Pneumococcal meningitis and vaccine effects in the era of conjugate vaccination: Results of 20 years of nationwide surveillance in Germany
Abstract and Figures
Long-term complications and a case mortality rate of 7.5% make meningitis caused by Streptococcus pneumoniae a serious clinical threat. In 2006, a general pneumococcal conjugate vaccination (PCV) recommendation was issued for all children under 2 years in Germany. Here, we investigate serotype changes in meningitis cases after this vaccine recommendation.
The German National Reference Center for Streptococci (NRCS) has conducted surveillance for invasive pneumococcal disease (IPD) in Germany since 1992. Pneumococcal isolates were serotyped by the Neufeld's Quellung reaction and antibiotic susceptibility was tested using the broth microdilution method.
Of 22,204 IPD isolates sent to the NRCS from July 1992 to June 2013, 3,086 were meningitis cases. Microbiological and statistical investigations were performed to characterize and quantify all meningitis cases, focusing on changes reflecting implementation of the national PCV recommendation. 1,766 isolates (57.2% of meningitis cases) were from adults (≥16 years) and 1,320 isolates (42.8%) originated from children (<16 years). Overall, the leading serotypes were 14 (9.7%), 7F (7.8%), 3 (6.9%), 19F (5.7%) and 23F (5.0%). Among children, serotypes 14 (16.2%), 7F (8.9%) and 19F (7.1%) were most common, whereas among adults, serotypes 3 (9.6%), 7F (6.9%), 22F (5.0%), 23F (4.9%) and 14 (4.8%) were most prevalent. After the introduction of general PCV7/10/13 vaccination a significant decrease for most vaccine serotypes was observed. Generally, the differences in antibiotic nonsusceptibility between children <16 years and adults ≥16 were low. For macrolides in the pre-PCV7 period, a significantly higher proportion of resistant isolates was found in children (25.1%), compared to the post-vaccination period (9.7%; p<0.0001).
Implementation of the pneumococcal conjugate vaccines broadly reduced vaccine-type meningitis cases. Changes in serotype prevalence must be continuously monitored to observe future trends concerning pneumococcal meningitis.
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... Similar to many large observational studies, we observed a reduction in PCV13 VT IPD for serotypes 1, 5 and 6A significantly in all ages [2,13,15,21,27,30]. We did not see a significant change in serotype 3 disease, which corroborates findings from other studies [15,20,24,31,32], however, it should be noted that several recent studies have shown a significant increase in IPD from serotype 3 [30,[33][34][35]. For example, a recent study from Ontario, Canada that examined the shifting pneumococcal serotypes after introduction of PCV13 found it had no impact on incidence due to serotype 3, which continued to rise in their study population [34]. ...
... In another study, Grau et al described significant increases in PCV13 serotypes 7F and 19A during PCV7 period in adults [32]. Like our study, where we saw a slow but steady decline, many have reported control of 19A after introduction of PCV13 vaccine [16,20,26,[31][32][33][34]38]. But the evidence behind a substantial decline in 7F is not as clear, with the majority studies reporting declines in cases with this serotype [13,15,16,21,27,30,34,39,40], whilst several studies, like ours, report an increase [2,12,20,[31][32][33]41]. ...
... Like our study, where we saw a slow but steady decline, many have reported control of 19A after introduction of PCV13 vaccine [16,20,26,[31][32][33][34]38]. But the evidence behind a substantial decline in 7F is not as clear, with the majority studies reporting declines in cases with this serotype [13,15,16,21,27,30,34,39,40], whilst several studies, like ours, report an increase [2,12,20,[31][32][33]41]. For example, a German study reporting on pneumococcal meningitis long term trends, from 20 year period, found proportion of isolates of PCV13 serotype 7F and 19A continued to increase in adults following the PCV13 introduction [31]. ...
Background:
A significant reduction in invasive pneumococcal disease (IPD) has been reported, across all ages, following the implementation of 7-valent conjugate pneumococcal vaccine (PCV7) globally, as part of infant immunization programs. We explored the additional impact of PCV13 on IPD over a 14-year period.
Methods:
Using provincial laboratory surveillance and hospitalization data (N = 5791), we calculated the annual incidence of IPD following the implementation of PCV13 vaccine. Poisson regression was used to evaluate changes in the overall incidence of IPD, and serotype-specific IPD between PCV7 (2004-10) and PCV13 (2011-2015) eras.
Results:
Overall, IPD rates have seen a modest decline in the PCV13 compared to the PCV7 era (IRR 0.84; 95% CI: 0.79-0.89); this was seen in children ≤2 years of age, and the majority of the adult cohort. Rates of vaccine-type IPD (PCV7 and PCV13) also decreased in the PCV13 era. In contrast, IPD incidence related to non-PCV13 (IRR: 1.56; 95%CI:1.43-1.72) and non-vaccine serotypes (IRR: 2.12; 95%CI:1.84-2.45) increased in the PCV13 era compared to the PCV7 era.
Conclusions:
A modest reduction in IPD from the PCV13 vaccine was observed, with gains limited to the immunized cohort and adults. However, a significant increase in non-vaccine serotypes emphasizes the need for continued surveillance.
... Jayaraman, Y. et al. reported that S. pneumoniae serotypes causing bacterial meningitis in hospitalized children under five years of age in India were serotypes 6B, 14, 6A, and 19F which is included in pneumococcal vaccine (PCV) [5]. It was reported that introduction of the pneumococcal conjugate vaccines broadly reduced vaccine-type meningitis in different regions [6][7][8]. Currently, there is very limited data available on pneumococcal meningitis including pneumococcus serotype causing pneumococcal meningitis and its antimicrobial susceptibility profile in Indonesia. Recently, Imran et al. reported that tuberculosis, toxoplasmosis, and cryptococcosis are common causes of CNS infections in adult patients in a referral hospital in Jakarta, Indonesia [9]. ...
... Kernig and Brudzinski signs 8 (6) Antibiotic use prior to lumbal puncture Yes 88 (60) No 46 (31) No data 13 (9) (13%), nuchal rigidity (7%), and Kernig and Brudzinski signs (6%). We observed that most (60%) of the patients received antibiotic treatments prior to CSF specimen collection (Table 1). ...
CNS infection is a life-threatening condition in developing countries and Streptococcus pneumoniae has been reported as the most common cause of bacterial meningitis; however, there is limited data on pneumococcal meningitis in Indonesia. This cross-sectional study aimed to isolate and identity S. pneumoniae strains from cerebrospinal fluid (CSF) specimens collected as part of routine testing from patients with clinically diagnosed central nervous system infection at a national referral hospital in Jakarta, Indonesia in 2017. S. pneumoniae isolation and identification were performed using conventional culture and molecular tools. Antibiotic susceptibility patterns were monitored through minimum inhibitory concentration testing. From 147 CSF specimens, one S. pneumoniae strain was identified from a patient with bacterial meningitis symptoms. The isolate was serotype 6B (ST5661) and susceptible to 18 antimicrobial agents tested, including penicillin, tetracycline, and the macrolide group. Our data provide insights into the epidemiology of invasive pneumococcal disease in Indonesia.
... In children and immunocompromised and elderly individuals, pneumococci cause a broad spectrum of local infections such as otitis media, sinusitis, and severe invasive diseases including lobar pneumonia, meningitis, and septicemia (Bogaert et al., 2004;Kadioglu et al., 2008;Henriques-Normark and Tuomanen, 2013;Valles et al., 2016). Despite the implementation of a 13-valent pneumococcal conjugate vaccine (PCV), the morbidity and mortality rates remain at rather high levels, especially in the elderly and the immunocompromised subpopulation (Kadioglu et al., 2008;Imohl et al., 2015;Valles et al., 2016). ...
Bloodstream infections caused by Streptococcus pneumoniae induce strong inflammatory and procoagulant cellular responses and affect the endothelial barrier of the vascular system. Bacterial virulence determinants, such as the cytotoxic pore-forming pneumolysin, increase the endothelial barrier permeability by inducing cell apoptosis and cell damage. As life-threatening consequences, disseminated intravascular coagulation followed by consumption coagulopathy and low blood pressure is described. With the aim to decipher the role of pneumolysin in endothelial damage and leakage of the vascular barrier in more detail, we established a c hamber- s eparation cell m igration a ssay (CSMA) used to illustrate endothelial wound healing upon bacterial infections. We used chambered inlets for cell cultivation, which, after removal, provide a cell-free area of 500 μm in diameter as a defined gap in primary endothelial cell layers. During the process of wound healing, the size of the cell-free area is decreasing due to cell migration and proliferation, which we quantitatively determined by microscopic live cell monitoring. In addition, differential immunofluorescence staining combined with confocal microscopy was used to morphologically characterize the effect of bacterial attachment on cell migration and the velocity of gap closure. In all assays, the presence of wild-type pneumococci significantly inhibited endothelial gap closure. Remarkably, even in the presence of pneumolysin-deficient pneumococci, cell migration was significantly retarded. Moreover, the inhibitory effect of pneumococci on the proportion of cell proliferation versus cell migration within the process of endothelial gap closure was assessed by implementation of a fluorescence-conjugated nucleoside analogon. We further combined the endothelial CSMA with a microfluidic pump system, which for the first time enabled the microscopic visualization and monitoring of endothelial gap closure in the presence of circulating bacteria at defined vascular shear stress values for up to 48 h. In accordance with our CSMA results under static conditions, the gap remained cell free in the presence of circulating pneumococci in flow. Hence, our combined endothelial cultivation technique represents a complex in vitro system, which mimics the vascular physiology as close as possible by providing essential parameters of the blood flow to gain new insights into the effect of pneumococcal infection on endothelial barrier integrity in flow.
... T he etiology of childhood meningoencephalitis has changed significantly over the past decades with the introduction of national immunization programs against previous common causes of childhood meningoencephalitis. [1][2][3][4][5] Pathogens that are not included in these vaccination programs (Escherichia coli, group B streptococci, enteroviruses and herpes simplex viruses) are now considered the leading causes of childhood meningoencephalitis. [6][7][8][9][10] Despite the significant decrease in the total incidence of childhood meningoencephalitis following effective national immunization programs, morbidity and mortality rates remain high in childhood meningoencephalitis cases, especially in newborns and in low-income countries. [11][12][13][14] Although rare, autoimmune processes are associated with encephalitis in children, most commonly acute disseminated encephalomyelitis and anti-N-methyl-d-aspartate receptor encephalitis. ...
Supplemental Digital Content is available in the text.
... The Imohl et al. (2015) in Germany. ...
The objective of this study was to assess the impact of 10-valent pneumococcal conjugate (PCV10) vaccination on the incidence and mortality of pneumococcal meningitis in children under 5 in Brazil. A descriptive ecological, population-based quantitative study of secondary data from SINAN records for 2003-2009 and 2011-2017 and on vaccine coverage for 2011-2017 was conducted. The study was approved under permit CAAE 23629719.6.0000.5181. After PCV10 vaccine introduction, a substantial consistent reduction in incidence of and mortality rates of pneumococcal meningitis (70.33% Northeast, 69.49% Southeast) was observed across all regions of Brazil. Although the Human Development Index (HDI) improved during the study period, lethality rates remained high (North = 34.45% pre versus 40.08% post-vaccination), with no clear pattern of reduction associated with improved HDI in Brazil. In the final years of the study, a concerning decline in vaccination coverage rates was evident. Only the South (96.52%) and Mid-West (96.17%) regions attained the ≥ 95% vaccine coverage recommended by the Ministry of Health. This situation highlights the need for urgent measures to restore coverage rates and prevent recrudescence in cases and deaths associated with potentially preventable diseases.
... Initially, the reduction in infections with antibiotic resistant serotypes suggested that vaccines could reduce antimicrobial resistance. However, long-term analyses revealed that the beneficial effects on antibiotic susceptibility profiles could not be maintained after serotype replacement (16)(17)(18)(19). ...
Increasing antibiotic resistance in bacteria causing endogenous infections has entailed a need for innovative approaches to therapy and prophylaxis of these infections and raised a new interest in vaccines for prevention of colonization and infection by typically antibiotic resistant pathogens. Nevertheless, there has been a long history of failures in late stage clinical development of this type of vaccines, which remains not fully understood. This article provides an overview on present and past vaccine developments targeting nosocomial bacterial pathogens; it further highlights the specific challenges associated with demonstrating clinical efficacy of these vaccines and the facts to be considered in future study designs. Notably, these vaccines are mainly applied to subjects with preexistent immunity to the target pathogen, transient or chronic immunosuppression and ill-defined microbiome status. Unpredictable attack rates and changing epidemiology as well as highly variable genetic and immunological strain characteristics complicate the development. In views of the clinical need, re-thinking of the study designs and expectations seems warranted: first of all, vaccine development needs to be footed on a clear rationale for choosing the immunological mechanism of action and the optimal time point for vaccination, e.g., (1) prevention (or reduction) of colonization vs. prevention of infection and (2) boosting of a preexistent immune response vs. altering the quality of the immune response. Furthermore, there are different, probably redundant, immunological and microbiological defense mechanisms that provide protection from infection. Their interplay is not well-understood but as a consequence their effect might superimpose vaccine-mediated resolution of infection and lead to failure to demonstrate efficacy. This implies that improved characterization of patient subpopulations within the trial population should be obtained by pro- and retrospective analyses of trial data on subject level. Statistical and systems biology approaches could help to define immune and microbiological biomarkers that discern populations that benefit from vaccination from those where vaccines might not be effective.
... We chose serotype 3 for our pneumococcal meningitis mouse model as it was the most common serotype in our nationwide prospective cohort of communityacquired bacterial meningitis [3]. Although the proportion of serotype 3 cases decreased due to the introduction of conjugate vaccines, it is still among the most common clinical serotypes in pneumococcal meningitis [1,54]. Additionally S. pneumoniae is known to bind human FH but not to murine FH [55]. ...
Background:
The complement system is a vital component of the inflammatory response occurring during bacterial meningitis. Blocking the complement system was shown to improve the outcome of experimental pneumococcal meningitis. Complement factor H (FH) is a complement regulatory protein inhibiting alternative pathway activation but is also exploited by the pneumococcus to prevent complement activation on its surface conferring serum resistance.
Methods:
In a nationwide prospective cohort study of 1009 episodes with community-acquired bacterial meningitis, we analyzed whether genetic variations in CFH influenced FH cerebrospinal fluid levels and/or disease severity. Subsequently, we analyzed the role of FH in our pneumococcal meningitis mouse model using FH knock-out (Cfh-/-) mice and wild-type (wt) mice. Finally, we tested whether adjuvant treatment with human FH (hFH) improved outcome in a randomized investigator blinded trial in a pneumococcal meningitis mouse model.
Results:
We found the major allele (G) of single nucleotide polymorphism in CFH (rs6677604) to be associated with low FH cerebrospinal fluid concentration and increased mortality. In patients and mice with bacterial meningitis, FH concentrations were elevated during disease and Cfh-/- mice with pneumococcal meningitis had increased mortality compared to wild-type mice due to C3 depletion. Adjuvant treatment of wild-type mice with purified human FH led to complement inhibition but also increased bacterial outgrowth which resulted in similar disease outcomes.
Conclusion:
Low FH levels contribute to mortality in pneumococcal meningitis but adjuvant treatment with FH at a clinically relevant time point is not beneficial.
Purpose:
In this study, we aimed to clarify the risk factors associated with unfavorable outcomes in adults with pneumococcal meningitis (PnM).
Methods:
Surveillance was conducted between 2006 and 2016. Adults with PnM (n = 268) were followed up for outcomes within 28 days after admission using the Glasgow Outcome Scale (GOS). After classifying the patients into the unfavorable (GOS1-4) and favorable (GOS5) outcome groups, i) the underlying diseases, ii) biomarkers at admission, and iii) serotype, genotype, and antimicrobial susceptibility for all isolates were compared between both groups.
Results:
Overall, 58.6% of patients with PnM survived,15.3% died, and 26.1% had sequelae. The number of living days in the GOS1 group was highly heterogeneous. Motor dysfunction, disturbance of consciousness, and hearing loss were the commonest sequelae. Of the underlying diseases identified in 68.9% of the PnM patients, liver and kidney dysfunctions were significantly associated with unfavorable outcomes. Of the biomarkers, creatinine and blood urea nitrogen, followed by platelet and C-reactive protein had the most significant associations with unfavorable outcomes. There was a significant difference in the high protein concentrations in the cerebrospinal fluid between the groups. Serotypes 23F, 6C, 4, 23A, 22F, 10A, and 12F were associated with unfavorable outcomes. These serotypes were not penicillin-resistant isolates possessing three abnormal pbp genes (pbp1a, 2x, and 2b), except for 23F. The expected coverage rate of the pneumococcal conjugate vaccine (PCV) was 50.7% for PCV15 and 72.4% for PCV20.
Conclusions:
In the introduction of PCV for adults, the risk factors for underlying diseases should be prioritized over age, and serotypes with unfavorable outcomes should be considered.
Background:
No previous studies have reported long-term follow-up of ten-valent pneumococcal conjugate vaccine (PCV10) program impact on pneumococcal meningitis (PM). We assessed the effects of infant PCV10 program on PM incidence, mortality and serotype distribution in children and adults during 7 years after introduction.
Methods:
We conducted a population-based observational study. A case of PM was defined as isolation of Streptococcus pneumoniae from cerebrospinal fluid or, a patient with S. pneumoniae isolated from blood and an ICD-10 hospital discharge diagnosis of bacterial meningitis within 30 days before or after positive culture date.We compared age- and serotype-specific incidence and associated 30-day mortality rates in 2011-2017 (PCV10 period) with those in 2004-2010 (pre-PCV10 baseline) by using Poisson regression models. Absolute rate differences and 95% confidence intervals (CIs) were calculated from the parameter estimates by using delta method.
Results:
During the PCV10 period, the overall incidence of PCV10 serotype meningitis decreased by 68% (95%CI 57%-77%), and the overall PM incidence by 27% (95%CI: 12%-39%). In age groups 0-4, 50-64, and ≥ 18 years, the overall PM incidence was reduced by 64%, 34% and 19%, respectively. In adults ≥ 65 years of age, a 69% reduction in PCV10 serotypes was offset by 157% (56%-342%) increase in non-PCV10 serotypes. The overall PM-related mortality rate decreased by 42% (95%CI 4%-65%). Overall case fatality proportion (CFP) was 16% in pre-PCV10 period and 12% in PCV10 period (p = 0.41); among persons 50-64 years the CFP decreased from 25% to 10% (p = 0.04).
Conclusions:
We observed substantial impact and herd protection for vaccine-serotype PM and associated mortality after infant PCV10 introduction. However, in older adults ≥ 65 years of age, PM burden remains unchanged due to serotype replacement.
Introduction:
Streptococcus pneumoniae can cause invasive pneumococcal diseases (IPD), such as bacteremic pneumonia, bacteremia, meningitis, and sepsis, and non-IPDs, such as otitis media, nonbacteremic pneumonia, and upper respiratory tract infections. It was estimated in 2000 that, worldwide, S. pneumoniae was responsible for 826,000 deaths annually in children aged between 1 month and 5 years. A 7-valent pneumococcal conjugate vaccine (PCV7) was licensed in 2000 in the USA and in 2001 in Europe.
Methods:
A literature search was performed in PubMed to identify studies assessing the impact of routine childhood PCV7 vaccination on pneumococcal morbidity and mortality. Here, the impact on IPD is reported.
Results:
A total of 37 articles reporting impact data on IPD were included in this review: four from Australia, 17 from western Europe, and 16 from North America. In vaccine-eligible children in the postvaccination period, a reduction ranging from 39.9% in Spain to 99.1% in the USA in vaccine-type (VT) IPD incidence, compared with the prevaccination period, was reported in 18 studies. All but one of the 30 studies assessing the impact of PCV7 on all-type IPD reported a reduction ranging from 1.7% in Spain to 76.3% in Australia. In addition, the majority of studies reported reductions in VT and all-type IPD incidence in age groups that were not vaccine eligible.
Conclusions:
The results from this review illustrate that PCV7 has had a significant impact on IPD across all ages through its use in pediatric immunization programs. With the introduction of 13-valent pneumococcal conjugate vaccine (PCV13) further reductions in the incidence of IPD due to the six additional serotypes included, as well as continued protection against IPD due to PCV7 serotypes may be expected. Robust surveillance systems are essential for the evaluation of the impact of PCV13 on all-type IPD and for monitoring the evolution of non-VT IPD.
The introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in September 2006 has markedly reduced the burden of invasive pneumococcal disease (IPD) including meningitis in England and Wales. This study examined changes in the molecular epidemiology of pneumococcal isolates causing meningitis during July 2004-June 2009. The Health Protection Agency conducts enhanced pneumococcal surveillance in England and Wales. In addition to serotyping, pneumococcal isolates causing meningitis were genotyped by Multi Locus Sequence Typing (MLST). A total of 1,030 isolates were both serotyped and genotyped over the 5 year-period. Fifty-two serotypes, 238 sequence types (STs) and 87 clonal complexes were identified, with no significant difference in the yearly Simpson's Diversity Index (range, 0.974-0.984). STs commonly associated with PCV7 serotypes declined following PCV implementation, with a proportionally greater decline in ST124 (commonly associated with serotype 14). No other ST showed significant changes in distribution, even within individual serotypes. Replacement disease following PCV7 introduction was mainly due to serotypes 1, 3, 7F, 19A, 22F and 33F through clonal expansion. A single instance of possible capsule switching was identified where one ST4327 clone expressed a 14 capsule in 2005 and a 28A capsule in 2009. In 2008-09, ST191 (7F) became the most prevalent clone causing meningitis (10.3%). Case fatality (145/1,030; 14.1%) was high across all age groups and serotype groups. Thus, the introduction of PCV7 resulted in an increase in non-PCV7 serotypes, including some not covered by the 13-valent vaccine such as serotypes 22F and 33F, emphasising the importance of long-term epidemiological and molecular surveillance.
We assessed known risk factors, clinical presentation, and outcome of invasive pneumococcal disease (IPD) in children 3-59 months of age after introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in England and Wales. During September 2006-March 2010, a total of 1,342 IPD episodes occurred in 1,332 children; 14.9% (198/1,332) had comorbidities. Compared with IPD caused by PCV7 serotypes (44/248; 17.7%), comorbidities were less common for the extra 3 serotypes in the 10-valent vaccine (15/299; 5.0%) but similar to the 3 additional PCV13 serotypes (45/336; 13.4%) and increased for the 11 extra serotypes in 23-valent polysaccharide vaccine (PPV23) (39/186; 21.0%) and non-PPV23 serotypes (38/138; 27.5%). Fifty-two (3.9%) cases resulted from PCV7 failure; 9 (0.7%) case-patients had recurrent IPD. Case-fatality rate was 4.4% (58/1,332) but higher for meningitis (11.0%) and children with comorbidities (9.1%). Thus, comorbidities were more prevalent in children with IPD caused by non-PCV13 serotypes and were associated with increased case fatality.
Pneumococcus is the most common and aggressive cause of bacterial meningitis and induces a novel apoptosis-inducing factor-dependent (AIF-dependent) form of brain cell apoptosis. Loss of production of two pneumococcal toxins, pneumolysin and H2O2, eliminated mitochondrial damage and apoptosis. Purified pneumolysin or H2O2 induced microglial and neuronal apoptosis in vitro. Both toxins induced increases of intracellular Ca2+ and triggered the release of AIF from mitochondria. Chelating Ca2+ effectively blocked AIF release and cell death. In experimental pneumococcal meningitis, pneumolysin colocalized with apoptotic neurons of the hippocampus, and infection with pneumococci unable to produce pneumolysin and H2O2 significantly reduced damage. Two bacterial toxins, pneumolysin and, to a lesser extent, H2O2, induce apoptosis by translocation of AIF, suggesting new neuroprotective strategies for pneumococcal meningitis.
Objective
To determine the incidence, as well as the implicated serotypes and patterns of antibiotic resistance of Streptococcus pneumoniae meningitis in Spanish children.
Material and method
We performed a prospective, multicenter study in five Autonomous Communities (Catalonia, Galicia, Madrid, Navarre and the Basque Country) for 1 year (1 February 2000 – 31 January 2001). All children aged 0–14 years with pneumococcal meningitis from all the hospitals in the Autonomous Communities studied were included. Diagnosis was based on clinical findings and isolation of S. pneumonia in the cerebrospinal fluid/blood using routine methods or polymerase chain reaction. Serotyping was performed using the guellung reaction and/or immunoblotting and susceptibility to antibiotics was evaluated by the technique of agar dilution. The pediatric population aged 0–14 years in the Autonomous Communities studied comprises 2,290,304 children.
Results
Fifty-two cases were identified. One patient was aged less than 2 months old, 25 (48 %) were aged 2–12 months, and 12 patients (23 %) were aged 12–24 months. The annual incidence per 100,000 children aged between 1 and 2 years was 17.75 cases (95 % CI: 11.59 – 26.01) and 8.39 cases (95 % CI: 4.67 – 15.79) respectively, and that for children in the first 2 and 5 years of life was 13.13 (95% CI: 9.29 – 18.02) and 6.29 (95 % CI: 4.57 – 8.,45) cases respectively. Nearly half the strains isolated (47.6%) showed reduced sensitivity to penicillin. The most frequent serotype was 19F (12 cases [28.6 %]). Eighty percent of the isolated serotypes were included in the formula of the heptavalent conjugate vaccine.
Conclusion
The incidence of pneumococcal meningitis in children from five Spanish Autonomous Communities is high, nearly twice that found in a prior retrospective studied performed in the same population 1–3 years previously. Almost all the isolated serotypes were included in the heptavalent conjugate vaccine. Half the strains showed reduced sensitivity to penicillin.
Les méningites à pneumocoque représentent une cause majeure de morbidité et de mortalité chez l’enfant. A partir des données de l’Observatoire National des Méningites Bactériennes de l’enfant du GPIP/ACTIV (Groupe de Pathologie Infectieuse Pédiatrique et Association Clinique et Thérapeutique Infantile du Val de Marne), l’objectif de ce travail a été de décrire les caractéristiques cliniques ainsi que les principaux changements épidémiologiques des méningites à pneumocoque depuis l’introduction du vaccin anti-pneumococcique conjugué heptavalent (PCV7) en France.
Three bacteria-Haemophilus influenzae, Streptococcus pneumoniae, and Neisseria meningitidis-account for most acute bacterial meningitis. Measurement of the effect of protein-polysaccharide conjugate vaccines is most reliable for H influenzae meningitis because one serotype and one age group account for more than 90% of cases and the incidence has been best measured in high-income countries where these vaccines have been used longest. Pneumococcal and meningococcal meningitis are caused by diverse serotypes and have a wide age distribution; measurement of their incidence is complicated by epidemics and scarcity of surveillance, especially in low-income countries. Near elimination of H influenzae meningitis has been documented after vaccine introduction. Despite greater than 90% reductions in disease attributable to vaccine serotypes, all-age pneumococcal meningitis has decreased by around 25%, with little data from low-income settings. Near elimination of serogroup C meningococcal meningitis has been documented in several high-income countries, boding well for the effect of a new serogroup A meningococcal conjugate vaccine in the African meningitis belt.
Vaccination with pneumococcal conjugate vaccine (PCV) for all children <2 years was recommended in Germany in July 2006. Initially PCV7 was exclusively used; PCV10 became available from April 2009 and PCV7 was replaced by PCV13 in December 2009.
To compare the incidence and serotype distribution of invasive pneumococcal disease (IPD) for pneumococcal meningitis and non-meningitis IPD in children from 2007 to 2010 with reference to the pre-vaccination period from 1997 to 2001.
Nationwide surveillance of IPD for children <16 years in Germany was based on two independent reporting sources: active surveillance in paediatric hospitals and passive web-based surveillance through microbiological laboratories. Serotyping was performed using the Neufeld Quellung reaction. Case definition: isolation of Streptococcus pneumoniae from a normally sterile body site. IPD incidence was estimated by capture-recapture analysis. Rate ratios comparing post- to pre-vaccination incidence were calculated as well as PCV7 and non-PCV7 serotype specific incidences.
While PCV7 incidence decreased by 88% (95%CI: 83 to 91) in children <16 years both in pneumococcal meningitis and non-meningitis IPD, an increase in Non-PCV7 serotypes was observed which was more pronounced in non-meningitis cases (168%; 95%CI: 140-257) than in pneumoccocal meningitis (65%; 95%CI: 23-123). The changes in incidence after four years were: <16 years: -35% (95%CI: -49 to -19), <2 years: -46% (95%CI: -61 to -27) for pneumococcal meningitis and+11% (95%CI: -4 to +29) and -26% (95%CI: -41 to -7) for non-meningitis IPD respectively.
Infant PCV7 vaccination in Germany prompted a decrease in the incidence of pneumococcal meningitis similar to that observed in England/Wales. In non-meningitis IPD the decrease was smaller and confined to the age group <2 years with no change or an increase in incidence in other age groups pointing to potential ascertainment bias due to increased blood-culturing.