Last data update: Nov 04, 2024. (Total: 48056 publications since 2009)
Records 1-15 (of 15 Records) |
Query Trace: McNall RJ[original query] |
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Co-circulating mumps lineages at multiple geographic scales (preprint)
Wohl S , Metsky HC , Schaffner SF , Piantadosi A , Burns M , Lewnard JA , Chak B , Krasilnikova LA , Siddle KJ , Matranga CB , Bankamp B , Hennigan S , Sabina B , Byrne EH , McNall RJ , Park DJ , Gharib S , Fitzgerald S , Barreira P , Fleming S , Lett S , Rota PA , Madoff LC , Yozwiak NL , MacInnis BL , Smole S , Grad YH , Sabeti PC . bioRxiv 2018 343897 Despite widespread vaccination, eleven thousand mumps cases were reported in the United States (US) in 2016–17, including hundreds in Massachusetts, primarily in college settings. We generated 203 whole genome mumps virus (MuV) sequences from Massachusetts and 15 other states to understand the dynamics of mumps spread locally and nationally, as well as to search for variants potentially related to vaccination. We observed multiple MuV lineages circulating within Massachusetts during 2016–17, evidence for multiple introductions of the virus to the state, and extensive geographic movement of MuV within the US on short time scales. We found no evidence that variants arising during this outbreak contributed to vaccine escape. Combining epidemiological and genomic data, we observed multiple co-circulating clades within individual universities as well as spillover into the local community. Detailed data from one well-sampled university allowed us to estimate an effective reproductive number within that university significantly greater than one. We also used publicly available small hydrophobic (SH) gene sequences to estimate migration between world regions and to place this outbreak in a global context, but demonstrate that these short sequences, historically used for MuV genotyping, are inadequate for tracing detailed transmission. Our findings suggest continuous, often undetected, circulation of mumps both locally and nationally, and highlight the value of combining genomic and epidemiological data to track viral disease transmission at high resolution. |
Maintenance of measles elimination status in the United States for 20 years despite increasing challenges
Mathis AD , Clemmons NS , Redd SB , Pham H , Leung J , Wharton AK , Anderson R , McNall RJ , Rausch-Phung E , Rosen JB , Blog D , Zucker JR , Bankamp B , Rota PA , Patel M , Gastañaduy PA . Clin Infect Dis 2021 75 (3) 416-424 BACKGROUND: Measles elimination (interruption of endemic measles virus transmission) in the United States was declared in 2000; however, the number of cases and outbreaks have increased in recent years. We characterized the epidemiology of measles outbreaks and measles transmission patterns post-elimination to identify potential gaps in the U.S. measles control program. METHODS: We analyzed national measles notification data from January 1, 2001-December 31, 2019. We defined measles infection clusters as single cases (isolated cases not linked to additional cases), 2-case clusters, or outbreaks with 3 or more linked cases. We calculated the effective reproduction number (R) to assess changes in transmissibility and reviewed molecular epidemiology data. RESULTS: During 2001-2019, 3,873 measles cases, including 747 international importations, were reported in the United States; 29% of importations were associated with outbreaks. Among 871 clusters, 69% were single cases and 72% had no spread. Larger and longer clusters were reported since 2013, including seven outbreaks with >50 cases lasting >2 months, 5 of which occurred in known underimmunized, close-knit communities. No measles lineage circulated in a single transmission chain for >12 months. Higher estimates of R were noted in recent years, although R remained below the epidemic threshold of 1. CONCLUSIONS: Current epidemiology continues to support the interruption of endemic measles virus transmission in the United States. However, larger and longer outbreaks in recent post-elimination years and emerging trends of increased transmission in underimmunized communities emphasize the need for targeted approaches to close existing immunity gaps and maintain measles elimination. |
Functional Characterization of Circulating Mumps Viruses with Stop Codon Mutations in the Small Hydrophobic Protein.
Stinnett RC , Beck AS , Lopareva EN , McNall RJ , Latner DR , Hickman CJ , Rota PA , Bankamp B . mSphere 2020 5 (6) Between 2015 and 2017, routine molecular surveillance in the United States detected multiple mumps viruses (MuVs) with mutations in the small hydrophobic (SH) gene compared to a reference virus of the same genotype. These mutations include an unusual pattern of uracil-to-cytosine hypermutations and other mutations resulting in the generation of premature stop codons or disruption of the canonical stop codon. The mumps virus SH protein may serve as a virulence factor, based on evidence that it inhibits apoptosis and innate immune signaling in vitro and that recombinant viruses that do not express the SH protein are attenuated in an animal model. In this study, mumps viruses bearing variant SH sequences were isolated from contemporary outbreak samples to evaluate the impact of the observed mutations on SH protein function. All isolates with variant SH sequences replicated in interferon-competent cells with no evidence of attenuation. Furthermore, all SH-variant viruses retained the ability to abrogate induction of NF-κB-mediated innate immune signaling in infected cells. Ectopic expression of variant mumps SH genes is consistent with findings from infection experiments, indicating that the observed abrogation of signaling was not mediated by other viral factors that may modulate innate immune signaling. Molecular surveillance is an important public health tool for monitoring the diversity of circulating mumps viruses and can provide insights into determinants of disease. These findings, in turn, will inform studies employing reverse genetics to elucidate the specific mechanisms of MuV pathogenesis and potential impacts of observed sequence variants on infectivity, fitness, and virulence.IMPORTANCE Mumps virus (MuV) outbreaks occur in the United States despite high coverage with measles, mumps, rubella (MMR) vaccine. Routine genotyping of laboratory-confirmed mumps cases has been practiced in the United States since 2006 to enhance mumps surveillance. This study reports the detection of unusual mutations in the small hydrophobic (SH) protein of contemporary laboratory-confirmed mumps cases and is the first to describe the impact of such mutations on SH protein function. These mutations are predicted to profoundly alter the amino acid sequence of the SH protein, which has been shown to antagonize host innate immune responses; however, they were neither associated with defects in virus replication nor attenuated protein function in vitro, consistent with detection in clinical specimens. A better understanding of the forces governing mumps virus sequence diversity and of the functional consequences of mutations in viral proteins is important for maintaining robust capacity for mumps detection and disease control. |
Genetic Characterization of Mumps Viruses Associated with the Resurgence of Mumps in the United States: 2015-2017.
McNall RJ , Wharton AK , Anderson R , Clemmons N , Lopareva EN , Gonzalez C , Espinosa A , Probert WS , Hacker JK , Liu G , Garfin J , Strain A , Boxrud D , Bryant PW , George KS , Davis T , Griesser RH , Shult P , Bankamp B , Hickman CJ , Wroblewski K , Rota PA . Virus Res 2020 281 197935 Despite high coverage with measles, mumps, and rubella vaccine in the United States, outbreaks of mumps occur in close contact settings such as schools, colleges, and camps. Starting in late 2015, outbreaks were reported from several universities, and by the end of 2017, greater than 13,800 cases had been reported nation-wide. In 2013, the CDC and the Association of Public Health Laboratories contracted four Vaccine Preventable Diseases Reference Centers (VPD-RCs) to perform real-time reverse transcription PCR (RT-qPCR) to detect mumps RNA in clinical samples and to determine the genotype. Twelve genotypes of mumps virus are currently recognized by the World Health Organization, and the standard protocol for genotyping requires sequencing the entire gene coding for the small hydrophobic (SH) protein. Phylogenetic analysis of the 1862 mumps samples genotyped from 2015 through 2017 showed that the overall diversity of genotypes detected was low. Only 0.8% of the sequences were identified as genotypes C, H, J, or K, and 0.5% were identified as vaccine strains in genotypes A or N, while most sequences (98.7%) were genotype G. The majority of the genotype G sequences could be included into one of two large groups with identical SH sequences. Within genotype G, a small number of phylogenetically significant outlier sequences were associated with epidemiologically distinct chains of transmission. These results demonstrate that molecular and epidemiologic data can be used to track transmission pathways of mumps virus; however, the limited diversity of the SH sequences may be insufficient for resolving transmission in all outbreaks. |
Combining genomics and epidemiology to track mumps virus transmission in the United States.
Wohl S , Metsky HC , Schaffner SF , Piantadosi A , Burns M , Lewnard JA , Chak B , Krasilnikova LA , Siddle KJ , Matranga CB , Bankamp B , Hennigan S , Sabina B , Byrne EH , McNall RJ , Shah RR , Qu J , Park DJ , Gharib S , Fitzgerald S , Barreira P , Fleming S , Lett S , Rota PA , Madoff LC , Yozwiak NL , MacInnis BL , Smole S , Grad YH , Sabeti PC . PLoS Biol 2020 18 (2) e3000611 Unusually large outbreaks of mumps across the United States in 2016 and 2017 raised questions about the extent of mumps circulation and the relationship between these and prior outbreaks. We paired epidemiological data from public health investigations with analysis of mumps virus whole genome sequences from 201 infected individuals, focusing on Massachusetts university communities. Our analysis suggests continuous, undetected circulation of mumps locally and nationally, including multiple independent introductions into Massachusetts and into individual communities. Despite the presence of these multiple mumps virus lineages, the genomic data show that one lineage has dominated in the US since at least 2006. Widespread transmission was surprising given high vaccination rates, but we found no genetic evidence that variants arising during this outbreak contributed to vaccine escape. Viral genomic data allowed us to reconstruct mumps transmission links not evident from epidemiological data or standard single-gene surveillance efforts and also revealed connections between apparently unrelated mumps outbreaks. |
Notes from the field: Mumps in detention facilities that house detained migrants - United States, September 2018-August 2019
Leung J , Elson D , Sanders K , Marin M , Leos G , Cloud B , McNall RJ , Hickman CJ , Marlow M . MMWR Morb Mortal Wkly Rep 2019 68 (34) 749-750 On October 12, 2018, five confirmed cases of mumps among migrants who had been transferred between two detention facilities were reported by the facilities to the Texas Department of State Health Services (TDSHS). By December 11, eight Texas detention facilities and six facilities in five other states had reported 67 mumps cases to U.S. Immigration and Customs Enforcement (ICE) Health Service Corps (IHSC) or local health departments. On December 12, TDSHS contacted CDC to discuss mumps control in detention facilities and facilitate communication with IHSC. During January 4–17, 2019, six more state health departments reported new cases in detention facilities, which prompted CDC and IHSC to launch a coordinated national outbreak response. |
Increase in measles cases - United States, January 1-April 26, 2019
Patel M , Lee AD , Redd SB , Clemmons NS , McNall RJ , Cohn AC , Gastanaduy PA . MMWR Morb Mortal Wkly Rep 2019 68 (17) 402-404 As of April 26, 2019, CDC had reported 704 cases of measles in the United States since the beginning of 2019, representing the largest number of cases reported in the country in a single year since 1994, when 963 cases occurred, and since measles was declared eliminated* in 2000 (1,2). Measles is a highly contagious, acute viral illness characterized by fever and a maculopapular rash; complications include pneumonia, encephalitis, and death. Among the 704 cases, 503 (71%) were in unvaccinated persons and 689 (98%) occurred in U.S. residents. Overall, 66 (9%) patients were hospitalized. Thirteen outbreaks have been reported in 2019, accounting for 663 cases, 94% of all reported cases. Six of the 13 outbreaks were associated with underimmunized close-knit communities and accounted for 88% of all cases. High 2-dose measles vaccination coverage in the United States has been critical to limiting transmission (3). However, increased global measles activity poses a risk to U.S. elimination, particularly when unvaccinated travelers acquire measles abroad and return to communities with low vaccination rates (4). Health care providers should ensure persons are up to date with measles, mumps, rubella (MMR) vaccine, including before international travel, and rapidly report all suspected cases of measles to public health authorities. |
Notes From The Field: Mumps outbreak in a recently vaccinated population - Kosrae, Federated States of Micronesia, August-December, 2017
McKay SL , Kambui A , Taulung LA , Tippins A , Eckert M , Wharton AK , McNall RJ , Hickman C , Hancock WT , Apaisam C , Judicpa P , Patel M , Routh J . MMWR Morb Mortal Wkly Rep 2019 68 (4) 95-96 On August 6, 2017, the Kosrae Department of Health Services (KDHS) in the Federated States of Micronesia identified a confirmed case of mumps in a Kosrae resident who had 2 documented doses of measles-mumps-rubella (MMR) vaccine. The patient aged 18 years had recently traveled to Seattle, Washington, which was experiencing a mumps outbreak among members of its Pacific Islander population. Other Pacific Islands were concurrently experiencing large mumps outbreaks (1,2), in some places exceeding 500 cases, raising concern about the possibility of a similar outbreak in Kosrae. By October 6, KDHS had identified 17 cases (nine laboratory confirmed and eight suspected [clinically diagnosed as parotitis]) on the island (population 6,600) (Figure), with an attack rate of 14 cases per 1,000 residents in the primary affected municipality. At the request of KDHS, CDC deployed a team on October 17 to assist KDHS in investigation and control activities. The KDHS-CDC team conducted active surveillance to assess outbreak magnitude, interviewed mumps patients, collected specimens for laboratory testing, and reviewed patients’ vaccination records. KDHS conducted islandwide awareness campaigns about the outbreak and mumps prevention measures, and highlighted the importance of vaccination. |
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. |
Notes from the field: Absence of asymptomatic mumps virus shedding among vaccinated college students during a mumps outbreak - Washington, February-June 2017
Bonwitt J , Kawakami V , Wharton A , Burke RM , Murthy N , Lee A , Dell B , Kay M , Duchin J , Hickman C , McNall RJ , Rota PA , Patel M , Lindquist S , DeBolt C , Routh J . MMWR Morb Mortal Wkly Rep 2017 66 (47) 1307-1308 On February 8, 2017, a suspected case of mumps in a member of a fraternity or sorority at the University of Washington, Seattle campus (UW) was reported to Public Health—Seattle & King County (PHSKC). Additional confirmed and probable mumps cases were subsequently identified among UW students and staff members according to the national case definition.* By July 19, 2017, a total of 42 (16 confirmed and 26 probable) mumps cases were reported among UW students and associated community members, with symptom onset February 6–June 4 (Figure). |
Rapid identification of measles virus vaccine genotypes by real time PCR.
Roy F , Mendoza L , Hiebert J , McNall RJ , Bankamp B , Connolly S , Ludde A , Friedrich N , Mankertz A , Rota PA , Severini A . J Clin Microbiol 2016 55 (3) 735-743 During measles outbreaks, it is important to be able to rapidly distinguish between measles cases and vaccine reactions to avoid unnecessary outbreak response measures such as case isolation and contact investigations. We have developed a real-time RT-PCR method specific for genotype A measles virus (MeVA RT-qPCR), that can identify measles vaccine strains rapidly, with high throughput, and without the need for sequencing to determine the genotype. We have evaluated the method independently in three measles reference laboratories using two platforms, the Roche Lightcycler(R) 480 and the Applied Biosystems (ABI) 7500 Real-Time PCR System. In comparison to the standard real time RT-PCR method, the MeVA RT-qPCR showed 99.5% specificity for genotype A and 94% sensitivity for both platforms. The new assay was able to detect RNA from five currently used vaccine strains, AIK-C, CAM-70, Edmonston-Zagreb, Moraten, and Shanghai-191. The MeVA RT qPCR assay has been used successfully for measles surveillance in reference laboratories and it could be readily deployed to national and subnational laboratories on a wide scale. |
High concentrations of measles neutralizing antibodies and high-avidity measles IgG accurately identify measles reinfection cases
Sowers SB , Rota JS , Hickman CJ , Mercader S , Redd S , McNall RJ , Williams N , McGrew M , Walls ML , Rota PA , Bellini WJ . Clin Vaccine Immunol 2016 23 (8) 707-16 In the United States, approximately 9% of the measles cases reported from 2012 to 2014 occurred in vaccinated individuals. Laboratory confirmation of measles in vaccinated individuals is challenging since IgM assays can give inconclusive results. Although a positive reverse transcription (RT)-PCR assay result from an appropriately timed specimen can provide confirmation, negative results may not rule out a highly suspicious case. Detection of high-avidity measles IgG in serum samples provides laboratory evidence of a past immunologic response to measles from natural infection or immunization. High concentrations of measles neutralizing antibody have been observed by plaque reduction neutralization (PRN) assays among confirmed measles cases with high-avidity IgG, referred to here as reinfection cases (RICs). In this study, we evaluated the utility of measuring levels of measles neutralizing antibody to distinguish RICs from noncases by receiver operating characteristic curve analysis. Single and paired serum samples with high-avidity measles IgG from suspected measles cases submitted to the CDC for routine surveillance were used for the analysis. The RICs were confirmed by a 4-fold rise in PRN titer or by RT-quantitative PCR (RT-qPCR) assay, while the noncases were negative by both assays. Discrimination accuracy was high with serum samples collected ≥3 days after rash onset (area under the curve, 0.953; 95% confidence interval [CI], 0.854 to 0.993). Measles neutralizing antibody concentrations of ≥40,000 mIU/ml identified RICs with 90% sensitivity (95% CI, 74 to 98%) and 100% specificity (95% CI, 82 to 100%). Therefore, when serological or RT-qPCR results are unavailable or inconclusive, suspected measles cases with high-avidity measles IgG can be confirmed as RICs by measles neutralizing antibody concentrations of ≥40,000 mIU/ml. |
Detection of Measles Virus RNA in Air and Surface Specimens in a Hospital Setting
Bischoff WE , McNall RJ , Blevins MW , Turner J , Lopareva EN , Rota PA , Stehle JR Jr . J Infect Dis 2015 213 (4) 600-3 Measles virus (MeV) is known to be highly contagious with an infectious period lasting from the four days preceding to the four days following rash onset. An unvaccinated, young, female patient with measles confirmed by direct epidemiologic link was hospitalized on day five after rash onset. Environmental samples were collected over the four day hospitalization period in a single room. MeV RNA was detectable in air, on surfaces, and respirators on days 5-8 after rash onset. This is the first report of environmental surveillance for MeV and the results suggest that measles infected fomites may be present in healthcare settings. |
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. |
Comparison of the sensitivity of laboratory diagnostic methods from a well-characterized outbreak of mumps in New York city in 2009.
Rota JS , Rosen JB , Doll MK , McNall RJ , McGrew M , Williams N , Lopareva EN , Barskey AE , Punsalang A Jr , Rota PA , Oleszko WR , Hickman CJ , Zimmerman CM , Bellini WJ . Clin Vaccine Immunol 2013 20 (3) 391-6 A mumps outbreak in upstate New York in 2009 at a summer camp for Orthodox Jewish boys spread into Orthodox Jewish communities in the Northeast including New York City. The availability of epidemiologic information including vaccination records and parotitis onset dates allowed an enhanced analysis of laboratory methods for mumps testing. Serum and buccal swab samples were collected from 296 confirmed cases with onsets from September through December, 2009. All samples were tested using the CDC capture IgM EIA and a real-time RT-PCR (rRT-PCR) that targets the short hydrophobic gene. A subset of the samples (n=205) was used to evaluate 3 commercial mumps IgM assays and to assess the sensitivity of using an alternative target gene (nucleoprotein) in the rRT-PCR protocol. Among 115 cases of mumps with 2 documented doses of measles, mumps, and rubella (MMR) vaccine, the CDC capture IgM EIA detected IgM in 51% of serum samples compared to 9%-24% using three commercial IgM assays. The rRT-PCR that targeted the nucleoprotein gene increased RNA detection by 14% compared to that obtained with the original protocol. The ability to detect IgM improved when serum was collected 3 days or more after onset whereas sensitivity of RNA detection by rRT-PCR declined when buccal swabs were collected later than 2 days after onset. Selection of testing methods and timing of sample collection are important factors in the ability to confirm infection among vaccinated persons. These results reinforce the need to use virus detection assays in addition to serologic tests. |
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