In December 2012, the Food and Drug Administration (FDA) approved VariZIG, a varicella zoster immune globulin preparation (Cangene Corporation, Winnipeg, Canada) for use in the United States for postexposure prophylaxis of varicella for persons at high risk for severe disease who lack evidence of immunity to varicella* and for whom varicella vaccine is contraindicated. Previously available under an investigational new drug (IND) expanded access protocol, VariZIG, a purified immune globulin preparation made from human plasma containing high levels of anti-varicella-zoster virus antibodies (immunoglobulin G), is the only varicella zoster immune globulin preparation currently available in the United States. VariZIG is now approved for administration as soon as possible following varicella-zoster virus exposure, ideally within 96 hours (4 days) for greatest effectiveness. CDC recommends administration of VariZIG as soon as possible after exposure to the varicella-zoster virus and within 10 days. CDC also has revised the patient groups recommended by the Advisory Committee on Immunization Practices (ACIP) to receive VariZIG by extending the period of eligibility for previously recommended premature infants from exposures to varicella-zoster virus during the neonatal period to exposures that occur during the entire period for which they require hospital care for their prematurity. The CDC recommendations for VariZIG use are now harmonized with the American Academy of Pediatrics (AAP) recommendations. This report summarizes data on the timing of administration of varicella zoster immune globulin in relation to exposure to varicella-zoster virus and provides the CDC updated recommendations for use of VariZIG that replace the 2007 ACIP recommendations.

This report presents new recommendations adopted in June 2009 by CDC's Advisory Committee on Immunization Practices (ACIP) regarding use of the combination measles, mumps, rubella, and varicella vaccine (MMRV, ProQuad, Merck & Co., Inc.). MMRV vaccine was licensed in the United States in September 2005 and may be used instead of measles, mumps, rubella vaccine (MMR, M-M-RII, Merck & Co., Inc.) and varicella vaccine (VARIVAX, Merck & Co., Inc.) to implement the recommended 2-dose vaccine schedule for prevention of measles, mumps, rubella, and varicella among children aged 12 months-12 years. At the time of its licensure, use of MMRV vaccine was preferred for both the first and second doses over separate injections of equivalent component vaccines (MMR vaccine and varicella vaccine), which was consistent with ACIP's 2006 general recommendations on use of combination vaccines (CDC. General recommendations on immunization: recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR 2006;55;[No. RR-15]). Since July 2007, supplies of MMRV vaccine have been temporarily unavailable as a result of manufacturing constraints unrelated to efficacy or safety. MMRV vaccine is expected to be available again in the United States in May 2010. In February 2008, on the basis of preliminary data from two studies conducted postlicensure that suggested an increased risk for febrile seizures 5-12 days after vaccination among children aged 12-23 months who had received the first dose of MMRV vaccine compared with children the same age who had received the first dose of MMR vaccine and varicella vaccine administered as separate injections at the same visit, ACIP issued updated recommendations regarding MMRV vaccine use (CDC. Update: recommendations from the Advisory Committee on Immunization Practices [ACIP] regarding administration of combination MMRV vaccine. MMWR 2008;57:258-60). These updated recommendations expressed no preference for use of MMRV vaccine over separate injections of equivalent component vaccines for both the first and second doses. The final results of the two postlicensure studies indicated that among children aged 12--23 months, one additional febrile seizure occurred 5-12 days after vaccination per 2,300-2,600 children who had received the first dose of MMRV vaccine compared with children who had received the first dose of MMR vaccine and varicella vaccine administered as separate injections at the same visit. Data from postlicensure studies do not suggest that children aged 4--6 years who received the second dose of MMRV vaccine had an increased risk for febrile seizures after vaccination compared with children the same age who received MMR vaccine and varicella vaccine administered as separate injections at the same visit. In June 2009, after consideration of the postlicensure data and other evidence, ACIP adopted new recommendations regarding use of MMRV vaccine for the first and second doses and identified a personal or family (i.e., sibling or parent) history of seizure as a precaution for use of MMRV vaccine. For the first dose of measles, mumps, rubella, and varicella vaccines at age 12--47 months, either MMR vaccine and varicella vaccine or MMRV vaccine may be used. Providers who are considering administering MMRV vaccine should discuss the benefits and risks of both vaccination options with the parents or caregivers. Unless the parent or caregiver expresses a preference for MMRV vaccine, CDC recommends that MMR vaccine and varicella vaccine should be administered for the first dose in this age group. For the second dose of measles, mumps, rubella, and varicella vaccines at any age (15 months-12 years) and for the first dose at age >or=48 months, use of MMRV vaccine generally is preferred over separate injections of its equivalent component vaccines (i.e., MMR vaccine and varicella vaccine). This recommendation is consistent with ACIP's 2009 provisional general recommendations regarding use of combination vaccines (available at http://www.cdc.gov/vaccines/recs/provisional/downloads/combo-vax-Aug2009-508.pdf), which state that use of a combination vaccine generally is preferred over its equivalent component vaccines.

Varicella is an illness with a characteristic maculopapular, vesicular rash that, during the prevaccine era, infected almost everyone in the population during childhood. The causative agent is varicella-zoster virus (VZV), an alphaherpesvirus. After the primary varicella infection, VZV establishes latency in sensory ganglia and may reactivate years or decades later to cause herpes zoster (HZ). Most children with varicella recover without sequelae and historically the disease was generally regarded as benign. However, varicella can lead to serious complications and deaths in healthy as well as immunocompromised persons [13]. Additionally, varicella during the first 20 weeks of pregnancy can lead to a collection of severe birth defects and complications for the fetus manifested as congenital varicella syndrome [4].

BACKGROUND: In 2017, the Vietnam Ministry of Health conducted a demonstration project to introduce seasonal influenza vaccination to health care workers. A total of 11,000 doses of influenza vaccine, single-dose prefilled syringes, were provided free to HCWs at 29 selected hospitals, clinics, and research institutes in four provinces: Hanoi, Khanh Hoa, Dak Lak and Ho Chi Minh City. METHODS: Before the campaign, a workshop was organized to discuss an implementation plan including technical requirements, cold chain, uptake reporting, and surveillance for adverse events following immunization. All sites distributed communication materials and encouraged their staff to register for vaccination. Following immunization sessions, sites sent reports on uptake and adverse events following immunization. Left-over vaccine was transferred to other sites to maximize vaccine use. RESULTS: The average uptake was 57% for all health care workers, with 11 sites achieving 90% and above. These 11 sites were small with less than 500 staff, including 5 primary hospitals, 3 preventive medicine units, and 2 referral hospitals. Among the six biggest sites with over 1000 staff, four sites had the lowest uptake (14-47%). Most of the high-uptake sites were from the central to the south; only one site, a referral hospital, was from the north. After redistribution of left-over vaccine, only 130 vaccine doses (1.2%) were not used and destroyed. Based on factors that affected uptake, including registration levels, differing communication strategies, availability of vaccination, and commitment by health facility leaders, we recommended ways to increase health care worker coverage; recommendations to improve reporting adverse events following immunization were also made. CONCLUSIONS: The project demonstrated that it was feasible to conduct influenza vaccination campaigns among health care workers in Vietnam. Improvements in promotion of registration, more intense pre-planning, especially at larger facilities, and wider, more consistent availability of communication materials will result in increased efficiency and coverage in this program's future expansion.

INTRODUCTION: A demonstration project in Vietnam provided 11,000 doses of human seasonal influenza vaccine free of charge to healthcare workers (HCWs) in 4 provinces of Vietnam. Through this project, we conducted an acceptability survey to identify the main reasons that individuals chose to be vaccinated or not to inform and improve future immunization activities. METHODS: We conducted a descriptive cross-sectional survey from May to August 2017 among HCWs at 13 selected health facilities. We employed logistic regression to determine the association between demographic and professional factors, and the decision to receive seasonal influenza vaccine. We performed post-hoc pairwise comparisons among reasons for and against vaccination using Chi square and Fisher's exact tests (for cell sizes <5). RESULTS: A total of 1,450 HCWs participated in the survey, with a higher proportion of females than males (74% versus 26%). The median age of the participating HCWs was 35 years (median range 25.8-44.2). Among those surveyed, 700 (48%) HCWs were vaccinated against seasonal influenza during the first half of 2017. Younger HCWs under 30 and 30-39 years old were less likely to get vaccinated against seasonal influenza than HCWs >/=50 years old (OR = 0.5; 95%CI 0.4-0.8 and OR = 0.6; 95%CI 0.4-0.8 respectively). Nurses and other employees were more likely to get seasonal influenza vaccination than physicians (OR = 1.5; 95%CI 1.0-2.4 and OR = 2.0; 95%CI 1.2-3.2 respectively). The most common reason for accepting vaccination was fear of getting influenza (66%) and the most common reason for not getting vaccinated was concern about vaccine side effects (23%). CONCLUSION: Acceptability of seasonal influenza vaccines in this setting varied among HCWs by age group and job category. Interventions to increase acceptance of vaccine among HCWs in this setting where influenza vaccine is being introduced free for the first time should include targeted risk communication on vaccine safety and efficacy.

National Immunization Technical Advisory Groups (NITAGs) are multidisciplinary national experts who provide independent, evidence-informed vaccine policy recommendations to national health authorities. An essential NITAG function is to ensure that these decisions are grounded in the best available evidence generated through a systematic, transparent process. However, in many low- and middle-income countries (LMICs), experience with this decision making method is limited. The Task Force for Global Health manages the Partnership for Influenza Vaccine Introduction (PIVI) program in collaboration with the Centers for Disease Control and Prevention, Ministries of Health, corporate partners and others. During 2017, PIVI worked with its country partners and the World Health Organization regional and local offices to assess NITAG strengthening needs and to provide technical assistance in 7 LMIC countries (Laos Peoples Democratic Republic, Mongolia, Vietnam, Armenia, Cote d'Ivoire; Moldova and the Republic of Georgia). Our workshops supported general NITAG capacity building and the evidence-based review process using vaccines of interest to the country. For NITAGs reviewing evidence on seasonal influenza, we developed an influenza resource package to support their review and provide country-relevant information in an easy to use format. Of the seven NITAGs trained, six have applied some of the concepts learnt: revision or development of formal transparent, systematic procedures for their operations; preparation of recommendations on seasonal influenza vaccination using quality-assessed data from systematic searches and local data; and have applied the principles learned for making other new vaccine recommendations. Our experience confirms that LMIC NITAGs are considerably under-resourced without adequate technical support or access to global peer-reviewed literature. Ongoing support from NITAG partners must be secured and creative approaches might be needed to help countries achieve the GVAP 2020 target and support development of sustainable vaccine policies and programs.

Clinical Trials Registration: ClinicalTrials.gov [NCT02378753] and Pan African Clinical Trials Registry [PACTR201502001037220].

We think of this Supplement of the Journal of Infectious Diseases as a figurative manual of operations for how to build an airplane while flying it through a storm. The human toll of the Ebola virus disease (Ebola) epidemic of 2014–2016 was worse than that experienced in all previously recognized Ebola epidemics put together. The idea of testing experimental vaccines that were just entering Phase 1 studies in humans felt both essential and incredibly daunting, given the chaos of this epidemic and the setting of an ongoing epidemic where medical management and monitoring capacity were already strained and most commercial air carriers had cancelled routes. Nonetheless, our team of figurative airplane designers built the airplane, flew it, and landed it safely. Our airplane, the Sierra Leone Trial to Introduce a Vaccine Against Ebola (STRIVE) (Figure 1), forged strong partnerships between institutions in Sierra Leone and the broader public health and research community. With the successful collection of safety data on approximately 8000 vaccinated persons, the study findings also bring the world closer to having a safe and effective vaccine for preventing Ebola. (Clinical Trial Registration. ClinicalTrials.gov [NCT02378753] and Pan African Clinical Trials Registry [PACTR201502001037220].)

Clinical Trials Registration: ClinicalTrials.gov [NCT02378753] and Pan African Clinical Trials Registry [PACTR201502001037220].

The Sierra Leone Trial to Introduce a Vaccine against Ebola (STRIVE), a phase 2/3 trial of investigational rVSVG-ZEBOV-GP vaccine, was conducted during an unprecedented Ebola epidemic. More than 8600 eligible healthcare and frontline response workers were individually randomized to immediate (within 7 days) or deferred (within 18-24 weeks) vaccination and followed for 6 months after vaccination for serious adverse events and Ebola virus infection. Key challenges included limited infrastructure to support trial activities, unreliable electricity, and staff with limited clinical trial experience. Study staff made substantial infrastructure investments, including renovation of enrollment sites, laboratories, and government cold chain facilities, and imported equipment to store and transport vaccine at </=-60oC. STRIVE built capacity by providing didactic and practical research training to >350 staff, which was reinforced with daily review and feedback meetings. The operational challenges of safety follow-up were addressed by issuing mobile telephones to participants, making home visits, and establishing a nurse triage hotline. Before the Ebola outbreak, Sierra Leone had limited infrastructure and staff to conduct clinical trials. Without interfering with the outbreak response, STRIVE responded to an urgent need and helped build this capacity. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov [NCT02378753] and Pan African Clinical Trials Registry [PACTR201502001037220].

Clinical Trials Registration: ClinicalTrials.gov [NCT02378753] and Pan African Clinical Trials Registry [PACTR201502001037220].

Clinical Trials Registration: ClinicalTrials.gov [NCT02378753] and Pan African Clinical Trials Registry [PACTR201502001037220].

Clinical Trials Registration: ClinicalTrials.gov [NCT02378753] and Pan African Clinical Trials Registry [PACTR201502001037220].

In October 2014, the College of Medicine and Allied Health Sciences of the University of Sierra Leone, the Sierra Leone Ministry of Health and Sanitation, and CDC joined the global effort to accelerate assessment and availability of candidate Ebola vaccines and began planning for the Sierra Leone Trial to Introduce a Vaccine against Ebola (STRIVE). STRIVE was an individually randomized controlled phase II/III trial to evaluate efficacy, immunogenicity, and safety of the recombinant vesicular stomatitis virus Ebola vaccine (rVSV-ZEBOV). The study population was health care and frontline workers in select chiefdoms of the five most affected districts in Sierra Leone. Participants were randomized to receive a single intramuscular dose of rVSV-ZEBOV at enrollment or to receive a single intramuscular dose 18-24 weeks after enrollment. All participants were followed up monthly until 6 months after vaccination. Two substudies separately assessed detailed reactogenicity over 1 month and immunogenicity over 12 months. During the 5 months before the trial, STRIVE and partners built a research platform in Sierra Leone comprising participant follow-up sites, cold chain, reliable power supply, and vaccination clinics and hired and trained at least 350 national staff. Wide-ranging community outreach, informational sessions, and messaging were conducted before and during the trial to ensure full communication to the population of the study area regarding procedures and current knowledge about the trial vaccine. During April 9-August 15, 2015, STRIVE enrolled 8,673 participants, of whom 453 and 539 were also enrolled in the safety and immunogenicity substudies, respectively. As of April 28, 2016, no Ebola cases and no vaccine-related serious adverse events, which by regulatory definition include death, life-threatening illness, hospitalization or prolongation of hospitalization, or permanent disability, were reported in the study population. Although STRIVE will not produce an estimate of vaccine efficacy because of low case frequency as the epidemic was controlled, data on safety and immunogenicity will support decisions on licensure of rVSV-ZEBOV.The activities summarized in this report would not have been possible without collaboration with many U.S. and international partners (http://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/partners.html).

BACKGROUND: During late summer/fall 2014, pediatric cases of acute flaccid myelitis (AFM) occurred in the U.S., coincident with a national outbreak of enterovirus-D68 (EV-D68)-associated severe respiratory illness. METHODS: Clinicians and health departments reported to Centers for Disease Control and Prevention (CDC) standardized clinical, epidemiologic, and radiologic information on AFM cases, and submitted biological samples for testing. Cases were≤21 years old, with acute onset of limb weakness 01 August-31 December 2014 and spinal MRI showing lesions predominantly restricted to gray matter. RESULTS: From August-December 2014, 120 AFM cases were reported from 34 states. Median age was 7.1 years (interquartile range, 4.8-12.1 years); 59% were male. Most experienced respiratory (81%) or febrile (64%) illness before limb weakness onset. MRI abnormalities were predominantly in the cervical spinal cord (103/118). All but one case was hospitalized; none died. CSF pleocytosis (>5 white blood cells/mm3) was common (81%). At CDC, one CSF specimen was positive for EV-D68 and Epstein-Barr virus by real-time PCR, although the specimen had >3,000 red blood cells/mm3 The most common virus detected in upper respiratory tract specimens was EV-D68 (from 20%, and 47% with specimen collected ≤7 days from respiratory illness/fever onset). Continued surveillance in 2015 identified 14 AFM cases reported from 11 states. CONCLUSIONS: Epidemiologic data suggest this AFM cluster was likely associated with the large outbreak of EV-D68-associated respiratory illness, although direct laboratory evidence linking AFM with EV-D68 remains inconclusive. Continued surveillance will help define the incidence, epidemiology and etiology of AFM.

CONTEXT: Several varicella vaccines are available worldwide. Countries with a varicella vaccination program use 1- or 2-dose schedules. OBJECTIVE: We examined postlicensure estimates of varicella vaccine effectiveness (VE) among healthy children. DATA SOURCES: Systematic review and descriptive and meta-analysis of Medline, Embase, Cochrane libraries, and CINAHL databases for reports published during 1995-2014. STUDY SELECTION: Publications that reported original data on dose-specific varicella VE among immunocompetent children. DATA EXTRACTION: We used random effects meta-analysis models to obtain pooled one dose VE estimates by disease severity (all varicella and moderate/severe varicella). Within each severity category, we assessed pooled VE by vaccine and by study design. We used descriptive statistics to summarize 1-dose VE against severe disease. For 2-dose VE, we calculated pooled estimates against all varicella and by study design. RESULTS: The pooled 1-dose VE was 81% (95% confidence interval [CI]: 78%-84%) against all varicella and 98% (95% CI: 97%-99%) against moderate/severe varicella with no significant association between VE and vaccine type or study design (P > .1). For 1 dose, median VE for prevention of severe disease was 100% (mean = 99.4%). The pooled 2-dose VE against all varicella was 92% (95% CI: 88%-95%), with similar estimates by study design. LIMITATIONS: VE was assessed primarily during outbreak investigations and using clinically diagnosed varicella. CONCLUSIONS: One dose of varicella vaccine was moderately effective in preventing all varicella and highly effective in preventing moderate/severe varicella, with no differences by vaccine. The second dose adds improved protection against all varicella.

In response to severe measles, the first measles vaccine was licensed in the United States in 1963. Widespread use of measles vaccines for more than 50 years has significantly reduced global measles morbidity and mortality. However, measles virus continues to circulate, causing infection, illness, and an estimated 400 deaths worldwide each day. Measles is preventable by vaccine, and humans are the only reservoir. Clinicians should promote and provide on-time vaccination for all patients and keep measles in their differential diagnosis of febrile rash illness for rapid case detection, confirmation of measles infection, isolation, treatment, and appropriate public health response.

Infection with varicella zoster virus (VZV) causes varicella (chickenpox), which can be severe in immunocompromised individuals, infants and adults. Primary infection is followed by latency in ganglionic neurons. During this period, no virus particles are produced and no obvious neuronal damage occurs. Reactivation of the virus leads to virus replication, which causes zoster (shingles) in tissues innervated by the involved neurons, inflammation and cell death - a process that can lead to persistent radicular pain (postherpetic neuralgia). The pathogenesis of postherpetic neuralgia is unknown and it is difficult to treat. Furthermore, other zoster complications can develop, including myelitis, cranial nerve palsies, meningitis, stroke (vasculopathy), retinitis, and gastroenterological infections such as ulcers, pancreatitis and hepatitis. VZV is the only human herpesvirus for which highly effective vaccines are available. After varicella or vaccination, both wild-type and vaccine-type VZV establish latency, and long-term immunity to varicella develops. However, immunity does not protect against reactivation. Thus, two vaccines are used: one to prevent varicella and one to prevent zoster. In this Primer we discuss the pathogenesis, diagnosis, treatment, and prevention of VZV infections, with an emphasis on the molecular events that regulate these diseases. For an illustrated summary of this Primer, visit: http://go.nature.com/14xVI1.

BACKGROUND: Enterovirus D68 (EV-D68) has been infrequently reported historically, and is typically associated with isolated cases or small clusters of respiratory illness. Beginning in August, 2014, increases in severe respiratory illness associated with EV-D68 were reported across the USA. We aimed to describe the clinical, epidemiological, and laboratory features of this outbreak, and to better understand the role of EV-D68 in severe respiratory illness. METHODS: We collected regional syndromic surveillance data for epidemiological weeks 23 to 44, 2014, (June 1 to Nov 1, 2014) and hospital admissions data for epidemiological weeks 27 to 44, 2014, (June 29 to Nov 1, 2014) from three states: Missouri, Illinois and Colorado. Data were also collected for the same time period of 2013 and 2012. Respiratory specimens from severely ill patients nationwide, who were rhinovirus-positive or enterovirus-positive in hospital testing, were submitted between Aug 1, and Oct 31, 2014, and typed by molecular sequencing. We collected basic clinical and epidemiological characteristics of EV-D68 cases with a standard data collection form submitted with each specimen. We compared patients requiring intensive care with those who did not, and patients requiring ventilator support with those who did not. Mantel-Haenszel chi2 tests were used to test for statistical significance. FINDINGS: Regional and hospital-level data from Missouri, Illinois, and Colorado showed increases in respiratory illness between August and September, 2014, compared with in 2013 and 2012. Nationwide, 699 (46%) of 1529 patients tested were confirmed as EV-D68. Among the 614 EV-D68-positive patients admitted to hospital, age ranged from 3 days to 92 years (median 5 years). Common symptoms included dyspnoea (n=513 [84%]), cough (n=500 [81%]), and wheezing (n=427 [70%]); 294 (48%) patients had fever. 338 [59%] of 574 were admitted to intensive care units, and 145 (28%) of 511 received ventilator support; 322 (52%) of 614 had a history of asthma or reactive airway disease; 200 (66%) of 304 patients with a history of asthma or reactive airway disease required intensive care compared with 138 (51%) of 270 with no history of asthma or reactive airway disease (p=0.0004). Similarly, 89 (32%) of 276 patients with a history of asthma or reactive airway disease required ventilator support compared with 56 (24%) of 235 patients with no history of asthma or reactive airway disease (p=0.039). INTERPRETATION: In 2014, EV-D68 caused widespread severe respiratory illness across the USA, disproportionately affecting those with asthma. This unexpected event underscores the need for robust surveillance of enterovirus types, enabling improved understanding of virus circulation and disease burden. FUNDING: None.

OBJECTIVE: We evaluated the extent to which children and adolescents were not vaccinated against measles ("unvaccinated"), clustering within U.S. counties, and factors associated with unvaccination, including parents' vaccine-related beliefs and missed opportunities. METHODS: We analyzed data from the 2010-2013 National Immunization Survey (NIS) and NIS-Teen Survey of households with 19- to 35-month-old children and 13- to 17-year-old adolescents, respectively. We used provider-reported vaccination histories to assess measles vaccination status. RESULTS: In 2013, 7.5% of children and 4.5% of adolescents were unvaccinated against measles. Four-fifths (80.0%) of unvaccinated children lived in counties containing 41.9% of the nation's children, and 80.0% of unvaccinated adolescents lived in counties containing 30.4% of the nation's adolescents. Multivariable statistical analyses found that 74.6% of children who were unvaccinated against measles missed being vaccinated for reasons other than parents' negative vaccine-related beliefs, and 89.6% could be deemed as having at least one missed opportunity for being vaccinated against measles because they were administered at least one dose of other recommended vaccines after 12 months of age. Among adolescents, multivariable analyses found that only demographic factors, not vaccine-related parental beliefs, were independently associated with being unvaccinated. CONCLUSIONS: Reasons other than negative vaccine-related beliefs, including missed opportunities, accounted for the vast majority of unvaccinated children and adolescents.

In the prevaccine era, infection with wild poliovirus (WPV) was common worldwide, with seasonal peaks and epidemics in the summer and fall in temperate areas. The incidence of poliomyelitis in the United States declined rapidly after the licensure of inactivated polio vaccine (IPV) in 1955 and live oral polio vaccine (OPV) in the 1960s. The last cases of indigenously acquired WPV in the United States occurred in 1979, the last WPV case in a U.S. resident traveling abroad occurred in 1986, and the last WPV imported case was in 1993. Since 2000, the United States has exclusively used IPV, resulting in prevention of 8-10 vaccine-associated paralytic poliomyelitis cases annually. In 2005, an unvaccinated U.S. adult traveling abroad acquired vaccine-associated paralytic poliomyelitis after contact with an infant recently vaccinated with OPV.

Measles is a highly contagious, acute viral illness that can lead to serious complications and death. Although measles elimination (i.e., interruption of year-round endemic transmission) was declared in the United States in 2000, importations of measles cases from endemic areas of the world continue to occur, leading to secondary measles cases and outbreaks in the United States, primarily among unvaccinated persons. To update national measles data in the United States, CDC evaluated cases reported by states from January 1 through May 23, 2014. A total of 288 confirmed measles cases have been reported to CDC, surpassing the highest reported yearly total of measles cases since elimination (220 cases reported in 2011). Fifteen outbreaks accounted for 79% of cases reported, including the largest outbreak reported in the United States since elimination (138 cases and ongoing). The large number of cases this year emphasizes the need for health-care providers to have a heightened awareness of the potential for measles in their communities and the importance of vaccination to prevent measles.

IMPORTANCE: To verify the elimination of endemic measles, rubella, and congenital rubella syndrome (CRS) from the Western hemisphere, the Pan American Health Organization requested each member country to compile a national elimination report. The United States documented the elimination of endemic measles in 2000 and of endemic rubella and CRS in 2004. In December 2011, the Centers for Disease Control and Prevention convened an external expert panel to review the evidence and determine whether elimination of endemic measles, rubella, and CRS had been sustained. OBJECTIVE: To review the evidence for sustained elimination of endemic measles, rubella, and CRS from the United States through 2011. DESIGN, SETTING, AND PARTICIPANTS: Review of data for measles from 2001 to 2011 and for rubella and CRS from 2004 to 2011 covering the US resident population and international visitors, including disease epidemiology, importation status of cases, molecular epidemiology, adequacy of surveillance, and population immunity as estimated by national vaccination coverage and serologic surveys. MAIN OUTCOMES AND MEASURES: Annual numbers of measles, rubella, and CRS cases, by importation status, outbreak size, and distribution; proportions of US population seropositive for measles and rubella; and measles-mumps-rubella vaccination coverage levels. RESULTS: Since 2001, US reported measles incidence has remained below 1 case per 1 000 000 population. Since 2004, rubella incidence has been below 1 case per 10 000 000 population, and CRS incidence has been below 1 case per 5 000 000 births. Eighty-eight percent of measles cases and 54% of rubella cases were internationally imported or epidemiologically or virologically linked to importation. The few cases not linked to importation were insufficient to represent endemic transmission. Molecular epidemiology indicated no endemic genotypes. The US surveillance system is adequate to detect endemic measles or rubella. Seroprevalence and vaccination coverage data indicate high levels of population immunity to measles and rubella. CONCLUSIONS AND RELEVANCE: The external expert panel concluded that the elimination of endemic measles, rubella, and CRS from the United States was sustained through 2011. However, international importation continues, and health care providers should suspect measles or rubella in patients with febrile rash illness, especially when associated with international travel or international visitors, and should report suspected cases to the local health department.

Measles transmission has been well documented in healthcare facilities. Healthcare personnel who are unvaccinated and who lack other evidence of measles immunity put themselves and their patients at risk for measles. We conducted a systematic literature review of measles vaccination policies and their implementation in healthcare personnel, measles seroprevalence among healthcare personnel, measles transmission and disease burden in healthcare settings, and impact/costs incurred by healthcare facilities for healthcare-associated measles transmission. Five database searches yielded 135 relevant articles; 47 additional articles were found through cross-referencing. The risk of acquiring measles is estimated to be 2 to 19 times higher for susceptible healthcare personnel than for the general population. Fifty-three articles published worldwide during 1989-2013 reported measles transmission from patients to healthcare personnel; many of the healthcare personnel were unvaccinated or had unknown vaccination status. Eighteen articles published worldwide during 1982-2013 described examples of transmission from healthcare personnel to patients or to other healthcare personnel. Half of European countries have no measles vaccine policies for healthcare personnel. There is no global policy recommendation for the vaccination of healthcare personnel against measles. Even in countries such as the United States or Finland that have national policies, the recommendations are not uniformly implemented in healthcare facilities. Measles serosusceptibility in healthcare personnel varied widely across studies (median 6.5%, range 0-46%) but was consistently higher among younger healthcare personnel. Deficiencies in documentation of two doses of measles vaccination or other evidence of immunity among healthcare personnel presents challenges in responding to measles exposures in healthcare settings. Evaluating and containing exposures and outbreaks in healthcare settings can be disruptive and costly. Establishing policies for measles vaccination for healthcare personnel is an important strategy towards achieving measles elimination and should be a high priority for global policy setting groups, governments, and hospitals.

BACKGROUND: Routine childhood varicella vaccination, implemented in 1995, has resulted in significant declines in varicella-related hospitalizations in the United States. Varicella hospitalization rates among the American Indian and Alaska Native (AI/AN) population have not been previously documented. METHODS: We selected varicella-related hospitalizations, based on a published definition, from the Indian Health Service inpatient database for AI/ANs in the Alaska, Southwest and Northern Plains regions (1995-2010) and from the Nationwide Inpatient Sample for the general US population (2007-2010). We analyzed average annual hospitalization rates pre-vaccine (1995-1998) and post-vaccine (2007-2010) for the AI/AN population, and post-vaccine for the general US population. RESULTS: From 1995-1998 to 2007-2010, the average annual varicella-related hospitalization rate for AI/ANs in the three regions decreased 95% (0.66 to 0.03/10,000 persons); the post-vaccine rate appears lower than the general US rate (0.06, 95% CI 0.05-0.06). The rate declined in all AI/AN pediatric age groups. Infants experienced the highest pre-vaccine (14.07) and post-vaccine (0.83) hospitalization rates. Adults experienced low rates in both time periods. Varicella vaccination rates in 19-35 month old AI/AN children during fiscal years 2008-2010 were 88.1% to 91.0%. CONCLUSIONS: Widespread use of varicella vaccine in AI/AN children was accompanied by substantial declines in varicella-related hospitalizations consistent with high varicella vaccine effectiveness in preventing severe varicella outcomes.

BACKGROUND: Despite high two-dose measles-mumps-rubella (MMR) vaccine coverage, a large mumps outbreak occurred on the U.S. Territory of Guam during 2009-2010, primarily in school-aged children. METHODS: We implemented active surveillance in April 2010 during the outbreak peak and characterized the outbreak epidemiology. We administered third doses of MMR vaccine to eligible students aged 9-14 years in 7 schools with the highest attack rates (ARs) between 5/18/2010-5/21/2010. Baseline surveys, follow-up surveys, and case-reports were used to determine mumps vaccine ARs. Adverse events post-vaccination were monitored. RESULTS: Between 12/1/2009-12/31/2010, 505 mumps cases were reported. Self-reported Pohnpeians and Chuukese had the highest relative risks (54.7 and 19.7, respectively) and highest crowding indices (mean: 3.1 and 3.0 persons/bedroom, respectively). Among 287 (57%) school-aged case-patients, 270 (93%) had ≥2 MMR doses. A third MMR dose was administered to 1068 (33%) eligible students. Three-dose vaccinated students had an AR of 0.9/1000 compared with 2.4/1000 among students vaccinated with ≤2 doses more than1 incubation period pos-intervention, but the difference was not significant (p= 0.67). No serious adverse events were reported. CONCLUSIONS: This mumps outbreak occurred in a highly vaccinated population. The highest ARs occurred in ethnic minority populations with the highest household crowding indices. After the third dose MMR intervention in highly affected schools, three-dose recipients had an AR 60% lower than students with ≤2 doses, but the difference was not statistically significant and the intervention occurred after the outbreak peaked. This outbreak may have persisted due to crowding at home and high student contact rates.

Widespread global vaccination with highly effective measles vaccines, first licensed in 1963, has resulted in a decline in estimated global measles deaths, from 2.6 million in 1980 to 164 000 by 2008 [1, 2], and in measles elimination in many countries [3–6]. The World Health Organization (WHO) Region of the Americas has had no year-round endemic measles circulation since 2002 and may become the first region to achieve measles elimination [7]. Because measles is highly contagious, achieving and maintaining elimination requires extremely high population immunity through high 2-dose vaccine coverage. Measles postelimination epidemiology is characterized by importations and limited outbreaks, primarily in unvaccinated persons, provided population immunity remains high [8]. However, if population immunity declines, as occurred in the United Kingdom, when vaccination coverage declined because parents were deterred from vaccinating by misinformation about the safety of the measles, mumps, and rubella vaccine, endemic measles transmission can be rapidly reestablished, bringing with it preventable complications and deaths [9].

OBJECTIVE: To describe varicella disease in infants since implementation of the varicella vaccination program in the United States. PATIENTS AND METHODS: From 1995 to 2008, demographic, clinical, and epidemiologic data on cases of varicella in infants were collected prospectively through a community-based active surveillance project. We examined disease patterns for infants in 2 age groups: 0 to 5 and 6 to 11 months. RESULTS: Infant varicella disease incidence declined 89.7% from 1995 to 2008. Infants aged 0 to 5 months had milder clinical disease than those aged 6 to 11 months: ≥50 lesions, 49% vs 58% (P = .038); fever (body temperature > 38 degrees C), 12% vs 21% (P = .014); and varicella-related complications, 6% vs 14% (P = .009), respectively. Age was an independent predictor of the occurrence of complications. CONCLUSIONS: The varicella vaccination program has resulted in substantial indirect benefits for infants, who are not eligible for vaccination. Presence of maternal varicella-zoster virus antibodies might explain attenuated disease in very young infants likely born to mothers with history of varicella. Although varicella disease incidence has declined, exposure to varicella-zoster virus continues to occur. Improving varicella vaccination coverage in all age groups will further reduce the risk of varicella exposure and protect those not eligible for varicella vaccination.

OBJECTIVE: Varicella has been preventable by vaccination in the United States since 1995. Previous studies reported a 66% decline in mortality rate during the first 6 years of the program. Since then, vaccination coverage has increased substantially. We updated the analysis of US varicella mortality for 2002-2007 and assessed the impact of the first 12 years of the US varicella vaccination program on varicella deaths. METHODS: National data on deaths for which varicella was listed as an underlying or contributing cause were obtained from the Mortality Multiple Cause-of-Death records from the US National Center for Health Statistics. We calculated the age-adjusted and age-specific mortality rates for 2002-2007 and trends since the prevaccine years. RESULTS: During the 12 years of the mostly 1-dose US varicella vaccination program, the annual average mortality rate for varicella listed as the underlying cause declined 88%, from 0.41 per million population in 1990-1994 to 0.05 per million population in 2005-2007. The decline occurred in all age groups, and there was an extremely high reduction among children and adolescents younger than 20 years (97%) and among subjects younger than 50 years overall (96%). In the last 6 years analyzed (2002-2007), a total of 3 deaths per age range were reported among children aged 1 to 4 and 5 to 9 years, compared with an annual average of 13 and 16 deaths, respectively, during the prevaccine years. CONCLUSIONS: The impressive decline in varicella deaths can be directly attributed to successful implementation of the 1-dose vaccination program. With the current 2-dose program, there is potential that these most severe outcomes of a vaccine-preventable disease could be eliminated.

BACKGROUND: On 12 February 2008, an infected Swiss traveler visited hospital A in Tucson, Arizona, and initiated a predominantly health care-associated measles outbreak involving 14 cases. We investigated risk factors that might have contributed to health care-associated transmission and assessed outbreak-associated hospital costs. METHODS: Epidemiologic data were obtained by case interviews and review of medical records. Health care personnel (HCP) immunization records were reviewed to identify non-measles-immune HCP. Outbreak-associated costs were estimated from 2 hospitals. RESULTS: Of 14 patients with confirmed cases, 7 (50%) were aged ≥18 years, 4 (29%) were hospitalized, 7 (50%) acquired measles in health care settings, and all (100%) were unvaccinated or had unknown vaccination status. Of the 11 patients (79%) who had accessed health care services while infectious, 1 (9%) was masked and isolated promptly after rash onset. HCP measles immunity data from 2 hospitals confirmed that 1776 (25%) of 7195 HCP lacked evidence of measles immunity. Among these HCPs, 139 (9%) of 1583 tested seronegative for measles immunoglobulin G, including 1 person who acquired measles. The 2 hospitals spent US$799,136 responding to and containing 7 cases in these facilities. CONCLUSIONS: Suspecting measles as a diagnosis, instituting immediate airborne isolation, and ensuring rapidly retrievable measles immunity records for HCPs are paramount in preventing health care-associated spread and in minimizing hospital outbreak-response costs. (See the editorial commentary by Ostroff, on pages 1507-9.)