Last data update: Apr 22, 2024. (Total: 46599 publications since 2009)
Records 1-30 (of 135 Records) |
Query Trace: Rota PA [original query] |
---|
Measles - United States, January 1, 2020-March 28, 2024
Mathis AD , Raines K , Masters NB , Filardo TD , Kim G , Crooke SN , Bankamp B , Rota PA , Sugerman DE . MMWR Morb Mortal Wkly Rep 2024 73 (14) 295-300 Measles is a highly infectious febrile rash illness and was declared eliminated in the United States in 2000. However, measles importations continue to occur, and U.S. measles elimination status was threatened in 2019 as the result of two prolonged outbreaks among undervaccinated communities in New York and New York City. To assess U.S. measles elimination status after the 2019 outbreaks and to provide context to understand more recent increases in measles cases, CDC analyzed epidemiologic and laboratory surveillance data and the performance of the U.S. measles surveillance system after these outbreaks. During January 1, 2020-March 28, 2024, CDC was notified of 338 confirmed measles cases; 97 (29%) of these cases occurred during the first quarter of 2024, representing a more than seventeenfold increase over the mean number of cases reported during the first quarter of 2020-2023. Among the 338 reported cases, the median patient age was 3 years (range = 0-64 years); 309 (91%) patients were unvaccinated or had unknown vaccination status, and 336 case investigations included information on ≥80% of critical surveillance indicators. During 2020-2023, the longest transmission chain lasted 63 days. As of the end of 2023, because of the absence of sustained measles virus transmission for 12 consecutive months in the presence of a well-performing surveillance system, U.S. measles elimination status was maintained. Risk for widespread U.S. measles transmission remains low because of high population immunity. However, because of the increase in cases during the first quarter of 2024, additional activities are needed to increase U.S. routine measles, mumps, and rubella vaccination coverage, especially among close-knit and undervaccinated communities. These activities include encouraging vaccination before international travel and rapidly investigating suspected measles cases. |
A measles IgM rapid diagnostic test to address challenges with national measles surveillance and response in Malaysia
Senin A , Noordin NM , Sani JAM , Mahat D , Donadel M , Scobie HM , Omar A , Chem YK , Zahari MI , Ismail F , Rahman RA , Hussin HM , Selvanesan S , Aziz ZA , Arifin Wnawm , Bakar RSA , Rusli N , Zailani MH , Soo P , Lo YR , Grabovac V , Rota PA , Mulders MN , Featherstone D , Warrener L , Brown DW . PLoS One 2024 19 (3) e0298730 INTRODUCTION: A lateral flow rapid diagnostic test (RDT) enables detection of measles specific immunoglobulin M (IgM) antibody in serum, capillary blood, and oral fluid with accuracy consistent with enzyme immunoassay (EIA). The objectives of the study were: 1) to assess measles RDT inter-reader agreement between two clinic staff; 2) to assess the sensitivity and specificity of the measles RDT relative to standard surveillance testing in a low transmission setting; 3) to evaluate the knowledge, attitudes, and practices of staff in clinics using the RDT; and 4) to assess the impact of RDT testing on the measles public health response in Malaysia. MATERIALS AND METHODS: The clinic-based prospective evaluation included all suspected measles cases captured by routine measles surveillance at 34 purposely selected clinics in 15 health districts in Malaysia between September 2019 and June 2020, following day-long regional trainings on RDT use. Following informed consent, four specimens were collected from each suspected case, including those routinely collected for standard surveillance [serum for EIA and throat swabs for quantitative reverse transcriptase polymerase chain reaction (RT-qPCR)] together with capillary blood and oral fluid tested with RDTs during the study. RDT impact was evaluated by comparing the rapidity of measles public health response between the pre-RDT implementation (December 2018 to August 2019) and RDT implementation periods (September 2019 to June 2020). To assess knowledge, attitudes, and practices of RDT use, staff involved in the public health management of measles at the selected sites were surveyed. RESULTS: Among the 436 suspect cases, agreement of direct visual readings of measles RDT devices between two health clinic staff was 99% for capillary blood (k = 0.94) and 97% for oral fluid (k = 0.90) specimens. Of the total, 45 (10%) were positive by measles IgM EIA (n = 44, including five also positive by RT-qPCR) or RT-qPCR only (n = 1), and 38 were positive by RDT (using either capillary blood or oral fluid). Using measles IgM EIA or RT-qPCR as reference, RDT sensitivity using capillary blood was 43% (95% CI: 30%-58%) and specificity was 98% (95% CI: 96%-99%); using oral fluid, sensitivity (26%, 95% CI: 15%-40%) and specificity (97%, 95% CI: 94%-98%) were lower. Nine months after training, RDT knowledge was high among staff involved with the public health management of measles (average quiz score of 80%) and was highest among those who received formal training (88%), followed by those trained during supervisory visits (83%). During the RDT implementation period, the number of days from case confirmation until initiation of public response decreased by about 5 days. CONCLUSION: The measles IgM RDT shows >95% inter-reader agreement, high retention of RDT knowledge, and a more rapid public health response. However, despite ≥95% RDT specificity using capillary blood or oral fluid, RDT sensitivity was <45%. Higher-powered studies using highly specific IgM assays and systematic RT-qPCR for case confirmation are needed to establish the role of RDT in measles elimination settings. |
Epidemiologic and genetic characteristics of mumps viruses isolated in China from 1995 to 2010.
Cui A , Zhu Z , Chen M , Zheng H , Liu L , Wang Y , Ma Y , Wang C , Fang X , Li P , Guan R , Wang S , Zhou J , Zheng L , Gao H , Ding Z , Li L , Bo F , Sun Z , Zhang Z , Feng D , He J , Chen H , Jin L , Rota PA , Xu W . Infect Genet Evol 2014 21 384-90 The epidemiologic and genetic characteristics of mumps viruses detected in China from 1995 to 2010 were analyzed in this study. Mumps remains endemic in China with a high overall incidence rate. The incidence of mumps in Western China was higher than that in other regions of the country. Each year, most of mumps cases occurred between April and July, but a small peak also occurred in November and December. Mumps cases primarily affected the under 15 year old age group. Virologic data demonstrated that genotype F was the predominant circulating genotype throughout China for at least 15 years and no other genotype was detected between 1995 and 2010. Analysis of sequence data from the small hydrophobic (SH) gene indicated that multiple transmission chains of genotype F were found in various provinces of China, with no apparent chronologic and geographic restriction. This is the first report describing the epidemiology of mumps and genetic characterization of mumps viruses at the national level in China. |
Brain tropism acquisition: The spatial dynamics and evolution of a measles virus collective infectious unit that drove lethal subacute sclerosing panencephalitis
Yousaf I , Hannon WW , Donohue RC , Pfaller CK , Yadav K , Dikdan RJ , Tyagi S , Schroeder DC , Shieh WJ , Rota PA , Feder AF , Cattaneo R . PLoS Pathog 2023 19 (12) e1011817 It is increasingly appreciated that pathogens can spread as infectious units constituted by multiple, genetically diverse genomes, also called collective infectious units or genome collectives. However, genetic characterization of the spatial dynamics of collective infectious units in animal hosts is demanding, and it is rarely feasible in humans. Measles virus (MeV), whose spread in lymphatic tissues and airway epithelia relies on collective infectious units, can, in rare cases, cause subacute sclerosing panencephalitis (SSPE), a lethal human brain disease. In different SSPE cases, MeV acquisition of brain tropism has been attributed to mutations affecting either the fusion or the matrix protein, or both, but the overarching mechanism driving brain adaptation is not understood. Here we analyzed MeV RNA from several spatially distinct brain regions of an individual who succumbed to SSPE. Surprisingly, we identified two major MeV genome subpopulations present at variable frequencies in all 15 brain specimens examined. Both genome types accumulated mutations like those shown to favor receptor-independent cell-cell spread in other SSPE cases. Most infected cells carried both genome types, suggesting the possibility of genetic complementation. We cannot definitively chart the history of the spread of this virus in the brain, but several observations suggest that mutant genomes generated in the frontal cortex moved outwards as a collective and diversified. During diversification, mutations affecting the cytoplasmic tails of both viral envelope proteins emerged and fluctuated in frequency across genetic backgrounds, suggesting convergent and potentially frequency-dependent evolution for modulation of fusogenicity. We propose that a collective infectious unit drove MeV pathogenesis in this brain. Re-examination of published data suggests that similar processes may have occurred in other SSPE cases. Our studies provide a primer for analyses of the evolution of collective infectious units of other pathogens that cause lethal disease in humans. |
Progress toward measles elimination - Worldwide, 2000-2022
Minta AA , Ferrari M , Antoni S , Portnoy A , Sbarra A , Lambert B , Hatcher C , Hsu CH , Ho LL , Steulet C , Gacic-Dobo M , Rota PA , Mulders MN , Bose AS , Caro WP , O'Connor P , Crowcroft NS . MMWR Morb Mortal Wkly Rep 2023 72 (46) 1262-1268 Measles is a highly contagious, vaccine-preventable disease that requires high population immunity for transmission to be interrupted. All six World Health Organization regions have committed to eliminating measles; however, no region has achieved and sustained measles elimination. This report describes measles elimination progress during 2000-2022. During 2000-2019, estimated coverage worldwide with the first dose of measles-containing vaccine (MCV) increased from 72% to 86%, then declined to 81% in 2021 during the COVID-19 pandemic, representing the lowest coverage since 2008. In 2022, first-dose MCV coverage increased to 83%. Only one half (72) of 144 countries reporting measles cases achieved the measles surveillance indicator target of two or more discarded cases per 100,000 population in 2022. During 2021-2022, estimated measles cases increased 18%, from 7,802,000 to 9,232,300, and the number of countries experiencing large or disruptive outbreaks increased from 22 to 37. Estimated measles deaths increased 43% during 2021-2022, from 95,000 to 136,200. Nonetheless, an estimated 57 million measles deaths were averted by vaccination during 2000-2022. In 2022, measles vaccination coverage and global surveillance showed some recovery from the COVID-19 pandemic setbacks; however, coverage declined in low-income countries, and globally, years of suboptimal immunization coverage left millions of children unprotected. Urgent reversal of coverage setbacks experienced during the COVID-19 pandemic can be accomplished by renewing efforts to vaccinate all children with 2 MCV doses and strengthening surveillance, thereby preventing outbreaks and accelerating progress toward measles elimination. |
Characterizing infection of B cells with wild-type and vaccine strains of measles virus
Melot L , Bankamp B , Rota PA , Coughlin MM . iScience 2023 26 (10) 107721 Acute infection with measles virus (MeV) causes transient immunosuppression often leading to secondary infections. MeV infection of B lymphocytes results in changes in the antibody repertoire and memory B cell populations for which the mechanism is unknown. In this study, we characterize the infection of primary B cells with wild-type and vaccine strains of MeV. Vaccine-infected B cells were characterized by a higher percentage of cells positive for viral protein, a higher level of viral transcription and reduced cell death compared to wild-type infected cells, regardless of B cell subtype. Vaccine-infected cells showed more production of TNF-α and IL-10 but less production of IL-8 compared to wild-type infected cells. IL-4 and IL-6 levels detected were increased during both vaccine and wild-type infection. Despite evidence of replication, measles-infected B cells did not produce detectable viral progeny. This study furthers our understanding of the outcomes of MeV infection of human B cells. |
Measles virus transmission patterns and public health responses during Operation Allies Welcome: a descriptive epidemiological study
Masters NB , Beck AS , Mathis AD , Leung J , Raines K , Paul P , Stanley SE , Weg AL , Pieracci EG , Gearhart S , Jumabaeva M , Bankamp B , Rota PA , Sugerman DE , Gastañaduy PA . Lancet Public Health 2023 8 (8) e618-e628 BACKGROUND: On Aug 29, 2021, Operation Allies Welcome (OAW) was established to support the resettlement of more than 80 000 Afghan evacuees in the USA. After identification of measles among evacuees, incoming evacuee flights were temporarily paused, and mass measles vaccination of evacuees aged 6 months or older was introduced domestically and overseas, with a 21-day quarantine period after vaccination. We aimed to evaluate patterns of measles virus transmission during this outbreak and the impact of control measures. METHODS: We conducted a measles outbreak investigation among Afghan evacuees who were resettled in the USA as part of OAW. Patients with measles were defined as individuals with an acute febrile rash illness between Aug 29, 2021, and Nov 26, 2021, and either laboratory confirmation of infection or epidemiological link to a patient with measles with laboratory confirmation. We analysed the demographics and clinical characteristics of patients with measles and used epidemiological information and whole-genome sequencing to track transmission pathways. A transmission model was used to evaluate the effects of vaccination and other interventions. FINDINGS: 47 people with measles (attack rate: 0·65 per 1000 evacuees) were reported in six US locations housing evacuees in four states. The median age of patients was 1 year (range 0-26); 33 (70%) were younger than 5 years. The age distribution shifted during the outbreak towards infants younger than 12 months. 20 (43%) patients with wild-type measles virus had rash onset after vaccination. No fatalities or community spread were identified, nor further importations after flight resumption. In a non-intervention scenario, transmission models estimated that a median of 5506 cases (IQR 10-5626) could have occurred. Infection clusters based on epidemiological criteria could be delineated into smaller clusters using phylogenetic analyses; however, sequences with few substitution count differences did not always indicate single lines of transmission. INTERPRETATION: Implementation of control measures limited measles transmission during OAW. Our findings highlight the importance of integration between epidemiological and genetic information in discerning between individual lines of transmission in an elimination setting. FUNDING: US Centers for Disease Control and Prevention. |
Comparison of Illumina MiSeq and the Ion Torrent PGM and S5 platforms for whole-genome sequencing of picornaviruses and caliciviruses (preprint)
Marine RL , Magana LC , Castro CJ , Zhao K , Montmayeur AM , Schmidt A , Diez-Valcarce M , Fan Ng TF , Vinje J , Burns CC , Allan Nix W , Rota PA , Oberste MS . bioRxiv 2019 705632 Next-generation sequencing is a powerful tool for virological surveillance. While Illumina® and Ion Torrent® sequencing platforms are used extensively for generating viral RNA genome sequences, there is limited data comparing different platforms. We evaluated the Illumina MiSeq, Ion Torrent PGM and Ion Torrent S5 platforms using a panel of sixteen specimens containing picornaviruses and human caliciviruses (noroviruses and sapoviruses). The specimens were processed, using combinations of three library preparation and five sequencing kits, to assess the quality and completeness of assembled viral genomes, and an estimation of cost per sample to generate the data was calculated. The choice of library preparation kit and sequencing platform was found to impact the breadth of genome coverage and accuracy of consensus viral genomes. The Ion Torrent S5 outperformed the older Ion Torrent PGM platform in data quality and cost, and generated the highest proportion of reads for enterovirus D68 samples. However, indels at homopolymer regions impacted the accuracy of consensus genome sequences. For lower throughput sequencing runs (i.e., Ion Torrent 510 or Illumina MiSeq Nano V2), the cost per sample was lower on the MiSeq platform, whereas with higher throughput runs (Ion Torrent 530 or Illumina MiSeq V2) the cost per sample was comparable. These findings suggest that the Ion Torrent S5 and Illumina MiSeq platforms are both viable options for genomic sequencing of RNA viruses, each with specific advantages and tradeoffs. |
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. |
Performance Characteristics of Six Immunoglobulin M (IgM) ELISA Assays Used for Laboratory Confirmation of Measles (preprint)
Sowers SB , Anthony K , Mercader S , Colley H , Crooke SN , Rota PA , Latner DR , Hickman CJ . medRxiv 2022 04 Laboratory confirmation of infection is an essential component of measles surveillance. Detection of measles specific IgM in serum by enzyme linked immunosorbent assay (ELISA) is the most used method for confirming measles infection. ELISA formats vary as does the sensitivity and specificity of each assay. Specimens collected within 3 days of rash onset can yield a false negative result, which can delay confirmation of measles cases. Interfering substances can yield a false positive result, leading to unnecessary public health interventions. The IgM capture assay developed at the Centers for Disease Control (CDC) was compared against 5 commercially available ELISA kits for the ability to detect measles virus-specific IgM in a panel of 90 well-characterized specimens. Serum samples were tested in triplicate using each commercial kit as recommended by the manufacturer. Using the CDC measles IgM capture assay as the reference test; sensitivity and specificity for the commercial kits ranged from 50 to 83% and 86.9 to 98%, respectively. Discrepant results were observed for samples tested with all five commercial kits and ranged from 13.8 to 28.8% of the specimens tested. False positive results occurred in 2.0 to 13.1% of sera while negative results were observed in 16.7 to 50% of sera that were positive by the CDC measles IgM capture assay. Evaluation and interpretation of measles IgM serologic results can be complex, particularly in measles elimination settings. The performance characteristics of a measles IgM assay should be carefully considered when selecting an assay to achieve high quality measles surveillance. 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. |
Use of a rapid digital microfluidics-powered immunoassay for assessing measles and rubella infection and immunity in outbreak settings in the Democratic Republic of the Congo
Knipes AK , Summers A , Sklavounos AA , Lamanna J , de Campos RPS , Narahari T , Dixon C , Fobel R , Ndjakani YD , Lubula L , Magazani A , Muyembe JJ , Lay Y , Pukuta E , Waku-Kouomou D , Hao L , Kayembe JK , Fobel C , Dahmer J , Lee A , Ho M , Valenzuela JGC , Rackus DG , Shih R , Seale B , Chang A , Paluku G , Rota PA , Wheeler AR , Scobie HM . PLoS One 2022 17 (12) e0278749 The Democratic Republic of the Congo (DRC) has a high measles incidence despite elimination efforts and has yet to introduce rubella vaccine. We evaluated the performance of a prototype rapid digital microfluidics powered (DMF) enzyme-linked immunoassay (ELISA) assessing measles and rubella infection, by testing for immunoglobulin M (IgM), and immunity from natural infection or vaccine, by testing immunoglobulin G (IgG), in outbreak settings. Field evaluations were conducted during September 2017, in Kinshasa province, DRC. Blood specimens were collected during an outbreak investigation of suspected measles cases and tested for measles and rubella IgM and IgG using the DMF-ELISA in the field. Simultaneously, a household serosurvey for measles and rubella IgG was conducted in a recently confirmed measles outbreak area. DMF-ELISA results were compared with reference ELISA results tested at DRC's National Public Health Laboratory and the US Centers for Disease Control and Prevention. Of 157 suspected measles cases, rubella IgM was detected in 54% while measles IgM was detected in 13%. Measles IgG-positive cases were higher among vaccinated persons (87%) than unvaccinated persons (72%). In the recent measles outbreak area, measles IgG seroprevalence was 93% overall, while rubella seroprevalence was lower for children (77%) than women (98%). Compared with reference ELISA, DMF-ELISA sensitivity and specificity were 82% and 78% for measles IgG; 88% and 89% for measles IgM; 85% and 85% for rubella IgG; and 81% and 83% for rubella IgM, respectively. Rubella infection was detected in more than half of persons meeting the suspected measles case definition during a presumed measles outbreak, suggesting substantial unrecognized rubella incidence, and highlighting the need for rubella vaccine introduction into the national schedule. The performance of the DMF-ELISA suggested that this technology can be used to develop rapid diagnostic tests for measles and rubella. |
Progress toward regional measles elimination - Worldwide, 2000-2021
Minta AA , Ferrari M , Antoni S , Portnoy A , Sbarra A , Lambert B , Hauryski S , Hatcher C , Nedelec Y , Datta D , Ho LL , Steulet C , Gacic-Dobo M , Rota PA , Mulders MN , Bose AS , Perea WA , O'Connor P . MMWR Morb Mortal Wkly Rep 2022 71 (47) 1489-1495 All six World Health Organization (WHO) regions have committed to eliminating measles.* The Immunization Agenda 2021-2030 (IA2030)(†) aims to achieve the regional targets as a core indicator of impact and positions measles as the tracer of a health system's ability to deliver essential childhood vaccines. IA2030 highlights the importance of ensuring rigorous measles surveillance systems to document immunity gaps and achieve 95% coverage with 2 timely doses of measles-containing vaccine (MCV) among children. This report describes progress toward measles elimination during 2000-2021 and updates a previous report (1). During 2000-2021, estimated global coverage with a first MCV dose (MCV1) increased from 72% to a peak of 86% in 2019, but decreased during the COVID-19 pandemic to 83% in 2020 and to 81% in 2021, the lowest MCV1 coverage recorded since 2008. All countries conducted measles surveillance, but only 47 (35%) of 135 countries reporting discarded cases(§) achieved the sensitivity indicator target of two or more discarded cases per 100,000 population in 2021, indicating surveillance system underperformance in certain countries. Annual reported measles incidence decreased 88% during 2000-2016, from 145 to 18 cases per 1 million population, then rebounded to 120 in 2019 during a global resurgence (2), before declining to 21 in 2020 and to 17 in 2021. Large and disruptive outbreaks were reported in 22 countries. During 2000-2021, the annual number of estimated measles deaths decreased 83%, from 761,000 to 128,000; an estimated 56 million measles deaths were averted by vaccination. To regain progress and achieve regional measles elimination targets during and after the COVID-19 pandemic, accelerating targeted efforts is necessary to reach all children with 2 MCV doses while implementing robust surveillance and identifying and closing immunity gaps to prevent cases and outbreaks. |
Performance characteristics of six immunoglobulin m enzyme-linked immunosorbent assays used for laboratory confirmation of measles
Sowers SB , Anthony K , Mercader S , Colley H , Crooke SN , Rota PA , Latner DR , Hickman CJ . J Clin Microbiol 2022 60 (12) e0122722 Laboratory confirmation of infection is an essential component of measles surveillance. Detection of measles-specific IgM in serum by enzyme-linked immunosorbent assay (ELISA) is the most common method used to confirm measles infection. ELISA formats vary, as does the sensitivity and specificity of each assay. Specimens collected within 3 days of rash onset can yield a false-negative result, which can delay confirmation of measles cases. Interfering substances can yield a false-positive result, leading to unnecessary public health interventions. The IgM capture assay developed at the Centers for Disease Control (CDC) was compared against five commercially available ELISA kits for the ability to detect measles virus-specific IgM in a panel of 90 well-characterized specimens. Serum samples were tested in triplicate using each commercial kit as recommended by the manufacturer. Using the CDC measles IgM capture assay as the reference test; the sensitivity and specificity for each commercial kit ranged from 50 to 83% and 86.9 to 98%, respectively. Discrepant results were observed for samples tested with all five commercial kits and ranged from 13.8 to 28.8% of the specimens tested. False-positive results occurred in 2.0 to 13.1% of sera, while negative results were observed in 16.7 to 50% of sera that were positive by the CDC measles IgM capture assay. Evaluation and interpretation of measles IgM serologic results can be complex, particularly in measles elimination settings. The performance characteristics of a measles IgM assay should be carefully considered when selecting an assay to achieve high-quality measles surveillance. |
Diagnostic and immunologic testing for varicella in the era of high-impact varicella vaccination: An evolving problem
Dollard S , Chen MH , Lindstrom S , Marin M , Rota PA . J Infect Dis 2022 226 S450-s455 The clinical presentation of varicella in unvaccinated persons, with skin vesicles and scabs, has facilitated the use of rapid diagnostic methods for confirming disease. Polymerase chain reaction (PCR) assays are the diagnostic method of choice. The sharp decline in unmodified cases of varicella due to the US varicella vaccination program has led to fewer healthcare providers being familiar with varicella presentation and an increased reliance on laboratory diagnosis to confirm suspected cases. The mild, atypical presentation of the disease in vaccinated persons (fewer skin lesions, mostly maculopapular) has made it more challenging for providers to recognize and also to collect samples to detect the virus. Nonetheless, PCR is highly sensitive and specific in confirming modified disease if adequate samples are provided. While a positive PCR result is confirmatory, interpreting a negative result can prove to be more challenging in determining whether suspected varicella is falsely negative or attributable to other causes. Enhanced education of healthcare providers is critical for adequate specimen collection from modified varicella cases. In addition, more sensitive commercial serologic assays are needed in the United States for varicella immunity testing in the vaccine era. |
Study protocol for a phase 1/2, single-centre, double-blind, double-dummy, randomized, active-controlled, age de-escalation trial to assess the safety, tolerability and immunogenicity of a measles and rubella vaccine delivered by a microneedle patch in healthy adults (18 to 40 years), measles and rubella vaccine-primed toddlers (15 to 18 months) and measles and rubella vaccine-nave infants (9 to 10 months) in The Gambia [Measles and Rubella Vaccine Microneedle Patch Phase 1/2 Age De-escalation Trial]
Adigweme I , Akpalu E , Yisa M , Donkor S , Jarju LB , Danso B , Mendy A , Jeffries D , Njie A , Bruce A , Royals M , Goodson JL , Prausnitz MR , McAllister D , Rota PA , Henry S , Clarke E . Trials 2022 23 (1) 775 BACKGROUND: New strategies to increase measles and rubella vaccine coverage, particularly in low- and middle-income countries, are needed if elimination goals are to be achieved. With this regard, measles and rubella vaccine microneedle patches (MRV-MNP), in which the vaccine is embedded in dissolving microneedles, offer several potential advantages over subcutaneous delivery. These include ease of administration, increased thermostability, an absence of sharps waste, reduced overall costs and pain-free administration. This trial will provide the first clinical trial data on MRV-MNP use and the first clinical vaccine trial of MNP technology in children and infants. METHODS: This is a phase 1/2, randomized, active-controlled, double-blind, double-dummy, age de-escalation trial. Based on the defined eligibility criteria for the trial, including screening laboratory investigations, 45 adults [18-40 years] followed by 120 toddlers [15-18 months] and 120 infants [9-10 months] will be enrolled in series. To allow double-blinding, participants will receive either the MRV-MNP and a placebo (0.9% sodium chloride) subcutaneous (SC) injection or a placebo MNP and the MRV by SC injection (MRV-SC). Local and systemic adverse event data will be collected for 14 days following study product administration. Safety laboratories will be repeated on day 7 and, in the adult cohort alone, on day 14. Unsolicited adverse events including serious adverse events will be collected until the final study visit for each participant on day 180. Measles and rubella serum neutralizing antibodies will be measured at baseline, on day 42 and on day 180. Cohort progression will be dependent on review of the unblinded safety data by an independent data monitoring committee. DISCUSSION: This trial will provide the first clinical data on the use of a MNP to deliver the MRV and the first data on the use of MNPs in a paediatric population. It will guide future product development decisions for what may be a key technology for future measles and rubella elimination. TRIAL REGISTRATION: Pan-African Clinical Trials Registry 202008836432905 . CLINICALTRIALS: gov NCT04394689. |
Accelerating measles elimination in the Western Pacific Region during the calm between the storms
Durrheim DN , Baker MG , Capeding MR , Goh KT , Lee D , Papania M , Rota PA , Soo TL , Tsang TH , Xu A . Lancet Reg Health West Pac 2022 23 100495 The 2018-19 global measles resurgence was the largest measles epidemic in over two decades and prompted calls for the declaration of a Public Health Emergency of International Concern. The enormous number of measles cases with global spread and ensuing deaths was characterised as an extraordinary event that may constitute a public health risk to other countries through international spread of disease and may require an international coordinated response.1 However, this momentous epidemic was soon overshadowed as the world wrestled with the immense threat posed by the COVID-19 pandemic. |
Public health actions to control measles among Afghan evacuees during Operation Allies Welcome - United States, September-November 2021
Masters NB , Mathis AD , Leung J , Raines K , Clemmons NS , Miele K , Balajee SA , Lanzieri TM , Marin M , Christensen DL , Clarke KR , Cruz MA , Gallagher K , Gearhart S , Gertz AM , Grady-Erickson O , Habrun CA , Kim G , Kinzer MH , Miko S , Oberste MS , Petras JK , Pieracci EG , Pray IW , Rosenblum HG , Ross JM , Rothney EE , Segaloff HE , Shepersky LV , Skrobarcek KA , Stadelman AM , Sumner KM , Waltenburg MA , Weinberg M , Worrell MC , Bessette NE , Peake LR , Vogt MP , Robinson M , Westergaard RP , Griesser RH , Icenogle JP , Crooke SN , Bankamp B , Stanley SE , Friedrichs PA , Fletcher LD , Zapata IA , Wolfe HO , Gandhi PH , Charles JY , Brown CM , Cetron MS , Pesik N , Knight NW , Alvarado-Ramy F , Bell M , Talley LE , Rotz LD , Rota PA , Sugerman DE , Gastañaduy PA . MMWR Morb Mortal Wkly Rep 2022 71 (17) 592-596 On August 29, 2021, the United States government oversaw the emergent establishment of Operation Allies Welcome (OAW), led by the U.S. Department of Homeland Security (DHS) and implemented by the U.S. Department of Defense (DoD) and U.S. Department of State (DoS), to safely resettle U.S. citizens and Afghan nationals from Afghanistan to the United States. Evacuees were temporarily housed at several overseas locations in Europe and Asia* before being transported via military and charter flights through two U.S. international airports, and onward to eight U.S. military bases,(†) with hotel A used for isolation and quarantine of persons with or exposed to certain infectious diseases.(§) On August 30, CDC issued an Epi-X notice encouraging public health officials to maintain vigilance for measles among Afghan evacuees because of an ongoing measles outbreak in Afghanistan (25,988 clinical cases reported nationwide during January-November 2021) (1) and low routine measles vaccination coverage (66% and 43% for the first and second doses, respectively, in 2020) (2). |
In elimination settings, measles antibodies wane following vaccination but not following infection - a systematic review and meta-analysis
Bolotin S , Osman S , Hughes SL , Ariyarajah A , Tricco AC , Khan S , Li L , Johnson C , Friedman L , Gul N , Jardine R , Faulkner M , Hahné SJM , Heffernan JM , Dabbagh A , Rota PA , Severini A , Jit M , Durrheim DN , Orenstein WA , Moss WJ , Funk S , Turner N , Schluter W , Jawad JS , Crowcroft NS . J Infect Dis 2022 226 (7) 1127-1139 BACKGROUND: We conducted a systematic review to assess whether measles humoral immunity wanes in previously infected or vaccinated populations in measles elimination settings. METHODS: After screening 16,822 citations, we identified nine articles from populations exposed to wild-type measles and 16 articles from vaccinated populations that met our inclusion criteria. RESULTS: Using linear regression, we found that geometric mean titers (GMTs) decreased significantly in individuals who received two doses of measles-containing vaccine (MCV) by 121.8 mIU/mL (95% CI -212.4, -31.1) per year since vaccination over one to five years, 53.7 mIU/mL (95% CI -95.3, -12.2) five to ten years, 33.2 mIU/mL (95% CI -62.6, -3.9) ten to 15 years, and 24.1 mIU/mL (95% CI -51.5,3.3) 15 to 20 years since vaccination. Decreases in GMT over time were not significant after one dose of MCV or after infection. Decreases in the proportion of seropositive individuals over time were not significant after one or two doses of MCV, or after infection. CONCLUSIONS: Measles antibody waning in vaccinated populations should be considered in planning for measles elimination. |
VPipe: an Automated Bioinformatics Platform for Assembly and Management of Viral Next-Generation Sequencing Data.
Wagner DD , Marine RL , Ramos E , Ng TFF , Castro CJ , Okomo-Adhiambo M , Harvey K , Doho G , Kelly R , Jain Y , Tatusov RL , Silva H , Rota PA , Khan AN , Oberste MS . Microbiol Spectr 2022 10 (2) e0256421 Next-generation sequencing (NGS) is a powerful tool for detecting and investigating viral pathogens; however, analysis and management of the enormous amounts of data generated from these technologies remains a challenge. Here, we present VPipe (the Viral NGS Analysis Pipeline and Data Management System), an automated bioinformatics pipeline optimized for whole-genome assembly of viral sequences and identification of diverse species. VPipe automates the data quality control, assembly, and contig identification steps typically performed when analyzing NGS data. Users access the pipeline through a secure web-based portal, which provides an easy-to-use interface with advanced search capabilities for reviewing results. In addition, VPipe provides a centralized system for storing and analyzing NGS data, eliminating common bottlenecks in bioinformatics analyses for public health laboratories with limited on-site computational infrastructure. The performance of VPipe was validated through the analysis of publicly available NGS data sets for viral pathogens, generating high-quality assemblies for 12 data sets. VPipe also generated assemblies with greater contiguity than similar pipelines for 41 human respiratory syncytial virus isolates and 23 SARS-CoV-2 specimens. IMPORTANCE Computational infrastructure and bioinformatics analysis are bottlenecks in the application of NGS to viral pathogens. As of September 2021, VPipe has been used by the U.S. Centers for Disease Control and Prevention (CDC) and 12 state public health laboratories to characterize >17,500 and 1,500 clinical specimens and isolates, respectively. VPipe automates genome assembly for a wide range of viruses, including high-consequence pathogens such as SARS-CoV-2. Such automated functionality expedites public health responses to viral outbreaks and pathogen surveillance. |
Innovations in vaccine delivery: increasing access, coverage, and equity and lessons learnt from measles and rubella elimination
Goodson JL , Rota PA . Drug Deliv Transl Res 2022 12 (5) 1-9 Disease eradication and elimination programs drive innovations based on progress toward measurable objectives, evaluations of new strategies and methods, programmatic experiences, and lessons learned from the field. Following progress toward global measles elimination, reducing measles mortality, and increasing introductions of measles and rubella vaccines to national programs, the measles and rubella immunization program has faced setbacks in recent years. Currently available vaccine delivery methods have complicated logistics and drawbacks that create barriers to vaccination; innovations for easier, more efficient, and safer vaccine delivery are needed. Progress can be accelerated by new technologies like microarray patches (MAPs) that are now widely recognized as a potential new tool for enhancing global immunizations efforts. Clinical trials of measles-rubella vaccine MAPs have begun, and several other vaccine MAPs are in the pre-clinical development pathway. MAPs could significantly contribute to Immunization Agenda 2030 priorities, including reaching zero-dose children; increasing vaccine access, demand, coverage, and equity; and achieving measles and rubella elimination. With strong partnerships between public health agencies and biotechnology companies, translational novel vaccine delivery systems can be developed to help solve public health problems and achieve global health priorities. |
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. |
Progress Toward Regional Measles Elimination - Worldwide, 2000-2020
Dixon MG , Ferrari M , Antoni S , Li X , Portnoy A , Lambert B , Hauryski S , Hatcher C , Nedelec Y , Patel M , Alexander JP Jr , Steulet C , Gacic-Dobo M , Rota PA , Mulders MN , Bose AS , Rosewell A , Kretsinger K , Crowcroft NS . MMWR Morb Mortal Wkly Rep 2021 70 (45) 1563-1569 In 2012, the World Health Assembly endorsed the Global Vaccine Action Plan,* with the objective of eliminating measles(†) in five of the six World Health Organization (WHO) regions by 2020 (1). The Immunization Agenda 2021-2030 (IA2030)(§) uses measles incidence as an indicator of the strength of immunization systems. The Measles-Rubella Strategic Framework 2021-2030(¶) and the Measles Outbreaks Strategic Response Plan 2021-2023** are aligned with the IA2030 and highlight robust measles surveillance systems to document immunity gaps, identify root causes of undervaccination, and develop locally tailored solutions to ensure administration of 2 doses of measles-containing vaccine (MCV) to all children. This report describes progress toward World Health Assembly milestones and measles elimination objectives during 2000-2020 and updates a previous report (2). During 2000-2010, estimated MCV first dose (MCV1) coverage increased globally from 72% to 84%, peaked at 86% in 2019, but declined to 84% in 2020 during the COVID-19 pandemic. All countries conducted measles surveillance, although fewer than one third achieved the sensitivity indicator target of ≥2 discarded(††) cases per 100,000 population in 2020. Annual reported measles incidence decreased 88% during 2000-2016, from 145 to 18 cases per 1 million population, rebounded to 120 in 2019, before falling to 22 in 2020. During 2000-2020, the annual number of estimated measles deaths decreased 94%, from 1,072,800 to 60,700, averting an estimated 31.7 million measles deaths. To achieve regional measles elimination targets, enhanced efforts are needed to reach all children with 2 MCV doses, implement robust surveillance, and identify and close immunity gaps. |
Performance characteristics of the Abbott BinaxNOW SARS-CoV-2 antigen test in comparison to real-time RT-PCR and viral culture in community testing sites during November 2020.
Almendares O , Prince-Guerra JL , Nolen LD , Gunn JKL , Dale AP , Buono SA , Deutsch-Feldman M , Suppiah S , Hao L , Zeng Y , Stevens VA , Knipe K , Pompey J , Atherstone C , Bui DP , Powell T , Tamin A , Harcourt JL , Petway M , Bohannon C , Folster JM , MacNeil A , Salerno R , Kuhnert-Tallman W , Tate JE , Thornburg N , Kirking HL , Villanueva JM , Rose DA , Neatherlin JC , Anderson M , Rota PA , Honein MA , Bower WA . J Clin Microbiol 2021 60 (1) Jcm0174221 Point-of-care antigen tests are an important tool for SARS-CoV-2 detection. Antigen tests are less sensitive than real-time reverse-transcriptase PCR (rRT-PCR). Data on the performance of the BinaxNOW antigen test compared to rRT-PCR and viral culture by symptom and known exposure status, timing during disease or exposure period and demographic variables are limited. During November 3(rd)-17(th), 2020, we collected paired upper respiratory swab specimens to test for SARS-CoV-2 by rRT-PCR and Abbott BinaxNOW (BinaxNOW) antigen test at two community testing sites in Pima County, Arizona. We administered a questionnaire to capture symptoms, known exposure status and previous SARS-CoV-2 test results. Specimens positive by either test were analyzed by viral culture. Previously we showed overall BinaxNOW sensitivity was 52.5%. Here we showed BinaxNOW sensitivity increased to 65.7% among currently symptomatic individuals reporting a known exposure. BinaxNOW sensitivity was lower among participants with a known exposure and previously symptomatic (32.4%) or never symptomatic (47.1%) within 14 days of testing. Sensitivity was 71.1% in participants within a week of symptom onset. In participants with a known exposure, sensitivity was highest 8-10 days post-exposure (75%). The positive predictive value for recovery of virus in cell culture was 56.7% for BinaxNOW-positive and 35.4% for rRT-PCR-positive specimens. Result reporting time was 2.5 hours for BinaxNOW and 26 hours for rRT-PCR. Point-of-care antigen tests have a shorter turn-around time compared to laboratory-based nucleic acid amplification tests, which allows for more rapid identification of infected individuals. Antigen test sensitivity limitations are important to consider when developing a testing program. |
Measles in the 21st century: Progress toward achieving and sustaining elimination
Gastañaduy PA , Goodson JL , Panagiotakopoulos L , Rota PA , Orenstein WA , Patel M . J Infect Dis 2021 224 S420-s428 The global measles vaccination program has been extraordinarily successful in reducing measles-related disease and deaths worldwide. Eradication of measles is feasible because of several key attributes, including humans as the only reservoir for the virus, broad access to diagnostic tools that can rapidly detect measles-infectious persons, and availability of highly safe and effective measles-containing vaccines (MCVs). All 6 World Health Organization (WHO) regions have established measles elimination goals. Globally, during 2000-2018, measles incidence decreased by 66% (from 145 to 49 cases per million population) and deaths decreased by 73% (from 535 600 to 142 300), drastically reducing global disease burden. Routine immunization with MCV has been the cornerstone for the control and prevention of measles. Two doses of MCV are 97% effective in preventing measles, qualifying MCV as one of the most effective vaccines ever developed. Mild adverse events occur in <20% of recipients and serious adverse events are extremely rare. The economic benefits of measles vaccination are highlighted by an overall return on investment of 58 times the cost of the vaccine, supply chains, and vaccination. Because measles is one of the most contagious human diseases, maintenance of high (≥95%) 2-dose MCV coverage is crucial for controlling the spread of measles and successfully reaching measles elimination; however, the plateauing of global MCV coverage for nearly a decade and the global measles resurgence during 2018-2019 demonstrate that much work remains. Global commitments to increase community access to and demand for immunizations, strengthen national and regional partnerships for building public health infrastructure, and implement innovations that can overcome access barriers and enhance vaccine confidence, are essential to achieve a world free of measles. |
Point-of-Care Antigen Test for SARS-CoV-2 in Asymptomatic College Students.
Tinker SC , Szablewski CM , Litvintseva AP , Folster J , Shewmaker PL , Medrzycki M , Bowen MD , Bohannon C , Bagarozzi D Jr , Petway M , Rota PA , Kuhnert-Tallman W , Thornburg N , Prince-Guerra JL , Barrios LC , Tamin A , Harcourt JL , Honein MA . Emerg Infect Dis 2021 27 (10) 2662-2665 We used the BinaxNOW COVID-19 Ag Card to screen 1,540 asymptomatic college students for severe acute respiratory syndrome coronavirus 2 in a low-prevalence setting. Compared with reverse transcription PCR, BinaxNOW showed 20% overall sensitivity; among participants with culturable virus, sensitivity was 60%. BinaxNOW provides point-of-care screening but misses many infections. |
Thermostability of measles and rubella vaccines in a microneedle patch
Joyce JC , Collins ML , Rota PA , Prausnitz MR . Adv Ther 2021 4 (10) Measles and rubella vaccinations are highly effective at reducing disease prevalence; however, logistic issues related to subcutaneous administration and vaccine wastage limit the extent of vaccination coverage. Microneedle (MN) patches can increase coverage by easing logistics through simplified administration and improved stability. This study demonstrates the thermostability of a bivalent measles and rubella vaccine MN patch. The data show that rubella vaccine stability requires pH buffering during drying; potassium phosphate buffer at neutral pH is optimal for both vaccines. Screening 43 excipients for their ability to retain potency during drying and storage yields sucrose-threonine-potassium phosphate buffer formulation at pH 7.5 as an optimal formulation. MN patches made with this formulation have no significant loss of vaccine titer after 1 month and remain within a one log10 titer loss cutoff after 3–4 months at 5, 25, and 40 °C. Finally, these patches are shown to be immunogenic in juvenile rhesus macaques. This work demonstrates the potential for MN patches for measles and rubella vaccination to be removed from the cold chain, which is expected to decrease vaccine cost and wastage, and increase vaccination coverage. This article is a U.S. Government work and is in the public domain in the USA. |
Development of a Measles and Rubella Multiplex Bead Serological Assay for Assessing Population Immunity
Coughlin MM , Matson Z , Sowers SB , Priest JW , Smits GP , van der Klis FRM , Mitchell A , Hickman CJ , Scobie HM , Goodson JL , Alexander JPJr , Rota PA , Bankamp B . J Clin Microbiol 2021 59 (6) Serosurveys are important tools for estimating population immunity and providing immunization activity guidance. The measles and rubella multiplex bead assay (MBA) offers multiple advantages over standard serological assays and was validated by comparison with the enzyme-linked immunosorbent assay (ELISA) and the measles plaque reduction neutralization (PRN) assay. Results from a laboratory-produced purified measles whole virus antigen MBA (MeV WVA(L)) correlated better with ELISA and PRN than results from the baculovirus-expressed measles nucleoprotein (N) MBA. Therefore, a commercially produced whole virus antigen (MeV WVA(C)) was evaluated. Serum IgG antibody concentrations correlated significantly with a strong linear relationship between the MeV WVA(C) and MeV WVA(L) MBAs (R=0.962, R(2)=0.926). IgG concentrations from the MeV WVA(C) MBA showed strong correlation with PRN titers (R=0.846) with a linear relationship comparable to values obtained with the MeV WVA(L) MBA and PRN assay (R(2)=0.716 and R(2)=0.768, respectively). Receiver-operating characteristic (ROC) curve analysis of the MeV WVA(C) using PRN titer as the comparator resulted in a seroprotection cutoff of 153 mIU/ml, similar to the established correlate of protection of 120 mIU/ml, with a sensitivity of 98% and a specificity of 84%. IgG concentrations correlated strongly between the rubella WVA MBA and ELISA (R=0.959 and R(2)=0.919). ROC analysis of the rubella MBA using ELISA as the comparator yielded a cutoff of 9.36 IU/ml, similar to the accepted cutoff of 10 IU/ml for seroprotection, with a sensitivity of 99% and a specificity of 100%. These results support use of the MBA for multi-antigen serosurveys assessing measles and rubella population immunity. |
Evaluation of Abbott BinaxNOW Rapid Antigen Test for SARS-CoV-2 Infection at Two Community-Based Testing Sites - Pima County, Arizona, November 3-17, 2020.
Prince-Guerra JL , Almendares O , Nolen LD , Gunn JKL , Dale AP , Buono SA , Deutsch-Feldman M , Suppiah S , Hao L , Zeng Y , Stevens VA , Knipe K , Pompey J , Atherstone C , Bui DP , Powell T , Tamin A , Harcourt JL , Shewmaker PL , Medrzycki M , Wong P , Jain S , Tejada-Strop A , Rogers S , Emery B , Wang H , Petway M , Bohannon C , Folster JM , MacNeil A , Salerno R , Kuhnert-Tallman W , Tate JE , Thornburg NJ , Kirking HL , Sheiban K , Kudrna J , Cullen T , Komatsu KK , Villanueva JM , Rose DA , Neatherlin JC , Anderson M , Rota PA , Honein MA , Bower WA . MMWR Morb Mortal Wkly Rep 2021 70 (3) 100-105 Rapid antigen tests, such as the Abbott BinaxNOW COVID-19 Ag Card (BinaxNOW), offer results more rapidly (approximately 15-30 minutes) and at a lower cost than do highly sensitive nucleic acid amplification tests (NAATs) (1). Rapid antigen tests have received Food and Drug Administration (FDA) Emergency Use Authorization (EUA) for use in symptomatic persons (2), but data are lacking on test performance in asymptomatic persons to inform expanded screening testing to rapidly identify and isolate infected persons (3). To evaluate the performance of the BinaxNOW rapid antigen test, it was used along with real-time reverse transcription-polymerase chain reaction (RT-PCR) testing to analyze 3,419 paired specimens collected from persons aged ≥10 years at two community testing sites in Pima County, Arizona, during November 3-17, 2020. Viral culture was performed on 274 of 303 residual real-time RT-PCR specimens with positive results by either test (29 were not available for culture). Compared with real-time RT-PCR testing, the BinaxNOW antigen test had a sensitivity of 64.2% for specimens from symptomatic persons and 35.8% for specimens from asymptomatic persons, with near 100% specificity in specimens from both groups. Virus was cultured from 96 of 274 (35.0%) specimens, including 85 (57.8%) of 147 with concordant antigen and real-time RT-PCR positive results, 11 (8.9%) of 124 with false-negative antigen test results, and none of three with false-positive antigen test results. Among specimens positive for viral culture, sensitivity was 92.6% for symptomatic and 78.6% for asymptomatic individuals. When the pretest probability for receiving positive test results for SARS-CoV-2 is elevated (e.g., in symptomatic persons or in persons with a known COVID-19 exposure), a negative antigen test result should be confirmed by NAAT (1). Despite a lower sensitivity to detect infection, rapid antigen tests can be an important tool for screening because of their quick turnaround time, lower costs and resource needs, high specificity, and high positive predictive value (PPV) in settings of high pretest probability. The faster turnaround time of the antigen test can help limit transmission by more rapidly identifying infectious persons for isolation, particularly when used as a component of serial testing strategies. |
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. |
Progress toward regional measles elimination - worldwide, 2000-2019
Patel MK , Goodson JL , Alexander JP Jr , Kretsinger K , Sodha SV , Steulet C , Gacic-Dobo M , Rota PA , McFarland J , Menning L , Mulders MN , Crowcroft NS . MMWR Morb Mortal Wkly Rep 2020 69 (45) 1700-1705 In 2010, the World Health Assembly (WHA) set the following three milestones for measles control to be achieved by 2015: 1) increase routine coverage with the first dose of measles-containing vaccine (MCV1) among children aged 1 year to ≥90% at the national level and to ≥80% in every district, 2) reduce global annual measles incidence to <5 cases per 1 million population, and 3) reduce global measles mortality by 95% from the 2000 estimate* (1). In 2012, WHA endorsed the Global Vaccine Action Plan,(†) with the objective of eliminating measles(§) in five of the six World Health Organization (WHO) regions by 2020. This report describes progress toward WHA milestones and regional measles elimination during 2000-2019 and updates a previous report (2). During 2000-2010, estimated MCV1 coverage increased globally from 72% to 84% but has since plateaued at 84%-85%. All countries conducted measles surveillance; however, approximately half did not achieve the sensitivity indicator target of two or more discarded measles and rubella cases per 100,000 population. Annual reported measles incidence decreased 88%, from 145 to 18 cases per 1 million population during 2000-2016; the lowest incidence occurred in 2016, but by 2019 incidence had risen to 120 cases per 1 million population. During 2000-2019, the annual number of estimated measles deaths decreased 62%, from 539,000 to 207,500; an estimated 25.5 million measles deaths were averted. To drive progress toward the regional measles elimination targets, additional strategies are needed to help countries reach all children with 2 doses of measles-containing vaccine, identify and close immunity gaps, and improve surveillance. |
- Page last reviewed:Feb 1, 2024
- Page last updated:Apr 22, 2024
- Content source:
- Powered by CDC PHGKB Infrastructure