International Circumpolar Surveillance System for invasive pneumococcal disease, 1999-2005

The International Circumpolar Surveillance System is a population-based surveillance network for invasive bacterial disease in the Arctic. The 7-valent pneumococcal conjugate vaccine (PCV7) was introduced for routine infant vaccination in Alaska (2001), northern Canada (2002-2006), and Norway (2006). Data for invasive pneumococcal disease (IPD) were analyzed to identify clinical findings, disease rates, serotype distribution, and antimicrobial drug susceptibility; 11,244 IPD cases were reported. Pneumonia and bacteremia were common clinical findings. Rates of IPD among indigenous persons in Alaska and northern Canada were 43 and 38 cases per 100,000 population, respectively. Rates in children <2 years of age ranged from 21 to 153 cases per 100,000 population. In Alaska and northern Canada, IPD rates in children <2 years of age caused by PCV7 serotypes decreased by >80% after routine vaccination. IPD rates are high among indigenous persons and children in Arctic countries. After vaccine introduction, IPD caused by non-PCV7 serotypes increased in Alaska.     

Whole-Genome Analysis of Streptococcus pneumoniae Serotype 4 Causing Outbreak of Invasive Pneumococcal Disease,Alberta, Canada

After the introduction of pneumococcal conjugate vaccines for children, invasive pneumococcal disease caused by Streptococcus pneumoniae serotype 4 declined in all ages in Alberta, Canada, but it has reemerged and spread in adults in Calgary, primarily among persons who are experiencing homelessness or who use illicit drugs. We conducted clinical and molecular analyses to examine the cases and isolates. Whole-genome sequencing analysis indicated relatively high genetic variability of serotype 4 isolates. Phylogenetic analysis identified 1 emergent sequence type (ST) 244 lineage primarily associated within Alberta and nationally distributed clades ST205 and ST695. Isolates from 6 subclades of the ST244 lineage clustered regionally, temporally, and by homeless status. In multivariable logistic regression, factors associated with serotype 4 invasive pneumococcal disease were being male, being <65 years of age, experiencing homelessness, having a diagnosis of pneumonia or empyema, or using illicit drugs.     

Estimated effect of pneumococcal conjugate vaccination on invasive pneumococcal disease and associated mortality, Denmark 2000-2005

In order to provide an estimation of the direct and indirect benefits of pneumococcal vaccination with three protein-conjugate pneumococcal vaccines (PCV) we described the epidemiology and mortality from invasive pneumococcal disease (IPD) in Denmark between 2000 and 2005. Approximately 1080 cases were registered annually during the period. The overall incidence of IPD increased significantly, from 15.4 cases per 100,000 population in 2000 to 20.7 cases per 100,000 in 2005 (p<0.01), mainly due to an increase in bacteraemia cases. The serotype coverage in children under 5 years varied from 64% to 91% depending on the PCV used. The mean mortality proportion after IPD was 18%, with approximately 190 deaths annually. One to two deaths among children younger than 5 years and approximately 50 deaths related to IPD caused by vaccine serotypes among older age groups could be prevented annually by introducing a PCV. Approximately 70% of all deaths occurred in adults over 65 years, underlining the need for protection against IPD in this age group.     

Streptococcus pneumoniae serotype 19A in children, South Korea

Despite the concern of replacement disease, notably by serotype 19A after 7-valent conjugate vaccine (PCV7) use, serotype 19A was increasingly recognized in Korean children before the introduction of PCV7. To understand the dynamics of serogroup 19 prevalence from 1991-2006, we serotyped 538 pediatric pneumococcal isolates. Serogroup 19 isolates (n = 126) were characterized by antimicrobial drug susceptibility, presence of mefA/ermB, and multilocus sequence typing. Overall, the proportion of serotype 19A isolates increased but serotype 19F decreased. Among children <5 years of age, the proportion of serotype 19A isolates in invasive pneumococcal disease increased from 0% in 1991-1994 to 8%-10% in 1995-2000, reached 26% in 2001-2003, and remained at 20% in 2004-2006 when vaccine coverage did not exceed 25% (p = 0.005 for trend). This study demonstrates that the expansion of multidrug-resistant ST320 was responsible for the increase in serotype 19A before PCV7 use.     

Epidemiology of Serotype 1 Invasive Pneumococcal Disease,South Africa, 2003–2013

In South Africa, 7-valent pneumococcal conjugate vaccine (PCV) was introduced in April 2009 and replaced with 13-valent PCV in April 2011. We describe the epidemiology of serotype 1 Streptococcus pneumoniae disease during the pre- and post-PCV eras (2003–2013). Using laboratory-based invasive pneumococcal disease (IPD) surveillance, we calculated annual incidences, identified IPD clusters, and determined serotype 1–associated factors. Of 46,483 IPD cases, 4,544 (10%) were caused by serotype 1. Two clusters of serotype 1 infection were detected during 2003–2004 and 2008–2012, but incidence decreased after 2011. Among children <5 years of age, those who had non–serotype 1 IPD had shorter hospital stays, fewer cases of penicillin-nonsusceptible disease, and lower HIV prevalence and in-hospital death rates than did those with serotype 1 IPD; similar factors were noted for older patients. Serotype 1 IPD had distinctive clinical features in South Africa, and annual incidences fluctuated, with decreases noted after the introduction of PCV13.     

Serotype Replacement after Introduction of 10-Valent and 13-Valent Pneumococcal Conjugate Vaccines in 10 Countries,Europe

We evaluated invasive pneumococcal disease (IPD) during 8 years of infant pneumococcal conjugate vaccine (PCV) programs using 10-valent (PCV10) and 13-valent (PCV13) vaccines in 10 countries in Europe. IPD incidence declined during 2011–2014 but increased during 2015–2018 in all age groups. From the 7-valent PCV period to 2018, IPD incidence declined by 42% in children <5 years of age, 32% in persons 5–64 years of age, and 7% in persons >65 years of age; non-PCV13 serotype incidence increased by 111%, 63%, and 84%, respectively, for these groups. Trends were similar in countries using PCV13 or PCV10, despite different serotype distribution. In 2018, serotypes in the 15-valent and 20-valent PCVs represented one third of cases in children <5 years of age and two thirds of cases in persons >65 years of age. Non-PCV13 serotype increases reduced the overall effect of childhood PCV10/PCV13 programs on IPD. New vaccines providing broader serotype protection are needed.     

Effectiveness of thirteen-valent pneumococcal conjugate vaccine to prevent serotype 3 invasive pneumococcal disease in Quebec in children,Canada

In the province of Quebec, Canada, a 2 + 1 dose pneumococcal conjugate vaccine (PCV) program for children was implemented in 2004. PCV7 was replaced by PCV10 in 2009, by PCV13 in 2011 and by PCV10 in 2018, without catch-up in all instances. The objective was to estimate PCV13 effectiveness to prevent serotype 3 invasive pneumococcal disease in children aged less than 5 years, using 2010–2018 mandatory notification and laboratory surveillance data, an indirect cohort design and multivariate logistic regression models. A total of 29 cases of serotype 3 and 290 non-vaccine serotype cases as controls were analysed. Overall vaccine effectiveness (≥1 dose) was estimated at 59% [-39% to 88%]. During the first year after the last dose effectivness was 88% [47% to 97%] whereas no protection was observed thereafter. There was no trend towards increased effectiveness with the number of doses. PCV13 protection against serotype 3 IPD seems to be short-lived.     

Can pneumococcal meningitis surveillance be used to assess the impact of pneumococcal conjugate vaccine on total invasive pneumococcal disease? A case-study from South Africa, 2005–2016

IntroductionSouth Africa introduced seven-valent pneumococcal conjugate vaccine (PCV7) in 2009 and PCV13 in 2011. We aimed to compare the estimated impact of PCV on pneumococcal meningitis (PM) to impact of PCV on total invasive pneumococcal disease (tIPD) based on risk reduction after PCV introduction.MethodsWe conducted national, laboratory-based surveillance for tIPD during 2005–2016. We estimated and compared rates of PCV13 and non-PCV13 serotype disease among tIPD and PM in individuals aged <5 years and ≥5 years, and compared these rates between the 2005–2008 pre-PCV introduction period and two time points after PCV introduction, 2012 and 2016.ResultsWe enrolled 45,853 tIPD cases; 17,251 (38%) were PM. By 2016, IPD caused by all serotypes decreased 55% (95%CI −57% to −53%) for tIPD, and 54% for PM (95%CI −58% to −51%), 0.7% difference between estimates (p = 0.7). No significant differences were observed between PCV7-serotype disease reduction in tIPD and PM in both age groups or the additional 6 serotypes included in PCV13 in <5 year olds in 2012 and 2016. In 2012 there was a significant difference between increases in non-PCV13 serotype disease in those ≥5 years for tIPD and PM (32% greater increase in PM, p < 0.001), but this difference was absent by 2016. There was a significant difference between the estimated decrease in additional PCV13 type disease in 2016 between tIPD and PM for those aged ≥5 years (28% greater reduction in PM, p = 0.008).ConclusionPM showed similar reductions to tIPD seven years after PCV introduction in vaccine serotype disease in those <5 years, and increases in non-vaccine serotype disease in all ages.     

Risk Factors for Death from Invasive Pneumococcal Disease,Europe, 2010

We studied the possible association between patient age and sex, clinical presentation, Streptococcus pneumoniae serotype, antimicrobial resistance, and death in invasive pneumococcal disease cases reported by 17 European countries during 2010. The study sample comprised 2,921 patients, of whom 56.8% were men and 38.2% were >65 years of age. Meningitis occurred in 18.5% of cases. Death was reported in 264 (9.0%) cases. Older age, meningitis, and nonsusceptibility to penicillin were significantly associated with death. Non–pneumococcal conjugate vaccine (PCV) serotypes among children <5 years of age and 7-valent PCV serotypes among persons 5–64 years of age were associated with increased risk for death; among adults >65 years of age, risk did not differ by serotype. These findings highlight differences in case-fatality rates between serotypes and age; thus, continued epidemiologic surveillance across all ages is crucial to monitor the long-term effects of PCVs.     

Invasive pneumococcal disease: association between serotype, clinical presentation and lethality

To ascertain the factors linked to invasive pneumococcal disease (IPD) caused by the different serotypes in the period 2007-2009, following the conjugate vaccine's inclusion in the childhood vaccination schedule, a total of 2013 IPD cases were reviewed. The mean annual incidence in this period was 10.74 cases per 100,000 inhabitans and the lethality was 8.8%. Overall serotype distribution displayed certain peculiarities, such as the high frequency of serotype 5. Serotype 3, male gender, sepsis and presence of risk factors were significantly associated with lethality. Vaccinated children under 5 years of age had a higher risk of disease due to serotype 19A. Serotype 8 was associated with the presence of underlying risk factors.     

Population Structure and Antimicrobial Resistance of Invasive Serotype IV Group B Streptococcus,Toronto, Ontario,Canada

We recently showed that 37/600 (6.2%) invasive infections with group B Streptococcus (GBS) in Toronto, Ontario, Canada, were caused by serotype IV strains. We report a relatively high level of genetic diversity in 37 invasive strains of this emerging GBS serotype. Multilocus sequence typing identified 6 sequence types (STs) that belonged to 3 clonal complexes. Most isolates were ST-459 (19/37, 51%) and ST-452 (11/37, 30%), but we also identified ST-291, ST-3, ST-196, and a novel ST-682. We detected further diversity by performing whole-genome single-nucleotide polymorphism analysis and found evidence of recombination events contributing to variation in some serotype IV GBS strains. We also evaluated antimicrobial drug resistance and found that ST-459 strains were resistant to clindamycin and erythromycin, whereas strains of other STs were, for the most part, susceptible to these antimicrobial drugs.     

Epidemiology of invasive pneumococcal disease in Kumasi, Ghana

There are few data on the epidemiology of invasive pneumococcal disease in Africa. We undertook a prospective study of these infections in Kumasi, Ghana, collecting clinical data on all patients with laboratory-confirmed pneumococcal meningitis, pneumonia or systemic sepsis associated with bacteraemia. A total of 140 cases were identified in the period from January 2002 to April 2005. The disease was most prevalent among patients <5 years of age and immediately following the peak of the harmattan wind. The majority of patients were treated with a combination of antibiotics, in part reflecting concerns regarding antibiotic resistance. Mortality was high (47%), with no evidence of an improved prognosis compared with earlier studies in the region. Although most isolates of pneumococci were resistant to tetracyclines and co-trimoxazole, there was no high-level resistance to penicillin and only 12% of isolates showed intermediate level resistance. Serotype 1 was the most common serotype (36%), whilst intermediate-level penicillin resistance was associated with serotype 14. Theoretical coverage by existing 7-, 9-, 11- and 23-valent vaccines was 26%, 63%, 64% and 76%, respectively. Vaccination may improve control of pneumococcal disease in Ghana, although modified vaccine formulations are required for local use.     

Pneumococcal meningitis before the introduction of 10-valent pneumococcal conjugate vaccine into the National Childhood Immunization Program in Poland

Background

Poland introduced the 10-valent conjugate pneumococcal vaccine (PCV10) into the childhood immunization program in January 2017. During previous decades, considerable changes had occurred in the surveillance system for invasive pneumococcal disease. Therefore, to provide baseline data on pneumococcal diseases before PCV10 introduction, we evaluated the epidemiology of pneumococcal meningitis (PM), the only syndrome monitored consistently since 1970.

Laboratory surveillance of invasive pneumococcal disease in Australia, 2003 predicting the future impact of the universal childhood conjugate vaccine program.

A comprehensive invasive pneumococcal disease (IPD) laboratory surveillance program was carried out in Australia in 2003. This program provided data on the prevalence of pneumococcal serotypes and antimicrobial resistance. There were 1,995 isolates tested with 34 per cent (683) from children aged less than five years and 27 per cent (535) from the elderly aged more than 65 years. One thousand eight hundred and sixty were isolates from blood, 79 from CSF and 56 from other sterile sites. In young children, 84 per cent of isolates were a serotype and 92 per cent a serogroup in the 7-valent pneumococcal conjugate vaccine (7vPCV). Of penicillin resistant isolates in children less than five years of age 85 per cent and 98 per cent were a serotype and serogroup in the 7vPCV respectively. When the universal 7vPCV vaccine program in young children is introduced in 2005, a proportion of cases of IPD should also be prevented in young adults (estimated reduction of 54 cases annually) and elderly Australians (an estimated reduction of 110 cases annually) as a result of improved herd immunity. Pneumococcal serotypes with higher rates of penicillin resistance (19F, 14 and 6B) were more prevalent in the elderly than in young children. In contrast, erythromycin resistance was more common in children less than five years of age (24%) compared to the elderly (15%). The predominant serotype with erythromycin resistance in Australia was serotype 14 and thus there is likely to be a major reduction in erythromycin resistance as a result of 7vPCV vaccination. Continued surveillance of pneumococcal serotype distribution and antibiotic susceptibility will be essential in order to identify serotype replacement by non-vaccine serotypes and to monitor the overall impact of current and future vaccine programs on invasive pneumococcal disease in Australia, not only in young children but also in other age groups.     

Emergence of serotype 10A-ST11189 among pediatric invasive pneumococcal diseases,South Korea, 2014–2019

Replacement with nonvaccine serotypes (NVTs) among invasive pneumococcal diseases (IPDs) after the introduction of extended-valency pneumococcal conjugate vaccines varies in predominant serotypes across countries. This study analyzed changes in serotype distribution through serotyping, multilocus sequence typing, and antimicrobial susceptibility testing of 168 pediatric IPD isolates obtained from a multihospital-based surveillance system during 2014–2019 in South Korea. Vaccine serotypes (VTs) accounted for 16.1% (19A, 10.1%; 6A, 1.8%; and 19F 1.8%), 82.1% were NVTs (10A, 23.8%; 15A, 8.3%; 12F, 6.5%; 15C, 6.5%; and 15B, 6.0%), and three (1.8%) were nontypeable. Serotype 10A was the most common serotype, with a significant increase from 11.5% in 2014 to 33.3% in 2019 (p < 0.05 for the trend). Other NVTs decreased from 70.4% to 41.7% between 2015 and 2019, most notably in serotype 12F (from 14.8% to 0%). Almost all (95.0%) serotype 10A isolates were ST11189, which were multidrug resistant.     

Persistent serotype 3 and 19A invasive pneumococcal diseases in adults in vaccine era: Serotype-dependent difference in ceftriaxone susceptibility

BackgroundInvasive pneumococcal disease (IPD) is associated with substantial morbidity and mortality in children and elderly populations. Serotype distribution and antibiotic susceptibility of IPD isolates are changing with the implementation of pneumococcal vaccination and increasing antibiotic use worldwide. We aimed to determine serotype distribution, antibiogram, and molecular epidemiology of pneumococci in the late stage of PCV13 era.MethodsProspective multicenter IPD surveillance study was conducted for adults aged ≥ 19 years from July 2019 to June 2021. Clinical and epidemiologic data were collected. In addition, antibiotic susceptibility test, serotype identification and multi-locus sequence typing (MLST) was taken for pneumococcal isolates.ResultsA total of 160 IPD cases were collected with mean age of 65.1 years (male, 72.5%). Serotyping was taken for 116 available pneumococcal isolates. PCV13 and PPSV23 serotypes were 32.8% (n = 38) and 56.0% (n = 65), respectively. Serotype 3 (13.8%) and 19A (9.5%) were the most common causative agents of IPD, followed by serogroup 11 (6.9%), 23A (6.9%), 10A (4.3%), and 15B (4.3%). Notably, 32.5% of invasive pneumococcal isolates were non-susceptible to ceftriaxone. Serotypes 11A, 11E and 19A pneumococci showed high ceftriaxone non-susceptible rate (80%, 100% and 81.8% respectively), and they were related to sequence type (ST) 166 and ST320. In comparison, most serotype 3 isolates were ceftriaxone susceptible and related to ST180.ConclusionsPCV serotypes, especially 3 and 19A, are still prevalent in adult IPDs, suggesting that individual PCV13 immunization would be necessary for the elderly people and chronically ill patients. Ceftriaxone non-susceptible rate was remarkably high in invasive pneumococcal isolates.     

Molecular characterization of Latin American invasive Streptococcus pneumoniae serotype 19A isolates

Streptococcus pneumoniae is a major cause of morbidity and mortality worldwide, especially among children and the elderly. S. pneumoniae serotype 19A has emerged as a major cause of invasive disease in many countries, regardless of whether pneumococcal conjugate vaccines are used. The aim of this study was molecular characterization of invasive S. pneumoniae serotype 19A isolates recovered between 2000 and 2015 from 13 National Laboratories through the laboratory-based surveillance of invasive S. pneumoniae program SIREVA II in Latin American countries. The isolates were submitted with antimicrobial susceptibility tests and were genotyped by a combination of pulsed field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Of the 185 isolates assayed, notable rates of resistance to penicillin (MIC ≥ 0.125 µg/mL; 68.6%), tetracycline (63.7%), trimethoprim-sulfamethoxazole (63.2%), and erythromycin (43.2%) were observed, while 44.3% of isolates were multidrug resistant. The most frequently observed sequence types (ST) were ST320 (32.4%), ST199 (14.1%), ST172 (10.8%) and ST5204 (7.1%). The distribution of STs indicated regional differences in the epidemiology of the clonal groups. The present study showed a diverse genetic background of the pneumococcal population in Latin American countries. Continuous surveillance of the pneumococcal serotype 19A population in the region will be necessary to obtain information about geographical differences and changes in the spread and the establishment of particular clones.     

Incidence of invasive pneumococcal disease in Scotland, 1988-99

A review of the epidemiology of invasive pneumococcal disease in Scotland was carried out using data from laboratory-based systems during the period 1988-99. This comprised 5456 (90.8%) isolates of Streptococcus pneumoniae from blood, 467 (7.8%) from cerebrospinal fluid (CSF) and 84 (1.4%) from other sterile sites. The mean annual incidence of invasive disease was 9.8/10(5) population (9.0/10(5) for bacteraemia and 0.8/10(5) for meningitis). Invasive disease was highest in children < 2 years of age and in the elderly > or = 65 years (44.9/10(5) and 28.4/10(5) population in these age groups respectively). The highest incidence of pneumococcal meningitis, 11.8/10(5) persons occurred in children < 2 years of age. Males had a higher incidence of pneumococcal bacteraemia and meningitis than females (male:female = 1.2:1 for bacteraemia (RR = 1.17, 95 % CI 1.11, 1.24) and 1.5:1 for meningitis (RR = 1.41, 95 % CI 1.18, 1.70)). Pneumococcal disease was highest in winter periods and coincided with influenza activity. The proportion of penicillin and erythromycin non-susceptible isolates increased from 4.2% in 1992 to 12.6% in 1999 and from 5.6% in 1994 to 16.3% in 1999 respectively. Our data confirm the substantial and increasing disease burden from pneumococcal disease and rise in prevalence of antibiotic non-susceptibility among pneumococci in Scotland. Continued surveillance of groups at increased risk for pneumococcal disease and the antibiotic susceptibility and serotype distribution of isolates are important to develop appropriate policies for the prevention of pneumococcal disease in Scotland.     

Invasive pneumococcal disease in Catalonian elderly people, 2002-2009: serotype coverage for different anti-pneumococcal vaccine formulations at the beginning of the new conjugate vaccines era

Population-based surveillance study conducted among persons 65 years or older from the region of Tarragona (Southern Catalonia, Spain) during 2002-2009. All cases with isolation of pneumococcus from normally sterile bodily fluids were included. Incidence rates of invasive pneumococcal disease (IPD) and prevalence of infections caused by serotypes included in different pneumococcal conjugate vaccines (PCVs) and the 23-valent pneumococcal polysaccharide vaccine (PPV-23) were calculated. Overall, 176 IPD cases were observed, which means an incidence of 48 episodes per 100,000 person-year throughout the study period. The most dominant serotypes were 7F (10.1%), 14 (9.4%), 19A (9.4%), 3 (8.6%), 6A (7.9%) and 1 (7.2%). IPD cases due to PCV-7 types (from 37.2% to 14.6%; p = 0.003) and PCV-10 types (from 60.5% to 32.3%; p = 0.002) considerably decreased between 2002-2005 and 2006-2009 periods. Percentage of cases due to PCV-13 types (76.7% vs 62.5%; p = 0.099) and PPV-23 types (81.4% vs 68.8%; p = 0.122) did not significantly change between both periods. As main conclusion, in our setting, the PCV-13 has almost similar serotype coverage to the PPV-23 in preventing IPD among the elderly population, which suggests a possible future use of the conjugate vaccine in all age groups.     

Invasive pneumococcal disease in Australia, 2005

Enhanced surveillance for invasive pneumococcal disease (IPD) was carried out in all Australian states and territories in 2005 with comparative data available since 2001. There were 1,680 cases of IPD notified to the National Notifiable Diseases Surveillance System in Australia in 2005; a notification rate of 8.3 cases per 100,000 population. The rates varied between states and territories and by geographical region with the highest rates in the Northern Territory, the jurisdiction with the largest proportion of Indigenous people. Invasive pneumococcal disease was reported most frequently in those aged 85 years or over (41 cases per 100,000 population) and in 1-year-old children (36.5 cases per 100,000 population). Enhanced data provided additional information on 1,015 (60%) of all notified cases. The overall rate of IPD in Indigenous Australians was 8.6 times the rate in non-Indigenous Australians. There were 126 deaths attributed to IPD resulting in an overall case fatality rate of 7.5%. While the rate of IPD in the Indigenous under 2-year-old population decreased from 219 cases per 100,000 population since targeted introduction of the 7-valent conjugate pneumococcal vaccine (7vPCV) in 2001, the rate in 2005 (94 cases per 100,000 population) was significantly greater than in non-Indigenous children (20.4 cases per 100,000 population). Rates of disease in all children aged less than 2 years, caused by serotypes in the 7vPCV decreased by 75% between 2004 and 2005 as a result of the introduction of a universal childhood 7vPCV immunisation program. Significant decreases in IPD caused by 7vPCV serotypes also occurred in the 2-14 years and 65 years or over age groups. There is no evidence of replacement disease with non-vaccine serotypes. Serotypes were identified in 90% of all notified cases, with 61% of disease caused by serotypes in the 7vPCV and 88% caused by serotypes in the 23-valent polysaccharide pneumococcal vaccine (23vPPV). Reduced penicillin susceptibility remains low and reduced susceptibility to 3rd generation cephalosporins is rare.