Serotype 19A Research Articles

Effects of PCV10 and PCV13 on pneumococcal serotype 6C disease, carriage, and antimicrobial resistance

BackgroundThe cross-protection of pneumococcal conjugate vaccines (PCV) against serotype 6C is not clearly documented, although 6C represents a substantial burden of pneumococcal disease in recent years. A systematic review by the World Health Organization that covered studies through 2016 concluded that available data were insufficient to determine if either PCV10 (which contains serotype 6B but not 6A) or PCV13 (containing serotype 6A and 6B) conferred protection against 6C. MethodsWe performed a systematic review of randomized controlled trials and observational studies published between January 2010 – August 2022 (Medline/Embase), covering the direct, indirect, and overall effect of PCV10 and PCV13 against 6C invasive pneumococcal disease (IPD), non-IPD, nasopharyngeal carriage (NPC), and antimicrobial resistance (AMR). ResultsOf 2548 publications identified, 112 were included. Direct vaccine effectiveness against 6C IPD in children ranged between 70 and 85 % for ≥ 1 dose PCV13 (n = 3 studies), was 94 % in fully PCV13 vaccinated children (n = 2), and −14 % for ≥ 1 dose of PCV10 (n = 1). Compared to PCV7, PCV13 efficacy against 6C NPC in children was 66 % (n = 1). Serotype 6C IPD rates or NPC prevalence declined post-PCV13 in most studies in children (n = 5/6) and almost half of studies in adults (n = 5/11), while it increased post-PCV10 for IPD and non-IPD in all studies (n = 6/6). Changes in AMR prevalence were inconsistent. ConclusionsIn contrast to PCV10, PCV13 vaccination consistently protected against 6C IPD and NPC in children, and provided some level of indirect protection to adults, supporting that serotype 6A but not 6B provides cross-protection to 6C. Vaccine policy makers and regulators should consider the effects of serotype 6A-containing PCVs against serotype 6C disease in their decisions.

Serotype Distribution and Antimicrobial Susceptibility Pattern of Streptococcus pneumoniae in COVID-19 Pandemic Era in Brazil.

Despite the introduction of the pneumococcal vaccine, Streptococcus pneumoniae remains a cause of invasive diseases in Brazil. This study provides the distribution of serotypes and antimicrobial susceptibility patterns for pneumococcal isolates before and during the years of the COVID-19 pandemic in two age groups, <5 and ≥50 years. This is a national laboratory-based surveillance study that uses data from the Brazilian national laboratory for invasive S. pneumoniae from the pre-COVID-19 (January 2016 to January 2020) and COVID-19 (February 2020 to May 2022) periods. Antimicrobial resistance was evaluated by disk diffusion and minimum inhibitory concentration. The year 2020 was marked by a 44.6% reduction in isolates received and was followed by an upward trend from 2021 onwards, which became evident in 2022. No differences were observed in serotypes distribution between the studied periods. The COVID-19 period was marked by the high prevalence of serotypes 19A, 3, and 6C in both age groups. Serotypes 19A and 6C were related to non-antimicrobial susceptibility. We observed a reduction in S. pneumoniae, without changes in serotypes distribution and epidemiological capsular switch during the COVID-19 period. We observed elevated resistance rates, mainly to penicillin and ceftriaxone for non-meningitis cases in children under 5 years of age.

Pneumococcal population genomics changes during the early time period of conjugate vaccine uptake in southern India.

Streptococcus pneumoniae is a major cause of invasive disease of young children in low- and middle-income countries. In southern India, pneumococcal conjugate vaccines (PCVs) that can prevent invasive pneumococcal disease began to be used more frequently after 2015. To characterize pneumococcal evolution during the early time period of PCV uptake in southern India, genomes were sequenced and selected characteristics were determined for 402 invasive isolates collected from children <5 years of age during routine surveillance from 1991 to 2020. Overall, the prevalence and diversity of vaccine type (VT) and non-vaccine type (NVT) isolates did not significantly change post-uptake of PCV. Individually, serotype 1 and global pneumococcal sequence cluster (GPSC or strain lineage) 2 significantly decreased, whereas serotypes 6B, 9V and 19A and GPSCs 1, 6, 10 and 23 significantly increased in proportion post-uptake of PCV. Resistance determinants to penicillin, erythromycin, co-trimoxazole, fluoroquinolones and tetracycline, and multidrug resistance significantly increased in proportion post-uptake of PCV and especially among VT isolates. Co-trimoxazole resistance determinants were common pre- and post-uptake of PCV (85 and 93 %, respectively) and experienced the highest rates of recombination in the genome. Accessory gene frequencies were seen to be changing by small amounts across the frequency spectrum specifically among VT isolates, with the largest changes linked to antimicrobial resistance determinants. In summary, these results indicate that as of 2020 this pneumococcal population was not yet approaching a PCV-induced equilibrium and they highlight changes related to antimicrobial resistance. Augmenting PCV coverage and prudent use of antimicrobials are needed to counter invasive pneumococcal disease in this region.

A clade of Streptococcus pneumoniae clonal complex 320 with increased tolerance to β-lactam antibiotics in a Chinese metropolitan city

ObjectivesWe characterized the population structure and features of clinical Streptococcus pneumoniae isolates associated with invasive pneumococcal disease (IPD) from 2009 to 2017 in a Chinese metropolitan city using a whole-genome sequencing approach. MethodsSeventy-nine pneumococcal strains, including 60 serogroup-19 strains from children enduring IPD from a paediatric hospital in Shenzhen, were subjected to whole-genome sequencing. Population structure was characterized through phylogenetic analysis, sequence typing, serotyping, virulence factor, and antimicrobial drug resistance (AMR) gene profiling, combining the publicly available related WGS data. Clinical demography and antibiotic susceptibility profiles were compared among different populations to emphasize the higher-risk populations. Genetic regions associated with AMR gene mobilization were identified through comparative genomics. ResultsThese IPD strains mainly belonged to clonal complex 320 (CC320) and were composed of serotypes 19A and 19F. In addition to sporadic possible importation-related isolates (ST320), we identified an independent clade, CC320_SZpop (ST271), that predominantly circulated in Shenzhen and possibly expanded its range. Clinical features and antibiotic susceptibility analysis revealed that CC320_SZpop might manifest much higher pathogenicity and tolerance to β-lactams. Specific virulence factors in Shenzhen isolates of CC320_SZpop were identified. Furthermore, an ca. 40 kb hotspot genomic region enduring frequent recombination was identified, possibly associated with the divergence of S. pneumoniae strains. ConclusionA novel pneumococcal clade, CC320_SZpop, circulating in Shenzhen and other regions in China, possibly under expansion, was found and deserves more study and surveillance. Our study also emphasizes the importance of continuous genomic surveillance of clinical S. pneumoniae isolates, especially IPD isolates.

Strain features of pneumococcal isolates in the pre- and post-PCV10 era in Pakistan.

Pakistan is amongst the four countries with the highest number of pneumococcal deaths. While the PCV10 vaccine was introduced in Pakistan in October 2012, data regarding the impact of the vaccine on the population dynamics of Streptococcus pneumoniae in Pakistan remain obscure. Using whole genome sequencing of 190 isolates (nasopharyngeal carriage=75, disease=113, unknown sites=2) collected between 2002 and 2020, this study presents characteristics of pneumococcal strains in Pakistan in the pre- and post-vaccine era. The isolates were characterized on the basis of serotype distribution, genetic lineages (or Global Pneumococcal Sequence Cluster, GPSC) and antibiotic resistance. A high level of diversity in serotype and genetic lineages of pneumococci was observed in Pakistan. Among 190 isolates, we identified 54 serotypes, 67 GPSCs and 116 sequence types (STs) including 23 new STs. The most prevalent GPSCs and their associated serotypes in nasopharyngeal carriage were GPSC54 (expressing serotype 9V), GPSC5 (15A and 7B, and serogroup 24), GPSC25 (15B/15C), GPSC67 (18C) and GPSC376 (6A and 6D). Similarly, among 113 disease-causing isolates, the most prevalent GPSC/serotype combinations were GPSC2 (serotype 1), GPSC10 (serotypes 14, 10A, 19A and 19F), GPSC43 (serotypes 13, 11A, 23B, 35A and 9V), GPSC67 (serotypes 18A and 18C) and GPSC642 (serotype 11A). Of the 190 isolates, the highest levels of resistance were observed against penicillin (58.9 %, n=122), erythromycin (29.5 %, n=56), clindamycin (13.2 %, n=25), co-trimoxazole (94.2 %, n=179) and tetracycline/doxycycline (53.2 %, n=101). A higher proportion of disease-causing isolates were multidrug resistant as compared to carriage isolates (54 % vs 25 %). Our data suggest limited coverage of PCV10 in nasopharyngeal (21.6 %, 16/74) as well as disease-causing (38.1 %, 16/42) isolates among children ≤5 years old; however, higher valent vaccine PCV13 would increase the coverage rates to 33.8 % in nasopharyngeal and 54.8 % in disease-causing isolates, whereas PCV24/25 would offer the highest coverage rates. Owing to the diversity of serotypes observed during the post-vaccine period, the suggested inclusion of serotype in future vaccine formulations will require investigations with larger data sets with an extended temporal window. This article contains data hosted by Microreact.

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.

Efficacy of delafloxacin alone and in combination with cefotaxime against cefotaxime non-susceptible invasive isolates of Streptococcus pneumoniae.

We assessed the in vitro activity of delafloxacin and the synergy between cefotaxime and delafloxacin among cefotaxime non-susceptible invasive isolates of Streptococcus pneumoniae (CNSSP). A total of 30 CNSSP (cefotaxime MIC > 0.5 mg/L) were studied. Serotyping was performed by the Pneumotest-Latex and Quellung reaction. Minimum inhibitory concentrations (MICs) of delafloxacin, levofloxacin, penicillin, cefotaxime, erythromycin and vancomycin were determined by gradient diffusion strips (GDS). Synergistic activity of delafloxacin plus cefotaxime against clinical S. pneumoniae isolates was evaluated by the GDS cross method. Delafloxacin showed a higher pneumococcal activity than its comparator levofloxacin (MIC50, 0.004 versus 0.75 mg/L and MIC90, 0.047 versus >32 mg/L). Resistance to delafloxacin was identified in 7/30 (23.3%) isolates, belonging to serotypes 14 and 9V. Synergy between delafloxacin and cefotaxime was detected in 2 strains (serotypes 19A and 9V). Antagonism was not observed. Addition of delafloxacin increased the activity of cefotaxime in all isolates. Delafloxacin susceptibility was restored in 5/7 (71.4%) strains. CNSSP showed a susceptibility to delafloxacin of 76.7%. Synergistic interactions between delafloxacin and cefotaxime were observed in vitro among CNSSP by GDS cross method.

Fowl Adenovirus Induced Gizzard Erosion in Broiler Chickens in Southern India

Background: In Southern India, feed passage syndrome was on the rise in the late half of 2019 affecting broiler chicken flocks. The feed passage syndrome is an indication of poor gastrointestinal health in chickens, in which poorly digested coarse feed particles are observed to be more in the feces. This study investigated the causative factors for the feed passage syndrome in broiler flocks. Methods: Affected commercial broiler farms having incidences of feed passage syndrome, low body weight gain and poor feed conversion ratio, were visited in several regions of Karnataka and Andhra Pradesh. But there was no increase in mortality. Feed samples were collected from these regions for mycotoxin analysis. Intestinal health was examined in these flocks for lesions of coccidiosis and bacterial enteritis/dysbacteriosis. The common observation in all the birds examined was the presence of gizzard erosions. The gizzard in most of the birds was flaccid and moderate to severe erosions in the koilin layer of the gizzard were observed. In some birds, there were mild to moderate lesions caused by Eimeria maxima and Eimeria tenella. Tissue impressions on FTA cards were collected from gizzards having erosion on the koilin layer and submitted for identification of Fowl Adenovirus (FAdV) through the polymerase chain reaction (PCR) method. Result: All the samples were found positive for FAdV. Four samples were further processed for sequencing of the Hexone gene to identify the serotype of the virus. FAdV serotype 11 was detected in three samples and serotype 8a was detected in one. Among major mycotoxins, low levels of Aflatoxin B1 were the predominant finding in feed samples. Thus, it can be concluded that fowl adenovirus-induced gizzard erosions in commercial broiler birds along with mild coccidiosis could be leading to feed passage syndrome.

Serotype distribution, clinical characteristics, and antimicrobial resistance of pediatric invasive pneumococcal disease in Colombia during PCV10 mass vaccination (2017-2022).

Invasive Pneumococcal Disease (IPD) causes significant morbidity and mortality in children under 5 y. Colombia introduced PCV10 vaccination in 2012, and the Neumocolombia network has been monitoring IPD in pediatric patients since 2008. This study is a secondary analysis of a prospective cohort involving pediatric patients with IPD admitted to 17 hospitals in Colombia, from January 1st, 2017, to December 31st, 2022. We present data on serotypes (Spn), clinical characteristics, and resistance patterns. We report 530 patients, 215 (40.5%) were younger than 24 months. Among these, 344 cases (64.7%) presented with pneumonia, 95 (17.9%) with primary bacteremia, 53 (10%) with meningitis, 6 (1.1%) had pneumonia and meningitis, and 32 (6%) had other IPD diagnosis. The median hospital stay was 12 days (RIQ 8-14 days), and 268 (50.6%) were admitted to the ICU, of whom 60 (11.3%) died. Serotyping was performed in 298 (56.1%). The most frequent serotypes were Spn19A (51.3%), Spn6C (7.7%), Spn3 (6.7%), Spn6A (3.6%), and Spn14 (3.6%). Of 495 (93%) isolates with known susceptibility, 46 (9.2%) were meningeal (M) and 449 (90.7%) non-meningeal (NM). Among M isolates, 41.3% showed resistance to penicillin, and 21.7% decreased susceptibility to ceftriaxone. For NM isolates, 28.2% had decreased susceptibility to penicilin, and 24.2% decreased susceptibility to ceftriaxone. Spn19A showed the highest resistant to penicillin at 47% and was linked to multiresistance. The prevalence of PCV10-included serotypes decreased, while serotypes 19A and 6C increased, with Spn19A being associated with multiresistance. These findings had played a crucial role in the decision made by Colombia to modify its immunization schedule by switching to PCV13 in July 2022.

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

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

PCV13 vaccine prevents pneumococcal biofilms without affecting Staphylococcus aureus population within the polymicrobial biofilm.

In respiratory pathogens such as Streptococcus pneumoniae, biofilm formation is associated with the colonization of the nasopharynx and chronic respiratory infection. Previous data have shown that pneumococcal conjugate vaccines (PCVs) had an impact on S. pneumoniae colonization and a potential replacement by other respiratory pathogens such as Staphylococcus aureus. The objective of this work was to evaluate the evasion of the immune system by monospecific biofilms and by S. aureus-S. pneumoniae mixed biofilms. We performed opsonophagocytosis assays (OPA) using human HL-60 against previously disaggregated monospecific biofilms of MSSA, MRSA and S. aureus-S. pneumoniae mixed biofilms. We used pre-immune and post-immune serum from immunocompetent adult patients vaccinated with PCV13. Immune sera had a clear effect in reducing pneumococcal biofilms of serotypes 3, 14, 18C, 19F and 19A, whereas had no effect in non-PCV13 serotypes such as 8, 11A and 24F. Our study confirmed that serum from vaccinated patients with PCV13 did not have any effect in reducing S. aureus population in monospecific biofilms, regardless the methicillin resistance phenotype. Moreover, immunized sera from vaccinated patients with PCV13 did not have any effect in S. aureus population in the mixed biofilm, whereas significantly reduced the population of pneumococcal serotype 19A strain in the mixed biofilm which is of great interest because this serotype is included in PCV13, and it is associated with vaccine failures.

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.

Adult non-invasive pneumococcal pneumonia in Portugal is dominated by serotype 3 and non-PCV13 serotypes 3-years after near universal PCV13 use in children.

Non-invasive pneumococcal pneumonia (NIPP) is possibly the most frequent infection by Streptococcus pneumoniae in adults. However, the herd effect of vaccinating children in adult NIPP (aNIPP) remains poorly characterized. We determined the serotype distribution and antimicrobial susceptibility of isolates causing aNIPP (>18 years) in 2016-2018 in Portugal; 3 years with near universal vaccination of children with the 13-valent conjugate vaccine (PCV13), following over a decade of significant PCV use in children in the private market. Among the 1,149 aNIPP isolates, the most frequent serotypes detected were: 3 (n = 168, 14.6%), 11A (n = 102, 8.9%), 19F (n = 70, 6.1%), 23A and 23B (n = 62, 5.4% each), 9N (n = 60, 5.2%), 8 and 29/35B (n = 43, 3.7% each); together accounting for 53% of all isolates. The serotype distribution causing aNIPP was stable in 2016-2018, with the serotypes included in PCV7 still being important causes of disease and serotype 3, a PCV13 serotype, remaining the leading cause of aNIPP. There was an increase in penicillin non-susceptibility from 17% in 2016 to 24% in 2018 (p = 0.018). Some PCV13 serotypes, such as 14, 19A and 19F were associated to resistance, which may have contributed to their persistence. The fact that close to 20% of aNIPP is caused by four non-vaccine serotypes (23A, 23B, 9N, and 29/35B) and that there were significant differences in serotype distribution relative to invasive disease, stress the importance of maintaining the surveillance of these infections. The lack of a continued herd effect from vaccinating children and the significant fraction of aNIPP potentially preventable by PCV13 (30%), PCV15 (34%), PCV20 (53%) and the 23-valent polysaccharide vaccine (61%) underscore the importance of considering the broader use of pneumococcal vaccines in adults.

Predicted serotype-specific effectiveness of pneumococcal conjugate vaccines V114 and PCV20 against invasive pneumococcal disease in children

ABSTRACT Background Next-generation, higher-valency pneumococcal conjugate vaccines (PCVs), 15-valent PCV V114 and 20-valent PCV (PCV20), have been assessed by comparing their immune responses across serotypes shared with the 13-valent PCV (PCV13). Without efficacy or real-world vaccine effectiveness (VE) it becomes important to relate IgG titers to VE to aid in the interpretation of the immune response elicited by V114 and PCV20. Methods We estimated the protective antibody concentrations for each serotype in 7-valent PCV (PCV7) and PCV13 which were then used to predict the serotype-specific VE for each PCV7 and PCV13 non PCV7 serotype present in V114 and PCV20. Results The predicted effectiveness of V114 was comparable to PCV7 and PCV13 for 11 of the 13 shared serotypes (1, 4, 5, 6B, 7F, 9 V, 14, 18C, 19A, 19F, and 23F), with improved effectiveness against serotype 3 and decreased effectiveness against serotype 6A. PCV20 had predicted effectiveness comparable to PCV7 and PCV13 for 7 of the 13 shared serotypes (5, 6A, 7F, 9 V, 18C, 19F, and 23F), with decreased effectiveness against the remaining serotypes (1, 3, 4, 6B, 14, and 19A). Conclusions Prediction of serotype-specific VE values suggests that V114 retains greater effectiveness than PCV20 toward most serotypes present in PCV7 and PCV13.

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

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

Effectiveness of 13-valent pneumococcal conjugate vaccine against invasive disease caused by serotype 19A in children: a meta-analysis

Objective: Using Meta-analysis to evaluate the vaccine effectiveness of 13-valent pneumococcal conjugate vaccine (PCV13) against invasive Streptococcus pneumoniae disease (IPD) caused by serotype 19A in children <5 years old. Methods: "Streptococcus pneumoniae infection""invasive pneumococcal disease""13-valent pneumococcal polysaccharide conjugate vaccine""PCV13""effectiveness""infant""child" and related terms were searched from China National Knowledge Infrastructure (CNKI), WANFANG DATA, PubMed, SCOPUS and Web of science with no limited on language, region and research institution. The retrieval time was limited from January 2010 to February 2023 and cohort study, case-control study and randomized controlled trial were included. Data were extracted from eligible studies by two independent reviewers, and after study quality assessment by NOS scale, Meta-analysis was completed using Stata 16.0 software. Results: A total of 2 340 related literatures were searched, and 10 literatures were finally included, including 5 case-control studies and 5 indirect cohort studies, which showed good literature quality. The vaccine effectiveness against serotype 19A IPD of PCV13 in children was 83.91% (95%CI: 78.92%-88.89%), and the subgroup analysis (P=0.240) showed there was no significant difference among the case-control study (VE=87.34%, 95%CI:79.74%-94.94%) and the indirect cohort study (VE=81.30%, 95%CI:74.69%-87.92%). The funnel plot and Egger test suggested that the possibility of publication bias was small. Conclusion: The present evidence indicates that PCV13 has a good vaccine effectiveness against serotype 19A IPD in children, and it is recommended to further increase the vaccination rate of PCV13 to reduce the disease burden of IPD in children <5 years old.

Prevalence and Antimicrobial Resistance Patterns of Pathogenic Bacterial Isolates of Hospitalized Sickle Cell Disease Patients Admitted in Our Tertiary Hospital in the Gambia

Background: Sickle Cell Disease (SCD) patients are predisposed to several SCD related complications such as vasocclusive crisis, asplenia, haemolytic crisis and bacterial infection. Despite several other complications encountered by SCD patients during the first few years of life, invasive bacterial infections caused by Streptococcus pneumoniae, Haemophilus influenzae type b, and non-typhi Salmonella species have been reported to be the predominant cause of morbidity and mortality in sickle cell disease patients in many countries (Williams et al. 2009). This is because most SCD patients develop functional asplenism in their early years of life because of repeated episodes of sickling-induced splenic infarction which predisposes them to episodes of infections caused by encapsulated bacteria such as such as Streptococcus Pneumoniae, Haemophilus influenzae type b, and non-typhoidal Salmonella species. The two major prophylactic interventions are vaccination, and daily oral penicillin at least until the fifth year to protect the SCD populations from encapsulated bacterial infections. Aims The aim of this study was to determine the prevalence of invasive bacterial infections and their antimicrobial resistance patterns in SCD patients admitted at the Medical Research Council the Gambia (MRCG) Ward in the era of Pneumococcal Conjugate Vaccine and Haemophilus Influenzae b vaccination in the Gambia. Methods and Results This study was conducted in the clinical laboratory department of MRCG. We retrospectively generated haematological, and blood culture data from our electronic medical records from 2015 to 2022 of SCD patients admitted to MRCG Ward. Of 380 SCD patients, blood culture was requested for 159. Of the 159 admitted SCD, 11 patients had qualified positive blood cultures. Five different types of pathogens were isolated from these positive blood cultures: 4 Staphylococcus aureus, 3 Streptococcus pneumoniae, 2 Salmonella species, 1 Enterococcus species, and 1 Shigella boydii. No episode of bacteremia caused by Haemophilus influenzae type b was identified. The molecular serotyping of the Streptococcus pneumoniae isolates revealed non-vaccine serotypes 10A, 12F and 12F. From our AST result, two of the three Streptococcus pneumoniae were resistant to penicillin antibiotics. The Staphylococcus aureus isolates were penicillin resistant but cefoxitin sensitive, hence no methicillin (oxacillin) resistant Staphylococcus aureus was reported., Generally, the isolated pathogens were all sensitive to chloramphenicol, and vancomycin. Conclusion: Streptococcus pneumoniae and Staphylococcus aureus were the most common cause of bacteremia in these admitted SCD patients. The presence of non-typhoidal Salmonella and Shigella infection coupled with penicillin resistance should be considered during penicillin prophylaxis and empirical treatment regimens for SCD patients and future SCD management policies in the Gambia.

1718. Effectiveness of 13-valent pneumococcal conjugate vaccine for prevention of invasive pneumococcal disease among children in the United States between 2010 and 2019: an indirect cohort study

Abstract Background The 13-valent pneumococcal conjugate vaccine (PCV13) was introduced for infant use in the United States in 2010, replacing PCV7. A U.S. case-control study (2010–2014) demonstrated vaccine effectiveness (VE) for ≥1 dose of PCV13 at 86%; however, this study lacked statistical power to examine VE by number of doses and against individual serotypes. Methods We used the indirect cohort method to estimate VE of PCV13 against vaccine-type invasive pneumococcal disease among children &amp;lt; 5 years in the U.S. from May 1, 2010 to December 31, 2019. We included IPD cases identified through CDC’s Active Bacterial Core surveillance in 10 U.S. states; during 2010 – 2014, we additionally included cases enrolled in a post-licensure matched case-control study from expanded sites. Cases and controls were defined as individuals with PCV13-type-IPD (VT-IPD) and non-PCV13-type-IPD (NVT), respectively; serotype 6C was categorized as VT. We used logistic regression to estimate the adjusted odds of prior PCV13 receipt, controlling for confounders identified a priori including age category, race/ethnicity, sex, state, year, and any immunocompromising and/or chronic conditions. Results A total of 1,161 IPD cases were identified; 223 (19.2%) were VT cases and 938 (80.8%) were non-VT controls. Of those, 108 cases (48.4%; 108/223) and 600 controls (64.0%; 600/938) had received &amp;gt;3 PCV13 doses; 47 cases (21.1%) and 53 controls (5.7%) had received no PCV doses. Serotypes 19A (N=96), 3 (N=60), and 19F (N=45) caused 90.1% (201/223) of VT-IPD. VE of &amp;gt;1 or ≥3 PCV13 doses against VT-IPD was 81.7% (95% Confidence Interval: 69.1–89.1%) and 87.8% (75.2–94.0%), respectively. VE of ≥3 PCV13 doses was 87.0% (75.8–93.0%), 54.6% (-8.8–81.0%), and 92.9% (74.4–98.0%) against serotypes 19A, 3, and 19F, respectively. VE was 87.6% (67.9-95.2%) for three primary doses before 12 months of age and 92.4% (78.2–97.2%) for three primary doses and a booster at 12 months of age or older. Vaccine effectiveness estimates against PCV13-type IPD among US children under five years of age, 2010 - 2019 Conclusion VE of ≥1 PCV13 dose against IPD was consistent with the previous estimate from the case-control study, and ≥3 doses appear to provide substantial protection. Among the most commonly circulating VT-IPD, PCV13 was protective against serotypes 19A and 19F IPD; protection against serotype 3 IPD did not reach statistical significance. Disclosures Lee Harrison, MD, GSK: Advisor/Consultant|Merck: Advisor/Consultant|Pfizer: Advisor/Consultant|Sanofi: Advisor/Consultant Tamara Pilishvili, PhD MPH, GSK: Employed by GSK since February 2023. At the time of data collection and analysis for this work was employed by the CDC

1725. Differences in serotype 3 antibody response and antibody functionality compared to serotype 19A following 13-valent pneumococcal conjugate immunization in children

Abstract Background Background. 13-valent pneumococcal conjugate vaccine (PCV13) includes serotype 3 and 19A. However, prevention of infections with PCV13 may be less effective against serotype 3 than 19A. In young children, determine differences in IgG antibody levels, functionality of antibody by OPA and antibody avidity for serotype 3 compared to 19A following PCV13 immunization; determine IgG antibody levels following natural immunization for serotype 3 and 19A; reassess effectiveness of PCV13 against serotype 3 and 19A in prevention of acute otitis media (AOM) and colonization. Methods Samples were secured during a prospective longitudinal study conducted in Rochester NY of children age 6-36 months old. Pneumococcal detection was determined by culture. 713 serum samples were tested for antibody levels by ELISA, 68 serum for functional antibody by OPA, and 47 serum for antibody avidity by thiocyanate bond disruption. Age effects on antibody levels was modeled by generalized estimating equations. PCV13 effectiveness was assessed compared to pre-PCV13. Results The proportion children who did not reach protective threshold against IPD (&amp;lt; 0.35 µg/ml) after PCV13 immunization was higher for serotype 3 antibody compared to 19A. PCV13-induced antibody levels to serotype 3 were1.4 to 3.4 fold lower than 19A. OPA titers were not significantly different for serotype 3 compared to 19A, but antibody avidity at child age 6 and 15 months was significantly lower. Serotype 3 natural- immunized children showed a positive trend of increase in antibody level as children got older. In contrast, PCV13-immunized children showed a negative trend of antibody levels with age. For serotype 19A, both natural immunization and PCV13 immunization showed a positive trend in antibody levels over age. PCV13 effectiveness was not identified in preventing AOM or colonization for serotype 3 but effectiveness of 19A was re-confirmed. Conclusion Conclusions: PCV13 elicits lower antibody levels and lower avidity antibody to serotype 3 than 19A. PCV13 does not elicit antibody levels that increase over age despite a booster dose for serotype 3, as occurs for serotype 19A. Post PCV13-induced antibody levels for serotype 3 may be insufficient to prevent AOM and colonization in young children. Disclosures All Authors: No reported disclosures

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

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