Immunization Series Research Articles

Initiating the first DTP vaccination age-appropriately: a model for understanding vaccination coverage.

Our earlier research found that the strongest predictor of not being up to date on the full series of immunizations by 24 months is failure to receive the first diphtheria vaccine and tetanus toxoid and pertussis vaccine (DTP1) on time. To learn more about the relationship between successful vaccination during the DTP1 age-appropriate (DTP1-AA) period (between 42 and 92 days of life, inclusive) and an infant's early visit to the physician (before 42 days of life), we quantified children's progression through a sequence of provider visits and outcomes. This study analyzed data from 426 children living in the 57 poorest census tracts in Baltimore. For each DTP1-AA visit, we calculated the percentage of times a DTP1-AA vaccination, provider missed opportunity, or deferral for a valid contraindication occurred. Relative and attributable risks were computed to assess associations between DTP1-AA vaccination and early visits and missed opportunities. We found the following: 1) Children who made a visit before 42 days of life were more than twice as likely to receive a DTP1-AA vaccination; 2) the missed opportunity rate for children who did not make an early visit was approximately twice that of the early-visit group; and 3) well visits were more likely to result in DTP1-AA immunization than sick visits. Attributable risk calculations show that DTP1-AA vaccination rates could be increased in this population by one third if all infants had an early visit. Early in-office visits seem to make DTP1-AA vaccination more likely. These rates may be amenable to intervention by increasing early visits and reducing DTP1-AA missed opportunities. Introduction of the hepatitis B vaccine to the recommended series may place more emphasis on early visits and result in increased DTP1-AA rates and, ultimately, higher vaccination coverage rates.

ORAL IMMUNIZATION WITH A HELICOBACTER PYLORI (Hp) VACCINE DECREASES ENDOSCOPIC AND HISTOLOGIC DISEASE AND BACTERIAL LOAD IN H. MUSTELAE (Hm) CHALLENGED FERRETS.

38 Naturally occurring Hm infection of ferrets results in a similar spectrum of gastroduodenal disease as human Hp infection. However, previous studies of therapeutic vaccination in ferrets using vaccines of a“monovalent” Hp urease protein and cholera toxin adjuvant resulted in moderate reduction of Hm colonization and mucosal disease. Our study aims were to evaluate a combination of Hp proteins conjugated with a novel co-polymer adjuvant to determine ifHm infection and mucosal disease could be both prevented and treated. 4 groups of 4 “Hm-free” juvenile ferrets were given a vaccine consisting of whole-cell Hp proteins from acag A, vacA (+) isolate conjugated with a novel, mucosal bioavailable co-polymer adjuvant in 4 different combinations of administration routes as a primary and boost vaccination (oral or parenteral - primary; oral or parenteral - boost). ELISA was used to determine IgG antibody response to both Hp and Hm antigens at baseline, and following primary and boost immunizations. EGD was performed under conscious sedation after immunization series, 1 and 2 weeks post-Hm challenge. Biopsies were obtained at EGD and Hm infection status established by histologic evidence of organisms on Warthin-Starry stain, positive CLO™ test, or positive primary culture. Gastroduodenal pathology was determined using the Dubois method and bacterial numbers quantitated in a blinded, independent fashion. Additionally, 8 Hm-infected animals were either randomly treated with Hp vaccine/copolymer adjuvant (4) or with placebo. EGD was performed with similar biopsy analyses performed at baseline and following treatment. ELISA determination of ferret sera revealed both an Hp and Hm-specific IgG response in all animals evaluated. A rise inHp- specific IgG was observed in all immunized animals but significantly higher in those immunized parenterally. A subsequent significant rise in Hp-specific IgG was observed in the group that was crossed over with a parenteral boost, with only moderate IgG titer increase in the group receiving parenteral primary and boost vaccination. A clear difference was observed endoscopically and histologically in all animals that had been orally immunized, with concurrent decreased numbers of Hm bacteria. A moderate decrease in endoscopic and histologic disease was seen in vaccine-treated animals v. placebo controls. We conclude that prevention ofHelicobacter colonization and resultant disease can be achieved in a ferret model, but systemic antibody titers do not correlate with the protective mucosal response. Oral polyvalent Hp vaccines conjugated with novel, copolymer mucosal adjuvants show great promise as an effective method for both prevention and treatment of Helicobacter infection in a ferret model.

Antibody responses of three Haemophilus influenzae type b conjugate vaccines after one, two and three doses in Filipino children

Differences in the magnitude of antibody response after one, two or three doses of Haemophilus influenzae type b conjugate vaccines have been reported which may influence decision-making regarding which vaccine should be used. This is of particular importance in developing countries where children many not receive a full immunization series and the vaccination schedule may be delayed. Serum antibody responses to three Hib capsular polysaccharide protein conjugate vaccines (PRP-OMP, HbOC and PRP-T) were evaluated in 102 Filipino infants. Vaccination was carried out at 6, 10 and 14 weeks of age based on the national Expanded Programme on Immunization (EPI) schedule together with diphtheria-tetanus-pertussis, hepatitis B and oral poliomyelitis vaccines. Sera were collected at 6 weeks and 1 month after each vaccination. Anti-Hib polysaccharide antibody concentrations were determined by Farr-type radioimmunoassay (RIA) and enzymeimmunoassay (EIA). Following the first dose, the geometric mean concentrations (GMC, μg ml −1) for PRP-OMP, HbOC and PRP-T were 0.69, 0.27 and 0.38, respectively. After two doses, there was a significant response ( P < 0.05) to PRP-OMP and PRP-T (0.89 and 1.47) but not for HbOC (0.37). Differences in the GMC after the primary series were significant (pairwise P < 0.05): GMC was highest for PRP-T (4.0), followed by HbOC (1.6) and PRP-OMP (1.1). All three Hib vaccines were immunogenic when given in the local EPI schedule in Filipino infants although significant differences in the kinetics and magnitude of antibody responses were noted. The anti-Hib antibody concentrations determined by RIA and EIA were also compared in order to validate the latter for use in laboratories where it is feasible. There was a good correlation ( r 2 = 76%; P = 0.0001) in the Hib antibody titres obtained by both assays.

Three-year follow-up of vaccine response in extremely preterm infants.

To assess whether the adequate antibody response observed in former extremely premature infants after the primary series of immunizations is sustained after the first booster vaccines. Sixteen former extremely premature (<29 weeks, <1000 g at birth) and 17 former full-term (>37 weeks) infants had sera obtained for antibody titer measurement at 3 to 4 years of age. All had received the primary series and first booster vaccines for diphtheria, pertussis, tetanus, polio, and Haemophilus influenzae type b. Twelve preterm and 14 full-term children had completed the hepatitis B vaccine series. At 3 to 4 years of age, former preterm and full-term children had similar geometric mean titer (GMT) values of antibodies to tetanus, diphtheria, and pertussis. Preterm children had a lower GMT value of Haemophilus polyribosylribitol phosphate (PRP) antibody than did full-term children (0.99 vs 3.06 microg/mL). Fifty percent of preterm and 88% of full-term children had PRP antibody >1.0 microg/mL; 100% of preterm and 94% of full-term children had anti-PRP titers >0.15 microg/mL. GMT values of neutralizing antibodies to polio serotypes 1 and 2 were similar, with 94% to 100% of both groups above protective levels (>/=1:8). The difference in GMT values of polio serotype 3 approached significance (29 vs 73); fewer preterm children had protective titer values (75% vs 100%). Among children vaccinated against hepatitis B, 75% of preterm and 71% of full-term children were protected (10 mIU/mL). Preterm children immunized at the recommended chronological ages displayed antibody responses similar to those for full-term children for most immunizing antigens. Responses to PRP and polio serotype 3 were less robust than those of full-term children.

Interleukin-6 (IL-6), C-reactive protein (CRP), and Cardiorespiratory Responses to Primary Routine Immunization Series in Premature Infants with Bronchopulmonary Dysplasia (BPD) 1467

Interleukin-6 (IL-6), C-reactive protein (CRP), and Cardiorespiratory Responses to Primary Routine Immunization Series in Premature Infants with Bronchopulmonary Dysplasia (BPD) 1467

Differential Effects of a State Universal Purchase Program on Children's Immunization Rates According to Insurance Status ♦ 632

Background: To eliminate financial barriers to immunization, North Carolina implemented a universal vaccine purchase program, in which the state purchases vaccine serum for all children and distributes it free to all participating providers. Providers may charge an established administration fee only. Objective: This study examined the impact of the UP program on immunization rates for children with different types of insurance. Methods: From a random birth-certificate sample of 4,000 children born in 1994 and 1995, parents were interviewed to obtain children's sites of medical care and insurance history. Chart abstraction was performed in all sites of preventive care; details of insurance coverage were verified with insurance companies, employers, and the Division of Medical Assistance. Results: Parent interviews were completed for 71% of eligible children; chart abstraction and insurance data were obtained for 97% of those with parent interviews. In month-by-month comparisons, children born in 1995 had immunization rates 4%-10% higher than their 1994 counterparts. By 24 months of age, 84% of the 1995 cohort had completed the primary immunization series, compared with 79% of the 1994 cohort (p<0.001). In all insurance subgroups (i.e., fully insured for well-child care, partially insured for well-child care, insured but with no well-child benefits, enrolled in Medicaid exclusively or in combination with private insurance, or having some periods of being uninsured), 1995 immunization rates were higher than 1994 rates. The biggest increases in immunization rates from 1994 to 1995 occurred for children who were privately insured with no well-child coverage, children who had periods of being uninsured, and children enrolled in Medicaid exclusively or with private insurance. More children in the 1995 cohort received all immunizations in the private sector. Conclusion: The North Carolina universal purchase program appears to have had a significant, positive impact on immunization rates, especially for children with inadequate insurance for well-child care. However, insurance status still influences the ability of children to receive immunizations on schedule.

Update on childhood immunization.

Changes made in 1997 and 1998 in the U.S. childhood immunization schedule are discussed, with a focus on the use of poliovirus, pertussis, and combination vaccines. Oral poliovirus vaccine (OPV), the vaccine of choice for all four doses in the polio immunization series since 1962, can cause vaccine-associated paralytic poliomyelitis (VAPP). The inactivated poliovirus vaccine (IPV) has not been associated with VAPP but must be administered by injection and provides inferior intestinal immunity. With the reduced threat of poliovirus importation into the United States, the risk of VAPP, although low, has become less acceptable. The Centers for Disease Control and Prevention accordingly recommended a shift from OPV to IPV in the childhood immunization schedule for the United States, effective January 1997. A sequential OPV and IPV series is recommended, but the schedule includes an OPV-only option, which may be preferred in order to avoid the required injections, and an IPV-only option, which is recommended for immunocompromised persons and their contacts. Concern over local and systemic reactions associated with whole-cell pertussis vaccines, in addition to controversy over a possible relationship between the whole-cell vaccine and neurologic damage, has led to the development of new diphtheria and tetanus toxoids and acellular pertussis vaccine products for use in the diphtheria and tetanus toxoids and pertussis immunization series. Several combination products were licensed in 1997, and more are on the way. This will mean fewer inoculations for children. Increased use of IPV and acellular pertussis products could reduce the frequency of VAPP due to OPV and the local and systemic reactions associated with whole-cell pertussis vaccine.

Prediction of response to hepatitis B vaccine in health care workers: whose titers of antibody to hepatitis B surface antigen should be determined after a three-dose series, and what are the implications in terms of cost-effectiveness?

We identified the demographics of 385 health care workers (HCWs) to identify those whose chance of developing a protective response to a standard primary hepatitis B immunization series was so high that the need for testing for antibodies to hepatitis B surface antigen (anti-HBs) would be obviated following immunization. In addition, using sensitivity analysis, we analyzed the economic consequences of not determining anti-HBs titers for any individual after primary immunization and of using the Centers for Disease Control and Prevention (CDC)-recommended post-hepatitis B exposure prophylaxis for high-risk HCWs. Nonsmoking women < 50 years old with a weight-height index of < 42 had a 98.2 +/- 0.9% chance of developing a protective anti-HBs titer. Male nonsmokers < 50 years old with a weight-height index of < 29 had a 94.7 +/- 1.8% chance of a protective response. Economic analysis revealed that use of the CDC guidelines for post-hepatitis B exposure prophylaxis in male HCWs whose anti-HBs status is unknown is always more cost-effective than determining anti-HBs titers following primary immunization for those at high risk. In female HCWs, post-hepatitis B exposure prophylaxis is more cost-effective until hepatitis B exposure rats are approximately 50%. It is possible to predict who will have a high probability of developing a protective response to hepatitis B vaccine; for these people, determining postimmunization anti-HBs titers is unnecessary and not cost-effective.

Linear epitope mapping of humoral responses induced by vaccination with recombinant HIV-1 envelope protein gp160.

To enhance utility of the linear epitope mapping (Pepscan) technique for assay of humoral responses linked to vaccination, two modifications were tested. First, peptides were incubated with serum contained in baths rather than individual wells. Second, a rigorous statistical model was developed to determine which peptide/antibody-binding interactions were significant. The modifications increased the ability to detect signal in these experiments by 15- to 45-fold. These two modifications were applied to linear epitope mapping of HIV seropositive volunteers under treatment with recombinant HIV gp160 and also to rabbits immunized with the same product. Changes in fine specificity of response were observed in animal models and human vaccine recipients over the course of an immunization series with this antigen.

Diagnosis, treatment, and prevention of tetanus

The disease tetanus results primarily from the contamination of wounds with the bacterium Clostridium tetani. C tetani is a grampositive, anaerobic bacillus that produces two exotoxins, one of which is responsible for the clinical manifestations of the disease. Generalized tetanus, the most frequent form of the disease, presents with symptoms of muscle rigidity and spasms, and the characteristic feature, trismus (lockjaw). Diagnosis is made primarily by clinical observation combined with a supporting history of a wound and lack of proper immunization. Prevention of the disease is paramount as treatment is mainly supportive, and fatality rates are as high as 75%. Primary prevention consists of a series of immunizations administered in infancy and early childhood of tetanus toxoid combined with diphtheria and pertussis vaccines. Boosters are recommended at 10-year intervals. Secondary prevention involves debridement of wounds and administration of tetanus immune globulin and tetanus toxoid as needed, depending on the type of wound and the immunization history. Despite the excellent rates of immunization in the United States, approximately 50% of adults older than 50 years of age are susceptible to tetanus, either due to declining levels of antibodies or to lack of complete vaccination.

Use of Health Care Services by Inner-City Infants in an Early Discharge Program

Cooper, William O.; Kotagal, Uma R.; Atherton, Harry D.; Lippert, Carrie A.; Bragg, Elizabeth; Donovan, Edward F.; Perlstein, Paul H. Author Information

Safety and immunogenicity of two inactivated poliovirus vaccines in combination with an acellular pertussis vaccine and diphtheria and tetanus toxoids in seventeen- to nineteen-month-old infants

Objectives: To compare the safety and immunity of an acellular pertussis vaccine containing pertussis toxoid, filamentous hemagglutinin, 69 kd protein, fimbriae 2 and 3 combined with diphtheria and tetanus toxoids given as single or separate injection with inactivated poliovirus vaccine (MRC-5– or Vero cell–derived) or live attenuated polio vaccine. Methods: A total of 425 healthy children between 17 and 19 months of age who were receiving the fourth dose of their routine immunization series were randomly allocated to receive either the acellular pertussis vaccine and oral poliovirus vaccine or one of two inactivated poliovirus vaccines as a combined injection or separate injections. Results: Although minor adverse events were commonly reported, differences between the groups were few. Fever and decreased feeding were less common in recipients of live attenuated poliovirus vaccine than the combination vaccine containing MRC-5 cell–derived inactivated poliovirus vaccine. A significant antibody response was demonstrated in all groups against all the antigens contained in the vaccines. Antibodies against poliovirus were higher in the groups immunized with the inactivated poliovirus vaccine than the live attenuated vaccine. Anti–69 kd protein antibodies were higher in the group given the MRC-5 cell–derived inactivated poliovirus vaccine as a combined injection than in the group given the separate injection or the group immunized with the live attenuated poliovirus vaccine. Conclusion: The five-component acellular pertussis vaccine combined with diphtheria and tetanus toxoids is safe and immunogenic when combined with either MRC-5– or Vero cell– derived inactivated poliovirus vaccine. This will facilitate the implementation of acellular pertussis vaccine and the movement to inactivated poliovirus vaccine programs.

Safety and Immunogenicity of a DTaP-IPV Combination Vaccine in Infants for the Primary Immunization Series † 543

Safety and Immunogenicity of a DTaP-IPV Combination Vaccine in Infants for the Primary Immunization Series † 543

Safety and immunogenicity of an acellular pertussis diphtheria tetanus vaccine given as a single injection with Haemophilus influenzae b conjugate vaccine

To determine if an acellular pertussis-diphtheria-tetanus vaccine could be combined with a Haemophilus influenzae b conjugate vaccine as a single injection, we randomized 468 children between 17 and 21 months of age previously immunized with three doses of each vaccine to receive a five-component acellular pertussis vaccine combined with diphtheria and tetanus toxoids, and Haemophilus influenzae b-tetanus toxoid conjugate vaccine either as separate injections on separate days, separate injections on the same day, or as a single combined injection. Rates of adverse reactions were similar amongst the groups except for increased injection site tenderness (29.2% vs 17%, RR 1.76, 95% CI 1.09–2.85) and fussiness (36.4% vs 23.3%, RR 1.59, 95% CI 1.05–2.41) in the group given the combined injection rather than separate injections on separate days. Antibody levels against the capsular polysaccharide of H. influenzae b after the single combined injection (47.1 μg ml −1) were lower than after separate injections on the same day (66.0 μg ml −1; P<0.05) but higher than when the injections were administered on separate days (28.4 μg ml −1; P<0.001). We conclude that the five-component acellular pertussis vaccine is safe and immunogenic when combined with diphtheria and tetanus toxoids and H. influenzae b-tetanus toxoid conjugate vaccine in children receiving the fourth dose of the immunization series.

Future bright for more DTaP vaccines, expanded combinations

A flurry of activity in the development and licensing of DTaP (diphtheria-tetanus-acellular pertussis) vaccines coincides with the Academy9s release of a related policy statement, recommending the use of acellular over the whole-cell vaccine (DTwP) for the initial series in infants and children. These events may bode well for DTaP9s potential use in adults and for the future availability of more combined vaccines. The most recent event came at the close of 1996, with licensure of the first DTaP product for use in all five doses in the DTP immunization series. Licensed by Wyeth-Leder-le Vaccines and Pediatrics, the use of Acel-Imune (Diptheria and Tetanus Toixoids and Acellular Pertussis Vaccine Adsorbed), has been expanded to include infants at 2, 4 and 6 months of age. Until now, Acel-Imune had been approved for booster use in the fourth and fifth doses in children who had received the whole-cell vaccine in the first three doses.

Increasing immunization: a Medicaid managed care model.

To evaluate the impact of an immunization outreach program on immunization rates. A Pennsylvania independent practice association model managed care organization (100% Medicaid). Retrospective cohort study (N = 2511) of children 30 to 35 months of age from two age cohorts that compared immunization rates for Advisory Committee on Immunization Practices schedules for diphtheria-tetanus-pertussis, oral polio vaccine, measles-mumps-rubella, and Haemophilus influenza type b. An evaluation of the outreach component of the program compared treatment and nontreatment subgroups of one age cohort (N = 1002). The immunization program targeted approximately 19 000 members from birth to 6 years of age. The program components included computerized tracking and reminders, member and provider education, provider incentives, member incentives, and home visiting outreach. Data indicate that the treatment group has higher completed immunization rates at 35 months of age than does the control group. Furthermore, data show that members with home visits have significantly higher completed immunization rates than do other members. The corresponding comparisons for age-appropriate immunizations by 24 months indicate a nonsignificant trend of increased rates. The data provide evidence supporting a correlation between comprehensive strategies (computerized tracking, member and provider education and incentives, and home visiting) and increased immunization rates. Those individuals who received home visits were more likely to complete an immunization series by 35 months of age than those who did not. However, within the Mercy Health Plan program, age-appropriate immunizations are not significantly affected by home-visiting outreach.

Oral administration of Escherichia coli in enteric coated microparticles induces serum antibodies against lipopolysaccharide antigens

Heat-killed Escherichia coli O55:B5 were encapsulated in microcapsules coated with a pH-sensitive enteric coating (methacrylic acid copolymer). Oral immunization of C57BI/6 x DBA/2 (BDF1) mice with encapsulated bacteria resulted in a humoral immune response directed against bacterial lipopolysaccharide (LPS). This response was greatly boosted by a second series of immunization and differed both quantitatively and qualitatively from that induced by intraperitoneal immunization with non-encapsulated heat-killed bacteria. The anti-LPS response following oral immunization was comprised almost exclusively of IgG1 subclass antibodies and was highly specific for the LPS of the immunizing bacteria. The anti-LPS response following intraperitoneal immunization consisted mainly of IgM and IgG2a antibodies which were crossreactive with several bacterial strains. Our results demonstrate that whole killed bacteria, encapsulated by an enteric coating and administered orally, effectively induces an antibody response to LPS in mice which shows a typical memory response following secondary challenge.

Newborn hepatitis B immunization rates in primary care practices.

To assess the hepatitis B immunization rate and to identify the reasons for an incomplete immunization series in newborns and infants seen in primary care practices. An inception cohort study enrolling newborns and infants and assessing their hepatitis B immunization status at 9 and 18 months of age. Six primary care offices, most in rural environments. All newborns and infants seen at 1 of 6 offices. Infants born between January 1, 1993, and September 30, 1994, were followed up through June 30, 1995. Hepatitis B immunization status and the reasons for an incomplete status were recorded at each visit. Hepatitis B immunization rates at 9 and 18 months of age, and the reasons for immunization failure. The immunization rates of infants aged 9 and 18 months were 60% and 77%, respectively. The most common reasons for inadequate immunization of the 247 infants followed up through age 18 months were patient transfer (7%), failing to return for a scheduled visit (4%), and guardians refusing the immunization (4%). Failure to return for a scheduled visit was the reason for the incomplete immunization in 13% of the 9-month-old infants. Immunization of these patients was the most important factor in the higher immunization rate at 18 months of age. By the age of 18 months, 95% of all infants had received at least 2 doses of the hepatitis B immunization. A hepatitis B newborn immunization rate of 77% by age 18 months was achieved in a primary care office setting. Barriers to complete immunization by the age of 18 months include patient transfer, patient failure to return, and parental refusal of immunization.

Use of Health Care Services by Inner-city Infants in an Early Discharge Program

To assess the use of health care services by inner-city infants enrolled in an early discharge program who received care in tertiary care children's hospital primary care clinic. Retrospective cohort study. Large, metropolitan university hospital and a children's hospital. Term infants cared for in a single full-term nursery, before and after implementation of a coordinated early discharge program, who received primary care at the children's hospital. The coordinated Early Discharge Program was characterized by in-hospital visits by hospital-based coordinating nurses, home visits by nurses from a home nursing agency, and communication with physicians for necessary adjustments in postdischarge care. After linking birth hospital records and the children's hospital medical records, a retrospective chart review was performed to obtain maternal demographic information and birth hospital length of stay, as well as the infants' attendance at primary care clinic, immunizations, emergency department visits, and rehospitalization. Number of primary care visits in the first 3 months of life, completion of one series of immunizations by 3 months of life, and number of emergency department visits and rehospitalization during the first 3 months of life. The early discharge group (n = 253) had a significantly shorter birth hospital length of stay (35 +/- 24 hours, mean +/- SD) when compared with the control group (n = 212) (52 +/- 14 hours). The early discharge group was also younger than the control group at the first primary care visit, with significantly more infants visiting the primary care clinic in the first month of life. There was also a significant difference between the groups in the mean number of emergency department visits (early discharge = .61 visits/patient, control = .79 visits/patient) and the proportion of patients with no emergency department visits during the first 3 months of life (early discharge = 57%, control = 43%). There was no difference between the two groups in the proportion of infants completing one series of immunizations or in the number of infants rehospitalized during the study period. Coordinated early discharge with home nursing visits for inner-city infants may result in earlier use of primary care services. Furthermore, there is a significant decrease in use of the emergency department during the first 3 months of life, and no increase in rehospitalization.

Ten yearsʼ experience with Haemophilus influenzae type b (Hib) conjugate vaccines in Finland

Polysaccharide-protein conjugate vaccines against invasive infections caused by Haemophilus influenzae type b (Hib) bacteria have been studied intensively in Finland since 1983. The vaccines were shown to be immunogenic in young infants and to induce immunologic memory. The protective efficacy against Hib meningitis and bacteremic infections was 87–95% after the primary immunization series in two consecutive efficacy trials. Hib conjugate vaccines also reduced oropharyngeal carriage of Hib bacteria among healthy children. Large scale vaccinations have led to elimination of Hib disease in Finland.