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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

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 9 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 2 doses of measles-containing vaccine (MCV) by 121.8 mIU/mL (95% confidence interval [CI], −212.4 to −31.1) per year since vaccination over 1 to 5 years, 53.7 mIU/mL (95% CI, −95.3 to −12.2) 5 to 10 years, 33.2 mIU/mL (95% CI, −62.6 to −3.9), 10 to 15 years, and 24.1 mIU/mL (95% CI, −51.5 to 3.3) 15 to 20 years since vaccination. Decreases in GMT over time were not significant after 1 dose of MCV or after infection. Decreases in the proportion of seropositive individuals over time were not significant after 1 or 2 doses of MCV or after infection. Conclusions Measles antibody waning in vaccinated populations should be considered in planning for measles elimination.

Hendra virus (HeV) and Nipah virus (NiV) emerged in the last decade of the twentieth century. They were the cause of a number of outbreaks of respiratory and neurological disease infecting horses and pigs respectively. Transmission from infected domestic animal species resulted in human infections as well, with high case fatality rates a feature. Today they continue to cause outbreaks of human and animal disease. NiV causes yearly disease outbreaks in humans in Bangladesh, and HeV causes sporadic disease outbreaks in horses in north eastern Australia. Due to their zoonotic nature, they have been ideal candidates for collaborative projects in the One Health space, bringing public health and animal health professionals together. This has lead to insightful epidemiological studies, which has resulted in practical disease prevention solutions including a horse vaccine for HeV and NiV spill-over prevention interventions in the field. As more surveillance is undertaken, their known distributions have expanded, as has the range of reservoir host species. The majority of bat species for which there is evidence of henipavirus infection belong to the group known as the Old World family of fruit and nectar feeding bats (Family Pteropodidae, Suborder Megachiroptera). This review of the bat borne henipaviruses discusses the epidemiology, pathology, transmission and disease symptoms in these closely related viruses which belong to the Genus Henipavirus, Family Paramyxoviridae.

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 after elimination to identify potential gaps in the US measles control program. Methods We analyzed national measles notification data from 1 January 2001 to 31 December 2019. We defined measles infection clusters as single cases (isolated cases not linked to additional cases), 2-case clusters, or outbreaks with ≥3 linked cases. We calculated the effective reproduction number (R) to assess changes in transmissibility and reviewed molecular epidemiology data. Results During 2001–2019, a total of 3873 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 7 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 postelimination 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.

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.

All six World Health Organization (WHO) regions have committed to eliminating measles.* The Immunization Agenda 2021-2030 (IA2030)

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.

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

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.

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.govNCT04394689

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.

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.

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

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.

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.

Recently, a lateral flow rapid diagnostic test (RDT) with good accuracy has been described. This test enables measles specific IgM antibody detection in serum, capillary blood and oral fluid. RDTs have the potential to transform measles surveillance by allowing real-time case confirmation outside of central/regional laboratories and by facilitating a timely public health response. Measles virus genes can also be amplified and sequenced consistently from dried IgM-positive RDTs stored outside of cold chain, which will enable more complete virologic surveillance. Critical questions remain regarding operational use of RDTs as part of global measles surveillance. Projects to evaluate RDT use as part of national surveillance programs and to commercialize the RDT are underway.

While morbidity and mortality associated with measles and rubella (MR) have dramatically decreased, there are still >100 000 estimated deaths due to measles and an estimated 100 000 infants born with congenital rubella syndrome annually. Given highly effective MR vaccines, the primary barrier to global elimination of these diseases is low vaccination coverage, especially among the most underserved populations in resource-limited settings. In contrast to conventional MR vaccination by hypodermic injection, microneedle patches are being developed to enable MR vaccination by minimally trained personnel. Simplified supply chain, reduced need for cold chain storage, elimination of vaccine reconstitution, no sharps waste, reduced vaccine wastage, and reduced total system cost of vaccination are advantages of this approach. Preclinical work to develop a MR vaccine patch has proceeded through successful immunization studies in rodents and non-human primates. On-going programs seek to make MR vaccine patches available to support MR elimination efforts around the world.

During January 1-October 1, 2019, a total of 1,249 measles cases and 22 measles outbreaks were reported in the United States. This represents the most U.S. cases reported in a single year since 1992 (1), and the second highest number of reported outbreaks annually since measles was declared eliminated* in the United States in 2000 (2). Measles is an acute febrile rash illness with an attack rate of approximately 90% in susceptible household contacts (3). Domestic outbreaks can occur when travelers contract measles outside the United States and subsequently transmit infection to unvaccinated persons they expose in the United States. Among the 1,249 measles cases reported in 2019, 1,163 (93%) were associated with the 22 outbreaks, 1,107 (89%) were in patients who were unvaccinated or had an unknown vaccination status, and 119 (10%) measles patients were hospitalized. Closely related outbreaks in New York City (NYC) and New York State (NYS; excluding NYC), with ongoing transmission for nearly 1 year in large and close-knit Orthodox Jewish communities, accounted for 934 (75%) cases during 2019 and threatened the elimination status of measles in the United States. Robust responses in NYC and NYS were effective in controlling transmission before the 1-year mark; however, continued vigilance for additional cases within these communities is essential to determine whether elimination has been sustained. Collaboration between public health authorities and undervaccinated communities is important for preventing outbreaks and limiting transmission. The combination of maintenance of high national vaccination coverage with measles, mumps, and rubella vaccine (MMR) and rapid implementation of measles control measures remains the cornerstone for preventing widespread measles transmission (4).

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 less than five 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 updates a previous report (2) and describes progress toward WHA milestones and regional measles elimination during 2000-2018. During 2000-2018, estimated MCV1 coverage increased globally from 72% to 86%; annual reported measles incidence decreased 66%, from 145 to 49 cases per 1 million population; and annual estimated measles deaths decreased 73%, from 535,600 to 142,300. During 2000-2018, measles vaccination averted an estimated 23.2 million deaths. However, the number of measles cases in 2018 increased 167% globally compared with 2016, and estimated global measles mortality has increased since 2017. To continue progress toward the regional measles elimination targets, resource commitments are needed to strengthen routine immunization systems, close historical immunity gaps, and improve surveillance. To achieve measles elimination, all communities and countries need coordinated efforts aiming to reach ≥95% coverage with 2 doses of measles vaccine (3).

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 3rd-17th, 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.

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.

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. Rubella vaccine stability required pH buffering during drying; potassium phosphate buffer at neutral pH was optimal for both vaccines. Screening 43 excipients for their ability to retain potency during drying and storage yielded sucrose-threonine-potassium phosphate buffer formulation at pH 7.5 as an optimal formulation. MN patches made with this formulation had no significant loss of vaccine titer after one month and remained within a one log(10) titer loss cutoff after 3 – 4 months at 5°C, 25°C and 40°C. Finally, these patches were 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.

During January 1-October 1, 2019, a total of 1,249 measles cases and 22 measles outbreaks were reported in the United States. This represents the most U.S. cases reported in a single year since 1992 (1), and the second highest number of reported outbreaks annually since measles was declared eliminated* in the United States in 2000 (2). Measles is an acute febrile rash illness with an attack rate of approximately 90% in susceptible household contacts (3). Domestic outbreaks can occur when travelers contract measles outside the United States and subsequently transmit infection to unvaccinated persons they expose in the United States. Among the 1,249 measles cases reported in 2019, 1,163 (93%) were associated with the 22 outbreaks, 1,107 (89%) were in patients who were unvaccinated or had an unknown vaccination status, and 119 (10%) measles patients were hospitalized. Closely related outbreaks in New York City (NYC) and New York State (NYS; excluding NYC), with ongoing transmission for nearly 1 year in large and close-knit Orthodox Jewish communities, accounted for 934 (75%) cases during 2019 and threatened the elimination status of measles in the United States. Robust responses in NYC and NYS were effective in controlling transmission before the 1-year mark; however, continued vigilance for additional cases within these communities is essential to determine whether elimination has been sustained. Collaboration between public health authorities and undervaccinated communities is important for preventing outbreaks and limiting transmission. The combination of maintenance of high national vaccination coverage with measles, mumps, and rubella vaccine (MMR) and rapid implementation of measles control measures remains the cornerstone for preventing widespread measles transmission (4).

In the past decade, multiple mumps outbreaks have occurred in the United States, primarily in close-contact, high-density settings such as colleges, with a high attack rate among young adults, many of whom had the recommended 2 doses of mumps-measles-rubella (MMR) vaccine. Waning humoral immunity and the circulation of divergent wild-type mumps strains have been proposed as contributing factors to mumps resurgence. Blood samples from 71 healthy 18- to 23-year-old college students living in a non-outbreak area were assayed for antibodies and memory B cells (MBCs) to mumps, measles, and rubella. Seroprevalence rates of mumps, measles, and rubella determined by IgG enzyme-linked immunosorbent assay (ELISA) were 93, 93, and 100%, respectively. The index standard ratio indicated that the concentration of IgG was significantly lower for mumps than rubella. High IgG avidity to mumps Enders strain was detected in sera of 59/71 participants who had sufficient IgG levels. The frequency of circulating mumps-specific MBCs was 5 to 10 times lower than measles and rubella, and 10% of the participants had no detectable MBCs to mumps. Geometric mean neutralizing antibody titers (GMTs) by plaque reduction neutralization to the predominant circulating wild-type mumps strain (genotype G) were 6-fold lower than the GMTs against the Jeryl Lynn vaccine strain (genotype A). The majority of the participants (80%) received their second MMR vaccine ≥10 years prior to study participation. Additional efforts are needed to fully characterize B and T cell immune responses to mumps vaccine and to develop strategies to improve the quality and durability of vaccine-induced immunity.

The Measles & Rubella Initiative (M&RI) identified five key strategies to achieve measles and rubella elimination, including research and innovation to support cost-effective operations and improve vaccination and diagnostic tools. In 2016, the M&RI Research and Innovation Working Group (R&IWG) completed a research prioritization process to identify key research questions and update the global research agenda. The R&IWG reviewed meeting reports and strategic planning documents and solicited programmatic inputs from vaccination experts at the program operational level through a web survey, to identify previous research priorities and new research questions. The R&IWG then convened a meeting of experts to prioritize the identified research questions in four strategic areas: (1) epidemiology and economics, (2) surveillance and laboratory, (3) immunization strategies, and (4) demand creation and communications. The experts identified 19 priority research questions in the four strategic areas to address key areas of work necessary to further progress toward elimination. Future commitments from partners will be needed to develop a platform for improved coordination with adequate and predictable resources for research implementation and innovation to address these identified priorities.

Vaccines prevent 2–3 million childhood deaths annually; however, low vaccine efficacy and the resulting need for booster doses create gaps in immunization coverage. In this translational study, we explore the benefits of extended release of licensed vaccine antigens into skin to increase immune responses after a single dose in order to design improved vaccine delivery systems. By administering daily intradermal injections of inactivated polio vaccine according to six different delivery profiles, zeroth-order release over 28 days resulted in neutralizing antibody titers equivalent to two bolus vaccinations administered one month apart. Vaccinations following this profile also improved immune responses to tetanus toxoid and subunit influenza vaccine but not a live-attenuated viral vaccine, measles vaccine. Finally, using subunit influenza vaccine, we demonstrated that daily vaccination by microneedle patch induced a potent, balanced humoral immunity with an increased memory response compared to bolus vaccination. We conclude that extended presentation of antigen in skin via intradermal injection or microneedle patch can enhance immune responses and reduce the number of vaccine doses, thereby enabling increased vaccination efficacy.

In 2010, the World Health Assembly set three milestones for measles prevention 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 less than five cases per million population; and 3) reduce global measles mortality by 95% from the 2000 estimate (1).* In 2012, the World Health Assembly endorsed the Global Vaccine Action Plan (GVAP),† with the objective of eliminating measles§ in four of the six World Health Organization (WHO) regions by 2015 and in five regions by 2020. Countries in all six WHO regions have adopted goals for measles elimination by 2020. This report describes progress toward global measles control milestones and regional measles elimination goals during 2000-2017 and updates a previous report (2). During 2000-2017, estimated MCV1 coverage increased globally from 72% to 85%; annual reported measles incidence decreased 83%, from 145 to 25 cases per million population; and annual estimated measles deaths decreased 80%, from 545,174 to 109,638. During this period, measles vaccination prevented an estimated 21.1 million deaths. However, measles elimination milestones have not been met, and three regions are experiencing a large measles resurgence. To make further progress, case-based surveillance needs to be strengthened, and coverage with MCV1 and the second dose of measles-containing vaccine (MCV2) needs to increase; in addition, it will be important to maintain political commitment and ensure substantial, sustained investments to achieve global and regional measles elimination goals.

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 virus 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 and 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 83%. 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 multiantigen serosurveys assessing measles and rubella population immunity.

Unfortunately, the inclusion of original names (in non-Latin script) of the following authors caused problems with author name indexing in PubMed. Therefore, these original names were removed from XML data to correct the PubMed record. Mengji Cao, Yuya Chiaki, Hideki Ebihara, Jingjing Fu, George Fú Gāo, Tong Han, Jiang Hong, Ni Hong, Seiji Hongo, Masayuki Horie, Dàohóng Jiāng, Fujio Kadono, Hideki Kondō, Kenji Kubota, Shaorong Li, Longhui Li, Jiànróng Lǐ, Huazhen Liu, Tomohide Natsuaki, Sergey V. Netesov, Anna Papa, Sofia Paraskevopoulou, Liying Qi, Takahide Sasaya, Mang Shi, Xiǎohóng Shí, Zhènglì Shí, Yoshifumi Shimomoto, Jin‑Won Song, Ayato Takada, Shigeharu Takeuchi, Yasuhiro Tomitaka, Keizō Tomonaga, Shinya Tsuda, Changchun Tu, Tomio Usugi, Nikos Vasilakis, Jiro Wada, Lin‑Fa Wang, Guoping Wang, Yanxiang Wang, Yaqin Wang, Tàiyún Wèi, Shaohua Wen, Jiangxiang Wu, Lei Xu, Hironobu Yanagisawa, Caixia Yang, Zuokun Yang, Lifeng Zhai, Yong‑Zhen Zhang, Song Zhang, Jinguo Zhang, Zhe Zhang, Xueping Zhou. In addition, the publication call-out in the supplementary material was updated from issue 11 to issue 12. The original article has been corrected.

In March 2020, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was amended and emended. At the genus rank, 20 new genera were added, two were deleted, one was moved, and three were renamed. At the species rank, 160 species were added, four were deleted, ten were moved and renamed, and 30 species were renamed. This article presents the updated taxonomy of Negarnaviricota as now accepted by the ICTV., La lista completa de autores que integran el documento puede consultarse en el archivo., Facultad de Ciencias Agrarias y Forestales, Centro de Investigaciones en Fitopatología, Facultad de Ciencias Exactas, Instituto de Biotecnologia y Biologia Molecular

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., 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.

Measurement of measles virus-specific IgG is used to assess presumptive evidence of immunity among immunocompetent individuals with uncertain immune or vaccination status. False-negative test results may lead to unnecessary quarantine and exclusion from activities such as employment, education, and travel or result in unnecessary revaccination. In contrast, false-positive results may fail to identify susceptible individuals and promote spread of disease by those who are exposed and unprotected. To better understand the performance characteristics of tests to detect measles IgG, we compared five widely used, commercially available measles IgG test platforms using a set of 223 well-characterized serum samples. Measles virus neutralizing antibodies were also measured by in vitro plaque reduction neutralization, the gold standard method, and compared to IgG test results. Discrepant results were observed for samples in the low-positive ranges of the most sensitive tests, but there was good agreement across platforms for IgG-negative sera and for samples with intermediate to high levels of IgG. False-negative test results occurred in approximately 11% of sera, which had low levels of neutralizing antibody.

INTRODUCTION: In the last two decades, the evidence related to using vaccine patches with multiple short projections (≤ 1 mm) to deliver vaccines through the skin increased significantly and demonstrated their potential as an innovative delivery platform. AREAS COVERED: We review the vaccine patch literature published in English as of March 1, 2019, as well as available information from key stakeholders related to vaccine patches as a platform. We identify key research topics related to basic and translational science on skin physical properties and immunobiology, patch development, and vaccine manufacturing. EXPERT OPINION: Currently, vaccine patch developers continue to address some basic science and other platform issues in the context of developing a potential vaccine patch presentation for an existing or new vaccine. Additional clinical data and manufacturing experience could shift the balance toward incentivizing existing vaccine manufactures to further explore the use vaccine patches to deliver their products. Incentives for innovation of vaccine patches differ for developed and developing countries, which will necessitate different strategies (e.g., public-private partnerships, push or pull mechanisms) to support the basic and applied research needed to ensure a strong evidence base and to overcome translational barriers for vaccine patches as a delivery platform.

In late September 2016, the Americas became the first region in the world to have eliminated endemic transmission of measles virus. Several other countries have also verified measles elimination, and countries in all six World Health Organization regions have adopted measles elimination goals. The public health strategies used to respond to measles outbreaks in elimination settings are thus becoming relevant to more countries. This review highlights the strategies used to limit measles spread in elimination settings: (1) assembly of an outbreak control committee; (2) isolation of measles cases while infectious; (3) exclusion and quarantining of individuals without evidence of immunity; (4) vaccination of susceptible individuals; (5) use of immunoglobulin to prevent measles in exposed susceptible high-risk persons; (6) and maintaining laboratory proficiency for confirmation of measles. Deciding on the extent of containment efforts should be based on the expected benefit of reactive interventions, balanced against the logistical challenges in implementing them.

Background New methods to increase measles and rubella (MR) vaccination coverage are needed to achieve global and regional MR elimination goals. Methods Here, we developed microneedle (MN) patches designed to administer MR vaccine by minimally trained personnel, leave no biohazardous sharps waste, remove the need for vaccine reconstitution, and provide thermostability outside the cold chain. This study evaluated the immunogenicity of MN patches delivering MR vaccine to infant rhesus macaques. Results Protective titers of measles neutralizing antibodies (>120 mIU/mL) were detected in 100% of macaques in the MN group and 75% of macaques in the subcutaneous (SC) injection group. Rubella neutralizing antibody titers were >10 IU/mL for all groups. All macaques in the MN group were protected from challenge with wild-type measles virus, whereas 75% were protected in the SC group. However, vaccination by the MN or SC route was unable to generate protective immune responses to measles in infant macaques pretreated with measles immunoglobulin to simulate maternal antibody. Conclusions These results show, for the first time, that MR vaccine delivered by MN patch generated protective titers of neutralizing antibodies to both measles and rubella in infant rhesus macaques and afforded complete protection from measles virus challenge.

Measles is a highly infectious human viral disease caused by measles virus (MeV). An estimated 114 900 measles deaths occurred worldwide in 2014. There are currently eight clades (A–H) comprised 24 MeV genotypes. We sought to characterise MeVs among Central African Republic (CAR) refugees during the 2014 measles epidemic in Cameroon. Samples were collected from children

Wild-type (w.t.) measles virus (MeV) infection can result in immunosuppression that does not occur following vaccination. A rhesus macaque model indicated that B cells are a target of infection. The role of B cell infection in MeV-induced immune suppression is not fully understood. We characterize the differences in viral replication in human B cells infected with vaccine (Edmonston Zagreb [EZ]) or w.t. virus. B cells from healthy donor blood were infected (MOI 1.0) with a GFP-expressing EZ virus or a w.t. virus to evaluate viral replication after 24 and 48 hours. The number of GFP+ cells (EZ infected) or hemagglutinin (H)+ cells (w.t. infected) was measured via flow cytometry. Transcription of the viral nucleoprotein (N) gene was measured by mRNA-specific cDNA generation and N gene specific qPCR. Production of infectious viral particles was measured via endpoint dilution. In B cells infected with EZ, 30% of cells expressed GFP at 24 hours and 45% of cells expressed GFP at 48 hours. There was a 4.4-fold increase in N gene transcription from 0 to 48 hours. There was no detectable increase in viral titer over input after 48 hours. In B cells infected with w.t. virus, 10% of cells expressed viral H at 24 hours with no increase in H expression at 48 hours. The w.t. virus had a 2.4-fold increase in viral transcription from 0 to 48 hours. There was no detectable increase in viral titer over input after 48 hours. MeV-infected B cells show viral protein production and N gene transcription at 24 and 48 hours. However, w.t. virus replication may be less efficient as shown by lower percentages of H+ cells at 24 and 48 hours and lower levels of N gene transcription at 48 hours. There is no evidence of infectious virus production by either strain of MeV despite evidence of replication.

The fourth United Nations Millennium Development Goal, adopted in 2000, set a target to reduce child mortality by two thirds by 2015. One indicator of progress toward this target was measles vaccination coverage (1). In 2010, the World Health Assembly (WHA) set three milestones for measles control by 2015: 1) increase routine coverage with the first dose of a 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

BACKGROUND. In 2015, a large nationwide measles outbreak occurred in Mongolia, with very high incidence in the capital city of Ulaanbaatar and among young adults. METHODS. We conducted an outbreak investigation including a matched case-control study of risk factors for laboratory-confirmed measles among young adults living in Ulaanbaatar. Young adults with laboratory-confirmed measles, living in the capital city of Ulaanbaatar, were matched with 2–3 neighborhood controls. Conditional logistic regression was used to estimate adjusted matched odds ratios (aMORs) for risk factors, with 95% confidence intervals. RESULTS. During March 1–September 30, 2015, 20 077 suspected measles cases were reported; 14 010 cases were confirmed. Independent risk factors for measles included being unvaccinated (adjusted matched odds ratio [aMOR] 2.0, P < .01), being a high school graduate without college education (aMOR 2.6, P < .01), remaining in Ulaanbaatar during the outbreak (aMOR 2.5, P < .01), exposure to an inpatient healthcare facility (aMOR 4.5 P < .01), and being born outside of Ulaanbaatar (aMOR 1.8, P = .02). CONCLUSIONS. This large, nationwide outbreak shortly after verification of elimination had high incidence among young adults, particularly those born outside the national capital. In addition, findings indicated that nosocomial transmission within health facilities helped amplify the outbreak.

BACKGROUND. In response to a mumps outbreak at the University of Iowa and surrounding community, university, state, and local health officials implemented a vaccination campaign targeting students