Serotype 19A Research Articles

Effect of a Reduced PCV10 Dose Schedule on Pneumococcal Carriage in Vietnam

BackgroundAfter pneumococcal disease and colonization have been controlled through vaccination campaigns, a reduced pneumococcal conjugate vaccine (PCV) schedule may be sufficient to sustain that control at reduced costs.MethodsWe investigated whether a single primary dose and booster dose (1p+1) of the 10-valent PCV (PCV10) would be noninferior to alternative dose schedules in sustaining control of carriage of pneumococcal serotypes included in the vaccine. In Nha Trang, Vietnam, an area in which PCV had not been used previously, a PCV10 catch-up campaign was conducted in which the vaccine was offered to children younger than 3 years of age, after which a cluster-randomized trial was conducted in which children received PCV10 at 2, 3, and 4 months of age (3p+0 group); at 2, 4, and 12 months of age (2p+1 group); at 2 and 12 months of age (1p+1 group); or at 12 months of age (0p+1 group). Annual carriage surveys in infants (4 to 11 months of age) and toddlers (14 to 24 months of age) were conducted from 2016 through 2020. The primary end point was protection against carriage of vaccine serotypes, evaluated in a noninferiority analysis in the 1p+1 group as compared with the 2p+1 and 3p+0 groups, 3.5 years after vaccine introduction (noninferiority margin, 5 percentage points). Noninferiority of the 0p+1 schedule was also evaluated.ResultsIn 2016, before the introduction of PCV10, vaccine-serotype carriage was found in 160 of 1363 infants (11.7%); in 2020, vaccine-serotype carriage was found in 6 of 333 (1.8%), 5 of 340 (1.5%), and 4 of 313 (1.3%) infants in the 1p+1, 2p+1, and 3p+0 groups, respectively, indicating noninferiority of 1p+1 to 2p+1 (difference, 0.3 percentage points; 95% confidence interval [CI], −1.6 to 2.2) and to 3p+0 (difference, 0.5 percentage points; 95% CI, −1.4 to 2.4). Similarly, 1p+1 was noninferior to 2p+1 and 3p+0 for protection against vaccine-serotype carriage among toddlers. In 2016, carriage of serotype 6A was found in 99 of 1363 infants (7.3%); in 2020, it was found in 12 of 333 (3.6%), 10 of 340 (2.9%), and 3 of 313 (1.0%) infants in the 1p+1, 2p+1, and 3p+0 groups, respectively. The 0p+1 schedule was also noninferior to the other three dose schedules among infants and toddlers, although cross-protection against serotype 6A was less common than with the other vaccination schedules. No PCV10-associated severe adverse effects were observed.ConclusionsA reduced vaccination schedule involving a single primary dose and booster dose of PCV10 was noninferior to alternative schedules in protecting against vaccine-serotype carriage in infants and toddlers. (Funded by the Bill and Melinda Gates Foundation and others; ClinicalTrials.gov number, NCT02961231.)

Serotype distribution and antimicrobial resistance of Streptococcus pneumoniae isolated from children in Japan, 2023

BackgroundThe prevalence of serotypes and antimicrobial resistance of Streptococcus pneumoniae was characterized among children thirteen years after the licensure of the pneumococcal conjugate vaccine (PCV) in Japan. MethodsA total of 353 pneumococcal isolates were collected from Japanese children between March and July 2023. All the isolates were serotyped using genetic methods and tested for susceptibility to 14 antimicrobial agents. ResultsAmong the 353 isolates, the prevalence rates of non-PCV13 and non-PCV20 serotypes were 96.9 % and 77.9 %, respectively, including the dominant non-PCV13/PCV20 serotypes 23A (16.1 %), 35B (15.3 %), 15A (10.5 %), 15C (9.3 %), and 34 (9.1 %), which accounted for 60.3 % of all isolates. The high non-susceptibility rates were observed for macrolides (erythromycin, azithromycin, and clarithromycin; ≥81.9 %) and tetracycline (80.7 %). Penicillin non-susceptibility and multidrug resistance (MDR) were detected in 49.9 % (6.8 % resistant and 43.1 % intermediate) and 68.3 % of the isolates, respectively. The three most common non-PCV13/PCV20 serotypes 15A, 23A, and 35B exhibited high prevalence rates of penicillin non-susceptibility (≥89.5 %) and MDR (≥81.5 %). Extensive drug resistance was observed in 10.5 % of all isolates belonging to six different serotypes (12F, 23A, 11A, 15A, 35B, and 15B) and in the non-encapsulated strains of S. pneumoniae. ConclusionsOur study revealed a higher prevalence of non-susceptibility to penicillin with MDR in the three most common non-PCV13/PCV20 serotypes 15A, 23A, and 35B, in Japan, suggesting their persistence in the PCV13 era.

Complete hybrid genome assembly of Mannheimia haemolytica serotype A2 strain D95 isolated from ovine lung.

Mannheimia haemolytica is a major bacterial pathogen associated with broncho- and fibrinous pneumonia in ruminants. Here, we report the complete genome sequence of an isolate of serotype A2 M. haemolytica (D95) recovered from a pneumonic ovine lung. The D95 genome has a size of 2.7 Mb and contains 2,720 genes.

Invasive pneumococcal disease in a tertiary hospital in Madrid: are we using pneumococcal vaccine correctly?

IntroductionInvasive pneumococcal disease (IPD) is of concern. We describe the epidemiology and assess the vaccination schedule adequacy of IPD episodes (2019–2021) in northern Madrid. MethodsClinical, laboratory and vaccination data were collected from clinical/epidemiological records. Antimicrobial susceptibility testing was performed according to EUCAST and serotyping by Pneumotest-agglutination/Quellung. ResultsIPD was identified in 103 patients (71 [IQR 23.5] year-old; 50.4% males), 85.4% associated with bacteremia and a high mortality rate (19.4%). Serotypes 8 (29.9%), 3 and 22F (8% each) were dominant (45.9%), all antibiotic-susceptible. β-Lactams increased MICs and macrolide resistance were mainly linked to serotypes 19A, 23F, 24F, 6C, and 15A. Only 10.5% of adults eligible for vaccination had an adequate vaccine regimen before IPD being 40% due to nonvaccine-preventable serotypes (13, 23B, 24F, 31). ConclusionIPD episodes were dominated by antibiotic-susceptible ST8 and frequently occurred in adults at risk. Despite recommendations, vaccination adherence rates were very low.

Effectiveness of the ten- and thirteen-valent pneumococcal conjugate vaccines to prevent serotype 19A invasive pneumococcal disease in Quebec, Canada. A Canadian immunization research network (CIRN) study

In the province of Quebec, Canada, a 2 + 1 dose pneumococcal conjugate vaccine (PCV) program for children was implemented in 2004. PCV7, PCV10, PCV13 and a mixed PCV10/PCV13 schedule were sequentially used without catch-up. The effectiveness of vaccination schedules to prevent serotype 19A invasive pneumococcal disease (IPD) in <5-year-old children was estimated by the indirect cohort method during 2009–2023. A total of 248 19A IPD cases and 457 IPD controls were included in the analysis. Adjusted vaccine effectiveness (VEa) for ≥1 dose was 57 % [95 %CI: −1 %,82 %] for PCV10 and 62 % [16 %,83 %] for PCV13. VEa for 3 doses was 69 % [17 %,88 %] for PCV10, 76 % [39 %,90 %] for PCV13 and 86 % [64 %,95 %] for the 2PCV10 + 1PCV13 schedule. Protection provided by the PCV10-only schedule tended to be of lower magnitude compared to the two other schedules. The mixed PCV10 + PCV13 schedule showed a protection against 19A IPD at least comparable to that of 3 PCV-13 doses.

Severe Invasive Pneumococcal Disease Caused by Serotype 19A in Children Under Five Years in Tāmaki Makaurau Auckland, Aotearoa New Zealand.

Increases in childhood invasive pneumococcal disease (IPD) have been reported in several countries following the easing of COVID-19 pandemic mitigations. In Aotearoa New Zealand (AoNZ), a surge in IPD is occurring in young children concurrent with changes in pneumococcal vaccines and declining immunization coverage. We sought to examine epidemiologic and clinical features of IPD among children under 5 years in a large urban region of AoNZ in the 3 years post-COVID-19. Demographic, clinical and laboratory data were collated from children under 5 years with Streptococcus pneumoniae identified from normally sterile sites between January 1, 2021, and December 31, 2023, in Tāmaki Makaurau Auckland, AoNZ. We identified 93 episodes of IPD (annual incidence of 18-40 cases per 100,000 population per year). Serotype was identified in 68 episodes and 46 (68%) were serotype 19A. Incidence was higher in Pacific children compared with non-Māori, non-Pacific children (incidence rate ratio: 2.3; 95% confidence interval: 1.4-3.7). Bacteremia occurred in 65 (70%) episodes, empyema in 47 (51%), meningitis in 11 (12%) and hemolytic uremic syndrome in 7 (7.5%). All cases of hemolytic uremic syndrome and empyema were only among children with serotype 19A. Two children died, both had serotype 19A, and 13/91 survivors (14%) experienced serious sequelae. The use of the pneumococcal conjugate vaccine with lower valency and easing of COVID-19 containment measures each may have contributed to an increase in IPD in AoNZ. Serotype 19A is associated with empyema and causes severe disease in young children. Urgent efforts are required to improve PCV13 coverage in AoNZ.

Molecular genetic characteristics of Streptococcus pneumoniae serogroups 15 and 11 representatives circulating in Russia and their relationship with global genetic lineages

Aim of the study. Genetic analysis of Streptococcus pneumoniae serogroups 15 and 11 circulating in Russia according to the following parameters: serotype affiliation; clonal complex (CC); presence of resistance and virulence determinants; relatedness to genetic lineages circulating in the world, and justification of inclusion of the actual serotypes of serogroups 15 and 11 in the future conjugate vaccine composition. Materials and methods. The study included whole genome data of S. pneumoniae serogroups 11 and 15. Results. Genomes of serogroup 15 strains from Russia are represented mainly by serotypes 15B and 15C, the majority of which belong to CC-1025 and CC-1262. CC-1025 is characterized by a more frequent association with invasive diseases. Representatives of CC-1025 and CC-1262 contain virulence determinants unique to these genetic lineages within the studied population of serogroup 15: oligopeptide transporters, fructose-specific PTS system, unique hydrolase variants, additional iron ion transporters, the gene of zinc metalloprotease ZmpC (activating human MMP9). The genomes of serogroup 11 are represented mainly by serotype 11A, the majority belong to CC-62 and CC-1012. The virulence determinants unique to CC-62 (within the studied serogroup 11) include bacteriocins, components of oligopeptide transport, flavin reductase-like protein (adhesin, also protects bacteria from oxidative stress), fucose processing operon, PsaA (adhesin, also a component of the ATP-binding cassette transporter that imports manganese ions). Conclusion. In the Russian Federation, serogroups 15 and 11 are the most common non-vaccine serogroups. No antimicrobial resistance determinants have been identified in the genomes of representatives of these serogroups. For each of the genetic lineages prevalent in Russia and associated with serogroups 15 and 11, unique virulence determinants within the studied serogroup have been identified, which may contribute to the success of these lineages. It is advisable to include serotypes 15B and 11A in vaccines promising for the Russian Federation.

Characterization of azithromycin-resistant Shigella flexneri serotype 2a isolates using whole genome sequencing in Ontario from 2016 to 2018.

Azithromycin-resistant shigellosis is increasing globally. This retrospective analysis of Shigella flexneri serotype 2a isolates from 2016 to 2018 in Ontario found nearly half were azithromycin (47.7%, 72/151) and ciprofloxacin (50.7%, 77/152) resistant. Moreover, 34.7% (25/72) of azithromycin-resistant isolates were also ciprofloxacin-resistant. Four isolates were ceftriaxone-resistant, although all azithromycin-resistant isolates were ceftriaxone-susceptible. Overall, 83.6% (127/152) of all S. flexneri 2a isolates were recovered from males and 97.2% (70/72) of the azithromycin-resistant cases were males. Among the azithromycin-resistant cases, some (8/72) reported international travel. Phylogenetic analysis of azithromycin-resistant isolates revealed two large male-dominated clusters, and one cluster may have been due to importation of resistant strain. Comparison of plasmids isolated from the clusters in Ontario revealed the presence of incFII plasmid with high percentage of similarity to plasmids present in global outbreaks affecting mostly males including men who have sex with men (MSM). These two large azithromycin-resistant clusters are suggestive of an outbreak among MSM, though disease exposure or sexual orientation of patients was unknown. The presence of plasmid-borne azithromycin resistance in ciprofloxacin-resistant isolates is a public health concern. Antimicrobial surveillance is important for patient management, understanding the spread of novel resistance types in local communities which sometimes is introduced by travel. We found ongoing multidrug-resistant outbreaks spanning multiple years affecting males. Reduction of future outbreaks in high-risk communities like MSM requires consorted information flow between laboratory, public health, and physicians. We impart genomic and antimicrobial characteristics of multidrug S. flexneri 2a which may serve as reference by clinicians and public health.IMPORTANCEOral ciprofloxacin and azithromycin are generally considered as the first-line therapy of shigellosis. Here, we report the emergence and transmission of azithromycin and ciprofloxacin-resistant S. flexneri serotype 2a among male adults in Ontario during 2016-2018. The percentage of azithromycin and ciprofloxacin resistance among S. flexneri 2a is higher compared to previous reports from Canada and United States. Here, we show the genetic basis of the antimicrobial resistance among these unique groups of S. flexneri 2a isolates. We describe a domestically acquired azithromycin-resistant and ciprofloxacin-resistant S. flexneri 2a lineage in Ontario. Combining whole-genome sequencing (WGS) data with travel-associated data helped in understanding dissemination and transmission. We employed WGS, which not only helped us in understanding the genetic-relationship between isolates but also mine information regarding plasmids. In the future, linking WGS, travel-related data, and clinical data can provide enhanced contact tracing and improve public-health management.

Molecular and phenotypic characterization of Streptococcus pneumoniae isolates in a Japanese tertiary care hospital.

This study aimed to investigate the bacterial characteristics of pneumococcal isolates obtained from a tertiary care hospital in Japan. We analyzed the antimicrobial susceptibility, possession of macrolide resistance genes, pneumococcal serogroup/serotype, and sequence type (ST) of pneumococcal isolates from patients aged 15 years or older between 2011 and 2020 at Nagasaki University Hospital. Of the 73 isolates analyzed, 86.3% showed resistance to macrolides, and 28.8%, 46.6%, and 11.0% harbored mefA, ermB, and both, respectively. Of the isolates possessing ermB, 97.6% showed high levels of macrolide resistance [minimal inhibitory concentration (MIC) range, > 16 µg/mL]. Solithromycin (MIC range, 0.03-0.25 µg/mL), regardless of the presence of macrolide resistance genes, and lascufloxacin (MIC range, 0.06-0.5 µg/mL) showed potent in vitro activity against pneumococci. Serotype 19A was the most prevalent (six isolates), followed by serotypes 10A, 15A, and 15B/C (five isolates each). Four serotypes (11A, 19A, 22F, and 23B) and five STs (36, 99, 433, 558, and 3111) were significantly correlated with the presence of macrolide resistance genes. All four isolates with serotype 11A/ST99 and three isolates with serotype 19A/ST3111 harbored both mefA and ermB. No macrolide resistance genes were detected in either of the two isolates with serotype 22F/ST433, while all ten isolates with serogroup 15 (serotypes 15A and 15B/C, five isolates each) possessed ermB alone. Our study revealed the bacterial characteristics of the pneumococcal isolates obtained from our hospital. In vitro activity of solithromycin and lascufloxacin against these isolates was confirmed.

Characterization of Streptococcus pneumoniae isolates obtained from the middle ear fluid of US children, 2011-2021.

Pneumococcal conjugate vaccines (PCVs), including higher valency vaccines such as PCV20, have the potential to reduce pediatric otitis media. We assessed serotype distribution, potential PCV coverage, and antimicrobial susceptibility of Streptococcus pneumoniae isolates cultured from middle ear fluid (MEF) of US children age ≤5 years. S. pneumoniae isolates identified from US hospitals participating in the SENTRY Antimicrobial Surveillance program from 2011 to 2021 were included. Serotypes were determined by in silico analysis based on Pneumococcal Capsular Typing methodology. The percentage of isolates belonging to serotypes included in PCV13 (serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F), PCV15 (PCV13 plus 22F, 33F), and PCV20 (PCV13 plus, 8, 10A, 11A, 12F, 15B, 22F and 33F) was calculated. Antimicrobial susceptibility testing was performed by broth microdilution and interpreted using CLSI criteria. Nonsusceptibility was defined as isolates that were intermediate or resistant to a selected antimicrobial. Among the 199 S. pneumoniae isolates that were identified, 56.8% were from children age <2 years. Six serotypes accounted for around 60% of isolates: 35B (16.6%), 15B (14.6%), 15A (7.5%), 19A (7.5%), 19F (7.5%), and 3 (7.0%). Serotypes included in PCV13, PCV15, and PCV20 accounted for 23.1%, 30.2%, and 54.8% of isolates, respectively. Overall, 45.2% of isolates were penicillin non-susceptible, and 13.6% were MDR, of which 48% were serotype 19A. Seven serotypes (19A, 15A, 15B, 15C, 23A, 33F, and 35B) accounted for the majority of non-susceptible isolates. PCVs, particularly PCV20, may prevent a substantial fraction of S. pneumoniae otitis media (OM), including OM due to non-susceptible serotypes. The addition of serotypes 15A, 23A, and 35B would improve coverage against susceptible and non-susceptible pneumococcal OM.

Multidrug-resistant Shigella flexneri outbreak associated with a high-mortality spillover event into nonhuman primates.

Shigellosis is a gastrointestinal infection caused by species of Shigella. A large outbreak of Shigella flexneri serotype 2a occurred in Albuquerque, New Mexico (NM) between May 2021 and November 2023 that involved humans and nonhuman primates (NHP) from a local zoo. We analyzed the genomes of 202 New Mexico isolates as well as 15 closely related isolates from other states, and four from NHP. The outbreak was initially detected within men who have sex with men (MSM) but then predominantly affected people experiencing homelessness (PEH). Nearly 70% of cases were hospitalized and there was one human death. The outbreak extended into Albuquerque's BioPark Zoo, causing high morbidity and six deaths in NHPs. The NHP isolates were identical to those in the human outbreak. All isolates were multidrug-resistant, including towards fluoroquinolones, a first line treatment option which led to treatment failures in human and NHP populations. We demonstrate the transmission of this S. flexneri strain between humans and NHPs, causing fatalities in both populations. This study demonstrates the threat of antimicrobial resistant organisms to vulnerable human and primate populations and emphasizes the value of vigilant genomic surveillance within a One Health framework.

Long-term impact of 10-valent pneumococcal conjugate vaccine in Kenya: Nasopharyngeal carriage among children in a rural and an urban site six years after introduction

BackgroundKenya introduced Synflorix™ (GlaxoSmithKline, PCV10-GSK), a 10-valent pneumococcal conjugate vaccine, in 2011, using three primary doses and, in select areas, catch-up campaigns. Surveys conducted 1–2 years post-introduction showed a stable prevalence of pneumococcal colonization, with declines in vaccine-type carriage. However, little is known about the long-term impact of PCV10-GSK in Kenya. MethodsWe conducted a cross-sectional survey of pneumococcal carriage among children aged <5 years in November–December 2017 in Kibera (Nairobi informal settlement, no catch-up) and Asembo (rural western Kenya, 2-dose catch-up for children 1–4 years), using the same methods and settings as prior annual surveys from 2009 to 2013. Participants were randomly selected from an ongoing population-based surveillance platform. Nasopharyngeal swabs were frozen in skim milk-tryptone-glucose-glycerin media within 4 h and underwent culture with broth enrichment for pneumococcus. Isolates were serotyped by polymerase chain reaction and Quellung. ResultsWe enrolled 504 children, including 252 from each site; >90 % of participants had received 3 doses of PCV10-GSK. Pneumococcal colonization was detected in 210 (83.3 %) participants in Kibera and 149 (59.1 %) in Asembo, which was significantly lower than the prevalence observed in 2013 (92.9 % and 85.7 %, respectively). PCV10-GSK serotypes were detected in 35/252 (13.9 %) participants in Kibera and 23/252 (9.1 %) in Asembo, respectively; these prevalences were lower, but not statistically different, from vaccine-type carriage prevalences in 2013 (17.3 % and 13.3 %, respectively). In 2017 in both sites, serotypes 3, 6A, 19A, 19F, and 35B were among the most common serotypes. ConclusionSix years post-PCV10-GSK introduction, the prevalence of pneumococcal carriage among children has decreased, and the impact of PCV10-GSK on vaccine-type carriage has plateaued. Kenya recently changed from PCV10-GSK to Pneumosil™ (Serum Institute of India), a 10-valent PCV that includes serotypes 6A and 19A; these data provide historical context for interpreting changes in vaccine-type carriage following the PCV formulation switch.

Chemical Synthesis of Truncated Capsular Oligosaccharide of Serotypes 6C and 6D of Streptococcus pneumoniae with Their Immunological Studies.

Serotypes 6C and 6D of Streptococcus pneumoniae are two major variants that cause invasive pneumococcal disease (IPD) in serogroup 6 alongside serotypes 6A and 6B. Since the introduction of the pneumococcal conjugate vaccines PCV7 and PCV13, the number of cases of IPD caused by pneumococcus in children and the elderly population has greatly decreased. However, with the widespread use of vaccines, a replacement effect has recently been observed among different serotypes and lowered the effectiveness of the vaccines. To investigate protection against the original serotypes and to explore protection against variants and replacement serotypes, we created a library of oligosaccharide fragments derived from the repeating units of the capsular polysaccharides of serotypes 6A, 6B, 6C, and 6D through chemical synthesis. The library includes nine pseudosaccharides with or without exposed terminal phosphate groups and four pseudotetrasaccharides bridged by phosphate groups. Six carbohydrate antigens related to 6C and 6D were prepared as glycoprotein vaccines for immunogenicity studies. Two 6A and two 6B glycoconjugate vaccines from previous studies were included in immunogenicity studies. We found that the conjugates containing four phosphate-bridged pseudotetrasaccharides were able to induce good immune antibodies and cross-immunogenicity by showing superior activity and broad cross-protective activity in OPKA bactericidal experiments.

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

BackgroundA U.S. case-control study (2010–2014) demonstrated vaccine effectiveness (VE) for ≥ 1 dose of the thirteen-valent pneumococcal conjugate vaccine (PCV13) against vaccine-type (VT) invasive pneumococcal disease (IPD) at 86 %; however, it lacked statistical power to examine VE by number of doses and against individual serotypes. MethodsWe used the indirect cohort method to estimate PCV13 VE against VT-IPD among children aged < 5 years in the United States from May 1, 2010 through December 31, 2019 using cases from CDC’s Active Bacterial Core surveillance, including cases enrolled in a matched case-control study (2010–2014). Cases and controls were defined as individuals with VT-IPD and non-PCV13-type-IPD (NVT-IPD), respectively. We estimated absolute VE using the adjusted odds ratio of prior PCV13 receipt (1-aOR x 100 %). ResultsAmong 1,161 IPD cases, 223 (19.2 %) were VT cases and 938 (80.8 %) were NVT controls. Of those, 108 cases (48.4 %; 108/223) and 600 controls (64.0 %; 600/938) had received > 3 PCV13 doses; 23 cases (17.6 %) and 15 controls (2.4 %) had received no PCV doses. VE ≥ 3 PCV13 doses against VT-IPD was 90.2 % (95 % Confidence Interval75.4–96.1 %), respectively. Among the most commonly circulating VT-IPD serotypes, VE of ≥ 3 PCV13 doses was 86.8 % (73.7–93.3 %), 50.2 % (28.4–80.5 %), and 93.8 % (69.8–98.8 %) against serotypes 19A, 3, and 19F, respectively. ConclusionsAt least three doses of PCV13 continue to be effective in preventing VT-IPD among children aged < 5 years in the US. PCV13 was protective against serotypes 19A and 19F IPD; protection against serotype 3 IPD did not reach statistical significance.

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

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

Immunogenicity and safety of a 14-valent pneumococcal polysaccharide conjugate vaccine (PNEUBEVAX 14™) administered to 6–8 weeks old healthy Indian Infants: A single blind, randomized, active-controlled, Phase-III study

BackgroundIntroduction of pneumococcal conjugate vaccines (PCVs) reduced the number of cases of pneumococcal disease (PD). However, there is an increase in clinical and economic burden of PD from serotypes that are not part of the existing pneumococcal vaccines, particularly impacting pediatric and elder population. In addition, the regions where the PCV is not available, the disease burden remains high. In this study, immunogenicity and safety of the BE’s 14-valent PCV (PNEUBEVAX 14™; BE-PCV-14) containing two additional epidemiologically important serotypes (22F and 33F) was evaluated in infants in comparison to licensed vaccine, Prevenar-13 (PCV-13). MethodsThis is a pivotal phase-3 single blind randomized active-controlled study conducted at 12 sites across India in 6–8 weeks old healthy infants at 6–10–14 weeks dosing schedule to assess immunogenic non-inferiority and safety of a candidate BE-PCV-14. In total, 1290 infants were equally randomized to receive either BE-PCV-14 or PCV-13. Solicited local reactions and systemic events, adverse events (AEs), serious AEs (SAEs), and medically attended AEs (MAAEs) were recorded. Immunogenicity was assessed by measuring anti-PnCPS (anti-pneumococcal capsular polysaccharide) IgG concentration and functional antibody titers through opsonophagocytic activity (OPA), one month after completing three dose schedule. Cross protection to serotype 6A offered by serotype 6B was also assessed in this study. FindingsThe safety profile of BE-PCV-14 was comparable to PCV-13 vaccine. Majority of reported AEs were mild in nature. No severe or serious AEs were reported in both the treatment groups. For the twelve common serotypes and for the additional serotypes (22F and 33F) in BE-PCV-14, NI criteria was demonstrated as defined by WHO TRS-977. Primary immunogenicity endpoint was met in terms of IgG immune responses for all 14 serotypesof BE-PCV-14. Moreover, a significant proportion of subjects (69%) seroconverted against serotype 6A, even though this antigen was not present in BE-PCV-14. This indicates that serotype 6B of BE-PCV-14 cross protects serotype 6A. BE-PCV-14 also elicited comparable serotype specific functional OPA immune responses to all the serotypes common to PCV-13. InterpretationsBE-PCV-14 was found to be safe and induced robust and functional serotype specific immune responses to all 14 serotypes. It also elicited cross protective immune response against serotype 6B.These findings suggest that BE-PCV-14 can be safely administered to infants and achieve protection against pneumococcal disease caused by serotypes covered in the vaccine.The study was prospectively registered with clinical trial registry of India – CTRI/2020/02/023129.

Differential mechanism between Listeria monocytogenes strains with different virulence contaminating ready-to-eat sausages during the simulated gastrointestinal tract

Listeria monocytogenes exhibits varying levels of pathogenicity when entering the host through contaminated food. However, little is known regarding the stress response and environmental tolerance mechanism of different virulence strains to host gastrointestinal (GI) stimuli. This study analyzed the differences in the survival and genes of stress responses among two strains of L. monocytogenes 10403S (serotype 1/2a, highly virulent strain) and M7 (serotype 4a, low-virulence strain) during simulated gastrointestinal digestion. The results indicated that L. monocytogenes 10403S showed greater acid and bile salt tolerance than L. monocytogenes M7, with higher survival rates and less cell deformation and cell membrane permeability during the in vitro digestion. KEGG analysis of the transcriptomes indicated that L. monocytogenes 10403S displayed significant activity in amino acid metabolism, such as glutamate and arginine, associated with acid tolerance. Additionally, L. monocytogenes 10403S demonstrated a higher efficacy in promoting activities that preserve bacterial cell membrane integrity and facilitate flagellar protein synthesis. These findings will contribute valuable practical insights into the tolerance distinctions among different virulence strains of L. monocytogenes in the GI environment.

Nasopharyngeal Carriage of Streptococcus pneumoniae in Tunisian Healthy under-Five Children during a Three-Year Survey Period (2020 to 2022).

We aimed to assess the prevalence of nasopharyngeal pneumococcal carriage and to determine serotype distribution, antibiotic susceptibility patterns, and evolutionary dynamics of Streptococcus pneumoniae isolates in healthy under-five children. Nasopharyngeal swabs were collected from healthy children over three survey periods between 2020 and 2022. All pneumococcal isolates were serotyped and tested for antimicrobial susceptibility. A total of 309 S. pneumoniae isolates were collected, with an overall prevalence of nasopharyngeal pneumococcal carriage of 24.4% (CI95%: [22-26.8%]). These isolates were classified into 25 different serotypes. The most common serotypes were 14 (14.9%), 19F (12%), 6B (10.4%), and 23F (7.4%), which are covered by the PCV10 vaccine, as well as 19A (8.4%) and 6A (7.8%), which are covered by the PCV13 vaccine. A significant decrease in the proportion of serotype 19F (p = 0.001) and an increase in serotypes 19A (p = 0.034) and 6A (p = 0.029) were observed between the three survey periods. Multidrug resistance (MDR) was noted for 56.6% of the isolates. A significant association with antimicrobial resistance was observed for the most frequent serotypes, mainly serotype 19A. In conclusion, one-quarter of healthy under-five children in Tunisia carried S. pneumoniae in their nasopharynx. A dominance of vaccine serotypes significantly associated with antimicrobial resistance was recorded.

Complete genome sequence of invasive Streptococcus pneumoniae serotype 11A causing meningitis in an adult patient, Italy 2022.

Streptococcus pneumoniae is a major global health concern, being a common cause of meningitis in both children and adults. Here, we report the complete genome sequence of P10_PNE_LCR, a S. pneumoniae 11A strain isolated in Northern Italy from an adult patient diagnosed with meningitis.

Antibiotic-Resistance Profiles and Genetic Diversity of Shigella Isolates in China: Implications for Control Strategies.

The urgent need for comprehensive and systematic analyses of Shigella as the key pathogen led us to meticulously explore the epidemiology and molecular attributes of Shigella isolates. Accordingly, we procured 24 isolates (10 from Xinjiang and 14 from Wuhan, China) and performed serotype identification and antimicrobial susceptibility testing. Resistance gene detection and homology analysis by polymerase chain reaction and pulsed-field gel electrophoresis (PFGE), respectively, were performed for genetic diversity analysis. All isolates were identified as Shigella flexneri, with 70% (35.4-91.9%) and 30% (8.1-64.6%) of the Xinjiang isolates and 85.7% (56.2-97.5%) and 14.3% (2/14, 2.5-43.9%) of the Wuhan isolates belonging to serotype 2a and serotype 2b, respectively. All isolates displayed resistance to at least two antibiotics and complete resistance to ampicillin. Multidrug resistance (MDR) was recorded in 70.8% (48.8-86.6%) of isolates, with Xinjiang isolates exhibiting relatively higher resistance to ampicillin-sulbactam, piperacillin, ceftriaxone, and aztreonam. Conversely, Wuhan isolates displayed higher MDR and resistance to tetracycline, ciprofloxacin, levofloxacin, and cefepime relative to Xinjiang isolates. Molecular scrutiny of antibiotic-resistance determinants revealed that blaTEM was the main mechanism of ampicillin resistance, blaCTX-M was the main gene for resistance to third- and fourth-generation cephalosporins, and tetB was the predominant gene associated with tetracycline resistance. Four Xinjiang and seven Wuhan isolates shared T1-clone types (>85%), and two Xinjiang and one Wuhan isolates were derived from the T6 clone with a high similarity of 87%. Six PFGE patterns (T1, T2, T5, T6-3, T8, and T10) of S. flexneri were associated with MDR. Thus, there is a critical need for robust surveillance and control strategies in managing Shigella infections, along with the development of targeted interventions and antimicrobial stewardship programs tailored to the distinct characteristics of Shigella isolates in different regions of China.