Invasive Pneumococcal Disease Cases Research Articles

1180. Comparing Changes in Pneumococcal Meningitis Incidence to all Invasive Pneumococcal Disease Following Introduction of PCV10 and PCV13: The PSERENADE Project

BackgroundThe introduction of higher valency pneumococcal conjugate vaccines (PCV10 and PCV13) has reduced invasive pneumococcal disease (IPD) incidence. It is unknown whether the degree of reduction differs for pneumococcal meningitis, a small subset of pneumococcal disease but a major cause of severe childhood morbidity and mortality globally. We compared the impact of PCV10/13 on pneumococcal meningitis and all IPD by estimating the changes in incidence following the introduction of PCV10/13 among children < 5 years of age.MethodsData on confirmed positive cases for pneumococcus in cerebrospinal fluid (CSF) were obtained directly from surveillance sites. PCV10/13 impact on all-serotype pneumococcal meningitis and all IPD were estimated using site-specific incidence rate ratios (IRRs) at each post-PCV10/13 year relative to the pre-PCV period, using Bayesian multi-level, mixed effects Poisson regression. All-site weighted average IRRs were estimated using linear mixed-effects regression. Results were stratified by product (PCV10 vs. PCV13) and amount of prior PCV7 use (none; some (1-3 years or 4-5 years with < 70% uptake); or many (≥ 4 years with ≥ 70% uptake).Results40 surveillance sites (9 PCV10, 31 PCV13) in 28 countries, primarily high-income (82%) that had both CSF and IPD data were included in analyses. CSF+ accounted for 9.0% of IPD cases (IQR across sites: 6.2%-15.6%). The rate and amount of decline was generally similar between meningitis and IPD across all strata. At 5 years after PCV10/13 introduction, the IRRs across PCV7-use strata were 0.28-0.32 for pneumococcal meningitis and 0.22-0.43 for all IPD at PCV10-using sites, and 0.27-0.41 and 0.21-0.32, respectively, for PCV13-using sites. Only one site from the African meningitis belt contributed eligible data, which lacked pre-PCV data to estimate IRRs, but incidence rate of both IPD and meningitis decreased following PCV introduction. Figure 1. All-Site Weighted Average Incidence Rate Ratios, Children < 5 years * Total sites indicate the number of sites with incidence rate data included and pre/post sites indicate the number of sites with both pre− and post−PCV data to estimate site−specific IRRs for each outcome. The size of point estimates is relative to the number of sites with both pre− and post− data. ** Year 0 indicates the year of PCV10/13 introduction and year −1 indicates the last year of PCV7 use prior to PCV10/13 introduction.ConclusionNet declines in all-serotype IPD and CSF+ meningitis in children < 5 years were similar on average for both PCV10 and PCV13. Data from low-income, high-burden, and meningitis-belt regions were limited. Disclosures Maria Deloria Knoll, PhD, Merck (Research Grant or Support)Pfizer (Research Grant or Support)

Antibiotics prescription for targeted therapy of pediatric invasive pneumococcal diseases in China: a multicenter retrospective study

BackgroundStreptococcus pneumoniae (S. pneumoniae) is a major cause of bacterial meningitis, septicemia and pneumonia in children. Inappropriate choice of antibiotic can have important adverse consequences for both the individual and the community. Here, we focused on penicillin/cefotaxime non-susceptibility of S. pneumoniae and evaluated appropriateness of targeted antibiotic therapy for children with IPD (invasive pneumococcal diseases) in China.MethodsA multicenter retrospective study was conducted in 14 hospitals from 13 provinces in China. Antibiotics prescription, clinical features and resistance patterns of IPD cases from January 2012 to December 2017 were collected. Appropriateness of targeted antibiotics therapy was assessed.Results806 IPD cases were collected. The non-susceptibility rates of S. pneumoniae to penicillin and cefotaxime were 40.9% and 20.7% respectively in 492 non-meningitis cases, whereas those were 73.2% and 43.0% respectively in 314 meningitis cases. Carbapenems were used in 21.3% of non-meningitis cases and 42.0% of meningitis cases for targeted therapy. For 390 non-meningitis cases with isolates susceptible to cefotaxime, vancomycin and linezolid were used in 17.9% and 8.7% of cases respectively for targeted therapy. For 179 meningitis cases with isolates susceptible to cefotaxime, vancomycin and linezolid were prescribed in 55.3% and 15.6% of cases respectively. Overall, inappropriate targeted therapies were identified in 361 (44.8%) of 806 IPD cases, including 232 (28.8%) cases with inappropriate use of carbapenems, 169 (21.0%) cases with inappropriate use of vancomycin and 62 (7.7%) cases with inappropriate use of linezolid.ConclusionsAntibiotic regimens for IPD definite therapy were often excessive with extensive prescription of carbapenems, vancomycin or linezolid in China. Antimicrobial stewardship programs should be implemented to improve antimicrobial use.

Impact of previous macrolide use on invasive pneumococcal disease due to erythromycin-resistant serotypes in adults over 59 years of age

The major goals of the study were to describe the invasive pneumococcal disease (IPD) cases due to erythromycin-resistant serotypes and to evaluate the association between these cases and recent macrolide use in individuals aged over 59 years. We selected cases of IPD reported between 2007 and 2016 in persons aged over 59 years living in the Community of Madrid (CM). We followed the European Committee on Antimicrobial Susceptibility Testing (EUCAST). The explanatory variables (age, sex, year of onset of symptoms, clinical presentation, serotypes, vaccination status) were taken from the Mandatory Notification System for Infectious Diseases System and from the Vaccination Information System. The cases were classified as either included in the 13-valent pneumococcal conjugate vaccine (PCV13) or not (nonPCV13). Associations between cases due to erythromycin-resistant serotypes and previous macrolide use (total, long and short-term) were adjusted with a logistic regression multivariate analysis. A total of 1,831 cases were identified, of whom 408 were erythromycin-resistant serotypes. PCV13 cases were associated with previous macrolide use (OR: 5.07), particularly long-acting types (OR: 8.61). NonPCV13 cases were associated with the use of total macrolides (OR: 3.48) and long-acting macrolides (OR: 4.26) suggesting that PCV13 did not reduce the IPD cases in patients with previous use of macrolides. Our results confirmed that previous macrolide consumption was associated with the presence of IPD due to erythromycin-resistant serotypes. The risk was higher with the use of long-term macrolides.

Invasive pneumococcal disease burden in hospitalized adults in Bogota, Colombia

BackgroundThe incidence of invasive pneumococcal disease (IPD) varies depending on a number of factors, including vaccine uptake, in both children and adults, the geographic location, and local serotype prevalence. There are limited data about the burden of Streptococcus pneumoniae (Spn), serotype distribution, and clinical characteristics of adults hospitalized due to IPD in Colombia. The objectives of this study included assessment of Spn serotype distribution, clinical characteristics, mortality, ICU admission, and the need for mechanical ventilation.MethodsThis was an observational, retrospective, a citywide study conducted between 2012 and 2019 in Bogotá, Colombia. We analyzed reported positive cases of IPD from 55 hospitals in a governmental pneumococcal surveillance program. Pneumococcal strains were isolated in each hospital and typified in a centralized laboratory. This is a descriptive study stratified by age and subtypes of IPD obtained through the analysis of medical records.ResultsA total of 310 patients with IPD were included, of whom 45.5% were female. The leading cause of IPD was pneumonia (60%, 186/310), followed by meningitis. The most frequent serotypes isolated were 19A (13.87%, 43/310) and 3 (11.94%, 37/310). The overall hospital mortality rate was 30.3% (94/310). Moreover, 52.6% (163/310 patients) were admitted to the ICU, 45.5% (141/310) required invasive mechanical ventilation and 5.1% (16/310) non-invasive mechanical ventilation.ConclusionPneumococcal pneumonia is the most prevalent cause of IPD, with serotypes 19A and 3 being the leading cause of IPD in Colombian adults. Mortality due to IPD in adults continues to be very high.

Invasive Pneumococcal Disease in Latvia in PCV10 Vaccination Era, 2012-2018.

In 2010 in Latvia, invasive pneumococcal disease (IPD) became a cause for concern and vaccination of infants with four doses of 7–valent pneumococcal conjugate vaccine (PCV7) commenced. In 2012, 10–valent pneumococcal conjugate vaccine (PCV10) (three doses at 2, 4, and 12–15 month of age) vaccination was introduced. We described incidence and serotype distribution of IPD in Latvia and investigated serotypes associated with death from IPD based on surveillance data. Adult vaccination against pneumococcal infection is not included in the national immunization program. Laboratory confirmed IPD cases are passively notified to the Center for Disease Prevention and Control of Latvia (CDPC) by laboratories and clinicians. We calculated incidence by age, sex, case fatality, and trend in serotypes by conducting a retrospective population-based cross-sectional study based on national IPD surveillance data. From 2012 to 2018 466 cases of IPD were reported. The highest notified incidence was in 2015 at 4.4/100,000, which fell to 3.9 in 2018. The highest mean annual IPD incidence was in infants (4.8) and in the elderly (6.0). PCV10 vaccine serotypes were the most prevalent in IPD cases up to 2015 with a decreasing trend from 50% (20/40) in 2012 to 19% (14/74) in 2018 (chi2 test for trend of odds = 0.000). PCV23nonPCV13 vaccine serotypes had an increasing trend and rose from 18% (7/40) to 34% (25/74) (chi2 test for trend of odds = 0.000). Non-Vaccine serotypes had an increasing trend and rose from 13% (5/40) to 27% (20/74) (chi2 test for trend of odds = 0.038). Reported total case fatality was 19% (87/466). The highest, at 36% (20/56), was reported in 2013. After adjusting for age, Streptococcus pneumoniae serotype 3 was associated with death from IPD (adjusted OR 2.3 95%CI 1.25–4.12 p 0.007). Surveillance data indicate evidence of serotype replacement with an increasing trend of serotype 19A and PPV23nonPCV13 and Non-Vaccine serotypes. Serotype 3 and age were associated with fatal IPD outcome. Further studies of S. pneumoniae carriage would be useful in providing more evidence to characterize serotypes' circulation.

Effectiveness of the 13-Valent Pneumococcal Conjugate Vaccine on Invasive Pneumococcal Disease in Greenland

The 13-valent pneumococcal conjugate vaccine (PCV13) was introduced in 2010 to the childhood vaccination program in Greenland. This study aimed to estimate the effectiveness of the PCV13 on the incidence of invasive pneumococcal disease (IPD) in children and in adults in Greenland. IPD cases from the pre-PCV13 period (January 1995–September 2010) were compared with the post-PCV13 period (September 2010–October 2020). Register data were collected from laboratory records, IPD reports, the national registry on admissions, and medical files. A total of 295 IPD cases were identified in the study period. Overall IPD incidence rate (IR) declined from the pre-PCV13 period to the post-PCV13 period (IR 23.3 to 15.3 per 100,000 person years). Overall IPD incidence among children decreased significantly, whereas overall IPD incidence among the elderly increased significantly. During the post-PCV13 period, the incidence of vaccine serotype (VT) IPD decreased in all ages, while the incidence of non-vaccine serotype (NVT) IPD increased. This increase was most substantial among elderly ≥60 years. In conclusion, the PCV13 has reduced incidence rates of IPD in Greenland. However, the increase in NVT IPD among the elderly is noteworthy, and sup-ports continued surveillance of IPD in the population of Greenland.

Impact of COVID-19 social distancing measures on future incidence of invasive pneumococcal disease in England and Wales: a mathematical modelling study

ObjectivesIn January 2020, the UK moved to a 1+1 schedule for the 13-valent pneumococcal conjugate vaccine (PCV13) with a single priming dose at 3-month and a 12-month booster. We modelled...

Estimating the risk of recurrent invasive pneumococcal disease in Australia, 1991–2016

BackgroundIndividuals who experience an initial episode of invasive pneumococcal disease (IPD) are at increased risk of recurrent episodes. However, the magnitude of risk has not been well-quantified in the pneumococcal conjugate vaccine era. Individuals with a previous episode of IPD are not commonly identified as a high-risk group in vaccination guidelines. MethodsAustralian residents with at least one case of IPD between 1991 and 2016 were identified using routine public health surveillance data which included identified IPD risk factors. Incidence of recurrent IPD was calculated from 2001 onwards (after IPD became nationally notifiable) using time-to-event analyses with individuals contributing person-time at risk of recurrence if they survived greater than 14 days after initial episode onset. ResultsFrom 1991 to 2016 there were 28,809 IPD episodes in 28,218 individuals. A total of 512 (1.8%) persons experienced 591 recurrent episodes. From 2001 to 2016 the incidence of recurrent IPD was 216.2 per 100,000 person-years, 27 times greater than the population rate of primary IPD during this period (8.0 per 100,000 population per year). Between 2011 and 2016, more than one-quarter of individuals experiencing recurrence had no IPD risk factors identified at first episode. ConclusionsThere is substantially increased risk of recurrent IPD after an initial episode. At least one-quarter of those with recurrent episodes have no identified risk factors at the initial episode. Given the potential preventability of future episodes, those with a previous IPD episode should be identified as a high-risk group and receive pneumococcal vaccination.

370Measuring pneumococcal conjugate vaccine impact in a low-resource setting with minimal baseline data

Abstract Background We aimed to measure 13-valent pneumococcal conjugate vaccine (PCV13) impact on various pneumococcal endpoints with minimal baseline data. Methods PCV13 was introduced in October 2013 in Lao People’s Democratic Republic. We implemented studies to evaluate PCV13 impact: retrospective record review of pneumonia cases for three years pre-PCV13; prospective study of acute respiratory infection (ARI) for 4.5 years post-PCV to demonstrate effectiveness against hypoxic pneumonia; invasive pneumococcal disease (IPD) surveillance (2004-2019); carriage in children hospitalised with ARI (2013-2019); and community carriage surveys pre- and two years post-PCV13. Results Annual incidence of hospitalized pneumonia pre-PCV13 in children 2-59 months was 1,530 (95% confidence interval [CI] 1,477-1,584) per 100,000. Vaccine effectiveness against hypoxic pneumonia was 37% (95% CI 6-57%). In children &amp;lt;5 years, 85% (11/13) of IPD cases were due to PCV13 serotypes pre-PCV13, and 43% (3/7) post-PCV13; and in individuals ≥5 years, 61% (27/44) and 42% (17/40), respectively. In hospitalised children, vaccine type carriage prevalence reduced from 20.0% (95% CI 15.2-24.9%) in 2013 to 12.8% (95% CI 8.5-17.1%) in 2019 with increasing vaccine coverage. Results were consistent with community carriage studies. Conclusions Despite limited baseline data in Laos, we found evidence of PCV13 impact using a variety of methods. Our approach could be used in similar settings to augment existing WHO guidelines. Key messages A combination of methods may be useful to determine the impact of vaccine introduction in countries with limited surveillance.

Relationship between serotypes, disease characteristics and 30-day mortality in adults with invasive pneumococcal disease.

Invasive pneumococcal disease (IPD) is responsible for substantial mortality and morbidity worldwide. We aimed to identify host and bacterial factors associated with 30-day mortality in 18-year-old patients hospitalized with IPD in France from 2013 to 2015. This study analyzed data collected from consecutives IPD cases included in two parallel multi-center cohort studies: COMBAT study (280 patients with pneumococcal community-acquired bacterial meningitis) and SIIP study (491 patients with non-meningitis IPD). Factors associated with 30-day mortality were identified using logistic regression. Among the 771 enrolled patients (median age 66years, IQR [52.0-79.7]), 592/767 (77.2%) had at least one chronic disease. Patients with meningitis were younger (60.2 vs 70.9years; p < 0.001) and had fewer chronic diseases than those with non-meningitis IPD (73.3% vs 79.4%; p = 0.05). Non-vaccine serotypes were more frequent in meningitis patients than in those with other IPD (36.1% vs 23.1%; p < 0.001). The overall 30-day mortality was 16.7% and patients with concurrent meningitis and extra-cerebral IPD had the highest 30-day mortality rate (26.5%). On multivariate analyses, older age, history of malignant solid tumor, meningeal IPD and serotypes previously identified with high mortality potential were independently associated with 30-day mortality. Of the serotypes with high mortality potential, 80% were included in licensed (PCV13 or PPV23) vaccines. We observed an effect of both host factors and pneumococcal serotypes on 30-day mortality in IPD. This highlights the need for a focused strategy to vaccinate at-risk patients. ClinicalTrial. Gov identification number: NCT01730690.

The Risk of Invasive Pneumococcal Disease Differs between Risk Groups in Norway Following Widespread Use of the 13-Valent Pneumococcal Vaccine in Children.

The elderly and adults with medical risk conditions remain at high risk of invasive pneumococcal disease (IPD), highlighting the importance of adequate preventive efforts. In an observational population-based study in Norway (pop ≥ 5 years, 2009–2017) covering six years post-PCV13 implementation, we explored the incidence and risk of IPD associated with age and comorbidities. We obtained the data on 5535 IPD cases from the Norwegian Surveillance System for Communicable Diseases and the population data from Statistics Norway. To define comorbidities, we obtained ICD-10 codes from the Norwegian Patient Registry for the cases and the Norwegian population. The average annual decrease in PCV13 IPD incidence was significant in all risk groups and decreased post-PCV13 introduction by 16–20% per risk group, implying a nondifferential indirect protection from the childhood vaccination. The IPD incidence remained high in the medical risk groups. The relative importance of medical risk conditions was 2.8 to 6 times higher in those aged 5–64 versus ≥65 years for all types of IPD, since age itself is a risk factor for IPD. In groups without medical risk, the risk of IPD was eight times higher in those aged ≥65 compared to those 5–64 years (RR 8.3 (95% CI 7.3–9.5)). Our results underscore the need for age- and risk-group-based prevention strategies.

Invasive pneumococcal disease in persons with predisposing factors is dominated by non-vaccine serotypes in Southwest Sweden

BackgroundThe pneumococcal conjugate vaccine PCV7 was introduced in Southwest Sweden in the child vaccination program in 2009, followed by PCV13 in 2010 and PCV10 in 2015. In this retrospective cohort study we assessed the pneumococcal serotype distribution in relation to predisposing factors, clinical manifestations and outcome during seven years after PCV introduction.MethodsClinical data from 1278 patients with 1304 episodes of invasive pneumococcal disease (IPD) between January 2009 and December 2015 in Region Västra Götaland, Sweden, were retrospectively collected from medical records. Pneumococcal isolates were serotyped by gel diffusion and/or Quellung reactions performed at the Public Health Agency in Sweden. Associations between serotypes and clinical characteristics were statistically evaluated by use of Fisher’s exact test, Mann-Whitney U test and Logistic regression analysis, whereas IPD episodes caused by serotypes over time were analyzed by Mantel-Haenszel chi-square test.ResultsWith the exception of serotype 3, the prevalence of PCV13 serotypes decreased during the study period, from 76% (n = 157) of all IPD episodes in 2009 to 25% (n = 42) in 2015 (p < 0.001) while non-PCV13 serotypes increased, mainly among patients ≥65 years and in patients with predisposing factors, including cardiovascular disease, pulmonary disease and malignancy (p < 0.001 for all). Patients with predisposing factors, including those with malignancy, immune deficiency or renal disease, were more likely to have IPD caused by a serotype not included in PCV13 rather than a vaccine-included serotype. Serotype 3 was associated with intensive care unit admissions while serotype 1 and 7F caused IPD among healthier and younger patients. PCV13 serotypes were associated with invasive pneumonia, and non-PCV13 serotypes were associated with bacteremia with unknown focus and with manifestations other than pneumonia or meningitis.ConclusionsNon-PCV13 serotypes caused the majority of IPD cases in Southwest Sweden, especially in patients ≥65 years and in patients with predisposing factors. Serotype 3, included in PCV13, was prevalent and often caused severe disease.

Cost-effectiveness analysis for PCV13 in adults 60 years and over with underlying medical conditions which put them at an elevated risk of pneumococcal disease in Japan

ABSTRACT Background: The objective of this study was to conduct a cost-effectiveness analysis of PCV13 vs. PPV23 and no vaccination and PPV23 vs. no vaccination in adults aged ≥ 60 years with underlying medical conditions which put them at an elevated risk of pneumococcal disease in a Japanese healthcare setting. Research design and methods: A natural history model was developed with a life-long time horizon and 1-year cycle length, with microsimulation as a modeling technique. The expected costs from a public payer’s and societal perspective, quality-adjusted life-years (QALYs), and prevented cases and deaths caused by IPD (invasive pneumococcal disease) and NBP (non-bacteremic pneumococcal pneumonia) were estimated. Results: In the base-case scenario, the cost per QALY gained from a public payer’s perspective for PCV13 vs, PPV23 and no vaccination were 500,255JPY and 1,139,438JPY, respectively, The cost per QALY gained for PPV23 vs no vaccination was 1,687,057JPY. Over the life-long time horizon for 1 million patients, when compared to PPV23, PCV13 resulted in 65 fewer IPD cases, 2,894 fewer NBP cases, and 384 fewer deaths caused by pneumococcal disease. Conclusions: In adults aged 60 years and over with underlying medical conditions, PCV13 was shown to be a more cost-effective alternative to PPV23.

Dynamics of Invasive Pneumococcal Disease in Israel in Children and Adults in the 13-Valent Pneumococcal Conjugate Vaccine (PCV13) Era: A Nationwide Prospective Surveillance.

Following 13-valent pneumococcal conjugate vaccine (PCV13) implementation in infants worldwide, overall and vaccine-type invasive pneumococcal disease (IPD) rates declined in children, with variable indirect impact on adults. A population-based, prospective, nationwide active surveillance of IPD in Israel, 2004-2019 (for adults ≥18 years, 2009-2019). The 7-valent PCV (PCV7)/PCV13 were implemented in Israel in July 2009/November 2010, respectively, with >90% uptake in children <2 years. The 23-valent pneumococcal polysaccharide vaccine (PPV-23) uptake among those >65 years was ~75%. For pre-PCV episodes with missing serotype, extrapolations were applied. Overall, PCV13 serotypes (VT13) and non-VT13 (NVT) incidence rate ratios (IRRs) comparing pre-PCV (2004-2008), early-PCV (2009-2011), and late-PCV13 (2016-2019) periods were calculated for different age groups. Overall, 8614 IPD cases were recorded. IPD rates declined by 67% in children <5 and 5-17 years, comparing late-PCV13 versus pre-PCV periods (IRR [95% CI]: .33 [.27-.40] and .33 [.21-.50], respectively). For adults, comparing late-PCV13 with early-PCV periods, rates significantly declined by 53% in those aged 18-44, while rates did not decline significantly in other age groups. VT13 rates significantly declined in all ages, with decline rates ranging between 94% in children <5 years and 60% in adults ≥85 years. NVT rates significantly increased in <5-, 50-64-, and ≥65-year age groups. In the late-PCV13 period, serotypes 3, 14, and 19A remained the predominant VT13, while serotypes 8 and 12F emerged as predominant NVTs. Continuous monitoring of circulating serotypes in all ages demonstrated direct and indirect PCV effects, which are essential for the development of new vaccination strategies.

Impact of the introduction of pneumococcal conjugate vaccination on invasive pneumococcal disease and pneumonia in The Gambia: 10 years of population-based surveillance

SummaryBackgroundThe Gambia introduced seven-valent pneumococcal conjugate vaccine (PCV7) in August 2009, followed by PCV13 in May, 2011, using a schedule of three primary doses without a booster dose or catch-up immunisation. We aimed to assess the long-term impact of PCV on disease incidence.MethodsWe did 10 years of population-based surveillance for invasive pneumococcal disease (IPD) and WHO defined radiological pneumonia with consolidation in rural Gambia. The surveillance population included all Basse Health and Demographic Surveillance System residents aged 2 months or older. Nurses screened all outpatients and inpatients at all health facilities using standardised criteria for referral. Clinicians then applied criteria for patient investigation. We defined IPD as a compatible illness with isolation of Streptococcus pneumoniae from a normally sterile site (cerebrospinal fluid, blood, or pleural fluid). We compared disease incidence between baseline (May 12, 2008–May 11, 2010) and post-vaccine years (2016–2017), in children aged 2 months to 14 years, adjusting for changes in case ascertainment over time.FindingsWe identified 22 728 patients for investigation and detected 342 cases of IPD and 2623 cases of radiological pneumonia. Among children aged 2–59 months, IPD incidence declined from 184 cases per 100 000 person-years to 38 cases per 100 000 person-years, an 80% reduction (95% CI 69–87). Non-pneumococcal bacteraemia incidence did not change significantly over time (incidence rate ratio 0·88; 95% CI, 0·64–1·21). We detected zero cases of vaccine-type IPD in the 2–11 month age group in 2016–17. Incidence of radiological pneumonia decreased by 33% (95% CI 24–40), from 10·5 to 7·0 per 1000 person-years in the 2–59 month age group, while pneumonia hospitalisations declined by 27% (95% CI 22–31). In the 5–14 year age group, IPD incidence declined by 69% (95% CI −28 to 91) and radiological pneumonia by 27% (95% CI −5 to 49).InterpretationRoutine introduction of PCV13 substantially reduced the incidence of childhood IPD and pneumonia in rural Gambia, including elimination of vaccine-type IPD in infants. Other low-income countries can expect substantial impact from the introduction of PCV13 using a schedule of three primary doses.FundingGavi, The Vaccine Alliance; Bill & Melinda Gates Foundation; UK Medical Research Council; Pfizer Ltd.

The Impact of 10-Valent Pneumococcal Vaccine Introduction on Invasive Disease in Fiji: A Retrospective Review

Background: In 2012, Fiji introduced the 10-valent pneumococcal conjugate vaccine (PCV10). We assessed the impact of PCV10 on invasive pneumococcal disease (IPD), probable bacterial or pneumococcal meningitis (PBPM), meningitis and sepsis 3-5 years post-introduction. Methods: Laboratory-confirmed IPD and PBPM cases were extracted from national laboratory records. ICD-10-AM coded all-cause meningitis and sepsis cases were extracted from national hospitalisation records. Incidence rate ratios were used to compare outcomes pre/post-PCV10, stratified by age groups: 1-23m, 2-4y, 5-9y, 10-19y, 20-54y, ≥55y. To account for different detection and serotyping methods in the pre-and post-PCV10 period, a Bayesian inference model estimated serotype-specific changes in IPD, using pneumococcal carriage and surveillance data. Findings: There were 423 IPD, 1,029 PBPM, 1,391 all-cause meningitis and 7,611 all-cause sepsis cases. Five years post-PCV10 introduction, IPD declined by 60% (95%CI: 37%, 76%) in children 1-23m months old, and in age groups 2-4y, 5-9y, 10-19y although confidence intervals spanned zero. PBPM declined by 36% (95%CI: 21%, 48%) among children 1-23 months old, and in all other age groups, although some confidence intervals spanned zero. Among children <5y of age, PCV10-type IPD declined by 83% (95%CI; 70%, 90%) and with no evidence of change in non-PCV10-type IPD (9%, 95%CI; -69, 43%). There was no change in all-cause meningitis or sepsis. Post-PCV10, the most common serotypes in vaccine age-eligible and non-age eligible people were serotypes 8 and 23B, and 3 and 7F, respectively. Interpretations: Our study demonstrates the effectiveness of PCV10 against IPD in a low- to middle-income country in the Asia-Pacific of which there is a paucity of data. Funding: This study was support by the Department of Foreign Affairs and Trade of the Australian Government and Fiji Health Sector Support Program (FHSSP). FHSSP is implemented by Abt JTA on behalf of the Australian Government. Declaration of Interest: KM and CS are investigators on a collaborative study on PCV impact on adult pneumonia funded by Pfizer. All other authors have no competing interests.

National surveillance of antimicrobial susceptibilities to dalbavancin, telavancin, tedizolid, eravacycline, omadacycline and other comparator antibiotics and serotype distribution of invasive Streptococcus pneumoniae isolates in adults: results from the Surveillance of Multicenter Antimicrobial Resistance in Taiwan (SMART) programme in 2017–2020

ObjectivesThe aim of this study was to investigate the trends in serotypes and in vitro antimicrobial susceptibility of Streptococcus pneumoniae causing adult invasive pneumococcal disease (IPD) to dalbavancin, telavancin, tedizolid, eravacycline, omadacycline and other comparator antibiotics from 2017–2020 following implementation of the 13-valent pneumococcal conjugate vaccine (PCV-13) and during the COVID-19 (coronavirus disease 2019) pandemic.MethodsDuring the study period, 237 S. pneumoniae isolates were collected from non-duplicate patients, covering 15.0% of IPD cases in Taiwan. Antimicrobial susceptibility testing was performed using a Sensititre® system. A latex agglutination method (ImmuLex™ Pneumotest Kit) was used to determine serotypes.ResultsSusceptibility rates were high for vancomycin (100%), teicoplanin (100%) and linezolid (100%), followed by ceftaroline (non-meningitis) (98.3%), moxifloxacin (94.9%) and quinupristin/dalfopristin (89.9%). MIC50 and MIC90 values of dalbavancin, telavancin, tedizolid, eravacycline and omadacycline were generally low. Non-vaccine serotype 23A was the leading cause of IPD across the adult age range. Isolates of serotype 15B were slightly fewer than those of PCV-13 serotypes in patients aged ≥65 years. The overall case fatality rate was 15.2% (36/237) but was especially high for non-PCV-13 serotype 15B (21.4%; 3/14). Vaccine coverage was 44.7% for PCV-13 and 49.4% for the 23-valent pneumococcal polysaccharide vaccine (PPSV-23), but was 57% for both PCV-13 and PPSV-23.ConclusionThe incidence of IPD was stationary after PCV-13 introduction and only dramatically decreased in the COVID-19 pandemic in 2020. The MIC50 and MIC90 values of dalbavancin, telavancin, tedizolid, eravacycline, omadacycline were generally low for S. pneumoniae causing adult IPD.

Validation of a Novel Forecasting Method for Estimating the Impact of Switching Pneumococcal Conjugate Programs: Evidence from Belgium.

IntroductionSince 2010, 10-valent (PCV10) and 13-valent pneumococcal conjugate vaccines (PCV13) have been available as part of infant national immunization programs. Belgium is as one of the few countries that implemented PCV13 (2007–2015), switched to PCV10 (2015–2018) and then switched back to PCV13 (2018–present) after observing increases in disease. We assessed the impacts of both historical and prospective PCV choice in the context of the Belgian health care system and used this experience to validate previously developed economic models.MethodsUsing historical incidence (2007–2018) of pneumococcal disease for Belgian children aged < 16 years, observed invasive pneumococcal disease (IPD) trends from surveillance data were used to estimate future disease in a given PCV13- or PCV10-based program. We compared observed incidence data with two modeled scenarios: (1) the 2015 switch to PCV10 and (2) a hypothetical continuation of PCV13 in 2015. Finally, we explored the potential impact of PCV choice from 2019 to 2023 by comparing three scenarios: (3) continued use of PCV10; (4) a switch back to PCV13; (5) a hypothetical scenario in which Belgium never switched from PCV13.ResultsModel predictions underestimated observed data from 2015 to 2018 by 100 IPD cases among ages < 16 years. Comparing observed data with scenario 2 suggests that PCV13 would have prevented 105 IPD cases from 2015 to 2018 compared with PCV10. Switching to PCV13 in 2019 would avert 625 IPD cases through 2023 compared with continuing PCV10. Scenario never switching from PCV13 would have resulted in a reduction of 204 cases from 2016 to 2023 compared with switching to PCV10 and switching back to PCV13.ConclusionThe findings from this study suggest that previously published modeling results of PCV13 versus PCV10 in other countries may have underestimated the benefit of PCV13. These results highlight the importance of continually protecting against vaccine-preventable pneumococcal serotypes.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40121-021-00485-9.

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

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

Stable Incidence of Invasive Pneumococcal Disease in Children in Northern France From 2014 Through 2018.

The 13-valent pneumococcal conjugate vaccine (PCV13) has been recommended in France since June 2010. The aim of this study was to evaluate the trends in the incidence of invasive pneumococcal disease (IPD) resulting in hospitalization of children younger than 18 years of age, to identify the vaccination status of these patients and to analyze the serotypic evolution of the pneumococci involved in the various types of IPD. This multicenter retrospective study reviewed all admissions of children younger than 18 years of age for IPD from 2014 through 2018 in all hospitals with a pediatric or neonatal unit in northern France. Data completeness was obtained by matching 3 independent databases. The incidence of IPD resulting in hospitalization was calculated per age group. The clinical course and the vaccine and nonvaccine types were described overall and by the IPD type. One hundred thirty cases of IPD were identified: 51 with bacteremia, 45 meningitis, 28 pneumonia or pleuropneumonia and 6 arthritis. The IPD incidence ranged from 2.4 to 3.0/100,000 in children under 18 years of age (95% confidence intervals, 1.4-3.3 and 1.9-4.1, respectively), and from 9.5 to 15.9/100,000 in children under 2 years of age, with no significant differences over time. Nonvaccine types were predominant (81%), mainly 24F, 23B and 10A. Vaccine serotype 3 was involved in 10 cases of IPD, 2 of which were in correctly vaccinated children. Two cases of IPD could have been prevented by vaccination. Neurologic sequelae affected 26% of these children (62% of those with meningitis). Six children died from IPD (5%). The incidence of IPD resulting in hospitalization remained stable in northern France during the study period, with no significant increase in nonvaccine types. Further surveillance is needed to adjust the vaccination strategy if necessary.