The Global Vaccine Action Plan - insights into its utility, application, and ways to strengthen future plans.

BACKGROUND: The pace of global progress must increase if the Global Vaccine Action Plan (GVAP) goals are to be achieved by 2020. We administered a two-phase survey to key immunization stakeholders to assess the utility and application of GVAP, including how it has impacted country immunization programs, and to find ways to strengthen the next 10-year plan. METHODS: For the Phase I survey, an online questionnaire was sent to global immunization stakeholders in summer 2017. The Phase II survey was sent to regional and national immunization stakeholders in summer 2018, including WHO Regional Advisors on Immunization, Expanded Programme on Immunization managers, and WHO and UNICEF country representatives from 20 countries. Countries were selected based on improvements (10) versus decreases (10) in DTP3 coverage from 2010 to 2016. RESULTS: Global immunization stakeholders (n = 38) cite global progress in improving vaccine delivery (88%) and engaging civil society organizations as advocates for vaccines (83%). Among regional and national immunization stakeholders (n = 58), 70% indicated reaching mobile and underserved populations with vaccination activities as a major challenge. The top ranked activities for helping country programs achieve progress toward GVAP goals include improved monitoring of vaccination coverage and upgrading disease surveillance systems. Most respondents (96%) indicated GVAP as useful for determining immunization priorities and 95% were supportive of a post-2020 GVAP strategy. CONCLUSIONS: Immunization stakeholders see GVAP as a useful tool, and there is cause for excitement as the global immunization community looks toward the next decade of vaccines. The next 10-year plan should attempt to increase political will, align immunization activities with other health system agendas, and address important issues like reaching mobile/migrant populations and improving data reporting systems.

Hepatitis B Surface Antigen Seroprevalence among Prevaccine and Vaccine Era Children in Bangladesh.

Bangladesh introduced hepatitis B vaccine in a phased manner during 2003-2005 into the routine childhood vaccination schedule. This study was designed to evaluate the impact of the introduction of hepatitis B vaccine in Bangladesh by comparing hepatitis B surface antigen (HBsAg) prevalence among children born before and after vaccine introduction and to estimate the risk of vertical transmission of chronic hepatitis B virus (HBV) infection from mother to infant. We also evaluated the field sensitivity and specificity of an HBsAg point-of-care test strip. We selected a nationally representative sample of 2,100 prevaccine era and 2,100 vaccine era children. We collected a 5-mL blood sample from each child. One drop of blood was used to perform rapid HBsAg testing. If a child had a positive HBsAg test result with the rapid test, a blood sample was collected from the mother of the HBsAg-positive child and from the mothers of two subsequently enrolled HBsAg-negative children. All samples were tested for serologic markers of HBV infection using standard enzyme-linked immunosorbent assay. One (0.05%) child in the vaccine era group and 27 (1.2%; 95% confidence interval [CI]: 0.8-1.7%) children in the prevaccine era group were HBsAg positive. Mothers of HBsAg-positive children were more likely to be HBsAg positive than mothers of HBsAg-negative children (odds ratios = 4.7; 95% CI: 1.0-21.7%). Sensitivity of the HBsAg rapid test was 91.2% (95% CI: 76.6-98.1%) and specificity was 100% (95% CI: 99.9-100%). The study results suggest that even without a birth dose, the hepatitis B vaccine program in Bangladesh was highly effective in preventing chronic HBV infection among children.

Possible eradication of wild poliovirus type 3--worldwide, 2012.

In 1988, the World Health Assembly resolved to eradicate polio worldwide. Since then, four of the six World Health Organization (WHO) regions have been certified as polio-free: the Americas in 1994, the Western Pacific Region in 2000, the European Region in 2002, and the South-East Asia Region in 2014. Currently, nearly 80% of the world's population lives in areas certified as polio-free. Certification may be considered when ≥3 years have passed since the last isolation of wild poliovirus (WPV) in the presence of sensitive, certification-standard surveillance. Although regional eradication has been validated in the European Region and the Western Pacific Region, outbreaks resulting from WPV type 1 (WPV1) imported from known endemic areas were detected and controlled in these regions in 2010 and 2011, respectively. The last reported case associated with WPV type 2 (WPV2) was in India in 1999, marking global interruption of WPV2 transmission. The completion of polio eradication was declared a programmatic emergency for public health in 2012, and the international spread of WPV1 was declared a public health emergency of international concern in May 2014. The efforts needed to interrupt all indigenous WPV1 transmission are now being focused on the remaining endemic countries: Nigeria, Afghanistan, and Pakistan. WPV type 3 (WPV3) has not been detected in circulation since November 11, 2012. This report summarizes the evidence of possible global interruption of transmission of WPV3, based on surveillance for acute flaccid paralysis (AFP) and environmental surveillance.

Recommendations for identification and public health management of persons with chronic hepatitis B virus infection.

Early identification of persons with chronic HBV infection enables infected persons to receive necessary care to prevent or delay onset of liver disease, and enables the identification and vaccination of susceptible household contacts and sex partners, interrupting ongoing transmission. Testing has been recommended previously to enable primary prevention of HBV infection among close contacts for pregnant women, household contacts and sex partners of HBV-infected persons, persons born in countries with hepatitis B surface antigen (HBsAg) prevalence of more than 8%, persons who are the source of blood or body fluid exposures that might warrant postexposure prophylaxis (e.g., needlestick injury to a healthcare worker or sexual assault), and to enable appropriate treatment for infants born to HBsAg-positive mothers and persons infected with human immunodeficiency virus. Recently, with the increasing availability of efficacious hepatitis B treatment, the Centers for Disease Control and Prevention published new recommendations for public health evaluation and management for chronically infected persons and their contacts and extended testing recommendations to include persons born in geographic regions with HBsAg prevalence of greater than 2%, men who have sex with men, and injection drug users. Patient and provider education, developing partnerships between health departments and community organizations, and other resources will be needed to assure appropriate populations are tested and care provided for persons newly identified as HBsAg-positive.

Recommendations for identification and public health management of persons with chronic hepatitis B virus infection.

Serologic testing for hepatitis B surface antigen (HBsAg) is the primary way to identify persons with chronic hepatitis B virus (HBV) infection. Testing has been recommended previously for pregnant women, infants born to HBsAg-positive mothers, household contacts and sex partners of HBV-infected persons, persons born in countries with HBsAg prevalence of >/=8%, persons who are the source of blood or body fluid exposures that might warrant postexposure prophylaxis (e.g., needlestick injury to a health-care worker or sexual assault), and persons infected with human immunodeficiency virus. This report updates and expands previous CDC guidelines for HBsAg testing and includes new recommendations for public health evaluation and management for chronically infected persons and their contacts. Routine testing for HBsAg now is recommended for additional populations with HBsAg prevalence of >/=2%: persons born in geographic regions with HBsAg prevalence of >/=2%, men who have sex with men, and injection-drug users. Implementation of these recommendations will require expertise and resources to integrate HBsAg screening in prevention and care settings serving populations recommended for HBsAg testing. This report is intended to serve as a resource for public health officials, organizations, and health-care professionals involved in the development, delivery, and evaluation of prevention and clinical services.

Ischemic cardiac events during the Department of Health and Human Services Smallpox Vaccination Program, 2003.

Ten ischemic cardiac events (ICEs) were reported among 37,901 initial US Department of Health and Human Services (DHHS) smallpox vaccinees. Symptoms developed a median of 10 days after vaccination (range, 0-28 days). The median age of case patients was 56 years (range, 42-65 years), and 60% were male. Seven (70%) of the case patients had >/=3 cardiac risk factors or probable coronary artery disease before vaccination. Two women, 55 and 57 years of age, experienced acute myocardial infarction and fatal cardiac arrests. Background rates of ICEs during a 3-week period for civilian populations that were age and sex matched to DHHS vaccinees were estimated. The observed number of myocardial infarctions exceeded estimated expectations (5 vs. 2) but remained within the 95% predictive interval (PI) (0.6-5.4). New onset angina was observed significantly less frequently than estimated expectations (1 vs. 10; 95% PI, 3.5-15.7). After persons with >/=3 cardiac risk factors or known heart disease were deferred from vaccination, no ICEs were reported among an additional 6638 vaccinees.

A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP) Part II: immunization of adults.

Hepatitis B vaccination is the most effective measure to prevent hepatitis B virus (HBV) infection and its consequences, including cirrhosis of the liver, liver cancer, liver failure, and death. In adults, ongoing HBV transmission occurs primarily among unvaccinated persons with behavioral risks for HBV transmission (e.g., heterosexuals with multiple sex partners, injection-drug users [IDUs], and men who have sex with men [MSM]) and among household contacts and sex partners of persons with chronic HBV infection. This report, the second of a two-part statement from the Advisory Committee on Immunization Practices (ACIP), provides updated recommendations to increase hepatitis B vaccination of adults at risk for HBV infection. The first part of the ACIP statement, which provided recommendations for immunization of infants, children, and adolescents, was published previously (CDC. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices [ACIP]. Part 1: immunization of infants, children, and adolescents. MMWR 2005;54[No. RR-16]:1-33). In settings in which a high proportion of adults have risks for HBV infection (e.g., sexually transmitted disease/human immunodeficiency virus testing and treatment facilities, drug-abuse treatment and prevention settings, health-care settings targeting services to IDUs, health-care settings targeting services to MSM, and correctional facilities), ACIP recommends universal hepatitis B vaccination for all unvaccinated adults. In other primary care and specialty medical settings in which adults at risk for HBV infection receive care, health-care providers should inform all patients about the health benefits of vaccination, including risks for HBV infection and persons for whom vaccination is recommended, and vaccinate adults who report risks for HBV infection and any adults requesting protection from HBV infection. To promote vaccination in all settings, health-care providers should implement standing orders to identify adults recommended for hepatitis B vaccination and administer vaccination as part of routine clinical services, not require acknowledgment of an HBV infection risk factor for adults to receive vaccine, and use available reimbursement mechanisms to remove financial barriers to hepatitis B vaccination.

Adverse events associated with smallpox vaccination in the United States, January-October 2003.

CONTEXT: On January 24, 2003, the US Department of Health and Human Services (DHHS) implemented a preparedness program in which smallpox (vaccinia) vaccine was administered to federal, state, and local volunteers who might be first responders during a bioterrorism event. OBJECTIVE: To describe results from the comprehensive DHHS smallpox vaccine safety monitoring and response system. DESIGN, SETTING, AND PARTICIPANTS: Descriptive study of adverse event reports from the DHHS smallpox vaccine safety monitoring and response system received between January 24 and October 31, 2003, through the Vaccine Adverse Event Reporting System (VAERS) and the Centers for Disease Control and Prevention. A total of 37,901 volunteers in 55 jurisdictions received at least 1 dose of smallpox vaccine. MAIN OUTCOME MEASURES: Number of vaccinations administered and description of adverse events and reporting rates. RESULTS: A total of 38,885 smallpox vaccinations were administered, with a take rate of 92%. VAERS received 822 reports of adverse events following smallpox vaccination (overall reporting rate, 217 per 10,000 vaccinees). A total of 590 adverse events (72%) were reported within 14 days of vaccination. Nonserious adverse events (n = 722) included multiple signs and symptoms of mild and self-limited local reactions. One hundred adverse events (12%) were designated as serious, resulting in 85 hospitalizations, 2 permanent disabilities, 10 life-threatening illnesses, and 3 deaths. Among the serious adverse events, 21 cases were classified as myocarditis and/or pericarditis and 10 as ischemic cardiac events that were not anticipated based on historical data. Two cases of generalized vaccinia and 1 case of postvaccinial encephalitis were detected. No preventable life-threatening adverse reactions, contact transmissions, or adverse reactions that required treatment with vaccinia immune globulin were identified. Serious adverse events were more common among older revaccinees than younger first-time vaccinees. CONCLUSIONS: Rigorous smallpox vaccine safety screening, educational programs, and older vaccinees may have contributed to low rates of preventable life-threatening adverse reactions. Other rare, clinically significant, or unexpected cardiac adverse events were detected by timely review of VAERS data and intensive clinical case investigation.

A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP) part 1: immunization of infants, children, and adolescents.

This report is the first of a two-part statement from the Advisory Committee on Immunization Practices (ACIP) that updates the strategy to eliminate hepatitis B virus (HBV) transmission in the United States. The report provides updated recommendations to improve prevention of perinatal and early childhood HBV transmission, including implementation of universal infant vaccination beginning at birth, and to increase vaccine coverage among previously unvaccinated children and adolescents. Strategies to enhance implementation of the recommendations include 1) establishing standing orders for administration of hepatitis B vaccination beginning at birth; 2) instituting delivery hospital policies and procedures and case management programs to improve identification of and administration of immunoprophylaxis to infants born to mothers who are hepatitis B surface antigen (HBsAg) positive and to mothers with unknown HBsAg status at the time of delivery; and 3) implementing vaccination record reviews for all children aged 11-12 years and children and adolescents aged <19 years who were born in countries with intermediate and high levels of HBV endemicity, adopting hepatitis B vaccine requirements for school entry, and integrating hepatitis B vaccination services into settings that serve adolescents. The second part of the ACIP statement, which will include updated recommendations and strategies to increase hepatitis B vaccination of adults, will be published separately.

Risk factors for perinatal transmission of hepatitis C virus (HCV) and the natural history of HCV infection acquired in infancy.

BACKGROUND: The goal of the present study was to assess risk factors for perinatal hepatitis C virus (HCV) transmission and the natural history of infection among HCV-infected infants. METHODS: In a cohort study, 244 infants born to HCV-positive mothers were followed from birth until age > or =12 months. Maternal serum was collected at enrollment and delivery; infant serum was collected at birth and at 8 well-child visits. Testing included detection of antibody to HCV, detection of HCV RNA (qualitative and quantitative), and genotyping. HCV-infected infants were followed annually until age 5 years. RESULTS: Overall, 9 of 190 (4.7% [95% confidence interval (CI), 2.3%-9.1%]) infants born to mothers who were HCV RNA positive at delivery became infected, compared with 0 of 54 infants born to HCV RNA-negative mothers (P=.10). Among HCV RNA-positive mothers, the rate of transmission was 3.8% (95% CI, 1.7%-8.1%) from the 182 who were human immunodeficiency virus (HIV) negative, compared with 25.0% (95% CI, 4.5%-64.4%) from the 8 who were HIV positive (P<.05). Three infected infants resolved their infection (i.e., became HCV RNA negative). In multivariate analysis restricted to HCV RNA-positive mothers, membrane rupture > or =6 h (odds ratio [OR], 9.3 [95% CI, 1.5-179.7]) and internal fetal monitoring (OR, 6.7 [95% CI, 1.1-35.9]) were associated with transmission of HCV to infants. CONCLUSION: If duration of membrane rupture and internal fetal monitoring are confirmed to be associated with transmission, interventions may be possible to decrease the risk of transmission.

A mathematical model to estimate global hepatitis B disease burden and vaccination impact.

BACKGROUND: Limited data are available regarding global hepatitis B virus (HBV)-related morbidity and mortality and potential reduction in disease burden from hepatitis B vaccination. METHODS: A model was developed to calculate the age-specific risk of acquiring HBV infection, acute hepatitis B (illness and death), and progression to chronic HBV infection. HBV-related deaths among chronically infected persons were determined from HBV-related cirrhosis and hepatocellular carcinoma (HCC) mortality curves, adjusted for background mortality. The effect of hepatitis B vaccination was calculated from vaccine efficacy and vaccination series coverage, with and without administration of the first dose of vaccine within 24 h of birth (i.e. birth dose) to prevent perinatal HBV infection. RESULTS: For the year 2000, the model estimated 620,000 persons died worldwide from HBV-related causes: 580,000 (94%) from chronic infection-related cirrhosis and HCC and 40,000 (6%) from acute hepatitis B. In the surviving birth cohort for the year 2000, the model estimated that without vaccination, 64.8 million would become HBV-infected and 1.4 million would die from HBV-related disease. Infections acquired during the perinatal period, in early childhood (<5 years old), and > or = 5 years of age accounted for 21, 48, and 31% of deaths, respectively. Routine infant hepatitis B vaccination, with 90% coverage and the first dose administered at birth would prevent 84% of global HBV-related deaths. CONCLUSION: Globally, most HBV-related deaths result from the chronic sequelae of infection acquired in the perinatal and early childhood periods. Inclusion of hepatitis B vaccine into national infant immunization programs could prevent >80% of HBV-related deaths.

Mother-to-infant hepatitis C virus transmission and breastfeeding.

Hepatitis C virus (HCV) is a blood-borne virus that is transmitted most efficiently by irect percutaneous exposures to blood. Infants are at risk of HCV infection primarily as a result of transmission from their infected mothers. However, there is no evidence of mother-to-infant transmission from breastfeeding. According to guidelines from the Centers for Disease Control and Prevention and the American Academy of Pediatrics, maternal HCV infection is not a contraindication to breastfeeding. It may be prudent for mothers who are HCV-infected and who choose to breastfeed to consider abstaining from breastfeeding if their nipples are cracked and bleeding.

Injection practices in Romania: progress and challenges.

OBJECTIVE: To identify breaks in infection control practices that might put Romanians at risk for transmission of hepatitis B virus (HBV) from injections. METHODS: A standardized questionnaire was administered to a systematic sample of the 1,906 nurses in Vâlcea District, Romania, to collect information on their knowledge, attitudes, and practices regarding injection administration and universal precautions. RESULTS: Of the 180 nurses interviewed, 91% (95% confidence interval [CI95], 86% to 95%) reported having attended training for universal precautions; 58% (CI95, 49% to 67%) accurately reported that HBV remains infectious for at least 1 week in the environment; and 4% (CI95, 2% to 8%) knew that HBV is transmitted more efficiently than HIV through percutaneous exposures. No nurses reported reusing syringes or needles on different patients, but 4 (2%; CI, 1% to 6%) would reuse a syringe and 3 (2%; CI95, 0% to 5%) would reuse a needle on the same patient in an emergency. Fifty-three percent (CI95, 44% to 61%) of nurses reported having a dedicated area for the preparation of injectable medications separate from where blood-contaminated items were handled. Shortages of infection control supplies were common. CONCLUSIONS: Although nurses in Vâlcea do not report reusing injection equipment without sterilization, other unsafe practices occur that may facilitate HBV transmission through injections, including preparing injectable medications in areas potentially contaminated with blood. Inadequate knowledge of blood-borne pathogen transmission and shortages of infection control supplies may contribute to these unsafe practices. Addressing these deficits could improve injection safety in Romania.

Bioterrorism-related inhalational anthrax in an elderly woman, Connecticut, 2001.

On November 20, 2001, inhalational anthrax was confirmed in an elderly woman from rural Connecticut. To determine her exposure source, we conducted an extensive epidemiologic, environmental, and laboratory investigation. Molecular subtyping showed that her isolate was indistinguishable from isolates associated with intentionally contaminated letters. No samples from her home or community yielded Bacillus anthracis, and she received no first-class letters from facilities known to have processed intentionally contaminated letters. Environmental sampling in the regional Connecticut postal facility yielded B. anthracis spores from 4 (31%) of 13 sorting machines. One extensively contaminated machine primarily processes bulk mail. A second machine that does final sorting of bulk mail for her zip code yielded B. anthracis on the column of bins for her carrier route. The evidence suggests she was exposed through a cross-contaminated bulk mail letter. Such cross-contamination of letters and postal facilities has implications for managing the response to future B. anthracis-contaminated mailings.

Bioterrorism-related anthrax surveillance, Connecticut, September-December, 2001.

On November 19, 2001, a case of inhalational anthrax was identified in a 94-year-old Connecticut woman, who later died. We conducted intensive surveillance for additional anthrax cases, which included collecting data from hospitals, emergency departments, private practitioners, death certificates, postal facilities, veterinarians, and the state medical examiner. No additional cases of anthrax were identified. The absence of additional anthrax cases argued against an intentional environmental release of Bacillus anthracis in Connecticut and suggested that, if the source of anthrax had been cross-contaminated mail, the risk for anthrax in this setting was very low. This surveillance system provides a model that can be adapted for use in similar emergency settings.

Fatal inhalational anthrax in a 94-year-old Connecticut woman.

We describe the 11th case of bioterrorism-related inhalational anthrax reported in the United States. The presenting clinical features of this 94-year-old woman were subtle and nondistinctive. The diagnosis was recognized because blood cultures were obtained prior to administration of antibiotics, emphasizing the importance of this diagnostic test in evaluating ill patients who have been exposed to Bacillus anthracis. The patient's clinical course was characterized by progression of respiratory insufficiency, pleural effusions and pulmonary edema, and, ultimately, death. Although her B anthracis bacteremia was rapidly sterilized after initiation of antibiotic therapy, viable B anthracis was present in postmortem mediastinal lymph node specimens. The source of exposure to B anthracis in this patient is not known. Exposure to mail that was cross-contaminated as it passed through postal facilities contaminated with B anthracis spores is one hypothesis under investigation.