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Do too many shots due lead to missed vaccination opportunities? Does it matter?

BACKGROUND: Missed childhood vaccination opportunities have been generally described, yet not since the immunization schedule's recent rapid expansion. Little is known about the relationship between the number of vaccine doses due and whether all scheduled doses are administered, and the effect of dose deferral on immunization coverage. METHODS: 32 private pediatrics centers reviewed medical records covering the first 2 years of life for 858 patients. For each visit during ages 2-8 months, we determined the numbers of vaccine doses due versus administered. Logistic regression was used to assess the effect of dose deferral on immunization coverage at ages 1 and 2 years. RESULTS: Of 2224 visits during ages 2-8 months at which > or =1 dose was administered, > or =1 due dose was deferred at 26%, 34%, and 48% of the visits at which < or =3, 4, and 5 doses were due, respectively. Absence of a deferred dose visit predicted increased coverage at age 1 (adjusted odds ratio: 2.4, 95% confidence interval: 1.8-3.2) and 2 years (2.1, 1.4-3.0). CONCLUSIONS: Administering some but not all vaccine doses at visits during ages 2-8 months impairs immunization coverage through age 2 years.

Female↗

Combined immunization of infants with oral and inactivated poliovirus vaccines: results of a randomized trial in The Gambia, Oman, and Thailand. WHO Collaborative Study Group on Oral and Inactivated Poliovirus Vaccines.

To assess an immunization schedule combining oral (OPV) and inactivated poliovirus vaccines (IPV), a clinical trial was conducted in The Gambia, Oman, and Thailand. Children were randomized to receive OPV at birth and at 6, 10, and 14 weeks of age; OPV at birth followed by both OPV and IPV at 6, 10, and 14 weeks of age; or placebo at birth followed by IPV at 6, 10, and 14 weeks of age. Serum specimens were available at 24 weeks for 1291 (77%) of 1685 enrolled infants. In the combined-schedule group, the proportion of children seropositive at 24 weeks was 95%-99% for type 1, 99%- 100% for type 2, and 97%-100% for type 3. In The Gambia and Oman, the combined schedule performed significantly better than OPV for type 1 (95%-97% vs. 88%-90%) and type 3 (97%-99% vs. 72%-73%). Across the study sites, IPV given at 6, 10, and 14 weeks of age provided inadequate protection against poliovirus. The combined schedule provided the highest levels of serum antibody response, with mucosal immunity equivalent to that produced by OPV alone.

Antibodies, Viral↗

Physician knowledge of catch-up regimens and contraindications for childhood immunizations.

OBJECTIVES: To determine physician success at designing catch-up regimens for children delayed in immunizations and physician knowledge regarding contraindications to immunization. METHODS: A self-administered survey was completed by pediatricians, general practitioners, and family practitioners in Cook County, Illinois. Surveys included 6 open-ended vignettes describing hypothetical children delayed in immunization for whom participants were asked to design catch-up regimens. Bivariate and multivariate logistic regression were used to determine predictors of correct response. The surveys also inquired about management of scenarios that might be perceived as contraindications to immunize with the Haemophilus influenzae type b or measles-mumps-rubella vaccines. RESULTS: The mean score of correct responses was 1.83 of a possible 6.0. Almost one third of respondents answered all 6 vignettes incorrectly. The proportion of incorrect responses was high for all 6 vignettes (39%-86%), but higher for questions that addressed the immunization of children older than 12 months. Errors in vaccine administration were most commonly attributed to omitted vaccines, with varicella-zoster vaccine and pneumococcal conjugate vaccine omitted most frequently. Pediatricians were >4 times more likely to answer correctly than were family practitioners. Participants in the Vaccines for Children (VFC) program were more than twice as likely to answer correctly than were non-VFC providers. Knowledge of contraindications was inconsistent, particularly for measles-mumps-rubella vaccine. CONCLUSIONS: Childhood vaccine providers have substantial knowledge deficits of recommended immunization schedules and vaccine contraindications that may contribute to missed opportunities to immunize. Pediatricians and participants in the VFC program were more successful at designing catch-up regimens for children with immunization delay.

Age Factors↗

Combined immunization of infants with oral and inactivated poliovirus vaccines: results of a randomized trial in The Gambia, Oman, and Thailand. WHO Collaborative Study Group on Oral and Inactivated Poliovirus Vaccines.

To assess an immunization schedule combining oral (OPV) and inactivated poliovirus vaccines (IPV), we conducted a clinical trial in the Gambia, Oman, and Thailand. Children were randomized to receive one of the following schedules: OPV at birth, 6, 10, and 14 weeks of age; OPV at birth followed by both OPV and IPV at 6, 10, and 14 weeks of age: or placebo at birth followed by IPV at 6, 10, and 14 weeks of age. A total of 1685 infants were enrolled; 24-week serum specimens were available for 1291 infants (77%). Across the study sites at 24 weeks of age, the proportion of seropositive children in the combined schedule group was 95-99% for type 1, 99-100% for type 2, and 97-100% for type 3. In the Gambia and Oman, the combined schedule performed significantly better than OPV for type 1 (95-97% versus 88-90%) and type 3 (97-99% versus 72-73%). In the Gambia and Oman, seroprevalences in the IPV group were lower for type 1 (significantly lower in the Gambia); significantly lower for type 2; and significantly higher for type 3, compared with the OPV group. In Thailand, the IPV group had significantly lower proportions of children who were seropositive for each of the three types, compared with the OPV group. The responses to OPV in the Gambia, Oman, and Thailand were consistent with previous studies from these countries. IPV given at 6, 10, and 14 weeks of age provided inadequate serological protection against poliovirus, especially type 1. The combined schedule provided the highest levels of serum antibody response, with mucosal immunity equivalent to that produced by OPV alone.

Gambia↗

Poliomyelitis prevention. Immunization Practices Advisory Committee Centers for Disease Control.

This revised Immunization Practices Advisory Committee recommendation on poliomyelitis prevention addresses issues important in poliomyelitis prevention addresses issues important in poliomyelitis control in the United States today. Specifically, situations that constitute increased risk are defined, and alternatives for protection are outlined. Recommendations for immunization of adults are presented, clarifying the role of inactivated polio vaccine in immunizing adults. These recommendations also address the problems of interrupted immunization schedules and completion of primary immunization. Oral polio vaccine remains the vaccine of choice for primary immunization of children.

Adolescent↗

Control of hepatitis B: evaluation of two different vaccinal schedules in newborns from HBsAg negative mothers.

504 healthy infants, born to HBsAg negative mothers from May 1st to December 31st 1991, were randomly allocated to an accelerated (group A) or traditional (group B) immunization schedule. The group A infants were immunized at 4 days, 1 month and 3 months of life with 10 micrograms of recombinant HBV vaccine (Engerix B, SKF) while the group B infants were immunized at 4 days, 1 month and 6 months of life with the same dose of vaccine. One month after the first dose of vaccine, 9.2% of the infants in both groups had an HBsAb serum level > 10 mIU/ml. One month after the booster dose, at 4 months of life for group A and at 7 months for group B, 97.40% and 98.53% of the infants presented a serum level > 10 mIU/ml respectively. None in group A and only 2 patients in group B could be considered non-responders (serum concentration below 2 mIU/ml) and 4 infants in group A and 4 in group B were considered hypo-responders (serum level between 2.1 and 9.9 mIU/ml). Immunogenetic study performed on the 2 non-responders and 6 of the hypo-responders, revealed the presence in all but two of the HLA haplotypes, classically involved in the lack of hyporesponsiveness to foreign peptides, namely: HLA-DR7; DQ2, DR4; DQ3, DR15; DQ6 and DR3; DQ2. Surprisingly, 2 hypo-responders carried the HLA haplotypes (DR11, DQ7 and DR13, DQ6), usually associated with hyperresponsiveness. Both vaccinal cycles provided evidence that infants respond well to vaccination, started at birth, against hepatitis B virus with a high degree of protection.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation Studies as Topic↗

Specific and nonspecific protection of mice by Pseudomonas aeruginosa lipopolysaccharides.

The role of lipopolysaccharide (LPS) in eliciting a predominant cellular or humoral protection of mice is determined by the amount administered and the immunization schedule. Three basically different experimental conditions could be characterized. Five days after immunization with 100 micrograms of LPS, a nonspecific protection was observed due to the immunomodulatory capacity of lipid A. After 14 days, the same amount of LPS results in an O-specific humoral protection. On the other hand, 0.1 micrograms of LPS lead to a specific protection within 5 days after immunization due to a synergistic action of a specific humoral response (induced by the O-side chain) and a nonspecific signal modulated by lipid A. In order to study the role of each LPS region for protection, the free side chain was conjugated to albumin, followed by complexation with lipid A. To induce a nonspecific protection 5 days after immunization, the presence of lipid A was mandatory, in either the conjugated or free form. Removal of ester-linked fatty acids from free lipid A reduced its protective and mitogenic capacities by 50, and 25%, respectively.

Animals↗

[A calendar of prophylactic inoculations in wide practical use].

The validity of immunizations, made in due time in children aged up to 7 years in accordance with the approved immunization schedule, is analyzed in this work. The content of antibodies to diphtheria, tetanus and poliomyelitis antigens in children immunized in accordance with the old and new schedules has been studied. This study has revealed that the injection of adsorbed DPT vaccine to children aged 3-4 months induces fully valid immune response to all antigens under study. The level of measles and parotitis antibodies after the injections of measles and parotitis vaccines, introduced separately and simultaneously, has been measured. The simultaneous administration of these preparations did not decrease the levels of immunity to parotitis and measles.

Antibody Formation↗

How do physicians immunize their own children? Differences among pediatricians and nonpediatricians.

CONTEXT: Immunization has an essential impact on public health worldwide. Numerous studies have shown the efficacy of different vaccines to protect individuals from various diseases. However, some parents choose not to vaccinate their children for reasons such as, among others, doubts regarding their usefulness, concerns over safety or efficacy, etc. Physicians are known to exert a direct influence on immunization rates by answering questions and clarifying misconceptions. Yet, it is unknown how they immunize their own children. OBJECTIVE: We sought to assess how physicians interested in vaccination issues immunized, or would immunize, their own children. DESIGN, SETTING, AND PARTICIPANTS: An 11-question, Web-based survey with a total of 102 discrete answers was sent to 2070 Swiss physicians in October 2004. All physicians were subscribers to a nonprofit, Web-based expert network (InfoVac, www.infovac.ch) that distributes monthly newsletters and answers question within 2 days on immunization issues. The InfoVac network reaches > 95% of pediatricians in Switzerland but < 20% of general practitioners. All responses were anonymous, and no identifier could be used to trace the participants of the survey. Questions were divided into 2 parts: (1) physicians who were parents were asked which vaccines they gave to their own children and at what age, and (2) all physicians were asked which vaccines they would give to their own child and at what age if they had a newborn child in 2004. Vaccines available in Switzerland at the time of the survey were offered as possible replies, and recommended vaccines were considered as those noted in the Swiss federal immunization schedule issued yearly. One question compared their immunization practice between their own children and their patients. Sociodemographics, qualifying year, membership in different professional groups, and their type of practice were also requested. Statistics. Standard descriptive statistics were used for sociodemographic characteristics. Univariate statistical analyses were performed for each variable to determine its relationship to the dependent variable, being a pediatrician or nonpediatrician. Logistic-regression analysis was used to calculate the adjusted odds ratios (ORs) and 95% confidence intervals (CIs), controlling for any statistically significant demographic variables that might function as confounders (gender, parenthood, workplace, year of diploma, and type of practice). For all statistical tests, differences were considered significant at P < .05. MAIN OUTCOME MEASURE: We performed a comparison of past and projected immunization rates in the children of pediatricians and nonpediatricians. RESULTS: One thousand seventeen valid questionnaires were received (response rate: 49.1%; pediatricians: 53.3%). Nine hundred fifteen physicians (90%) had > or = 1 child. All physicians reported immunizing children in their practice. Pediatricians were more likely to be women and to work in private practice than nonpediatricians but less likely to belong to a self-reported alternative medicine association. Among the nonpediatricians, 317 were general practitioners, 144 were internists, and 95 were other specialists. Ninety-two percent of pediatricians followed the official immunization recommendations for their own children. In contrast, after controlling for gender, workplace, type of practice, and year of diploma, nonpediatricians were more likely not to have immunized their children against measles, mumps, hepatitis B, or Haemophilus influenzae type b. They more frequently postponed diphtheria-tetanus-pertussis (DTP) (OR: 4.5; 95% CI: 2.0-10.19) and measles-mumps-rubella (MMR) vaccination. Although projected immunization rates were higher than effective rates, 10% of nonpediatricians would still not follow the official immunization recommendations in 2004. They would more frequently refrain from using combination vaccines and postpone DTP and MMR immunization to later in life. Several comparisons confirmed the weaker use of the more recently licensed vaccines by nonpediatricians. In addition to vaccines currently recommended in Switzerland, both groups of physicians added hepatitis A, influenza, and varicella vaccines to the vaccination schedule of their own children. Pediatricians were more likely to give pneumococcal (OR: 2.26; 95% CI: 1.004-4.68) and meningococcal C (OR: 2.26; 95% CI: 1.62-3.17) vaccines to their own children. In contrast, they were less likely to give tick-borne encephalitis virus vaccine (OR: 0.65; 95% CI: 0.44-0.95). CONCLUSIONS: Ninety-three percent of the surveyed physicians agree with the current official vaccination recommendations and would apply them to their own children. However, the observation that 5% of nonpediatricians would not use Haemophilus influenzae type b vaccine if they had a child born in 2004 is unexpected and concerning. In contrast, both groups gave additional vaccines than those recommended to their own children. Among physicians in Switzerland interested in immunization, a significant proportion of nonpediatricians decline or delay the immunization of their own children with the recommended MMR- or DTP-based combination vaccines, which indicates that clarification of misconceptions such as fear of "immune overload" has not yet reached important targets among health care providers who thus are unlikely to answer parental concerns adequately.

Adolescent↗

The use of tolerization in the production of monoclonal antibodies against minor antigenic determinants.

An initial attempt to prepare monoclonal antibodies specific for the Dictyostelium discoideum lysosomal enzyme beta-glucosidase was unsuccessful. All of the antibodies resulting from this fusion recognized an extremely immunogenic epitope that is present on all of the lysosomal enzymes of Dictyostelium. In two succeeding fusions, changes in the immunization schedule intended to increase the immune response to enzyme-specific epitopes were not entirely successful. Although nine hybridomas producing antibodies specific for beta-glucosidase resulted from these two fusions, most (70%) of the cell lines isolated secrete antibodies that recognize the shared, immunodominant epitope. Moreover, the nine beta-glucosidase-specific antibodies proved to be of limited utility since none recognize the native enzyme. Therefore, we attempted to tolerize a BALB/c mouse to the common epitope by injecting the lysosomal enzyme, N-acetylglucosaminidase, within 40 h after birth. As an adult, this animal was immunized with beta-glucosidase. Fusion of the spleen cells from this mouse with myeloma cells resulted in the isolation of nine hybridoma lines that produce antibodies specific for beta-glucosidase. No antibodies reactive with the common epitope were detected. These results suggest that tolerization may provide a means whereby an undesired class of antibody-producing cell lines can be selectively eliminated from the products of a fusion.

Acetylglucosaminidase↗

Biodegradable poly(lactic-co-glycolic acid) microparticles for injectable delivery of vaccine antigens.

Injectable biodegradable polymeric particles (usually microspheres) represent an exciting approach to control the release of vaccine antigens to reduce the number of doses in the immunization schedule and optimize the desired immune response via selective targeting of antigen to antigen presenting cells. After the first couple of decades of their study, much progress has been made towards the clinical use of antigen-loaded microspheres. Poly(lactide-co-glycolic acids) (PLGAs) have been studied most commonly for this purpose because of their proven safety record and established use in marketed products for controlled delivery of several peptide drugs. PLGA microspheres have many desirable features relative to standard aluminum-based adjuvants, including the microspheres' ability to induce cell-mediated immunity, a necessary requirement for emergent vaccines against HIV and cancer. This review examines several impediments to PLGA microparticle development, such as PLGA-encapsulated antigen instability and deficiency of animal models in predicting human response, and describes new trends in overcoming these important issues. PLGA microparticles have displayed unprecedented versatility and safety to accomplish release of one or multiple antigens of varying physical-chemical characteristics and immunologic requirements, and have now met numerous critical benchmarks in development of long-lasting immunity after a single injected dose.

Animals↗

Occurrence of Haemophilus influenzae strains in three Brazilian states since the introduction of a conjugate Haemophilus influenzae type b vaccine.

Few vaccines in history have induced such a dramatic decline in incidence over such a short period of time as the Haemophilus influenzae type b (Hib) conjugate. This vaccine was introduced in 1988 in the United States, but only in 1999 was Hib immunization introduced by the Brazilian Ministry of Health as part of the routine infant National Immunization Program. The authors analyzed 229 H. influenzae (Hi) isolates from Public Health Laboratories in three Brazilian states: Pernambuco (Northeast, N = 54), Santa Catarina (South, N = 19), and Rio de Janeiro (Southeast, N = 156). The isolates were collected from Brazilian children 0-10 years of age with meningitis and other infections from 1990 to 2003 and were part of the research collection of the National Institute of Quality Control in Health, FIOCRUZ. Bacterial strains were characterized by serotyping and biotyping. During the pre-vaccination period the prevalence infection due to Hib was of 165 isolates and only 2 non-b Hi among all the notified meningitis infections caused by Hi. Our results showed a significant decrease in the prevalence of Hib meningitis from 165 to 33 isolates after 1999. However, during the post-vaccination period of 2001-2003 we observed an increase in the number of non-b Hi isolates: only 2 non-b strains isolated from 1990 to 1999 and 29 from 1999 to 2003. Based on the present data, the authors emphasize the need for more sensitive epidemiological and bacteriological studies aiming the improvement of the available Hib vaccine, in order to protect the susceptible population to infections due to other serological types of Hi and the reevaluation of immunization schedules used by the National Immunization Program.

Bacterial Capsules↗

General recommendations on immunization. Recommendations of the Advisory Committee on Immunization Practices (ACIP).

This revision of the General Recommendations on Immunization updates the 1989 statement. Changes in the immunization schedule for infants and children include recommendations that the third dose of oral polio vaccine be administered routinely at 6 months of age rather than at age 15 months and that measles-mumps-rubella vaccine be administered routinely to all children at 12-15 months of age. Other updated or new sections include a) a listing of vaccines and other immunobiologics available in the United States by type and recommended routes, advice on the proper storage and handling of immunobiologics, a section on the recommended routes for administration of vaccines, and discussion of the use of jet injectors; b) revisions in the guidelines for spacing administration of immune globulin preparations and live virus vaccines, a discussion of vaccine interactions and recommendations for the simultaneous administration of multiple vaccines, a section on the interchangeability of vaccines from different manufacturers, and a discussion of hypersensitivity to vaccine components; c) a discussion of vaccination during pregnancy, a section on breast-feeding and vaccination, recommendations for the vaccination of premature infants, and updated schedules for immunizing infants and children (including recommendations for the use of Haemophilus influenzae type b conjugate vaccines); d) sections on the immunization of hemophiliacs and immunocompromised persons; e) discussion of the Standards for Pediatric Immunization Practices (including a new table of contraindications and precautions to vaccination), information on the National Vaccine Injury Compensation Program, the Vaccine Adverse Events Reporting System, and Vaccine Information Pamphlets; and f) guidelines for vaccinating persons without documentation of immunization, a section on vaccinations received outside the United States, and a section on reporting of vaccine-preventable diseases. These recommendations are based on information available before publishing and are not comprehensive for each vaccine. The most recent Advisory Committee on Immunization Practices (ACIP) recommendations for each specific vaccine should be consulted for more details.

Adolescent↗

Serological response to early measles vaccination.

This study compares the persistence of measles IgG antibody in 239 children vaccinated at 6-8 months of age with 76 children vaccinated after 8 months of age. Among the children vaccinated prior to 9 months, 49 per cent of the children between 16 and 44 months and 33 per cent of children over 54 months had levels of measles IgG antibody conventionally considered protective. Among the children older than 48 months, 67 per cent of children vaccinated before 9 months and 13 per cent of children vaccinated after 8 months had antibody levels below the conventionally accepted protective levels of 0.2 IU/ml. Older children had lower antibody levels than younger children. Measles immunization before 9 months with the standard titer Edmonston-Zagreb vaccine has not provided a large proportion of under-five children with protective levels of measles IgG antibody. A significant proportion of children vaccinated at the currently recommended age also had suboptimal levels. It is difficult to protect the majority of the measles-susceptible population with a single dose regardless of the immunization schedule used. A second dose of measles vaccine may be necessary to increase the herd immunity.

Child, Preschool↗

[The expanded WHO vaccination program and the vaccination strategy in East Germany].

Evaluating the current stage and future trends of WHO's Expanded Programme on Immunization (EPI), conclusions for national immunization strategies have been considered. The global eradication of poliomyelitis is an important target. In 1988, an Immunization Advisory Group of the Ministry of Health has been founded. Recommendations regarding the update of immunization schedule have been elaborated. Changes are foreseen for BCG (deletion of revaccination), rubella (implementation of immunization for all girls aged 11/12 years), diphtheria (diphtheria/tetanus booster for adults), and measles (2-shot-strategy for young children and schoolchildren.

Child↗

Local immune response in mice to Vibrio cholerae.

Cholera immunization schedules were investigated in mice, with emphasis placed on obtaining an immune response in the intestine. The most effective schedule for producing a good local response was found to be several orally-given priming doses of the organism followed after 14 days by an intravenous boosting dose. Major differences between the immune responses in the spleen and the intestine were noted.

Animals↗

[Vaccination: 1982 status].

This review discusses the indications for the routine immunizations covered by the Swiss "Immunization Schedule 1981" (diphtheria, tetanus, pertussis, poliomyelitis, measles, mumps, rubella, BCG), as well as the indications for special immunizations (hepatitis B, influenza, pneumococci, rabies, tickencephalitis) and for the immunisations for travellers (cholera, yellow fever, meningococci, typhoid fever). Vaccination against measles, mumps and rubella should be given to girls and boys at the age of 18 (to 24) months as a combined injection. In view of the low prevalence of tuberculosis BCG vaccination is justifiable only at school leaving age, if at all. The indications for influenza and pneumococcal vaccines are still limited, the value of a general vaccination of all over 65 year old individuals is not proven for either vaccine. A nationwide vaccination campaign against hepatitis B was started early this year with a newly licensed vaccine for all population groups at risk. Only HDC-vaccines should be used for immunisation against rabies. The newly licensed, highly protective oral attenuated live typhoid vaccine will probably replace the parenteral typhoid vaccine.

Adolescent↗