful in assessing the likelihood that a sporadic case of parotitis without laboratory confirmation is mumps. |
A phase 3 trial of RTS,S/AS01 malaria vaccine in African infants
Agnandji ST , Lell B , Fernandes JF , Abossolo BP , Methogo BG , Kabwende AL , Adegnika AA , Mordmüller B , Issifou S , Kremsner PG , Sacarlal J , Aide P , Lanaspa M , Aponte JJ , Machevo S , Acacio S , Bulo H , Sigauque B , Macete E , Alonso P , Abdulla S , Salim N , Minja R , Mpina M , Ahmed S , Ali AM , Mtoro AT , Hamad AS , Mutani P , Tanner M , Tinto H , D'Alessandro U , Sorgho H , Valea I , Bihoun B , Guiraud I , Kaboré B , Sombié O , Guiguemdé RT , Ouédraogo JB , Hamel MJ , Kariuki S , Oneko M , Odero C , Otieno K , Awino N , McMorrow M , Muturi-Kioi V , Laserson KF , Slutsker L , Otieno W , Otieno L , Otsyula N , Gondi S , Otieno A , Owira V , Oguk E , Odongo G , Woods JB , Ogutu B , Njuguna P , Chilengi R , Akoo P , Kerubo C , Maingi C , Lang T , Olotu A , Bejon P , Marsh K , Mwambingu G , Owusu-Agyei S , Asante KP , Osei-Kwakye K , Boahen O , Dosoo D , Asante I , Adjei G , Kwara E , Chandramohan D , Greenwood B , Lusingu J , Gesase S , Malabeja A , Abdul O , Mahende C , Liheluka E , Malle L , Lemnge M , Theander TG , Drakeley C , Ansong D , Agbenyega T , Adjei S , Boateng HO , Rettig T , Bawa J , Sylverken J , Sambian D , Sarfo A , Agyekum A , Martinson F , Hoffman I , Mvalo T , Kamthunzi P , Nkomo R , Tembo T , Tegha G , Tsidya M , Kilembe J , Chawinga C , Ballou WR , Cohen J , Guerra Y , Jongert E , Lapierre D , Leach A , Lievens M , Ofori-Anyinam O , Olivier A , Vekemans J , Carter T , Kaslow D , Leboulleux D , Loucq C , Radford A , Savarese B , Schellenberg D , Sillman M , Vansadia P . N Engl J Med 2012 367 (24) 2284-95 BACKGROUND: The candidate malaria vaccine RTS,S/AS01 reduced episodes of both clinical and severe malaria in children 5 to 17 months of age by approximately 50% in an ongoing phase 3 trial. We studied infants 6 to 12 weeks of age recruited for the same trial. METHODS: We administered RTS,S/AS01 or a comparator vaccine to 6537 infants who were 6 to 12 weeks of age at the time of the first vaccination in conjunction with Expanded Program on Immunization (EPI) vaccines in a three-dose monthly schedule. Vaccine efficacy against the first or only episode of clinical malaria during the 12 months after vaccination, a coprimary end point, was analyzed with the use of Cox regression. Vaccine efficacy against all malaria episodes, vaccine efficacy against severe malaria, safety, and immunogenicity were also assessed. RESULTS: The incidence of the first or only episode of clinical malaria in the intention-to-treat population during the 14 months after the first dose of vaccine was 0.31 per person-year in the RTS,S/AS01 group and 0.40 per person-year in the control group, for a vaccine efficacy of 30.1% (95% confidence interval [CI], 23.6 to 36.1). Vaccine efficacy in the per-protocol population was 31.3% (97.5% CI, 23.6 to 38.3). Vaccine efficacy against severe malaria was 26.0% (95% CI, -7.4 to 48.6) in the intention-to-treat population and 36.6% (95% CI, 4.6 to 57.7) in the per-protocol population. Serious adverse events occurred with a similar frequency in the two study groups. One month after administration of the third dose of RTS,S/AS01, 99.7% of children were positive for anti-circumsporozoite antibodies, with a geometric mean titer of 209 EU per milliliter (95% CI, 197 to 222). CONCLUSIONS: The RTS,S/AS01 vaccine coadministered with EPI vaccines provided modest protection against both clinical and severe malaria in young infants. (Funded by GlaxoSmithKline Biologicals and the PATH Malaria Vaccine Initiative; RTS,S ClinicalTrials.gov number: NCT00866619.). |
Novel genetic variation identified at fixed loci in ORF62 of the Oka varicella vaccine and in a case of vaccine-associated herpes zoster.
Quinlivan ML , Jensen NJ , Radford KW , Schmid DS . J Clin Microbiol 2012 50 (5) 1533-8 The live attenuated Oka varicella vaccine (vOka), derived from clade 2 wild type (wt) virus, pOka, is used for routine childhood immunization in several countries including the United States (US), causing dramatic declines in varicella incidence. vOka can cause varicella, establish latency and reactivate to cause herpes zoster (HZ). Three loci in varicella-zoster virus (VZV) open reading frame (ORF) 62 (106262, 107252, 108111) are used to distinguish vOka from wt VZV. A 4(th) position (105705) is also fixed for the vOka allele in nearly all vaccine batches. These 4 positions and two vOka mutations (106710 & 107599) reportedly absent from Varivax were analyzed on Varivax-derived ORF62 TOPO TA clones. The wt allele was detected at positions 105705 and 107252 on 3% and 2% of clones, respectively, but was absent at positions 106262 and 108111. Position 106710 was fixed for the wt allele whereas the vOka allele was present on 18.4% of clones at position 107599. We also evaluated the 4 vOka markers in an isolate obtained from a case of vaccine HZ. The isolate carried the vOka allele at positions 105705, 106262 and 108111. However, at position 107252 the wt allele was present. Thus, all of the ORF62 vOka markers previously regarded as fixed occur as the wt allele in a small percentage of vOka strains. Characterization of all four vOka markers in ORF62 and the Clade 2 subtype marker in ORF38 is now necessary to confirm vOka adverse events. |
Cytomegalovirus survival on common environmental surfaces: opportunities for viral transmission
Stowell JD , Forlin-Passoni D , Din E , Radford K , Brown D , White A , Bate SL , Dollard SC , Bialek SR , Cannon MJ , Schmid DS . J Infect Dis 2012 205 (2) 211-4 Congenital cytomegalovirus (CMV) affects approximately 1 of 150 births and is a leading cause of hearing loss and intellectual disability. It has been suggested that transmission may occur via contaminated surfaces. CMV AD169 in filtered human saliva, applied to environmental surfaces, was recovered at various time points. Samples were evaluated by culture and real-time polymerase chain reaction. CMV was found viable on metal and wood to 1 hour, glass and plastic to 3 hours, and rubber, cloth, and cracker to 6 hours. CMV was cultured from 83 of 90 wet and 5 of 40 dry surfaces. CMV was more likely to be isolated from wet, highly absorbent surfaces at earlier time points. |
First results of phase 3 trial of RTS,S/AS01 malaria vaccine in African children
Agnandji ST , Lell B , Soulanoudjingar SS , Fernandes JF , Abossolo BP , Conzelmann C , Methogo BG , Doucka Y , Flamen A , Mordmüller B , Issifou S , Kremsner PG , Sacarlal J , Aide P , Lanaspa M , Aponte JJ , Nhamuave A , Quelhas D , Bassat Q , Mandjate S , Macete E , Alonso P , Abdulla S , Salim N , Juma O , Shomari M , Shubis K , Machera F , Hamad AS , Minja R , Mtoro A , Sykes A , Ahmed S , Urassa AM , Ali AM , Mwangoka G , Tanner M , Tinto H , D'Alessandro U , Sorgho H , Valea I , Tahita MC , Kaboré W , Ouédraogo S , Sandrine Y , Guiguemdé RT , Ouédraogo JB , Hamel MJ , Kariuki S , Odero C , Oneko M , Otieno K , Awino N , Omoto J , Williamson J , Muturi-Kioi V , Laserson KF , Slutsker L , Otieno W , Otieno L , Nekoye O , Gondi S , Otieno A , Ogutu B , Wasuna R , Owira V , Jones D , Onyango AA , Njuguna P , Chilengi R , Akoo P , Kerubo C , Gitaka J , Maingi C , Lang T , Olotu A , Tsofa B , Bejon P , Peshu N , Marsh K , Owusu-Agyei S , Asante KP , Osei-Kwakye K , Boahen O , Ayamba S , Kayan K , Owusu-Ofori R , Dosoo D , Asante I , Adjei G , Adjei G , Chandramohan D , Greenwood B , Lusingu J , Gesase S , Malabeja A , Abdul O , Kilavo H , Mahende C , Liheluka E , Lemnge M , Theander T , Drakeley C , Ansong D , Agbenyega T , Adjei S , Boateng HO , Rettig T , Bawa J , Sylverken J , Sambian D , Agyekum A , Owusu L , Martinson F , Hoffman I , Mvalo T , Kamthunzi P , Nkomo R , Msika A , Jumbe A , Chome N , Nyakuipa D , Chintedza J , Ballou WR , Bruls M , Cohen J , Guerra Y , Jongert E , Lapierre D , Leach A , Lievens M , Ofori-Anyinam O , Vekemans J , Carter T , Leboulleux D , Loucq C , Radford A , Savarese B , Schellenberg D , Sillman M , Vansadia P . N Engl J Med 2011 365 (20) 1863-75 BACKGROUND: An ongoing phase 3 study of the efficacy, safety, and immunogenicity of candidate malaria vaccine RTS,S/AS01 is being conducted in seven African countries. METHODS: From March 2009 through January 2011, we enrolled 15,460 children in two age categories--6 to 12 weeks of age and 5 to 17 months of age--for vaccination with either RTS,S/AS01 or a non-malaria comparator vaccine. The primary end point of the analysis was vaccine efficacy against clinical malaria during the 12 months after vaccination in the first 6000 children 5 to 17 months of age at enrollment who received all three doses of vaccine according to protocol. After 250 children had an episode of severe malaria, we evaluated vaccine efficacy against severe malaria in both age categories. RESULTS: In the 14 months after the first dose of vaccine, the incidence of first episodes of clinical malaria in the first 6000 children in the older age category was 0.32 episodes per person-year in the RTS,S/AS01 group and 0.55 episodes per person-year in the control group, for an efficacy of 50.4% (95% confidence interval [CI], 45.8 to 54.6) in the intention-to-treat population and 55.8% (97.5% CI, 50.6 to 60.4) in the per-protocol population. Vaccine efficacy against severe malaria was 45.1% (95% CI, 23.8 to 60.5) in the intention-to-treat population and 47.3% (95% CI, 22.4 to 64.2) in the per-protocol population. Vaccine efficacy against severe malaria in the combined age categories was 34.8% (95% CI, 16.2 to 49.2) in the per-protocol population during an average follow-up of 11 months. Serious adverse events occurred with a similar frequency in the two study groups. Among children in the older age category, the rate of generalized convulsive seizures after RTS,S/AS01 vaccination was 1.04 per 1000 doses (95% CI, 0.62 to 1.64). CONCLUSIONS: The RTS,S/AS01 vaccine provided protection against both clinical and severe malaria in African children. (Funded by GlaxoSmithKline Biologicals and the PATH Malaria Vaccine Initiative; RTS,S ClinicalTrials.gov number, NCT00866619 .) |
A 2009 varicella outbreak in a Connecticut residential facility for adults with intellectual disability
Leung J , Kudish K , Wang C , Moore L , Gacek P , Radford K , Lopez A , Sosa L , Schmid DS , Cartter M , Bialek S . J Infect Dis 2010 202 (10) 1486-91 We investigated a varicella outbreak in a residential facility for adults with intellectual disabilities. A case of varicella was defined as a generalized maculopapular rash that developed in a facility resident or employee. Immunoglobulin M testing was conducted on serologic samples, and polymerase chain reaction testing was performed on environmental and skin lesion samples. Eleven cases were identified among 70 residents and 2 among 145 staff. An unrecognized case of herpes zoster was the likely source. Case patients first entered any residential facility at a younger age than non-case residents (9.5 vs 15.0 years; P< .01). Varicella zoster virus DNA was detected 2 months after the outbreak in environmental samples obtained from case patients’ residences. This outbreak exemplifies the potential for at-risk pockets of varicella-susceptible adults, especially among those who have lived in residential facilities from a young age. Evidence of immunity should be verified for all adults and healthcare staff in similar residential settings. |
Lack of evidence for human herpesvirus-8 transmission via blood transfusion in a historical US cohort
Cannon MJ , Operskalski EA , Mosley JW , Radford K , Dollard SC . J Infect Dis 2009 199 (11) 1592-8 BACKGROUND: Recent studies have found evidence of occasional human herpesvirus (HHV)-8 transmission via blood transfusion. However, because these studies were conducted outside the United States or did not have linked donor-recipient pairs, they have a limited ability to inform US blood-banking policy. METHODS: We investigated HHV-8 transmission via blood transfusion in the United States by conducting HHV-8 serologic testing among participants of the Transfusion-Transmitted Viruses Study (TTVS), who enrolled during the 1970s. RESULTS: HHV-8 seroprevalence was 2.8% (29/1023) among blood donors, 7.1% (96/1350) among transfusion recipients, 7.7% (46/599) among surgical control patients who did not receive transfusions, and 96.3% (77/80) among control patients with Kaposi sarcoma. One transfusion recipient seroconverted (0.08% [1/1259]), but this patient did not receive any HHV-8-seropositive blood units, suggesting that the infection was not related to blood transfusion. One of the surgical control patients who did not receive transfusions also seroconverted (0.18% [1/556]). Rates of seroconversion were 1.6 per 1000 person-years (95% confidence interval [CI], 0.04-8.9 per 1000 person-years) for the transfusion recipients and 3.6 per 1000 person-years (95% CI, 0.09-20.1 per 1000 person-years) for the surgical control patients who did not receive transfusions (P = .61). CONCLUSIONS: Rates of HHV-8 seroconversion in the transfusion and nontransfusion groups were not statistically different, and the historical nature of the cohort (e.g., before leukoreduction) suggests that any current transmission via blood transfusion is rare. |
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