Incidence Of Invasive Pneumococcal Disease Research Articles

Invasive Pneumococcal Disease (IPD) epidemiology and serotype replacement after the introduction of the 13-valent pneumococcal conjugate vaccine in Ontario, Canada, 2007-2022

Abstract Introduction New vaccine products were recently authorized for protection against invasive pneumococcal disease (IPD) in Canada. Our aim was to determine age- and serotype-specific trends in IPD incidence and severity in Canada’s largest province, Ontario. Methods We included all confirmed IPD cases reported in Ontario and defined the pre-PCV13 era (01/2007 to 12/2010), post-PCV13 era (01/2011 to 12/2019), and COVID-19 pandemic era (01/2020 to 12/2022). We estimated incidence, hospitalization, and case fatality rate (CFR) by age. We grouped IPD cases by vaccine-specific serotypes (PCV13; PCV15-non-PCV13; PCV20-non-PCV13; PCV20-non-PCV15; PPV23-non-PCV20; and non-vaccine preventable [NVP]). We then compared incidence rates by age and serotype groups in the pre- and post-PCV13 era by calculating rate ratios (RR) and their 95% confidence intervals (CI). Results Incidence and hospitalizations declined from the pre- to post-PCV13 era in children aged <5 years (RR = 0.7, 95%CI = 0.6-0.8 and RR = 0.8, 95%CI = 0.7-0.9, respectively) but the CFR increased (1.4% to 2.3%). Other age groups saw smaller declines or more stable incidence rates across the years; hospitalizations increased in adults aged 50-64 years (RR = 1.2, 95%CI 1.1-1.4) and ≥65 years (RR = 1.1, 95%CI 1.0-1.1). For all ages, IPD cases and hospitalizations attributable to PCV13 serotypes declined and those attributable to PCV15-non-PCV13, PCV20-non-PCV-13, and NVP serotypes increased. IPD incidence declined during the COVID-19 era. Conclusions IPD incidence and hospitalizations due to PCV13 serotypes decreased after PCV13 introduction but increased for other serotypes. Continued surveillance is required to evaluate changes to pneumococcal vaccination programs and ongoing changes to the distribution of IPD-causing serotypes.

The impact of pneumococcal serotype replacement on the effectiveness of a national immunization program: a population-based active surveillance cohort study in New Zealand

In Aotearoa New Zealand (NZ) PCV7 was introduced in 2008, then PCV10 in 2011 and PCV13 in 2014. In 2017 PCV10 was re-introduced, replacing PCV13. In the present study, we investigate the resultant rapidly changing invasive pneumococcal disease (IPD) epidemiology. We compare the IPD incidence rate ratio (IRR) in NZ (2022 versus 2020) with other countries, and describe the IPD epidemiology (including trends in overall IPD and serotype 19A, and antimicrobial resistance) within NZ. Additionally, we performed a genomic-epidemiology investigation identifying the most common 19A sequence types and associated risk factors. Though IPD incidence rates have increased in the US and Australia (2021-22) after declines in 2020, in NZ the incidence rate is the highest since 2011 with a significantly higher IRR than US (p<0.01). Incidence rates among children <2 and adults 65 or over in 2022 are the highest since 2009, driven by significant increases of serotype 19A (p=0.01). Māori and Pacific peoples are experiencing the highest rates since 2009. Further, penicillin resistance among 19A isolates has increased from 39% (2012) to 84% (2021) (p=0.02). Genomic sequencing identified the more virulent ST-2062 as most common among 19A isolates sequenced, increasing from 5% (2010) to 55% (2022). With very high incidence rates of IPD in NZ, inadequate protection against 19A, increasing resistance, and a more virulent 19A clade, targeted public health campaigns and increased PCV13 availability are needed. The NZ Ministry of Health funds IPD surveillance and typing in NZ.

Streptococcus pneumoniae serotype 3 population structure in the era of conjugate vaccines, 2001-2018.

Background. Despite use of highly effective conjugate vaccines, invasive pneumococcal disease (IPD) remains a leading cause of morbidity and mortality and disproportionately affects Indigenous populations. Although included in the 13-valent pneumococcal conjugate vaccine (PCV13), which was introduced in 2010, serotype 3 continues to cause disease among Indigenous communities in the Southwest USA. In the Navajo Nation, serotype 3 IPD incidence increased among adults (3.8/100 000 in 2001-2009 and 6.2/100 000 in 2011-2019); in children the disease persisted although the rates dropped from 5.8/100 000 to 2.3/100 000.Methods. We analysed the genomic epidemiology of serotype 3 isolates collected from 129 adults and 63 children with pneumococcal carriage (n=61) or IPD (n=131) from 2001 to 2018 of the Navajo Nation. Using whole-genome sequencing data, we determined clade membership and assessed changes in serotype 3 population structure over time.Results. The serotype 3 population structure was characterized by three dominant subpopulations: clade II (n=90, 46.9 %) and clade Iα (n=59, 30.7 %), which fall into Clonal Complex (CC) 180, and a non-CC180 clade (n=43, 22.4 %). The proportion of clade II-associated IPD cases increased significantly from 2001 to 2010 to 2011-2018 among adults (23.1-71.8 %; P<0.001) but not in children (27.3-33.3 %; P=0.84). Over the same period, the proportion of clade II-associated carriage increased; this was statistically significant among children (23.3-52.6 %; P=0.04) but not adults (0-50.0 %, P=0.08).Conclusions. In this setting with persistent serotype 3 IPD and carriage, clade II has increased since 2010. Genomic changes may be contributing to the observed trends in serotype 3 carriage and disease over time.

Incidence of pneumococcal disease in children ≤48 months old in the United States: 1998–2019

BackgroundPneumococcal disease (PD) is a major cause of morbidity and mortality among children, particularly in the youngest age groups. This study aimed to assess the incidence of PD over time by age group in young children with commercial or Medicaid coverage in the US. MethodsEpisodes of invasive pneumococcal disease (IPD), all-cause pneumonia (ACP), and acute otitis media (AOM) were identified in the MarketScan® Commercial and Medicaid claims databases using diagnosis codes among children aged ≤ 48 months with confirmed date of birth (DoB), at any time during the study period (1998–2019). DoB was assigned using diagnosis codes for birth or delivery using the child’s or mother’s medical claims to ensure accurate age determination. Annual incidence rates (IRs) were calculated as number of disease episodes/100,000 person-years (PY) for IPD and ACP and episodes/1,000 PY for AOM, for children aged 0–6, 7–12, 12–24, and 25–48 months. ResultsAnnual IPD IRs declined from 53 to 7 episodes/100,000 PY between 1998 and 2019 in commercially-insured and 58 to 9 episodes/100,000 PY between 2001 and 2019 in Medicaid-insured children. Annual ACP IRs declined from 5,600 to 3,952 episodes/100,000 PY, and from 6,706 to 4,521 episodes/100,000 PY, respectively, over these periods. In both populations, children aged 0–6 months had the highest incidence of IPD and inpatient ACP. Annual AOM IRs declined from 1,177 to 738 episodes/1,000 PY (commercially-insured) and 633 to 624 episodes/1,000 PY (Medicaid-insured), over these periods. IRs were higher in rural vs. urban areas for all disease manifestations. ConclusionsIncidence rates of IPD, ACP, and AOM decreased in children with commercial insurance and Medicaid coverage from 1998 to 2019. However, burden of disease remained substantial, with higher annual IRs for IPD and ACP for Medicaid-insured vs. commercially-insured children. IPD and inpatient ACP were most common in the youngest children 0–6 months old, followed by the 7–12-month age group.

Impact of Demographic Developments and PCV13 Vaccination on the Future Burden of Pneumococcal Diseases in Germany—An Integrated Probabilistic Differential Equation Approach

Streptococcus pneumonia is the primary cause of morbidity and mortality in infants and children globally. Invasive pneumococcal disease (IPD) incidence is affected by various risk factors such as age and comorbidities. Additionally, this bacterium is a major cause of community-acquired pneumonia (CAP), leading to higher rates of hospitalization, especially among older adults. Vaccination with pneumococcal conjugate vaccines (PCVs) has proven effective, but the demographic transition in Germany poses a challenge. This study introduces a novel stochastic approach by integrating a population forecast model into a transmission dynamic model to investigate the future burden of pneumococcal diseases in three age groups (0–4, 5–59, and 60 and older). Our simulations, presented through mean predictions and 75% prediction intervals, indicate that implementing PCV13 (13-valent pneumococcal conjugate vaccine) until the year 2050 results in reduced cases of IPD and CAP in all age groups compared to scenarios without infant vaccination. However, cases with non-vaccine serotypes may persist at higher levels compared to scenarios without infant vaccination. Consequently, there may be a need for improvement in the current national vaccine policy, such as implementing the use of higher-valent PCVs and strengthening adult vaccination uptake.

Exploring factors shaping antibiotic resistance patterns in Streptococcus pneumoniae during the 2020 COVID-19 pandemic.

Non-pharmaceutical interventions implemented to block SARS-CoV-2 transmission in early 2020 led to global reductions in the incidence of invasive pneumococcal disease (IPD). By contrast, most European countries reported an increase in antibiotic resistance among invasive Streptococcus pneumoniae isolates from 2019 to 2020, while an increasing number of studies reported stable pneumococcal carriage prevalence over the same period. To disentangle the impacts of the COVID-19 pandemic on pneumococcal epidemiology in the community setting, we propose a mathematical model formalizing simultaneous transmission of SARS-CoV-2 and antibiotic-sensitive and -resistant strains of S. pneumoniae. To test hypotheses underlying these trends five mechanisms were built into the model and examined: (1) a population-wide reduction of antibiotic prescriptions in the community, (2) lockdown effect on pneumococcal transmission, (3) a reduced risk of developing an IPD due to the absence of common respiratory viruses, (4) community azithromycin use in COVID-19 infected individuals, (5) and a longer carriage duration of antibiotic-resistant pneumococcal strains. Among 31 possible pandemic scenarios involving mechanisms individually or in combination, model simulations surprisingly identified only two scenarios that reproduced the reported trends in the general population. They included factors (1), (3), and (4). These scenarios replicated a nearly 50% reduction in annual IPD, and an increase in antibiotic resistance from 20% to 22%, all while maintaining a relatively stable pneumococcal carriage. Exploring further, higher SARS-CoV-2 R0 values and synergistic within-host virus-bacteria interaction mechanisms could have additionally contributed to the observed antibiotic resistance increase. Our work demonstrates the utility of the mathematical modeling approach in unraveling the complex effects of the COVID-19 pandemic responses on AMR dynamics.

Mortality of Invasive Pneumococcal Disease following Introduction of the 13-Valent Pneumococcal Conjugate Vaccine in Greenland.

Before the incorporation of the 13-valent pneumococcal conjugate vaccine (PCV13) into the childhood vaccination regimen in Greenland in 2010, Inuit populations experienced a substantial prevalence of invasive pneumococcal disease (IPD). The PCV13 introduction has been shown to markedly reduce the incidence of IPD. This current study estimated the impact of PCV13 introduction on IPD mortality in Greenland. This was a nationwide register-based study using all available data on IPD cases 1995-2020 in Greenland. Thirty-one-day IPD case fatality rates (CFR), and all-cause and mortality rates associated with IPD during the period before the introduction of PCV13 (January 1995 to September 2010) were compared with those observed in the post-PCV13 era (September 2010 to October 2020). Standardized mortality ratios (SMRs) expressed differences in mortality by sex, age, region, ethnicity, comorbidity, and serotype. IPD CFR decreased with 24.5% from the pre- to the post-PCV13 period. SMR in IPD patients decreased by 57% (95% CI, 36-75%), and a reduction occurred in all age groups. While SMR in IPD persons ≥60 years remained virtually unchanged, there were no IPD-related deaths in persons ≤39 years in the post-PCV13 period. In conclusion, IPD-related mortality has decreased in Greenland following PCV13 introduction in 2010 in the country.

Invasive pneumococcal disease 3 years after introduction of a reduced 1 + 1 infant 13-valent pneumococcal conjugate vaccine immunisation schedule in England: a prospective national observational surveillance study

The UK transition from a 2 + 1 to a 1 + 1 infant immunisation schedule with the 13-valent pneumococcal conjugate vaccine (PCV13) on Jan 1, 2020, coincided with the start of the COVID-19 pandemic. We describe the epidemiology of invasive pneumococcal disease (IPD) in England over 6 financial years (April 1 to March 31) between 2017-18 and 2022-23. We used prospective national surveillance data, including serotyping and whole-genome sequencing of invasive isolates, to analyse IPD trends in England by age and financial year. We compared breakthrough infections and vaccine failure rates in 2022-23 among children eligible for the 1 + 1 schedule with rates in cohorts of children eligible for the 2 + 1 schedule between 2017-18 and 2019-20. We assessed genomic changes over time by comparing Global Pneumococcal Sequencing Clusters and multilocus sequence types among PCV13 serotypes causing IPD. There were 4598 laboratory-confirmed IPD cases in 2022-23, 3025 in 2021-22, 1240 in 2020-21, and 5316 in 2019-20. IPD incidence in 2022-23 was 14% lower than in 2019-20 (incidence rate ratio [IRR] 0·86, 95% CI 0·81-0·91; p<0·001). IPD incidence in 2022-23 compared with 2019-20 was 34% higher in children (aged <15 years) (378 cases vs 292 cases; IRR 1·34, 95% CI 1·08-1·68; p=0·009) and 17% lower in adults (aged 15 years and older; 4220 vs 5024; 0·83, 0·78-0·88; p<0·001). The proportion of PCV13-type IPD increased from 19·4% (95% CI 18·2-20·4; 957 of 4947) in 2019-20 to 29·7% (28·3-31·0; 1283 of 4326) in 2022-23, mainly due to serotype 3, but also serotypes 19F, 19A, and 4, alongside a decrease in non-PCV13 serotypes 8, 12F, and 9N. The increase in IPD incidence due to serotypes 3, 19A, and 19F was driven by clonal expansion of previously circulating strains, whereas serotype 4 expansion was driven by newer strains (ie, sequence types 801 and 15603). Breakthrough infections and vaccine failure rates were similar in children eligible for the 1 + 1 (1·08 per 100 000 person-years) and 2 + 1 (0·76 per 100 000 person-years; IRR 1·42, 95% CI 0·78-2·49; p=0·20) PCV13 schedules. Overall, IPD incidence in England was lower in 2022-23, 2 years after removal of pandemic restrictions, than in 2019-20. Breakthrough and vaccine failure rates were not significantly different between children who received the 1 + 1 compared with the 2 + 1 PCV13 immunisation schedule. The post-pandemic increase in childhood IPD incidence and especially PCV13-type IPD will require close monitoring. None.

Cost-effectiveness of the 20-valent pneumococcal conjugate vaccine versus the 23-valent pneumococcal polysaccharide vaccine for older adults in South Korea

BackgroundDespite the demonstrated immunogenicity and safety of the 20-valent pneumococcal conjugate vaccine (PCV20) in older adults, the cost-effectiveness of the PCV20 was not examined compared to the 23-valent pneumococcal polysaccharide vaccine (PPSV23) in South Korea. Therefore, this study aimed to evaluate the cost-effectiveness of PCV20 compared with PPSV23 in adults aged 65 years and older in South Korea. MethodsWe constructed a Markov model that included susceptible states, invasive pneumococcal disease (IPD), non-bacteremic pneumonia (NBP), and death. The population was categorized by disease risk status (low risk, moderate risk, and high risk) and age group (65–74/75–84/85–99 years) at model entry. The annual incidence and mortality of IPD and NBP associated with PCV20 and PPSV23 were estimated based on serotype coverage, vaccine coverage, and vaccine effectiveness. The disease costs and utilities were obtained from previous studies. The incremental cost-effectiveness ratio (ICER) was used to evaluate cost-effectiveness within the threshold of 16,824 USD per quality-adjusted life-year (QALY). ResultsAmong the total population (n = 8,843,072), PCV20 prevented 1941 and 50,575 cases of IPDs and NBPs, respectively, and 898 and 8593 deaths due to IPDs and NBPs compared to PPSV23. The total medical cost per person was 12.11 USD higher in PCV20, with a gain of 0.0053 LYs and 0.0045 QALYs per person. The ICER for PCV20 and PPSV23 was 2270 USD/LY and 2677 USD/QALY. ConclusionsIn South Korea, PCV20 is a cost-effective option compared with PPSV23 for adults aged 65 years and older. These cost-effectiveness results provide evidence for decision-making regarding the approval and National Immunization Program implementation of PCV20.

Long-term surveillance of invasive pneumococcal disease: The impact of 10-valent pneumococcal conjugate vaccine in the metropolitan region of Salvador, Brazil

BackgroundIn 2010, Brazil introduced the ten-valent pneumococcal conjugate vaccine (PCV10) in the national infant immunization program. Limited data on the long-term impact of PCV10 are available from lower-middle-income settings. We examined invasive pneumococcal disease (IPD) in Salvador, Bahia, over 11 years. MethodsProspective laboratory-based surveillance for IPD was carried out in 9 hospitals in the metropolitan region of Salvador from 2008 to 2018. IPD was defined as Streptococcus pneumoniae cultured from a normally sterile site. Serotype was determined by multiplex polymerase chain reaction and/or Quellung reaction. Incidence rates per 100,000 inhabitants were calculated for overall, vaccine-type, and non-vaccine-type IPD using census data as the denominator. Incidence rate ratios (IRRs) were calculated to compare rates during the early (2010–2012), intermediate (2013–2015), and late (2016–2018) post-PCV10 periods in comparison to the pre-PCV10 period (2008–2009). ResultsPre-PCV10, overall IPD incidence among all ages was 2.48/100,000. After PCV10 introduction, incidence initially increased (early post-PCV10 IRR 3.80, 95% CI 1.18–1.99) and then declined to 0.38/100,000 late post-PCV10 (IRR 0.15; 95% CI 0.09–0.26). The greatest reductions in the late post-PCV10 period were observed in children aged ≤2 years, with no cases (IRR not calculated) and those ≥60 years (IRR 0.11, 95% CI 0.03–0.48). Late post-PCV10, significant reductions were observed for both PCV10 serotypes (IRR 0.02; 95% CI 0.0–0.15) and non-PCV10 serotypes (IRR 0.27; 95%CI 0.14–0.53). Non-PCV10 serotypes 15B, 12F, 3, 17F, and 19A became predominant late post-PCV10 without a significant increase in serotype-specific IPD incidence compared to pre-PCV10. ConclusionSignificant declines in IPD, including among adults not eligible for vaccination, suggest direct and indirect protection up to nine years after PCV10 introduction, without evidence of significant replacement disease. Continued surveillance is needed to monitor changes in non-vaccine serotypes and inform decisions about introducing higher valent PCVs.

Invasive Pneumococcal Disease After 2 Decades of Pneumococcal Conjugate Vaccine Use.

We sought to describe the evolving epidemiology of invasive pneumococcal disease (IPD) among children in Massachusetts, United States, over the last 2 decades during which sequential 7-valent pneumococcal conjugate vaccines (PCV7) and 13-valent PCVs (PCV13) were implemented. Cases of IPD in children aged <18 years were detected between 2002 and 2021 through an enhanced population-based, statewide surveillance system. Streptococcus pneumoniae isolates from normally sterile sites were serotyped and evaluated for antimicrobial susceptibility. IPD incidence rates and rate ratios with 95% confidence intervals (CIs) were calculated. We identified 1347 IPD cases. Incidence of IPD in children aged <18 years declined 72% over 2 decades between 2002 and 2021 (incidence rate ratios 0.28, 95% CI 0.18-0.45). IPD rates continued to decline after replacement of PCV7 with PCV13 (incidence rate ratios 0.25, 95% CI 0.16-0.39, late PCV7 era [2010] versus late PCV13 era [2021]). During the coronavirus disease 2019 pandemic years, 2020 to 2021, the rate of IPD among children aged <18 years reached 1.6 per 100 000, the lowest incidence observed over the 20 years. In PCV13 era, approximately one-third of the IPD cases in children aged >5 years had at least 1 underlying condition (98, 30.3%). Serotypes 19A and 7F contributed 342 (48.9%) of all cases before implementation of PCV13 (2002-2010). Serotype 3 (31, 8.6%), and non-PCV13 serotypes 15B/C (39, 10.8%), 33F (29, 8.0%), 23B (21, 0.8%), and 35B (17, 4.7%) were responsible for 37.8% of cases in PCV13 era (2011-2021). Penicillin nonsusceptibility continued to decline (9.8% vs 5.3% in pre-/late PCV13 era, P = .003), however has become more common among non-PCV13 serotypes compared with vaccine serotypes (14.8% vs 1.4%, P < .001). Robust ongoing surveillance networks are critical for identifying emerging serotypes and development of next-generation vaccine formulations.

Effectiveness of ten-valent pneumococcal conjugate vaccine on invasive pneumococcal disease among children

The 10-valent pneumococcal conjugate vaccine (PCV10) was introduced in March 2015 in Bangladesh. In this study, we aimed to estimate the impact of PCV10 on invasive pneumococcal disease (IPD) identified by blood cultures and severe pneumonia identified clinically and its effectiveness on invasive disease caused by vaccine serotypes.We conducted population-based surveillance among children aged 2- <24 months between April 2012 through March 2019 in Mirzapur, a rural sub-district of Bangladesh. We compared incidence of IPD and severe pneumonia before (April 2012 to March 2015) and after (April 2015 to March 2019) the introduction of PCV10. Vaccine effectiveness was measured using an indirect cohort analysis of data from four sentinel sites in which PCV10 vaccination status was compared between children with IPD caused by vaccine serotype vs. non-vaccine serotypes.We identified 24 IPD cases by blood culture and 1,704 severe pneumonia hospitalizations during the surveillance period. IPD incidence in under-2-year-old children fell 25 % (95 % CI: −1.2 % to 76 %; p-value = 0.59) from 106 cases per 100,000 child-years at baseline to 79.3 in April 2018- March 2019. Vaccine serotype-IPD incidence was lower (77 % reduction, 95 % CI: −0.45 % to 96 %; p-value = 0.068) in April 2018 - March 2019 than in the pre-vaccine period (85.7 cases to 19.8/100,000 child-years). A significant decline of 54.0 % (95 % CI: 47.0 % to 59.0 %; p-value < 0.001) was observed in hospitalizations due to severe pneumonia. From indirect cohort analysis, the effectiveness of PCV10 against vaccine serotype IPD was 37 % (95 % CI: −141.0 % to 83.5 %; p = 0.5) after the 1st dose and 63.1 % (95 % CI: −3.3 % to 85.9 %, p = 0.0411) after the 2nd or the 3rd dose.This study demonstrates that PCV10 introduction prevented hospitalizations with severe pneumonia and provided individual protection against vaccine serotypes.

Age-Specific Resurgence in Invasive Pneumococcal Disease Incidence in the COVID-19 Pandemic Era and Its Association With Respiratory Virus and Pneumococcal Carriage Dynamics: A Time-Series Analysis.

Using multiple national surveillance systems, we found an increase in the incidence of invasive pneumococcal disease during after the relaxation of non-pharmaceutical interventions against COVID-19, which strongly varied by age. Age groups with higher incidence of respiratory syncytial virus and influenza also experienced higher increase in invasive pneumococcal disease incidence, with no change in pneumococcal carriage.

Pneumococcal Vaccine Breakthrough and Failure in Infants and Children: A Narrative Review.

Globally, Streptococcus pneumoniae is a leading cause of vaccine-preventable morbidity and mortality in infants and children. In recent decades, large-scale pediatric immunization programs have substantially reduced the incidence of invasive pneumococcal disease. Despite this, residual vaccine-type pneumococcal disease remains in the form of vaccine breakthrough and vaccine failure. This targeted literature review aims to discuss aspects of vaccine breakthrough and failure in infants and children, including disease epidemiology, clinical presentation, risk factors, vaccination schedules, vaccine serotypes, correlates of protection, comorbidities, disease surveillance, and potential implications for future vaccine development.

Genomic analysis of penicillin-binding proteins and recombination events in an emerging amoxicillin- and meropenem-resistant PMEN3 (Spain9V-3, ST156) variant in Taiwan and comparison with global descendants of this lineage.

From 2008 to 2020, the Taiwan National Notifiable Disease Surveillance System database demonstrated that the incidence of non-vaccine serotype 23A invasive pneumococcal disease (IPD) approximately doubled. In this study, 276 non-repetitive pneumococcal clinical isolates were collected from two medical centers in Taiwan between 2019 and 2021. Of these 267 pneumococci, 60 were serotype 23A. Among them, 50 (83%) of serotype 23A isolates belonged to the sequence type (ST) 166 variant of the Spain9V-3 clone. Pneumococcal 23A-ST166 isolates were collected to assess their evolutionary relationships using whole-genome sequencing. All 23A-ST166 isolates were resistant to amoxicillin and meropenem, and 96% harbored a novel combination of penicillin-binding proteins (PBPs) (1a:2b:2x):15:11:299, the newly identified PBP2x-299 in Taiwan. Transformation of the pbp1a, pbp2b, and pbp2x alleles into the β-lactam-susceptible R6 strain revealed that PBP2x-299 and PBP2b-11 increased the MIC of ceftriaxone and meropenem by 16-fold, respectively. Prediction analysis of recombination sites in PMEN3 descendants (23A-ST166 in Taiwan, 35B-ST156 in the United States, and 11A-ST838/ST6521 in Europe) showed that adaptive evolution involved repeated, selectively favored convergent recombination in the capsular polysaccharide synthesis region, PBPs, murM, and folP genome sites. In the late 13-valent pneumococcal conjugate vaccine era, PMEN3 continuously displayed an evolutionary capacity for global dissemination and persistence, increasing IPD incidence, leading to an offset in the decrease of pneumococcal conjugate vaccine serotype-related diseases, and contributing to high antibiotic resistance.A clonal shift with a highly β-lactam-resistant non-vaccine serotype 23A, from ST338 to ST166, increased in Taiwan. ST166 is a single-locus variant of the Spain9V-3 clone, which is also called the PMEN3 lineage. All 23A-ST166 isolates, in this study, were resistant to amoxicillin and meropenem, and 96% harbored a novel combination of penicillin-binding proteins (PBPs) (1a:2b:2x):15:11:299. PBP2x-299 and PBP2b-11 contributed to the increasing MIC of ceftriaxone and meropenem, respectively. Prediction analysis of recombination sites in PMEN3 descendants showed that adaptive evolution involved repeated, selectively favored convergent recombination in the capsular polysaccharide synthesis region, PBPs, murM, and folP genome sites. In the late 13-valent pneumococcal conjugate vaccine era, PMEN3 continuously displays the evolutionary capacity for dissemination, leading to an offset in the decrease of pneumococcal conjugate vaccine serotype-related diseases and contributing to high antibiotic resistance.

Invasive Pneumococcal Disease and Potential Impact of Pneumococcal Conjugate Vaccines Among Adults, Including Persons Experiencing Homelessness-Alaska, 2011-2020.

Adults aged ≥65 years, adults with certain underlying medical conditions, and persons experiencing homelessness are at increased risk for invasive pneumococcal disease (IPD). Two new pneumococcal conjugate vaccines, 15-valent pneumococcal conjugate vaccine (PCV15) and 20-valent pneumococcal conjugate vaccine (PCV20), were recently approved for use in US adults. We describe the epidemiology of IPD among Alaska adults and estimate the proportion of IPD cases potentially preventable by new vaccines. We used statewide, laboratory-based surveillance data to calculate and compare IPD incidence rates and 95% confidence intervals (CIs) among Alaska adults aged ≥18 years during 2011-2020 and estimate the proportion of IPD cases that were caused by serotypes in PCV15 and PCV20. During 2011-2020, 1164 IPD cases were reported among Alaska adults for an average annual incidence of 21.3 cases per 100 000 adults per year (95% CI, 20.1-22.5). Incidence increased significantly during the study period (P < .01). IPD incidence among Alaska Native adults was 4.7 times higher than among non-Alaska Native adults (95% CI, 4.2-5.2). Among adults experiencing homelessness in Anchorage, IPD incidence was 72 times higher than in the general adult population (95% CI, 59-89). Overall, 1032 (89%) Alaska adults with IPD had an indication for pneumococcal vaccine according to updated vaccination guidelines; 456 (39%) and 700 (60%) cases were caused by serotypes in PCV15 and PCV20, respectively. Use of PCV15 and PCV20 could substantially reduce IPD among adults in Alaska, including Alaska Native adults and adults experiencing homelessness.

Penicillin Prophylaxis in Patients With Sickle Cell Disease Beyond Age 5 Years.

Patients with sickle cell disease (SCD) are at increased risk for invasive pneumococcal disease (IPD) caused by Streptococcus pneumoniae. Immunization and antimicrobial prophylaxis may prevent this complication, and landmark clinical trials support discontinuation of antimicrobial prophylaxis at age 5 years. However, antimicrobial prophylaxis continues in some patients indefinitely. The objective of this study was to evaluate the incidence of culture-positive IPD and other infections in the setting of penicillin prophylaxis in the pediatric SCD population. This was a single-center, retrospective cohort study of patients with SCD who continued antimicrobial prophylaxis with penicillin, compared with those whose antimicrobial prophylaxis was discontinued. Included patients were aged 5 to 18 years during the study period and had no history of IPD or surgical splenectomy. Patient charts were reviewed for demographics, immunizations, penicillin prescription history, and microbiologic culture data. Antimicrobial prophylaxis continued beyond age 5 years in 65% of patients, a higher percentage of whom had hemoglobin SS or S beta-zero disease. No patients whose antimicrobial prophylaxis was discontinued experienced IPD; 1 patient who continued antimicrobial prophylaxis died of S pneumoniae sepsis. Rates of other infections were comparable between groups (21% in prophylaxis versus 18% in no prophylaxis). These results support appropriate de-prescribing of antimicrobial prophylaxis in patients with SCD who are not at high risk for IPD. Further multicenter studies are needed to evaluate consequences of antimicrobial prophylaxis with alternative agents on antibiotic resistance, examine provider rationale for continuation of antimicrobial prophylaxis, and assess quality of life effects (e.g., medication adherence, adverse drug reactions) of antimicrobial prophylaxis.

Changes in Invasive Pneumococcal Disease in the Paediatric Population in the Second COVID-19 Pandemic Year.

Incidence of invasive pneumococcal disease (IPD) decreased worldwide in 2020, coinciding with the implementation of measures to reduce COVID-19 transmission. We evaluated the impact of the COVID-19 pandemic on healthcare demand and IPD in children in 2021 compared to the pre-pandemic period (2018-2019) and the early pandemic period (2020) in a study carried out during 2018-2021 in Catalonia. Incidence rates were compared by calculating the incidence rate ratio (IRR), and expressing percentage changes in IRR as (1-IRR)x100. Compared to 2018-2019, emergency room (ER) visits declined by 21% in 2021 (p < 0.001), mainly in the first quarter (-39%), and compared to 2020, ER visits increased by 22% in 2021 (p < 0.001), except in the first quarter. IPD incidence overall was 11.0 in 2018-2019 and 4.6 in 2021 (-58%, p < 0.001); the reduction in incidence was similar in the 0-4 age group and was higher in the first quarters. Compared to 2020, in 2021, IPD incidence decreased during the first quarter (-86%, p < 0.001), but increased from 0.0 to 1.2 in the second quarter (p = 0.02) and from 0.6 to 2.1 (p=0.03) in the fourth quarter. The decreased IPD incidence observed in 2021 compared to 2018-2019 (most especially in the first quarter) was greater than the decrease in healthcare demand and PCR test requests. Compared to 2020, IPD incidence decreased in the first quarter when a second state of alarm was in force. In 2021, compared to 2018-2019, there was a greater reduction in PCV13 serotypes than in non-PCV13 serotypes.

Pneumococcal infections in children with sickle cell disease before and after pneumococcal conjugate vaccines

AbstractChildren with sickle cell disease (SCD) are at increased risk of invasive pneumococcal disease (IPD). Over 25 years, the Georgia Emerging Infections Program/Centers for Disease Control and Prevention Active Bacterial Core Surveillance network identified 104 IPD episodes among 3707 children with hemoglobin SS (HbSS) or HbSC aged <10 years, representing 6% of IPD in Black or African American children residing in Metropolitan Atlanta (reference population). Children with IPD and HbSS/SC were older than those with IPD in the reference population (P < .001). From 1994-1999 to 2010-2018, IPD declined by 87% in children with HbSS aged 0 to 4 years, and by 80% in those aged 5 to 9 years. However, IPD incidence rate ratios when comparing children with SCD with the reference population increased from 20.2 to 29.2 over these periods. Among children with HbSS and IPD, death declined from 14% to 3% after 2002, and meningitis declined from 16% to 8%. Penicillin resistance was more prevalent in children with SCD before 7-valent pneumococcal conjugate vaccine (PCV7) licensure. After 2010, all IPD serotypes were not included in the 13-valent PCV (PCV13). Within 3 years of vaccination, the effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) against non-PCV13 serotypes included in PPSV23 plus 15A/15C was 92% (95% confidence interval, 40.8- 99.0, P = .014; indirect-cohort effect adjusted for age and hydroxyurea). PPSV23 would cover 62% of non-PCV13 serotype IPD in children with SCD, whereas PCV15, PCV20, and PCV21/V116 (in development) could cover 16%, 51%, and 92%, respectively. Although less frequent, IPD remains a life-threatening risk in children with SCD. Effective vaccines with broader coverage could benefit these children.

Impact of the progressive uptake of pneumococcal conjugate vaccines on the epidemiology and antimicrobial resistance of invasive pneumococcal disease in Gipuzkoa, northern Spain, 1998-2022.

To analyze the impact of pneumococcal conjugate vaccines (PCVs) on the incidence of invasive pneumococcal diseases (IPDs) and pneumococcal antibiotic resistance in Gipuzkoa, northern Spain for a 25 years period. All cases of IPD confirmed by culture between 1998 and 2022 in a population of around 427,416 people were included. Pneumococci were serotyped and antimicrobial susceptibility was assessed by the EUCAST guidelines. Overall, 1,516 S. pneumoniae isolates were collected. Annual IPD incidence rates (per 100,000 people) declined from 19.9 in 1998-2001 to 11.5 in 2017-19 (42.2% reduction), especially in vaccinated children (from 46.7 to 24.9) and non-vaccinated older adult individuals (from 48.0 to 23.6). After PCV13 introduction, the decrease in the incidence of infections caused by PCV13 serotypes was balanced by the increase in the incidence of non-PCV13 serotypes. In the pandemic year of 2020, IPD incidence was the lowest: 2.81. The annual incidence rates of penicillin-resistant isolates also decreased, from 4.91 in 1998-2001 to 1.49 in 2017-19 and 0.70 in 2020. Since 2017, serotypes 14, 19A, and 11A have been the most common penicillin-resistant types. The incidence of erythromycin-resistant strains declined, from 3.65 to 1.73 and 0.70 in the same years. PCV use was associated with declines in the incidence of IPD and the spread of non-vaccine serotypes, that balanced the beneficial effect off PCV13, some of them showing high rates of antibiotic resistance.