Paralytic syndromes in children: epidemiology and relationship to vaccination.

Acute flaccid paralysis is a standard outcome for detection of poliomyelitis globally and an ongoing potential vaccine-associated adverse event concern for polio, influenza, and meningococcal vaccines. No systematic population-based data on the epidemiologic and clinical features of this condition, or its potential association with immunization, have been reported from the United States. The present retrospective cohort study of acute flaccid paralysis in the Southern and Northern California Kaiser Permanente Health Care Plans was conducted using computerized diagnosis data and medical record review of potential cases among children aged 1 month to <15 years and diagnosed from January 1, 1992 through December 31, 1998. In all, 3297 potential cases were identified; of these, 2682 cases (81%) did not meet the case definition, and of the remaining 615 cases, 245 (7% of the total) were included. The incidence of disease was 1.4 per 100,000 children/year (95% confidence interval = 1.2-1.6); predicting approximately 844 children/year in the United States. Disease incidence did not vary with season or sex, varied inversely with age, and declined 28% during the study period. No cases of vaccine-associated acute flaccid paralysis were identified. In nonendemic countries, ongoing acute flaccid paralysis surveillance is often conducted, because of the risk of poliovirus importation, but this practice may be difficult to justify, given low disease incidence and breadth of clinical presentation.

Evaluation of vaccine coverage for low birth weight infants during the first year of life in a large managed care population.

OBJECTIVE: There are few recent population-based assessments of vaccine coverage in premature infants available. This study assesses and compares age- and dose-specific immunization coverage in children of different birth weight categories during the first year of life. METHODS: We performed a retrospective cohort analysis of computerized vaccination data from a large managed care organization in southern California. The participants were children born between January 1, 1997, and December 31, 2002, and continuously enrolled from birth to at least 12 months of age in the Southern California Kaiser Permanente health plan. We measured age-specific up-to-date and age-appropriate immunization rates according to birth weight (extremely low birth weight: <1000 g; very low birth weight: 1000-1499 g; low birth weight: 1500-2499 g; normal birth weight: >/=2500 g) for 4 vaccines (hepatitis B, diphtheria and tetanus toxoids with pertussis, Haemophilus influenzae type b, and poliovirus) through the first year of life. RESULTS: We identified 127 833 infants born during the study period and continuously enrolled through the first year of life; 120 048 were normal birth weight infants; 6491 were low birth weight infants; 788 were very low birth weight infants; and 506 were extremely low birth weight infants. Vaccine-specific age-appropriate immunization rates were 3% to 15% lower for low birth weight infants and 17% to 33% lower for extremely low birth weight infants compared with the rates for normal birth weight infants in the first 6 months of life. Extremely low birth weight infants had the lowest age-specific up-to-date immunization levels (5%-31% lower) compared with normal birth weight infants at each age assessed. By 12 months, extremely low birth weight infants still had significantly lower up-to-date levels (87%) compared with very low birth weight, low birth weight, and normal birth weight infants (91%-92%). CONCLUSIONS: Despite recommendations that lower birth weight infants be vaccinated as the same chronological age as normal birth weight infants, extremely low birth weight and very low birth weight infants are immunized at significantly lower rates relative to low birth weight and normal birth weight infants at 2, 4, and 6 months of age. However, by 12 months of age this finding persists only in extremely low birth weight infants.

A population-based, postlicensure evaluation of the safety of a combination diphtheria, tetanus, acellular pertussis, hepatitis B, and inactivated poliovirus vaccine in a large managed care organization.

BACKGROUND: Prelicensure studies of diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated polio virus vaccine suggested that there were higher rates of fever after its administration than when its component antigens were given separately. METHODS: We conducted an open, controlled, cohort study to evaluate selected potential adverse events after receipt of diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated poliovirus vaccine in the Southern California Kaiser Permanente Health Care Plan. From April 2003 through June 2005, we identified 61,004 infants who received >or=1 dose of vaccine (120000 total doses). This group was compared with a previous cohort of 58,251 age-, gender-, and medical center-matched infants (116,637 doses) who received diphtheria, tetanus, acellular pertussis vaccine and separate doses of hepatitis B and inactivated poliovirus vaccines from January 2002 through March 2003. We compared the incidence of seizures, medically attended events that were associated with fever, and other selected adverse outcomes. RESULTS: We identified 16 infants (8 with fever) who had a seizure in the diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated poliovirus cohort and 15 infants (6 with fever) among control subjects in the 8-day period after receipt of any dose of vaccine. The incidence of all seizures or seizures associated with fever was not significantly different between cohorts. The incidence of medically attended events that were associated with fever in the 4-day period after any dose of vaccine was also similar in both cohorts. As well, no significant differences between the diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated poliovirus and control cohorts, were noted in the incidence of allergic reactions within 48 hours of any dose of vaccine, outpatient visits within 21 days, hospitalizations within 21 days, or death within 1 year. CONCLUSIONS: We did not observe a statistically significant increase in any of several clinically important safety events after diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated poliovirus vaccination compared with a historical cohort who received separate component vaccines.

Bordetella Pertussis infections in vaccinated and unvaccinated adolescents and adults, as assessed in a national prospective randomized Acellular Pertussis Vaccine Trial (APERT).

BACKGROUND: Acellular pertussis (aP) booster immunizations have been recommended for adolescents and older persons to enhance long-term protection and to possibly reduce community transmission of infections. METHODS: This was a multicenter, randomized, double-blind vaccine trial in which one-half of the subjects received aP vaccine and one-half received hepatitis A vaccine (control subjects). All subjects were observed for almost 2 years for cough illnesses, and all underwent microbiologic and serologic studies for detection of pertussis infection. Immunoglobulin G (IgG) and immunoglobulin A (IgA) antibodies to pertussis toxin, filamentous hemagglutinin, pertactin, and fimbriae 2/3 were measured by enzyme-linked immunosorbent assay in serum samples obtained 1 and 12 months after immunization. Infection rates were determined with a variety of serologic criteria for control and vaccinated subjects. The incidence of prolonged cough illness was ascertained for subjects with and subjects without serologic evidence of infection. RESULTS: Infection rates among control subjects are particularly representative of those in nonimmunized adults. Among control subjects, 0.4%-2.7% had increases in pertussis antibody of various types and degrees over 1 year, and 20%-46% had prolonged cough illnesses during this interval. Pertussis toxin antibody had the greatest specificity for detecting increases in antibody levels. Asymptomatic infections were approximately 5 times more common than clinical illnesses that met a strict clinical and microbiologic case definition. Relative to control subjects, aP-immunized subjects may have fewer increases in the antibody level (i.e., infections), especially for antibodies to fimbriae 2/3 (an antigen not in the vaccine). CONCLUSIONS: Pertussis infections in older persons are largely asymptomatic. aP boosters confer protection for adolescents and adults against symptomatic pertussis and likely confer protection against mild and asymptomatic infections, and use of boosters may reduce transmission to others, especially infants.

Haemophilus influenzae type B meningitis among children in Hanoi, Vietnam: epidemiologic patterns and estimates of H. Influenzae type B disease burden.

From March 2000 to February 2002, a population-based study of Haemophilus influenzae type b (Hib) meningitis was conducted among children less than five years of age in Hanoi, Vietnam. Children with suspected bacterial meningitis were referred to hospitals and each patient underwent standardized clinical examination and microbiologic testing. In Hanoi, 580 children were evaluated for bacterial meningitis and 23 (4%) had confirmed or probable Hib meningitis. The incidence of all Hib meningitis was 12/100,000 child-years less than five years of age and 26/100,000 child-years less than two years of age. Nationally, an estimated 1,005 children less than five years of age are hospitalized for Hib meningitis and 5,107 are hospitalized for Hib pneumonia. Among children with Hib meningitis, at least 100 will develop severe neurologic sequelae and 40 will die. These data suggest there is a substantial burden of Hib disease in Vietnam. National leaders will be provided with these data to facilitate development of national vaccination policies for children in Vietnam.

Efficacy of an acellular pertussis vaccine among adolescents and adults.

BACKGROUND: Pertussis immunization of adults may be necessary to improve the control of a rising burden of disease and infection. This trial of an acellular pertussis vaccine among adolescents and adults evaluated the incidence of pertussis, vaccine safety, immunogenicity, and protective efficacy. METHODS: Bordetella pertussis infections and illnesses were prospectively assessed in 2781 healthy subjects between the ages of 15 and 65 years who were enrolled in a national multicenter, randomized, double-blind trial of an acellular pertussis vaccine. Subjects received either a dose of a tricomponent acellular pertussis vaccine or a hepatitis A vaccine (control) and were monitored for 2.5 years for illnesses with cough that lasted for more than 5 days. Each illness was evaluated with use of a nasopharyngeal aspirate for culture and polymerase-chain-reaction assay, and serum samples from patients in both acute and convalescent stages of illness were analyzed for changes in antibodies to nine B. pertussis antigens. RESULTS: Of the 2781 subjects, 1391 received the acellular pertussis vaccine and 1390 received the control vaccine. The groups had similar ages and demographic characteristics, and the median duration of follow-up was 22 months. The acellular pertussis vaccine was safe and immunogenic. There were 2672 prolonged illnesses with cough, but the incidence of this nonspecific outcome did not vary between the groups, even when stratified according to age, season, and duration of cough. On the basis of the primary pertussis case definition, vaccine protection was 92 percent (95 percent confidence interval, 32 to 99 percent). Among unimmunized controls with illness, 0.7 percent to 5.7 percent had B. pertussis infection, and the percentage increased with the duration of cough. On the basis of other case definitions, the incidence of pertussis in the controls ranged from 370 to 450 cases per 100,000 person-years. CONCLUSIONS: The acellular pertussis vaccine was protective among adolescents and adults, and its routine use might reduce the overall disease burden and transmission to children.

Economic considerations for pertussis booster vaccination in adolescents.

BACKGROUND: Despite good acellular pertussis vaccine safety and protective efficacy, as well as high vaccination rates among young children, the incidence of pertussis in the United States has steadily increased since the 1980s. This is especially true for adolescents and adults who are susceptible because of waning immunity, which is not long lived. Other populations are at increased risk for morbidity of infection, although infants younger than 6 months of age who have not completed the primary immunization series have the greatest morbidity and mortality. Other groups who might benefit from booster immunizations include hospital workers, family contacts, and individuals with compromised health. Although older individuals generally have milder illnesses, they are often the source of infection for younger children. An adolescent/adult formulation of acellular pertussis vaccine requires a lower dose of pertussis antigens and can be combined with currently recommended diphtheria and tetanus toxoids (Tdap). These new vaccines for adolescents and adults are safe, immunogenic, and protective. METHODS: Through an extensive review of the literature, the direct and indirect costs associated with pertussis and its complications are examined, cost-benefit analyses of pertussis booster vaccination are evaluated for different groups, and the economic considerations involved in implementing a pertussis booster vaccination program in adolescents are discussed. RESULTS: Pertussis infections cause outbreaks in schools, families, and workplaces, resulting in prolonged morbidity and significant costs for medical care, lost time, and wages. Physician visits, chest radiographs, and antibiotics comprise the majority of direct costs, and costs associated with work loss often comprise the majority of indirect costs related to pertussis illness. Adolescents and adults also transmit their infections to nonimmune children. A cost-benefit analysis evaluated the health and economic benefits of seven strategies for administering a pertussis booster. The most economical strategy is to immunize all adolescents 10-19 years of age, which may prevent 0.4-1.8 million cases of pertussis and save US 0.3-1.6 billion dollars in a decade. A tetanus and diphtheria booster (Td) is currently recommended for children 11-12 years of age. The Tdap vaccine offers an enhancement for the Td booster by providing protection against pertussis, and it will not require an additional injection or office visit. CONCLUSIONS: Immunizing adolescents with a pertussis booster in the form of Tdap is the most economical and easiest-to-implement strategy and should provide significant health and economic benefits.

A bovine parainfluenza virus type 3 vaccine is safe and immunogenic in early infancy.

BACKGROUND: A phase 2 trial was conducted to assess in young infants the safety, tolerability, infectivity, and immunogenicity of multiple doses of an intranasal vaccine using bovine parainfluenza virus type 3 (bPIV3). METHODS: One hundred ninety-two healthy 2-month-old infants were randomized 1 : 1 : 1 to receive 1x10(5) median tissue culture infective dose (TCID(50)) bPIV3 vaccine, 1x10(6) TCID(50) bPIV3 vaccine, or placebo at 2, 4, 6, and 12-15 months of age. Safety information was collected by use of diary sheets and telephone interviews. Nasal wash and serum specimens were collected for assessment of infectivity and immunogenicity. RESULTS: The safety profiles of both dosages of bPIV3 were similar to that of placebo, with the exception of fever with temperature of >/=38.1 degrees C after dose 2 only, occurring in 34% of the 1x10(5) TCID(50) group, 35% of the 1x10(6) TCID(50) group, and 12% of the placebo group (P<.01). No vaccine-related serious adverse events were reported. The cumulative vaccine infectivity (isolation of bPIV3 and/or bPIV3 seroconversion) after dose 3 was similar in the 2 vaccine groups (87% in the 1x10(5) TCID(50) group and 77% in the 1x10(6) TCID(50) group) (P=.46). Seroconversion rates after dose 3, assessed by means of hemagglutination inhibition assay, after adjustment for decrease in maternal antibody titers, were 67% in the 1x10(5) TCID(50) group, 57% in the 1x10(6) TCID(50) group, and 12% in the placebo group (P<.01). Isolation of bPIV3 was common after dose 1, dose 2, or dose 3, but only 1 of 51 participants in the vaccine groups had bPIV3 isolated after dose 4. CONCLUSIONS: Multiple doses of bPIV3 vaccine were well tolerated and immunogenic in young infants.

Compliance with national immunization guidelines for children younger than 2 years, 1996-1999.

OBJECTIVES: To evaluate compliance with national immunization guidelines among a large cohort of children cared for at health maintenance organizations (HMOs) and to examine effects on immunization status. METHODS: A cohort study of 176134 children born between January 1, 1994, and December 31, 1997, and monitored from birth to the second birthday was performed. Subjects belonged to the Vaccine Safety Datalink Project, a study of children enrolled in 1 of 4 HMOs. Children were continuously enrolled in a HMO for the first 2 years of life. Prevailing recommendations regarding optimal ages of immunization and intervals between doses were applied to define appropriate immunization timing and immunization status. Noncompliance was defined as having a missing or late immunization or an immunization error. Immunization errors included invalid immunizations (too early to be acceptable), extra immunizations (superfluous immunizations or make-up immunizations for invalid immunizations), and missed opportunities resulting in late or missing immunizations. RESULTS: Although 75.4% of children in these HMOs were up to date for all immunizations at 2 years, only 35.6% of children were fully compliant with recommended immunization practices. Less than 8% of children received all immunizations in accordance with strict interpretation of recommended guidelines. Fifty-one percent of children had at least 1 immunization error by age 2 years; 29.7% had a missed opportunity with subsequent late or missing immunization, 20.4% had an invalid immunization, and 11.6% had an extra immunization. Common reasons for noncompliance included missed opportunities for the fourth Haemophilus influenzae type b vaccine (14.6%), invalid fourth diphtheria-tetanus-pertussis/acellular pertussis immunizations (11.0%), and superfluous polio immunizations (9.8%). CONCLUSIONS: Approximately 35.6% of children were compliant with prevailing childhood immunization recommendations from 1996 to 1999. Efforts to improve compliance with guidelines are recommended, to optimize childhood infectious disease prevention.

Prevalence of antibody to Bordetella pertussis antigens in serum specimens obtained from 1793 adolescents and adults.

Serum specimens were obtained from all subjects in the adolescent and adult acellular pertussis (aP) vaccine efficacy trial before and after immunization to study the prevalence of IgG and IgA antibody and geometric mean titers to 4 Bordetella pertussis antigens. Of 1793 adolescents and adult subjects who received aP vaccine, only 20%, 68%, 59%, and 39% had concentrations of IgG antibodies to pertussis toxin, filamentous hemagglutinin, pertactin, and fimbriae types 2 and 3, respectively, that were greater than or equal to the limit of quantitation of the enzyme-linked immunosorbent assay used in the analysis. There was minimal variation in antibody prevalence with respect to geographic area, age, sex, or race.

Acellular pertussis vaccines and complement killing of Bordetella pertussis.

Antibody-dependent complement killing of Bordetella pertussis after immunization with a three-component acellular pertussis vaccine was characterized. Postimmunization activity was unchanged for about half of the adult vaccine recipients. The responses of the other individuals were complex, with evidence of both beneficial and antagonistic responses occurring, sometimes in the same individual.

Immune responses and antibody decay after immunization of adolescents and adults with an acellular pertussis vaccine: the APERT Study.

As part of a prospective acellular pertussis (ACP) vaccine efficacy trial, 5 serum samples were obtained, over an 18-month period, from 101 ACP-vaccine recipients and 99 control subjects, to assess ACP antibody response and decay. Immunoglobulin (Ig) G and IgA antibodies to pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin (PRN), and fimbriae 2/3 (FIM) were measured by enzyme-linked immunosorbant assay, and titers of agglutinin were determined. Of the subjects, 16%-19% had preimmunization values of antibodies to PT that were above the assay's limit of quantitation (LOQ); in contrast, 36%-63% of the subjects had preimmunization values of antibodies to FHA, PRN, or FIM that were above the LOQ. Substantial increases in titers of IgG and IgA antibodies to the 3 ACP antigens (PT, FHA, and PRN) were observed. Over the 18-months, the percent decay in IgG and IgA antibodies ranged from 56% to 73% and from 57% to 70%, respectively; the IgG antibody response and decay suggests that geometric mean titers likely remain above the LOQ for 2-9 years and above the threshold of detection for 4-13 years. These findings support the use of ACP booster immunizations for adolescents and adults, to provide sustained levels of antibody.

Lack of association between hepatitis B birth immunization and neonatal death: a population-based study from the vaccine safety datalink project.

BACKGROUND: There have been no population-based studies of the potential association between neonatal death and newborn immunization with hepatitis B vaccine (HBV). METHODS: As part of the Vaccine Safety Datalink Project, we defined a birth cohort at Southern and Northern California Kaiser Permanente Health Plans of more than 350,000 live births from 1993 to 1998 and ascertained all deaths occurring under 29 days of age. We compared the proportions of deaths among birth HBV-vaccinated and unvaccinated newborns and reviewed the causes and circumstances of their deaths. We performed detailed clinical reviews of all HBV-vaccinated neonates who died and a sample of unvaccinated neonates who died and who were matched to vaccinated deaths for days of life, sex, birth year and site of care. To avoid confounding, we categorized the causes of death as either "expected" or "unexpected" and performed a stratified analysis to compare mortality with immunization status. RESULTS: There were 1363 neonatal deaths during the study period. Whereas 67% of the entire birth cohort received HBV at birth, only 72 (5%) of the neonates who died were HBV-vaccinated at birth (P < 0.01). We found no significant difference in the proportion of HBV-vaccinated (31%) and unvaccinated (35%) neonates dying of unexpected causes (P = 0.6). Further we could not identify a plausible causal or temporal relationship between HBV administration and death for the 22 vaccinated neonates who died unexpectedly. CONCLUSIONS: A relationship between HBV and neonatal death was not identified.

Evaluation of strategies for use of acellular pertussis vaccine in adolescents and adults: a cost-benefit analysis.

Pertussis is increasingly recognized as a source of infection in adults who then commonly infect young children. Immunity to illness caused by Bordetella pertussis is not long-lived, so optimal control of pertussis may require booster immunizations. In a cost-benefit analysis, we evaluated the benefits of 7 independent strategies for administering a pertussis booster, in the form of a diphtheria-tetanus-acellular pertussis vaccine, to adolescents and adults. Break-even vaccine costs for each strategy were calculated by dividing costs preventable by vaccine by the number of persons eligible for vaccination. Of these strategies, the most economical would be to immunize adolescents 10-19 years of age, which would prevent 0.7-1.8 million pertussis cases and save 0.6 dollars-1.6 billion dollars over a decade. Although justified by our analysis, routine adult booster vaccinations every decade would be more expensive and more difficult to implement. A recommendation for booster vaccinations every 10 years requires more information about duration of immunity, program costs, compliance, and nonmedical costs associated with pertussis.

Antibody-mediated neutralization of pertussis toxin-induced mitogenicity of human peripheral blood mononuclear cells.

Antibody-mediated neutralization of pertussis toxin-induced proliferation of human peripheral blood mononuclear cells (PBMC) was assessed using alamarBlue and compared with results from the Chinese hamster ovary (CHO) cell assay using sera from vaccinated adults and convalescent children. Neutralization values for the CHO assay were similar for vaccinated and convalescent subjects; however. the convalescent group had higher titers in the PBMC assay. Results for pertussis toxin neutralization with the CHO assay appear to be distinct from those with the PBMC assay.

Heptavalent pneumococcal vaccine conjugated to outer membrane protein of Neisseria meningitidis serogroup b and nasopharyngeal carriage of Streptococcus pneumoniae in infants.

BACKGROUND: Streptococcus pneumoniae (Sp) is an important bacterial pathogen in children. Nasopharyngeal (NP) colonization of S. pneumoniae is necessary for person-to-person transmission and often precedes invasive disease. METHODS: NP carriage of Sp was studied in 49 infants following administration of a heptavalent pneumococcal conjugate vaccine (PCV) conjugated to the outer membrane protein of serogroup b Neisseria meningitidis (vaccine serotypes: 4, 6B, 9V, 14, 18C, 19F, 23F). The vaccine was administered at 2, 4, 6, and 12 months of age and carriage rates were compared to a concurrent group of 32 infants not given PCV and evaluated over the first 15 months of life. RESULTS: Overall, Sp was isolated in 86/367 (23%) of NP cultures and 49% of infants. Serotype 23F was significantly less prevalent in the PCV group (1.9%) than the control group (16.1%) (P<0.05). Analysis of the proportion of children with prevalent carriage or acquisition of carriage did not differ between groups when evaluated by age or serotype. We noted, however, decreased acquisition and carriage in the vaccine group 1 month following the 12 month dose of PCV for vaccine serotypes (76 and 52% reduction, respectively), but this did not reach statistical significance (P=0.3). Adjustment for age, daycare and antibiotic use by multivariate modeling revealed no difference in carriage of vaccine containing serotypes or non-vaccine serotypes between groups. CONCLUSION: We did not show a significant effect of this heptavalent PCV on NP carriage. Further study of this issue, including a larger population size, is needed.

Safety and immunogenicity of a heptavalent pneumococcal conjugate vaccine in infants.

OBJECTIVE: To evaluate the safety and immunogenicity of two lots of a heptavalent Streptococcus pneumoniae conjugate vaccine (PCV) containing seven capsular polysaccharide serotypes (4, 6B, 9V, 14, 18C, 19F, and 23F) conjugated to the outer membrane complex of Neisseria meningitidis serogroup B (OMPC) and administered to infants at 2, 4, 6, and 12 months of age. METHODS: One hundred twenty infants were randomly assigned to concurrently receive PCV-OMPC and one of two Haemophilus influenzae type b (Hib) conjugate-DTwP combination vaccines: (1) Hib with a heterologous protein carrier (CRM(197), TETRAMUNE, Group 1) or (2) an experimental Hib-hepatitis b combination vaccine with the homologous carrier (OMPC, Group 2). All infants in Groups 1 and 2 received PCV-OMPC (lot 1) at 12 months of age. Another separate group of 120 infants (Group 3) received a different lot of PCV-OMPC concurrently with Hib-CRM(197) (TETRAMUNE) at 2, 4, and 6 months of age and then were randomized to receive either PCV-OMPC or a 23-valent polysaccharide (PS) pneumococcal vaccine at 12 months of age. RESULTS: Each PCV-OMPC lot was generally well tolerated and no vaccine-related serious adverse events were reported. Following the primary series, serotype-specific anti-pneumococcal geometric mean concentrations (GMC) were highest for serotypes 14, 19F, and 4 and lowest for serotypes 6B and 23F. GMC and seroconversion rates in Group 3 (lot 2) were lower than in Group 1 (lot 1) for serotypes 6B, 14, 18C, and 23F. Antibody responses to serotypes 6B, 14, and 18C were significantly lower in Group 2 compared to Group 1. Following a booster dose of PCV-OMPC at 12 months of age, each lot was immunogenic with at least a 5-10-fold increase in antibody levels, and responses were significantly higher among those who received the PS vaccine. CONCLUSIONS: PCV-OMPC is generally safe in infants, displays variable immune response by serotype, and concomitant receipt of Hib vaccine with homologous carrier may impact on its immunogenicity.

Polio extraimmunization in children younger than 2 years after changes in immunization recommendations.

OBJECTIVE: To investigate trends over time in polio extraimmunization among children in 4 large health maintenance organizations and to study the association with recent changes in polio immunization policy. METHODS: Using 176 169 children who were born after 1994 and enrolled for their first 2 years of life, we assessed rates and trends of polio extraimmunization in the Vaccine Safety Datalink project. We used logistic regression to test the association of extraimmunization with different polio immunization schedules and with sociodemographic characteristics and used Poisson regression to test changes in rates over time. RESULTS: Overall, 10.5% were extraimmunized for poliovirus; children on the all inactivated polio virus or sequential schedule were one half as likely as those on the all oral polio virus schedule to be extraimmunized by 2 years of age. There was a significant decrease in extraimmunization over time, with <5% of children born at the end of 1997 being extraimmunized, compared with >15% at the beginning of 1994. CONCLUSIONS: Poliovirus extraimmunization rates have fallen dramatically in association with the change-over to the all inactivated polio virus schedule.

Childhood vaccinations and risk of asthma.

BACKGROUND: A few previous studies have suggested that childhood vaccines, particularly whole cell pertussis vaccine, may increase the risk of asthma. We evaluated the suggested association between childhood vaccinations and risk of asthma. METHODS: Cohort study involving 167,240 children who were enrolled in 4 large health maintenance organizations during 1991 to 1997, with follow-up from birth until at least 18 months to a maximum of 6 years of age. Vaccinations were ascertained through computerized immunization tracking systems, and onset of asthma was identified through computerized data on medical care encounters and medication dispensings. RESULTS: In the study 18,407 children (11.0%) developed asthma, with a median age at onset of 11 months. The relative risks (95% confidence intervals) of asthma were: 0.92 (0.83 to 1.02) for diphtheria, tetanus and whole cell pertussis vaccine; 1.09 (0.9 to 1.23) for oral polio vaccine; 0.97 (0.91 to 1.04) for measles, mumps and rubella (MMR) vaccine; 1.18 (1.02 to 1.36) for Haemophilus influenzae type b (Hib); and 1.20 (1.13 to 1.27) for hepatitis B vaccine. The Hib result was not consistent across health maintenance organizations. In a subanalysis restricted to children who had at least 2 medical care encounters during their first year, the relative risks decreased to 1.07 (0.71 to 1.60) for Hib and 1.09 (0.88 to 1.34) for hepatitis B vaccine. CONCLUSION: There is no association between diphtheria, tetanus and whole cell pertussis vaccine, oral polio vaccine or measles, mumps and rubella vaccine and the risk of asthma. The weak associations for Hib and hepatitis B vaccines seem to be at least partially accounted for by health care utilization or information bias.