Primary Immunization Of Infants Research Articles

Maternal pertussis immunization and the blunting of routine vaccine effectiveness: a meta-analysis and modeling study

A key goal of pertussis control is to protect infants too young to be vaccinated, the age group most vulnerable to this highly contagious respiratory infection. In the last decade, maternal immunization has been deployed in many countries, successfully reducing pertussis in this age group. Because of immunological blunting, however, this strategy may erode the effectiveness of primary vaccination at later ages. Here, we systematically reviewed the literature on the relative risk (RR) of pertussis after primary immunization of infants born to vaccinated vs. unvaccinated mothers. The four studies identified had ≤6 years of follow-up and large statistical uncertainty (meta-analysis weighted mean RR: 0.71, 95% CI: 0.38–1.32). To interpret this evidence, we designed a new mathematical model with explicit blunting mechanisms and evaluated maternal immunization’s short- and long-term impact on pertussis transmission dynamics. We show that transient dynamics can mask blunting for at least a decade after rolling out maternal immunization. Hence, the current epidemiological evidence may be insufficient to rule out modest reductions in the effectiveness of primary vaccination. Irrespective of this potential collateral cost, we predict that maternal immunization will remain effective at protecting unvaccinated newborns, supporting current public health recommendations.

Reduced reactogenicity of primary vaccination with DT3aP-HBV-IPV/Hib compared with DT2aP-HBV-IPV-Hib among infants: Mathematical projections in six countries

ABSTRACT The hexavalent vaccines DT3aP-HBV-IPV/Hib and DT2aP-HBV-IPV-Hib are routinely used for primary immunization of infants against diphtheria, tetanus, pertussis, hepatitis B virus, poliomyelitis, and Haemophilus influenzae type b. A recent publication showed that after primary immunization with these vaccines, the odds ratios of adverse reactions (ARs) were significantly lower for DT3aP-HBV-IPV/Hib than for DT2aP-HBV-IPV-Hib. Our aim is to understand the impact of the various reactogenicity profiles at country level by comparing the ARs induced by one dose of DT3aP-HBV-IPV/Hib versus DT2aP-HBV-IPV-Hib in the primary infant immunization course. A mathematical projection tool was developed to simulate vaccination of infants with both vaccines in six countries: Austria, the Czech Republic, France, Jordan, Spain, and the Netherlands. Proportions of three local and five systemic ARs of interest for both vaccines were based on findings from a previous meta-analysis of ARs in infants. The absolute risk reductions calculated ranged from 3.0% (95% confidence interval [CI]: 2.8%–3.2%) for “Swelling at the injection site, any grade” to 10.0% (95% CI: 9.5%–10.5%) for “Fever, any grade.” The difference in occurrence of the AR “Fever, any grade” between vaccines in 2020 ranged from over 7,000 in Austria to over 62,000 in France. Over 5 years, this would amount to a reduction of over 150,000 ARs in Austria and over 1.4 million ARs in France when using DT3aP-HBV-IPV/Hib instead of DT2aP-HBV-IPV-Hib. In conclusion, the estimated numbers of ARs following hexavalent vaccination in six countries showed that vaccination of infants with DT3aP-HBV-IPV/Hib could lead to fewer ARs than vaccination with DT2aP-HBV-IPV-Hib.

A phase IV, multi-centre, randomized clinical trial comparing two pertussis-containing vaccines in pregnant women in England and vaccine responses in their infants

BackgroundPertussis vaccines containing three or five pertussis antigens are recommended in pregnancy in many countries, but no studies have compared the effect on infants’ antigen-specific immunoglobulin G (IgG) concentrations. The aim of this study was to compare anti-pertussis IgG responses following primary immunization in infants of mothers vaccinated with TdaP5-IPV (low dose diphtheria toxoid, tetanus toxoid, acellular pertussis [five antigens] and inactivated polio) or TdaP3-IPV in pregnancy (three pertussis antigens).MethodsThis multi-centre phase IV randomized clinical trial was conducted in a tertiary referral centre and primary care sites in England. Women were randomized to receive TdaP5-IPV (n = 77) or TdaP3-IPV (n = 77) at 28–32 gestational weeks. A non-randomized control group of 44 women who had not received a pertussis-containing vaccine in pregnancy and their 47 infants were enrolled post-partum.ResultsFollowing infant primary immunization, there was no difference in the geometric mean concentrations (GMCs) of anti-pertussis toxin, filamentous haemagglutinin or pertactin IgG between infants born to women vaccinated with TdaP5-IPV (n = 67) or TdaP3-IPV (n = 63). However, the GMC of anti-pertussis toxin IgG was lower in infants born to TdaP5-IPV- and TdaP3-IPV-vaccinated mothers compared to infants born to unvaccinated mothers (n = 45) (geometric mean ratio 0.71 [0.56–0.90] and 0.78 [0.61–0.98], respectively); by 13 months of age, this difference was no longer observed.ConclusionBlunting of anti-pertussis toxin IgG response following primary immunization occurs in infants born to women vaccinated with TdaP5-IPV and TdaP3-IPV, with no difference between maternal vaccines. The blunting effect had resolved by 13 months of age. These results may be helpful for countries considering which pertussis-containing vaccine to recommend for use in pregnancy.Trial registrationClinicalTrials.gov, NCT02145624, registered 23 May 2014

Ensuring the Safety of Maternal Immunization

* Abbreviation: Tdap — : tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis, adsorbed Over the past decade, the acceptance and implementation of maternal vaccination strategies has bourgeoned.1 There are several reasons that immunizing pregnant women is an attractive vaccination strategy. First, by immunizing the pregnant woman, there is the potential to prevent the targeted infection in the woman and her infant. Second, there is a window of susceptibility in infants before the initiation of the primary infant immunization series. Maternal immunization can help bridge this window of susceptibility. Finally, pregnant women are often more adherent to medical care during their pregnancies than at other times in their lives, thus making vaccine administration more efficient. However, although we have made significant progress in the implementation of maternal-immunization programs, the uptake of maternal immunization in the United States for influenza and tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis, adsorbed (Tdap) vaccine hovers between 50% and 70%.2,3 When pregnant women are asked why they do not receive a vaccine, one of the more commonly reported reasons is concern about safety for the fetus and the long-term adverse risks to the infant.2 … Address correspondence to Kathryn M. Edwards, MD, Division of Pediatric Infectious Diseases, Department of Pediatrics, Vanderbilt University Medical Center, D-7221 Medical Center North, Nashville, TN 37232. E-mail: kathryn.edwards{at}vumc.org

Sustained Effectiveness of the Maternal Pertussis Immunization Program in England 3 Years Following Introduction.

The effectiveness of maternal immunization in preventing infant pertussis was first demonstrated in England, 1 year after the program using diphtheria–tetanus–5-component acellular pertussis–inactivated polio vaccine (dT5aP-IPV) was introduced in 2012. Vaccine effectiveness against laboratory-confirmed pertussis has been sustained >90% in the 3 years following its introduction, despite changing to another acellular vaccine with different antigen composition. Consistent with this, disease incidence in infants <3 months of age has remained low despite high activity persisting in those aged 1 year and older. Vaccine effectiveness against infant deaths was estimated at 95% (95% confidence interval, 79%–100%). Additional protection from maternal immunization is retained in infants who received their first dose of the primary series. There is no longer evidence of additional protection from maternal vaccination after the third infant dose. Although numbers are small and ongoing assessment is required, there is no evidence of increased risk of disease after primary immunization in infants whose mothers received maternal vaccination.

Combined tetanus-diphtheria and pertussis vaccine during pregnancy: transfer of maternal pertussis antibodies to the newborn

Background and objectivesPertussis is currently an emerging public health concern in some countries with high vaccination coverage. It is expected that maternal pertussis immunization could provide newborn protection. We compared pertussis toxin antibody (anti-PT) levels in women during pregnancy (pre- and post-vaccination) with respect to levels in the newborn at delivery in women vaccinated during pregnancy. We also estimated anti-PT titers at primary infant vaccination. MethodsObservational study of pregnant women vaccinated with Tdap (≥20 weeks gestation) and their newborns between May 2012 and August 2013. Anti-PT levels were determined by ELISA in maternal (pre- and post-vaccination) and newborn blood. ResultsPre-vaccination, post-vaccination maternal and newborn samples were available in 132 subjects. Mean maternal age was 34.2 (SD 4.3) years. Median weeks of gestation at vaccination were 27.2 (Q1–Q3 21.7–30.8). Anti-PT (≥10IU/ml) levels were found in 37.1% of maternal pre-vaccination samples (geometric mean titer (GMT) 7.9IU/ml (95% CI 6.8–9.2)), 90.2% of post-vaccination samples (GMT 31.1IU/ml (95% CI 26.6–36.3)) and 94.7% of newborns (GMT 37.8IU/ml (95% CI 32.3–44.1)). The Lin concordance index between post-vaccination maternal and newborn samples was 0.8 (95% CI 0.8–0.9). Transplacental transfer ratio was 146.6%. At two months of age, 66% of newborns had estimated anti-PT levels ≥10IU/ml. ConclusionsThere was a high correlation between anti-PT levels in mothers and newborns, with higher levels in newborns, which should be sufficient to provide protection against pertussis during the first months of life. Vaccination of pregnant women seems to be an immunogenic strategy to protect newborns until primary infant immunization.

Primary Immunization of Infants and Toddlers in Thailand with Japanese Encephalitis Chimeric Virus Vaccine in Comparison with SA14-14-2

The live, attenuated Japanese encephalitis (JE) chimeric virus vaccine (JE-CV) is licensed in Thailand and Australia for prophylaxis of JE in individuals at the age of 12 months. JE-CV has not yet been compared with the SA14-14-2 JE vaccine, which is also licensed in Thailand. In this phase 3, observer-blinded trial, 300 children at the age of 9-18 months were randomized 1:1 to receive 1 dose of JE-CV or SA14-14-2. JE neutralizing antibody titers were assessed using PRNT50. The primary endpoint was the noninferiority of seroconversion against JE on Day 28 after JE-CV compared with SA14-14-2, as assessed using the 95% confidence interval of the difference between the groups. Safety and reactogenicity were described in each group using conventional methods, including the reporting of solicited and unsolicited adverse events. The seroconversion rate on Day 28 was 99.2% in each group. Noninferiority was demonstrated as the difference between the JE-CV and SA14-14-2 groups was -0.012 percentage points (95% confidence interval: -3.6 to 3.6), which was above the required -10%. The seroprotection rate remained very high at Month 6 and comparable between groups, but a slight decrease was observed in the JE-CV group between Months 6 and 12. Current recommendations for both vaccines call for a booster dose 12-24 months after primary immunization to maintain high seroprotection rates in the long term. Geometric mean titers (GMTs) on Day 28 after vaccination were 507 (1/dil) in the JE-CV group and 370 (1/dil) in the SA14-14-2 group, decreasing by 4.3-fold and 3.6-fold, respectively, to Month 6 before remaining stable to Month 12 and comparable between groups. Solicited reactions were all reported at lower rates after vaccination with JE-CV compared with SA14-14-2. A single dose of JE-CV elicited a noninferior immune response compared with SA14-14-2 and had a satisfactory safety profile.

Factors Affecting Completeness Basic Immunization Village District of North Krembangan

ABSTRACTEach state issues have particular regard to infectious diseases, many ways to eradication of infectious diseases, one of them with the basic immunization. This study was conducted to determine the factors that affect the completeness of the basic immunization in infants or toddlers in the District of North Kembangan Village of Surabaya as PD3I disease prevention. The design used a case-control (case control) by the number of sample cases as much as 22 respondents and the amount of control by 44 respondents. Research subjects are taken by simple random sampling. Dependent variable of this study is the age of the respondent, education level, income level, employment status, knowledge about immunization, traditions and beliefs, as well as family support, attendance officer, location and attitude of staff immunization. The results showed the influence of tradition on the completeness of immunization (p = 0.015) and family support (p = 0.001). Completeness of primary immunization in infants as efforts to prevent PD3I disease affected family tradition that used to immunize baby or toddler in a baby or toddler will likely get a complete immunization and family who support immunization infant or toddler chance to get a complete immunization. For that we need a health promotion approach to the public in order to change the traditions that are not used to immunize a support for immunization and to give sense to the decision makers benefit families that immunization in infants or toddler. Keywords: immunization status, family tradition, family support

Factors Affecting Completeness Basic Immunization Village District of North Krembangan

ABSTRACTEach state issues have particular regard to infectious diseases, many ways to eradication of infectious diseases, one of them with the basic immunization. This study was conducted to determine the factors that affect the completeness of the basic immunization in infants or toddlers in the District of North Kembangan Village of Surabaya as PD3I disease prevention. The design used a case-control (case control) by the number of sample cases as much as 22 respondents and the amount of control by 44 respondents. Research subjects are taken by simple random sampling. Dependent variable of this study is the age of the respondent, education level, income level, employment status, knowledge about immunization, traditions and beliefs, as well as family support, attendance officer, location and attitude of staff immunization. The results showed the influence of tradition on the completeness of immunization (p = 0.015) and family support (p = 0.001). Completeness of primary immunization in infants as efforts to prevent PD3I disease affected family tradition that used to immunize baby or toddler in a baby or toddler will likely get a complete immunization and family who support immunization infant or toddler chance to get a complete immunization. For that we need a health promotion approach to the public in order to change the traditions that are not used to immunize a support for immunization and to give sense to the decision makers benefit families that immunization in infants or toddler. Keywords: immunization status, family tradition, family support

Safety and Immunogenicity of 2 Mixed Primary Infant Immunization Schedules of Pentavalent Diphtheria, Tetanus, Acellular Pertussis, Inactivated Poliomyelitis, and Haemophilus influenzae Type b Vaccines at 2, 4, and 6 Months of Age

Two pentavalent infant vaccines that contain either 5 or 3 component acellular pertussis antigens are authorized in Canada. Because of changes in vaccine use by provinces over time and movement of families across jurisdictions, it is possible that children are exposed to different combination vaccines during the primary infant immunization schedule. The safety and immunogenicity of mixed primary infant schedules is unknown. In a double-blind multicenter trial, 2-month-old healthy infants were randomized to 1 of 2 schedules at 2, 4, and 6 months of age (either Pediacel, Pediacel, Infanrix [PPI] or Infanrix, Pediacel, Pediacel [IPP]). Solicited local and systemic adverse events (AEs) were collected by parent diary on days 0 through 7; unsolicited AEs were collected for 31 days after each dose. Immune responses to polypolyribosylribitol phosphate capsular polysaccharide (PRP) (Haemophilus influenzae type b) and pertussis antigens were assessed before the first dose and 28 days after the 6 month (third) dose. In all, 127 infants were randomized to IPP and 126 to PPI. The percentage of children with anti-PRP responses ≥0.15 μg/mL after dose 3 was higher in the IPP than in the PPI group (98.3, 95% CI: 94.1, 99.8 vs. 86.1%, 95% CI: 78.6, 91.7, P < 0.001). Antipertussis toxin and anti-fimbriae 2 and 3 responses were statistically significantly higher in the IPP than in the PPI group. Higher filamentous hemagglutinin responses occurred in PPI than in IPP. No difference between groups was observed in pertactin responses.Systemic AEs were similar between the 2 vaccine schedules. Irritability (67.2 vs. 51.6, P = 0.014) and mild crying (35.2% vs. 23.0%, P = 0.037) were more common after the 6-month dose in the PPI compared with the IPP group, as were overall systemic reactions (any intensity) for the PPI group after this dose (80.0 vs. 68.0, P = 0.042). Mixed 2-, 4-, 6-month pentavalent infant vaccine schedules had different immunogenicity and reactogenicity, with a PPI schedule being more reactogenic, and less immunogenic for PRP and fimbriae 2 and 3 antigens at 7 months. It is preferable to complete the primary infant 3-dose vaccine series with the same vaccine, rather than considering infant vaccines as interchangeable.

Pediatric combined formulation DTaP–IPV/Hib vaccine

Combination vaccines have been used for many years in the USA as part of the primary infant immunization series. However, the current program still requires up to 24 injections by 18 months of age. The Advisory Committee on Immunization Practices in the USA recommends the use of combination vaccines whenever possible. A combination vaccine was recently licensed in the USA for the prevention of diphtheria, tetanus, pertussis, polio and Haemophilus influenzae type b (DTaP–IPV/Hib). This product has been used exclusively for childhood immunizations in Canada for the last decade and shown to be safe and effective as part of a primary infant series and toddler booster immunization program. This article summarizes the available safety, immunogenicity and effectiveness data of this combination vaccine and provides a brief review of future trends in combination vaccine use.

A New Combination Haemophilus influenzae Type B and Neisseria meningitidis Serogroup C-Tetanus Toxoid Conjugate Vaccine for Primary Immunization of Infants

We conducted a phase 3 randomized controlled trial looking at the immunogenicity and safety of a novel combined Haemophilus influenzae type b and Neisseria meningitidis serogroup C tetanus toxoid conjugate vaccine, Hib-MenC-TT in a 2-, 3-, and 4-month primary infant immunization schedule. SBA MenC titers > or =1:8 and anti-PRP concentrations > or =0.15 microg/mL were measured in 99.2% and 100%, respectively, of the infants receiving Hib-MenC-TT.

The kinetics and phenotype of the human B‐cell response following immunization with a heptavalent pneumococcal‐CRM197 conjugate vaccine

Primary immunization of infants with protein-polysaccharide conjugate vaccines induces antipolysaccharide antibody and is highly effective in preventing invasive disease caused by encapsulated bacteria. However, recent experience from the UK indicates that this immunity is not sustained in the absence of booster doses of vaccine. This study aimed to establish the kinetics and phenotype of B-cell subpopulations responding to booster immunization with a heptavalent pneumococcal conjugate vaccine (Pnc7), which is to be introduced into the primary immunization schedule in the UK during 2006. Six adult volunteers received a booster dose of Pnc7 12-18 months after primary immunization. CD27hi CD38hi CD20(+/-) IgG antibody-forming cells were detected in peripheral blood with maximum frequency at days 6-7 after immunization. This was accompanied by a more prolonged rise in memory B cells that required in vitro stimulation with Staphylococcus aureus Cowan strain and interleukin-2 to induce antibody secretion. These data provide evidence for at least two subsets of antibody-forming cells involved in the secondary humoral response to a glycoconjugate vaccine in primed individuals. A briefly circulating subset of B cells that spontaneously secrete immunoglobulin G may be responsible for early defence against re-encountered encapsulated bacteria. However, the kinetics of the appearance of these cells may indicate that the humoral immune response is too slow in defence against an organism that invades within days of acquisition. The more sustained presence of a memory population may provide persistence of antipolysaccharide antibody after a booster dose of vaccine and may also include re-circulatory populations responsible for further anamnestic responses.

Immunological Memory

Protein-polysaccharide conjugate vaccines that protect against Haemophilus influenzae type b (Hib), serogroup C Neisseria meningitidis, and multiple capsular serotypes of Streptococcus pneumoniae have had a major impact on invasive bacterial disease in childhood when incorporated into routine infant immunization schedules. However, effectiveness data from the United Kingdom suggest that primary infant immunization alone may not be associated with long-term protection. Both immunological priming and antibody persistence are important aspects of long-term protection induced by these vaccines. An improved understanding of the immunobiology of the B-cell response to these vaccines may direct development of immunization strategies that provide sustained protection.

Epidemiology of Pertussis

The World Health Organization recommended that a pertussis incidence of <1 case per 100,000 population be achieved in Europe by 2000. Available data indicate that this goal has generally not been achieved, and the incidence is actually rising in some countries. Understanding the reasons for this increased incidence may lead to better global control of pertussis. In the majority of countries where pertussis is a notifiable disease, a case-based national surveillance system is in place. However, different case definitions, methods of diagnosis and reporting and surveillance systems make direct intercountry comparisons difficult, and pertussis is not a statutory notifiable disease in every country. Nevertheless the general consensus is that reported incidences are probably considerably lower than the actual incidence of pertussis; underreporting is common. Prolonged cough may be the only clinical feature in adolescents or adults, who may present for diagnosis late (precluding laboratory confirmation) or not at all. When they do present, their condition is often misdiagnosed because, in part, clinicians continue to perceive pertussis as a childhood disease. Despite underreporting, an increased incidence of infant, adolescent and adult pertussis has been observed worldwide since the introduction of widespread vaccination. This is of concern because adolescents and adults have been identified as a source of transmission of pertussis to very young infants who are unimmunized or partially immunized and thus more vulnerable to disease-related complications and higher mortality. In recent years, acellular pertussis vaccines have been incorporated into the immunization schedules of many developed countries, gradually replacing whole cell vaccines. Dosing schedules vary between countries, although primary immunization with 3 doses of the pertussis vaccine within the first 6 months of life exists in most countries. Only Australia, Austria, Canada, France and Germany have incorporated an adolescent booster dose into their current immunization schedules, in recognition of the rising incidence of pertussis in adolescents and adults. Despite high coverage rates for primary immunization in infants and children, pertussis continues to be a global concern, with increased incidence widely noted. This global epidemiologic summary highlights differences worldwide in pertussis reporting, incidence and approaches to prevention. It underscores a general shift in the age distribution of pertussis toward older groups. Understanding the link between these observations may lead to better informed global control strategies, especially those pertaining to immunization schedules and use of pertussis vaccine.

Lot-to-Lot Consistency of a Combined Hexavalent Diptheria-Tentanus-Acellular-Pertussis, Hepatitis B, Inactivated Polio and Haemophilus b Conjugate Vaccine, Adminstered to Healthy Chilean Infants at 2, 4 and 6 Months of Age

Objectives: To assess the safety, immunogenicity and lot consistency of a liquid hexavalent combined vaccine (DTaP-IPV-PRP~T-HBs, HEXAVAC®) (Sanofi-Pasteur MSD, France) administered to infants at 2, 4, and 6 months of age.Methods: A total of 1028 infants were vaccinated with one of 3 vaccine lots, in a randomized, double-blind fashion. Equivalence testing was used to compare post-vaccination seroprotection/seroconversion rates and geometric mean titers (GMTs) for each antigen between the three lots. Blood samples were drawn before vaccination and one month after the third dose. Local and systemic adverse events were monitored for 3 days following each injection.Results: Equivalence between lots was demonstrated for all antigens, on post-dose 3 seroprotection/seroconversion rates and GMTs. Reported rates of local and systemic adverse events tended to increase with subsequent doses. Altogether, 11.8% of the infants reported at least one adverse local event (mainly redness and induration/swelling) after the first dose and 36.1% after the third dose. Systemic adverse events (mainly irritability and fever) were reported by 39.2% of the infants after the first dose and by 57.5% after the third one.Conclusion: Three separate lots of the liquid hexavalent combined vaccine induced consistently protective antibody responses against all antigens. These results and the well established clinical tolerability of this combined vaccine make it suitable for primary immunization of infants at 2, 4, and 6 months of age.

Safety, reactogenicity and immunogenicity of a combined hexavalent tetanus, diphtheria, acellular pertussis, hepatitis B, inactivated poliovirus vaccine and Haemophilus influenzae type b conjugate vaccine, for primary immunization of infants

Safety, reactogenicity and immunogenicity of a combined hexavalent tetanus, diphtheria, acellular pertussis, hepatitis B, inactivated poliovirus vaccine and Haemophilus influenzae type b conjugate vaccine, for primary immunization of infants

Safety, reactogenicity and immunogenicity of a combined hexavalent tetanus, diphtheria, acellular pertussis, hepatitis B, inactivated poliovirus vaccine and Haemophilus influenzae type b conjugate vaccine, for primary immunization of infants

Safety, reactogenicity and immunogenicity of GSK Biologicals’ hexavalent DTPa–HBV–IPV/Hib vaccine (Infanrix ®hexa) was assessed when used for primary vaccination at 3, 4 and 5 months of age ( N=2163), compared to the separate administration of DTPa–IPV/Hib and HBV vaccines ( N=720). A similar safety and reactogenicity profile was demonstrated for both vaccine regimens, as well as a good immune response for all antigen components. By offering protection against six diseases in a series of single injections, the hexavalent DTPa–HBV–IPV/Hib vaccine was shown to be a safe, well tolerated and immunogenic alternative to primary immunization with licensed separately administered vaccines.

Haemophilus influenzae type b disease: impact and effectiveness of diphtheria-tetanus toxoids-acellular pertussis (-inactivated poliovirus)/H. influenzae type b combination vaccines.

Since 1996 in Germany primary infant immunization against Haemophilus influenzae has been most commonly given in the form of diphtheria-tetanus toxoids-acellular pertussis/H. influenzae type b (DTaP/Hib) or diphtheria-tetanus toxoids-acellular pertussis (-inactivated poliovirus)/H. influenzae type b (DTaP-IPV/Hib) combination vaccines. These combination vaccines elicit lower anti-Hib antibody concentrations than the equivalent Hib conjugate administered as a separate injection, but the clinical relevance of this phenomenon is unknown. To assess the impact of DTaP/Hib combination vaccines on the incidence of invasive Hib disease in Germany, two independent surveillance systems, one hospital- and one laboratory-based, were used during 1998 and 1999 for detection of cases. Vaccination histories of all cases detected were obtained by telephone contact with parents or health care providers. During the 2-year study period invasive H. influenzae disease in the <5-year age group continued to fall, with a mean annual incidence of 1.01/100 000 children. National vaccination coverage rates revealed that only 70% of children given DTaP/Hib or DTaP-IPV/Hib received the recommended three doses in their first year of life, but the overall effectiveness of these vaccines was high at 97.5% (95% confidence interval, 96.3 to 98.4) for those who had received at least one dose. In subjects who received the full 3-dose schedule, effectiveness was 98.8% (95% confidence interval, 98.2 to 99.3). Although it is well-documented that DTaP/Hib vaccines elicit lower anti-Hib titers than separate vaccines, such combinations are effective in reducing the incidence of invasive H. influenzae type b disease.

Cell-mediated immunity and antibody responses to Bordetella pertussis antigens in children with a history of pertussis infection and in recipients of an acellular pertussis vaccine.

Cell-mediated immunity (CMI) and antibody responses to Bordetella pertussis antigens were assessed 4-6 years after primary infant immunization with diphtheria-tetanus tricomponent acellular pertussis (DTaP) or diphtheria-tetanus (DT) vaccine in a country with high endemicity of B. pertussis infection. CMI to the B. pertussis antigens (especially to the pertussis toxin [PT]) was more frequent and/or intense in DTaP than in DT recipients. No lymphoproliferation differences were found between those with and without a history of pertussis although the DT recipients produced very little interferon-gamma after antigen (particularly PT and filamentous hemagglutinin [FHA]) stimulation. In contrast, seropositivity to PT, but not to pertactin or FHA, was more frequent in DT recipients with history of pertussis than in all other subjects. Thus, years after disease or vaccination, CMI response to PT or circulating PT antibodies appears to be the main distinctive feature of pertussis-protected DTaP recipients or pertussis-affected DT recipients.