Decrease In Invasive Pneumococcal Disease Research Articles

Spatial and temporal analysis of invasive pneumococcal disease due to erythromycinresistant serotypes

ObjectivesTo study the spatio-temporal distribution of cases of invasive pneumococcal disease (IPD) due to serotypes resistant to erythromycin and its relationship with community consumption of macrolides and childhood vaccination coverage. MethodsWe selected IPD cases in adults over 59 years old, residents in the Community of Madrid (MC), notified in the period 2007–2016. The variables studied were obtained from the Vaccination Information Systems and the Pharmaceutical Service. The cut-off point (minimum inhibitory erythromycin concentration > 0.5 mg/L) of the EUCAST classification was used to define erythromycin resistant serotypes. We used JointPoint to estimate the incidence trends by erythromycin resistant serotypes included in the 13-valent vaccine (STPCV13) and not included in it (STnoPCV13). The association of these incidences with the community consumption of macrolides and vaccination coverage was made using Poisson models. Statistical scanning was used for the detection of temporal-spaces clusters of cases. Results1936 cases were identified, of which 427 erythromycin resistant serotypes were identified. The incidence of all cases due to resistant serotypes was decreasing (AAPC: −5,40%). During the period studied, the incidence of cases due to erythromycin resistant STPCV13 was decreasing with an annual percentage change (APC): −13.8 and was inversely associated with childhood vaccination coverage (IRR 0.641), while that of cases due to erythromycin resistant STnoPCV13 was ascending (APC): 4.5; and was not associated with coverage. 1 cluster was detected by STnoPCV13 and none by STPCV13 after the date of inclusion of the 13-valent in the childhood vaccination calendar. ConclusionsThe decrease in IPD due to resistant STPCV13 was associated with an increase in childhood vaccination coverage. The presence of clusters due to STnoPCV13 after the date of inclusion of the 13-valent vaccine in the childhood vaccination calendar indicates serotypes replacement. The increase in cases of resistant STnoPCV13 could be related to the replacement of vaccine serotypes in nasopharyngeal colonization, facilitated by the consumption of macrolides still at high levels in MC.

Distribution of Serotypes Causing Invasive Pneumococcal Disease in Children From High-Income Countries and the Impact of Pediatric Pneumococcal Vaccination.

The introduction and adoption of pneumococcal conjugate vaccines (PCVs) into pediatric national immunization programs (NIPs) has led to large decreases in invasive pneumococcal disease (IPD) incidence caused by vaccine serotypes. Despite these reductions, the global IPD burden in children remains significant. We collected serotype-specific IPD data from surveillance systems or hospital networks of all 30 high-income countries that met inclusion criteria. Data sources included online databases, surveillance system reports, and peer-reviewed literature. Percentage of serotyped cases covered were calculated for all countries combined and by PCV type in the pediatric NIP. We identified 8012 serotyped IPD cases in children <5 or ≤5 years old. PCV13 serotype IPD caused 37.4% of total IPD cases, including 57.1% and 25.2% for countries with PCV10 or PCV13 in the pediatric NIP, respectively, most commonly due to serotypes 3 and 19A (11.4% and 13.3%, respectively, across all countries). In PCV10 countries, PCV15 and PCV20 would cover an additional 45.1% and 55.6% of IPD beyond serotypes contained in PCV10, largely due to coverage of serotype 19A. In PCV13 countries, PCV15 and PCV20 would cover an additional 10.6% and 38.2% of IPD beyond serotypes contained in PCV13. The most common IPD serotypes covered by higher valency PCVs were 10A (5.2%), 12F (5.1%), and 22F and 33F (3.5% each). Much of the remaining IPD burden is due to serotypes included in PCV15 and PCV20. The inclusion of these next generation PCVs into existing pediatric NIPs may further reduce the incidence of childhood IPD.

183. Decrease in Invasive Pneumococcal Disease in 7 United States Children’s Hospitals during the COVID-19 Pandemic

BackgroundDuring the 2020 SARS-CoV-2 pandemic, physical distancing and mask use guidelines were implemented resulting in a decline in the number of infections caused by influenza, respiratory syncytial virus and otitis media. A surveillance analysis from England and Taiwan showed a decline in invasive pneumococcal disease (IPD) (Clin Infect Dis. 2021;72: e65-75 and J Infect. 2021;82:296-297). We hypothesized that COVID mitigation efforts resulted in a decrease in incidence of pediatric IPD within the U.S. during 2020 compared to previous years.MethodsWe reviewed all cases of IPD among 7 children’s hospitals from the U.S. Pediatric Multicenter Pneumococcal Surveillance Group from 2017-2020. IPD was defined by the isolation of Streptococcus pneumoniae from normally sterile sites (eg. blood, cerebrospinal, pleural, synovial or peritoneal fluid). Pneumococcal pneumonia was defined as an abnormal chest radiograph in the presence of a positive blood, pleural fluid or lung culture. Mastoiditis was identified by positive middle ear, subperiosteal abscess or mastoid bone culture. Serotypes were determined by the capsular swelling method. Hospital admission numbers were obtained for incidence calculations. Statistical analyses were performed using STATA11. A p< 0.05 was considered significant.ResultsA total of 410 IPD cases were identified. The cumulative incidence of IPD (0-22 years of age) decreased from 99.2/100,000 admissions in 2017-2019 to 53.8/100,000 admissions in 2020 (risk ratio 0.54, CI: 0.40-0.72, p< 0.00001). Pneumococcal bacteremia and pneumonia decreased significantly in 2020 (p< 0.05), and although not statistically significant, there were fewer cases of meningitis and mastoiditis when compared to previous years (p=0.08) (Figure 1). Sex, race, age or presence of comorbidities were not significantly different between groups. Most common serotypes in 2020 were 35B, 3 and 15B/C (Figure 2). ConclusionThe observed decline in IPD cases during the first year of the SARS-CoV-2 pandemic is likely associated with mask use and physical distancing limiting transmission of S. pneumoniae via droplets and viral infections frequently preceding IPD. These precautions might be useful in the future to decrease IPD, especially in high-risk patients.Disclosures Sheldon L. Kaplan, MD, Pfizer (Research Grant or Support) Tina Q. Tan, MD, GSK (Individual(s) Involved: Self): Advisor or Review Panel member, Grant/Research Support; ILiAD (Individual(s) Involved: Self): Advisor or Review Panel member; Merck (Individual(s) Involved: Self): Advisor or Review Panel member, Grant/Research Support; Moderna (Individual(s) Involved: Self): Advisor or Review Panel member; Pfizer (Individual(s) Involved: Self): Advisor or Review Panel member Pia S. Pannaraj, MD, MPH, Pfizer (Grant/Research Support)Sanofi-Pasteur (Advisor or Review Panel member)Seqirus (Advisor or Review Panel member) Larry Givner, MD, AstraZeneca (Advisor or Review Panel member) Kristina G. Hulten, PhD, Pfizer (Research Grant or Support)

Análisis espacial y temporal de la enfermedad neumocócica invasora por serotipos resistentes a eritromicina

ObjectivesTo study the spatio-temporal distribution of cases of invasive pneumococcal disease (IPD) due to serotypes resistant to erythromycin and its relationship with community consumption of macrolides and childhood vaccination coverage. MethodsWe selected IPD cases in adults over 59 years old, residents in the Community of Madrid (MC), notified in the period 2007-2016. The variables studied were obtained from the Vaccination Information Systems and the Pharmaceutical Service. The cut-off point (minimum inhibitory erythromycin concentration > 0.5 mg/L) of the EUCAST classification was used to define erythromycin resistant serotypes. We used JointPoint to estimate the incidence trends by erythromycin resistant serotypes included in the 13-valent vaccine (STPCV13) and not included in it (STnoPCV13). The association of these incidences with the community consumption of macrolides and vaccination coverage was made using Poisson models. Statistical scanning was used for the detection of temporal-spaces clusters of cases. Results1936 cases were identified, of which 427 erythromycin resistant serotypes were identified. The incidence of all cases due to resistant serotypes was decreasing (AAPC: -5,40%). During the period studied, the incidence of cases due to erythromycin resistant STPCV13 was decreasing with an annual percentage change (APC): -13.8 and was inversely associated with childhood vaccination coverage (IRR 0.641), while that of cases due to erythromycin resistant STnoPCV13 was ascending (APC): 4.5; and was not associated with coverage. 1 cluster was detected by STnoPCV13 and none by STPCV13 after the date of inclusion of the 13-valent in the childhood vaccination calendar. ConclusionsThe decrease in IPD due to resistant STPCV13 was associated with an increase in childhood vaccination coverage. The presence of clusters due to STnoPCV13 after the date of inclusion of the 13-valent vaccine in the childhood vaccination calendar indicates serotypes replacement. The increase in cases of resistant STnoPCV13 could be related to the replacement of vaccine serotypes in nasopharyngeal colonization, facilitated by the consumption of macrolides still at high levels in MC.

Impact of PCV-13 vaccine on invasive pneumococcal disease in hospitalised children: A multi-institutional analysis.

We aimed to describe changes in invasive pneumococcal disease (IPD) hospitalisations after introduction of the pneumococcal conjugate vaccine (PCV13). This was a retrospective analysis of the Pediatric Health Information System (PHIS) database, including children with IPD pre-PCV13 (2004-2009) and post-PCV13 (2012-2017). Healthy children and those with chronic conditions were analysed separately. The primary outcome was IPD incidence. Secondary outcomes included length of stay, intensive care unit (ICU) admission, mechanical ventilation and mortality. 9160 hospitalisations for IPD were included. The IPD rate per 100000 discharges was 180 pre-PVC13 and 150 post-PCV13 [17% decrease (P=0.085)]. The observed IPD rate in 2017 was 45.5% lower than the rate predicted by the pre-PCV13 trend (95% CI: 44%-46%). While a significant decrease in IPD (32%, P=0.026) was observed among healthy children, there was no change in those with chronic conditions (9%, P=0.24). In the post-PCV13 period, more IPD patients had chronic conditions, ICU admissions and longer ICU stays. Although there was no overall reduction in IPD after PCV13, we observed a significant decrease in IPD among healthy patients. Further research is needed to elucidate microbiology or other factors contributing to persistent IPD hospitalisations.

Asthma and Invasive Pneumococcal Disease in the Age of Pneumococcal Conjugate Vaccines.

The widespread use of pneumococcal conjugate vaccines (PCVs) in the United States has led to a significant decrease in invasive pneumococcal disease (IPD) and pneumonia in the pediatric population. On the basis of data reported by the Centers for Disease Control and Prevention (CDC), the overall incidence of IPD among children <5 years of age in the United States decreased from 95 cases per 100 000 in 1998 to 9 cases per 100 000 in 2016, and, similarly, the incidence of IPD caused by 13-valent PCV serotypes decreased from 88 cases per 100 000 in 1998 to 2 cases per 100 000 in 2016.1,2 However, IPD still remains a leading cause of morbidity and mortality in the United States and worldwide. In 2017, the CDC’s Active Bacterial Core surveillance network reported that there were 31 000 cases of IPD (meningitis, bacteremia, and bacteremic pneumonia) and 3590 deaths, of which 147 cases and 9 deaths occurred in children <5 years of age.2Asthma has been described as the most common chronic disease of childhood. In the United States, the CDC estimates that 6 million children <18 years of age have asthma, with a higher incidence in boys and African American children.3 Of note, male sex and African American race are also considered risk factors for the development of IPD and pneumonia.4–6 The combination of these risk factors places these children at a significantly higher risk for developing both of these illnesses, the combination of which may lead to more complications and less favorable clinical outcomes.Multiple studies performed in both children and adults with asthma have revealed that these patients are at higher risk for both IPD and pneumococcal pneumonia, with odds ratios between 1.3 and 13.5 for pneumonia and 1.3 and 16.8 for IPD. The risk was found to be substantially higher for persons receiving inhaled or systemic corticosteroid therapy and those with more severe asthma at baseline. These patients are at higher risk not only for IPD and pneumonia but also for the development of complications associated with pneumococcal infections.7–10 In the review being published in this issue of Pediatrics, Castro-Rodriguez et al11 performed a meta-analysis of 4 electronic databases to evaluate the risk of IPD or pneumococcal pneumonia among children who had been diagnosed with asthma compared with children without asthma in the age of widespread use of PCV. Their meta-analysis was based on data from 4 studies, (3 retrospective cohort studies representing an estimated 26 million person-years and 1 case-control study of 3294 children). The meta-analysis revealed that despite widespread PCV use, children with asthma continued to have a substantially higher risk of IPD and pneumococcal pneumonia compared with children without asthma.The findings of this meta-analysis reveal several important facts of which pediatric health care providers need to be cognizant. First, asthma remains a risk factor for IPD and pneumococcal pneumonia even in the era of widespread use of PCV. Second, it is important that all patients, especially those with asthma, are receiving their vaccinations on time and, most notably, are up to date on their pneumococcal vaccinations. This will provide the best protection against pneumococcal infections and their complications for pediatric patients with asthma.

Changes in Invasive Pneumococcal Disease Spectrum After 13-Valent Pneumococcal Conjugate Vaccine Implementation.

Pneumococcal conjugate vaccine (PCV) implementation has led to a sharp decrease in invasive pneumococcal disease (IPD) due to the reduction in PCV serotypes. We aimed to describe the changes in the spectrum of IPD and its clinical presentations after 13-valent PCV (PCV13) implementation. This prospective, hospital-based, active surveillance involved 130 pediatric wards and microbiology departments throughout France. We analyzed IPD cases from 2011 to 2016 for which a pneumococcal isolate was sent to the National Reference Center for Pneumococci for serotyping. Clinical data recorded were medical history, vaccination status, type of IPD, clinical features, and short-term evolution. Among 1082 IPD cases, we observed a 35.3% decrease (95% confidence interval, 29.2%-41.8%]) and the median age shifted from 38.3 months to 23.7 months (P = .007). The change in IPD type was mostly due to a reduction in bacteremic pneumonia frequency (from 42.1% to 19.1%; P < .001). Among the emerging non-PCV13 types (NVTs), those known to have the highest disease potential (8, 12F, 24F, and 33F) were isolated more frequently in patients without underlying conditions and were able to induce all IPD clinical presentations including bacteremic pneumonia. Conversely, serotypes with lower disease potential (15A, 15BC, 16F, and 23B) were rarely isolated from bacteremic pneumonia cases and were particularly involved in IPD in patients with underlying conditions (35.8%). Besides the decrease in IPD after 7-valent, then 13-valent PCV implementation, the spectrum of the remaining IPD cases showed significant changes, with substantial discrepancies across NVTs implicated in terms of clinical features and underlying conditions.

2295. Streptococcus pneumoniae-Related Hemolytic Uremic Syndrome (pHUS) and the Identification of Matched Cross Country Serotypes by Plasma Next-Generation Sequencing (NGS)

BackgroundHemolytic uremic syndrome (HUS) describes a clinical presentation of acute kidney injury, microangiopathic hemolytic anemia and thrombocytopenia. Five to 15% of HUS cases are related to Streptococcus pneumoniae infection, most often meningitis or pneumonia. Despite the introduction of PCV13 and a decrease in invasive pneumococcal disease in children, the incidence of pneumococcal-related HUS (pHUS) cases is rising for unclear reasons. Efforts to determine whether certain serotypes increase the risk of pHUS are often hampered by negative cultures in patients with suspected pneumococcal disease. Direct microbiologic detection methods, such as next-generation sequencing (NGS), may be useful in identifying pHUS cases. We describe four children with pHUS from two institutions that were identified via NGS of cell-free plasma.MethodsFour patients with HUS and negative initial cultures were identified. Blood was sent to Karius (Redwood City, CA) for pathogen detection via plasma NGS. Cell-free DNA was extracted and NGS performed. Human sequences were removed and remaining sequences were aligned to a curated pathogen database including over 1000 organisms. Organisms present above a predefined statistical threshold were reported. For serotyping by NGS, sequences were aligned to a collection of 90 serotype-associated cps alleles.ResultsAll four patients were found be positive for S. pneumoniae at extremely high levels (Table 1). Three out of four samples were identified as serotype 3 by NGS and similar to the same strain (SPN034183). The fourth sample was consistent with serotype 12A and no strain call was made.ConclusionIn this case series, we report on four patients with pHUS identified via plasma NGS. These cases demonstrate the potential of NGS for pathogen detection and quantitation in plasma to assist in identification of culture-negative infections, as well as the potential to identify clusters of disease that would likely otherwise have gone undetected.Table 1:Karius NGS DataPatientImmunizations Up to DateOrganism IDMPM (Molecules/µL)*Serotype18 Months (CNMC)Y S. pneumoniae 1,957,238311 Months (Rady)Y S. pneumoniae 9,122,698326 Months (Rady)Y S. pneumoniae 151,941,20712A42 Months (Rady)N S. pneumoniae 1,435,7483*Median MPM in non-HUS S. pneumoniae positive samples over the last 90 days was 1202 MPMDisclosures S. Venkatasubrahmanyam, Karius, Inc.: Employee, Salary. D. Hong, Karius, Inc.: Employee, Salary.

Streptococcus pneumoniae: Antimicrobial Resistance and Serotypes of Strains Carried by Children and Causing Invasive Disease in the Faroe Islands.

Knowledge about pneumococcal carriage, antibacterial resistance, serotype prevalence, and prevalence of invasive pneumococcal disease (IPD) after introduction of pneumococcal conjugate vaccines (PCVs) is lacking in the Faroe Islands. PCV-7 was introduced in 2008 and PCV-13 in 2010. The aim was to obtain knowledge on serotypes and antimicrobial resistance in pneumococci from carriage in children attending day-care centers (DCCs) and invasive isolates. Nasopharyngeal swabs were collected from 607 healthy children attending DCCs in the Faroe Islands in January to March in 2009, 2010, and 2011. Pneumococci were cultured selectively, tested for antibacterial susceptibility, and serotyped. Data from IPD isolates from 1974 to 2016 from the Department of Microbiology, National Hospital of the Faroe Islands, and typed and stored at Staten Serum Institute were also analyzed. Of the 607 screened children, 45% were pneumococcal carriers, 50% in 2009, 40% in 2010, and 42% in 2011. Antibiotic resistance in pneumococci was rare both in carriers and patients. Five penicillin nonsusceptible pneumococci were found in carriers (1.8%) and one among the invasive isolates (1.7%). The most common serotypes in carriage were 6B and 6A in 2009, serotype 3 and 6C in 2010, and serotype 11 and 6C in 2011. Serotype 6B was not found in 2011. The most common serotypes among IPD were 7F and 3. Pneumococcal carriage prevalence in healthy children attending DCCs in the Faroe Islands was low and antibacterial resistance was rare, compared with Iceland. The results suggest a possible serotype shift, reduction in antibacterial use, and PCV-7/13 serotype decrease in IPD after the introduction of pneumococcal vaccinations in children.

Invasive pneumococcal disease in Northern Alberta, not a Red Queen but a dark horse

BackgroundThe consequences of the introduction of various pneumococcal protein conjugate vaccines (PCV) for children and adults is poorly understood. ObjectiveWe undertook a population-based cohort study of invasive pneumococcal disease (IPD) in Northern Alberta (Canada) from 2000 to 2014, years spanning pre-and early PCV (2000–2004) vs PCV-7 (2005–2009) vs PCV-13 (2010–2014) time periods. DesignWe collected clinical, laboratory, and Streptococcus pneumoniae serotype information on all patients from 2000 to 2014. We determined changes in presentation, outcomes, serotypes, and incidence in children and adults across time periods. SettingThere were 509 cases of IPD in children, an 80% decrease over time. Rates of empyema (4.0–15.7%, p < 0.001), ICU admission (13.1–20%), and mortality (1.8–8.4%, p < 0.001) increased over time. There were 2417 cases of IPD in adults. Unlike children, incidence of IPD did not change nor did rates of empyema. ICU admissions increased (p = 0.004) and mortality decreased (18.7–16.5%, p = 0.002). The total number of serotypes causing IPD remained stable in children (22 vs 26 vs 20) while they decreased in adults (49 vs 47 vs 42). Conclusions and relevanceFor children, PCV vaccination strategies resulted in decreased overall rates of IPD and we observed increased rates of empyema and mortality; for adults, there was no change in IPD rates although disease severity increased while mortality decreased. On a population-wide basis, our results suggest that current PCV vaccination strategies are associated with an overall decrease in IPD but disease severity seems to be increasing in both children and adults.

Decrease of invasive pneumococcal disease (IPD) in adults after introduction of pneumococcal 13-valent conjugate vaccine in Spain.

A prospective laboratory-based multicenter study that collected all adult invasive pneumococcal disease (IPD) episodes from 6 Spanish hospitals before (2008–2009) and after (2012–2013). The 13-valent pneumococcal conjugate vaccine (PCV13) licensure was conducted in order to analyze the impact of PCV13 introduction for children on adult IPD. A total of 1558 IPD episodes were detected. The incidence of IPD decreased significantly in the second period by -33.9% (95% CI, -40.3% to -26.8%). IPD due to PCV7 serotypes (-52.7%; 95% CI, -64.2% to -37.5%) and to PCV13 additional serotypes (-55.0% 95% CI, -62.0% to -46.7%) significantly decreased whereas IPD due to non-PCV13 serotypes remained stable (1.0% 95% CI, -12.9% to 17.2%). IPD due to all PCV13 additional serotypes significantly declined with the exception of serotype 3 (-11.3%; 95%CI -35.0% to 21.1%). IPD due to two non-PCV13 serotypes varied: serotype 6C that rose (301.6%; 95%CI, 92.7% to 733.3%, p<0.001), related to the expansion of ST3866C, and serotype 8 that decreased (-34.9%, 95%CI, -57.1 to -1.2, p = 0.049), related to a decline of the ST638. The recombinant clone ST652111A (variant of ST1569V) increased in frequency. The decrease of serotype 19A IPD was linked to a fall in those antibiotic susceptible clones. In the last period, rates of penicillin- and cefotaxime-resistance remained under 10% and 4%, respectively. Adult IPD decreased after the PCV13 introduction in Spain due to herd protection. The spread of multidrug resistant clones (ST3866C, ST652111A) related to non-PCV13 serotypes needs further surveillance.

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.

Have changing pneumococcal vaccination programmes impacted disease in Ontario?

BackgroundPublicly funded infant 7-valent pneumococcal conjugate vaccine (PCV7) was introduced in Ontario, Canada in 2005 and was replaced by 10- and 13-valent vaccines (PCV10, PCV13) in October 2009 and November 2010, respectively. Among adults≥65 years, a 23-valent polysaccharide vaccine (PPV23) has been universally available since 1996. In January 2012, PCV13 was approved for adults ≥50 years. This study examines the impact of publicly funded vaccination programmes on invasive pneumococcal disease (IPD). MethodsLaboratory data from population-based surveillance for IPD conducted at the Toronto Invasive Bacterial Disease Network and from Public Health Ontario Laboratories between January 1, 2008 and December 31, 2010 were analyzed. ResultsBetween 2008 and 2010 there were 3259 cases of IPD; overall incidence was 7.4/9.3/8.3 per 100,000 in 2008/9/10, respectively. Incidence increased significantly among adults 65+ years during the period; this group had the highest incidence (21.5–25.6/100,000). The second highest incidence in 2008 and 2009 was in infants <1 year, whereas in 2010 it was in children 1–4 years. Among children <5 years, 68% and 19% of serotypes were covered by PCV13 and PCV10, respectively, between 2008 and 2010. In 2009, 6 cases with the 3 additional PCV10 serotypes were reported in infants compared with 2 in 2010. Among persons eligible for PCV7 (born≥2004), there was a 77% decrease in the rate of IPD due to PCV7 serotypes between 2008 and 2010 and a 60% decrease in PCV7 serotypes among persons not vaccine-eligible (born<2004). There was a 15% difference in serotype coverage between PCV13 and the 23-valent polysaccharide vaccine in adults≥50 years. ConclusionsDuring Ontario's PCV7 programme, serotype-specific decreases in IPD were observed, suggesting vaccine programme success, including herd immunity. Our results also suggest some early impact among infants from PCV10 introduction. A substantial burden of disease was also observed among older adults.

Navigating difficult dosing guidelines for PCV13 and PPSV23

At its June 2012 meeting, the Advisory Committee on Immunization Practices (ACIP) voted to recommend pneumococcal 13-valent protein conjugate vaccine (PCV13; Prevnar-13–Pfizer) in adults 19 years or older with specific immunocompromising conditions. The recommendations were posted on October 12, 2012. 1

Rapid reduction in invasive pneumococcal disease after introduction of PCV7 into the National Immunization Plan in Israel

BackgroundThe 7-valent conjugated vaccine (PCV7) was introduced into the Israeli National Immunization Program (NIP) in July 2009 (2, 4, 12 months schedule; 2 dose catch-up in second year of life). Nationwide active prospective surveillance on invasive pneumococcal disease (IPD) has been conducted in children since 1989. In the current study, IPD epidemiology in children <5 years during the 20 years before and 18 months after PCV7 NIP initiation, is reported. MethodsAll 27 centers performing blood/cerebrospinal fluid (CSF) cultures in children reported monthly IPD cases. Capture–recapture approach was used for completeness. ResultsDuring 1989–2010, 6022 IPD cases were reported in children <5 years; PCV7 serotypes (7VST) caused ∼50% of all episodes. In 2009 and 2010, 7VST IPD incidences <5 years of age (per 100,000) were 15.9 and 5.4, respectively (a 43% and 81% decrease, respectively) compared to 2003–2007 (mean incidence 27.8). Serotype 6A dynamics resembled those of 7VST. The respective overall IPD incidence decreases were 23% and 42%. The incidence dynamics of serotypes 1, 3, 5, 7F and 19A IPD were characterized by considerable fluctuations over the study period without any upwards or downwards trend in any of the age groups. The overall incidence of serotypes not included in the 13-valent pneumococcal conjugate vaccine (PCV13) did not vary significantly during the study period. By the end of 2010, 72% of the remaining IPD was caused by pneumococcal serotypes included in PCV13. ConclusionsAn active prospective long-term surveillance, showed a rapid and sharp decline in IPD in children <5 years following initiation of NIP with PCV7. No serotype replacement has been observed so far. The transition from PCV7 to PCV13 initiated in October 2010 may lead to a further substantial decrease in IPD. Follow-up is needed to better determine the long-term PCV effects.

Invasive Pneumococcal Disease in HIV-Infected Adults

Few data exist on the implications of widespread use of 7-valent pneumococcal conjugate vaccine in children in the invasive pneumococcal disease (IPD) in HIV-infected adults. We conducted a multicenter study to analyze differences in clinical presentation of IPD between HIV-infected and non-HIV-infected adults in the prevaccine and postvaccine era. Study of all cases of IPD in HIV-infected adults diagnosed since 1996 to 2010. Episodes were classified into prevaccine (1996-2001), early postvaccine (2002-2004), and late postvaccine period (2005-2010). For each case, we identified an HIV-negative control patient with IPD matched by hospital, age, and vaccine period. Two hundred twenty-one episodes of IPD in HIV-infected patients were diagnosed. The incidence of IPD decreased from 7.81 to 3.69 episodes per 1000 patient-years (-53%; 95% confidence interval: -65% to -36%, P < 0.001) between prevaccine and late postvaccine period. There was an 81% (95% confidence interval: -88% to -69%, P < 0.001) decrease of IPD caused by vaccine serotypes. In late postvaccine period IPD in HIV-infected patients was associated to higher rates of respiratory failure (28.4% vs. 48.4%, P = 0.011), greater intensive care unit admission (8.2% vs. 21.7%, P = 0.02) and a higher need for mechanical ventilation (5.9% vs. 16.3%, P = 0.033). In the prevaccine period, non-HIV-infected patients had a more severe illness than in those with HIV infection; however, these differences disappeared in the late postvaccine period. In the late postvaccine era, the incidence of IPD in HIV-infected patients has decreased, however, clinical presentation seems to have changed to a more severe illness. The widespread use of highly active antiretroviral therapy, polyssacharide vaccine, and 7-valent pneumococcal conjugate vaccine has contributed to these changes.

Using the Indirect Cohort Design to Estimate the Effectiveness of the Seven Valent Pneumococcal Conjugate Vaccine in England and Wales

BackgroundThe 7-valent pneumococcal conjugate vaccine (PCV-7) was introduced in the United Kingdom in 2006 with a 2,3 and 13month schedule, and has led to large decreases in invasive pneumococcal disease (IPD) caused by the vaccine serotypes in both vaccinated and unvaccinated cohorts. We estimated the effectiveness of PCV-7 against IPD.Methods and FindingsWe used enhanced surveillance data, collated at the Health Protection Agency, on vaccine type (n = 153) and non vaccine type (n = 919) IPD cases eligible for PCV-7. The indirect cohort method, a case-control type design which uses non vaccine type cases as controls, was used to estimate effectiveness of various numbers of doses as well as for each vaccine serotype. Possible bias with this design, caused by differential serotype replacement in vaccinated and unvaccinated individuals, was estimated after deriving formulae to quantify the bias. The results showed good effectiveness, increasing from 56% (95% confidence interval (CI): -7-82) for a single dose given under one year of age to 93% (95% CI: 70-98) for two doses under one year of age plus a booster dose in the second year of life. Serotype specific estimates indicated higher effectiveness against serotypes 4, 14 and 18C and lower effectiveness against 6B. Under the assumption of complete serotype replacement by non vaccine serotypes in carriage, we estimated that effectiveness estimates may be overestimated by about 2 to 5%.ConclusionsThis study shows high effectiveness of PCV-7 under the reduced schedule used in the UK. This finding agrees with the large reductions seen in vaccine type IPD in recent years in England and Wales. The formulae derived to assess the bias of the indirect cohort method for PCV-7 can also be used when using the design for other vaccines that affect carriage such as the recently introduced 13 valent pneumococcal conjugate vaccine.

The 13-valent pneumococcal conjugate vaccine (PCV13) elicits cross-functional opsonophagocytic killing responses in humans to Streptococcus pneumoniae serotypes 6C and 7A

The introduction of a 7-valent pneumococcal conjugate vaccine (PCV7) in 2000 dramatically reduced the incidence of invasive pneumococcal disease (IPD) caused by the seven serotypes covered by the vaccine. Following the introduction of PCV7, which contains a serotype 6B conjugate, some decrease in IPD due to serotype 6A was noted suggesting that the serotype 6B conjugate provided some partial cross-protection against serotype 6A. However, no effect on serotype 6C was observed. In 2010, a pneumococcal conjugate vaccine with expanded serotype coverage (PCV13) was introduced that expanded the serotype coverage to 13 serotypes including serotype 6A. To assess whether the 6A conjugate in PCV13 could potentially induce functional anti-6C antibody responses, an opsonophagocytic assay (OPA) for serotype 6C was developed. Randomly chosen subsets of immune sera collected from infants receiving three doses of PCV7 or PCV13 were tested in OPA assays for serotype 6A, 6B and 6C. PCV7 immune sera demonstrated strong OPA responses, defined as percentage of subjects having an OPA titer ≥1:8, to serotype 6B (100% responders), partial responses to serotype 6A (70% responders) but only minimal responses to serotype 6C (22% responders). In contrast, PCV13 immune sera showed strong OPA responses to serotypes 6A (100% responders), 6B (100% responders) and 6C (96% responders). Furthermore, during pre-clinical work it was observed that serotype 7F (included in PCV13) and serotype 7A (not included in PCV13) shared serogroup-specific epitopes. To determine whether such epitopes also may be eliciting cross-functional antibody, PCV13 immune sera were also tested in serotype 7A and 7F OPA assays. All PCV13 immune sera demonstrated OPA responses to both of these serotypes. Taken together these results suggest that immunization with PCV13 has the potential to induce cross-protective responses to related serotypes not directly covered by the vaccine.

Community-acquired upper respiratory tract infections and the role of third-generation oral cephalosporins

Common community-acquired infections include those of the upper respiratory tract. In the 1990s, the antimicrobial treatment of upper respiratory tract infections focused on penicillin-resistant Streptococcus pneumoniae. However, following the introduction of a pneumococcal conjugate vaccine, a decrease in invasive pneumococcal disease occurred, and in the case of otitis media a shift towards Haemophilus influenzae as the predominant causative pathogen was observed. Future antimicrobial therapy for outpatient upper respiratory tract infections may need to focus on pathogens such as penicillin-susceptible S. pneumoniae, β-lactamase-producing H. influenzae, β-lactamase-negative amoxicillin-resistant H. influenzae and Moraxella catarrhalis. In these circumstances, third-generation oral cephalosporins, such as cefixime and cefdinir, could be increasingly used as an optional first-line therapy in community practice for upper respiratory tract infections suspected to be caused by these key pathogens, as an alternative to amoxicillin–clavulanate.

Declining invasive pneumococcal disease mortality in the United States, 1990–2005

PCV7 use in the U.S. has led to notable decreases in invasive pneumococcal disease (IPD). We examined PCV7 influence on IPD mortality for all age groups using National Multiple-Cause-of-Death data (1990–2005). Age-specific mortality rates were compared before and after PCV7 use. Average decreases in age-adjusted mortality rates for meningitis and septicemia accelerated post-PCV7, the greatest decline observed in septicemia-related deaths. The youngest and oldest age groups experienced large decreases in age-specific mortality rates after the introduction of PCV7. Mortality rate decline across all age groups strengthens evidence of vaccine-induced herd immunity and provides additional information for cost–benefit analyses of PCV7.