Invasive Pneumococcal Disease In Adults Research Articles

Early Streptococcus pneumoniae serotype changes in Utah adults after the introduction of PCV13 in children

IntroductionPneumococcal conjugate vaccines (PCV) have indirect effects due to decreased Streptococcus pneumoniae colonization in vaccine recipients. We sought to determine whether the introduction of PCV13 in children led to changes in the epidemiology and clinical manifestations of invasive pneumococcal disease (IPD) in adults. MethodsWe described demographics, comorbidities, clinical manifestations, and serotypes of IPD in Utah adults before (November 2009−February 2010) and after (March 2010−March 2012) the introduction of PCV13 in children. We also compare serotypes causing IPD in Utah adults and children. ResultsAfter the introduction of PCV13 in the childhood vaccine program, the proportion of IPD due to PCV13 exclusive serotypes decreased significantly in Utah adults (64−40%, p=0.009), primarily due to a decline in serotype 7F (36−15%, p=0.008). There were non-significant increases in IPD due to Pneumococcal polysaccharide 23 (PPV23) unique serotypes and non-vaccine serotypes, most notably serotype 22F. Changes in the proportions of vaccine and non-vaccine serotypes were similar in adults and children. Meningitis was more commonly due to non-vaccine serotypes relative to non-meningitis cases (47% vs. 18%, p=0.007). When stratified by sex, decreases in PCV13 serotype IPD were only noted in men (76−33%, p=0.001). ConclusionsSerotype epidemiology of IPD in adults closely follows that of children in the PCV13 era. Continued surveillance is needed to confirm whether replacement serotypes will lead to increases in pneumococcal meningitis and whether there are sex differences in the indirect effects of PCV vaccination in children.

Impact of PCV7 and PCV13 on the Serotype Distribution of Invasive Pneumococcal Disease in Adults in Kansas City

Impact of PCV7 and PCV13 on the Serotype Distribution of Invasive Pneumococcal Disease in Adults in Kansas City

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.

Serotype Changes and Drug Resistance in Invasive Pneumococcal Diseases in Adults after Vaccinations in Children, Japan, 2010-2013.

After 7-valent pneumococcal conjugate vaccine (PCV) for children was introduced in Japan in November 2010, we examined changes in Streptococcus pneumoniae serotypes and in genetic antimicrobial drug resistance of isolates from adults with invasive pneumococcal diseases. During April 2010-March 2013, a total of 715 isolates were collected from adults with invasive pneumococcal diseases. Seven-valent PCV serotypes in adults decreased from 43.3% to 23.8%, most noticeably for serotype 6B. Concomitantly, 23-valent pneumococcal polysaccharide vaccine (PPSV23) serotypes decreased from 82.2% to 72.2%; non-PPSV23 serotypes increased from 13.8% to 25.1%. Parallel with serotype changes, genotypic penicillin-resistant S. pneumoniae decreased from 32.4% to 21.1%, and 6 non-PPSV23 serotypes emerged (6D, 15A, 15C, 16F, 23A, and 35B). Respective vaccine coverage rates for 13-valent PCV and PPSV23 differed by disease: 73.9% and 84.3% for patients with pneumonia, 56.4% and 69.2% for patients with bacteremia and sepsis, and 45.7% and 69.3% for patients with meningitis.

The post-vaccine microevolution of invasive Streptococcus pneumoniae.

The 7-valent pneumococcal conjugated vaccine (PCV7) has affected the genetic population of Streptococcus pneumoniae in pediatric carriage. Little is known however about pneumococcal population genomics in adult invasive pneumococcal disease (IPD) under vaccine pressure. We sequenced and serotyped 349 strains of S. pneumoniae isolated from IPD patients in Nijmegen between 2001 and 2011. Introduction of PCV7 in the Dutch National Immunization Program in 2006 preluded substantial alterations in the IPD population structure caused by serotype replacement. No evidence could be found for vaccine induced capsular switches. We observed that after a temporary bottleneck in gene diversity after the introduction of PCV7, the accessory gene pool re-expanded mainly by genes already circulating pre-PCV7. In the post-vaccine genomic population a number of genes changed frequency, certain genes became overrepresented in vaccine serotypes, while others shifted towards non-vaccine serotypes. Whether these dynamics in the invasive pneumococcal population have truly contributed to invasiveness and manifestations of disease remains to be further elucidated. We suggest the use of whole genome sequencing for surveillance of pneumococcal population dynamics that could give a prospect on the course of disease, facilitating effective prevention and management of IPD.

Association Between Local Pediatric Vaccination Rates and Patterns of Pneumococcal Disease in Adults.

Pneumococcal conjugate vaccine (PCV) is now recommended for use in adults in the United States. Because vaccination of children with PCVs protects adults from the targeted serotypes, local variations in PCV uptake among children could influence disease patterns in adults. We obtained ZIP code-level data on invasive pneumococcal disease (IPD) from an active population-based surveillance system in Connecticut (study interval, 1998-2009) and ZIP code-level data on immunization with at least 3 or at least 4 doses of 7-valent PCV (PCV7) from the state immunization registry. We fit logistic regression models to estimate the proportion of IPD cases among adults aged >40 years that were caused by PCV7-targeted serotypes. Covariates included ZIP code-level socioeconomic indicators (eg, percentage of the population that was black and income per capita), the percentage of the population that received 3 or 4 doses of PCV7 (mean centered), and a linear spline to control for the average rate of decline across all ZIP codes. ZIP codes that had a higher proportion of children that did not complete the 4-dose PCV7 series had a higher proportion of adult IPD cases caused by PCV7 serotypes. Local variations in PCV uptake (and receipt of the booster dose) might influence the effectiveness of PCVs in preventing pneumococcal disease in adults.

Impact of the 13-valent pneumococcal conjugate vaccine (pcv13) on invasive pneumococcal disease and carriage in Alaska

BackgroundAlaska Native (AN) children have experienced high rates of invasive pneumococcal disease (IPD). In March 2010, PCV13 was introduced statewide in Alaska. We evaluated the impact of PCV13 on IPD in children and adults, 45 months after introduction. MethodsPneumococcal sterile site isolates, reported through state-wide surveillance, were serotyped using standard methods. We defined a pre-PCV13 time period 2005–2008 and post-PCV13 time period April 2010–December 2013; excluding Jan 2009–March 2010 because PCV13 was introduced pre-licensure in one high-risk region in 2009. ResultsAmong Alaska children <5 years, PCV13 serotypes comprised 65% of IPD in the pre-PCV13 period and 26% in the PCV13 period. Among all Alaska children <5 years, IPD rates decreased from 60.9 (pre) to 25.4 (post) per 100,000/year (P<0.001); PCV13 serotype IPD decreased from 37.7 to 6.4 (P<0.001). Among AN children <5 years, IPD rates decreased from 149.2 to 60.8 (P<0.001); PCV13 serotype IPD decreased from 87.0 to 17.4 (P<0.001); non-PCV13 serotype IPD did not change significantly. Among persons 5–17 and ≥45 years, the post-vaccine IPD rate was similar to the baseline period, but declined in persons 18–44 years (39%, P<0.001); this decline was similar in AN and non-AN persons (38%, P=0.016, 43%, P=0.014, respectively). ConclusionsForty-five months after PCV13 introduction, overall IPD and PCV13-serotype IPD rates had decreased 58% and 83%, respectively, in Alaska children <5 years of age when compared with 2005–2008. We observed evidence of indirect effect among adults with a 39% reduction in IPD among persons 18–44 years.

Impact of vaccination on invasive pneumococcal disease in adults with focus on the immunosuppressed

Pneumococcal conjugate vaccine (PCV13) has been recently added to the vaccine recommendations for immunosuppressed adults (ISP). We conducted a multicenter observational prospective study aimed to assess the evolving epidemiology of invasive pneumococcal disease (IPD) in adults, with especial focus on ISP. All IPD cases admitted from 1999 to 2014 were included. ISP was defined as patients on current cancer chemotherapy, immunosuppressive therapy for autoimmune disease, biological therapy, chronic systemic steroid use, hemodialysis, neutropenia or HIV infection. A total of 799 IPD episodes were analyzed, 198 were considered ISP. IPD incidence decreased from 20 to 8/100,000-population year (p<0.004) over the study period. No changes in mortality were observed. Penicillin resistance experienced a significant decline. In 694 episodes the serotype was known. Global vaccine coverage considering the whole study period, was for PCV7 21.6% vs. 28.8% in general and in immunosuppressed population (p=0.04) and for PCV13 64.5% and 56.6% respectively (p=0.05). The proportion of IPD isolates included in PCV7 and PCV13 significantly decreased over time. A reduction in the incidence of IPD in adults was seen late after the vaccine licensure, both in general population and in ISP. Coverage of PCV13 vaccine might be suboptimal for ISP in the coming years.

Minimum incidence of adult invasive pneumococcal disease in Blantyre, Malawi an urban african setting: a hospital based prospective cohort study.

Invasive pneumococcal disease causes substantial morbidity and mortality in Africa. Evaluating population level indirect impact on adult disease of pneumococcal conjugate vaccine (PCV) programmes in infants requires baseline population incidence rates but these are often lacking in areas with limited disease surveillance. We used hospital based blood culture and cerebrospinal fluid surveillance to calculate minimal incidence of invasive pneumococcal disease in the adult (≥15 years old) population of Blantyre, a rapidly growing urban centre in southern Malawi, in the period preceding vaccine introduction. Invasive pneumococcal disease incidence in Blantyre district was high, mean 58.1 (95% confidence interval (CI): 53.7, 62.7) per 100,000 person years and peaking among 35 to 40 year olds at 108.8 (95%CI: 89.0, 131.7) mirroring the population age prevalence of HIV infection. For pneumococcal bacteraemia in urban Blantyre, mean incidence was 60.6 (95% CI: 55.2, 66.5) per 100,000 person years, peaking among 35 to 40 year olds at 114.8 (95%CI: 90.3, 143.9). We suspected that our surveillance may under-ascertain the true burden of disease, so we used location data from bacteraemic subjects and projected population estimates to calculate local sub-district incidence, then examined the impact of community level socio-demographic covariates as possible predictors of local sub-district incidence of pneumococcal and non-pneumococcal pathogenic bacteraemia. Geographic heterogeneity in incidence was marked with localised hotspots but ward level covariates apart from prison were not associated with pneumococcal bacteraemia incidence. Modelling suggests that the current sentinel surveillance system under-ascertains the true burden of disease. We outline a number of challenges to surveillance for pneumococcal disease in our low-resource setting. Subsequent surveillance in the vaccine era will have to account for geographic heterogeneity when evaluating population level indirect impact of PCV13 introduction to the childhood immunisation program.

Increase of serotypes 15A and 23B in IPD in Germany in the PCV13 vaccination era.

BackgroundThis study presents an analysis of 1,491 serogroup 23 and 762 serogroup 15 isolates from invasive pneumococcal disease (IPD) in children and adults before and after the general recommendation for childhood pneumococcal conjugate vaccination in Germany in July 2006. Vaccination formulations used were PCV7 (from July 2006), PCV10 (from April 2009) and PCV13 (from December 2009, replacing PCV7).MethodsThe German National Reference Center for Streptococci (GNRCS) has conducted surveillance of IPD since 1992. Isolates were serotyped and tested for antibiotic susceptibility. Selected isolates were characterized using MLST.ResultsIn an analysis of 23,957 isolates from IPD in children and adults sent to the GNRCS between July 1992 and June 2014, we found a strongly significant increase of non-PCV13 serotypes in the late vaccination (PCV13) period (2010-2014). Among these, the proportions of serotypes 15A and 23B were the most strongly significantly increasing. After the recommendation for pneumococcal conjugate childhood vaccination in 2006 and the introduction of higher-valent vaccines in 2009, the proportion of 15A increased significantly from 0.5% in the early vaccination period (2007-2010) to 2.4% in the late vaccination period (2010-2014, p=3.14x10-22). The proportion of serotype 23B increased from 0.5% to 2.8% in the same period (p=1.55x10-29). Penicillin non-susceptibility levels of the serotype 15A (47.4%) and serotype 23B (46.5%) isolates were high, with MIC values ranging from 0.12-2 μg/ml (15A) and 0.12-0.5 μg/ml (23B). MLSTs of serotype 23B isolates grouped in two clonal complexes (CC): CC439, with sequence type (ST) 439 as the main representative and CC338 (linked to CC156), with ST1349 as most prevalent clone. Both CCs have been present over almost the whole surveillance period. All penicillin non-susceptible isolates occurred in CC338. Serotype 15A isolates appeared to be more diverse. Six CCs, one group of three STs and two singletons were found among 20 isolates. Most prevalent was CC63, with ST63 as most prominent representative (n=5). Most penicillin non-susceptible isolates were found among CC63 isolates.ConclusionsThe prevalence of non-PCV13 serotypes in Germany has increased significantly between July 2007 and June 2014, with 15A and 23B being the most strongly increasing serotypes of all. Both serotypes show a high proportion of penicillin non-susceptibility.

Visualization of &lt;em&gt;Streptococcus pneumoniae&lt;/em&gt; within Cardiac Microlesions and Subsequent Cardiac Remodeling

During bacteremia Streptococcus pneumoniae can translocate across the vascular endothelium into the myocardium and form discrete bacteria-filled microscopic lesions (microlesions) that are remarkable due to the absence of infiltrating immune cells. Due to their release of cardiotoxic products, S. pneumoniae within microlesions are thought to contribute to the heart failure that is frequently observed during fulminate invasive pneumococcal disease in adults. Herein is demonstrated a protocol for experimental mouse infection that leads to reproducible cardiac microlesion formation within 30 hr. Instruction is provided on microlesion identification in hematoxylin & eosin stained heart sections and the morphological distinctions between early and late microlesions are highlighted. Instruction is provided on a protocol for verification of S. pneumoniae within microlesions using antibodies against pneumococcal capsular polysaccharide and immunofluorescent microscopy. Last, a protocol for antibiotic intervention that rescues infected mice and for the detection and assessment of scar formation in the hearts of convalescent mice is provided. Together, these protocols will facilitate the investigation of the molecular mechanisms underlying pneumococcal cardiac invasion, cardiomyocyte death, cardiac remodeling as a result of exposure to S. pneumoniae, and the immune response to the pneumococci in the heart.

Visualization of Streptococcus pneumoniae within Cardiac Microlesions and Subsequent Cardiac Remodeling.

During bacteremia Streptococcus pneumoniae can translocate across the vascular endothelium into the myocardium and form discrete bacteria-filled microscopic lesions (microlesions) that are remarkable due to the absence of infiltrating immune cells. Due to their release of cardiotoxic products, S. pneumoniae within microlesions are thought to contribute to the heart failure that is frequently observed during fulminate invasive pneumococcal disease in adults. Herein is demonstrated a protocol for experimental mouse infection that leads to reproducible cardiac microlesion formation within 30 hr. Instruction is provided on microlesion identification in hematoxylin & eosin stained heart sections and the morphological distinctions between early and late microlesions are highlighted. Instruction is provided on a protocol for verification of S. pneumoniae within microlesions using antibodies against pneumococcal capsular polysaccharide and immunofluorescent microscopy. Last, a protocol for antibiotic intervention that rescues infected mice and for the detection and assessment of scar formation in the hearts of convalescent mice is provided. Together, these protocols will facilitate the investigation of the molecular mechanisms underlying pneumococcal cardiac invasion, cardiomyocyte death, cardiac remodeling as a result of exposure to S. pneumoniae, and the immune response to the pneumococci in the heart.

Use of pneumococcal vaccine in adults.

of the Clinical Problem Streptococcus pneumoniae is a commoncauseof upper respiratory tract infection and community-acquired pneumonia (CAP). It also causes invasivepneumococcaldisease(IPD)suchasbacteremia,bacterialmeningitis, endocarditis, andosteomyelitis. In2012, therewere anestimated31 600casesofpneumococcal infectionand3300related deaths in theUnited States. The highest rates of infection are among children and adults aged 65 years or older.1 PPSV23was licensed in theUnitedStates in 1983.According to a 2013meta-analysis, this vaccine is associated with prevention of IPD, but there is no consistent evidence that it is associatedwith reduced rates of all-cause pneumonia or all-causemortality.2 The addition of a 7-valent PCV (PCV7) in 2000 to the pediatric vaccine schedule was associated with decreases in both pediatric and adult IPD.3PCV13 isanotherconjugated vaccine that contains capsular polysaccharide antigens from 13 strains of S pneumoniae (includingthe6Astrain,astrainnot included inPPSV23)conjugated to inactivated diphtheria-tetanus toxoid. The conjugated vaccine formulation is thought to elicit a more robust T cell– dependent immune response than PPSV23, which is processed through a T cell–independent pathway.4

Effect of use of 13-valent pneumococcal conjugate vaccine in children on invasive pneumococcal disease in children and adults in the USA: analysis of multisite, population-based surveillance

In 2000, seven-valent pneumococcal conjugate vaccine (PCV7) was introduced in the USA and resulted in dramatic reductions in invasive pneumococcal disease (IPD) and moderate increases in non-PCV7 type IPD. In 2010, PCV13 replaced PCV7 in the US immunisation schedule. We aimed to assess the effect of use of PCV13 in children on IPD in children and adults in the USA. We used laboratory-based and population-based data on incidence of IPD from the Active Bacterial Core surveillance (part of the Centers for Disease Control and Prevention's Emerging Infections Program) in a time-series model to compare rates of IPD before and after the introduction of PCV13. Cases of IPD between July 1, 2004, and June 30, 2013, were classified as being caused by the PCV13 serotypes against which PCV7 has no effect (PCV13 minus PCV7). In a time-series model, we used an expected outcomes approach to compare the reported incidence of IPD to that which would have been expected if PCV13 had not replaced PCV7. Compared with incidence expected among children younger than 5 years if PCV7 alone had been continued, incidence of IPD overall declined by 64% (95% interval estimate [95% IE] 59-68) and IPD caused by PCV13 minus PCV7 serotypes declined by 93% (91-94), by July, 2012, to June, 2013. Among adults, incidence of IPD overall also declined by 12-32% and IPD caused by PCV13 minus PCV7 type IPD declined by 58-72%, depending on age. We estimated that over 30 000 cases of IPD and 3000 deaths were averted in the first 3 years after the introduction of PCV13. PCV13 reduced IPD across all age groups when used routinely in children in the USA. These findings provide reassurance that, similar to PCV7, PCVs with additional serotypes can also prevent transmission to unvaccinated populations. Centers for Disease Control and Prevention.

Early impact of PCV7/PCV13 sequential introduction to the national pediatric immunization plan, on adult invasive pneumococcal disease: A nationwide surveillance study

BackgroundPCV7 was introduced as a universal childhood vaccination in Israel on July 2009 and was gradually replaced by PCV13 from November 2010. We report data on adult invasive pneumococcal disease (IPD), two years post PCV13 implementation. MethodsAn ongoing nationwide active surveillance (all 27 laboratories performing blood/CSF cultures nationwide), initiated in 2009, providing all blood/CSF Streptococcus pneumoniae isolated from persons ≥18 years. Capture-recapture method assured reporting of >95% cases. All isolates were serotyped in one central laboratory. Medical history and outcomes were recorded in ∼90%. ResultsOf 1809 IPD episodes, S. pneumoniae was isolated from the blood in 95% and most cases had pneumonia. Predisposing comorbidities were present in >70%. During the four study years, overall IPD incidence decreased from 9.2 to 7.2/100,000, incidence of pneumonia and particularly severe pneumonia cases decreased significantly from 6.6 to 4.7/100,000, (p=0.029). Vaccine type (VT7/VT13) serotypes decreased by 70%/57% within 4 years. This was accompanied by a 52% increase in non-VT13 strains. These changes were most apparent in winter. PCV impact was most pronounced in younger adults (39% decrease in overall IPD with only a non-significant increase in non-VT13 cases) while in those >65 years a non-significant decrease in overall IPD was observed with a 64% increase in non-VT13 cases. Non-VT13 serotypes that increased significantly were 12F, 15A 10A and 6C. A continuous reduction in isolates with penicillin MIC>0.06μg/ml was observed (26% to 11%, p<0.001). ConclusionsFour years after PCV7 and 2.5 years after PCV13 universal implementation in children, incidence of adult IPD caused by VT7 and VT13 decreased in all ages, mainly in younger adults. Despite increase in non-VT13 IPD, overall IPD decreased. Additional follow-up is needed to determine the long-term impact of PCV13.

1105Chronic Kidney Disease and Invasive Pneumococcal Disease in Adults

1105Chronic Kidney Disease and Invasive Pneumococcal Disease in Adults

1093Regional Differences in Adult Invasive Pneumococcal Disease (IPD) Rates in Tennessee (TN)

1093Regional Differences in Adult Invasive Pneumococcal Disease (IPD) Rates in Tennessee (TN)

Global Pneumococcal Disease and Policies for Control

Global Pneumococcal Disease and Policies for Control

Clinical manifestations of invasive pneumococcal disease by vaccine and non-vaccine types.

Pneumococcal conjugated vaccines (PCVs) have shown protection against invasive pneumococcal disease by vaccine serotypes, but an increase in non-vaccine serotype disease has been observed. Type-specific effects on clinical manifestation need to be explored. Clinical data from 2096 adults and 192 children with invasive pneumococcal disease were correlated to pneumococcal molecular serotypes. Invasive disease potential for pneumococcal serotypes were calculated using 165 invasive and 550 carriage isolates from children. The invasive disease potential was lower for non-PCV13 compared to vaccine-type strains. Patients infected with non-PCV13 strains had more underlying diseases, were less likely to have pneumonia and, in adults, tended to have a higher mortality. Furthermore, patients infected with pneumococci belonging to clonal serotypes only expressing non-PCV13 capsules had a higher risk for septicaemia and mortality. PCV vaccination will probably lead to a decrease in invasive pneumococcal disease but an alteration in the clinical manifestation of invasive pneumococcal disease. Genetic lineages causing invasive pneumococcal disease in adults often express non-vaccine serotypes, which can expand after vaccination with an increased risk of infection in patients with underlying diseases.

Update pneumococcal infections

Pneumococci remain the most important cause for community-acquired pneumonia. The colonization of the nasopharynx is prerequisite for their transmission and the colonization of toddlers are an important reservoir also for infections in the elderly. Since pneumococcal conjugate vaccines reduce the colonization rate of children its widespread use has also resulted in a reduction of invasive pneumococcal disease in adults. Advanced age and comorbidity are the most important risk factors for pneumococcal pneumonia and the mortality in this risk group is still very high. The strongest risk factor for invasive pneumococcal infections, however, is HIV/AIDS and solid or hematologic malignancies. A more rapid identification could aid de-escalation of empiric antibiotic therapy. The pneumococcal urinary antigen test, however lacks sensitivity for this purpose. In contrast, the direct identification of pathogens from positive blood culture bottles by MALDI-TOF is a very encouraging development in diagnostic microbiology. In several cohort studies patients treated with a combination of a betalactam plus macrolide had a lower mortality than patients treated with betalactam monotherapy. If these observations reflect a truly beneficial effect of combination therapy or rather confounding of the studies remains unclear and evidence from interventional studies is needed.