Introduction Of Pneumococcal Conjugate Vaccine Research Articles

Impact of pneumococcal conjugate vaccine 13 introduction on severe lower respiratory tract infections associated with respiratory syncytial virus or influenza virus in hospitalized children in Ulaanbaatar, Mongolia

ObjectivesLimited data indicate a beneficial effect of pneumococcal conjugate vaccines (PCVs) on respiratory syncytial virus (RSV) and influenza infections in young children. We evaluated the impact of 13-valent PCV (PCV13) introduction on the incidence of severe lower respiratory tract infections (LRTIs) associated with RSV or influenza in hospitalized children. MethodsOur study was restricted to children aged <2 years with arterial oxygen saturation <93% and children with radiologically confirmed pneumonia nested in a pneumonia surveillance project in four districts of Ulaanbaatar city, Mongolia. We tested nasopharyngeal swabs collected on admission for RSV and influenza using quantitative reverse transcription-polymerase chain reaction. The impact of PCV13 on the incidence of LRTI outcomes associated with RSV or with influenza for the period April 2015-March 2020 was estimated. Incidence rate ratios comparing pre- and post-vaccine periods were estimated for each outcome for each district using negative binomial models and for all districts combined with a mixed-effects negative binomial model. Adjusted models accounted for seasonality. Sensitivity analyses were conducted to assess the robustness of our findings. ResultsAmong 5577 tested cases, the adjusted incidence rate ratios showed a trend toward a reduction in RSV-associated outcomes: all LRTIs (0.77, 95% confidence interval [CI] 0.44-1.36), severe LRTIs (0.88, 95% CI 0.48-1.62), very severe LRTIs (0.76, 95% CI 0.42-1.38), and radiologically confirmed pneumonia (0.66, 95% CI 0.32-1.38) but inconsistent trends in outcomes associated with influenza. ConclusionsNo significant reductions were observed in any outcomes associated with RSV and influenza after PCV introduction.

Estimated population-level impact of pneumococcal conjugate vaccines against all-cause pneumonia mortality among unvaccinated age groups in five Latin American countries.

Pneumococcal conjugate vaccines (PCVs) provide strong direct protection in children, while limited data are available on their indirect effect on mortality among older age groups. This multi-country study aimed to assess the population-level impact of pediatric PCVs on all-cause pneumonia mortality among ≥5 years of age, and invasive pneumococcal disease (IPD) cases in Chile. Demographic and mortality data from Argentina, Brazil, Chile, Colombia, and Mexico were collected considering the ≥ 5-year-old population, from 2000-2019, with 1,795,789 deaths due to all-cause pneumonia. IPD cases in Chile were also evaluated. Time series models were employed to evaluate changes in all-cause pneumonia deaths during the post-vaccination period, with other causes of death used as synthetic controls for unrelated temporal trends. No significant change in death rates due to all-cause pneumonia was detected following PCV introduction among most age groups and countries. The proportion of IPD cases caused by vaccine serotypes decreased from 29% (2012) to 6% (2022) among ≥65 years in Chile. While an effect of PCV against pneumonia deaths (a broad clinical definition that may not be specific enough to measure indirect effects) was not detected, evidence of indirect PCV impact was observed among vaccine-type-specific IPD cases.

Impact of pneumococcal conjugate vaccination on pneumococcal nasopharyngeal carriage in the Gambia: Population-based cross-sectional surveys

BackgroundThe introduction of pneumococcal conjugate vaccines (PCV) has reduced carriage of vaccine-type (VT) pneumococci in many settings. We determined the impact of The Gambia’s national PCV programme on carriage of VT pneumococci in the population. MethodsSeven-valent PCV (PCV7) was introduced in August 2009 without catch-up and with doses scheduled at 2, 3, 4 months of age; it was replaced by PCV13 in May 2011. We did cross-sectional carriage surveys in 2009, 2015, and 2017 in age-stratified, population-based samples. Nasopharyngeal specimens were collected and processed according to WHO guidelines. We calculated observed and adjusted prevalence ratios (PR) of VT carriage before and after PCV introduction. FindingsWe enrolled 2988, 3162, and 2709 participants in 2009, 2015, and 2017 respectively. The baseline (2009) prevalence of VT pneumococcal carriage among children aged 0–4 years was 42.6 %, which declined to 14.9 % and 17.5 % in 2015 and 2017 respectively (adjPR 0.32 [95 % CI 0.27, 0.38] and 0.38 [0.31, 0.46] respectively). VT prevalence among children aged 5–14 years was 16.6 %, 15.1 %, and 15.8 % in the three surveys (2017 vs 2009, adjPR 0.70 [0.58, 0.83]). VT prevalence among 15–44 year-olds was 6.4 %, 5.7 %, and 7.1 % in the three surveys (2017 vs 2009, adjPR 0.59 [0.46, 0.75]), while in those aged ≥ 45 years it was 4.5 %, 6.5 %, and 4.5 % respectively. Non-VT carriage increased in all age-groups. Prevalent residual serotypes were 34 and 15B (age 0–4 years), 3 and 34 (age 5–14 years), and 3 and 16F (age ≥ 15 years). ConclusionsIntroduction of PCV was associated with reduced VT pneumococcal carriage in young, and older children, although with substantial residual prevalence. Persisting VT, and non-VT, carriage indicate significant, persistent transmission of pneumococci in the population.

Nasopharyngeal carriage rate, serotype distribution, and antimicrobial profiles of Streptococcus pneumoniae among patients with acute respiratory tract infection in Manado, North Sulawesi, Indonesia.

We studied the carriage rate, distribution of serotype, and antimicrobial profile of Streptococcus pneumoniae (S. pneumoniae) among patients with acute respiratory tract infections (ARTI) in two primary health centres and a tertiary referral hospital from 2019 to 2020 in Manado, North Sulawesi, Indonesia before 13-valent pneumococcal conjugate vaccine (PCV13) introduction. A total of 106 nasopharyngeal swab samples were collected from children and adult patients. Serotyping of S. pneumoniae strain was performed by sequential multiplex PCR and Quellung reaction. Antimicrobial profile was performed by the disc diffusion method. We identified thirty-one patients carried S. pneumoniae strains (29 %). The S. pneumoniae carriage rate was found to be higher among children aged 2-5 years (13/32; 40.6 %) than in children under 1 year (8/27; 29.6 %), children and adolescents under 18 years of age (5/20; 25.0 %) and adult patients (5/27; 18.5 %). The distribution of serotypes varied, including 14, 18C, 19A, 23F, 19F and 35B (two strains each) and 1, 3, 6B, 6C, 31, 9V, 15C, 16F, 17F, 23A, 35F (one strain each) and non-typeable (9/31; 29 %). We found S. pneumoniae isolates were susceptible to vancomycin (30/31; 97 %), chloramphenicol (29/31; 94 %), clindamycin (29/31; 94 %), erythromycin (22/31; 71 %), azithromycin (22/31; 71 %), tetracycline (14/31; 45 %), penicillin (11/31; 35 %), and sulfamethoxazole/trimethoprim (10/31; 32 %). This study provides supporting baseline data on distribution of serotype and antimicrobial profile of S. pneumoniae among patients with ARTI before PCV13 introduction in Manado, North Sulawesi, Indonesia.

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.

Antimicrobial resistance of Streptococcus pneumoniae from invasive pneumococcal diseases in Latin American countries: a systematic review and meta-analysis.

Invasive pneumococcal disease has declined since pneumococcal conjugate vaccine introduction in Latin America and the Caribbean (LAC). However, serotype distribution and antimicrobial resistance patterns have changed. We conducted a systematic review to evaluate the frequency of antimicrobial resistance of Streptococcus pneumoniae from invasive disease in LAC. Articles published between 1 January 2000, and 27 December 2022, with no language restriction, were searched in major databases and gray literature. Pairs of reviewers independently selected extracted data and assessed the risk of bias in the studies. The quality of antimicrobial resistance (AMR) studies was evaluated according to WHO recommendations (PROSPERO CRD42023392097). From 8,600 records identified, 103 studies were included, with 49,660 positive samples of S. pneumoniae for AMR analysis processed. Most studies were from Brazil (29.1%) and Argentina (18.4%), were cross-sectional (57.3%), reported data on AMR from IPD cases (52.4%), and were classified as moderate risk of bias (50.5%). Resistance to penicillin was 21.7% (95%IC 18.7-25.0, I2: 95.9), and for ceftriaxone/cefotaxime it was 4.7% (95%IC 3.2-6.9, I2: 96.1). The highest resistance for both penicillin and ceftriaxone/cefotaxime was in the age group of 0 to 5 years (32.1% [95%IC 28.2-36.4, I2: 87.7], and 9.7% [95%IC 5.9-15.6, I2: 96.9] respectively). The most frequent serotypes associated with resistance were 14 for penicillin and 19A for ceftriaxone/cefotaxime. Approximately one-quarter of invasive pneumococcal disease isolates in Latin America and the Caribbean displayed penicillin resistance, with higher rates in young children. Ongoing surveillance is essential to monitor serotype evolution and antimicrobial resistance patterns following pneumococcal conjugate vaccine introduction.

Co-occurrence of bacteria and viruses and serotype distribution of Streptococcus pneumoniae in the nasopharynx of Tanzanian children below 2 years of age following introduction of the PCV13.

Pneumococcal conjugate vaccines have reduced severe disease attributed to vaccine-type pneumococci in children. However, the effect is dependent on serotype distribution in the population and disease development may be influenced by co-occurrence of viral and bacterial pathogens in the nasopharynx. Following introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) in Tanzania we performed repeated cross-sectional surveys, including 775 children below 2 years of age attending primary healthcare centers. All children were sampled from nasopharynx and pneumococci were detected by single-target PCR. Pneumococcal serotypes/groups and presence of viruses and other bacteria were determined by two multiplex PCR assays. The prevalence of PCV13 vaccine-type pneumococci decreased by 50%, but residual vaccine-types were still detected in 21% of the children 2 years after PCV13 introduction. An increase in the non-vaccine-type 15 BC was observed. Pneumococci were often co-occurring with Haemophilus influenzae, and detection of rhino/enterovirus was associated with higher pneumococcal load. We conclude that presence of residual vaccine-type and emerging non-vaccine-type pneumococci in Tanzanian children demand continued pneumococcal surveillance. High co-occurrence of viral and bacterial pathogens may contribute to the disease burden and indicate the need of multiple public health interventions to improve child health in Tanzania.

Nasopharyngeal carriage of Streptococcus pneumoniae among children

Pneumococcal conjugate vaccines (PCVs) prevent nasopharyngeal colonization with vaccine serotypes of Streptococcus pneumoniae, leading to reduced transmission of pneumococci and stronger population-level impact of PCVs. In 2017 we conducted a cross-sectional pneumococcal carriage study in Indonesia among children aged <5 years before 13-valent PCV (PCV13) introduction. Nasopharyngeal swabs were collected during visits to community integrated health service posts at one peri-urban and one rural study site. Specimens were analyzed by culture, and isolates were serotyped using sequential multiplex polymerase chain and Quellung reaction. Antibiotic susceptibility was performed by broth microdilution method. We enrolled 1,007 children in Gunungkidul District, Yogyakarta (peri-urban) and 815 in Southwest Sumba, East Nusa Tenggara (rural). Pneumococcal carriage prevalence was 30.9% in Gunungkidul and 87.6% in Southwest Sumba (combined: 56.3%). PCV13 serotypes (VT) carriage was 15.0% in Gunungkidul and 52.6% in Southwest Sumba (combined: 31.8%). Among pneumococcal isolates identified, the most common VT were 6B (16.4%), 19F (15.8%), and 3 (4.6%) in Gunungkidul (N = 323) and 6B (17.6%), 19F (11.0%), and 23F (9.3%) in Southwest Sumba (N = 784). Factors associated with pneumococcal carriage were age (1-2 years adjusted odds ratio (aOR) 1.9, 95% CI 1.4-2.5; 3-4 years aOR 1.5, 95% CI 1.1-2.1; reference <1 year), other children <5 years old in the household (aOR 1.5, 95% CI 1.1-2.0), and presence of ≥1 respiratory illness symptom (aOR 1.8, 95% CI 1.4-2.2). Overall, 61.5% of the pneumococcal isolates were non-susceptible to ≥1 antibiotic class and 13.2% were multi-drug non-susceptible (MDNS) (non-susceptible to ≥3 classes of antibiotics). Among 602 VT isolates, 73.9% were non-susceptible and 19.9% were MDNS. These findings are critical to establish a pre-PCV13 carriage prevalence and demonstrate the complexity in evaluating the impact of PCV13 introduction in Indonesia given the wide variability in the carriage prevalence as shown by the two study sites.

Antimicrobial Resistance in Streptococcus pneumoniae before and after the Introduction of Pneumococcal Conjugate Vaccines in Brazil: A Systematic Review.

Streptococcus pneumoniae causes serious illnesses, such as pneumonia, bacteremia, and meningitis, mainly in immunocompromised individuals and those of extreme ages. Currently, pneumococcal conjugate vaccines (PCVs) are the best allies against pneumococcal diseases. In Brazil, the 10-valent and 13-valent PCVs have been available since 2010, but the threat of antimicrobial resistance persists and has been changing over time. We conducted a systematic review of the literature with works published since 2000, generating a parallel between susceptibility data on isolates recovered from colonization and invasive diseases before and after the implementation of PCVs for routine childhood use in Brazil. This systematic review was based on the Cochrane Handbook for Systematic Reviews of Interventions and Preferred Reporting Items for Systematic Literature Reviews and Meta-Analyses (PRISMA) guidelines. Despite the inclusion of PCVs at a large scale in the national territory, high frequencies of non-susceptibility to important drugs used in pneumococcal diseases are still observed, especially penicillin, as well as increasing resistance to macrolides. However, there are still drugs for which pneumococci have a comprehensive sensitivity profile.

Serotype 3 Experimental Human Pneumococcal Challenge (EHPC) study protocol: dose ranging and reproducibility in a healthy volunteer population (challenge 3)

IntroductionSince the introduction of pneumococcal conjugate vaccines, pneumococcal disease rates have declined for many vaccine-type serotypes. However, serotype 3 (SPN3) continues to cause significant disease and is identified in colonisation...

Characteristics of Streptococcus pneumoniae strains serotype 19A isolated from children in Moscow during the post-vaccination period (2015–2022)

Introduction. Community-acquired pneumonia (CAP) is a leading cause of children mortality and morbidity worldwide. The introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) had a very good effect on the CAP prevalence. However, serotype 19A remains the leading cause of severe pneumococcal disease in both vaccinated and unvaccinated children. &#x0D; The purpose of the work. To analyze the clonal epidemiology and sensitivity to antibacterial drugs of pneumococcus serotype 19A strains in the post-vaccination period for monitoring and control of vaccination.&#x0D; Materials and methods. The study included twenty six isolates of pneumococci serotype 19A isolated in children in Moscow between 2015 and 2022. Serotyping was carried out using the Neufeld capsule swelling test. Sensitivity was determined using the microdilution method. Resistance genes and multilocus sequence typing was performed using the PCR method.&#x0D; Results. By 2019–2022 the detection rate of serotype 19A decreased from 61.5% to 38.5%. A total of 12 different sequence types were identified. Most isolates belonged to 2 clonal complexes: CC230 (n = 15), CC320 (n = 6). Sixteen isolates exhibited a multidrug resistance phenotype (MDR). The dominant phenotype was extremely drug-resistant in the combination of β/Eri/Cli/TMP/Tet (43.8%). The most of MDR isolates belonged to clonal complexes: CC230 (8/16), CC320 (6/16) and Singleton 16988 (12.5%).&#x0D; Conclusion. After the introduction of PCV13, the prevalence of serotype 19A decreased, but MDR isolates of this serotype continued to increase. These results highlight the need for continued monitoring of the pneumococcal population exhibiting high resistance to reduce the risk of severe disease caused by this organism.

Closing the pneumococcal conjugate vaccine (PCV) introduction gap: an archetype analysis of last-mile countries

ABSTRACT Background Pneumonia remains the leading infectious cause of global childhood deaths, despite the availability of pneumococcal conjugate vaccine (PCV) products and widespread evidence of their safety and efficacy. Objective To map the landscape of countries that are yet to fully include PCV in their National Immunization Programs, we conducted an archetype analysis of country indicators related to barriers and facilitators for PCV decision-making. Methods We created a country matrix focused on three key domains – health characteristics, immunisation factors, and policy framework, and identified ten related indicators. We scored countries based on indicator performance and subsequently ranked and grouped them into three archetypes of low-, moderate-, and high-barrier countries with regard to PCV introduction. Results Our results indicated 39 countries (33 low- and middle-income countries [LMICs] and 6 high-income countries) that are yet to introduce PCV. Among LMICs, 15 countries were classified as ‘low-barrier,’ indicating factors favourable for PCV introduction such as high immunisation coverage of common childhood vaccines, supportive governments, and substantial disease burden and eligibility for Gavi support. Countries classified in the ‘moderate-barrier’ (12) and ‘high-barrier’ (6) archetypes demonstrated adequate capacity in immunisation systems but had competing national priorities and cost barriers that impeded policy decision-making on PCV introduction. Conclusions The current health and policy indicator-based categorisation provides an actionable framework to design tailored PCV advocacy within these last-mile countries. Policy approaches emerging from this framework can lead to strengthened decision-making on vaccine introduction and sustained vaccine access that can enhance child survival worldwide.

Impact of childhood 13-valent pneumococcal conjugate vaccine introduction on adult pneumonia hospitalisations in Mongolia: a time series analysis

IntroductionFew studies have assessed the potential indirect effects of childhood pneumococcal conjugate vaccine (PCV) programs on the adult pneumonia burden in resource-limited settings. We evaluated the impact of childhood PCV13 immunisation on adult all-cause pneumonia following a phased program introduction from 2016. MethodsWe conducted a time-series analysis to assess changes in pneumonia hospitalisation incidence at four district hospitals in Mongolia. Adults (≥18 years) that met the clinical case definition for all-cause pneumonia were enrolled. A negative binomial mixed-effects model was used to assess the impact of PCV13 introduction on monthly counts of pneumonia admissions from January 2015—February 2022. We also performed a restricted analysis excluding the COVID-19 pandemic period. All models were stratified by age and assessed separately. Additional analyses assessed the robustness of our findings. FindingsThe average annual incidence of all-cause pneumonia hospitalisation was highest in adults 65+ years (62·81 per 10,000 population) and declined with decreasing age. After adjusting for the COVID-19 pandemic period, we found that rates of pneumonia hospitalisation remained largely unchanged over time. We did not observe a reduction in pneumonia hospitalisations in any age group. Results from restricted and sensitivity analyses were comparable to the primary results, finding limited evidence of a reduced pneumonia burden. InterpretationWe did not find evidence of indirect protection against all-cause pneumonia in adults following childhood PCV13 introduction. Direct pneumococcal vaccination and other interventions should be considered to reduce burden of pneumonia among older adults. FundingPfizer clinical research collaboration agreement (contract number: WI236621).

Accelerating Pneumococcal Conjugate Vaccine introductions in Indonesia: key learnings from 2017 to 2022

Despite high pneumococcal disease and economic burden in Indonesia and interest to introduce pneumococcal conjugate vaccine (PCV), there were challenges in establishing a comprehensive strategy to accelerate and enable the introduction in country in the early 2010s. Starting in 2017, Clinton Health Access Initiative and partners supported the government of Indonesia with evidence-based decision-making and implementation support for introducing PCV into the routine immunization program. Indonesia has since accelerated PCV roll out, with nationwide reach achieved in 2022. On the path to PCV introduction, several challenges were observed that impacted decision making on whether and on how to optimally roll out PCV, resulting in significant introduction delays; including (1) a complex country context with a devolved government structure, fragmented domestic funding streams, and an imminent transition out of major immunization donor (Gavi) support; (2) strong preference to use domestically sourced products, with limited experience accessing global pooled procurement mechanism including for vaccines; and (3) concerns around programmatic feasibility and sustainability. This case study documents key insights into the challenges experienced and how those were systematically addressed to accelerate new vaccine introduction in Indonesia, with support from local and global stakeholders over time. The learnings would be beneficial for other countries yet to introduce critical new vaccines, in particular those with similar archetype as Indonesia e.g., middle-income countries with domestic manufacturing capacity and/or countries recently transitioning out of Gavi support.

1688. Naturally-induced Serum Antibody Levels in Children to Pneumococcal Polysaccharide 15B that Correlate with Protection from Nasopharyngeal Colonization but Anti-serotype 15B Antibody has Low Functional Cross-reactivity with Serotype 15C.

Abstract Background Pneumococcal infections caused by non-vaccine serotypes, including serotype 15B and 15C, emerged after the introduction of pneumococcal conjugate vaccines (PCVs). Serotypes 15B and 15C have been added to new different pneumococcal-conjugate vaccines (PCV20 and V116, respectively). We sought to derive a serum anti-15B antibody level that would be a correlate of protection (COP) against acute otitis media (AOM) and nasopharyngeal colonization and assess functional cross-reactivity against serotype 15B and 15C in children following natural immunization. Methods Method: IgG antibody to serotype15B polysaccharide was measured by ELISA in 402 sera from 6-36 month olds collected before, at the time of, and after pneumococcal culture-confirmed AOM and colonization caused by serotypes 15B and 15C. 153 serum samples from 6-36 month olds where no colonization with either 15B or 15C was observed were included as controls. A two-step method was used for the construction of COP models: a generalized estimating equation followed by logistic-regression. Opsonophagocytic (OPA) assays were used to assess functional cross-reactivity between serotypes 15B and 15C. Results The COP for prevention of colonization was 1.41µg/ml for 15B and 0.63µg/ml for 15C with a predictive probability of 80%. Significantly higher anti-15B antibody levels were measured in children who had AOM caused by serotype 15B compared to control children and compared to children who had AOM caused by serotype 15C (p&amp;lt; 0.03). Consequently, a COP for serotypes 15B and 15C could not be calculated for AOM. ELISA-measured antibody levels did not correlate with OPA titers. Thirty percent of child samples, with varying moderate to high amounts of ELISA-measured antibody, showed no OPA titer against either serotype 15B or 15C. For the remaining samples, very low or no functional cross-reactivity between serotypes 15B and 15C was measured. Conclusion Conclusions: A COP for prevention of colonization in young children based on naturally-induced antibody levels was derived for serotype 15B and 15C that differed. A COP for AOM could not be derived. ELISA-measured antibody levels correlated poorly with OPA titers and low functional cross-reactivity between serotypes 15B and 15C in child sera was observed. Disclosures All Authors: No reported disclosures

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.

Indirect impact of PCV10 children vaccination on the serotype distribution and antimicrobial resistance of Streptococcus pneumoniae causing invasive disease in adults over 50 in Colombia, 2005–2019: Observational analysis

IntroductionThe introduction of pneumococcal conjugate vaccine (PCV) into childhood vaccination programmes has reduced the prevalence of vaccine serotypes (VTs) that cause invasive pneumococcal disease (IPD) in children. In the elderly population, an impact has also been seen through indirect protection (herd effect). The aim of this study was to estimate the changes in serotype distribution and antimicrobial susceptibility of Streptococcus pneumoniae isolates recovered from adult IPD and to evaluate the indirect effect of immunization with PCV10 based on laboratory records by analyzing the period from 2005 to 2019 for six years before and eight years after the universal PCV10 administration to Colombian children. MethodsA total of 2204 S. pneumoniae isolates from adults (≥50 years) with IPD were analyzed. The analysis examined the percentage changes in proportions (prevalence) and percentage variations in population rates (annual reported rates – ARR) of VTs between the pre-PCV10 (2005–2009) and post-PCV10 (2015–2019) periods. ResultsThe findings were (1) evidence of a significant percentage decrease of pneumococcal VT10 causing IPD in adults (50% pre-PCV10 and 16% post-PCV10); (2) significant increase of serotype 19A (from 1.6% to 14.8%) and less important increase of serotype 3 (from 10.5% to 14.5%) and non-vaccine serotypes (NVT) (from 21.4% to 38.4%) non-significant; and (3) meningitis and non-meningitis multidrug resistant isolates associated with serotype 19A. An improvement in the surveillance system is associated with the immunization of children, as noted by the increased ARRs across the analysis period. ConclusionsOur results show the indirect impact of PCV10 vaccination in children on the VT10 distribution and antimicrobial resistance of S. pneumoniae causing IPD in Colombian adults over 50 when comparing the pre-PCV10 (2005–2009) and post-PCV10 (2015–2019) periods.

A multicenter study on the epidemiology of complicated parapneumonic effusion in the era of currently available pneumococcal conjugate vaccines

BackgroundParapneumonic effusion (PPE) is a common complication of pneumonia. Streptococcus pneumoniae is the most common cause of bacterial pneumonia. A reduction in pneumonia hospitalizations has been observed since the introduction of the 7-valent pneumococcal conjugate vaccine (PCV7). Despite this apparent benefit, an increase in the incidence of PPE was recorded in some countries following PCV7 implementation. As the 13-valent pneumococcal conjugate vaccine (PCV13) was expected to provide a wider protection against PPE, the aim of the present study was to evaluate the impact of PCV13 introduction on the epidemiology of complicated parapneumonic effusion (c-PPE) among children in the Athens greater area. MethodsAll cases of community-acquired pneumonia (CAP) with PPE requiring chest tube insertion (complicated PPE, c-PPE) hospitalized in the 3 public Children’s hospitals in Athens between 01/01/2004 and 31/12/2019 were included in the study. ResultsA total of 426 cases of c-PPE associated with pneumonia were recorded of which 198 were admitted during 2004–2010 (period A, prePCV13/PCV −7 introduction period) and 228 during 2011–2018 (period B, post - PCV13 period). A definite bacterial etiology was established in 44.4 % of all cases and of those 25.4 % were caused by S. pneumoniae. An increasing trend in c-PPE incidence was observed during period A; although, a significant decrease on c-PPE annual rates was observed during the period B (p = 0.011), a remarkable increase in serotype 3 cases was recorded. ConclusionA decreasing time trend in c-PPE cases among children was shown after the introduction of PCV13 in our area. However, serotype 3 is nowadays a common cause of PPE. Hence, continuous surveillance is imperative in order to follow c-PPE epidemiology over time.

Assessing the utilization of antimicrobial agents in pediatric pneumonia during the era of the 13-valent pneumococcal conjugate vaccine: A retrospective, single-center study

Background and purposePneumonia and bronchopneumonia are the most common infectious diseases in children. This study aimed to analyze changes in causative pathogens and antibiotic use for bronchopneumonia or pneumonia after the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) in children. MethodsThis retrospective study was conducted from 2009 to 2019. Hospitalized children aged 6 months–3 years with a discharge diagnosis of bronchopneumonia or pneumonia were included to analyze changes in the potential mismatch between the diagnosed pathogen and antibiotic use. ResultsThe cohort comprised 1100 patients, including 648 (59%) and 452 (41%) with a discharge diagnosis of bronchopneumonia and pneumonia, respectively. The trend of viral pneumonia increased every year (rs = 0.101, p < 0.05) Antibiotics were administered in 97% patients, with an increasing annual trend in macrolide use (rs = 0.031, p = 0.009). Regarding antibiotic utilization, no significant variations were observed in the days of therapy (DOT) (rs = 0.076, p = 0.208) or length of therapy (LOT) (rs = −0.027, p = 0.534) per patient-year throughout the study duration. Interestingly, the LOT for combined therapy with macrolides and first-line beta-lactams was high (rs = 0.333, p = 0.028). In viral pneumonia treatment, neither the DOT nor LOT exhibited significant variations (rs = −0.006, p = 0.787 and rs = −0.156, p = 0.398). ConclusionAfter the introduction of PCV13 in Taiwan, no decrease in antibiotic use has been observed among children aged 6 months–3 years with a discharge diagnosis of bronchopneumonia and pneumonia.

Serotype distribution, antimicrobial susceptibility and molecular epidemiology of invasive Streptococcus pneumoniae in the nine-year period in Serbia.

Streptococcus pneumoniae is one of the leading bacterial pathogens that can cause severe invasive diseases. The aim of the study was to characterize invasive isolates of S. pneumoniae obtained during the nine-year period in Serbia before the introduction of the pneumococcal conjugate vaccines (PCVs) into routine vaccination programs by determining: serotype distribution, the prevalence and genetic basis of antimicrobial resistance, and genetic relatedness of the circulating pneumococcal clones. A total of 490 invasive S. pneumoniae isolates were included in this study. The serotype, antimicrobial susceptibility, and ST of the strains were determined by the Quellung reaction, disk- and gradient-diffusion methods, and multilocus sequence typing (MLST), respectively. The most common serotypes in this study were 3, 19F, 14, 6B, 6A, 19A, and 23F. The serotype coverages of PCV10 and PCV13 in children less than 2 years were 71.3 and 86.1%, respectively, while PPV23 coverage in adults was in the range of 85-96%, depending on the age group. Penicillin and ceftriaxone-non-susceptible isolates account for 47.6 and 16.5% of all isolates, respectively. Macrolide non-susceptibility was detected in 40.4% of isolates, while the rate of multidrug- and extensive-drug resistance was 20.0 and 16.9%, respectively. The MLST analysis of 158 pneumococci identified 60 different STs belonging to the 16 Clonal Complexes (CCs) (consisting of 42 STs) and 18 singletons. The most common CC/ST were ST1377, CC320, CC15, CC273, CC156, CC473, CC81, and CC180. Results obtained in this study indicate that the pre-vaccine pneumococcal population in Serbia is characterized by high penicillin and macrolides non-susceptibility, worrisome rates of MDR and XDR, as well as a high degree of genetic diversity. These findings provide a basis for further investigation of the changes in serotypes and genotypes that can be expected after the routine introduction of PCVs.