Serotype 19A Research Articles

Structural basis of botulinum neurotoxin serotype A1 binding to human SV2A or SV2C receptors

Botulinum neurotoxin A1 (BoNT/A1) is the most potent natural poison in human. BoNT/A1 recognize the luminal domain of SV2A (LD-SV2A) and its glycosylation at position N573 (N573g) or the luminal domain of SV2C (LD-SV2C) and its glycosylation at position N559 (N559g) to bind neural membrane. Our computational data suggest that the N-glycan at position 480 (N480g) in the luminal domain of SV2C (LD-SV2C) indirectly enhanced the contacts of the neurotoxin surface with the second N-glycan at position 559 (N559g) by acting as a shield to prevent N559g to interact with residues of LD-SV2C. The absence of an N-glycan homologous to N480g in LD-SV2A leads to a decrease of the binding of N573g to the surface of BoNT/A1. Concerning the intermolecular interactions between BoNT/A and the protein part of LD-SV2A or LD-SV2C, we showed that the high affinity of the neurotoxin for binding LD-SV2C are mediated by a better compaction of its F557–F562 part provided by a π-π network mediated by residues F547, F552, F557 and F562 coupled with the presence of two aromatic residues at position 563 and 564 that optimize the binding of BoNT/A1 via cation-pi and CH-pi interaction. Finally, in addition to the well-known ganglioside binding site which accommodates a ganglioside on the surface of BoNT/A1, we identified a structure we coined the ganglioside binding loop defined by the sequence 1253-HQFNNIAK-1260 that is conserved across all subtypes of BoNT/A and is predicted to has a high affinity to interact with gangliosides. These data solved the puzzle generated by mutational studies that could be only partially understood with crystallographic data that lack both a biologically relevant membrane environment and a full glycosylation of SV2.

Antibiotic resistance pattern, capsular types, and molecular characterization of invasive isolates of Streptococcus pneumoniae in the south of Tunisia from 2012 to 2018

BackgroundStreptococcus pneumoniae remains a leading cause of morbidity and mortality worldwide. In this study, we sought to analyze serotype distributions, antibiotic resistance, and genetic relationships of 106 clinical invasive pneumococcal isolates recovered in Tunisia between 2012 and 2018, prior to the routine use of pneumococcal conjugate vaccines (PCV).MethodsWe used multiplex PCR, the disk diffusion method and/or E-test, and multi-locus sequence typing (MLST).ResultsThe most frequent serotypes were 14 (17%), 19F (14.2%), and 3 (11.3%). Of the 106 S. pneumoniae isolates, 67.9% were penicillin non-susceptible (29.4% were resistant), 45.3% were amoxicillin non-susceptible (17% were resistant), and 16% were cefotaxime non-susceptible. For antibiotics other than β-lactams, resistance rates to erythromycin, tetracycline, cotrimoxazole, and chloramphenicol were 62.3, 33, 22.6, and 4.7%, respectively. Two isolates were non-susceptible to levofloxacin. Among 66 erythromycin-resistant pneumococci, 77.3% exhibited the cMLSB phenotype, and 87.9% carried ermB gene. All tetracycline-resistant strains harbored the tetM gene. The potential coverage by 7-, 10-, and 13-valent pneumococcal conjugate vaccines were 55.7, 57.5, and 81.1%, respectively. A multilocus sequence typing analysis revealed great diversity. Fifty different sequence types (STs) were identified. These STs were assigned to 10 clonal complexes and 32 singletons. The most common STs were 179, 2918, 386, and 3772 – related mainly to 19F, 14, 6B/C, and 19A serotypes, respectively.ConclusionsThis study demonstrated that the majority of the serotypes of invasive pneumococci in the Tunisian population were 14, 19F, and 3. Moreover, we noted a high degree of genetic diversity among invasive S. pneumoniae isolates. The highest proportions of antibiotic non-susceptible isolates were for penicillin, erythromycin, and tetracycline. Further molecular characteristics are required to monitor the genetic variations and to follow the emergence of resistant pneumococci for the post-vaccination era in Tunisia.

Evolution of Antimicrobial Susceptibility to Penicillin in Invasive Strains of Streptococcus pneumoniae during 2007-2021 in Madrid, Spain.

The use of pneumococcal conjugate vaccines has affected the epidemiology and distribution of Streptococcus pneumoniae serotypes causing Invasive Pneumococcal Disease (IPD). The aim of this study was to analyze the evolution of the phenotypical profiles of antimicrobial susceptibility to penicillin (PEN) in all IPD strains isolated in Madrid, Spain, during 2007-2021. In total, 7133 invasive clinical isolates were characterized between 2007 and 2021. Levels of PENR and PNSSDR were 2.0% and 24.2%, respectively. In addition, 94.4% of all the PENR belonged to four serotypes, including 11A (33.6%), 19A (30.8%), 14 (20.3%) and 9V (9.8%). All the strains of serotype 11A, which is a non-PCV13 serotype, were detected after the year 2011. Serotypes 6C, 15A, 23B, 24F, 35B, 19F, 16F, 6B, 23F, 24B, 24A, 15F and a limited number of strains of serogroups 16 and 24 (non-typed at serotype level) were associated with PNSSDR (p < 0.05). PNSSDR strains of non-PCV13 serotypes 11A, 24F, 23B, 24B, 23A and 16F were more frequent from 2014 to 2021. The changes in S. pneumoniae serotype distribution associated with the use of conjugate vaccines had caused in our region the emergence of non-PCV13 pneumococcal strains with different PENR or PNSSDR patterns. The emergence of serotype 11A resistant to penicillin as the most important non-PCV13 serotype is a worrisome event with marked relevance from the clinical and epidemiological perspective.

Magnetic bead-based separation of pneumococcal serotypes

The separation of pneumococcal serotypes from a complex polymicrobial mixture may be required for different applications. For instance, a minority strain could be present at a low frequency in a clinical sample, making it difficult to identify and isolate by traditional culture-based methods. We therefore developed anassay to separate mixed pneumococcal samples using serotype-specific antiserum and a magnetic bead-based separation method. Using qPCR and colony counting methods, we first show that serotypes (12F, 23F, 3, 14, 19A, and 15A) present at ∼0.1% of a dual serotype mixture can be enriched to between 10% and 90% of the final sample. We demonstrate two applications for this method: extraction of known pneumococcal serotypes from saliva samples and efficient purification of capsule switch variants from experimental transformation experiments. This method may have further laboratory or clinical applications when the selection of specific serotypes is required.

Exploring the Role of GMMA Components in the Immunogenicity of a 4-Valent Vaccine against Shigella.

Shigellosis is the leading cause of diarrheal disease, especially in children of low- and middle-income countries, and is often associated with anti-microbial resistance. Currently, there are no licensed vaccines widely available against Shigella, but several candidates based on the O-antigen (OAg) portion of lipopolysaccharides are in development. We have proposed Generalized Modules for Membrane Antigens (GMMA) as an innovative delivery system for OAg, and a quadrivalent vaccine candidate containing GMMA from S. sonnei and three prevalent S. flexneri serotypes (1b, 2a and 3a) is moving to a phase II clinical trial, with the aim to elicit broad protection against Shigella. GMMA are able to induce anti-OAg-specific functional IgG responses in animal models and healthy adults. We have previously demonstrated that antibodies against protein antigens are also generated upon immunization with S. sonnei GMMA. In this work, we show that a quadrivalent Shigella GMMA-based vaccine is able to promote a humoral response against OAg and proteins of all GMMA types contained in the investigational vaccine. Proteins contained in GMMA provide T cell help as GMMA elicit a stronger anti-OAg IgG response in wild type than in T cell-deficient mice. Additionally, we observed that only the trigger of Toll-like Receptor (TLR) 4 and not of TLR2 contributed to GMMA immunogenicity. In conclusion, when tested in mice, GMMA of a quadrivalent Shigella vaccine candidate combine both adjuvant and carrier activities which allow an increase in the low immunogenic properties of carbohydrate antigens.

Emergence of extensively drug-resistant and multidrug-resistant Shigella flexneri serotype 2a associated with sexual transmission among gay, bisexual, and other men who have sex with men, in England: a descriptive epidemiological study

Shigellosis, also known as bacillary dysentery, is caused by Shigella spp that spread through fecal-oral contact and was traditionally associated with international travel in England. However, sexual transmission of Shigella flexneri and Shigella sonnei among gay, bisexual, and other men who have sex with men (MSM) is now common. In September, 2021, emergence of extensively drug-resistant (XDR) S sonnei harbouring plasmid-encoded blaCTX-M-27 raised concerns over further spread of this extended-spectrum β-lactamase-producing gene. Using national surveillance in England, we identified and characterised isolates of S flexneri harbouring blaCTX-M-27. In this epidemiological study, we identified and phylogenetically characterised S flexneri isolates harbouring blaCTX-M-27 that were referred to the Gastrointestinal Bacterial Reference Unit (GBRU) at the UK Health Security Agency. All isolates referred to the GBRU undergo whole-genome sequencing, enabling antimicrobial resistance determination using genetic markers. Cases were defined as individuals diagnosed with S flexneri harbouring blaCTX-M-27 in England, with a specimen date between Sept 1, 2015, and June 12, 2022, who were phylogenetically confirmed as part of two t10 (approximately ten single nucleotide polymorphisms) clusters. Long-read sequencing elucidated the genomic location of blaCTX-M-27. Laboratory data, integrated with available demographic and clinical information from patient questionnaires, were summarised using descriptive statistics. A sustained increase in cases of S flexneri harbouring blaCTX-M-27 (n=26) occurred from September, 2021, having been sporadically reported (n=11) in the preceding 6 years. blaCTX-M-27 acquisition events within S flexneri 2a established an XDR paraphyletic (n=8) cluster and a multidrug-resistant monophyletic (n=18) cluster. Cases were among adult male individuals (median age 37 years [IQR 31-46]) and, of the 13 individuals who completed a patient questionnaire, ten (77%) identified as MSM. Antimicrobial treatment was received by seven (54%) of 13 individuals, and four (31%) individuals were admitted to hospital. The IncFII plasmids harbouring blaCTX-M-27 showed high similarity to the XDR S sonnei outbreak plasmid, with 82% and 99% nucleotide similarity between the cluster plasmids and the XDR S sonnei outbreak plasmid. We report emergence of XDR and multidrug-resistant S flexneri 2a harbouring blaCTX-M-27 among MSM in England. Epidemiological and plasmid similarities with the XDR S sonnei outbreak support horizontal acquisition events, emphasising the importance of mobilisable antimicrobial resistance and the need for genomic-based surveillance. National Institute for Health and Care Research Health Protection Research Unit in Gastrointestinal Infections at the University of Liverpool in partnership with the UK Health Security Agency.

Sexually acquired enteric infections among men who have sex with men

In The Lancet Infectious Diseases, Katie Thorley and colleagues1 describe the emergence of extensively drug-resistant (XDR) and multidrug-resistant Shigella flexneri serotype 2a among gay, bisexual, and other men who have sex with men (MSM) in England. This Article follows several previous reports of outbreaks of multidrug-resistant Shigella sonnei among MSM in England and other high-income countries and occurs on a wider backdrop of the re-emergence of other enteric infections, such as hepatitis A virus and lymphogranuloma venereum, among interconnected populations of MSM globally.

Progresión temporal de la distribución de los serotipos de Streptococcus pneumoniae productores de enfermedad neumocócica invasiva en Galicia (España) y su relación con la resistencia a antibióticos (periodo 2011-2021)

IntroductionStreptococcus pneumoniae causes serious diseases in the susceptible population. The 13-valent pneumococci conjugate vaccine (PCV13) was included in the children's calendar in 2011. The objective of the study was to analyze the evolution of pneumococcal serotypes and their resistance after PCV13. MethodsThis study included the pneumococci serotyped in Galicia in 2011-2021. Antibiotic susceptibility was analyzed following EUCAST criteria. The data was analyzed in 3 sub-periods: initial (2011-2013), middle (2014-2017) and final (2018-2021). The prevalence of serotypes and their percentage of resistance to the most representative antibiotics were calculated. ResultsA total of 2.869 isolates were included. Initially, 42.7% isolates presented capsular types included in PCV13, compared to 15.4% at the end. Those included in PCV20 and not in PCV13 and PCV15 were 12.5% at baseline and 41.3% at the end; 26.4% of the isolates throughout the study had serotypes not included in any vaccine. The prevalence of serotype 8 multiplied almost by 8 and that of 12F tripled. The 19A serotype was initially the most resistant, while the resistance of serotypes 11A and 15A increased throughout the study. ConclusionsThe introduction of PCV13 in the pediatric population determined a change in pneumococcal serotypes towards those included in PCV20 and those not included in any vaccine. Serotype 19A was initially the most resistant and the 15A, not included in any vaccine, deserves special follow-up. Serotype 8, which increased the most, did not show remarkable resistance.

Characterization of pediatric patients with necrotizing pneumonia treated at a quaternary care center in Bogotá, Colombia, 2010-2017

Introduction: The incidence of Necrotizing Pneumonia (NP) as a complication of pneumonia has increased. Between 0.6 and 2% of parapneumonic effusions result in empyema, while up to 20% are complicated by necrosis. Methodology: A observational, ambispective study was conducted. The retrospective phase included patients treated between 2010 and 2015; the prospective between 2015 and 2017. The clinical records of patients with pneumonia were reviewed. Patients with pneumatoceles in radiography (Rx) or chest tomography (CT), or bronchopleural fistulas diagnosed were included. Results: 69 patients were collected. Information on immunization was obtained in 67% of patients. Laboratory test results showed leukocytosis &gt; 15,000/mL (65%), thrombocytosis &gt; 450,000/mL (45%), and LDH in pleural fluid &gt; 2500 IU/L (61% of 18 patients). Imaging findings were consolidation (75% vs. 100%) and pneumatocele (33% vs 90%). Microbiological isolates were collected from 27 patients. Streptococcus pneumoniae (56%) and Staphylococcus aureus (30%) were the most common agents. Twelve (80%) pneumococci were identified: five serotype 3, two serotypes 14 and 19A, one serotypes 6A, 8, and 1. Conclusions: NP is a complication that should be suspected in children under 5 years of age with torpid evolution, leukocytosis, thrombocytosis, increased LDH levels in pleural fluid, and pneumatoceles in imaging scans.

P06 The 15-valent pneumococcal conjugate vaccine (PCV) V114 induces cross-reactive antibodies against pneumococcal serotype 6C

Abstract Background Pneumococcal serotype 6C has structural similarity with serotype 6A and, to a lesser degree, serotype 6B. The 13-valent PCV (PCV13), which contains serotypes 6A and 6B, induces cross-reactive opsonophagocytic killing activity (OPA) antibodies to serotype 6C, with an observed decline in 6C disease incidence. V114 is a 15-valent PCV containing the 13 serotypes in PCV13 and two unique serotypes (22F and 33F). This study evaluated whether V114 elicits cross-reactive OPA antibodies to serotype 6C. Methods OPA antibodies to serotypes 6A, 6B, and 6C were evaluated in serum samples taken pre-vaccination and 30 days post-vaccination (single dose) from adults ≥50 years of age, and 30 days pre- and post-dose 4 from toddlers 12–15 months of age at fourth dose, who received V114 or PCV13 in the adult and paediatric V114 phase II proof-of-concept studies, respectively. The degree of inhibition of OPA antibody activity for serotypes 6A, 6B, and 6C after adsorption with serogroup 6 polysaccharides was evaluated in adult samples. Results Samples from 250 adults (V114, n=150; PCV13, n=100) and 150 paediatric participants (V114, n=100; PCV13, n=50) were included. In both the adult and paediatric populations, observed OPA geometric mean titres (GMTs) to serotypes 6A, 6B, and 6C were comparable across vaccination groups; however, the cross-reactive response to serotype 6C was stronger in infants than adults. The inhibition analysis demonstrated the specificity of antibody responses. Conclusions V114 induces cross-reactive antibodies to serotype 6C in adult and paediatric populations that are specific and comparable to those induced by PCV13.

Epidemiología molecular de la colonización nasofaríngea neumocócica en niños de Sevilla, tras la implementación del programa de vacunación con VNC13 en Andalucía (España)

BackgroundThe 13-valent pneumococcal conjugate vaccine (PCV13) universal vaccination program was introduced in December 2016 in Andalusia. MethodsA cross-sectional study was conducted on the molecular epidemiology of pneumococcal nasopharyngeal colonization. A total of 397 healthy children were recruited from primary healthcare centres in Seville for the periods 1/4/2018 to 28/2/2020 and 1/11/2021 to 28/2/2022 (PCV13 period). Data from a previous carriage study conducted among healthy and sick children from 1/01/2006 to 30/06/2008 (PCV7 period) were used for comparison of serotype/genotype distributions and antibiotic resistance rates. ResultsOverall, 76 (19%) children were colonized with S. pneumoniae during the PCV13 period and there were information available from 154 isolates collected during the PCV7 period. Colonization with PCV13 serotypes declined significantly in the PCV13 period compared with historical controls (11 vs. 38%, P=0.0001), being serotypes 19F (8%), 3 (1%) and 6B (1%) the only circulating vaccine types. Serotypes 15B/C and 11A were the most frequently identified non-PCV13 serotypes during the PCV13 period (14% and 11%, respectively); the later one increased significantly between time periods (P=0.04). Serotype 11A was exclusively associated in the PCV13 period with ampicillin-resistant variants of the Spain9V-ST156 clone (ST6521 and genetically related ST14698), not detected in the preceding period. ConclusionsThere was a residual circulation of vaccine types following PCV13 introduction, apart from serotype 19F. Serotype 11A increased between PCV13 and PCV7 periods due to emergence and clonal expansion of ampicillin-resistant genotype ST6521.

Study of Streptococcus pneumoniae serotype 19A blood isolates from Thailand by enterobacterial repetitive intergenic consensus (ERIC)-PCR typing

Study of Streptococcus pneumoniae serotype 19A blood isolates from Thailand by enterobacterial repetitive intergenic consensus (ERIC)-PCR typing

A phase 3, multicenter, randomized, double-blind, active-comparator-controlled study to evaluate the safety, tolerability, and immunogenicity of a 4-dose regimen of V114, a 15-valent pneumococcal conjugate vaccine, in healthy infants (PNEU-PED)

BackgroundPneumococcal disease (PD) remains a major health concern with considerable morbidity and mortality in children. Currently licensed pneumococcal conjugate vaccines (PCVs) confer protection against PD caused by most vaccine serotypes, but non-vaccine serotypes contribute to residual disease. V114 is a 15-valent PCV containing all 13 serotypes in Prevnar 13™ (PCV13) and additional serotypes 22F and 33F. This pivotal phase 3 study compared safety and immunogenicity of V114 and PCV13. Methods1720 healthy infants were randomized 1:1 to receive a 4-dose regimen of V114 or PCV13 concomitantly with other routine pediatric vaccines. Safety was evaluated after each dose as proportion of participants with adverse events (AEs). Serotype-specific anti-pneumococcal immunoglobulin G (IgG) was measured at 1-month post-dose 3 (PD3), pre-dose 4, and 1-month post-dose 4 (PD4). IgG response rates, geometric mean concentrations (GMCs), and opsonophagocytic activity (OPA) were compared between vaccination groups. ResultsThe proportion, maximum intensity, and duration of injection-site, systemic, and serious AEs were generally comparable between V114 and PCV13 groups. In comparison to PCV13, V114 met non-inferiority criteria for all 15 serotypes based on IgG response rates at PD3. V114 met non-inferiority criteria by IgG GMCs for all serotypes at PD3 and PD4, except for serotype 6A at PD3. V114-induced antibodies had bactericidal activity as assessed by OPA. Further, V114 met superiority criteria for shared serotype 3 and unique serotypes 22F and 33F compared to PCV13 by serotype-specific IgG GMCs at both PD3 and PD4. Immunogenicity of concomitantly administered routine pediatric vaccines was comparable in V114 and PCV13 groups. ConclusionsIn healthy infants, V114 displays acceptable safety and tolerability profiles and generates comparable immune responses to PCV13. V114 also met superiority criteria for serotypes 3, 22F, and 33F. These results support use of V114 for prevention of PD as part of routine infant vaccination schedules.Trial registration:ClinicalTrials.gov: NCT03893448; EudraCT: 2018-004109-21.

Stimulating immunoglobulin response by intramuscular delivery of exopolysaccharides-adjuvanted mannheimiosis vaccine in goats.

Pneumonic mannheimiosis (PM) is a common respiratory bacterial disease among small ruminants. Despite numerous management methods, vaccination remains a suitable strategy to combat or reduce PM in goats and sheep. Thus, a study was conducted in Malaysia to evaluate the immunogenicity of exopolysaccharide-adjuvanted Mannheimia haemolytica A2 vaccine (EPS-MHA2) under laboratory and field conditions for its potential use as an efficient vaccine against PM. This study induced immunoglobulin (Ig) responses following intramuscular (IM) delivery of the EPS-MHA2 vaccine on 12 goats for about 7 months. Goats were divided into three groups, with three goats per group, and they were vaccinated intramuscularly as follows: Group 1 was vaccinated with an adjuvanted vaccine prepared from formalin-killed M. haemolytica serotypes A2 and EPS excipient; Group 2 was vaccinated with formalin-killed M. haemolytica seed only, whereas Group 3 was injected with phosphate-buffered saline (PBS) as the negative control. Measures of specific immunity included serum IgM, IgG, and IgA as well as bronchoalveolar lavage fluid secretory IgA and the size and number of the bronchus-associated lymphoid tissue (BALT). From the 1st day of vaccination, Groups 1 and 2 showed a significant (p < 0.05) increase in serum IgM, IgG, and IgA levels. However, the antibodies started to decline 5-week post-vaccination, indicating that the booster dose was necessary. On the second exposure to the same vaccine (booster), the level of antibodies showed a significant increase (p < 0.05), particularly IgG. All groups were challenged intratracheally by virulent MHA2 2 weeks after the decline of second antibodies on the administration of booster. All goats were euthanatized and necropsied 4-week post-challenge. The number and size of the BALT in Group 1 goats significantly increased compared with those in Group 2 and the unvaccinated control. Bacteriological parameters were evaluated, in which MHA2 was reisolated successfully from lung samples in Group 3. The IgA level produced by the group vaccinated with EPS-MHA2 was significantly (p < 0.001) higher than that the MHA2 vaccine and PBS groups. All data obtained were analyzed statistically using a one-way analysis of variance. The results indicate that IM injection of EPS-MHA2 vaccine significantly enhanced the immune response against MHA2. Therefore, the addition of EPS to MHA2 (EPS-MHA2 vaccine) can effectively protect goats from lethal mannheimiosis infection. Factors such as the ideal concentration of EPS should be further studied to verify its application potential as a vaccine adjuvant, and the extraction of EPS from different microalgae species should be further investigated. This study showed a novel and exciting set of data and a vaccination system, in which the suppressive effects of mannheimiosis may be further investigated.

Serotype 19A and 6C Account for One-Third of Pneumococcal Carriage Among Belgian Day-Care Children Four Years After a Shift to a Lower-Valent PCV.

Pneumococcal conjugate vaccines (PCVs) effectively reduce infection and asymptomatic carriage of Streptococcus pneumoniae vaccine serotypes. In 2016, Belgium replaced its infant PCV13 program by a 4-year period of PCV10. Concomitantly, S. pneumoniae serotype carriage was monitored together with the carriage of other nasopharyngeal pathogens in children attending day-care centers. From 2016 to 2019, a total of 3459 nasopharyngeal swabs were obtained from children aged 6-30 months. Culture and qPCR were used for the identification of S. pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Staphylococcus aureus and for serotyping and antimicrobial susceptibility assessment of S. pneumoniae strains. S. pneumoniae colonization was frequent and stable over the study years. H. influenzae and M. catarrhalis were more frequently carried (P < .001) than S. pneumoniae, by, respectively, 92.3% and 91.0% of children. Prevalence of all PCV13 serotypes together increased significantly over time from 5.8% to 19.6% (P < .001) and was attributable to the increasing prevalence of serotype 19A. Coincidently, non-vaccine serotype 6C increased (P < .001) and the overall pneumococcal non-susceptibility to tetracycline and erythromycin. Non-susceptibility to cotrimoxazole decreased (P < .001). The switch to a PCV program no longer covering serotypes 19A, 6A, and 3 was associated with a sustained increase of serotypes 19A and 6C in healthy children, similarly as in invasive pneumococcal disease. This resulted in a re-introduction of the 13-valent conjugate vaccine during the summer of 2019.

Distinct Mannheimia haemolytica serotypes isolated from fatal infections in veal calves and dairy cows

Fatal Mannheimia haemolytica (M. haemolytica) infections in cattle, which emerged in the Netherlands between 2004 and 2018, showed two distinct disease presentations: acute fibrinous polyserositis (FPS) in veal calves, and acute fibrinous pleuro-pneumonia (FPP) in adult dairy cattle. To determine whether these presentations were caused by different M. haemolytica genotypes, whole genome sequencing was performed on 96 isolates cultured after necropsy from inflamed sites of veal calves that died of M. haemolytica-associated FPS (n = 49) or with FPP lesions (n = 2), and from dairy cows that died of M. haemolytica-associated FPP (n = 45). Among the 96 M. haemolytica isolates, 93 were shown to belong to either of two large clusters, with 48/51 calf isolates belonging to one, and 43/45 cow isolates and two calf isolates from cases of FPP to the other. All M. haemolytica isolates from veal calves with FPS were of serotype A2, whereas the isolates from dairy cows and two calves with FPP were predominantly of serotypes A1 and A6. Most serotype A2 isolates from veal calves with FPS (95.6 %) contained multiple antibiotic resistance genes (ARGs) against three to five antimicrobial classes (phenicols, sulphonamides, tetracyclines, aminoglycosides or beta-lactams). In contrast, these ARGs were only present in 10.8 % of M. haemolytica A1 and A6 isolates from pneumonic adult cattle and absent in isolates from the two calves with FPP. These two disease presentations appear to be caused by genetically distinct strains with different antimicrobial resistance gene patterns. While M. haemolytica serotype A2 is generally considered to be a commensal microorganism of cattle, it was clearly associated with fatal FPS in veal calves in the Netherlands.

Potential of Pasteurella multocida (serotype A1) Isolated from Diseased Chicken to Establish Infection in African Catfish (Clarias gariepinus)

Potential of Pasteurella multocida (serotype A1) Isolated from Diseased Chicken to Establish Infection in African Catfish (Clarias gariepinus)

Specific antibody deficiency to pneumococcal polysaccharide in a young adult with recurrent respiratory infections: a case report.

Specific antibody deficiency against pneumococcal serotypes was detected in a patient with recurrent episodes of fever. A 21-year-old man presented with a two-month history of recurrent episodes of fever and shaking chills. He was diagnosed with recurrent episodes of pneumonia caused by Streptococcus pneumoniae serotype 19A and treated with amoxicillin. Serotype-specific antibodies were not produced against most of the serotypes, which were consistent with moderate specific antibody deficiency. After pneumococcal 13-valent conjugate vaccination and pneumococcal polysaccharide vaccination, he adequately responded to the infecting serotype with an antibody titer of 1.1 µg/mL. There were eventually no recurrent episodes of fever with pneumonia.

Burden of Shigella in South Asia: a systematic review and meta-analysis.

Shigella remains one of the most common causes of diarrhoea in South Asia. Current estimates of the prevalence of Shigella are critical for guiding control measures. We estimated the prevalence of Shigella species and serogroups in South Asia. We performed a systematic review using PubMed, EMBASE, Google Scholar and Web of Science for peer-reviewed studies published between 2000 and 19 June 2022. We also manually searched the reference lists of the reviewed studies to identify additional studies. We included studies that detected the presence of Shigella in stool by culture or polymerase chain reaction (PCR). Studies associated with outbreaks were excluded. Two investigators independently reviewed the studies, extracted the data and performed quality assessment. A random-effects meta-analysis was performed to determine the pooled prevalence of Shigella. Our search yielded 5707 studies, of which 91 studies from five South Asian countries were included in the systematic review, 79 in the meta-analysis of Shigella prevalence and 63 in the meta-analysis of Shigella serogroups prevalence. The pooled prevalence of Shigella was 7% [95% confidence interval (CI): 6-7%], with heterogeneity (I2= 98.7; P < 0.01). The prevalence of Shigella was higher in children aged <5years (10%; 95% CI: 8-11%), in rural areas (12%; 95% CI: 10-14%) and in studies using PCR (15%; 95% CI: 11-19%). Shigella flexneri (58%) was the most abundant serogroup, followed by Shigella sonnei (19%), Shigella boydii (10%) and Shigella dysenteriae (9%). Shigella flexneri 2a was the most frequently isolated serotype (36%), followed by serotype 3a (12%), serotype 6 (12%) and serotype 1b (6%). The prevalence of non-typeable Shigella was 10.0%. Although the prevalence of Shigella in South Asia remains generally high, it varies by age group and geographical area, with data lacking in some countries. Effective Shigella vaccines would be advantageous for both endemic communities and travellers.

Molecular Characterization and Antibiotic Susceptibility of Non-PCV13 Pneumococcal Serotypes among Vaccinated Children in Cape Coast, Ghana.

Preventive strategies involving the use of pneumococcal conjugate vaccines (PCVs) are known to drastically reduce pneumococcal disease. However, PCV vaccination has been plagued with serotype replacement by non-PCV serotypes. In this study, we describe the prevalence and molecular characteristics of non-PCV13 serotypes (non-vaccine serotypes, NVTs) from pneumococcal carriage isolates obtained from children < 5 years old in Cape Coast, Ghana, after PCV introduction. The isolates were subjected to antibiotic susceptibility testing and multilocus sequence typing (MLST), and molecular techniques were used to detect the presence of virulence genes. Serotypes 11A, 13, 15B, 23B, and 34 formed the top five of the 93 NVT isolates. As such, 20 (21.5%), 49 (48.4%), and 70 (74.3%) isolates were non-susceptible to penicillin, tetracycline, and cotrimoxazole, respectively. Sixteen (17.2%) multidrug-resistant isolates were identified. However, non-susceptibility to ceftriaxone and erythromycin was low and all isolates were fully susceptible to levofloxacin, linezolid, and vancomycin. Whereas pcpA, pavB, lytA, and psrP genes were detected in nearly all serotypes, pilus islet genes were limited to serotypes 11A, 13, and 23B. MLST for predominant serotype 23B isolates revealed three known and seven novel sequence types (STs). ST172 and novel ST15111 were the most dominant and both STs were related to PMEN clone Columbia23F-26 (ST338). In conclusion, non-PCV13 serotype 23B was the most prevalent, with characteristics of rapid clonal expansion of ST172 and ST15111, which are related to international clones of the pneumococcus. Continuous monitoring of NVTs in Ghana is, therefore, essential, as they have the potential to cause invasive disease, show high antibiotic resistance, and attenuate the effects of PCV vaccination.