Anette Siedler

Proportion of Invasive Pneumococcal Infections in German Children Preventable by Pneumococcal Conjugate Vaccines

The incidence and serotype distribution of Streptococcus pneumoniae as a cause of invasive diseases are unknown with regard to most European countries. From January 1997 through December 1998, population-based nationwide prospective surveillance was undertaken for invasive pneumococcal disease (IPD) in children in Germany, based on monthly independent reports from all pediatric hospitals and from clinical microbiology laboratories. On the basis of 896 reported IPD cases (including 404 with meningitis), the incidences per 10(5) children in different age groups were as follows: children aged <1 year, 18.9 (9.7 for meningitis); children aged <2 years, 16. 0 (7.2 for meningitis); for children aged <5 years, 8.9 (3.9 for meningitis); and for children aged <16 years, 3.2 (1.4 for meningitis). The proportions of cases involving strains (304 serotyped) included in conjugate vaccines were as follows: for the 7-valent vaccine, 52%; for the 9-valent, 62%; and for the 11-valent, 71%. None of the isolates were resistant to penicillin or cefotaxime. Although the rate for meningitis is similar, other manifestations of IPD are less commonly diagnosed in Germany than in other countries. The serotype distribution only partially matched that used in the recent development of pneumococcal conjugate vaccines.

Reduction in the incidence of invasive pneumococcal disease after general vaccination with 7-valent pneumococcal conjugate vaccine in Germany

General vaccination with the 7-valent pneumococcal conjugate vaccine was recommended in Germany in July 2006 for all children <2 years. The proportion of reported invasive pneumococcal disease (IPD) caused by vaccine serotypes before vaccine introduction was considerably lower than in the US. We report data from nationwide surveillance of IPD in children with two reporting sources, pediatric hospitals and microbiological laboratories in Germany. Incidence rates with regard to age groups and pneumococcal serotypes are based on capture recapture estimates combining the two reporting sources. Between July 1, 1997 and June 30, 2003, 2680 cases (an average 447 yearly cases) of IPD were observed in children <16 years in Germany compared to 223 cases between July 1, 2007 and June 30, 2008. A significant reduction in overall incidence (4/100,000-3.2/100,000) was attributed to significant reductions in children younger than 2 years (20.0/100,000-11.0/100,000). While the incidence of all serotypes included in the vaccine was reduced in the age group <2 years, the incidence of non-vaccine serotypes remained stable. These data show a first success of the pneumococcal vaccination program in Germany. Further changes in incidence and serotype distribution of IPD are subject to future surveillance.

Incidence and Clinical Presentation of Invasive Neonatal Group B Streptococcal Infections in Germany

OBJECTIVE. Streptococcus agalactiae (group B Streptococcus) is an important cause of morbidity and mortality in newborn infants. So far, there have been no published data on the incidence, morbidity, and mortality of invasive neonatal group B Streptococcus infections in Germany. METHODS. A prospective active surveillance study involving all of the pediatric hospitals, which reported their cases to the German Pediatric Surveillance Unit, and all of the microbiological laboratories serving pediatric hospitals, which reported their cases to the Laboratory Sentinel Group at Robert Koch Institute Berlin, was conducted between 2001 and 2003. Capture-recapture analysis was used to evaluate the completeness of reported neonatal invasive group B Streptococcus infections. RESULTS. We collected and analyzed data from 347 and 360 infants with invasive group B Streptococcus infection during the first 3 months of life, as reported by pediatricians to the German Pediatric Surveillance Unit and microbiologists to the Robert Koch Institute Berlin, respectively. Using capture-recapture analysis, we calculated an incidence of 0.47 per 1000 live births. Nearly 60% of the infants suffered from early-onset disease, and 16% of these presented with meningitis. In contrast, 61.8% of infants with late-onset disease presented with meningitis. Prematurity was present in 22.4% of early-onset disease and 39.7% of late-onset disease cases, respectively. A high proportion of infants suffered from sequelae because of group B Streptococcus infection at the time of discharge from the hospital. Most common sequelae were hydrocephalus and cerebral seizure. Case fatality rate was 4.3%. CONCLUSIONS. This study, which is the first to provide information on the current national incidence and morbidity of invasive group B Streptococcus infection in Germany, demonstrates remarkable country-specific variation in comparison with other European countries, which gather data in a similar fashion. Therefore, the importance of country-specific prevention guidelines has to be stressed.

Rapid replacement of endemic measles virus genotypes

Although vaccination campaigns have significantly reduced the number of measles cases worldwide, endemic transmission of measles virus (MV) continues to occur in several continents, including Europe. To obtain current information on measles incidence and molecular data on circulating MVs in Germany, a nationwide measles sentinel was established. Phylogenetic analysis based on the variable part of the N gene from 80 MVs isolated between November 1999 and October 2001 revealed the presence of at least six distinct MV genotypes: B3, C2, D4, D6, G2 and a new variant of D7. Both the incidence and the pattern of MV genotypes differed markedly between the former East and West Germany. In the eastern part, few measles cases, mainly caused by genotypes originating from other countries (B3, D4, G2), were detected. In the western and southern parts, genotypes C2, D6 and D7 were associated with endemic transmission. Surprisingly, the indigenous genotypes predominant during the 1990s - C2 and D6 - disappeared simultaneously over the period of observation coinciding with the emergence and the wide spread of D7 viruses. While the incidence of measles remained constant, all MVs isolated in 2001 were assigned to D7. We note that the haemagglutinin (H) sequence of D7 viruses shows distinct exchanges of certain amino acids in the stem and propeller domain compared to C2, D6 and the MV vaccine strains used. This raises the possibility of a selective advantage of D7 viruses transmitted in the presence of H-specific antibodies.

Further efforts needed to achieve measles elimination in Germany: results of an outbreak investigation

OBJECTIVE To determine morbidity and costs related to a large measles outbreak in Germany and to identify ways to improve the countrys national measles elimination strategy. METHODS We investigated a large outbreak of measles in the federal state of North Rhine-Westphalia (NRW) that occurred in 2006 after 2 years of low measles incidence (< 1 case per 100,000). WHOs clinical case definition was used, and surveillance data from 2006 and 2001 were compared. All cases notified in Duisburg, the most severely affected city, were contacted and interviewed or sent a questionnaire. Health-care provider costs were calculated using information on complications, hospitalization and physician consultations. FINDINGS In NRW, 1749 cases were notified over a 48-week period. Compared with 2001, the distribution of cases shifted to older age groups (especially the 10-14 year group). Most cases (n = 614) occurred in Duisburg. Of these, 81% were interviewed; 15% were hospitalized and two died. Of the 464 for whom information was available, 80% were reported as unvaccinated. Common reasons for non-vaccination were parents either forgetting (36%) or rejecting (28%) vaccination. The average cost per measles case was estimated at 373 euros. CONCLUSION An accumulation of non-immune individuals led to this outbreak. The shift in age distribution has implications for the effectiveness of measles control and the elimination strategy in place. Immediate nationwide school-based catch-up vaccination campaigns targeting older age groups are needed to close critical immunity gaps. Otherwise, the elimination of measles in Germany and thus in Europe by 2010 will not be feasible.

Large measles outbreak at a German public school, 2006.

Background: In 2006, a large measles outbreak (n = 614) occurred in Duisburg city, Germany, with 54% of cases aged >9 years. An investigation was launched to determine reasons for the resurgence of measles, assess vaccination coverage and vaccine effectiveness (VE). Methods: A retrospective cohort-study was undertaken at a Duisburg public school affected early in the outbreak. We distributed questionnaires to all 1250 students aged 10–21 years and abstracted vaccination records. Cases were identified according to a standard clinical case definition. Results: Questionnaires were returned by 1098 (88%) students. Vaccination records were abstracted from 859 students, of whom 820 (95.4%) had received at least one, 605 (70.4%) 2, and 39 (4.5%) no dose(s) of measles-containing vaccine (MCV). Coverage with 2 doses was higher in younger students. We identified 53 cases (attack rate = 5%). Measles-virus sequencing revealed genotype D6. After excluding students vaccinated in 2006 and those with a history of measles, the attack rate was 53% in unvaccinated students, 1.0% in students with one, and 0.4% in those with 2 MCV-doses. VE was 98.1% (95% CI: 92–100%) in students with one and 99.4% (95% CI: 97–100%) with 2 MCV-doses. Based on observed attack rates in vaccinated and unvaccinated students with vaccination records and in students without vaccination records, one-dose-coverage among all participating students was estimated at 91%. Conclusions: VE was high. Vaccination coverage was, however, insufficient to prevent the outbreak. Immunization gaps were found especially in older students. To prevent further outbreaks and to achieve the goal of measles elimination in Germany, vaccination coverage must be increased.

Herpes zoster in Germany: Quantifying the burden of disease

BackgroundHerpes zoster (HZ) is caused by a reactivation of the varicella-zoster-virus (VZV) and mainly affects individuals aged ≥ 50 years. Vaccines have been licensed or are under development that can protect against HZ and its main complication postherpetic neuralgia (PHN). In Germany, the burden of disease caused by HZ is not well known. To support the decision making process related to a potential vaccination recommendation, we estimated annual HZ disease burden in people aged ≥ 50 years in Germany by utilizing various data sources.MethodsWe assessed for 2007 and 2008 HZ-outpatient incidence (number of cases per 1,000 person-years, PY) by utilizing the Association of Statutory Health Insurance Physicians (ASHIP) database, which contains nationwide routine outpatient data. For the same time period annual number of HZ-inpatients and HZ-associated deaths were identified by using the Federal Health Monitoring System (FHM). PHN-incidence and loss of quality-adjusted life years (QALYs) caused by HZ were calculated by multiplying number of identified HZ-patients with upper and lower limit estimates for proportion of HZ-cases developing PHN and HZ-related QALY, respectively.ResultsFor the study period we identified an annual average of 306,511 HZ-outpatients aged 50+, resulting in a HZ-incidence of 9.6/1,000 PY. A total 14,249 HZ-associated inpatients and 66 deaths were reported in both years on average. HZ-incidence increased by age from 6.21 in people 50-54 years to 13.19 per 1,000 PY in people aged ≥ 90 years. Females were significantly more frequently affected than males in terms of outpatient HZ-incidence (11.12 vs. 7.8 per 1,000 PY), inpatient HZ-incidence (0.51 vs. 0.38 per 1,000 PY) and mortality (0.29 vs. 0.10 per 100,000 PY). PHN-incidence was estimated to range between 0.43 and 1.33 per 1,000 PY. Based on these figures, there were between 3,065 to 24,094 QALYs lost due to HZ in persons aged ≥ 50 years in Germany per annum.ConclusionOur study provides important baseline estimates for HZ-related disease burden in Germany. HZ poses a considerable burden on the health care system in Germany both in terms of outpatient and inpatient services. Follow-up assessments of HZ disease burden are needed to monitor the impact of VZV-vaccinations in Germany.

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 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). CONCLUSION 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.

Four and one-half-year follow-up of the effectiveness of diphtheria-tetanus toxoids-acellular pertussis/Haemophilus influenzae type b and diphtheria-tetanus toxoids-acellular pertussis-inactivated poliovirus/H. influenzae type b combination vaccines in Germany

Background: Recently an increase in the number of invasive Haemophilus influenzae type b (Hib) cases was observed in the United Kingdom, which coincided with a temporary change from diphtheria-tetanus toxoids-wild-type pertussis to diphtheria-tetanus toxoids-acellular pertussis (DTaP) Hib vaccines. A study in Germany based on approximately 2 years of follow-up, estimated vaccine effectiveness (VE) of DTaP/Hib and DTaP-inactivated poliovirus/Hib combination vaccines against invasive Hib disease to be high. Objectives: To assess VE of DTaP-containing Hib vaccines against Hib in Germany with the use of extended follow-up of case surveillance and vaccine uptake. Subjects and Methods: Cases with confirmed systemic Hib infections in children born between June 1, 1996 and December 31, 1998 were ascertained by a nationwide active surveillance system from January 1998 through June 2002. A representative subcohort of 667 children born in the same time frame was randomly sampled in a nationwide vaccine coverage survey. VE was determined with a case-cohort approach of Cox regression with time-dependent covariates. Results: Thirty-six cases of Hib disease were reported. Of these, 10 were vaccinated with DTaP-containing Hib vaccines only and 20 were not vaccinated. Of the 10 vaccinated cases, 4 had received an incomplete primary series (1–2 doses), and 6 had received the full primary series (3 doses), 3 of whom also received the booster dose. VE of combination vaccines against invasive Hib infection was 89.6% [95% confidence interval (CI), 67.0–96.7] for an incomplete primary series, 96.7% (95% CI 87.7–99.1) for a full primary series and 98.5% (95% CI 94.5–99.6) for a booster dose (irrespective of priming). Conclusion: Hib combination vaccines containing acellular pertussis antigens continue to be highly effective in Germany.

Serotype Distribution of Invasive Group B Streptococcal Isolates in Infants: Results from a Nationwide Active Laboratory Surveillance Study over 2 Years in Germany

We report the serotype distribution of invasive group B streptococci (GBS) isolated from 296 infants in Germany. Serotype distribution was as follows: serotype Ia, 15%; Ib, 5%; II, 5%; III, 65%; IV, 1%; and V, 8%. Analysis of serotype according to the source of isolation highlighted the considerable role of serotype III in meningitis in early-onset infection (82%) and late-onset infection (84%). Use of a trivalent GBS vaccine in Germany could theoretically provide protection against 84% and 94% of invasive early-onset and late-onset infections, respectively.