Mannose-binding lectin-deficient genotypes as a risk factor of pneumococcal meningitis in infants

OBJECTIVES: The objective of this study was to evaluate to evaluate the role of mannose-binding-lectin deficient genotypes in pneumococcal meningitis (PM) in children. METHODS: We performed a 16-year retrospective study (January 2001 to March 2016) including patients ≤ 18 years with PM. Variables including attack rate of pneumococcal serotype (high or low invasive capacity) and MBL2 genotypes associated with low serum MBL levels were recorded. RESULTS: Forty-eight patients were included in the study. Median age was 18.5 months and 17/48 episodes (35.4%) occurred in children ≤ 12 months old. Serotypes with high-invasive disease potential were identified in 15/48 episodes (31.2%). MBL2 deficient genotypes accounted for 18.8% (9/48). Children ≤ 12 months old had a 7-fold risk (95% CI: 1.6-29.9; p 12 months old. A sub-analysis of patients by age group revealed significant proportions of carriers of MBL2 deficient genotypes among those ≤ 12 months old with PM caused by opportunistic serotypes (54.5%), admitted to the PICU (Pediatric Intensive Care Unit) (46.7%) and of White ethnicity (35.7%). These proportions were significantly higher than in older children (all p<0.05). CONCLUSIONS: Our results suggest that differences in MBL2 genotype in children ≤12 months old affects susceptibility to PM, and it may have an important role in the episodes caused by non-high invasive disease potential serotypes

Effectiveness of the 23-valent pneumococcal polysaccharide vaccine against Invasive Pneumococcal Disease incidence in European adults aged 65 years and above : results of SpIDnet/I-MOVE+ multicentre study (2012-2016)

Background and Aims: We measured the effectiveness of 23-valent pneumococcal polysaccharidic vaccine(PPV23) against invasive pneumococcal disease (IPD) in 65+ year-olds, pooling surveillance data from seven European sites. PPV23 vaccination is recommended in all sites (8-69% uptake) and PCV13 in high risk groups in two sites (<5%uptake). Methods: We compared the vaccination status of IPD cases caused byPPV23 serotypes (cases) to that of nonPPV23 IPD (controls) notified between2012 and 2016. We defined PPV23 vaccination as at least one dose. PPV23 pooled effectiveness was calculated as (1 –odds ratio of vaccination)*100, adjusted for site, age, sex, underlying conditions and year. We stratified PPV23effectiveness by time since last dose of vaccine: <2, 2-4, 5-9 and 10+years. Results: We included 2011 cases and 878 controls. Compared to controls,cases were younger (p=0.001), less likely to have an underlying condition(p=0.025), more likely to be admitted for intensive care (p=0.038) and to have pneumonia (p=0.005). PPV23 effectiveness was 24% (95%CI: 4; 41) against PPV23-serotypes.By serotype, PPV23 effectiveness ranged between -2% (95%CI: -48; 30) against serotype 3 (n=687) and 55% (95%CI: 15; 76) against serotype 9N IPD (n=540). By years since vaccination, PPV23 effectiveness was 43% (95%CI: 3-66) and 15%(95%CI: -25; 43) for <2 years and 10+ years, respectively. Conclusion: Our findings suggest a low PPV23 effectiveness against IPD caused by PPV23serotypes in the elderly, varying by serotype, and higher in the first two years after vaccination. Despite low effectiveness, PPV23 in the elderly may prevent at least 25% of cases among vaccinated

Streptococcus pneumoniae Clonal Complex 199: Genetic Diversity and Tissue-Specific Virulence

Streptococcus pneumoniae is an important cause of otitis media and invasive disease. Since introduction of the heptavalent pneumococcal conjugate vaccine, there has been an increase in replacement disease due to serotype 19A clonal complex (CC)199 isolates. The goals of this study were to 1) describe genetic diversity among nineteen CC199 isolates from carriage, middle ear, blood, and cerebrospinal fluid, 2) compare CC199 19A (n = 3) and 15B/C (n = 2) isolates in the chinchilla model for pneumococcal disease, and 3) identify accessory genes associated with tissue-specific disease among a larger collection of S. pneumoniae isolates. CC199 isolates were analyzed by comparative genome hybridization. One hundred and twenty-seven genes were variably present. The CC199 phylogeny split into two main clades, one comprised predominantly of carriage isolates and another of disease isolates. Ability to colonize and cause disease did not differ by serotype in the chinchilla model. However, isolates from the disease clade were associated with faster time to bacteremia compared to carriage clade isolates. One 19A isolate exhibited hypervirulence. Twelve tissue-specific genes/regions were identified by correspondence analysis. After screening a diverse collection of 326 isolates, spr0282 was associated with carriage. Four genes/regions, SP0163, SP0463, SPN05002 and RD8a were associated with middle ear isolates. SPN05002 also associated with blood and CSF, while RD8a associated with blood isolates. The hypervirulent isolate's genome was sequenced using the Solexa paired-end sequencing platform and compared to that of a reference serotype 19A isolate, revealing the presence of a novel 20 kb region with sequence similarity to bacteriophage genes. Genetic factors other than serotype may modulate virulence potential in CC199. These studies have implications for the long-term effectiveness of conjugate vaccines. Ideally, future vaccines would target common proteins to effectively reduce carriage and disease in the vaccinated population

Survey of childhood empyema in Asia: Implications for detecting the unmeasured burden of culture-negative bacterial disease

<p>Abstract</p> <p>Background</p> <p>Parapneumonic empyema continues to be a disease of significant morbidity and mortality among children despite recent advances in medical management. To date, only a limited number of studies have assessed the burden of empyema in Asia.</p> <p>Methods</p> <p>We surveyed medical records of four representative large pediatric hospitals in China, Korea, Taiwan and Vietnam using <it>ICD</it>-10 diagnostic codes to identify children <16 years of age hospitalized with empyema or pleural effusion from 1995 to 2005. We also accessed microbiology records of cultured empyema and pleural effusion specimens to describe the trends in the epidemiology and microbiology of empyema.</p> <p>Results</p> <p>During the study period, we identified 1,379 children diagnosed with empyema or pleural effusion (China, n = 461; Korea, n = 134; Taiwan, n = 119; Vietnam, n = 665). Diagnoses of pleural effusion (n = 1,074) were 3.5 times more common than of empyema (n = 305), although the relative proportions of empyema and pleural effusion noted in hospital records varied widely between the four sites, most likely because of marked differences in coding practices. Although pleural effusions were reported more often than empyema, children with empyema were more likely to have a cultured pathogen. In addition, we found that median age and gender distribution of children with these conditions were similar across the four countries. Among 1,379 empyema and pleural effusion specimens, 401 (29%) were culture positive. <it>Staphylococcus aureus </it>(n = 126) was the most common organism isolated, followed by <it>Streptococcus pneumoniae </it>(n = 83), <it>Pseudomonas aeruginosa </it>(n = 37) and <it>Klebsiella </it>(n = 35) and <it>Acinetobacter </it>species (n = 34).</p> <p>Conclusion</p> <p>The age and gender distribution of empyema and pleural effusion in children in these countries are similar to the US and Western Europe. <it>S. pneumoniae </it>was the second leading bacterial cause of empyema and pleural effusion among Asian children. The high proportion of culture-negative specimens among patients with pleural effusion or empyema suggests that culture may not be a sufficiently sensitive diagnostic method to determine etiology in the majority of cases. Future prospective studies in different countries would benefit from standardized case definitions and coding practices for empyema. In addition, more sensitive diagnostic methods would improve detection of pathogens and could result in better prevention, treatment and outcomes of this severe disease.</p

Impact of Capsular Switch on Invasive Pneumococcal Disease Incidence in a Vaccinated Population

BACKGROUND: Despite the dramatic decline in the incidence of invasive pneumococcal disease (IPD) observed since the introduction of conjugate vaccination, it is feared that several factors may undermine the future effectiveness of the vaccines. In particular, pathogenic pneumococci may switch their capsular types and evade vaccine-conferred immunity. METHODOLOGY/PRINCIPAL FINDINGS: Here, we first review the literature and summarize the available epidemiological data on capsular switch for S. pneumoniae. We estimate the weekly probability that a persistently carried strain may switch its capsule from four studies, totalling 516 children and 6 years of follow-up, at 1.5x10(-3)/week [4.6x10(-5)-4.8x10(-3)/week]. There is not enough power to assess an increase in this frequency in vaccinated individuals. Then, we use a mathematical model of pneumococcal transmission to quantify the impact of capsular switch on the incidence of IPD in a vaccinated population. In this model, we investigate a wide range of values for the frequency of vaccine-selected capsular switch. Predictions show that, with vaccine-independent switching only, IPD incidence in children should be down by 48% 5 years after the introduction of the vaccine with high coverage. Introducing vaccine-selected capsular switch at a frequency up to 0.01/week shows little effect on this decrease; yearly, at most 3 excess cases of IPD per 10(6) children might occur due to switched pneumococcal strains. CONCLUSIONS: Based on all available data and model predictions, the existence of capsular switch by itself should not impact significantly the efficacy of pneumococcal conjugate vaccination on IPD incidence. This optimistic result should be tempered by the fact that the selective pressure induced by the vaccine is currently increasing along with vaccine coverage worldwide; continued surveillance of pneumococcal populations remains of the utmost importance, in particular during clinical trials of the new conjugate vaccines

Significant Reduction of Antibiotic Use in the Community after a Nationwide Campaign in France, 2002–2007

Didier Guillemot and colleagues describe the evaluation of a nationwide programme in France aimed at decreasing unnecessary outpatient prescriptions for antibiotics. The campaign was successful, particularly in reducing prescriptions for children

Environmental effects of ozone depletion, UV radiation and interactions with climate change : UNEP Environmental Effects Assessment Panel, update 2017

Peer reviewe

Serotype distribution of Streptococcus pneumoniae causing invasive disease in children in the post-PCV era:A systematic review and meta-analysis

BACKGROUND:Routine immunisation with pneumococcal conjugate vaccines (PCV7/10/13) has reduced invasive pneumococcal disease (IPD) due to vaccine serotypes significantly. However, an increase in disease due to non-vaccine types, or serotype replacement, has been observed. Serotypes' individual contributions to IPD play a critical role in determining the overall effects of PCVs. This study examines the distribution of pneumococcal serotypes in children to identify leading serotypes associated with IPD post-PCV introduction. METHODS:A systematic search was performed to identify studies and surveillance reports (published between 2000 and December 2015) of pneumococcal serotypes causing childhood IPD post-PCV introduction. Serotype data were differentiated based on the PCV administered during the study period: PCV7 or higher valent PCVs (PCV10 or PCV13). Meta-analysis was conducted to estimate the proportional contributions of the most frequent serotypes in childhood IPD in each period. RESULTS:We identified 68 studies reporting serotype data among IPD cases in children. We analysed data from 38 studies (14 countries) where PCV7 was administered and 20 (24 countries) where PCV10 or PCV13 have been introduced. Studies reported early and late periods of PCV7 administration (range: 2001∓13). In these settings, serotype 19A was the most predominant cause of childhood IPD, accounting for 21.8% (95%CI 18.6∓25.6) of cases. In countries that have introduced higher valent PCVs, study periods were largely representative of the transition and early years of PCV10 or PCV13. In these studies, the overall serotype-specific contribution of 19A was lower (14.2% 95%CI 11.1∓18.3). Overall, non-PCV13 serotypes contributed to 42.2% (95%CI 36.1∓49.5%) of childhood IPD cases. However, regional differences were noted (57.8% in North America, 71.9% in Europe, 45.9% in Western Pacific, 28.5% in Latin America, 42.7% in one African country, and 9.2% in one Eastern Mediterranean country). Predominant non-PCV13 serotypes overall were 22F, 12F, 33F, 24F, 15C, 15B, 23B, 10A, and 38 (descending order), but their rank order varied by region. CONCLUSION:Childhood IPD is associated with a wide number of serotypes. In the early years after introduction of higher valent PCVs, non-PCV13 types caused a considerable proportion of childhood IPD. Serotype data, particularly from resource-limited countries with high burden of IPD, are needed to assess the importance of serotypes in different settings. The geographic diversity of pneumococcal serotypes highlights the importance of continued surveillance to guide vaccine design and recommendations