Immunogenicity and reactogenicity of a Haemophilus influenzae type b tetanus conjugate vaccine when administered separately or mixed with concomitant diphtheria-tetanus-toxoid and acellular pertussis vaccine for primary and for booster immunizations

With an increasing number of new vaccines available for routine childhood immunization, combination vaccines are needed in order to maintain or achieve a high compliance with recommended immunization programmes. In a prospective, randomized, comparative, multi-centre study, 822 healthy infants were enrolled to receive three doses of either a candidate or a commercially available Haemophilus influenzae type b (Hib) vaccine concomitantly with diphtheria-, tetanus- acellular pertussis (DTaP) vaccine. Study subjects were randomly allocated to one of the following groups: (1) separate, or (2) mixed injection of DTaP and candidate Hib vaccine, or (3) separate injection of DTaP and commercial Hib …

Vaccination greatly reduces disease, disability, death and inequity worldwide

In low-income countries, infectious diseases still account for a large proportion of deaths, highlighting health inequities largely caused by economic differences. Vaccination can cut health-care costs and reduce these inequities. Disease control, elimination or eradication can save billions of US dollars for communities and countries. Vaccines have lowered the incidence of hepatocellular carcinoma and will control cervical cancer. Travellers can be protected against "exotic" diseases by appropriate vaccination. Vaccines are considered indispensable against bioterrorism. They can combat resistance to antibiotics in some pathogens. Noncommunicable diseases, such as ischaemic heart disease, c…

Efficacy of posaconazole and amphotericin B in experimental invasive pulmonary aspergillosis in dexamethasone immunosuppressed rats

Objectives: Invasive pulmonary aspergillosis is associated with high mortality. To assess new antifungal therapy options, animal models have to be developed to assess, in an appropriate setting, the activity of new drugs. Methods: Male albino CD rats (125–150 g) were fed with a protein-free diet and received dexamethasone thrice weekly subcutaneously during the whole experiment. After 2 weeks, an inoculum of 10 6 conidia of Aspergillus fumigatus (H11-20) was injected intratracheally. Antifungal treatment was initiated and continued for a total of 7 days. Animals were grouped in numbers of 10. One group of animals served as untreated control, whereas the others were treated with amphotericin…

Booster vaccination after neonatal priming with acellular pertussis vaccine.

After a birth dose of acellular pertussis (aP) and diphtheria (DT)aP-hepatitis B virus (HBV)-inactivated polio vaccine (IPV)/ Haemophilus influenza type b (Hib) at 2, 4, and 6 months, a booster dose of DTaP-HBV-IPV/Hib at 12 to 23 months induced strong anti-pertussis booster responses. Thus, neonatal aP priming did not lead to immune tolerance to pertussis antigens. However, it elicited bystander interference on HBV, Hib, and diphtheria responses.

Comparison of the BD Directigen Flu A+B Kit and the Abbott TestPack RSV with a multiplex RT-PCR ELISA for rapid detection of influenza viruses and respiratory syncytial virus

ABSTRACTThe Directigen Flu A+B enzyme immunoassay and the Abbott TestPack RSV enzyme immunoassay were each compared with a multiplex RT-PCR ELISA by testing 635 nasopharyngeal aspirates collected from children aged < 16 years who had been hospitalised with acute respiratory tract infection during the epidemic season 2002–2003. In this study, the sensitivity of the Directigen Flu A+B assay was unacceptably low (29.3% and 10.0%, respectively) for the detection of influenza A and B viruses. The sensitivity of the Abbott TestPack RSV assay (77.4%) was acceptable and in agreement with the multiplex RT-PCR ELISA.

Withdrawal of a mumps vaccine.

Effectiveness of hexavalent vaccines against invasive Haemophilus influenzae type b disease: Germany's experience after 5 years of licensure

Summary Vaccine effectiveness (VE) was determined with a case-cohort approach using Cox regression. Cases with confirmed systemic Hib infections in children born from 1 August 2000 to 31 December 2004 were ascertained through two independent nationwide active surveillance systems. A representative cohort of 1303 children born in the same time frame was randomly sampled in a nationwide immunisation survey. Thirty cases were eligible for VE calculation; 19 were unvaccinated and 11 vaccinated with hexavalent vaccines. VE was 68.4% (95% CI: 19.0–87.6) for incomplete primary series and 90.4% (95% CI: 70.6–96.8) for the full primary series. For full immunisation VE was 100.0% (95% CI: 52.7–100.0)…

Assessing vaccine efficacy for the prevention of acute otitis media by pneumococcal vaccination in children: a methodological overview of statistical practice in randomized controlled clinical trials.

Acute otitis media (AOM) is the most common bacterial infectious disease among children. Vaccination is proposed to prevent otitis and several clinical trials were performed to assess the efficacy of pneumococcal vaccines. The way vaccine efficacy is analysed varies among trials. However, the clinical meaning of an estimate of vaccine effect and its statistical test depends on the applied statistical method. We aim to bring the meaning and validity of statistical trial results to the attention of researchers. We consider all methodological approaches for analysing vaccine efficacy applied in pneumococcal vaccination trials included in a recent Cochrane Review. We demonstrate how different m…

The incidence of influenza-associated hospitalizations in children in Germany

Since new vaccines and anti-viral drugs for influenza have become available, collation of actual and country-specific epidemiological data is essential. Since respiratory syncytial virus (RSV) is a well known paediatric airway pathogen and some epidemiological data exist already, a comparison between influenza and RSV seems warranted. From July 1996 to June 2001 the naso-pharyngeal aspirates (NPA) of children from birth to 16 years of age, admitted to one of the two paediatric hospitals in Kiel, Germany, were investigated by a nine-valent multiplex reverse transcriptase PCR assay. NPA were investigated in 60·8% of 3469 children admitted with an acute respiratory tract infection. Community-a…

Assessment of nine candidate DTP-vaccines with reduced amount of antigen and/or without adjuvant as a fourth (booster-) dose in the second year of life

Abstract Background The incidence of local reactions to diphtheria-, tetanus and acellular pertussis (DTaP-) vaccines in infants and toddlers increases with each subsequent dose, and entire thigh swellings (ETS) have been reported. Lowering the amount of antigen or of adjuvant may decrease the reactogenicity of DTaP while maintaining a protective immune response. Objectives Following priming with three doses of a DTaP vaccine during infancy, the safety, reactogenicity and immunogenicity of nine different candidate DTaP-vaccines with reduced amounts of antigen and/or adjuvant given as fourth (booster) dose were evaluated. Methods Study participants were healthy infants aged 15–27 months at t…

Durchimpfungsraten bei Kindern in Deutschland 1999

Hintergrund. Daten aus Einschulungsuntersuchungen sind in Deutschland die einzig verfugbare Information zu Durchimpfungsraten bei Kindern. Diese Erhebung ist fraglich reprasentativ und erlaubt keine Beurteilung “zeitgerechter” Impfungen. Valide Daten zur Vollstandigkeit und zum Zeitpunkt der Impfung wurden deshalb 1999 in einer reprasentativen Stichprobe erhoben. Methode. Der Impfstatus von 837 Kindern wurde in 775 von 1345 bevolkerungsreprasentativen Haushalten mit Kindern unter 3 Jahren per Telefoninterview erfragt. Analysiert wurden Daten von 367 Kindern im Alter von 19–35 Monaten (geb. Juli 1996–November 1997). Berechnet wurden Pravalenzen mit exakten 95%-Konfidenzintervallen zu den Alt…

Lymphadenitis colli durch nichttuberkulöse Mykobakterien (NTM) im Kindesalter - Eine Fallserie und Literaturübersicht

Objective Lymphadenitis colli due to NTM should always be considered in children with cervical Lymphadenitis. For Germany there is a lack of data concerning the incidence, the epidemiology, the diversity and frequency of the different bacteria, the diagnosis, the clinical manifestation and the medical treatment. Methods By means of a questionnaire, which was retrospective for 1985 to 1994 and was sent to 277 children's hospitals in Germany, we collected data on Lymphadenitis colli in Germany. In our study we also incorporated cases from the "National Laboratory for Mycobacteria" in Borstel as well as six cases from our hospital in Mainz. Therefore our data includes both clinical (28) and la…

Evaluation of a multiplex reverse transcriptase PCR ELISA for the detection of nine respiratory tract pathogens.

A multiplex reverse transcription (RT) polymerase chain reaction combined with a microwell hybridization assay (m-RT-PCR-ELISA) was previously developed to detect nine different microorganisms: enterovirus (EV), influenza virus type A (IVA) and type B (IVB), respiratory syncytial virus (RSV), parainfluenzavirus type 1 (PIV1) and type 3 (PIV3), adenovirus (AV), Mycoplasma pneumoniae (Mpn), Chlamydia pneumoniae (Cpn) in a single test. These organisms do not usually colonize the respiratory tract of humans, but, if present, it may be assumed they are involved in respiratory disease.The m-RT-PCR-ELISA was tested on (i) culture supernatants of unknown contents, (ii) by determining the analytical…

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

Background. 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. Methods and findings. To assess the impact of DTaP/Hib combination vaccines on the incidence of invasive Hib disease in Germany, two independent s…

Immunogenicity, reactogenicity and safety of a 7-valent pneumococcal conjugate vaccine (PCV7) concurrently administered with a DTPa-HBV-IPV/Hib combination vaccine in healthy infants.

Abstract Background To evaluate immunogenicity, reactogenicity, and safety of a hexavalent combination vaccine diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated polio virus- Haemophilus influenzae type b (DTPa-HBV-IPV/Hib) when coadministered with a 7-valent pneumococcal conjugate vaccine (PCV7). Methods Infants received either a hexavalent diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated polio virus- H. influenzae type b vaccine concomitantly with PCV7 or DTPa-HBV-IPV/Hib alone infants were vaccinated at 2, 3 and 4 months (primary immunization) and 12–15 months of age (booster dose). Local and systemic reactions and adverse events were monitored following each do…

Immunogenicity and reactogenicity of the Biken acellular pertussis vaccine in young adults

Abstract To assess the reactogenicity and immunogenicity of the Biken acellular pertussis vaccine (Pa) following administration of a single vaccine dose to young adults with or without a history of prior pertussis immunization, 104 healthy, male and female adults without primary pertussis immunization were enrolled in Mainz (former West Germany; “not previously pertussis vaccinated”, N-PPV-group); in parallel, 103 adults with a history of having received ≥four doses of a combined diphtheria-, tetanus-toxoid, whole-cell pertussis vaccine (DTwP) were enrolled in Magdeburg (former East Germany; “previously pertussis-vaccinated”, PPV-group). Large areas of redness (>20 mm) were seen in 2.9%/1.0…

The safety, reactogenicity and immunogenicity of a 7-valent pneumococcal conjugate vaccine (7VPnC) concurrently administered with a combination DTaP-IPV-Hib vaccine.

To evaluate immune responses, safety and reactogenicity of the concomitant use of DTaP-IPV-Hib and the newly available 7-valent pneumococcal conjugate (7VPnC) vaccines when given as the primary immunization series in early infancy. A total of 231 healthy infants were enrolled at 11 German study centers and randomized to receive either 7VPnC plus DTaP-IPV-Hib vaccines concomitantly into opposite limbs at age 2, 3, 4 and 11-15 months (7VPnC group) or DTaP-IPV-Hib vaccine at the same ages plus a 7VPnC "catch-up vaccination" at ages 6, 7, 8 and 11-15 months (Control group). Blood samples were drawn before and 4 weeks after the first three vaccine doses and 4 weeks after the fourth dose. Local a…

DTPa-HBV-IPV/Hib Vaccine (Infanrix hexa???1)

Detection of delayed vaccinations: a new approach to visualize vaccine uptake

For the prevention of pertussis and invasive Haemophilus influenzae type b (Hib) infections, each with a peak for mortality and serious complications in the first year of life, early vaccination is important and needs adequate monitoring. In a 1999 national coverage survey the timing of uptake of these vaccines in German children was therefore assessed conventionally at defined age thresholds and with a new adaptation of the Kaplan–Meier (KM) method estimating immunization uptake over time by 1 minus the survival function s(t). Only 6% and 9% of children were vaccinated against pertussis and Hib in accordance with the national recommended primary vaccination schedule. Coverage levels for th…

Review of 8 years of experience with Infanrix hexa (DTPa-HBV-IPV/Hib hexavalent vaccine).

Combination vaccines that include multiple antigens within one formulation are now widely accepted as an effective means of eliciting protection against several diseases at the same time. Owing to improvements in quality and convenient modes of administration, they have become part of routine pediatric practice. Hexavalent vaccines, including diphtheria, tetanus, pertussis, hepatitis B, polio and Haemophilus influenzae type b antigens represent the latest advance in the development of combination vaccines. Over 8 years since its first licensure, this review looks at the immunogenicity, efficacy and safety profile of the only hexavalent pediatric vaccine currently in use--Infanrix hexa (diph…

Chapter 14: HPV vaccine introduction in industrialized countries.

Introduction of a vaccine requires the achievement of three initial milestones. These are licensure by a national control authority that determines the vaccine is safe and effective, development of recommendations for use by expert advisory bodies on immunization, and obtaining funding for vaccination. Once these milestones have been achieved, a successful vaccination program requires that a number of interlinked programmatic components be brought together in a coordinated fashion. These include vaccine purchase and supply, vaccination service delivery, high coverage rates, surveillance of the vaccination program, immunization finance policies and practices, and political will. Human papill…

Immunogenicity and reactogenicity of HbOC vaccine administered simultaneously with acellular pertussis vaccine (DTaP) into either arms or thighs of infants.

To evaluate the reactogenicity and immunogenicity of a Haemophilus influenzae type b conjugate vaccine (HbOC) and of a tricomponent acellular pertussis vaccine (DTaP) when injected simultaneously into either contralateral arms or into contralateral thighs, 110 infants were enrolled to receive three doses of DTaP at 3, 4, and 5 months and two HbOC doses at 3 and 5 months of age. Administration of either of the two vaccines into arms was associated with significantly more local side effects than administration into thighs. There was no difference in geometric mean concentration (GMC) values for any of the four vaccine antigens between subjects who had been vaccinated into arms or thighs. Afte…

Relevanz von Infektionskrankheiten in einer Kinderarztpraxis

According to official statistics, infectious diseases only play a minor role in German children. To test this assumption, 1685/3405 charts of a private pediatrician were randomly chosen for further evaluation. 1112/1685 children had been seen in the office during the study period, 934 of them because of an infectious disease (83%). 700/934 charts were further reviewed in a standardized fashion. Pharyngo-tonsillitis was the most frequent diagnosis (18.6%), followed by (non-obstructive) bronchitis (18.5%), infectious diseases of the skin (10.2%) and Otitis media (9.9%). Typical "childhood diseases" (measles, mumps, rubella, varicella) only played a minor role. For some diseases age-specific a…

Thoughts of a reviewer

Pertussis vaccines--1993.

Cellular immune response of a varicella vaccine following simultaneous DTaP and VZV vaccination.

Abstract Background : Chickenpox and zoster are an important cause of morbidity among children and adults. The ability of a new, thermostable vaccine to induce varicella–zoster-virus (VZV)-specific humoral and cell mediated immunity when given simultaneously with diphtheria–tetanus-acellular pertussis vaccine (DTaP) as a booster dose in the second year of life was investigated. Methods : A new, temperature stable varicella vaccine (OKA-strain, SB-Biologicals, Rixensart, Belgium) was given simultaneously with a booster dose of DTaP vaccine. VZV-specific humoral and cell-mediated immunity was studied in the first 27 out of 232 vaccinated children at 16–28 months of age, from blood samples dra…

Epidemiology of pneumococcal disease in children in Germany

UNLABELLED Recently published and as yet unpublished data allow a reasonable estimate of the annual burden of pneumococcal disease in Germany. At least 277,000 episodes of otitis media and at least 2,000 episodes of sinusitis occur in children under the age of 5 y. Pneumococcal meningitis was found in 200 children under the age of 16 y; the estimate for all age groups ranges from 450 to 1100 cases. Of approximately 150,000 cases of ambulatory pneumococcal pneumonia, at least 63,000-105,000 patients are hospitalized each year. CONCLUSION Further studies of pneumococcal epidemiology in Germany are needed, and continued surveillance will be necessary for a better understanding of the overall b…

Withdrawal of a mumps vaccine: Reasons and impacts