Non-vaccine Serotypes Research Articles

What do you get? Transmission of pneumococcal pneumonia.

Streptococcus pneumoniae is a polysaccharide encapsulated bacterium responsible for the majority of cases of community acquired pneumonia. The upper respiratory tract of children becomes colonized with pneumococci early in life, from the first weeks of life up to 18 months. Factors which influence timing of colonization include geographical localization, socio-economic circumstances, and household conditions. Pneumococcal pneumonia to a degree is a seasonal disease, peaking in the winter months. One of the epidemiological determinants is that viral infections (in particular influenza) predispose for pneumococcal pneumonia. The infectious nature of pneumococcal pneumonia was underscored during the COVID-19 pandemic. Due to societal restrictions imposed (face masks, social distancing) the incidence of invasive pneumococcal disease (IPD) dropped, and returned to pre-COVID-19 numbers after lifting of the restrictions. There are 100 different S. pneumoniae serotypes, based on differences in the capsular polysaccharide. Introduction of protein conjugated polysaccharide vaccines (PCV) has reduced the incidence of IPD in children. Because children are the reservoir for other risk groups, in particular the elderly, introduction of PCV has indirectly also reduced the burden of IPD in latter risk group. The first generation of PCV consisted of the seven most prevalent pneumococcal serotypes. After implementation, replacement colonization of the upper respiratory tract with non-vaccine serotypes was observed and also replacement disease. Upcoming 24-valent PCVs will have a much broader coverage, but whether replacement disease now has been eliminated remains to be seen.

Emerging pneumococcal serotypes in Iraq: scope for improved vaccine development.

Pneumococcal disease is a global public health concern as it affects the young, aged and the immunocompromised. The development of pneumococcal vaccines and their incorporation in the immunization programs has helped to reduce the global burden of disease. However, serotype replacement and the emergence of non-vaccine serotypes as well as the persistence of a few vaccine serotypes underscores the need for development of new and effective vaccines against such pneumococcal serotypes. In the Middle East, places of religious mass gatherings are a hotspot for disease transmission in addition to the global risk factors. Therefore, the periodic surveillance of pneumococcal serotypes circulating in the region to determine the effectiveness of existing prevention strategies and develop improved vaccines is warranted. Currently, there is a lack of serotype prevalence data for Iraq due to inadequate surveillance in the region. Thus, this review aims to determine the pneumococcal serotypes circulating in Iraq which may help in the development and introduction of improved pneumococcal vaccines in the country.

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.

Bacterial nasopharyngeal colonisation in children in South Africa before and during the COVID-19 pandemic: an observational study

Deployment of non-pharmaceutical interventions such as face masking and physical distancing during the COVID-19 pandemic could have altered the transmission dynamics and carriage of respiratory organisms. We evaluated colonisation with Streptococcus pneumoniae and other upper respiratory tract bacterial colonisers before and during the COVID-19 pandemic. We did two cross-sectional surveys in Soweto, South Africa from July 3 to Dec 13, 2018 (pre-COVID-19 period) and from Aug 4, 2021, to March 31, 2022 (COVID-19 period) in healthy children (aged ≤60 months) who had recorded HIV status and had not received antibiotics in the 21 days before enrolment. At enrolment, we collected nasopharyngeal swab samples from child participants. Following nucleic acid extraction, nanofluidic quantitative PCR was used to screen all samples for 92 S pneumoniae serotypes and 14 other bacteria. The primary objective was to compare the prevalence and density of pneumococcal nasopharyngeal colonisation, overall and stratified by 13-valent pneumococcal conjugate vaccine (PCV13) serotypes and non-vaccine serotypes. Secondary study objectives included a comparison of serotype-specific pneumococcal colonisation and density, as well as colonisation by the 14 other bacteria in the COVID-19 versus pre-COVID-19 period. We used an adjusted multiple logistic and linear regression model to compare the colonisation prevalence and density between study periods. We analysed nasopharyngeal swabs from 1107 children (n=571 in the pre-COVID-19 period; n=536 in the COVID-19 period). We observed no change in overall pneumococcal colonisation between periods (274 [51%] of 536 in the COVID-19 period vs 282 [49%] of 571 in the pre-COVID-19 period; adjusted odds ratio [aOR] 1·03 [95% CI 0·95-1·12]). The prevalence of PCV13 serotypes was lower in the COVID-19 than in the pre-COVID-19 period (72 [13%] vs 106 [19%]; 0·87 [0·78-0·97]), whereas the prevalence of non-typeable S pneumoniae was higher (34 [6%] vs 63 [12%]; 1·30 [1·12-1·50]). The mean log10 density for overall pneumococcal colonisation was lower in the COVID-19 period than in the pre-COVID-19 period (3·96 [95% CI 3·85-4·07] vs 4·72 [4·63-4·80] log10 genome equivalents per mL; p<0·0001). A lower density of non-vaccine serotypes (3·63 [3·51-3·74] vs 4·08 [3·95-4·22] log10 genome equivalents per mL; p<0·0001) and non-typeable S pneumoniae (3·11 [2·94-3·29] vs 4·41 [4·06-4·75] log10 genome equivalents per mL; p<0·00001) was also observed in the COVID-19 period. There was no difference in the density of PCV13 serotypes between the periods. The prevalence of colonisation during the COVID-19 versus pre-COVID-19 period was lower for non-typeable Haemophilus influenzae (280 [49%] vs 165 [31%]; aOR 0·77 [95% CI 0·71-0·84]), Moraxella catarrhalis (328 [57%] vs 242 [45%]; 0·85 [0·79-0·92]), and Neisseria lactamica (51 [9%] vs 13 [2%]; 0·64 [0·52-0·78]), but higher for Acinetobacter baumannii (34 [6%] vs 102 [19%]; 1·55 [1·35-1·77]) and Staphylococcus aureus (29 [5%] vs 52 [10%]; 1·28 [1·10-1·50]). There were variable effects on the colonisation prevalence and density of bacterial organisms during the COVID-19 compared with the pre-COVID-19 period. The lower prevalence of PCV13 serotype together with other respiratory organisms including non-typeable H influenzae and M catarrhalis could have in part contributed to a decrease in all-cause lower respiratory tract infections observed in South Africa during the initial stage of the COVID-19 pandemic. The pathophysiological mechanism for the increase in A baumannii and S aureus colonisation warrants further investigation, as does the clinical relevance of these findings. The Bill & Melinda Gates Foundation.

Antimicrobial susceptibility and serotype distribution of Streptococcus pneumoniae isolates among children in Suzhou, China.

Streptococcus pneumoniae (SP) is responsible for pneumococcal diseases with severe morbidity and mortality. High rates of drug resistance constitute serious public health concerns. Vaccination has proven to be an effective means of reducing disease burden. Epidemiological information of antibiotic susceptibilities and serotype distribution will be of great help to the management of pneumococcal infections. This study reported the serotype distribution and antibiotic resistance pattern of SP in hospitalized children in Suzhou during the years 2017-2018. The aim is to reduce pneumococcal resistance and guide vaccination. The clinical data of hospitalized children with SP were collected and analyzed. A total of 2,446 strains of SP were isolated from these patients. Serotypes were determined using the Quellung reaction. Antibiotic resistance was tested using the E-test diffusion method. The non-susceptible rates of the isolates to penicillin, amoxicillin, and cefotaxime were 9.5%, 27.7%, and 27.2%, respectively. And 97.6% of SP isolates showed multidrug-resistant (MDR). The most common resistance pattern of non-invasive isolates was macrolides + sulfamethoxazole + clindamycin + tetracycline. The major serotypes of this resistance pattern were 6A, 23F, 6B, 19F, 15B. The most extensive resistance pattern of invasive isolates was macrolides + β-lactams + sulfamethoxazole + clindamycin + tetracycline. The most common serotypes of the pattern were 19F, 19A, 6B, 23F, 6A. The most common serotypes were 19F (28.6%), 6B (11.9), 23F (11.2%), 6A (10.6%), and 19A (9.1%). In the isolates with MDR, the first five most common serotypes were 19F, non-vaccine serotype (NVT), 6B, 6A and 23F. Strains belonging to different serotypes exhibited distinct antimicrobial resistance patterns and were found to be associated with different diseases. The coverage rates of pneumococcal conjugate vaccine (PCV)7 and PCV13 in all isolates reached 60.4% (310/513) and 80.9% (415/513), respectively. The main serotypes of SP in Suzhou were 19F, 6B, 23F, 6A, and 19A. The use of PCV13 is beneficial to children in Suzhou.

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.

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

Antimicrobial resistance in Streptococcus pneumoniae: a retrospective analysis of emerging trends in the United Arab Emirates from 2010 to 2021.

Although pneumococcal conjugate vaccines (PCV) have been effective in reducing the burden of Streptococcus pneumoniae infections, there is a paucity of data on the relationship with antimicrobial resistance (AMR) trends in the Arabian Gulf region. This study was carried out to assess S. pneumoniae resistance trends in the United Arab Emirates (UAE) where PCV-13 vaccination was introduced in 2011. Retrospective analysis of S. pneumoniae demographic and microbiological data collected as part of the national AMR surveillance program from 2010 to 2021 was carried out. A survey of reporting sites and hand searching of annual reports of local health authorities was carried out to identify data on S. pneumoniae serotypes as this is not included in the AMR surveillance database. From 2010 to 2021, 11,242 non-duplicate S. pneumoniae isolates were reported, increasing from 324 in 2010 to 1,115 in 2021. Factoring in annual increment in the number of surveillance sites, the number of isolates per site showed an upward trajectory from 2015 to 2018 and declined in 2020 with the onset of the pandemic. The majority of isolates (n/N = 5,751/11,242; 51.2%) were from respiratory tract specimens with 44.5% (n/N = 2,557/5,751) being nasal colonizers. Up to 11.9% (n/N = 1,337/11,242) were invasive pneumococcal disease (IPD) isolates obtained from sterile site specimens including blood (n = 1,262), cerebrospinal (n = 52), pleural (n = 19) and joint (n = 4) fluid; and were predominantly from pediatric patients. The downward trend for amoxicillin and for penicillin G at the non-meningitis and meningitis as well as oral penicillin breakpoints was statistically significant. In contrast, increasing trends of resistance were seen for levofloxacin, moxifloxacin, trimethoprim/sulfamethoxazole and erythromycin. IPD and non-IPD isolates showed similar demographic and AMR trends. None of the surveillance sites carried out S. pneumoniae serotyping and handsearching of annual reports did not yield this information. The increasing trend of pneumococcal disease and AMR with emergence of isolates with MDR phenotype despite is of concern. In the absence of S. pneumoniae serotyping the role of non-vaccine serotypes in driving this pattern remains unknown. There is an urgent need for serotype, genomic and AMR surveillance of S. pneumoniae isolates in the UAE.

Serotype-Dependent Inhibition of Streptococcus pneumoniae Growth by Short-Chain Fatty Acids.

Streptococcus pneumoniae (pneumococcus) is an opportunistic pathogen that can cause severe infectious diseases such as pneumonia, meningitis, and otitis media. Despite the availability of antibiotics and pneumococcal vaccines against some invasive serotypes, pneumococcal infection remains a tremendous clinical challenge due to the increasing frequency of infection by antimicrobial resistant, nonencapsulated, and/or non-vaccine serotype strains. Short-chain fatty acids (SCFAs), which are produced at various mucosal sites in the body, have potent antimicrobial activity, including inhibition of pathogen growth and/or bacterial biofilm formation. In this study, we investigated the antimicrobial activity of SCFAs (acetate, propionate, and butyrate) against various serotypes pneumococci. Propionate generally inhibited the growth of S. pneumoniae serotypes included in the pneumococcal conjugate vaccine (PCV) 13, except for serotypes 3 and 7F, though butyrate and acetate showed no or low inhibition, depending on the serotypes. Of note, butyrate showed strong inhibition against serotype 3, the most prevalent invasive strain since the introduction of the PCV. No SCFAs showed inhibitory effects against serotype 7F. Remarkably, the nonencapsulated pneumococcal strain had more sensitivity to SCFAs than encapsulated parental strains. Taken together, these results suggest that propionate showing the most potent inhibition of pneumococcal growth may be used as an alternative treatment for pneumococcal infection, and that butyrate could be used against serotype 3, which is becoming a serious threat.

The metabolic, virulence and antimicrobial resistance profiles of colonising Streptococcus pneumoniae shift after PCV13 introduction in urban Malawi

Streptococcus pneumoniae causes substantial mortality among children under 5-years-old worldwide. Polysaccharide conjugate vaccines (PCVs) are highly effective at reducing vaccine serotype disease, but emergence of non-vaccine serotypes and persistent nasopharyngeal carriage threaten this success. We investigated the hypothesis that following vaccine, adapted pneumococcal genotypes emerge with the potential for vaccine escape. We genome sequenced 2804 penumococcal isolates, collected 4-8 years after introduction of PCV13 in Blantyre, Malawi. We developed a pipeline to cluster the pneumococcal population based on metabolic core genes into “Metabolic genotypes” (MTs). We show that S. pneumoniae population genetics are characterised by emergence of MTs with distinct virulence and antimicrobial resistance (AMR) profiles. Preliminary in vitro and murine experiments revealed that representative isolates from emerging MTs differed in growth, haemolytic, epithelial infection, and murine colonisation characteristics. Our results suggest that in the context of PCV13 introduction, pneumococcal population dynamics had shifted, a phenomenon that could further undermine vaccine control and promote spread of AMR.

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.

Genomic epidemiology of Streptococcus pneumoniae serotype 16F lineages.

Due to the emergence of non-vaccine serotypes in vaccinated populations, Streptococcus pneumoniae remains a major global health challenge despite advances in vaccine development. Serotype 16F is among the predominant non-vaccine serotypes identified among vaccinated infants in South Africa (SA). To characterize lineages and antimicrobial resistance in 16F isolates obtained from South Africa and place the local findings in a global context, we analysed 10 923 S. pneumoniae carriage isolates obtained from infants recruited as part of a broader SA birth cohort. We inferred serotype, resistance profile for penicillin, chloramphenicol, cotrimoxazole, erythromycin and tetracycline, and global pneumococcal sequence clusters (GPSCs) from genomic data. To ensure global representation, we also included S. pneumoniae carriage and disease isolates from the Global Pneumococcal Sequencing (GPS) project database (n=19 607, collected from 49 countries across 5 continents, 1995-2018, accessed 17 March 2022). Nine per cent (934/10923) of isolates obtained from infants in the Drakenstein community in SA and 2 %(419/19607) of genomes in the GPS dataset were serotype 16F. Serotype 16F isolates were from 28 different lineages of S. pneumoniae, with GPSC33 and GPSC46 having the highest proportion of serotype 16F isolates at 26 % (346/1353) and 53 % (716/1353), respectively. Serotype 16F isolates were identified globally, but most isolates were collected from Africa. GPSC33 was associated with carriage [OR (95 % CI) 0.24 (0.09-0.66); P=0.003], while GPSC46 was associated with disease [OR (95 % CI) 19.9 (2.56-906.50); P=0.0004]. Ten per cent (37/346) and 15 % (53/346) of isolates within GPSC33 had genes associated with resistance to penicillin and co-trimoxazole, respectively, and 18 % (128/716) of isolates within GPSC46 had genes associated with resistance to co-trimoxazole. Resistant isolates formed genetic clusters, which may suggest emerging resistant lineages. Serotype 16F lineages were common in southern Africa. Some of these lineages were associated with disease and resistance to penicillin and cotrimoxazole. We recommend continuous genomic surveillance to determine the long-term impact of serotype 16F lineages on vaccine efficacy and antimicrobial therapy globally. Investing in vaccine strategies that offer protection over a wide range of serotypes/lineages remains essential. This paper contains data hosted by Microreact.

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.

Exploring Streptococcus pneumoniae capsular typing through MALDI-TOF mass spectrometry and machine-learning algorithms in Argentina: Identifying prevalent NON PCV13 serotypes alongside PCV13 serotypes

IntroductionLaboratory surveillance of Streptococcus pneumoniae serotypes plays a crucial role in effectively implementing vaccines to prevent invasive pneumococcal diseases. The conventional method of serotyping, known as the Quellung reaction, is both time-consuming and expensive. However, the emergence of MALDI-TOF MS technology has revolutionized microbiology laboratories by enabling rapid and cost-effective serotyping based on protein profiles. ObjectivesIn this study, we aimed to investigate the viability of utilizing MALDI-TOF MS technology as an adjunctive and screening method for capsular typing of Streptococcus pneumoniae. Our approach involved developing classification models based on MALDI-TOF MS to discern between Streptococcus pneumoniae strains originating from PCV13 (13-valent pneumococcal conjugate vaccine) and NON PCV13 isolates. MethodsFirstly, we established a comprehensive spectral database comprising isolates of serotypes present in the PCV13 vaccine, along with the top 10 most prevalent NON PCV13 serotypes based on local epidemiological data. This database served as a foundation for developing unsupervised models utilizing MALDI-TOF MS spectra, which enabled us to identify inherent patterns and relationships within the data. Our analysis involved a dataset comprising 215 new isolates collected from nationwide surveillance in Argentina. Our approach involved developing classification models based on MALDI-TOF MS to discern between Streptococcus pneumoniae strains originating from PCV13 (13-valent pneumococcal conjugate vaccine) and NON PCV13 isolates. ResultsAlthough our findings revealed suboptimal performance in serotype classification, they provide valuable insights into the potential of machine learning algorithms in this context. The sensitivity of the models ranged from 0.41 to 0.46, indicating their ability to detect certain serotypes. The observed specificity consistently remained at 0.60, suggesting a moderate level of accuracy in identifying non-vaccine serotypes. These results highlight the need for further refinement and optimization of the algorithms to enhance their discriminative power and predictive accuracy in serotype identification.By addressing the limitations identified in this study, such as exploring alternative feature selection techniques or optimizing algorithm parameters, we can unlock the full potential of machine learning in robust and reliable serotype classification of S. pneumoniae. Our work not only provides a comprehensive evaluation of multiple machine learning models but also emphasizes the importance of considering their strengths and limitations. ConclusionOverall, our study contributes to the growing body of research on utilizing MALDI-TOF MS and machine learning algorithms for serotype identification purposes.

Clinical characteristics and antimicrobial susceptibility of non-vaccine serotype Streptococcus pneumoniae in adult Japanese patients with pneumonia

BackgroundNon-vaccine serotype (NVT) pneumococcal pneumonia in Japan has increased with the spread of pneumococcal vaccinations. However, there is no data regarding the clinical background and antimicrobial susceptibility of NVT isolates compared with those of vaccine serotype (VT) isolates in adult pneumococcal pneumonia. MethodsThe serotypes and antimicrobial susceptibilities of pneumococcal isolates obtained from patients with pneumonia at the University of Occupational and Environmental Health, Japan, from January 2011 to December 2020 were retrospectively evaluated along with the patients’ clinical information. ResultsIn total, 252 patients with pneumococcal pneumonia (98 NVT and 154 VT isolates) were included. Among NVTs, the most common serotype was 35B, followed by 15A, 34, 6C, 23A, and 15C. The MIC50 and MIC90 of each antibiotic in 35B and 15A tend to be higher than those in 34, 6C, and 23A. Regarding background characteristics, the percentages of patients with dementia and liver disease were significantly higher in patients in the VT group than in those in the NVT group (p = 0.048 and p = 0.012, respectively). There were no significant differences in the severity of pneumonia and mortality rate between patients with the VT and NVT isolates. This study first demonstrated that NVT isolates included those with reduced susceptibility to antibiotics in adult pneumonia in Japan. The data of the present study can be useful in optimizing treatment strategies for pneumococcal pneumonia because of the increasing number of NVT cases in Japan.

Bacteriological and molecular characterization of temperature- and CO2-dependent Streptococcus pneumoniae serotype 24F ST162 isolated from Japanese children.

Streptococcus pneumoniae serotype 24F is one of the most prevalent non-vaccine serotypes that causes invasive pneumococcal disease (IPD) in many countries, including Japan. This study aimed to analyze the bacteriological and molecular characteristics of serotype 24F sequence type (ST) 162, which has been increasingly isolated from pediatric patients with IPD in Japan recently. The examination of growth conditions, sequencing of genes associated with the CO2 dependence, and antimicrobial susceptibility testing at 35°C under 5% CO2 were performed for 10 isolates obtained from Japanese children with IPD caused by serotype 24F ST162. All isolates failed to grow at 35°C in ambient air; however, they showed growth at 30°C in ambient air and at 35°C under 5% CO2. Sequencing of murF involved in cell wall synthesis indicated that all isolates had a single amino acid substitution, MurFA179V. Additionally, all isolates were sensitive to penicillin G and resistant to trimethoprim-sulfamethoxazole. Furthermore, 25 non-capnophilic strains were obtained from all CO2-dependent isolates, and their murF sequences were compared. Thirteen of the 25 non-capnophilic strains displayed a different amino acid substitution, MurFV179A, whereas the other 12 presented the previously described MurFA179V. This suggests that a proportion of the CO2-dependent phenotype of serotype 24F ST162 may have been conferred by MurFA179V; however, the mechanism for the CO2 dependence of these isolates warrants further investigation. The CO2-dependent serotype 24F ST162 pneumococcal isolates shared common characteristics in terms of growth patterns, molecular basis, and antimicrobial susceptibility; therefore, future epidemiological trends of this clone must be closely monitored. IMPORTANCE We characterized Streptococcus pneumoniae serotype 24F sequence type (ST) 162 isolated from Japanese children with invasive pneumococcal disease (IPD). Owing to its highly invasive nature, serotype 24F is expected to be isolated from clinically significant cases. Serotype 24F ST162 isolates tested in the present study did not grow at 35°C in ambient air. Therefore, antimicrobial susceptibility testing using the broth microdilution method, which is usually conducted in ambient air, cannot be performed, posing a clinical challenge. Clinical practitioners and laboratory personnel should be aware of the epidemiological, bacteriological, and molecular characteristics of serotype 24F ST162. We believe that our findings can help diagnose and treat IPD caused by serotype 24F ST162, a serotype expected to become problematic in the post-13 valent pneumococcal conjugate vaccine era.

High Prevalence of Non-vaccine Serotypes among Pediatric Non-invasive Pneumococcal Isolates in the PCV10 Vaccine-era in Bulgaria

Streptococcus pneumoniae is a vaccine-preventable agent, due to the available pneumococcal conjugate vaccines (PCVs), but still is a leading bacterial pathogen of non-invasive pneumococcal diseases (NIPD). We conducted a study on the serotype distribution and antibiotic nonsusceptibility in 202 S. pneumoniae isolates recovered from children with NIPD during the PCV10-era in Bulgaria (2015–2020). Serogrouping/serotyping were performed using latex agglutination and capsular swelling reaction. Serogroup 6 strains were subjected to serotype-specific PCR's. The antibiotic susceptibilities were assessed by broth microdilution. The PCV10-vaccinated children were 190 (94.1%). The antimicrobial non-susceptibility showed highest levels in oral penicillin (53.5%), erythromycin (52.0%), trimethoprim-sulfamethoxazole (48.5%), clindamycin (47.5%), tetracycline (45.0%), ceftriaxone (14.8%) and chloramphenicol (13.4%). More than half of the strains (53.5%) were MDR. We disclosed 80.2% non-vaccinal serotypes (NVTs) and 17.8% PCV10-serotypes. Except serotype 19F (19.4%), all emergent pediatric NIPD serotypes in our geographic area during the studied PCV10-period were NVTs: 19A (15.8%), 3 (14.8%), 6C (9.9%), 15A (6.0%) and 23A (4.0%). MDR-serotypes were 19A (22.2%), 19F (17.6%), 6C (15.7%), 15A (8.3%), and 23A (8.3%). Surveillance studies must be performed systematically to monitor the vaccine-induced changes and trends in antimicrobial resistance.

Recent progress in pneumococcal protein vaccines.

Pneumococcal infections continue to pose a significant global health concern, necessitating the development of effective vaccines. Despite the progress shown by pneumococcal polysaccharide and conjugate vaccines, their limited coverage and the emergence of non-vaccine serotypes have highlighted the need for alternative approaches. Protein-based pneumococcal vaccines, targeting conserved surface proteins of Streptococcus pneumoniae, have emerged as a promising strategy. In this review, we provide an overview of the advancements made in the development of pneumococcal protein vaccines. We discuss the key protein vaccine candidates, highlight their vaccination results in animal studies, and explore the challenges and future directions in protein-based pneumococcal vaccine.

Impact of the progressive uptake of pneumococcal conjugate vaccines on the epidemiology and antimicrobial resistance of invasive pneumococcal disease in Gipuzkoa, northern Spain, 1998-2022.

To analyze the impact of pneumococcal conjugate vaccines (PCVs) on the incidence of invasive pneumococcal diseases (IPDs) and pneumococcal antibiotic resistance in Gipuzkoa, northern Spain for a 25 years period. All cases of IPD confirmed by culture between 1998 and 2022 in a population of around 427,416 people were included. Pneumococci were serotyped and antimicrobial susceptibility was assessed by the EUCAST guidelines. Overall, 1,516 S. pneumoniae isolates were collected. Annual IPD incidence rates (per 100,000 people) declined from 19.9 in 1998-2001 to 11.5 in 2017-19 (42.2% reduction), especially in vaccinated children (from 46.7 to 24.9) and non-vaccinated older adult individuals (from 48.0 to 23.6). After PCV13 introduction, the decrease in the incidence of infections caused by PCV13 serotypes was balanced by the increase in the incidence of non-PCV13 serotypes. In the pandemic year of 2020, IPD incidence was the lowest: 2.81. The annual incidence rates of penicillin-resistant isolates also decreased, from 4.91 in 1998-2001 to 1.49 in 2017-19 and 0.70 in 2020. Since 2017, serotypes 14, 19A, and 11A have been the most common penicillin-resistant types. The incidence of erythromycin-resistant strains declined, from 3.65 to 1.73 and 0.70 in the same years. PCV use was associated with declines in the incidence of IPD and the spread of non-vaccine serotypes, that balanced the beneficial effect off PCV13, some of them showing high rates of antibiotic resistance.

Laboratory indices of hospitalized sickle cell disease patients, prevalence and antimicrobial susceptibility of pathogenic bacterial isolates at MRCG ward in the Gambia

BackgroundThe aim of this study was to determine the prevalence of invasive bacterial infections and their antimicrobial resistance patterns in sickle cell disease (SCD) patients admitted at the Medical Research Council the Gambia (MRCG) Ward in the era of PCV and Hib vaccination in the Gambia.Methods and ResultsThis 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 only for 159. Of the 159 admitted SCD, 11 patients had qualified positive blood cultures. Five different types of bacterial 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 10 A, 12 F and 12 F. Penicillin resistance was recorded in two of the three Streptococcus pneumoniae. 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. The haematological indices were not significantly varied between SCD patients with and without microbiologically confirmed bacterial infection.ConclusionStreptococcus 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. The haematological parameters may not be reliable biomarkers in differentiating bacterial from non-bacterial infections in SCD patients.