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.

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].

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].

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].

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].

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.

Measles Outbreak Associated with Vaccine Failure in Adults--Federated States of Micronesia, February-August 2014.

On May 15, 2014, CDC was notified of two laboratory-confirmed measles cases in the Federated States of Micronesia (FSM), after 20 years with no reported measles. FSM was assisted by the World Health Organization (WHO), the United Nations Children's Fund (UNICEF), and CDC in investigating suspected cases, identify contacts, conduct analyses to guide outbreak vaccination response, and review vaccine cold chain practices. During February­August, three of FSM's four states reported measles cases: Kosrae (139 cases), Pohnpei (251), and Chuuk (3). Two thirds of cases occurred among adults aged ≥20 years; of these, 49% had received ≥2 doses of measles-containing vaccine (MCV). Apart from infants aged <12 months who were too young for routine vaccination, measles incidence was lower among children than adults. A review of current cold chain practices in Kosrae revealed minor weaknesses; however, an absence of historical cold chain maintenance records precluded an evaluation of earlier problems. Each state implemented vaccination campaigns targeting children as young as age 6 months through adults up to age 57 years. The preponderance of cases in this outbreak associated with vaccine failure in adults highlights the need for both thorough case investigation and epidemiologic analysis to guide outbreak response vaccination. Routine childhood vaccination coverage achieved in recent years limited the transmission of measles among children. Even in areas where transmission has not occurred for years, maintaining high 2-dose MCV coverage through routine and supplemental immunization is needed to prevent outbreaks resulting from increased measles susceptibility in the population.

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.

Acute neurologic illness of unknown etiology in children - Colorado, August-September 2014.

On September 12, 2014, CDC was notified by the Colorado Department of Public Health and Environment of a cluster of nine children evaluated at Children's Hospital Colorado with acute neurologic illness characterized by extremity weakness, cranial nerve dysfunction (e.g., diplopia, facial droop, dysphagia, or dysarthria), or both. Neurologic illness onsets occurred during August 8-September 15, 2014. The median age of the children was 8 years (range = 1-18 years). Other than neck, back, or extremity pain in some patients, all had normal sensation. All had a preceding febrile illness, most with upper respiratory symptoms, occurring 3-16 days (median = 7 days) before onset of neurologic illness. Seven of eight patients with magnetic resonance imaging of the spinal cord had nonenhancing lesions of the gray matter of the spinal cord spanning multiple levels, and seven of nine with magnetic resonance imaging of the brain had nonenhancing brainstem lesions (most commonly the dorsal pons). Two of five with magnetic resonance imaging of the lumbosacral region had gadolinium enhancement of the ventral nerve roots of the cauda equina. Eight children were up to date on polio vaccination. Eight have not yet fully recovered neurologically.

Health care-associated measles outbreak in the United States after an importation: challenges and economic impact.

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.

Recent resurgence of mumps in the United States.

BACKGROUND: The widespread use of a second dose of mumps vaccine among U.S. schoolchildren beginning in 1990 was followed by historically low reports of mumps cases. A 2010 elimination goal was established, but in 2006 the largest mumps outbreak in two decades occurred in the United States. METHODS: We examined national data on mumps cases reported during 2006, detailed case data from the most highly affected states, and vaccination-coverage data from three nationwide surveys. RESULTS: A total of 6584 cases of mumps were reported in 2006, with 76% occurring between March and May. There were 85 hospitalizations, but no deaths were reported; 85% of patients lived in eight contiguous midwestern states. The national incidence of mumps was 2.2 per 100,000, with the highest incidence among persons 18 to 24 years of age (an incidence 3.7 times that of all other age groups combined). In a subgroup analysis, 83% of these patients reported current college attendance. Among patients in eight highly affected states with known vaccination status, 63% overall and 84% between the ages of 18 and 24 years had received two doses of mumps vaccine. For the 12 years preceding the outbreak, national coverage of one-dose mumps vaccination among preschoolers was 89% or more nationwide and 86% or more in highly affected states. In 2006, the national two-dose coverage among adolescents was 87%, the highest in U.S. history. CONCLUSIONS: Despite a high coverage rate with two doses of mumps-containing vaccine, a large mumps outbreak occurred, characterized by two-dose vaccine failure, particularly among midwestern college-age adults who probably received the second dose as schoolchildren. A more effective mumps vaccine or changes in vaccine policy may be needed to avert future outbreaks and achieve the elimination of mumps.

Use of combination measles, mumps, rubella, and varicella vaccine: recommendations of the Advisory Committee on Immunization Practices (ACIP).

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.

Measles in the United States during the postelimination era.

BACKGROUND: Measles affected entire birth cohorts in the prevaccine era but was declared eliminated in the United States in 2000 because of a successful measles vaccination program. METHODS: We reviewed US surveillance data on confirmed measles cases reported to the Centers for Disease Control and Prevention and data on national measles-mumps-rubella (MMR) vaccination coverage during postelimination years 2001-2008. RESULTS: During 2001-2008, a total of 557 confirmed cases of measles (annual median no. of cases, 56) and 38 outbreaks (annual median no. of outbreaks, 4) were reported in the United States; 232 (42%) of the cases were imported from 44 countries, including European countries. Among case-patients who were US residents, the highest incidences of measles were among infants 6-11 months of age and children 12-15 months of age (3.5 and 2.6 cases/1 million person-years, respectively). From 2001 through 2008, national 1-dose MMR vaccine coverage among children 19-35 months of age ranged from 91% to 93%. From 2001 through 2008, a total of 285 US-resident case-patients (65%) were considered to have preventable measles (ie, the patients were eligible for vaccination but unvaccinated). During 2004-2008, a total of 68% of vaccine-eligible US-resident case-patients claimed exemptions for personal beliefs. CONCLUSIONS: The United States maintained measles elimination from 2001 through 2008 because of sustained high vaccination coverage. Challenges to maintaining elimination include large outbreaks of measles in highly traveled developed countries, frequent international travel, and clusters of US residents who remain unvaccinated because of personal belief exemptions.

Guidance for isolation precautions for mumps in the United States: a review of the scientific basis for policy change.

The 2006 mumps resurgence in the United States raised questions about the appropriate isolation period for people with mumps. To determine the scientific basis for isolation recommendations, we conducted a literature review and considered isolation of virus and virus load in saliva and respiratory secretions as factors that were related to mumps transmission risk. Although mumps virus has been isolated from 7 days before through 8 days after parotitis onset, the highest percentage of positive isolations and the highest virus loads occur closest to parotitis onset and decrease rapidly thereafter. Most transmission likely occurs before and within 5 days of parotitis onset. Transmission can occur during the prodromal phase and with subclinical infections. Updated guidance, released in 2007-2008, changed the mumps isolation period from 9 to 5 days. It is now recommended that mumps patients be isolated and standard and droplet precautions be followed for 5 days after parotitis onset.

Loss of vaccine-induced immunity to varicella over time.

BACKGROUND: The introduction of universal varicella vaccination in 1995 has substantially reduced varicella-related morbidity and mortality in the United States. However, it remains unclear whether vaccine-induced immunity wanes over time, a condition that may result in increased susceptibility later in life, when the risk of serious complications may be greater than in childhood. METHODS: We examined 10 years (1995 to 2004) of active surveillance data from a sentinel population of 350,000 subjects to determine whether the severity and incidence of breakthrough varicella (with an onset of rash >42 days after vaccination) increased with the time since vaccination. We used multivariate logistic regression to adjust for the year of disease onset (calendar year) and the subject's age at both disease onset and vaccination. RESULTS: A total of 11,356 subjects were reported to have varicella during the surveillance period, of whom 1080 (9.5%) had breakthrough disease. Children between the ages of 8 and 12 years who had been vaccinated at least 5 years previously were significantly more likely to have moderate or severe disease than were those who had been vaccinated less than 5 years previously (risk ratio, 2.6; 95% confidence interval [CI], 1.2 to 5.8). The annual rate of breakthrough varicella significantly increased with the time since vaccination, from 1.6 cases per 1000 person-years (95% CI, 1.2 to 2.0) within 1 year after vaccination to 9.0 per 1000 person-years (95% CI, 6.9 to 11.7) at 5 years and 58.2 per 1000 person-years (95% CI, 36.0 to 94.0) at 9 years. CONCLUSIONS: A second dose of varicella vaccine, now recommended for all children, could improve protection from both primary vaccine failure and waning vaccine-induced immunity.