Burden Of Invasive Pneumococcal Disease Research Articles

Understanding healthcare providers' preferred attributes of pediatric pneumococcal conjugate vaccines in the United States.

As higher-valent pneumococcal conjugate vaccines (PCVs) become available for pediatric populations in the US, it is important to understand healthcare provider (HCP) preferences for and acceptability of PCVs. US HCPs (pediatricians, family medicine physicians and advanced practitioners) completed an online, cross-sectional survey between March and April 2023. HCPs were eligible if they recommended or prescribed vaccines to children age <24 months, spent ≥25% of their time in direct patient care, and had ≥2 y of experience in their profession. The survey included a discrete choice experiment (DCE) in which HCPs selected preferred options from different hypothetical vaccine profiles with systematic variation in the levels of five attributes. Relative attribute importance was quantified. Among 548 HCP respondents, the median age was 43.2 y, and the majority were male (57.9%) and practiced in urban areas (69.7%). DCE results showed that attributes with the greatest impact on HCP decision-making were 1) immune response for the shared serotypes covered by PCV13 (31.4%), 2) percent of invasive pneumococcal disease (IPD) covered by vaccine serotypes (21.3%), 3) acute otitis media (AOM) label indication (20.3%), 4) effectiveness against serotype 3 (17.6%), and 5) number of serotypes in the vaccine (9.5%). Among US HCPs, the most important attribute of PCVs was comparability of immune response for PCV13 shared serotypes, while the number of serotypes was least important. Findings suggest new PCVs eliciting high immune responses for serotypes that contribute substantially to IPD burden and maintaining immunogenicity against serotypes in existing PCVs are preferred by HCPs.

Clinical and economic burden of invasive pneumococcal disease and noninvasive all-cause pneumonia in hospitalized US adults: A multicenter analysis from 2015 to 2020

To evaluate the clinical and economic outcomes in adults hospitalized with invasive pneumococcal disease (IPD) and noninvasive all-cause pneumonia (ACP) overall and by antimicrobial resistance (AMR) status. Hospitalized adults from the BD Insights Research Database with an ICD10 code for IPD, noninvasive ACP or a positive Streptococcus pneumoniae culture/urine antigen test were included. Descriptive statistics and multivariable analyses were used to evaluate outcomes (in-hospital mortality, length of stay [LOS], cost per admission, and hospital margin [costs - payments]). The study included 88,182 adult patients at 90 US hospitals (October 2015-February 2020). Most (98.6%) had noninvasive ACP and 40.2% were <65 years old. Of 1450 culture-positive patients, 37.7% had an isolate resistant to ≥1 antibiotic class. Observed mortality, median LOS, cost per admission, and hospital margins were 8.3%, 6 days, $9791, and $11, respectively. Risk factors for mortality included ≥50 years of age, higher risk of pneumococcal disease (based on chronic or immunocompromising conditions), and intensive care unit admission. Patients with IPD had similar mortality rates and hospital margins compared with noninvasive ACP, but greater costs per admission and LOS. IPD and noninvasive ACP are associated with substantial clinical and economic burden across all adult age groups. Expanded pneumococcal vaccination programs may help reduce disease burden and decrease hospital costs.

High Prevalence of Novel Sequence Types in Streptococcus pneumoniae That Caused Invasive Diseases in Kuwait in 2018.

Multilocus sequence typing (MLST) is used to gain insight into the population genetics of bacteria in the form of sequence type (ST). MLST has been used to study the evolution and spread of virulent clones of Streptococcus pneumoniae in many parts of the world. Such data for S. pneumoniae are lacking for the countries of the Arabian Peninsula, including Kuwait. We determined the STs of all 31 strains of S. pneumoniae from invasive diseases received at a reference laboratory from various health centers in Kuwait during 2018 by MLST. The relationship among the isolates was determined by phylogenetic analysis. We also determined the serotypes by Quellung reaction, and antimicrobial susceptibility by Etest, against 15 antibiotics belonging to 10 classes. There were 28 STs among the 31 isolates, of which 14 were new STs (45.2%) and 5 were rare STs (16.1%). Phylogenetic analysis revealed that 26 isolates (83.9%) were unrelated singletons, and the Kuwaiti isolates were related to those from neighboring countries whose information was gleaned from unpublished data available at the PubMLST website. Many of our isolates were resistant to penicillin, erythromycin, and azithromycin, and some were multidrug-resistant. Virulent serotype 8-ST53, and serotype 19A with new STs, were detected. Our study detected an unusually large number of novel STs, which may indicate that Kuwait provides a milieu for the evolution of novel STs. Novel STs may arise due to recombination and can result in capsular switching. This can impact the effect of vaccination programs on the burden of invasive pneumococcal disease. This first report from the Arabian Peninsula justifies the continuous monitoring of S. pneumoniae STs for the possible evolution of new virulent clones and capsular switching.

Potential Impact of Higher-Valency Pneumococcal Conjugate Vaccines Among Adults in Different Localities in Germany.

Next-generation pneumococcal conjugate vaccines (PCVs) have been approved for use. The serotype distribution of pneumococcal isolates can vary between regions. To understand the potential impacts of new PCVs, we evaluated trends in invasive pneumococcal disease (IPD) among adults in Germany at a local level using Bayesian hierarchical logistic regression. There was little spatial variation in IPD cases caused by 13-valent PCV serotypes, which dropped from 60% of IPD cases in 2006 to 30% in 2018. More than half of IPD cases in 2018 were attributable to serotypes covered by new PCVs (15-valent and 20-valent PCVs), which suggests they could further reduce the burden of IPD.

2593. Epidemiology and Clinical Burden of Invasive Pneumococcal Disease in Older Adults in the City of São Paulo, Brazil

Abstract Background The Brazilian National Immunization Program currently provides pneumococcal vaccination for children and high-risk adults. However, the burden of invasive pneumococcal disease (IPD) remains poorly described, especially among older adults. We evaluated the incidence, demographics, clinical characteristics, and outcomes among older adults hospitalized with IPD in São Paulo (SP), the largest city in Brazil. Methods Retrospective chart review of adults ≥ 60y hospitalized with IPD at three tertiary teaching hospitals from January 2016 to December 2018. Incidence was determined, only for people living in SP, using as numerator the number of IPD cases at study hospitals and as denominator the proportion of admissions at study hospitals considering the whole SP public system among people ≥ 60 living in SP. Demographic and clinical data were described for all patients with information. Results Ninety-four patients were included: 98.9% had ≥ 1 selected risk factor (most frequent: cancer, 68.2%), and 90% had unknown vaccination status (Table 1). The 3-year incidence was 121.8 per 100,000 people (60-74y: 117.6 and ≥ 75y: 132.6), while annual incidences per 100,000 people were 47.5 in 2016, 40.1 in 2017, and 34.2 in 2018. Most patients had community-onset disease (89.4%) and the main presentation was bacteremic pneumonia (68.1%), followed by meningitis (10.6%). The median hospitalization length was 10 days, 53.4% of patients had ICU stay (median duration of 7 days). About 22.2% had antimicrobial resistance to more than one class. During hospitalization, 85.1% of patients had ≥ 1 complication (Figure 1), 32.3% developed septic shock, 63.8% required supplemental oxygen, and 36.2% required mechanical ventilation (median: 5 days). In-hospital mortality was 42.6% and, among survivors (n=54), 20.4% reported sequelae (mostly chronic respiratory failure). Demographic and clinical characteristics of older adults with invasive pneumococcal disease, São Paulo city, 2016-2018 (n=94) Complications during hospitalization due to of invasive pneumococcal disease Note: Percentages calculated for all included patients. CNS, central nervous system. (a) More than one complication possible per patient. Only complications with frequency ≥10% are described. (b) Median (range) duration of mechanical ventilation support: 5 (1-28) days. Conclusion This study showed a high burden of IPD in older adults, with higher incidence than reported for other countries such as the USA (26 /100,000 people ≥ 65 y in 2018) or Chile (12.1 /100,000 people ≥ 65y in 2018). The important rates of morbidity and mortality, and a considerable burden on healthcare resources support the importance to expand and improve pneumococcal prevention for older population in Brazil. Disclosures Licieri Figueiredo, MD, MSD Brazil: This is an employee of the MSD company leading the study Cícera P. Marcelino, n/a, MSD LATAM: This is an employee of the MSD company responsible for the management and operation of the study Paula M. Batista, n/a, MSD LATAM: This is an employee of the MSD company responsible for the management and operation of the study Marina D N Paula, n/a, MSD Brazil: This is an employee of the MSD company who is the leader of the therapeutic area of the study Thais Moreira, MD, MSc, MSD LATAM: This is an employee of the MSD company that provides scientific support for the study regionally

Streptococcus pneumoniae serotype 19A in hospitalized children with invasive pneumococcal disease after the introduction of conjugated vaccines in Lima, Peru

BackgroundThe Pneumococcal conjugate vaccine (PCV) has decreased cases of invasive pneumococcal disease (IPD) worldwide. However, the impact of PCVs introduction may be affected by the serotype distribution in a specific context. MethodsCross-sectional multicenter passive surveillance study of IPD cases in pediatric patients hospitalized in Lima, Peru between 2016 and 2019 (after PCV13 introduction) to determine the serotype distribution and antimicrobial resistance of Streptococcus pneumoniae. Serotyping was performed by a sequential multiplex PCR and confirmed by whole genome sequencing. ResultsEighty-five S. pneumoniae isolates were recovered (4.07/100,000 among children <60 months of age). Serotype 19A was the most common (49.4%). Children infected with serotype 19A in comparison with children infected with other serotypes were younger, had a lower rate of meningitis and higher rates of pneumonia, complicated pneumonia and antimicrobial resistance; 28.6% of patients with serotype 19A have received at least one dose of PCV13 vs. 62.8% of patients with other serotypes. Using MIC-breakpoints, 81.2% (56/69) of non-meningitis strains and 31.2% (5/16) of meningitis strains were susceptible to penicillin; 18.8% (3/16) of meningitis strains had intermediate resistance to ceftriaxone. Resistance to azithromycin was 78.8% (67/85). Serotype 19A frequency increased over time in the same study population, from 4.2% (4/96) in 2006–2008, to 8.6% (5/58) in 2009–2011, to 49.4% (42/85) in the current study (2016–2019) (p < 0.001). ConclusionsAfter PCV13 introduction in Peru, serotype 19A remains the most prevalent; however, the vaccination coverage is still not optimal. Therefore, additonal surveillance studies are needed to determine the remaining IPD burden.

Molecular characterization of invasive Streptococcus pneumoniae clinical isolates from a tertiary children's hospital in eastern China.

Streptococcus pneumoniae is a common opportunistic pathogen that causes invasive pneumococcal disease (IPD), especially in children. This study aimed to determine the prevalence and molecular characteristics of S. pneumoniae isolated from children with IPD. A total of 78 S. pneumoniae isolates from aseptic body fluids of 70 IPD patients were collected at the Children's Hospital of Nanjing Medical University (Jiangsu Province, China) during 2017-2021. Whole-genome sequencing technology was used to analyze the serotype, sequence type (ST), virulence, and antibiotic resistance of the 78 invasive S. pneumoniae clinical isolates. Our results showed that the pneumococcal infection rate declined after the COVID-19 outbreak in 2019. Serotypes 19F, 14, 6A, 23F, 19A, and 6B were the most common strains. The pneumococcal conjugate vaccine (PCV) 13 serotype coverage rate was 87.1%. All isolates were classified by multi-locus sequence typing (MLST) analysis into 27 different STs, including 3 novel STs (ST17941, ST17942, and ST17944) and 1 novel allele [recP (558)]. The most predominant ST was ST271, followed by ST320 and ST876. All isolates carried the following virulence genes: cbpG, lytB, lytC, pce (cbpE), pavA, slrA, plr (gapA), hysA, nanA, eno, piuA, psaA, cppA, iga, htrA (degP), tig (ropA), zmpB, and ply. All isolates were multidrug resistant and had high levels of resistance to macrolides, tetracyclines, and sulfonamides. Taken together, this study revealed extensive genetic diversity among S. pneumoniae isolates from a single Chinese hospital. Wearing masks, universal infant vaccination with PCV13, and the launch of recombinant protein vaccine development programs could reduce the burden of IPD in children. IMPORTANCE Invasive pneumococcal disease (IPD) caused by Streptococcus pneumoniae in children remains a global burden and should be given more attention due to the fact that the pneumococcal vaccine is not fully covered globally. The molecular epidemiological characteristics of S. pneumoniae are not so clear, especially in these years of COVID-19. In this study, we collected S. pneumoniae isolates from the aseptic body fluid of children with IPD from 2017 to 2021 in a tertiary children's hospital in China and revealed the extensive genetic diversity of these isolates. Most importantly, we first found that the rate of pneumococcal infection has declined since the COVID-19 outbreak in 2019, which means that wearing masks could reduce the transmission of S. pneumoniae. In addition, it was shown that universal infant vaccination with PCV13 seems essential for reducing the burden of IPD in children.

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.

Decreased Pneumococcal Carriage Among Older Adults in Denmark During the COVID-19 Lockdown.

COVID-19 containment measures reduced the burden of invasive pneumococcal disease. Data on pneumococcal carriage rates among adults during the pandemic are scarce. Naso- and oropharyngeal swabs and questionnaires were collected during January 2019 to December 2021 from adults ≥64 years of age. Carriage was determined by lytA/piaB PCR. A total of 1556 participants provided paired naso- and oropharyngeal swabs. Their median age was 74 years (IQR, 70-79). Streptococcus pneumoniae DNA was detected in 146 (9.4%) oropharyngeal swabs and 34 (2.2%) nasopharyngeal. The carriage rate decreased from 12.9% (95% CI, 10.1%-16.1%, n = 66/511) prelockdown (January 2019-February 2020) to 4.2% (95% CI, 2.0%-7.5%, n = 10/240) during lockdown (March 2020-February 2021) and increased to 12.1% (95% CI, 9.8%-14.7%, n = 87/719) with the reopening of society (March 2021-December 2021; P = .0009). Pneumococcal carriage prevalence declined significantly during pandemic mitigation measures and rebounded to prepandemic levels as measures were lifted.

Invasive pneumococcal disease among the elderly in the later era of paediatric pneumococcal conjugate vaccination-A longitudinal study over 10 years based on public surveillance data in the Nordics.

Pneumococcal conjugate vaccines (PCVs) have proven effective in preventing both non-invasive and invasive pneumococcal disease (IPD) in small children and in older age groups. However, long-term observations and country comparisons of IPD incidence in the elderly following introduction of PCVs in paediatric national immunisation programmes (NIPs) are scarce. We aimed to estimate and compare incidence of IPD in the elderly in Denmark, Finland, Norway, and Sweden over a 10-year time span. During the study period Denmark and Norway used PCV13 in their paediatric NIP, Sweden both PCV10 and PCV13 and Finland used PCV10. Uptake of pneumococcal vaccines for the elderly was low. We collected longitudinal data on confirmed IPD cases and their serotypes among elderly people (aged ≥65 years) 2010-2019 in the four countries of interest. Annual IPD incidence rates were calculated per country, by vaccine-associated serotypes (PCV10, PCV13, PCV15, PCV20 and PPV23) and for non-vaccine serotypes. A regression model was used to estimate average annual change in incidence in each country. Incidence rates of IPD in the elderly in 2019 ranged from 31.4 to 41.8 per 100,000 people across the countries. Denmark and Norway showed an annual average decline in IPD incidence (-3.3; 95% CI: -5.6 to -1.1; p<0.01) and (-3.3; 95% CI: -5.5 to -1.0; p<0.01) respectively from 2010 to 2019, whereas no change was seen for Sweden (-0.5; 95% CI: -1.9 to 0.8; p = 0.39) or Finland (0.9; 95% CI: -1.0 to 2.7; p = 0.32). IPD incidence due to emerging serotypes, e.g., serotypes 8 and 12F, has increased. Serotype 19A remained a major cause of IPD in countries with PCV10 in paediatric NIPs. Despite paediatric PCV programmes, a considerable vaccine preventable IPD burden remains in the elderly. Further, choice of PCV in paediatric programs was associated with differences in serotype distribution and incidence amongst the elderly. Direct vaccination of the elderly with recently approved broad coverage PCVs holds promise for meaningful impact on disease burden with PCV20 covering a majority of IPD amongst the elderly in the four studied countries. Effectiveness of new vaccines in real-life clinical practice should be followed.

Optimal age targeting for pneumococcal vaccination in older adults; a modelling study

Invasive pneumococcal disease (IPD) risk increases with age for older adults whereas the population size benefiting from pneumococcal vaccines and robustness of immunogenic response to vaccination decline. We estimate how demographics, vaccine efficacy/effectiveness (VE), and waning VE impact on optimal age for a single-dose pneumococcal vaccination. Age- and vaccine-serotype-specific IPD cases from routine surveillance of adults ≥ 55 years old (y), ≥ 4-years after infant-pneumococcal vaccine introduction and before 2020, and VE data from prior studies were used to estimate IPD incidence and waning VE which were then combined in a cohort model of vaccine impact. In Brazil, Malawi, South Africa and England 51, 51, 54 and 39% of adults older than 55 y were younger than 65 years old, with a smaller share of annual IPD cases reported among < 65 years old in England (4,657; 20%) than Brazil (186; 45%), Malawi (4; 63%), or South Africa (134, 48%). Vaccination at 55 years in Brazil, Malawi, and South Africa, and at 70 years in England had the greatest potential for IPD prevention. Here, we show that in low/middle-income countries, pneumococcal vaccines may prevent a substantial proportion of residual IPD burden if administered earlier in adulthood than is typical in high-income countries.

Mathematical modeling of pneumococcal transmission dynamics in response to PCV13 infant vaccination in Germany predicts increasing IPD burden due to serotypes included in next-generation PCVs.

Two next-generation pneumococcal conjugate vaccines (PCVs), a 15- and a 20-valent PCV (PCV15 and PCV20), have recently been licensed for use in adults, and PCV15 has also been licensed in children. We developed a dynamic transmission model specific for Germany, with the aim to predict carriage prevalence and invasive pneumococcal disease (IPD) burden for serotypes included in these vaccines. The model allows to follow serotype distributions longitudinally both in the absence and presence of PCV vaccinations. We considered eight age cohorts and seven serotype groups according to the composition of different pneumococcal vaccines. This comprises the additional serotypes contained in PCV15 and PCV20 but not in PCV13. The model predicted that by continuing the current vaccine policy (standard vaccination with PCV13 in children and with PPSV23 in adults) until 2031, IPD case counts due to any serotype in children <2 years of age will remain unchanged. There will be a continuous decrease of IPD cases in adults aged 16-59y, but a 20% increase in adults ≥60y. Furthermore, there will be a steady decrease of the proportion of carriage and IPD due to serotypes included in PCV7 and PCV13 over the model horizon and a steady rise of non-PCV13 serotypes in carriage and IPD. The highest increase for both pneumococcal carriage and absolute IPD case counts was predicted for serotypes 22F and 33F (included in both PCV15 and PCV20) and serotypes 8, 10A, 11A, 12F, and 15B (included in PCV20 only), particularly in older adults. Between 2022 and 2031, serotypes included in PCV20 only are expected to cause 19.7-25.3% of IPD cases in adults ≥60y. We conclude that introduction of next-generation PCVs for adults may prevent a substantial and increasing proportion of adult IPDs, with PCV20 having the potential to provide the broadest protection against pneumococcal disease.

Incidence of pneumococcal disease from 2003 to 2019 in children ≤17 years in England

BackgroundPneumococcal disease is a leading cause of communicable disease morbidity and mortality globally. We aimed to estimate invasive pneumococcal disease (IPD), pneumococcal pneumonia (PP) and all-cause pneumonia (ACP) incidence rates (IRs) in children aged 0–17 years in England from 2003 to 2019.MethodsA retrospective study in children ≤17 years old from 2003 to 2019 using the Clinical Practice Research Datalink (CPRD) Gold and Hospital Episodes Statistics Admitted Patient Care (HES APC) databases. IPD episodes were identified in hospital records (HES APC). PP (caused by Streptococcus pneumoniae only) and ACP episodes (caused by any pathogen) were identified in primary care (CPRD) and in hospital records (HES APC). Annual IRs by age-group were calculated as the number of episodes/person-years (PY) at risk, with 95% confidence intervals (95% CI). Interrupted time series analyses were conducted to assess changes in IRs across the post-PCV7 (2007–2009), early post-PCV13 (2011–2014) and late post-PCV13 (2015–2019) periods compared to the pre-PCV7 period (2003–2005) using generalized linear models.Results170 IPD episodes, 769 PP episodes and 12,142 ACP episodes were identified in 1,500,686 children in 2003–2019. The overall IPD, PP and ACP IRs (per 100,000 PY) were 2.29 (95% CI 1.96–2.66), 10.34 (95% CI 9.62–11.10) and 163.37 (95% CI 160.47–166.30), respectively. The highest IPD, PP and ACP IRs were observed in children aged < 2 years compared to older children (2–4 and 5–17 years). IPD IRs decreased between the pre-PCV7 period and the late post-PCV13 period from 3.28 (95% CI 2.42–4.33) to 1.41 (95% CI 0.80–2.29), IRR 0.28 (95% CI 0.09–0.90), p-value 0.033. PP IRs declined between the pre-PCV7 period and the late post-PCV13 period from 14.65 (95% CI 12.77–16.72) to 3.87 (95% CI 2.81–5.20), IRR 0.19 (95% CI 0.09–0.38), p-value < 0.001. ACP IRs declined between the pre-PCV7 period and the late post-PCV13 period from 167.28 (95% CI 160.78–173.96) to 124.96 (95% CI 118.54–131.63), IRR 0.77 (95% CI 0.66–0.88), p-value < 0.001.ConclusionsThe clinical burden of IPD, PP and ACP declined in children in England aged 0–17 years between 2003 and 2019, especially in the late post-PCV13 period. This study highlights the importance of PCV vaccination in reducing the burden of PD and ACP in children in England.

The impact of vaccination on the burden of invasive pneumococcal disease from a nationwide surveillance program in Lebanon: an unexpected increase in mortality driven by non-vaccine serotypes

ABSTRACT Background The impact of pneumococcal conjugate vaccines (PCVs) on the burden of invasive pneumococcal disease (IPD) and serotype distribution was examined across age groups from data collected by the Lebanese Inter-Hospital Pneumococcal Surveillance Program. Methods Between 2005 and 2020, 593 isolates of invasive Streptococcus pneumoniae were collected from 79 hospitals throughout Lebanon. Serotypes and antimicrobial resistance (AMR) profiles were identified, and trends compared over 3 eras: PCV7, post-PCV7/ pre-PCV13, and PCV13 eras. Results The prevalence of PCV7 serotypes decreased significantly from 43.6% in the PCV7 era to 17.8% during the PCV13 era (p<0.001). PCV13-only serotypes remained stable in the PCV13 compared to the post-PCV7 eras, especially serotypes 1 and 3, whereas non-vaccine types (NVT) increased throughout the study period, especially 24 and 16F. The mortality rate increased substantially from 12.5% (PCV7 era) to 24.8% (PCV13 era). A significant decrease in AMR was observed across the three study eras. Conclusion: PCVs have a relative impact on IPD and AMR in vaccinated and unvaccinated populations despite an increase in mortality driven by NVT. Broadening the recommendation of vaccination to include older age-groups, using higher valency vaccines, and implementing stringent antimicrobial stewardship are likely to broaden the impact on the burden of IPD.

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

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

Changing Incidence of Invasive Pneumococcal Disease in Infants Less Than 90 Days of Age Before and After Introduction of the 13-Valent Pneumococcal Conjugate Vaccine in Blantyre, Malawi: A 14-Year Hospital Based Surveillance Study.

Background:Invasive pneumococcal disease (IPD) in young infants is uncommon but associated with high morbidity and mortality. Accurate data on the burden of IPD in young infants in low-income countries are lacking. We examined the burden of IPD in infants <90 days old in Blantyre, Malawi over a 14-year period and evaluated the indirect impact of the 13-valent pneumococcal conjugate vaccine (PCV13) on vaccine-serotype IPD (VT-IPD) in this population.Methods:We conducted laboratory-based prospective IPD surveillance in infants <90 days of age admitted to Queen Elizabeth Central Hospital in Blantyre between 2005 and 2018, including 7 years pre-PCV13 and 7 years post-PCV13 introduction. IPD was defined as Streptococcus pneumoniae identified by culture from blood or cerebrospinal fluid. Serotypes were determined by multiplex polymerase chain reaction and latex agglutination testing.Results:We identified 130 cases of culture-confirmed IPD in infants <90 days old between 2005 and 2018. Total IPD incidence was declining before PCV13 introduction. The mean incidence of IPD was significantly lower in the post-PCV13 era. Serotypes 5 (27.8%) and 1 (15.6%) were most prevalent. Even after PCV13 introduction, VTs remained the primary cause of IPD, with serotype 5 accounting for 17.4% and serotype 1 for 13.0% of cases in young infants.Conclusion:Vaccine serotypes 1 and 5 were the main cause of IPD in neonates and young infants, both before and after PCV13 introduction. This suggests incomplete indirect protection with persisting VT carriage across the population despite vaccination in this setting. Alternative vaccine schedules and other vaccine introduction approaches need to be considered to protect this vulnerable population.

A Retrospective Analysis to Estimate the Burden of Invasive Pneumococcal Disease and Non-Invasive Pneumonia in Children

Despite advances in preventative interventions, invasive pneumococcal disease and pneumonia cause significant morbidity and mortality in children. We studied the annual incidence of pneumococcal-specific and syndromic invasive disease and non-invasive pneumonia in children <15 years of age during the early (2010–2013) and late (2014–2017) 13-valent pneumococcal conjugate vaccine (PCV13) periods in Veneto, Italy. In this retrospective observational study, pneumococcal-specific and syndromic invasive disease and non-invasive pneumonia cases were identified from several sources, including the Pedianet database. Interrupted time series analysis and Mann–Kendall tests were conducted to explore trends in incidence rates (IRs). Among 72,570 patients <15 years of age between 2010–2017, 88 episodes of pneumococcal-specific and syndromic invasive disease and 3926 episodes of non-invasive pneumonia were reported. Overall IR of pneumococcal-specific and syndromic invasive disease was 0.4/1000 person-years and did not change significantly (p = 0.46) throughout the study. Overall IR of non-invasive pneumonia was 10/1000 person-years and decreased significantly (−0.64, p = 0.026) over the study period. Following PCV13 introduction, the IRs of non-invasive pneumonia in children <15 years of age declined significantly, with no significant change in the IRs of pneumococcal-specific and syndromic invasive disease. There is a continuing clinical burden associated with pediatric pneumococcal diseases in Veneto, Italy.

Impact of 13-Valent Pneumococcal Conjugate Vaccine on Invasive Pneumococcal Disease Among Adults With HIV-United States, 2008-2018.

People with HIV (PWH) are at increased risk for invasive pneumococcal disease (IPD). Thirteen-valent pneumococcal conjugate vaccine (PCV13) was recommended for use in US children in 2010 and for PWH aged 19 years or older in 2012. We evaluated the population-level impact of PCV13 on IPD among PWH and non-PWH aged 19 years or older. We identified IPD cases from 2008 to 2018 through the Active Bacterial Core surveillance platform. We estimated IPD incidence using the National HIV Surveillance System and US Census Bureau data. We measured percent changes in IPD incidence from 2008 to 2009 to 2017-2018 by HIV status, age group, and vaccine serotype group, including serotypes in recently licensed 15-valent (PCV15) and 20-valent (PCV20) PCVs. In 2008-2009 and 2017-2018, 8.4% (552/6548) and 8.0% (416/5169) of adult IPD cases were among PWH, respectively. Compared with non-PWH, a larger proportion of IPD cases among PWH were in adults aged 19-64 years (94.7%-97.4% vs. 56.0%-60.1%) and non-Hispanic Black people (62.5%-73.0% vs. 16.7%-19.2%). Overall and PCV13-type IPD incidence in PWH declined by 40.3% (95% confidence interval: -47.7 to -32.3) and 72.5% (95% confidence interval: -78.8 to -65.6), respectively. In 2017-2018, IPD incidence was 16.8 (overall) and 12.6 (PCV13 type) times higher in PWH compared with non-PWH; PCV13, PCV15/non-PCV13, and PCV20/non-PCV15 serotypes comprised 21.5%, 11.2%, and 16.5% of IPD in PWH, respectively. Despite reductions post-PCV13 introduction, IPD incidence among PWH remained substantially higher than among non-PWH. Higher-valent PCVs provide opportunities to reduce remaining IPD burden in PWH.

Invasive Pneumococcal Disease Characterization in Adults and Subgroups aged < 60 years and ≥ 60 years in Bogota, Colombia

There is scarce information on the burden of invasive pneumococcal disease (IPD) among adults in low- and middle-income countries. This study aimed to describe the clinical outcomes and microbiological characteristics associated with IPD in adults and subgroups aged 18-59 years and ≥60 years in Colombia. A retrospective chart review study was conducted in five institutions of Bogotá from January 2011 to December 2017. Analyses were carried out for overall population and stratified by age group (18-59; ≥ 60 years). There were 169 IPD cases; median age was 58 years, 51.5% were male, and 80.5% had at least one comorbidity. Bacteremic pneumonia was the most common presentation (63.9%). The median length of hospital stay was 12 days with high healthcare resource utilization (HCRU): 58.6% required ICU and 53.3% inotropic support. Overall case-fatality rate (CFR) was 41.4%. Clinical outcomes were worse in patients ≥60 years old with significantly higher CFR and HCRU (ICU admission, mechanical ventilation, and inotropic support) compared to those aged 18-59 years. The most frequent serotypes were 3, 6 A/C, 14, and 19A. The sensitivity to penicillin in meningitis and non-meningitis isolates were 75% and 89.1% respectively. IPD was associated with a substantial burden in adults and worse clinical outcomes and HCRU in older adults in Colombia. Surveillance data combined with clinical outcomes have the potential to inform age-based pneumococcal vaccination policies.

Evolution of pneumococcal serotype epidemiology in Botswana following introduction of 13-valent pneumococcal conjugate vaccine.

Pneumococcal conjugate vaccines reduce the burden of invasive pneumococcal disease, but the sustained effect of these vaccines can be diminished by an increase in disease caused by non-vaccine serotypes. To describe pneumococcal serotype epidemiology in Botswana following introduction of 13-valent pneumococcal conjugate vaccine (PCV-13) in July 2012, we performed molecular serotyping of 268 pneumococcal strains isolated from 221 children between 2012 and 2017. The median (interquartile range) age of the children included in this analysis was 6 (3,12) months. Fifty-nine percent of the children had received at least one dose of PCV-13 and 35% were fully vaccinated with PCV-13. While colonization by vaccine serotypes steadily declined following PCV-13 introduction, 25% of strains isolated more than 3 years after vaccine introduction were PCV-13 serotypes. We also observed an increase in colonization by non-vaccine serotypes 21 and 23B, which have been associated with invasive pneumococcal disease and antibiotic resistance in other settings.