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Introduction of Hib conjugate vaccines in the non-industrialized world: experience in four 'newly adopting' countries.

Hib conjugate vaccines are widely used in the industrialized world, but are just now beginning to be introduced into other countries. To identify factors facilitating rapid global introduction, we evaluated the decision-making process, mode of introduction, effectiveness, and impact on the immunization program of Hib conjugate vaccine introduction in four non- industrialized countries through site visits and use of a standardized questionnaire. The key promoters of Hib introduction were the pediatric community and ministries of health. Local surveillance and severity data were critical in the decision to adopt Hib vaccine. Assistance with surveillance, introduction guidelines, educational material, tenders, and funding is needed to accelerate wider adoption.

Chile↗

Impact of a mass immunization campaign to control an outbreak of severe respiratory infections in Nunavik, northern Canada.

OBJECTIVES: In spring 2002, a mass immunization campaign using a 23-valent pneumococcal polysaccharide vaccine (23-PPV) was launched in order to control an outbreak of severe pneumonia caused by a virulent clone of serotype 1 Streptococcus pneumoniae in Nunavik, Quebec, Canada. The objective of the study was to evaluate the impact of this campaign on the incidence of invasive pneumococcal disease (IPD) and hospitalizations possibly associated with pneumococcal infections (HPAPI) in the mostly Inuit population aged 10 to 64 years. STUDY DESIGN: Retrospective analysis of surveillance and administrative data. METHODS: Multivariate Poisson model comparing the frequency rates of selected outcomes before the outbreak, during the outbreak, and after implementation of the mass immunization program. RESULTS: The reported incidence of serotype 1 IPD decreased markedly after the implementation of the vaccination campaign (rate ratio = 0.16; p < 0.002). The frequency of HPAPI and the mean duration of hospital stay also decreased. However, vaccine failures were documented and the HPAPI rate remained higher than in the period prior to the outbreak. CONCLUSIONS: Although 23-PPV contributed to control the outbreak, better vaccines are needed for the prevention of infections caused by serotype 1 S. pneumoniae.

Adolescent↗

Prevention and monitoring of adverse events following immunization: the "Green Channel" of the Veneto region in Italy.

Measures to improve vaccine safety are essential for successful immunization programs. Therefore, an activity for vaccine adverse events prevention and surveillance, named the Green Channel, was established in the Veneto ion of Italy in 1992. This report summarizes the results of 10 years activity of a specialized pre-vaccination counseling service, offered to 543 selected at risk individuals referred for prior AEFIs or suspected contraindications (CI) to vaccine administration. Furthermore, data on 1762 AEFIs reported in this region are analyzed and discussed. This joint activity appeared effective and it is proposed as a model.

Adverse Drug Reaction Reporting Systems↗

Adverse reactions to vaccines.

(The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense.) Immunization healthcare is becoming increasingly complex as the number and types of vaccines have continued to expand. Like all prescription drugs, vaccines may be associated with adverse events. The majority of these reactions are self-limited and not associated with prolonged disability. The media, Internet and public advocacy groups have focused on potentially serious vaccine-associated adverse events with questions raised about causal linkages to increasing frequencies of diseases such as autism and asthma. Despite a lack of evidence of a causal relationship to a variety of vaccine safety concerns, including extensive reviews by the Institute of Medicine, questions regarding vaccine safety continue to threaten the success of immunization programs. Risk communication arid individual risk assessment is further challenged by the public health success of vaccine programs creating the perception that certain vaccines are no longer necessary or justified because of the rare reaction risk. There is a need for improved understanding of true vaccine contraindications and precautions as well as host factors and disease threat in order to develop a patient specific balanced risk communication intervention. When they occur, vaccine related adverse events must be treated, documented and reported through the VAERS system. The increasing complexity of vaccination health care has led the Center of Disease Control and Prevention (CDC) to identify Vaccine Safety Assessment and Evaluation as a potential new specialty.

Drug Hypersensitivity↗

Use of automated reminders for tuberculin skin test return.

INTRODUCTION: This study assessed the impact of automated telephone reminders on tuberculin skin test returns. METHODS: A total of 701 English-speaking and Spanish-speaking patients of a public health immunization program were randomly assigned to an intervention or a control group. Those in the intervention group received an automated telephone reminder to return for the reading of their skin test. RESULTS: Automated telephone reminders significantly reduced return failures 53% (from 14% to 7%) when the scheduled interval between test administration and reading was three days, but had no impact for a two-day interval. Effectiveness of reminders did not differ significantly by patient age, gender, or language (English versus Spanish). CONCLUSIONS: Results suggest the value of automated reminder calls for intra-appointment intervals as short as three days.

Adolescent↗

Surveillance for adverse events associated with anthrax vaccination--U.S. Department of Defense, 1998-2000.

Concerns about the potential use of anthrax as a biologic weapon prompted the U.S. Department of Defense (DoD) to announce on December 15, 1997, anthrax vaccination of all U.S. military personnel. This effort is coordinated by the Anthrax Vaccine Immunization Program (AVIP). AVIP plans a phased vaccination process to achieve total force protection against anthrax by 2004. The current phase of implementation includes vaccination of all service members and mission-essential DoD civilian employees assigned or deployed to high-threat areas. On the basis of program monitoring, as of April 12, 2000, 425,976 service members had received 1,620,793 doses of anthrax vaccine adsorbed (AVA) (Bioport, Inc., Lansing, Michigan). Some service members have cited concerns about vaccine safety and efficacy in their decision to refuse vaccination, despite the possibility of administrative or disciplinary actions. To assess anthrax vaccination safety, DoD has conducted surveys of vaccinated personnel. This report describes three completed or ongoing surveys. The findings indicate that rates of local reactions were higher in women than men and that no patterns of unexpected local or systemic adverse events have been identified.

Adverse Drug Reaction Reporting Systems↗

[Study on the cost of expanded programme on immunization in areas with different economic levels].

OBJECTIVE: The expanded programme on immunization (EPI) is an important part of the social commonwealth projects providing health care service by the government, which benefits communities. Government has the responsibility for EPI's financing which should be covered by the national budget. It is essential that the cost of EPI service be scientifically estimated to provide propriety information for policy makers. METHODS: This study, using the cost accounting theory of health economics, to calculate EPI service cost at different levels. 3 provinces, 3 prefectures, 9 counties, 18 towns and 12 villages were selected from three provinces Guizhou, Heilongjiang and Zhejiang from the western, central and eastern regions of the country. RESULTS: The average costs for one EPI-targeted child in Guizhou, Heilongjiang and Zhejiang, were 15.68 Yuan, 29.00 Yuan and 31.09 Yuan, and the costs for one dose were 10.99 Yuan, 18.64 Yuan and 16.51 Yuan, respectively. The costs for complete immunization program for one child were 131.88 Yuan, 242.32 Yuan and 280.67 Yuan, respectively. The main factors affecting the cost would include the average personnel cost (salary and benefit cost) by different economic levels of areas, the number of EPI items developed, and the number of total doses for one child. CONCLUSION: (1) Obvious differences were found between different areas. (2) The proportion of the cost was not reasonably set because of the shortage of input. (3) Guideline for different areas to compensate the working item cost according to the number of the items should be formulated.

China↗

The effect of a mass poliomyelitis vaccination program on the occurrence of enteroviruses in seawater.

A mass poliomyelitis immunization program undertaken in a coastal city correlated with a significant increase in the levels of vaccinal-type strains of poliovirus recovered in the surrounding seawater. These vaccinal strains were detected together with other wild strains regularly isolated that did not exceed the levels usually detected. The need for a serious monitoring of uncontrolled sewage discharges into the sea is discussed.

Humans↗

Vaccine-preventable disease susceptibility in a young adult Micronesian population.

Current US military recruit vaccination policy presumes that recruits have had a complete childhood immunization series. This assumption may not be appropriate for recruits from Micronesia, who may have had limited access to modern health care, including immunization programs. During 1988 and 1990, a cross-sectional serosurvey was conducted among 66 US military recruits, 56 from the Federated States of Micronesia and 10 from the Republic of the Marshall Islands, collectively referred to as Micronesia. Antibody seronegativity levels for 12 vaccine-preventable (or potentially so) diseases were: measles (52%), mumps (14%), rubella (21%), varicella (38%), diphtheria (39%) tetanus (0%), polio type 1 (4%), polio type 2 (0%), polio type 3 (14%), hepatitis A (9%), hepatitis B (17%), and hepatitis C (98%). Compared with Army recruits in general, Micronesian recruits were significantly more likely to be seronegative for measles and varicella and seropositive for hepatitis types A and B. Personal histories of disease were felt to be inadequate in predicting antibody status.

Adult↗

Vaccine injury compensation programs worldwide.

Approximately a dozen countries provide some form of compensation for injuries (or deaths) following vaccination. More than anything else, they were instituted in the belief governments have a special responsibility to those injured by properly manufactured and administered vaccines used in public health programs. Administratively, most are managed through the national government, including decisions on eligibility for and amount of compensation. Eligibility may depend on the recipient's age, citizenship or residency status, category of vaccine (e.g., recommended, compulsory), the location it is administered (public vs private ambulatory setting), or satisfying certain time frames for filing a claim. Since few vaccine-related injuries have a clinical or laboratory marker, proving actual causation is difficult. Causation decisions are usually based on the balance of probabilities standard of more likely than not. All countries require that the effects be long lasting (e.g., greater than 6 months), and nearly all provide coverage for medical costs, disability pensions, and death benefits, while noneconomic damages (pain and suffering) are included much less frequently. Funding is generally from the national treasury, with some programs receiving support from lower governmental entities or vaccine manufacturers. After nearly 4 decades of operation, vaccine injury compensation program appears to be an increasingly accepted component of immunization programs today. While we have a much better understanding of their statutory purpose, frame work, process and outcome, there is much more to be learned. Future research should focus on vaccine compensation programs and (1) decision-making at the administrative level; (2) the utilization of outcome indicators in order to gauge effectiveness, including immunization acceptance; (3) the knowledge and attitudes of the public and medical community in host countries; and (4) the overall perspective of vaccine manufacturers. Insight into these and other areas will no doubt aid other countries as they consider implementing programs of their own.

Humans↗

The effect of universal influenza immunization on vaccination rates in Ontario.

OBJECTIVES: This article examines the association between introduction of Ontario's Universal Influenza Immunization Program and changes in vaccination rates over time in Ontario, compared with the other provinces combined. DATA SOURCES: The data are from the 1996/97 National Population Health Survey and the 2000/01 and 2003 Canadian Community Health Survey, both conducted by Statistics Canada. ANALYTICAL TECHNIQUES: Cross-tabulations were used to estimate vaccination rates for the total population aged 12 or older, for groups especially vulnerable to the effects of influenza, and by selected socio-demographic variables. Z tests and multiple logistic regression were used to examine differences between estimates. MAIN RESULTS: Between 1996/97 and 2000/01, the increase in the overall vaccination rate in Ontario was 10 percentage points greater than the increase in the other provinces combined. Increases in Ontario were particularly pronounced among people who were: younger than 65, more educated, and had a higher household income. Between 2000/01 and 2003, vaccination rates were stable in Ontario, while rates continued to rise in the other provinces. Even so, Ontario's 2003 rates exceeded those in the other provinces.

Adolescent↗

Method for ascertaining denominators for evaluation of population coverage with pneumococcal vaccine.

BACKGROUND: Immunization programs may collect numerator data for the estimation of pneumococcal vaccine coverage, but program evaluators do not have appropriate denominator data for estimation of pneumococcal vaccine coverage, particularly among those eligible for vaccine on the grounds of having chronic health conditions. METHODS: We partitioned the Alberta population into 6 mutually exclusive groups, all but one of which met Canadian recommendations for pneumococcal vaccination. Age-sex specific prevalence rates for each group were estimated using data on chronic health conditions from the Alberta over-sample of the 1996 Household component of the National Population Health Survey, from Alberta Health and Wellness rosters of nursing home residents, and from the Alberta Health Care Insurance Plan Stakeholder Registry. We applied these to Alberta Population Projections to estimate the numbers of persons who should be vaccinated. RESULTS: The proportion of persons recommended for vaccination on the grounds of chronic health condition ranged from 1.5% among those aged less than 12 years to 36% among persons aged 80 years or older. The total number of persons recommended for vaccination at mid-year 2000 is estimated to be 638,561 (21.5% of the Alberta population). INTERPRETATION: This methodology provides denominators for the estimation of pneumococcal vaccine coverage and permits monitoring of local and regional progress towards national goals.

Adolescent↗

Attitudes of healthcare workers in U.S. hospitals regarding smallpox vaccination.

BACKGROUND: The United States is implementing plans to immunize 500,000 hospital-based healthcare workers against smallpox. Vaccination is voluntary, and it is unknown what factors drive vaccine acceptance. This study's aims were to estimate the proportion of workers willing to accept vaccination and to identify factors likely to influence their decisions. METHODS: The survey was conducted among physicians, nurses, and others working primarily in emergency departments or intensive care units at 21 acute-care hospitals in 10 states during the two weeks before the U.S. national immunization program for healthcare workers was announced in December 2002. Of the questionnaires distributed, 1,165 were returned, for a response rate of 81%. The data were analyzed by logistic regression and were adjusted for clustering within hospital and for different number of responses per hospital, using generalized linear mixed models and SAS's NLMIXED procedure. RESULTS: Sixty-one percent of respondents said they would definitely or probably be vaccinated, while 39% were undecided or inclined against it. Fifty-three percent rated the risk of a bioterrorist attack using smallpox in the United States in the next two years as either intermediate or high. Forty-seven percent did not feel well-informed about the risks and benefits of vaccination. Principal concerns were adverse reactions and the risk of transmitting vaccinia. In multivariate analysis, four variables were associated with willingness to be vaccinated: perceived risk of an attack, self-assessed knowledge about smallpox vaccination, self-assessed previous smallpox vaccination status, and gender. CONCLUSIONS: The success of smallpox vaccination efforts will ultimately depend on the relative weight in people's minds of the risk of vaccine adverse events compared with the risk of being exposed to the disease. Although more than half of the respondents thought the likelihood of a bioterrorist smallpox attack was intermediate or high, less than 10% of the group slated for vaccination has actually accepted it at this time. Unless new information about the threat of a smallpox attack becomes available, healthcare workers' perceptions of the vaccine's risks will likely continue to drive their ongoing decisions about smallpox vaccination.

Adult↗

Safety and immunogenicity of Haemophilus influenzae type b conjugate vaccine (PedvaxHIB) in Papua New Guinean children.

BACKGROUND: In view of high mortality and morbidity from Haemophilus influenzae type b (Hib) in young Papua New Guinean children, the incorporation of a Hib conjugate vaccine into a nationwide immunization program would be of major public health benefit. The choice of the Hib conjugate vaccine will be based on the evaluation of several Hib conjugate vaccines, after consideration of such factors as the ease of incorporation into the current vaccination schedule, cost, kinetics of antibody responses and safety. METHODS: This study evaluated the safety and immunogenicity of Hib polysaccharide-Neisseria meningitidis outer membrane protein complex conjugate vaccine (PRP-OMPC) in Papua New Guinea. 95 children were recruited at Goroka Base Hospital, Eastern Highlands Province, and enrolled in the study. PRP-OMPC was administered at ages 2, 4 and 12 to 15 months. Blood was collected before each dose, one month after the second and booster doses, and at ages 18 and 24 months. Antibody to PRP (anti-PRP) was measured by radioimmunoassay. RESULTS: PRP-OMPC was generally well tolerated. At successive sampling times from the prevaccination bleed through the 1-month post-booster bleed, geometric mean titres were 0.18, 1.45, 2.54, 1.03 and 8.05 micrograms/ml, respectively (n = 60). The proportions of subjects with anti-PRP titres > or = 1.0 microgram/ml were 2%, 62%, 73%, 47% and 93%, respectively (n = 60). Persistence of anti-PRP was ascertained in 41 subjects. The GMTs at 18 and 24 months were 3.42 and 2.0 micrograms/ml, respectively. CONCLUSIONS: PRP-OMPC was found to be immunogenic after the first dose and to elicit a robust booster response. Antibody titres persisted until age 24 months, at which time 100% of subjects had anti-PRP > or = 0.15 microgram/ml. These results are consistent with previous studies in US Native American infants and in Gambian infants.

Bacterial Outer Membrane Proteins↗

Protective efficacy, immunotherapeutic potential, and safety of hepatitis B vaccines.

Hepatitis B vaccines are highly effective and safe and have been incorporated into national immunization programs in over 150 countries. The major humoral immune response is to the common a determinant of the surface antigen protein of the virus. Approximately 5-10% of healthy immunocompetent subjects do not mount an antibody response (anti-HBs). Non-response is associated with different HLA-DR alleles and impaired Th cell response, among other factors such as route of injection, age, gender, body mass, and other factors. Important hepatitis B surface antigen variants have also been identified, which may have a potential impact on immunization and routine screening of blood, blood products and tissues, and organs for transplantation. Strategies for hepatitis B immunization are reviewed. Over 1,000 million doses of hepatitis B vaccine have been used with an outstanding record of safety. There is no evidence of an association between hepatitis B vaccines and the sudden infant death syndrome, chronic fatigue syndrome, and multiple sclerosis (MS). Several studies are in progress on treatment of chronic hepatitis B infection by immunization with multiple antigenic components, combination of vaccine with antiviral drugs and cytokines, T cell vaccines, DNA vaccines alone or with DNA encoded immunomodulatory cytokines, and direct genetic manipulation of antigen presenting cells.

Age Factors↗

Safety and immunogenicity of pneumococcal conjugate vaccine in combination with diphtheria, tetanus toxoid, pertussis and Haemophilus influenzae type b conjugate vaccine.

BACKGROUND: Pneumococcal polysaccharide/protein conjugate vaccines (PnCV) are immunogenic and effective in infancy. However, an addition to the nine currently recommended vaccine injections during the first year of life of African children may be a deterrent to participation in a PnCV program. Thus we have evaluated the safety and immunogenicity of a 9-valent PnCV (Wyeth Lederle Pediatrics and Vaccines) mixed with diphtheria, tetanus toxoid, cell pertussis and type b (TETRAMUNE). METHODS: Healthy Gambian infants were randomized at the age of 2 months to receive three doses 1 month apart of either (1) placebo reconstituted in TETRAMUNE in the right thigh (control) or (2) PnCV in the left thigh and TETRAMUNE in the right thigh (separate) or (3) PnCV reconstituted in TETRAMUNE as a single injection in the right thigh (combined). The vaccines were given together with routine Expanded Program on Immunization vaccines. Adverse reactions were recorded after vaccination, and antibody concentrations were measured by enzyme-linked immunosorbent assays. RESULTS: Local induration and tenderness were observed more commonly at the site of injection of TETRAMUNE than at the site of injection with PnCV after each dose of vaccination. Swelling at the site of injection was encountered more frequently at the site of administration of TETRAMUNE than at the site of administration PnCV ( P< 0.00001 for Doses 1 and 2 and P< 0.0009 for Dose 3). Swelling at the site of administration of TETRAMUNE mixed with PnCV was comparable with that observed for TETRAMUNE alone. Although most mothers reported that the babies "felt hot" 24 h after each injection, febrile reactions (temperature, >or=38 degrees C) were infrequent and resolved with antipyretics. Geometric mean titer for anti-polyribosylribitol phosphate antibody was 11.6 microg/ml [95% confidence limits (95% CI), 9.2, 14.6] in the control group and comparable with 13.3 microg/ml (95% CI 11.0, 16.0) in the combined group and significantly higher at 17.9 microg/ml (95% CI 14.7, 21.9; P= 0.01) in the separate group. Geometric mean concentrations of serotype-specific pneumococcal antibodies were higher in the combined group than the separate group for all nine serotypes. Antibody responses to diphtheria and pertussis antigens were similar in all groups. Anti-tetanus toxoid antibody concentrations were lowest in the combined group (6.66 IU/ml, 95% CI 5.77, 7.68 in the control group; 5.15 IU/ml, 95% CI 4.39, 6.03 in the combined group; P= 0.02). However, all vaccinees achieved protective antibody values. CONCLUSION: The combination of TETRAMUNE and PnCV is safe and immunogenic.

Bacterial Capsules↗

Responding to parental refusals of immunization of children.

The American Academy of Pediatrics strongly endorses universal immunization. However, for childhood immunization programs to be successful, parents must comply with immunization recommendations. The problem of parental refusal of immunization for children is an important one for pediatricians. The goal of this report is to assist pediatricians in understanding the reasons parents may have for refusing to immunize their children, review the limited circumstances under which parental refusals should be referred to child protective services agencies or public health authorities, and provide practical guidance to assist the pediatrician faced with a parent who is reluctant to allow immunization of his or her child.

Child↗

[Vaccination against Haemophilus influenzae type b in Uruguay: experience and impact].

Between 1979 and 1994, epidemiological surveillance of meningitides in Uruguay showed a progressive increase in suppurative meningitides due mainly to Neisseria meningitidis and Haemophilus influenzae type b (Hib). The cases were concentrated in children under 5; however, among the cases caused by Hib, 70% affected children from 1 to 11 months old. Facing this situation, the Ministry of Public Health resolved, as of August 1994, to include the Hib vaccine in the country's Expanded Program on Immunization, which has been in place since 1982. The Hib vaccination is done without charge and is obligatory for all children under 5 years of age. It is done using the following series of vaccinations: a) three doses, given at 2, 4, and 6 months, with a booster dose at age 1; b) children from 7 to 11 months old receive two doses two months apart and a booster dose a year later; and c) a single dose for children 12 months to 4 years old. Between August and December 1994 a coverage rate of 76.6% was reached among children between 2 months and 4 years old, and the coverage has remained above 80% in the new cohorts. In Uruguay, this vaccination strategy had a spectacular impact on morbidity and mortality due to meningitides caused by Hib. One of the results was that the incidence of 15.6 per 100,000 registered in children under 5 in the prevaccination years declined to 0.03 per 100,000 in 1996.

Child, Preschool↗