Outcome Of Invasive Pneumococcal Disease Research Articles

Abstract We063: CD73 EXPRESSION ON NEUTROPHILS PROTECTS AGAINST CARDIOMYOCYTE DAMAGE DURING INVASIVE STREPTOCOCCUS PNEUMONIAE INFECTION

In recent years, Streptococcus pneumoniae (pneumococcus)-induced cardiac events have emerged as one of the most serious and life-threatening infection outcomes of invasive pneumococcal disease (IPD), leading to major adverse cardiac events (MACE) with high mortality rates. S. pneumoniae has the ability to invade myocardium and damage cardiomyocytes through the release of bacterial factors and formation of bacterial-filled cardiac microlesions. We previously found that polymorphonuclear cells (PMNs) or neutrophils are crucial for host defense against S. pneumoniae lung infection and that extracellular adenosine (EAD) production, by the exonucleosidase CD73, controlled the anti-bacterial functions of these cells. The objective of this study was to explore the role of PMNs and CD73 in cardiac damage during invasive pneumococcal infection. Upon intra-peritoneal ( i.p .) injection with TIGR4, an invasive pneumococcal strain, C57BL/6 mice showed an increased influx of PMNs into the cardiac tissue as determined by flow cytometry. However, the increased PMN numbers failed to contain bacterial burden in the heart and showed a positive correlation with serum levels of the cardiac damage marker Troponin-1 as determined through ELISA. Depletion of PMNs prior infection reduced pneumococcal burden in the heart and lowered the Troponin-1 levels suggesting that PMNs induce cardiac damage during infection. While exploring the mechanisms underlying the detrimental PMN response, we found that the late stage of IPD was associated with reduced CD73 expression on PMNs. The role of CD73 in regulating cardiac damage was tested in vivo using CD73 -/- mice which had significantly higher bacterial burden and cardiac damage compared to wild-type mice despite similar PMN numbers. The role of CD73 expression on PMNs was also tested ex vivo using the HL-1 cardiomyocyte cell line which showed increased LDH release upon S. pneumoniae infection in presence of CD73 -/- PMNs, a phenotype reversed by supplementation of exogenous adenosine. Similar iincreased damage in presence of CD73 -/- PMNs was seen with C57BL/6 Mouse Primary Cardiac Microvascular Endothelial Cells which lead to increased migration of beads across endothelium. Our findings suggest that dysregulation of CD73 on PMNs during invasive pneumococcal infection leads to an inability to control bacterial numbers and increased cardiac damage, and that the EAD-pathway can be a potential pharmacological target to limit disease severity.

Clinical characteristics and risk factors for poor outcomes of invasive pneumococcal disease in pediatric patients in China

BackgroundInvasive pneumococcal disease (IPD) is a significant health concern in children worldwide. In this study, we aimed to analyze the clinical features, antibiotic resistance, and risk variables for poor outcomes in patients with IPD in Hangzhou.MethodsA retrospective single-centre study was performed using the pediatric intensive care (PIC) database from 2010 to 2018. The clinical characteristics, laboratory data, antimicrobial resistance, and risk factors for in-hospital mortality and sepsis in patients with IPD in intensive care units (ICUs) were analyzed systematically.ResultsA total of 178 IPD patients were included in the study. The majority of the IPD children were 2–10 years old. Antimicrobial resistance tests of S. pneumoniae isolates revealed high resistance to erythromycin, tetracycline and compound sulfamethoxazole (SMZ-Co). All the isolates were sensitive to vancomycin, linezolid, moxifloxacin, telithromycin, ofloxacin, and levofloxacin. IPD patients may experience poor outcomes, including death and sepsis. The in-hospital mortality was 3.93%, and 34.27% of patients suffered from sepsis. Temperature (OR 3.80, 95% CI 1.62–8.87; P = 0.0021), Partial Pressure of Oxygen in Arterial Blood (PaO2) (OR 0.99, 95% CI 0.98-1.00; P = 0.0266), and albumin (OR 0.89, 95% CI 0.80–0.99; P = 0.0329) were found to be independent risk factors for sepsis in children with IPD.ConclusionPediatric IPD deserves attention in China. Appropriate surveillance and antibiotic selection are crucial in managing resistant strains. Early identification of high-risk individuals with risk factors contributes to the development of appropriate treatment strategies.

Invasive pneumococcal disease due to 22F and 33F in England: A tail of two serotypes

BackgroundA 15-valent pneumococcal conjugate vaccine (PCV15) aims to protect against serotype 22F and 33F in addition to the serotypes within the 13-valent PCV (PCV13) which was introduced to the UK childhood immunisation programme in April 2010. Little is known about the specific epidemiology, clinical features or outcomes of invasive pneumococcal disease (IPD) due to these two serotypes. MethodsPublic Health England (PHE) conducts enhanced IPD surveillance in England. Hospital laboratories routinely submit invasive pneumococcal isolates to PHE for serotyping and enhanced clinical information is collected through questionnaires sent to general practitioners. IPD due to serotypes 22F and 33F diagnosed during 2014/15–2018/19 were compared with IPD due to PCV13 serotypes and remaining serotypes. ResultsIn total, 25,415 isolates (93.4%) were serotyped and questionnaires were completed for 22,097 (86.9%) cases. Serotype 22F was responsible for 1,788 (7.0%) and serotype 33F for 893 (3.5%) cases compared to 19.9% (n = 5,047) for PCV13 and 69.6% (n = 17,687) for the remaining serotypes. IPD incidence increased for both serotypes since 2005/06, especially in older adults, but plateaued after PCV13 introduction. Comorbidity prevalence was 68.7% (n = 1,037) for serotype 22F and 67.2% (n = 505) for serotype 33F, with invasive pneumonia being the most common clinical presentation 1,067/1,482; 72.0%, and 514/755; 68.1%, respectively. There were 3,617 deaths within 30 days of disease onset, including 236 (CFR, 15.4%) among 22F, 128 (CFR, 16.5%) among 33F and 21.3% (925/4,350) among PCV13-type IPD cases. When compared with PCV13-type IPD, serotype 22F (aOR 0.58, 95%CI 0.49–0.68, p < 0.001) and 33F (aOR 0.73, 95%CI 0.59–0.91, p = 0.004) were independently associated with lower odds of death. The major circulating sequence types (STs) in 22F (ST 433, ST698) and 33F (ST717, ST100, ST673) were not associated with an increased risk of death compared to the other STs. ConclusionsSerotype 22F and 33F-type IPD are associated with a lower risk of death compared to PCV13-type, with those presenting with septicaemia more likely to have a fatal outcome compared to pneumonia. PCV15 has the potential to prevent up to an additional 10% of IPD cases in England.

Asthma and the Risk of Invasive Pneumococcal Disease: A Meta-Analysis

JA Castro-Rodriguez, K Abarca, E Forno. Pediatrics . 2020;145(1):e20191200 To assess the risk of invasive pneumococcal disease (IPD) or pneumonia among children with asthma following the administration of pneumococcal conjugate vaccine (PCV). All case-controlled or cohort studies of IPD and pneumonia in populations who have received the PCV (predominantly 7-valent pneumococcal conjugate) that reported data on children with asthma and healthy controls. Two independent reviewers examined the studies for the primary outcome of IPD and pneumonia. Secondary outcomes were mortality, hospitalizations, length of stay, ICU admission, respiratory assistance, …

Early clinical predictors for the prognosis of invasive pneumococcal disease

BackgroundRisk factors related to mortality due to invasive pneumococcal disease (IPD) have been unveiled previously, but early clinical manifestations of IPD based on prognosis remain uncovered.MethodsThe demographic characteristics, clinical features, serotype, antibiotic susceptibility, and outcomes of 97 hospitalized children with laboratory-confirmed IPD from Suzhou, China, were collected and analyzed retrospectively.ResultsThe median age was 0.69 (0.49–1.55) years in the non-survivor group compared with 2.39 (0.90–3.81) years in the survivor group. The mortality of 97 children with laboratory-confirmed IPD was 17.5% (17/97), and 53.6% of them were aged less than 2 years. Pathogens were mainly from the blood and cerebrospinal fluid, and sepsis was the most frequent type. Statistically significant differences were found in hyperpyrexia, vomiting, anorexia, lethargy, poor perfusion of extremities, Hb level, and Plt count between the nonsurvival and survival groups. Further, the multivariate regression analysis showed that early signs, including hyperpyrexia, vomiting, anorexia, lethargy, and poor perfusion of extremities, were independent risk factors for the in-hospital mortality of children with laboratory-confirmed IPD. The mortality was also associated with antimicrobial sensitivity in pneumococcal isolates. The microbes in 1/17 (5.9%) children who were prescribed an antibiotic showed antimicrobial sensitivity in the nonsurvival group, compared with 21/80 (26.3%) children who survived. The most common serotypes identified were 6B (35.3%, 6/17), 14 (23.5%, 4/17), 19F (23.5%, 4/17), 19A (5.9%, 1/17), 23F (5.9%, 1/17), and 20 (5.9%, 1/17) in the nonsurvival group. The coverage of IPD serotypes of the 7-valent pneumococcal conjugate vaccine (PCV7) was 88.2% (15/17), while that of the 13-valent S. pneumoniae vaccine (PCV13) was 94.1% (16/17) of the coverage in the nonsurvival group.ConclusionsRecurrent hyperpyrexia, vomiting, anorexia, lethargy, and poor perfusion of extremities in the early stage were independent predictors for the in-hospital mortality of children with laboratory-confirmed IPD. Appropriate use of antibiotics and PCV immunization were the keys to improve the outcome of IPD.

Association of Influenza Activity and Environmental Conditions With the Risk of Invasive Pneumococcal Disease

Streptococcus pneumoniae is the most commonly identified cause of bacterial pneumonia, and invasive pneumococcal disease (IPD) has a high case fatality rate. The wintertime coseasonality of influenza and IPD in temperate countries has suggested that pathogen-pathogen interaction or environmental conditions may contribute to IPD risk. To evaluate the short-term associations of influenza activity and environmental exposures with IPD risk in temperate countries and to examine the generalizability of such associations across multiple jurisdictions. This case-crossover analysis of 19 566 individuals with IPD from 1998 to 2011 combined individual-level outcomes of IPD and population-level exposures. Participants lived in 12 jurisdictions in Canada (the province of Alberta and cities of Toronto, Vancouver, and Halifax), Australia (Perth, Sydney, Adelaide, Brisbane, and Melbourne), and the United States (Baltimore, Providence, and Philadelphia). Data were analyzed in 2019. Influenza activity, mean temperature, absolute humidity, and UV radiation at delays of 1 to 3 weeks before case occurrence in each jurisdiction. Matched odds ratios (ORs) for IPD associated with changes in exposure variables, estimated using multivariable conditional logistic regression models. Heterogeneity in effects across jurisdictions were evaluated using random-effects meta-analytic models. This study included 19 566 patients: 9629 from Australia (mean [SD] age, 42.8 [30.8] years; 5280 [54.8%] men), 8522 from Canada (only case date reported), and 1415 from the United States (only case date reported). In adjusted models, increased influenza activity was associated with increases in IPD risk 2 weeks later (adjusted OR [aOR] per SD increase, 1.07; 95% CI, 1.01-1.13). Increased humidity was associated with decreased IPD risk 1 week later (aOR per 1 g/m3, 0.98; 95% CI, 0.96-1.00). Other associations were heterogeneous; metaregression suggested that combinations of environmental factors might represent unique local risk signatures. For example, the heterogeneity in effects of UV radiation and humidity at a 2-week lag was partially explained by variation in temperature (UV index: coefficient, 0.0261; 95% CI, 0.0078 to 0.0444; absolute humidity: coefficient, -0.0077; 95% CI, -0.0125 to -0.0030). In this study, influenza was associated with increased IPD risk in temperate countries. This association was not explained by coseasonality or case characteristics and appears generalizable. Absolute humidity was associated with decreased IPD risk in the same jurisdictions. The generalizable nature of these associations has important implications for influenza control and advances the understanding of the seasonality of this important disease.

Twelve years of pneumococcal conjugate vaccination in the Netherlands: Impact on incidence and clinical outcomes of invasive pneumococcal disease

IntroductionIn 2006, the Netherlands introduced the 7-valent pneumococcal conjugate vaccine (PCV7) in their national immunisation programme. In 2011, PCV7 was replaced by the 10-valent vaccine (PCV10). We report on the impact of PCV on invasive pneumococcal disease (IPD) incidence, clinical syndromes and patient outcomes. MethodsPneumococcal isolates of hospitalised IPD patients between June 2004 and May 2018 were obtained from nine sentinel laboratories, covering 25% of the Dutch population. All isolates were serotyped. IPD incidence and clinical outcome were determined before and after introduction of PCV7 and after the switch to PCV10, stratified by age and serotype. ResultsCompared to before PCV7 introduction, significant declines in IPD incidence were observed in 2016–2018 in children <5 years (69%), 18–49 year olds (31%) and ≥65 year olds (19%). Compared to before PCV10 introduction, the IPD incidence in 2016–2018 declined in children <5 years (RR:0.68, 95%CI:0.42–1.11), 5–17 year olds (RR:0.58, 95%CI:0.29–1.14) and 18–49 year olds (RR:0.72, 95%CI:0.57–0.90), but not in 50–64 year olds (RR:0.94, 95%CI:0.81–1.10) and ≥65 year olds (RR:1.04, 95%CI:0.0.93–1.15). While the case fatality rate (CFR) decreased from 16.2% pre-PCV to 13.4% post-PCV10 (RR:0.83, 95%CI:0.70–0.99), the switch to PCV10 had no further impact on CFR (RR:1.14, 95%CI:0.96–1.36). ConclusionTwelve years of PCV in the Netherlands has resulted in a sustained reduction of IPD incidence in children and younger adults. The switch from PCV7 to PCV10 did not have additional impact on the IPD incidence in older adults and CFR due to emerging non-vaccine serotypes.

Outpacing the pneumococcus: Antibody dynamics in the first few days following pneumococcal capsular antigen stimulation

Children in developing countries are frequently exposed to the pneumococcus, but few develop invasive pneumococcal disease (IPD). We test the hypothesis that natural variation exists in the rapidity of IgG responses following exposure to pneumococcal polysaccharides, and that these differences are sufficiently great to affect susceptibility to and outcome of IPD. We recruited children aged 24–36 months, who had recovered from IPD, and age-matched healthy controls and vaccinated them with 1 dose of the 23-valent PPV to mimic natural exposure. We collected serum samples after vaccination and analysed the dynamics of anti-polysaccharide antibody responses to several capsular antigens. Mean IgG response times to different serotypes were 6.4–7.3 days, with standard deviations of 0.9–1.85 days, suggesting a natural range in response times of up to 7 days. Serotype 1 elicited the largest fold-rise, serotype 23F the smallest. The proportion of responses achieved by day 7 was similar in children with a history of IPD and healthy children. There was considerable natural variation in the rapidity of anti-capsular IgG responses extending over 4–7 days. There was no evidence to suggest that children who have experienced IPD respond more slowly to heterologous pneumococcal capsular antigens than do healthy children.

Invasive Pneumococcal Disease in UK Children

Invasive pneumococcal disease (IPD) has declined significantly since the introduction of pneumococcal conjugate vaccines (PCVs). It is not known whether certain infant populations remain at higher risk of IPD in countries with established 13-valent PCV (PCV13) programs. We aimed to describe the epidemiology, clinical characteristics, serotype distribution, and outcomes of IPD in infants, and to estimate the relative risk of PCV13-type, non-PCV13-type, and overall IPD in premature infants compared to term infants during a 4-year period after the PCV13 program was established. This was a prospective, enhanced national surveillance of laboratory-confirmed IPD in England in infants aged <1 year diagnosed during 2013-2016. There were 517 cases of IPD (incidence: 19/100000 infants). Incidence was significantly higher in premature infants compared with those born at term (49/100000 vs 17/100000; incidence rate ratio [IRR], 2.87; P < .001), with infants born before 28 weeks' gestation having the highest incidence (150/100000; IRR, 8.8; P < .001). Of the 454 IPD cases with serotyped isolates, most were caused by non-PCV13 serotypes (369 cases, 71.4%), with 85 cases (16.4%) due to PCV13 serotypes. There were 31 deaths (case fatality rate [CFR], 6.2% [95% confidence interval, 4.3%-8.6%]). Premature infants did not have a higher CFR than term infants (P = .62). IPD incidence in infants remains lower than rates reported prior to PCV7 introduction in England. The risk of IPD remains significantly higher in premature infants compared to infants born at term, for both PCV13 and non-PCV13 serotypes. Any changes to the infant PCV13 immunization schedule may disproportionally affect premature infants.

Risk of Invasive Pneumococcal Disease in Children with Sickle Cell Disease in England: A National Observational Cohort Study, 2010–2015

ObjectiveTo describe the clinical presentation, risk factors, serotype distribution and outcomes of invasive pneumococcal disease (IPD) in children with sickle cell disease (SCD) following the introduction of the 13-valent pneumococcal...

Effect of Age on the Manifestations and Outcomes of Invasive Pneumococcal Disease in Adults

BackgroundAlthough a considerable amount is known about the effect of age on the manifestations and outcomes of pneumonia, the same is not true for invasive pneumococcal disease. MethodsThis was a prospective observational study of all cases (2435) of invasive pneumococcal disease in adults in Northern Alberta from 2000 to 2014. Rates of invasive pneumococcal disease per 100,000, sociodemographic variables, clinical characteristics, and invasive pneumococcal disease–related outcomes were compared for the following age groups: 17-54, 55-64, 65-74, and ≥75 years. ResultsThe rate of invasive pneumococcal disease per 100,000 increased with increasing age. Although only 27.3% of the cases were in those aged ≥65 years, they accounted for 48% of the deaths. The case fatality rate increased with increasing age, from 9.6% for those aged 17-54 years to 31.7% for those aged ≥75 years. The rate of meningitis decreased with increasing age, as did admission to intensive care and use of mechanical ventilation. There was a marked reduction in the rate of invasive pneumococcal disease due to protein conjugate vaccine 7 and protein conjugate vaccine 13 serotypes in those aged ≥55 years but a much smaller decline in rates for those aged 17-54 years. Replacement with non-vaccine serotypes constituted approximately 50% of the cases. ConclusionsThe rate of invasive pneumococcal disease is highest in the very elderly, and manifestations of invasive pneumococcal disease are influenced by age.

Characteristics and Serotype Distribution of Childhood Cases of Invasive Pneumococcal Disease Following Pneumococcal Conjugate Vaccination in England and Wales, 2006-2014.

The 7-valent and 13-valent pneumococcal conjugate vaccines (PCV7 and PCV13, respectively) are highly effective in preventing invasive pneumococcal disease (IPD) caused by vaccine serotypes. Vaccine failure (vaccine-type IPD after age-appropriate immunization) is rare. Little is known about the risk, clinical characteristics, or outcomes of PCV13 compared to PCV7 vaccine failure. Public Health England conducts IPD surveillance and provides a national reference service for serotyping pneumococcal isolates in England and Wales. We compared the epidemiology, rates, risk factors, serotype distribution, clinical characteristics, and outcomes of IPD in children with PCV13 and PCV7 vaccine failure. A total of 163 episodes of PCV failure were confirmed in 161 children over 8 years (4 September 2006 to 3 September 2014) in 10 birth cohorts. After 3 vaccine doses, PCV7 and PCV13 failure rates were 0.19/100000 (95% confidence interval [CI], .10-.33 [57 cases]) and 0.66/100000 (95% CI, .44-.95 [104 cases]) vaccinated person-years, respectively. Children with PCV13 failure were more likely to be healthy (87/105 [82.9%] vs 37/56 [66.1%]; P = .02), present with bacteremic lower respiratory tract infection (LRTI) (61/105 [58.1%] vs 11/56 [19.6%]; P < .001), and develop empyema (41/61 [67.2%] vs 1/11 [9.1%]; P < .001) compared to PCV7 failures. Serotypes 3 (n = 38 [36.2%]) and 19A (n = 30 [28.6%]) were responsible for most PCV13 failures. Six children died (4% [95% CI, 1%-8%]), including 5 with comorbidities. PCV failure is rare and, compared to PCV7 serotypes, the additional PCV13 serotypes are more likely to cause bacteremic LRTI and empyema in healthy vaccinated children.

Invasive Pneumococcal Disease in Patients With Sickle Cell Disease.

Patients with sickle cell disease (SCD) are at risk of fatal sepsis with encapsulated bacteria, such as Streptococcus pneumoniae, because of the inherent autosplenectomy that occurs in SCD. This risk is thwarted with oral penicillin prophylaxis during the first 5 years of life, and with stringent vaccination against S. pneumoniae alongside routine childhood immunization. But compared with the general African American pediatric population, the rate of invasive pneumococcal disease (IPD) in patients with SCD still remains high, resulting in hospitalization and fatality. Patients with SCD who developed IPD from 2004 up to 2013 were identified using microbiology records. Descriptive analysis of presence of risk factors for IPD, type of SCD, pneumococcal vaccination and prophylaxis status, clinical presentation, microbiological data, and the outcome of IPD was performed. Eight patients with SCD developed IPD (7 bacteremia and 1 respiratory tract infection). Three of the 8 isolates underwent serotype analysis (15 C in 2 and 15A in 1), none covered with the current vaccination program. One patient had fatal outcome (15A). Breakthrough cases of IPD may involve nonvaccine isolates, and seem to occur after 5 years of age when oral penicillin prophylaxis has been terminated.

Clinical features and outcomes of invasive pneumococcal disease in pediatric intensive care unit

Objective To investigate the clinical features of invasive pneumococcal disease(IPD) in pediatric intensive care unit(PICU) and to analyze outcomes, so as to provide evidence for early and reasonable diagnosis and treatment as well as to improvement of prognosis. Methods A retrospective study was conducted at a research center for IPD in PICU in Beijing Children's Hospital from January 2013 to April 2016.Clinical data of children with IPD were collected and analyzed.All specimens were for bacteria culture, isolation, strain identification and drug sensitivity test. At the same time, the quellung test was used to identify serotypes of the streptococcus pneumoniae. Results A total of 30 children meeting inclusion criteria were included, 19 male and 11 female.The median age was 1.5 years (range 3 months to 7.5 years). The Pediatric Critical Illness Scores (PCIS) were 72 (64, 82) scores.There were 13 cases whose Glasgow Coma Scores (GCS) were below 15 scores.The 28-day mortality rate was 36.7% (11/30 cases). Among death cases, there were 7 cases of purulent meningitis, 3 cases of septicemia and 1 case of purulent pleurisy.The onset age, peripheral blood leucocytes count, PCIS and GCS of death group were significantly lower than those of survival group (all P<0.05). The mortality rate of children complicated with septic shock was significantly higher than that of children without septic shock [75.0%(6/8 cases) vs 22.7%(5/22 cases), P<0.05]. The most common serotypes were 19F and 19A.The coverage rate of pneumococcal conjugate vaccine 13 was 96.7%.The percentage of penicillin nonsusceptible streptococcus pneumoniae was 73.3%, and the percentage of penicillin resistant streptococcus pneumoniae was 53.3%, and multi-drug resistant was 90%. Conclusions The mortality rate of IPD in PICU is high, and the main serotypes were 19F and 19A. Most patients of death group were less than 2 years old.Peripheral blood white blood cell count, PCIS and GCS were significantly reduced, and more complicated with septic shock.Vaccination of pneumococcal conjugate vaccine 13 for children less than 2 years old may reduce the incidence of IPD. Key words: Pediatric intensive care unit; Invasive pneumococcal disease; Clinical feature; Outcome

Risk and outcomes of invasive pneumococcal disease in adults with underlying conditions in the post-PCV7 era, The Netherlands

BackgroundImmunocompromising conditions and advanced age (≥65 years) are associated with a high risk for invasive pneumococcal disease (IPD). We investigated the risk and outcomes of IPD in adults with underlying conditions in the post-PCV7 era in The Netherlands. MethodsIPD data from 2008 to 2012 was obtained from the national pneumococcal surveillance system, covering 25% of the Dutch population. Population estimates of underlying conditions were derived from the primary care data (2012). IPD incidence in adults with immunocompromising conditions (high risk group) and non-immunocompromising comorbidities (medium risk group) were compared to the “normal risk group” without diagnosed comorbidities. Case-fatality and ICU admission in the different risk groups was analyzed by logistic regression. Serotype specific propensities to affect high risk group IPD patients were calculated. ResultsAdults with a high risk condition have a 18-fold (95% CI 15.6–21.2) and 3-fold (95% CI 2.6–3.9) higher risk compared to the normal risk group for IPD at age 18–64 years and 65 years and older, respectively. In case of a medium risk condition, the risk is 5-fold (95% CI 4.3–5.7) and 2-fold (95% CI 1.9–2.6) higher in age groups 18–64 and ≥65 years old. Likewise, IPD patients with a high or medium risk condition have a higher case-fatality (after adjustment for age, odds ratio: 2-fold (95% CI 1.5–3.5) and 1.4-fold (95% CI 1.0–2.1), respectively). Several serotypes (e.g. 6A, 6B, 23A and 23B) are associated with a significantly higher propensity to cause disease in high risk patients. ConclusionsThe risk for IPD and death in the post-PCV7 era has remained considerably high in adults and elderly with underlying conditions. The identification of serotypes with a high propensity to affect risk groups can be important for selecting (future) vaccine serotypes.

Clinical features and outcomes of invasive pneumococcal disease in a pediatric intensive care unit.

BackgroundInvasive pneumococcal disease (IPD) results in high morbidity and mortality globally each year, although it is a vaccine-preventable disease. This study aimed to characterize the clinical features of IPD in a pediatric intensive care unit (PICU) in Taiwan. The seven-valent pneumococcal conjugate vaccine (PCV7) was introduced in the private sector in October 2005. The estimated coverage rate of PCV7 vaccination in 2010 was 45.5 % among children <5 years of age.MethodsWe conducted a retrospective study at a single center in northern Taiwan for invasive pneumococcal disease in a PICU from 2009 to 2013. Demographic characteristics, clinical courses, serotype, antibiotic susceptibility, and outcomes were analyzed.ResultsOver the 5-year study period, 2167 patients were admitted to the PICU; 48 (2.2 %) had IPD. There were 29 female and 19 male patients. Their mean age was 3.7 years (range 0.7–12.5 years, with the peak age at 2–5 years; n = 30, 63 %). Pneumonia was the most frequent type (n = 38, 79 %), followed by meningitis (n = 10, 21 %). In total, three patients died, all within 72 h after admission; the final diagnoses were all meningitis. Thirty-four children with pneumonia received chest tube insertion for pleural effusion drainage. Of them, 22 (65 %) finally still underwent video-assisted thoracoscopic surgery. Eight (17 %) children had hemolytic uremic syndrome, and seven of them underwent hemodialysis. In total, 37 serotypes were detected; 95 % were covered by PCV13. Serotype 19A was most common (54 %) overall; however, in those with meningitis, serotype 19 F was most common.ConclusionsMeningitis is the most severe type of invasive pneumococcal disease in our pediatric intensive care unit. It may progress rapidly even when subjects are given antibiotics promptly. The most common serotype in meningitis is 19 F, which is vaccine preventable. Thus, universal mass pneumococcal vaccination is still needed.

Impact of influenza season and environmental factors on the clinical presentation and outcome of invasive pneumococcal disease.

Influenza and meteorological factors have been associated with increases in the incidence of invasive pneumococcal disease (IPD). However, scant data regarding the impact of influenza and the environment on the clinical presentation of IPD are available. An observational study of all adults hospitalized with IPD was performed between 1996 and 2012 in our hospital. The incidence of IPD correlated with the incidence rates of influenza and with environmental data. A negative binominal regression was used to assess the relationship between these factors. Clinical presentation of IPD during the influenza and non-influenza periods was compared. During the study, 1,150 episodes of IPD were diagnosed. After adjusting for confounding variables, factors correlating with the rates of IPD were the incidence of influenza infection (IRR 1.229, 95% CI 1.025-1.472) and the average ambient temperature (IRR 0.921, 95% CI 0.88-0.964). Patients with IPD during the influenza period had a worse respiratory status. A greater proportion of patients had respiratory failure (45.6% vs 52%, p = 0.032) and higher requirements for ICU admission (19.3% vs 24.7%, p = 0.018) and mechanical ventilation (11% vs 15.1%, p = 0.038). When we stratified by invasiveness of pneumococcal serotypes and the presence of comorbid conditions, the increase in the severity of clinical presentation was focused on healthy adults with IPD caused by nonhighly invasive serotypes. Beyond the increase in the burden of IPD associated with influenza, a more severe clinical pattern of pneumococcal disease was observed in the influenza period. This effect varied according to pneumococcal serotype, host comorbidities, and age.

Epidemiology and outcome of invasive pneumococcal disease among adults in Belgium, 2009-2011.

This epidemiological study examined morbidity and case fatality of invasive pneumococcal disease (IPD) in adults in Belgium as well as distribution and antibiotic susceptibility of Streptococcus pneumoniae serotypes.Adults hospitalised with microbiologically proven IPD were prospectively enrolled. The study started in 2009 with patients aged ≥50 years, whereas in 2010 and 2011, patients aged ≥18 years were included. The clinical presentation, patient profile, treatment, outcome, and mortality were recorded during hospitalisation.Outcome was also assessed one month afterdischarge. Of the 1,875 patients with IPD identified, 1,332 were included in the analysis. Bacteraemic pneumonia, affecting 1,049 of the patients, was the most frequent IPD type (79%), and chronic obstructive pulmonary disease and cancer were the main comorbidities.One-third of patients required admission to intensive care unit. A total of 208 (16%) patients died during hospitalisation and an additional 21 (2%) within one month after discharge. Case fatality rates of ≥20%were observed in patients with chronic heart failure, hepatic disease, and renal insufficiency. Serotypes 7F, 1, 19A, and 3 were the most prevalent and together accounted for 47% (569/1,214) of all IPD cases and 42% (80/189) of mortality. Of the patient isolates, 21% (255/1,204) were resistant to erythromycin and 22% (264/1,204) to tetracycline. Penicillin non-susceptibility was mostly found in serotype 19A isolates. These baseline data are essential when assessing the impact of pneumococcal conjugate vaccination in adults in the future.

Vaccines for preventing pneumococcal infection in adults. Summary of the evidence and implications for public health programmes

An update of a Cochrane systematic review summarised the evidence for the efficacy of pneumococcal polysaccharide vaccines (PPVs) from randomized controlled trials (RCTs) or quasi-RCTs that compared PPV with placebo, control vaccines or no intervention; and from non-RCTs that assessed pneumococcal vaccine effectiveness against sterile site, culture confirmed IPD where the trial design allowed for the control of important confounding factors (case–control and cohort studies). Of 25 included studies, 18 were RCTs including 64,852 participants and seven were non-RCTs – five case–control studies and two cohort studies including 62,294 participants; the non-RCTs contributing outcomes for culture-confirmed invasive pneumococcal disease (IPD) only.The review found consistently strong evidence that the vaccine is effective in preventing the rarer outcome of invasive pneumococcal disease. Evidence from the included studies indicates vaccination might not afford as much protection in adults with chronic illness as it does for healthy adults. The available evidence did not demonstrate that pneumococcal polysaccharide vaccines prevent pneumonia (of all causes) or mortality in adults. This review did not consider adverse events.

Genetic Variation and Cerebrospinal Fluid Levels of Mannose Binding Lectin in Pneumococcal Meningitis Patients

It has been suggested that genetic variants in mannose binding lectin (MBL2) influence susceptibility and outcome of invasive pneumococcal disease. We assessed the influence of genetic variation in MBL2 on susceptibility, outcome and causative serotype of pneumococcal meningitis in a prospective nationwide cohort study including 299 white patients and 216 controls. We assessed functionality of the genetic polymorphisms by measuring levels of MBL, C3a, iC3b, C5a and sC5b-9 in cerebrospinal fluid. We also performed a meta-analysis of studies on MBL2 polymorphisms and susceptibility to invasive pneumococcal disease. The risk of contracting pneumococcal meningitis was substantially increased for white individuals homozygous with the defective MBL2 0/0 genotype (odds ratio [OR] 8.21, 95% confidence interval [CI] 1.05–64.1; p = 0.017). CSF MBL levels were significantly lower in patients with the A/0 and 0/0 genotype compared to homozygotes for the wild-type alleles (A/A; p<0.001). CSF MBL levels were positively correlated with C3a and iC3b levels, indicating complement activation by the lectin pathway. The effect of MBL2 genetic variants on susceptibility remained robust in a meta-analysis including 5 studies with 287 patients (OR 2.33, 99% CI 1.39–3.90). We conclude that MBL2 polymorphisms influence CSF MBL levels and substantially increase the risk of pneumococcal meningitis.