A case study of an influenza vaccination program for health care workers in Vietnam.

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.

Acceptability of seasonal influenza vaccines among health care workers in Vietnam in 2017.

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.

Supporting national immunization technical advisory groups (NITAGs) in resource-constrained settings. New strategies and lessons learned from the Task Force for Global Health's Partnership for influenza vaccine introduction.

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, Côte 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.

Rapid Establishment of a Cold Chain Capacity of -60°C or Colder for the STRIVE Ebola Vaccine Trial During the Ebola Outbreak in Sierra Leone.

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

Health Conditions in an Adult Population in Sierra Leone: Data Reported From the Sierra Leone Trial to Introduce a Vaccine Against Ebola (STRIVE).

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

Implementing a Multisite Clinical Trial in the Midst of an Ebola Outbreak: Lessons Learned From the Sierra Leone Trial to Introduce a Vaccine Against Ebola.

The Sierra Leone Trial to Introduce a Vaccine against Ebola (STRIVE), a phase 2/3 trial of investigational rVSV∆G-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].

The Sierra Leone Trial to Introduce a Vaccine Against Ebola: An Evaluation of rVSV∆G-ZEBOV-GP Vaccine Tolerability and Safety During the West Africa Ebola Outbreak.

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

Clinical Surveillance and Evaluation of Suspected Ebola Cases in a Vaccine Trial During an Ebola Epidemic: The Sierra Leone Trial to Introduce a Vaccine Against Ebola.

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

Monitoring Serious Adverse Events in the Sierra Leone Trial to Introduce a Vaccine Against Ebola.

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

Implementing an Ebola Vaccine Study - Sierra Leone.

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).

Acute Flaccid Myelitis in the United States, August-December 2014: Results of Nationwide Surveillance.

BACKGROUND: During late summer/fall 2014, pediatric cases of acute flaccid myelitis (AFM) occurred in the United States, coincident with a national outbreak of enterovirus D68 (EV-D68)-associated severe respiratory illness. METHODS: Clinicians and health departments reported standardized clinical, epidemiologic, and radiologic information on AFM cases to the Centers for Disease Control and Prevention (CDC), and submitted biological samples for testing. Cases were ≤21 years old, with acute onset of limb weakness 1 August-31 December 2014 and spinal magnetic resonance imaging (MRI) showing lesions predominantly restricted to gray matter. RESULTS: From August through 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 1 case was hospitalized; none died. Cerebrospinal fluid (CSF) pleocytosis (>5 white blood cells/µL) was common (81%). At CDC, 1 CSF specimen was positive for EV-D68 and Epstein-Barr virus by real-time polymerase chain reaction, although the specimen had >3000 red blood cells/µL. 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 16 AFM cases reported from 13 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.

Global Varicella Vaccine Effectiveness: A Meta-analysis.

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.

Measles 50 Years After Use of Measles Vaccine.

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.

Severe respiratory illness associated with a nationwide outbreak of enterovirus D68 in the USA (2014): a descriptive epidemiological investigation.

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 χ(2) 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.

Children and Adolescents Unvaccinated Against Measles: Geographic Clustering, Parents' Beliefs, and Missed Opportunities.

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.

Varicella zoster virus infection.

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.

Interim CDC guidance for polio vaccination for travel to and from countries affected by wild poliovirus.

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 - United States, January 1-May 23, 2014.

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.