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PubMed1992

Childhood immunizations: a practical approach for clinicians.

Family physicians can play a key role in reversing the resurgence of vaccine-preventable illnesses by making sure that patients are fully immunized. Childhood immunization schedules have recently changed. A second dose of measles, mumps and rubella (MMR) vaccine should be given at age four to six years. It has been recommended that hepatitis B vaccine be administered routinely to all infants in the United States. Both hepatitis B vaccine and hepatitis B immunoglobulin should be given to offspring of hepatitis B carriers. Haemophilus b conjugate vaccine (HbCV) should be administered to all infants, beginning at two months of age. Vaccines can be safely administered to patients with mild illnesses, allergic rhinitis, low-grade fever or penicillin allergy, as well as to those taking antibiotics. If indicated, several vaccines, such as diphtheria, tetanus and pertussis, oral poliovirus, HbCV and MMR, can be given simultaneously.

Child↗

PubMed2002

IL-4 and T cells are required for the generation of IgG1 isotype antibodies against cardiolipin.

Infection with Mycobacterium tuberculosis induces Abs against a vast array of mycobacterial lipids and glycolipids. One of the most prominent lipid Ags recognized is cardiolipin (CL). The kinetics of the generation of anti-CL Abs during infection reveals that IgM titers to CL increase over time. Interestingly, at day 30 postinfection CL-specific IgG1 appears, an isotype usually dependent on T cell help. Using an immunization schedule with CL/anti-CL Ab complexes, which induces antiphospholipid syndrome in mice, we show that the generation of IgG1 to CL requires IL-4 and that optimal production is T cell dependent. IgG1 production to CL was impaired in nude (nu/nu) mice devoid in conventional T cells, but was not affected in mice deficient for either alphabeta TCR(+), gammadelta TCR(+), CD4(+), CD8(+), or NK1.1(+) T cells. We conclude that IgG1 production to CL depends on T cell help and IL-4, which can be provided by different T cell populations. This is the first report that IL-4 is indispensable for the induction of IgG1 Abs to lipid Ags.

Animals↗

PubMed1960

Human and animal antibody responses to commercial poliomyelitis vaccine.

The evaluation of the poliomyelitis vaccine field trials conducted in the USA in 1954 showed that there was considerable variation in the antigenicity of the vaccines then in use. Since then, however, there have been changes both in manufacturing procedures and in immunization schedules; and a new study has therefore been conducted into the antibody response of triply negative children, aged 6months to 3 years, to commercial vaccine. The results show good response for all three poliovirus types after three injections. After two doses antibody levels were relatively low, but the rise in level after the third dose was substantial and resulted in aggregate conversion rates of over 80% for all three types at a serum dilution of >/= 1:4. The limited data available indicate that the correlation between animal tests and the results in man is low but sufficient to make it possible to rate vaccines as "good" or "poor". There was no demonstrable influence of geographical location on antibody response.

Antibodies, Viral↗

PubMed1993

A cross-sectional study on vaccine coverage and seroprevalence in schoolchildren in Andorra.

A cross-sectional study on vaccine coverage and vaccine effectiveness was carried out on a randomized sample of the cohort of schoolchildren born in 1983 attending school in Andorra, prior to the introduction of a Systematic Immunisation Plan that included centralised import and delivery of vaccines to vaccinating clinics, surveillance of the cold-chain during vaccine delivery, and a clearly-defined immunization schedule against diphtheria, tetanus, -pertussis, polio, mumps, rubella and measles. Vaccine coverage was estimated from vaccination card records; history of disease and sociodemographic variables were obtained through a questionnaire to the children's parents and vaccine effectiveness was estimated through serum antibody testing. Vaccine coverage levels for DTP and OPV were 97.8% for both. Protective serum antibody prevalence was correspondingly high except for the polio viruses. The authors suggest that decreased vaccine effectiveness, probably due to poor preservation of the cold chain, might be the cause of this finding. In countries or regions with an otherwise developed organisation of health services, an important issue like this can still be overlooked.

Andorra↗

PubMed1999

Effects of antigen dose and immunization regimens on antibody responses to a cytomegalovirus glycoprotein B subunit vaccine.

The purpose of this phase I study was to evaluate the safety and immunogenicity of 2 doses of cytomegalovirus glycoprotein B (CMV gB)/MF59 vaccine at 3 different immunization schedules. Ninety-five volunteers were randomized to 6 groups. Antibodies to gB represent the majority of the CMV-specific neutralizing response. Three groups received 5 microgram of gB antigen combined with MF59 (a proprietary adjuvant) and 3 groups received a 30-microgram dose at 0, 1, and 2 months; 0, 1, and 4 months; or 0, 1, and 6 months. The vaccine was well tolerated, and there was no significant difference in antibody production between the 2 doses. The vaccine induced highest antibody titers when given at 0, 1, and 6 months. A low dose of CMV gB/MF59 may be the preferred dose for future studies.

Adjuvants, Immunologic↗

PubMed2005

Progress in vaccination against hepatitis B in the Americas.

Hepatitis B is a serious public health problem leading to chronic infection, liver cirrhosis, and hepatocellular carcinoma. The World Health Organization (WHO) and the Pan American Health Organization (PAHO) recommend routine universal infant vaccination against hepatitis B as the main strategy for the control hepatitis B and its severe consequences. PAHO additionally recommends routinely vaccinating healthcare workers. As of 2005, all countries in the Americas, except Haiti and Dominica, have hepatitis B vaccine in their childhood immunization schedule; 13 countries/territories include a hepatitis B dose given at birth. Hepatitis B vaccine has been incorporated into national schedules using different modalities; notably, 28 countries use it as a combination vaccine diphtheria tetanus pertussis + Haemophilus influenzae type b + hepatitis B (DTP+Hib+Hep B) for infants. Coverage levels for the third dose of hepatitis B are usually over 80%; however, hepatitis B vaccine coverage overall is lower than for the third dose of DTP. Insufficient information is available at this time to assess the use of hepatitis B vaccine in healthcare workers in the Americas. The most important factor associated with the success in the implementation of hepatitis B vaccination has been the strong commitment of country governments. This experience can be used as a model when implementing new technologies in health as they become available. However, much still needs to be done to improve hepatitis B coverage.

Bacterial Capsules↗

PubMed2004

Assessing the impact of wastage on pediatric vaccine immunization formulary costs using a vaccine selection algorithm.

Pediatric immunization is an important factor in providing protection against numerous common preventable diseases. The success of the pharmaceutical industry in developing new pediatric vaccines has resulted in a crowded recommended immunization schedule requiring several clinic visits over the first 12 years of life. Operations research models have been developed and used to make economically sound procurement choices from among a growing number of competing vaccine products. One factor that has not been incorporated into such models is the economic impact of wastage on such decisions. This paper reports results obtained from a vaccine selection algorithm that incorporates vaccine wastage data. The lowest overall cost formularies comparing no wastage costs with wastage costs are presented. A sensitivity analysis of the vaccine formulary with respect to the wastage rates associated with each available vaccine is provided. The maximum permissible wastage rate for each vaccine is determined for which the vaccine earns a place in the lowest overall cost formulary. This research provides health maintenance organizations and healthcare providers information that can be used to gain a better understanding of wastage and its impact on pediatric formulary costs.

Algorithms↗

PubMed1999

Vaccination against tick-borne encephalitis under therapeutic immunosuppression. Reduced efficacy in heart transplant recipients.

Patients after organ transplantation are at an increased risk of microbial infections and might benefit from active vaccination. Due to therapeutic immunosuppression the efficacy of immunizations is, however, reduced and difficult to predict. Efficacy of vaccination against tick-borne encephalitis (TBE) using an abbreviated immunization schedule was compared in 31 heart transplant recipients (age: 54.5 +/- 11.5 years, mean time after transplantation: 53.5 +/- 23.7 months) under cyclosporine-based immunosuppression and 29 controls. TBE vaccination was well tolerated by the transplant recipients; spectrum and frequency of adverse events were similar to controls. In the transplant patients, seroconversion rate (35% versus 100%; p < 0.001) and the geometric mean of post-vaccinal antibody titres (0.98 (SF: 2.3) U/ml versus 5.46 (2.2) U/ml; p < 0.001) were markedly reduced in comparison to the control group. No clinical or demographic predictors of vaccination success could be established in the transplant patients. Due to the limited efficacy, TBE vaccination cannot be recommended as a routine procedure in heart transplant recipients at risk of TBE virus infection. TBE vaccination may be performed safely in selected cases, but repeated titre controls to confirm vaccination success would be required.

Adult↗

PubMed1994

Epidemiological views into possible components of paediatric combined vaccines in 2015.

Efforts to develop combined vaccines for childhood immunization schedules will during the next years focus on combined administration of the existing vaccines which have already shown their impact. First candidate components for more wide-spectrum combinations could be the new antigens against severe invasive infections caused by encapsulated bacteria. Multivalent pneumococcal and meningococcal group A and C conjugate vaccines are already in clinical trials, and the same is true of the first candidates for the meningococcal group B vaccine. Pneumococcal conjugate vaccines are also important in prevention of a large variety of respiratory infections. Since viruses are important causative agents of bronchiolitis and pneumonia, components of the paediatric combined vaccine should include at least respiratory syncytial virus, and possibly also other respiratory viruses like parainfluenza and adenoviruses. The third group of diseases to be considered from the preventive point of view are congenital infections, and vaccines against herpes simplex viruses, cytomegalovirus, or group B streptococci might be included in a combined vaccine to be administered to adolescents in order to afford protection to their future children.

Bacterial Infections↗

PubMed1981

Immunological delineation in normal and malignant cells of a membrane protein involved in glucose transport. I. Preparation and properties of the antibody.

Partially purified preparations of the 200000 Mr membrane glycoprotein described by Bramwell & Harris were used as antigens to generate monoclonal antibodies. Whether the protein was prepared from human or mouse tumours, the mice immunized with it yielded monoclonal antibodies of broadly similar specificities. All the antibodies obtained were of the immunoglobulin M class, despite a prolonged immunization schedule, and recognized an antigen that was present on the surface of mouse, rat and human cells. One such antibody, M/27, was studied in detail. With the exception of 2 rat kidney cell lines, the antigen detected by M/27 was found on the surface of all cells grown in culture, whether malignant or not. However, in the mouse, the species in which the antibody was generated, M/27 discriminated sharply between malignant tumours and normal tissues excised directly from the animal. In normal adult or embryonic mouse tissues, whether they were composed of multiplying cells or not, the antigen detected by M/27 was present on the cell surface only at the lower limit of detection, if at all. Malignant mouse tumours grown in the animal produced large amounts of the antigen. Explantation of embryonic mouse fibroblasts induced the expression of the antigen, which was not detected on these same cells in their normal habitat in the growing embryo. Conversely, non-malignant cells that express the antigen in vitro cease to do so when they are re-introduced into the animal. The antigenic determinant appeared to be polypeptide in nature rather than polysaccharide.

Animals↗

PubMed2006

Impact of conjugate Haemophilus influenzae type b (Hib) vaccine introduction in South Africa.

OBJECTIVE: To analyse trends in reported invasive Haemophilus influenzae disease in South Africa within the first five years of introduction of conjugate Haemophilus influenzae type b (Hib) vaccine in the routine child immunization schedule. METHODS: We used national laboratory-based surveillance data to identify cases of invasive H. influenzae disease between July 1999 and June 2004, and submitted isolates for serotyping and antimicrobial susceptibility testing. FINDINGS: The absolute number of Hib cases (reported to the national surveillance system) among children below one year of age decreased by 65%, from 55 cases in 1999-2000 to 19 cases in 2003-04. Enhanced surveillance initiated in 2003, identified human immunodeficiency virus (HIV)-infection and incomplete vaccination as contributing factors for Hib transmission. The total number of laboratory-confirmed cases of H. influenzae remained unchanged because non-type b disease was being increasingly reported to the surveillance system concomitant with system enhancements. Children with non-typable disease were more likely to be HIV-positive (32 of 34, 94%) than children with Hib disease (10 of 14, 71%), P = 0.051. Recent Hib isolates were more likely to be multidrug resistant (2% in 1999-2000 versus 19% in 2003-04, P = 0.001). CONCLUSION: Data from a newly established national laboratory-based surveillance system showed a decrease in Hib disease burden among South African children following conjugate vaccine introduction and identified cases of non-typable disease associated with HIV infection.

Bacterial Capsules↗

PubMedDate not supplied

Assessment of the anti-hepatitis B vaccination efficacy in high risk children.

In October 1995, The Ministry of Health has initiated the national immunization program of newborns against hepatitis B. Owing to the frequency of asymptomatic Hepatitis B clinical forms in children, as well as the deficiencies in the surveillance system, the assessment of the vaccination efficacy can be performed objectively only by the detection of the prevalence of anti HBs antibodies in children to whom the complete three doses of immunization schedule have been administered (at 0, 2 and 6 months of age). We report in this study the results of a seroprevalence research carried out on a group of 272 children from orphanages who have been vaccinated. A protective anti HBs titer (> 10 mIU) was recorded only in 66.3% of cases; other 10 samples contained antibodies at a titer lower than the protective level. In the 80 children without seroconversion the presence of anti HBc antibodies (marker for the natural infection) was investigated. 30% of the seronegative children have anti HBc antibodies from which 54.2% have also HbsAg. Significant differences were recorded in the seroconversion level and in the geometric mean of titers between the various units in which sera were collected. In four orphanages (district Arad, Jassy, Sibiu and Teleorman) the seroconversion exceeded 90%, in 5 orphanages it was over 80% and in the others it ranged from 30% to 70%. The lowest seroconversions were recorded in the orphanages in Bucharest, Botoşani, Galaţi and Olt. The possible causes of the low immunogenicity are analyzed: non-vaccination or incomplete vaccination; low immunoreactivity of children, many of whom are premature; high HbsAg carriage rate among the mother's etc. Although the evolution of the post vaccinal seroconversion is not a routine practice in the appraisement of Hepatitis B vaccine immunogenicity, our results require the extension of the study in order to adopt the most effective vaccinal strategy.

Hepatitis B↗

PubMed2006

Comparison of two hepatitis B vaccines (GeneVac-B and Engerix-B) in healthy infants in India.

Hepatitis B is a major problem in many parts of the world. The WHO has recommended the inclusion of hepatitis B vaccines in routine immunization schedules. We wanted to compare two recombinant hepatitis B vaccines in an infant population for immunogenicity and reactogenicity when given at 6, 10, and 14 weeks of age. One hundred seventy-three infants meeting eligibility criteria were given either GeneVac-B (Serum Institute of India Ltd.) or Engerix-B (GlaxoSmithKline Beecham) in a random fashion. Three 0.5-ml (10-mug) doses of the vaccines were given at 6, 10, and 14 weeks of age along with diphtheria-pertussis (whole cell)-tetanus (DTPw) vaccine. Blood samples were collected at baseline and 1 month after administration of the third dose of the vaccines to measure anti-HBs antibody levels. Seroconversion was defined as a titer of more than 1 x 10(-3) IU/ml, while seroprotection was defined as a titer of more than 10 x 10(-3) IU/ml. Of the GeneVac-B recipients, 98% seroconverted versus 99% of the Engerix-B group. The anti-HBs geometric mean titer was slightly greater for GeneVac-B (229 x 10(-3) IU/ml) than for Engerix-B (167 x 10(-3) IU/ml), but the difference was not significant. The seroprotection rates were similar for both vaccines (96% and 95%, respectively). The most common systemic reaction events were mild to moderate fever, excessive crying, local swelling, rash, and irritability, and the local reactions were redness, induration, and edema, which most probably were caused by the simultaneously administered DTPw vaccine. All events were transient and resolved without sequelae. Reactogenicity was similar for the two vaccines. The present study shows that GeneVac-B is as immunogenic and as well tolerated as Engerix-B when administered with DTPw vaccine at 6, 10, and 14 weeks of age.

Dose-Response Relationship, Immunologic↗

PubMed2000

Parents' preferences for outcomes associated with childhood vaccinations.

BACKGROUND: The number of shots in the childhood immunization schedule has been increasing and is likely to continue to increase in the coming years. Consideration of the psychologic costs of multiple injections, adverse events and vaccine-preventable disease is therefore growing in importance. METHODS: We assessed parent preferences, using both the time tradeoff (i.e. amount of parent time willing to trade) and willingness-to-pay (i.e. dollars willing to pay) metrics, for possible outcomes of vaccination among 206 parents of infants receiving care at Kaiser, Northern California Region. We also explored the relationship between preferences and subject characteristics. RESULTS: In general the amount of time subjects were willing to give up and the quantity of money they were willing to spend to avoid an outcome increased with the severity of the outcome. Preferences for our six main outcomes of interest all differed from one another (P < 0.0001, Tukey's multiple comparisons procedure). Rank correlation coefficients between time tradeoff and willingness-to-pay values for the six main outcomes ranged from 0.42 to 0.52 (all P < 0.004). Subject characteristics, including education, income, race/ethnicity and the child's birth order, did not explain the variation in parent preferences. CONCLUSIONS: In general subjects were willing to give up more money or time to avoid less desired outcomes. They were willing to give up only very small amounts of their own life expectancy or money to avoid minor, temporary outcomes (e.g. moderate fussiness, fever and pain) whereas they were willing to forego substantial lengths of their life or amounts of money to avoid a major, permanent outcome (i.e. permanent disability). Nonetheless much variation surfaced in the amount of time (or money) subjects were willing to trade to avoid outcomes. If this variation represents true differences in preferences, guideline developers must consider the role of individual parent preferences in decisions concerning vaccination.

Adult↗

PubMed1998

Addressing the challenges to immunization practice with an economic algorithm for vaccine selection.

The biotechnology revolution is producing a growing bounty of new vaccines which pose difficult choices in selecting among many products. Some major public and private purchasers of vaccine may offer individual physicians and clinics their choice in assembling vaccine inventories. Others might purchase only a limited stock of products that would satisfactorily immunize a typical child. In either case, current vaccine selection decisions are based principally on purchase price alone without systematic consideration of other factors of fiscal consequence. As a potential tool for decision making, we developed an economic algorithm for vaccine selection that would minimize the overall costs of disease control through immunization by considering: (1) purchase price, (2) number of doses needed, (3) preparation time, (4) route of administration, (5) cold storage needs, (6) shelf life, (7) earliest age of full immunity, (8) adverse events frequency, and (9) efficacy of protection. To demonstrate the algorithm, variables (1) to (4) above were incorporated into a pilot binary-integer linear programming model that satisfied the recommended immunization schedule for diphtheria, tetanus, pertussis, Haemophilus influenzae b, and hepatitis B, using eleven vaccines (DTaP, DTaP-Hib, Hib, HepB and Hib-HepB) from four manufacturers. Five (or six) opportunities to vaccinate were modeled at (1), 2, 4, 6, 12-18, and 60 months of life, assuming US$40 per clinic visit, $15 per injection, and $0.50 per minute of nurse preparation time. Vaccine costs were varied using actual March and September 1997 US Federal vaccine prices, as well as estimates for unpriced new vaccines. Over 16,000 distinct vaccine stocking lists by vaccine type and brand were possible. Including a 1-month visit, the lowest-cost 'solution' of the algorithm was $529.41 per child in the March cost-assumption case, and $490.32 in the September one (both included four doses of DTaP-Hib, three HepB, and one DTaP). Without a 1-month visit, the lowest-cost solution in the March case cost $486.67 (four DTaP, two Hib-HepB, one DTaP-Hib, and one HepB), while the September case cost $450.32 (four DTaP-Hib, three HepB, and one DTaP). Ensuring at least one product was selected from each of the four manufacturers increased costs about $13.00, and the needed injections rose from eight to nine. The most economical selection of vaccines to use cannot be intuitively predicted, as permutations are large and solutions are sensitive to minor changes in costs and constraints. A transparent, objective selection method that weighs the economic value of distinguishing features among competing vaccines might offer the 'best value' to vaccine purchasers, while also creating strong market incentives for continuing innovation and competition in the vaccine industry.

Adolescent↗

PubMed1993

Two-dose measles vaccination schedules.

As measles continues to exact a high toll on infant mortality, particularly in developing countries, optimal strategies for the control of the disease are under discussion. As part of this debate, the place of 2-dose measles immunization schedules is reviewed regarding their potential as a strategy to improve measles control. To date, WHO has not recommended the use of a 2-dose schedule. A number of industrialized countries have already adopted a 2-dose schedule, often choosing to administer measles vaccine in the same injection as mumps and rubella vaccines. However, at present not enough is known about such schedules in developing countries to make global recommendations. Further research should include randomized controlled trials of early 2-dose schedules to investigate both technical and epidemiological issues such as the effect of blunting immunity and the duration of antibody. Long-term safety should be determined through studies of adequate size. Programmes already using 2-dose schedules are encouraged to evaluate their impact on disease incidence, cost, vaccine usage, and effect on coverage. Until further evaluation is complete, a high and timely coverage with one dose of measles vaccine in all areas remains the first priority for all immunization programmes.

Child, Preschool↗

PubMed2005

Anti-HBs profiles in children treated for neoplastic disease who had been vaccinated against hepatitis B postnatally or as infants.

Children with cancer are a risk group for hepatitis B virus (HBV) infection. In Poland, the initiation of a national HBV vaccination programme in neonates and infants in 1995 has contributed to the prevention of HBV infection in children treated for neoplastic diseases. The objective of this study was to analyse the anti-HBs pattern and occurrence of HBV infections in children with cancer who had been vaccinated during infancy. The study included 96 children divided into three groups: Group A, children who had received a full vaccination course with an initial level of anti-HBs >/=100 IU/L; Group B, children who had received a full vaccination course with anti-HBs <100 IU/L, for whom an additional dose of vaccine was administered; and Group C, children who had further immunoprophylaxis because they did not complete the vaccination course before cancer diagnosis. A protective level of anti-HBs after the full vaccination programme was found in 80.5% of children after three months, 74.2% after six months, 61.5% after 12 months and 78.6% after 18 months. Among children who produced antibodies, a slow decrease in the level of anti-HBs was observed. It was still protective during follow-up in Group A, but occasionally fell below 100 IU/L in Group B. In Group C, five of 11 subjects had a protective level of anti-HBs throughout follow-up. Of 28 children who showed the presence of HBsAg during follow-up, 23 eradicated the virus. In children with cancer vaccinated against HBV according to the vaccination schedule, the immune response maintains a protective level of anti-HBs in more than 60% of cases, despite immunosuppression.

Biomarkers↗

PubMed1998

Analysis of intercurrent human immunodeficiency virus type 1 infections in phase I and II trials of candidate AIDS vaccines. AIDS Vaccine Evaluation Group, and the Correlates of HIV Immune Protection Group.

Among 2099 uninfected subjects in phase I and II trials of candidate AIDS vaccines, 23 were diagnosed with intercurrent human immunodeficiency virus type 1 (HIV-1) infection. High-risk sexual exposures accounted for 17 infections, and intravenous drug use accounted for 6. Four subjects received placebo, 13 received a complete immunization schedule (> or = 3 injections), and 6 were partially immunized (< or = 2 injections). There was no significant difference between vaccine recipients and control groups in incidence of HIV-1 infection, virus load, CD4 lymphocyte count, or V3 loop amino acid sequence. In summary, 19 vaccinated subjects acquired HIV-1 infection during phase I and II trials, indicating that immunization with the products described is < 100% effective in preventing or rapidly clearing infection. Laboratory analysis suggested that vaccine-induced immune responses did not significantly affect the genotypic or phenotypic characteristics of transmitted virus or the early clinical course of HIV-1 infection.

AIDS Vaccines↗