Laboratory surveillance of invasive pneumococcal disease in Australia in 2001 to 2002--implications for vaccine serotype coverage.

This paper reports the results of comprehensive laboratory surveillance of invasive pneumococcal disease (IPD) in Australia during 2001 and 2002. The 7-valent conjugate pneumococcal vaccine was introduced for high risk paediatric groups, including Indigenous children, in late 2001. Of 1,355 isolates from non-Indigenous children, 86 per cent belonged to serotypes and 93 per cent to serogroups represented in the 7-valent pneumococcal conjugate vaccine. Thirteen per cent and 24 per cent of isolates had reduced susceptibility to penicillin and erythromycin, respectively and of these, more than 99 per cent belonged to serogroups represented in the 7-valent vaccine. Of the 1,504 isolates from non-Indigenous adults, 96 per cent belonged to serotypes included in the 23-valent polysaccharide vaccine; 14 per cent and 15 per cent had reduced susceptibility to penicillin and erythromycin, respectively and more than 95 per cent of these belonged to serotypes included in the 7-valent conjugate vaccine. In Western Australia and the Northern Territory (the only states for which Indigenous status was consistently available), there were 29 cases of IPD in Indigenous children, of which 21 were due to 7-valent vaccine serotypes in 2001, compared with 24 cases, including 10 due to vaccine serotypes, in 2002. This represents a statistically significant increase in the proportion of total isolates due to non-vaccine serotypes (chi2 = 3.93, p = 0.048) following the introduction of the 7-valent conjugate vaccine, principally due to serotypes 7F and 12F. The number of episodes due to penicillin resistant isolates decreased from nine in 2001 to two in 2002. Ninety per cent of isolates from Indigenous adults were included in the 23-valent polysaccharide vaccine and six per cent and five per cent had reduced susceptibility to penicillin and erythromycin, respectively. Conjugate pneumococcal vaccines can be expected to reduce the incidence of IPD due to vaccine serotypes in vaccinated children and potentially, their adult contacts. It may also impact favourably on the incidence of IPD due to penicillin and erythromycin resistant strains. Continued surveillance of both serotype distribution and antibiotic susceptibility are required 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.     

Streptococcus pneumoniae serotypes in Utah adults at the end of the PCV7 era

While heptavalent pneumococcal conjugate vaccine (PCV) has decreased vaccine type invasive pneumococcal disease (IPD) nationwide, rapid serotype replacement and increasing parapneumonic empyema, has been reported in Utah children. The effect of pediatric vaccination on adults in this population is unknown.We identified 117 adults with IPD from the Intermountain Healthcare Central Laboratory between November 2009 and October 2010. We serotyped 61 (52%) stored isolates. We compared the serotype distribution of adult IPD isolates with that of pediatric isolates collected in 2009-2010.PCV7 serotypes were rare in adults (3%) and children (3%). Emerging 13-valent PCV serotypes 3, 7F, and 19A caused the majority of IPD in adults (63%) and children (56%). Fifty-one (84%) adult isolates were serotypes included in 23-valent polysaccharide vaccine and 66% in PCV13.Adult and pediatric IPD serotypes are closely associated in Utah. PCV13 vaccination in Utah children is likely to significantly impact IPD in Utah adults.     

Serotypes 1, 7F and 19A became the leading causes of pediatric invasive pneumococcal infections in Portugal after 7 years of heptavalent conjugate vaccine use

We characterized 353 isolates responsible for pediatric invasive pneumococcal infections (IPD) in Portugal between 2006 and 2008. Serotypes included in the seven-valent conjugate vaccine (PCV7) accounted for 17% of IPD. Serotypes 1, 7F and 19A were the most frequent causes of IPD and the later consolidated as the most frequent serotype among erythromycin and penicillin non-susceptible isolates. Serotype 1 was associated with older children and empyemas, while serotype 19A was associated with IPD in younger (<2 years) children. The higher valency vaccines PCV10 and PCV13 have a potentially superior coverage, 55% and 83% respectively, but non-vaccine serotypes are emerging as important causes of IPD. A decline of resistance with patient age was noted. Comparing with previous data from Portugal, this study showed a continued decline of PCV7 serotypes and that overall resistance has stabilized following the initial decline of the first post-PCV7 years.     

The impact of the changing pneumococcal national immunisation program among older Australians

Australia has a universal infant pneumococcal conjugate vaccination program and until recently a universal pneumococcal polysaccharide vaccine program for non-Indigenous adults aged ≥65 years and Indigenous adults aged ≥50 years. We documented the impacts of infant and adult vaccination programs on the epidemiology of invasive pneumococcal disease (IPD) in Indigenous and non-Indigenous adults.IPD notifications from the National Notifiable Disease Surveillance System were analysed from 2002 to 2017, grouped by age, vaccine serotype group and Indigenous status. Since the universal funding of infant and elderly pneumococcal vaccination programs in January 2005, total IPD decreased by 19% in non-Indigenous adults aged ≥65 years but doubled in Indigenous adults aged ≥50 years. Vaccine uptake was suboptimal in both groups but lower in Indigenous adults. IPD due to the serotypes contained in the pneumococcal conjugate vaccines (PCV) except for serotype 3 declined markedly over the study period but were replaced by non-PCV serotypes. Serotype 3 is currently the most common in older adults. In the populations eligible for the adult 23-valent pneumococcal polysaccharide vaccine (23vPPV) program, IPD rates due to its exclusive serotypes increased to a lower extent than non-vaccine types. In 2017, non-vaccine serotypes accounted for most IPD in the older population eligible for the 23vPPV program, while it's eleven exclusive serotypes accounted for the majority of IPD in younger adults.Infant and adult pneumococcal vaccination programs in Australia have shaped the serotype-specific epidemiology of IPD in older adults. IPD remains a significant health burden for the Indigenous population. Herd immunity impact is clear for PCV serotypes excluding serotype 3 and serotype replacement is evident for non-PCV serotypes. The adult 23vPPV immunisation program appears to have partially curbed replacement with IPD due to its eleven exclusive serotypes, highlighting a potential benefit of increasing adult 23vPPV coverage in Australia.     

Distribution of serotypes causing invasive pneumococcal disease in older adults from high-income countries and impact of pediatric and adult vaccination policies

BackgroundNeither indirect protection through use of 13-valent and 10-valent pneumococcal conjugate vaccines (PCV13 and PCV10) in pediatric National Immunization Programs (NIPs) nor direct vaccination with the 23-valent polysaccharide vaccine have eliminated vaccine serotype invasive pneumococcal disease (IPD) in older adults. Vaccinating older adults with higher-valency PCV15 and PCV20 could address remaining IPD due to pediatric PCV serotypes plus additional IPD due to serotypes included in these vaccines.MethodsWe collected serotype-specific IPD data in older adults (≥65 years in most countries), from national or regional surveillance systems or hospital networks of 33 high-income countries. Data were from official government websites, online databases, surveillance system reports, published literature, and personal communication with in-country investigators. Average percentages of IPD serotypes were calculated.ResultsAmong 52,905 cases of IPD with a serotype identified, PCV13 serotypes accounted for 33.7% of IPD (55.8% and 30.6% for countries with PCV10 and PCV13 in the pediatric NIP), most commonly serotypes 3 (14.9%) and 19A (7.0%). PCV15 and PCV20 would cover an additional 10.4% and 32.9% of older adult IPD beyond PCV13 serotypes (PCV10 countries: 7.7% and 23.3%; PCV13 countries: 10.6% and 34.6%). The most common of these additional serotypes were 8 (9.9%), 22F (7.9%), 12F (4.6%), and 11A (3.3%). PPSV23 policies for older adults were not correlated with lower IPD percentages due to PPSV23 serotypes.ConclusionsVaccinating older adults with higher-valency PCVs, especially PCV20, could substantially reduce the remaining IPD burden in high-income countries, regardless of current PCV use in pediatric NIPs and adult PPSV23 policies.     

Use of the 13-valent conjugate vaccine has the potential to eliminate pilus carrying isolates as causes of invasive pneumococcal disease

We examined the distribution of the two pilus island loci (PI-1 and PI-2) in all pediatric invasive pneumococcal disease (IPD) isolates recovered in Portugal over the ten year period 1999-2008 (n=575). While 199 isolates (35%) harbored PI-2, only 98 isolates (17%) harbored PI-1. A decline of isolates carrying PI-1 was observed in the post 7-valent conjugate vaccine (PCV7) period since most PI-1 carrying isolates expressed PCV7 serotypes. On the other hand, the PI-2 increase in the post-PCV7 period was associated mostly with serotypes 1 and 7F. The overall proportion of piliated isolates declined in the period following PCV7 but quickly recovered to pre-PCV7 levels (50%). Only serotypes 19F and 19A contained isolates carrying simultaneously PI-1 and PI-2 and the proportion of isolates carrying both pilus islands remained stable and low. All PI-1 clades were represented in our collection and were associated with multiple serotypes. Over 99% of pilus island carrying isolates belonged to the 13-valent conjugate vaccine serotypes.     

Impact and effectiveness of 23-valent pneumococcal polysaccharide vaccine against invasive pneumococcal disease in the elderly in England and Wales

In 2003 the existing 23-valent pneumococcal vaccine (PPV23) programme for high risk groups was extended to include all ≥65 year olds in England and Wales, starting with ≥80 year olds and moving to 75–79 and 65–74 year olds by 2005. We conducted an ecological study to assess the impact of the extended PPV23 programme on serotype-specific incidence of invasive pneumococcal disease (IPD) and a case–control study to assess vaccine effectiveness (VE) using the national IPD surveillance dataset. Between 1998 and 2006 IPD incidence caused by PPV23 serotypes in the targeted age-groups was unchanged. IPD caused by the serotypes covered by the 7-valent conjugate vaccine (PCV7) introduced for children in 2006 declined in ≥65 year olds after 2006 but was offset by an increase in non-PCV7 serotypes. This increase was similar for the additional 16 serotypes covered by PPV23 and the non-PPV23 serotypes. For the VE study, vaccine history was obtained for controls (n = 1270) with non-PPV23 IPD diagnosed between November 2003 and December 2010 and a subset of cases (n = 1272) matched for age and time period. VE declined from 48% (95% confidence interval; 32–60%) within two years of vaccination to 15% (−3% to 30%) after five years. Although differences in VE by age and having risk conditions were not statistically significant the highest estimates were in the youngest age group (65–74 years) and in those without risk conditions with a VE estimate of 65% (23–84%) within 2 years of vaccination for non-risk 65–74 year olds. VE differed by serotype (p = 0.005), from −23% (−85% to 19%) for serotype 3 to 63% (29–81%) for 12F. In conclusion PPV23 was effective, particularly in healthy under 75 year olds, but protection waned after 5 years. There was no discernible impact of PPV23 on IPD incidence or PCV7-induced serotype replacement, consistent with the modest overall effectiveness, the 45% increased coverage over the former risk-based programme and lack of herd immunity from the PPV23 programme. Based on the VE estimates PPV23 was still considered a cost-effective intervention for the low risk elderly.     

Serotypes/groups distribution and antimicrobial resistance of invasive pneumococcal isolates: implications for vaccine strategies

Based on the invasive pneumococcal isolates referred to reference laboratories in Scotland in 1988-99, we identified the distribution of serotypes/groups and their antimicrobial resistance patterns in order to evaluate the coverage of polysaccharide and the new pneumococcal conjugate vaccines. A total of 5659 invasive isolates were included. Of these, 5124 (90.5%) were blood isolates, 308 (5.5%) were CSF isolates, 143 (2.5%) were blood and CSF and 84 (1.5%) were other normally sterile isolates. The most prevalent 11 serotypes/groups were 14, 9, 19, 6, 23, 1, 3, 4, 7, 8 and 18, in numerical order. These accounted for 84% of total serotypes/groups. The serotypes/groups included in the 23 and 14-valent polysaccharide vaccines accounted for 96% and 88% of all isolates. Both vaccines accounted for 98% of penicillin non-susceptible and 100% of erythromycin non-susceptible isolates. The 7, 9, and 11-valent conjugate vaccines covered 61, 68 and 80% of invasive isolates respectively. The coverage of these vaccines was substantially higher in youngest age group with 84, 86 and 93% of invasive isolates in children < 2 years included in the 7, 9 and 11-valent conjugate vaccines compared with 58, 64 and 77% in adults > or = 65 years of age. The serotype/group distribution of invasive isolates in Scotland varied from year to year over the period 1993-9. The coverage of the 23-valent vaccine remained above 95% in each year but the coverage of the 7, 9 and 11-valent conjugate vaccines showed more marked fluctuation with coverage as low as 53, 60 and 75% in some years. Continued surveillance of invasive pneumococcal isolates is required to inform the development of appropriate vaccine strategies to prevent pneumococcal disease in Scotland.     

Invasive Pneumococcal Disease after Routine Pneumococcal Conjugate Vaccination in Children,England and Wales

We assessed known risk factors, clinical presentation, and outcome of invasive pneumococcal disease (IPD) in children 3–59 months of age after introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in England and Wales. During September 2006–March 2010, a total of 1,342 IPD episodes occurred in 1,332 children; 14.9% (198/1,332) had comorbidities. Compared with IPD caused by PCV7 serotypes (44/248; 17.7%), comorbidities were less common for the extra 3 serotypes in the 10-valent vaccine (15/299; 5.0%) but similar to the 3 additional PCV13 serotypes (45/336; 13.4%) and increased for the 11 extra serotypes in 23-valent polysaccharide vaccine (PPV23) (39/186; 21.0%) and non-PPV23 serotypes (38/138; 27.5%). Fifty-two (3.9%) cases resulted from PCV7 failure; 9 (0.7%) case-patients had recurrent IPD. Case-fatality rate was 4.4% (58/1,332) but higher for meningitis (11.0%) and children with comorbidities (9.1%). Thus, comorbidities were more prevalent in children with IPD caused by non-PCV13 serotypes and were associated with increased case fatality.     

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.     

Have changing pneumococcal vaccination programmes impacted disease in Ontario?

Background

Publicly 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).

Methods

Laboratory 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.

Results

Between 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.

Conclusions

During 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.     

Serotype distribution of invasive Streptococcus pneumoniae in adults 65 years of age and over after the introduction of childhood 13-valent pneumococcal conjugate vaccination programs in Canada, 2010–2016

The 13-valent conjugate vaccine (PCV13) was recommended for childhood immunization programs in 2010 in Canada and has decreased the incidence of invasive pneumococcal disease (IPD) in children and changed the epidemiology of IPD in adults. This study investigated the epidemiology of IPD in adults 65 years of age and older in Canada. A total of 7282 invasive S. pneumoniae isolated from adults ≥65 years old were serotyped from 2010 to 2016 and antimicrobial susceptibility was performed on 2527 isolates. Serotyping was performed by Quellung reaction using commercial antisera and antimicrobial susceptibilities were determined by broth microdilution. PCV7 serotypes decreased non-significantly from 2010 to 2016 from 9.1% (n = 96) to 6.7% (n = 72) while the additional six PCV13 serotypes declined significantly from 39.5% (n = 418) to 18.6% (n = 201) (p < 0.05). The 23-valent pneumococcal polysaccharide vaccine (PPV23) and non-vaccine (NVT) serotypes increased from 26.3% (n = 278) to 36.2% (n = 393) (p < 0.05), and from 25.1% (n = 266) to 38.4% (n = 416) (p < 0.05), respectively. There were no significant changes in antimicrobial resistance rates from 2011 to 2016: 24.1% of the IPD from adults ≥65 years were resistant to clarithromycin (n = 609), 10.0% to doxycycline (n = 254), 11.8% to penicillin (n = 299), 5.2% to cefuroxime (n = 131), 6.6% to clindamycin (n = 168), 6.0% to trimethoprim-sulfamethoxazole (n = 152), and 0.5% (n = 12) to ceftriaxone. Although overall incidence of IPD in adults ≥65 years has remained relatively constant from 2010 to 2016, childhood PCV13 vaccination programs have been successful in indirectly reducing IPD caused by PCV13 serotypes in adults through herd immunity effects.     

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.     

Safety and immunogenicity of 15-valent pneumococcal conjugate vaccine in pneumococcal vaccine-naïve adults ≥50 years of age

BackgroundPneumococcal disease remains a public health priority in adults. Safety and immunogenicity of 15-valent pneumococcal conjugate vaccine (PCV15) containing 13 serotypes included in 13-valent pneumococcal conjugate vaccine (PCV13) plus 2 additional serotypes (22F and 33F) was evaluated in adults ≥50 years old (NCT01513551).Methods691 adults received one dose of PCV15, PCV13, or 23-valent pneumococcal polysaccharide vaccine (PPV23) and were followed 14 days for safety. Serotype-specific IgG geometric mean concentrations (GMCs) and opsonophagocytic activity (OPA) geometric mean titers (GMTs) were measured immediately prior and 1-month postvaccination.ResultsSafety profiles were comparable across vaccination groups. PCV15 induced comparable levels of IgG GMCs and OPA GMTs to PCV13 and PPV23 for shared serotypes. Serotype-specific antibodies were numerically higher among recipients of PCV15 than PCV13 and PPV23 for 7 and 12 shared serotypes, respectively; and lower for 4 and 1 serotype(s), respectively. PCV15 induced higher IgG and OPA antibodies than PCV13 or PPV23 for serotypes unique to PCV15 (22F and 33F not in PCV13; 6A not in PPV23).ConclusionsPCV15 displayed an acceptable safety profile and induced IgG and OPA to all 15 serotypes included in the vaccine, at levels comparable to PCV13 and PPV23 for shared serotypes with these vaccines.Study identification: V114-002.CLINICALTRIALS.GOV identifier: NCT01513551.© 2018 Merck & Co., Inc.     

Incidence of invasive pneumococcal disease before and during an era of use of three different pneumococcal conjugate vaccines in Quebec

BackgroundIn Quebec, 7-valent (PCV7), 10-valent (PCV10) and 13-valent (PCV13) pneumococcal conjugate vaccines were successively used for the immunization of children according to a 2+1 doses schedule.ObjectiveOur aim was to assess the impact of this program on the epidemiology of invasive pneumococcal disease (IPD) in children and adults.MethodsNotification and laboratory surveillance data were analyzed and the immunization status of IPD cases in children was checked.ResultsIn children < 5 years, the IPD rate decreased from 69/100,000 in 2003 to 12/100,000 in 2016 (83% reduction). Following PCV7 introduction in 2004, there has been a rapid decline in PCV7-type IPD cases and 6A. 7F and 19A serotypes emerged but their incidence decreased following PCV10 introduction in 2009 and PCV13 in 2011, whereas decrease in serotype 3 IPD was modest. Non-PCV13 types increased and represented 79% of cases in 2016. The same pattern was seen in adults but replacement was complete and there was no decrease in overall IPD rate. In those 65 years and over, PCV13 serotypes represented 28% of cases in 2016 and 62% were serotypes included in the 23-valent polysaccharide vaccine. Out of 10 IPD cases caused by serotype 3 in children vaccinated with PCV13 in 2011–2016, 6 occurred more than one year following the booster dose, which suggests short-term protection. Out of 31 breakthrough 19A cases, 19 occurred in children aged between 8 and 14 months who had received the 2 primary PCV13 doses but not the toddler booster dose, which suggests a window of susceptibility in a 2+1 schedule.ConclusionPCVs had a major impact on the IPD rate in children but not in adults. Among elderly adults, the proportion of cases caused by serotypes included in PCV13 is diminishing year after year but a majority of cases remains covered by the 23-valent polysaccharide vaccine.     

Invasive pneumococcal disease in children 5 years after conjugate vaccine introduction--eight states, 1998-2005

Streptococcus pneumoniae (pneumococcus) is a major cause of meningitis, pneumonia, and bacteremia, especially among young children and older adults. Before the 7-valent pneumococcal conjugate vaccine (PCV7) was introduced in the United States in 2000, the seven pneumococcal serotypes covered by the vaccine (4, 6B, 9V, 14, 18C, 19F, and 23F) caused 80% of invasive pneumococcal disease (IPD) cases among young children, and the incidence of IPD was relatively stable. In October 2000, the Advisory Committee on Immunization Practices recommended PCV7 for all children aged <2 years and for older children at increased risk for IPD. Introduction of PCV7 in the United States led to substantial reductions in the incidence of IPD among the target population of children aged <5 years. Use of the vaccine also reduced IPD among unvaccinated populations through reductions in nasopharyngeal colonization and transmission of vaccine-type pneumococci from vaccinated children (i.e., indirect, or herd, effects of PCV7). To evaluate the effect of continued PCV7 use on IPD incidence among children aged <5 years in the United States, CDC analyzed population- and laboratory-based surveillance data. Results of that analysis indicated that in 2005, overall IPD rates among children aged <5 years were 77% lower, and an estimated 13,000 fewer cases of IPD occurred, compared with the years preceding vaccine introduction (1998-1999). Although IPD caused by PCV7 serotypes declined through 2005, overall IPD rates leveled off beginning in 2002, primarily because of increases in the incidence of IPD caused by non-PCV7 serotype 19A. Given these trends, use of expanded-valency conjugate vaccines might further reduce IPD incidence. Continued surveillance is needed to guide development of future formulations of conjugate vaccines and to monitor the effects of continued vaccine use.     

Pneumococcal Serotypes before and after Introduction of Conjugate Vaccines,United States, 1999–2011

Serotyping data for pneumococci causing invasive and noninvasive disease in 2008–2009 and 2010–2011 from >43 US centers were compared with data from preconjugate vaccine (1999–2000) and postconjugate vaccine (2004–2005) periods. Prevalence of 7-valent pneumococcal conjugate vaccine serotypes decreased from 64% of invasive and 50% of noninvasive isolates in 1999–2000 to 3.8% and 4.2%, respectively, in 2010–2011. Increases in serotype 19A stopped after introduction of 13-valent pneumococcal vaccine (PCV13) in 2010. Prevalences of other predominant serotypes included in or related to PCV13 (3, 6C, 7F) also remained similar for 2008–2009 and 2010–2011. The only major serotype that increased from 2008–2009 to 2010–2011 was nonvaccine serotype 35B. These data show that introduction of the 7-valent vaccine has dramatically decreased prevalence of its serotypes and that addition of serotypes in PCV13 could provide coverage of 39% of isolates that continue to cause disease.     

Direct effectiveness of pneumococcal polysaccharide vaccine against invasive pneumococcal disease and non-bacteremic pneumococcal pneumonia in elderly population in the era of pneumococcal conjugate vaccine: A case-control study

BackgroundWhile herd effects and serotype replacement by childhood pneumococcal protein conjugated vaccines (PCVs) continues to accumulate worldwide, direct effectiveness of 23-valent pneumococcal polysaccharide vaccine (PPV23) against pneumococcal diseases in the elderly has been challenged. We estimated the direct effectiveness of PPV23 in the elderly population.MethodsFor a hospital-based case-control study, cases of invasive pneumococcal disease (IPD) and non-bacteremic pneumococcal pneumonia (NBPP) (adults ≥ 65 years) were identified in 14 hospitals participated in the pneumococcal surveillance program from March 2013 to October 2015, following implementation of PPV23 national immunization program (NIP) for the elderly in the Republic of Korea. Controls matched by age, sex, and hospital were selected at ratios of 1:2 (IPD) or 1:1 (NBPP). Clinical data and vaccination records were collected. Vaccine effectiveness was calculated as (1-adjusted odds ratio) × 100.ResultsWe enrolled 148 IPD and 557 NBPP cases, and 295 IPD and 557 NBPP controls for analyses. Overall effectiveness of PPV23 against IPD was 28.5% [95% confidence interval (CI) −5.8%–51.6%] and against NBPP was 10.2% (-15.1-30.6) in all patients ≥ 65 years. However, in subgroup analysis of patients aged 65–74 years, PPV23 was protective against IPD [effectiveness 57.4% (19.4–77.5)] and against NBPP [effectiveness 35.0% (2.3–56.7)]. Furthermore, serotype-specific effectiveness of PPV23 against IPD was 90.6% (27.6–98.8) for PPV23-unique serotypes and 81.3% (38.6–94.3) for PPV23 serotypes excluding serotype 3.ConclusionsThis study indicates that PPV23 with broad serotype coverage might be beneficial in preventing IPD and NBPP due to non-PCV13 serotypes in the young-elderly, with potentially increasing effectiveness in the setting of childhood PCV NIP.     

Systemic pneumococcal disease in Norway 1995-2001: capsular serotypes and antimicrobial resistance

A total of 4624 pneumococcal isolates from episodes of systemic pneumococcal disease were received at the Norwegian Institute of Public Health during the period 1995-2001. All isolates were serotyped and tested for susceptibility to benzylpenicillin, lincomycin, erythromycin, tetracycline and trimethroprim sulphamethoxazole. The proportion of strains resistant to these antimicrobial agents remained stable at a low level, ranging from 0.1% for benzylpenicillin to 2.5% for erythromycin. The distribution of serotypes was also stable over the 7 years: serotypes 1, 4, 9, 14, 7, 6 and 23 were the most frequent, representing 70.5% of isolates. Overall, 95.8% of the isolates were of serotypes/groups included in the current 23-valent polysaccharide vaccine, 52.2% were of serotypes/groups included in the 7-valent conjugated vaccine and 85.5% were of serotypes/groups included in the 11-valent conjugated vaccine.     

Incidence of invasive pneumococcal disease in the Czech Republic and serotype coverage by vaccines, 1997-2006

We studied the incidence of invasive pneumococcal disease (IPD) in the Czech Republic by analysing two sources of data. The incidence of pneumococcal meningitis based on routine notification data varied between 0.4 and 0.6/100 000 population between 1997 and 2006. The incidence of IPD based on laboratory surveillance varied between 2.3 and 4.3/100 000 population between 2000 and 2006. The annual IPD incidence remained stable during the study period. Estimates of absolute IPD case-load in the entire country varied from 235 to 437 per year. The age-specific incidence was highest in the <1 year age group, reaching 4.3/100 000 for pneumococcal meningitis in routine notification and 15.7/100 000 for IPD in laboratory-based surveillance data, respectively. A total of 1236 Streptococcus pneumoniae isolates from cerebrospinal fluid and sterile body sites were investigated. The most frequent serotypes causing IPD in all ages were 3, 4, 14, 8 and 19F, accounting for 41.5% of all isolates. The most frequent serotypes by age group were: <1 year (6B and 19F); 1-4 years (14, 6B and 23F); 40-64 years (3, 8 and 4), and > or = 65 years (3, 4, 9N and 14). The coverage of serotypes in all age groups by pneumococcal vaccines ranged from 41.5% for 7-valent conjugate vaccine to 67.9% for 13-valent conjugate vaccine. The coverage of serotypes causing IPD is significantly different between infants/children and adults/elderly. PCV-7 coverage by age group was: <1 year (66.0%), 1-4 years (65.1%), 40-64 years (34.4%) and > or = 65 years (39.3%). Similar age differences between infants/children and adults/elderly were found in coverage by PCV-9, PCV-11 and PCV-13. The distribution of serotypes in the total population and individual age groups was stable during the period 2000-2006.