Heinz-J. Schmitt

Symptoms and complications of pertussis in adults

SummaryThere is increasing evidence that pertussis occurs frequently in adults, but there is limited information on the clinical course of this disease beyond childhood. A household contact study on the efficacy of an acellular pertussis vaccine was used to study the symptoms of pertussis in adults. Among 257 patients with pertussis identified in 121 families during a two-year period in one study center with a low whole-cell pertussis-vaccine uptake, 79 (30.7%) were adults, aged 19–83 years (mean age: 36 years) with a 1:1.8 male to female ratio. Ninety-one percent of the adults suffered from coughing (mean duration: 54 days), and in 80% this cough lasted ≥ 21 days. Whoops were rare (8%), whereas cough followed by vomiting and/or choking (53%) and cough disturbing sleep (52%) were common. This is the first report to describe sweating attacks as symptom of pertussis (14%). Pharyngeal symptoms (37%), influenza-like symptoms (30%), sneezing attacks (22%), hoarseness (18%), sinus pain (16%) and headaches (14%) were also observed. Various complications were seen in 23% of the patients. In order to minimize the spread of the organism, micro-biological diagnostics should be vigorously applied to all symptomatic contacts of a patient with pertussis but also to all patients with long lasting cough — irrespective of age.ZusammenfassungWährend viele Berichte belegen, daß Pertussis eine häufige Krankheit auch im Erwachsenenalter ist, gibt es nur wenige Studien zum klinischen Verlauf der Krankheit jenseits der Kindheit. Im Rahmen einer Haushalt-kontaktstudie zum Nachweis der Wirksamkeit einer azellulären Pertussis-Vakzine wurden in einem Studienzentrum mit bekannt niedriger Pertussis-Durchimpfungsrate Erwachsene mit Keuchhusten identifiziert und Symptome erfragt. Innerhalb von 2 Jahren wurden 257 Patienten mit Pertussis in 121 Familien gefunden. Davon waren 79 Erwachsene (30,7%) im Alter zwischen 19 und 83 Jahren (Durchschnittsalter: 36 Jahre). Das Verhältnis männlich zu weiblich betrug 1:1,8. Husten wurde von 91% der Erwachsenen angegeben (durch-schnittliche Dauer: 54 Tage). Er dauerte in 80% der Fälle ≥ 21 Tage an. Inspiratorischer Stridor war selten (8%), dagegen war der Husten häufig von Erbrechen und/oder Würgreiz gefolgt (53%) oder störte den Schlaf der Patienten (52%). Dies ist die erste Studic, in der anfallsweise auftretender Schweißausbruch als Symptom bei Pertussis beschrieben wird (14%). Über pharyngeale Symtome, (37%), Influenza-ähnliche Symptome (30%), Niesanfälle (22%), Heiserkeit (18%), schmerzhafte Sinus (16%) und Kopfschmerzen (14%) wurde ebenfalls berichtet. Komplikationen wurden bei 23% der erwachsenen Patienten beobachtet. Unabhängig vom Alter sollte die mikrobiologische Diagnostik bei allen symptomatischen Kontaktpersonen eines Patienten mit Pertussis und ebenso bei jedem Patienten mit lang anhaltendem Husten konsequent durchgeführt werden, damit die weitere Ausbreitung des Erregers zu einem möglichst frühen Zeitpunkt verhindert werden kann.

How to optimise the coverage rate of infant and adult immunisations in Europe

BackgroundAlthough vaccination has been proved to be a safe, efficacious, and cost-effective intervention, immunisation rates remain suboptimal in many European countries, resulting in poor control of many vaccine-preventable diseases.DiscussionThe Summit of Independent European Vaccination Experts focused on the perception of vaccines and vaccination by the general public and healthcare professionals and discussed ways to improve vaccine uptake in Europe.Despite the substantial impact and importance of the media, healthcare professionals were identified as the main advocates for vaccination and the most important source of information about vaccines for the general public. Healthcare professionals should receive more support for their own education on vaccinology, have rapid access to up-to-date information on vaccines, and have easy access to consultation with experts regarding vaccination-related problems. Vaccine information systems should be set up to facilitate promotion of vaccination.SummaryEvery opportunity to administer vaccines should be used, and active reminder systems should be set up. A European vaccine awareness week should be established.

A Global Perspective on Vaccine Safety and Public Health: The Global Advisory Committee on Vaccine Safety

Established in 1999, the Global Advisory Committee on Vaccine Safety advises the World Health Organization (WHO) on vaccine-related safety issues and enables WHO to respond promptly, efficiently, and with scientific rigor to issues of vaccine safety with potential global importance. The committee also assesses the implications of vaccine safety for practice worldwide and for WHO policies. We describe the principles on which the committee was established, its modus operandi, and the scope of the work undertaken, both present and future. We highlight its recent recommendations on major issues, including the purported link between the measles-mumps-rubella vaccine and autism and the safety of the mumps, influenza, yellow fever, BCG, and smallpox vaccines as well as that of thiomersal-containing vaccines.

Reactogenicity and immunogenicity of a booster dose of a combined diphtheria, tetanus, and tricomponent acellular pertussis vaccine at fourteen to twenty-eight months of age

OBJECTIVES The primary objective was to assess the nature and incidence of adverse events after a fourth dose of a tricomponent acellular pertussis-diphtheriatetanus vaccine given in the second year of life after primary vaccination with the same vaccine at 3, 4, and 5 months of age. A secondary objective was to analyze the immunogeniecity of the booster vaccination. DESIGN Of the 5361 children enrolled (aged 14 to 28 months), adverse reactions were specifically solicited from the first 1863 enrollees for the first 4 days after vaccination and then were unsolicited for the remainder of the 4 weeks of follow-up (group 1). In the next 3498 subjects, safety and reactogenicify were entirely unsolicited for this 4-week period (group 2). Immunogenicity was analyzed by means of prebooster and postbooster serum antibody titers for all vaccine components in a random subgroup of 197 children from group 1. RESULTS Soliciting symptoms elicited reports of at least one symptom in 1314 of 1809 children in group 1 (72.6%), including 993 (54.9%) with local and 885 (48.9%) with general symptoms during the first 4 days after vaccination. When symptoms were gathered in an unsolicited fashion, only 580 of 3498 children in group 2 (16.6%) had a reported symptom during this time, consisting of 344 (9.8%) local and 319 (9.1%) general symptoms, respectively. An unsolicited symptom, areactive edematous swelling of the whole thigh, occurred in 62 children (1.1%), with 45 and 17 reports in groups 1 and 2, respectively. The vast majority of all reported symptoms were mild to moderate, and all children recovered without sequelae. Fourteen serious adverse events were reported, but none was considered to be related to the vaccination. Immunogenicity analysis showed a vaccine response to pertussis toxin in 99.5% of subjects, to filamentous hemagglutinin in 98.5%, and to pertactin (69 kd outer membrane protein) in 99%. All subjects had postvaccination antibody titers of 0.1 IU/ml or greater against diphtheria and tetanus toxoids.

Immunogenicity, reactogenicity, and immune memory after primary vaccination with a novel Haemophilus influenzae-Neisseria meningitidis serogroup C conjugate vaccine.

ABSTRACT We evaluated two formulations of a new combined Haemophilus influenzae type b (Hib)-meningococcal serogroup C (MenC)-tetanus toxoid (TT) conjugated vaccine and two formulations of a new MenC-TT vaccine (trials 711202/001 and 711202/008; clinical trial register numbers NCT00135486 and NCT00135564 [www.ClinicalTrials.gov ]). A total of 520 healthy infants were randomized to receive primary vaccination (at 2, 3, and 4 months) with either MenC-TT plus diphtheria-tetanus-acellular pertussis (DTPa)-hepatitis B virus (HBV)-inactivated poliovirus (IPV)/Hib, Hib-MenC-TT plus DTPa-HBV-IPV, or MenC-CRM197 plus DTPa-HBV-IPV/Hib (control). At 12 to 15 months, subjects received a polysaccharide challenge with meningococcal polysaccharide C plus a DTPa-HBV-IPV/Hib booster. Immune responses were assessed 1 month after dose 2, 1 month after dose 3, and prior to and 1 month after the booster. After primary vaccination, there was no difference between groups in seroprotection rates as measured by titers of serum bactericidal antibody (SBA) to MenC (≥1:8) or concentrations of anti-polyribosyl ribitol phosphate (PRP) antibody (≥0.15 μg/ml). Prior to the booster, there was no difference between groups in SBA seroprotection rates, whereas anti-PRP seroprotection rates were significantly higher after priming with Hib-MenC-TT. Booster doses induced large increases in SBA and anti-PRP antibodies in primed groups, indicating successful priming with induction of immune memory. Reactogenicity and safety were similar in all groups during the primary and booster phases. A novel combined Hib-MenC-TT conjugate vaccine induced MenC and Hib responses comparable to those induced by licensed monovalent vaccines. A Hib-MenC-TT conjugate vaccine provides vaccination against two major pathogens in a single injection and is a suitable candidate for use in primary or booster vaccination schedules.

Age-Dependent Association of Human Mannose-Binding Lectin Mutations With Susceptibility to Invasive Meningococcal Disease in Childhood

Background: Mannose-binding lectin (MBL) is an important factor of the innate immune system, and MBL-initiated complement activation is an important early defense mechanism against various bacterial infections, including invasive meningococcal disease. Methods: In a pediatric cohort (ages 2–215 months) with invasive meningococcal disease, we investigated the overall and age-stratified frequency of 3 MBL exon 1 variations (C154T, G161A, G170A), previously shown to result in markedly decreased MBL plasma concentrations, by allele specific fluorescent hybridization probe real-time PCR assays and direct sequencing. Healthy age-matched volunteers with the same ethnic background and no history of meningococcal disease served as a control group. Results: The overall frequency of a MBL exon 1 variant genotype was significantly higher in patients than in controls (31.8% vs. 8.2%, P < 0.001). In the patient group with disease onset less than 24 months of age, the prevalence of MBL structural variant genotype was further increased (39.3%; P < 0.001) and most pronounced in children with disease onset less than 12 months of age (57.1%; P < 0.001) when compared with healthy controls. Analysis of clinical severity and outcome revealed no significant difference between patients with wild-type and mutant alleles. Conclusions: Our data suggest that MBL exon 1 structural variants are significantly associated with susceptibility to childhood meningococcal disease in an age-dependent manner.

Factors influencing vaccine uptake in Germany

While vaccines have virtually eliminated many infectious diseases in Germany, vaccination coverage in children, adolescents and adults is still unsatisfying. This situation is mainly due to inadequate remuneration of vaccination services, structural deficits in the health care system and a lack of motivation. Political support and leadership would most likely be able to change this situation.

Two versus three doses of a meningococcal C conjugate vaccine concomitantly administered with a hexavalent DTaP-IPV-HBV/Hib vaccine in healthy infants.

The immunogenicity and reactogenicity of a meningococcal serogroup C (MenC) conjugate vaccine given concomitantly with DTaP-IPV-HBV/Hib vaccine according to a two- or three-dose schedule in healthy infants was evaluated. At 1 month post-vaccination, 98% (two doses) and 100% (three doses) of subjects had serum bactericidal antibody using human complement assay (hSBA) titres > or =1:8; at 12 months of age > or =89% of subjects in each group remained seroprotected. Induction of immunological memory, as evaluated by administration of a meningococcal serogroup A/C polysaccharide vaccine challenge dose, was similar for both regimens and no interference was observed in the immune response to MenC or hepatitis B virus antigens. Reactogenicity was similar in each group. MenC conjugate vaccine given concomitantly with DTaP-IPV-HBV/Hib to healthy infants in the first year of life using a two-dose schedule is as safe and immunogenic as a three-dose regimen.

Immunogenicity and reactogenicity of a bicomponent and a tricomponent acellular pertussis-diphtheria-tetanus (DTaP) vaccine in primary immunization and as second year booster: A double-blind, randomized trial

Abstract Objectives: To compare the immunogenicities and reactogenicities of bicomponent (B) (pertussis toxoid, filamentous hemagglutinin) and tricomponent (T) (pertussis toxoid, filamentous hemagglutinin, pertactin) acellular pertussis vaccines when coadministered with diphtheria and tetanus toxoids in primary (3, 4, and 5 mo) and booster (15–19 mo) vaccinations. Design and Methods: A randomized, double-blind study involving 175 children aged 12 to 18 weeks. Reactogenicity was based on diary cards, immunogenicity assessed by ELISA measurements of serum IgG antibodies. Results: There were no clinically relevant differences in local (B = 34.5; T=31.3%) and general (B = 43.9; T=41.8%) reactogenicities between the two vaccines during the primary vaccinations. Booster doses caused significantly more adverse reactions than primary vaccination, but local (B = 77.6; T=66.2%) and general (B = 64.2; T=60.8%) reaction rates remained similar for the two vaccines. Both vaccines had almost identical immunogenicities with respect to the corresponding antigens and elicited seropositive antibody titers in 100% of the recipients of vaccines against diphtheria, tetanus, and the respective pertussis antigens 1 month after primary and booster vaccinations. Conclusions: The tricomponent vaccine was no more reactogenic than the bicomponent vaccine and at least as immunogenic for the respective antigens. Because tricomponent vaccine reliably induces antibodies to an additional antigen involved in immunoprotection, it may be preferable for use in primary as well as booster vaccination.

PID-ARI.net - a pediatric infectious diseases network on acute respiratory infections and the added value of a multilevel research network.

BACKGROUND PID-ARI.net was one of three infectious disease epidemiological research networks funded by the German Ministry of Education and Research (BMBF). Its objectives were to strengthen the national initiative on infectious diseases epidemiology and to focus on a health care problem of high relevance. PATIENTS AND METHODS A research network on the epidemiology of ARI in children was formed to generate data on several levels. Key structure was a centrally organized active surveillance system in three areas of Germany from north to south. RESULTS In the 6 years of funding by the BMBF, an integrated research network with a known population denominator was formed. In the laboratory-based surveillance of up to 19 respiratory pathogens, 18,899 samples were analyzed. The added value is utilization of data on time, place, person and pathogen of a disease episode at several levels - from surveillance and online publication via a website to descriptive, analytical and molecular epidemiology and further specialized projects. Its wide age range including children up to 16 years of age, an extensive panel of pathogens, a known population denominator and the diversity of 3 distant geographical areas should considerably reduce vulnerability due to bias. CONCLUSIONS Active surveillance systems for ARI are superior to passive systems. If a surveillance system such as the one used in PID-ARI.net is part of a research network which can utilize the data on several levels, the expenditure for such a system should be worthwhile and such a system would be an asset to any health care system.