19F Serotypes Research Articles

Serotype composition of Streptococcus pneumoniae in children with respiratory infections, optimization of molecular assessment methods

The paper presents optimized methods for PCR and sequence typing of Streptococcus pneumoniae. The serotype composition of pneumococci isolated from children under 5 years of age with infections of the upper respiratory tract was analyzed using optimized methods. Between 2016 and 2021, there was a decrease in the frequency of serotypes included in the pneumococcal 13-valent conjugate vaccine (PCV13) from 94.1 to 25.8%, mainly due to the 6ABCD serogroup and the 19F serotype. The coverage of serotypes circulating in children with PCV15 and PCV20 vaccines was 28.1% and 41.6% in 2021, respectively. During the study period, the number of non-vaccine serogroups 11AD and 15AF, as well as serotypes that are not detected under this capsular PCR typing protocol, increased most significantly.

Distribution and annual changes in the proportion of Streptococcus pneumoniae serotypes in Japanese adults with pneumococcal pneumonia from 2011 to 2017

In 2014, vaccinations with 23-valent pneumococcal polysaccharide vaccine (PPSV23) and 13-valent pneumococcal conjugate vaccine (PCV13) were implemented in Japan for all adults aged ≥65 years. We previously clarified reductions in the proportions of PCV7-, PCV13-, and PPSV23-covered serotypes in patients with pneumococcal pneumonia after the initiation of PCV7 and PCV13 vaccinations for Japanese children; however, information about the annual changes in the proportion of Streptococcus pneumoniae serotypes in patients with pneumococcal pneumonia after the initiation of routine PPSV23 vaccinations remains unclear. We retrospectively studied 229 adults with pneumococcal pneumonia which S. pneumoniae was cultured from their lower respiratory tract samples between 2011 and 2017 and investigated the annual changes in the proportion of S. pneumoniae serotypes. The proportion of PPSV23-covered serotypes decreased from 71.4% in 2011 to 52.2% in 2014, but it remained essentially unchanged from 2015 to 2017. The proportions of PCV7-covered serotypes decreased from 46.4% in 2011 to 4.3% in 2014; however, this rate increased beginning in 2015 and reached 20.6% in 2017. Among the PCV7-covered serotypes, the proportion of the 19F serotype increased from 2015 to 2017. In conclusion, there were no obvious changes in the proportion of PPSV23-covered and PCV13-covered serotypes in patients with pneumococcal pneumonia after the initiation of routine PPSV23 vaccinations.

Molecular Epidemiology of Streptococcus pneumoniae Isolates from Children with Recurrent Upper Respiratory Tract Infections.

A total of 125 isolates were recovered from adenoids and/or nasopharynx of 170 children aged 2 to 5 from south-east Poland; they had undergone adenoidectomy for recurrent and/or persistent symptoms of upper respiratory tract infections. Pneumococcal isolates were analyzed by phenotyping (serotyping and antimicrobial resistance tests) and genotyping together with the clonality of the pneumococcal isolates based on resistance determinants, transposon distribution and multilocus sequence typing (MLST). Serotypes 19F, 6B and 23F constituted 44.8% of the isolates. Among all of the strains, 44.8% showed decreased susceptibility to penicillin and resistance to co-trimoxazole (52.8%), tetracycline (38.4%), erythromycin (53.6%), clindamycin (52.8%) and chloramphenicol (27.2%) was observed. Tn6002 was found in 34.8% of erythromycin-resistant isolates while composite Tn2010—in 16.7% of erm(B)-carrying isolates that harboured also mef(E) gene. Tn3872-related elements were detected in 27.3% of erythromycin-resistant strains. In the majority of chloramphenicol-resistant catpC194-carrying isolates (79.4%), ICESp23FST81-family elements were detected. The genotyping showed that pneumococcal population was very heterogeneous; 82 sequence types (STs) were identified, and the most frequent contributed to not more than 8% of the isolates. Nearly 44% STs were novel, each of them was recovered only from one child. Four STs belonged to one of the 43 worldwide spread resistant pneumococcal clones currently accepted by Pneumococcal Molecular Epidemiology Network (PMEN), i.e. Spain 9V-3, Spain 23F-1, Norway NT-42 and Poland 6B-20, accounting for 12 (16.7%) of the 75 nonususceptible isolates, and five STs were single-locus variants of PMEN resistant clones (England 14–9, Spain 9V-3, Spain 23F-1, Greece 21–30, Denmark 14–32), accounting 9 (12%) of nonsusceptible isolates. A few MDR clones belonging to 6B and 19F serotypes found among preschool children emphasizes rather the role of clonal dissemination of local strains in the community than international clones spreading in the increase of resistance among pneumococcal strains.

Antibiotic susceptibility of Streptococcus pneumoniae in healthy carrier children in Murcia (Spain)

Abstract Introduction and objectives Streptococcus pneumoniae (SP) is a human pathogen that involves a high use of antibiotics. The objective of the study was to determine the susceptibility to commonly used antibiotics and their associated risk factors, in order to promote rational use of antibiotics. Patients and methods In a multicentre study was conducted in summer 2009 and winter 2010 on children attending paediatric clinics in the Region of Murcia. A nasopharyngeal sample was collected and an epidemiological questionnaire was completed. The study included 1562 children aged 1 and 4 years old. Results Almost one-third (31.3%, 489/1562) of children were nasal carriers. A sensitivity study was carried out on 376 isolates, of which 343 were serotyped. Almost two-thirds (61.7%, 964/1562) of children had received at least one dose of PCV7 (heptavalent pneumococcal conjugate vaccine), and 12.8% (44/343) of the isolates belonged to PCV7 serotypes. The prevalence rates of penicillin resistance (meningitis infections criteria CMI > 0.06 mg/L) were 28.1%; however, this percentage was 54% in PCV7 serotypes. None of the isolates had (MIC > 2 mg/L), so prevalence rates of susceptibility with non-meningitis infections criteria were 100%. There was a high percentage of erythromycin resistance (45.7%). The factors favouring resistance to penicillin and cefotaxime were the consumption of antibiotics in the previous month and the carrying of vaccine serotypes. On the other hand, the age of 4 years old was a protective factor of resistance. The 14, 35B, 19A, 15A, and 19F serotypes were less susceptible to penicillin. Conclusions Both oral amoxicillin given to outpatients and intravenous penicillin or ampicillin to hospitalized patients are excellent options for the treatment of non-meningeal infections, as seen with pneumonia in these kinds of environments, where there is low incidence of isolates highly resistant to penicillin (CMI ≥ 2 mg/L).

Sensibilidad de Streptococcus pneumoniae en niños portadores sanos en Murcia (España)

Introduction and objectivesStreptococcus pneumoniae (SP) is a human pathogen that involves a high use of antibiotics. The objective of the study was to determine the susceptibility to commonly used antibiotics and their associated risk factors, in order to promote rational use of antibiotics. Patients and methodsIn A multicentre study was conducted in summer 2009 and winter 2010 on children attending paediatric clinics in the Region of Murcia. A nasopharyngeal sample was collected and an epidemiological questionnaire was completed. The study included 1562 children aged 1 and 4 years old. ResultsAlmost one-third (31.3%, 489/1562) of children were nasal carriers. A sensitivity study was carried out on 376 isolates, of which 343 were serotyped. Almost two-thirds (61.7%, 964/1562) of children had received at least one dose of PCV7 (heptavalent pneumococcal conjugate vaccine), and 12.8% (44/343) of the isolates belonged to PCV7 serotypes. The prevalence rates of penicillin resistance (meningitis infections criteria CMI>0.06mg/L) were 28.1%; however, this percentage was 54% in PCV7 serotypes. None of the isolates had (MIC >2mg/L), so prevalence rates of susceptibility with non-meningitis infections criteria were 100%. There was a high percentage of erythromycin resistance (45.7%). The factors favouring resistance to penicillin and cefotaxime were the consumption of antibiotics in the previous month and the carrying of vaccine serotypes. On the other hand, the age of 4 years old was a protective factor of resistance. The 14, 35B, 19A, 15A, and 19F serotypes were less susceptible to penicillin. ConclusionsBoth oral amoxicillin given to outpatients and intravenous penicillin or ampicillin to hospitalized patients are excellent options for the treatment of non-meningeal infections, as seen with pneumonia in these kinds of environments, where there is low incidence of isolates highly resistant to penicillin (CMI ≥ 2mg/L).

Evidence for soft selective sweeps in the evolution of pneumococcal multidrug resistance and vaccine escape.

The multidrug-resistant Streptococcus pneumoniae Taiwan19F-14, or PMEN14, clone was first observed with a 19F serotype, which is targeted by the heptavalent polysaccharide conjugate vaccine (PCV7). However, “vaccine escape” PMEN14 isolates with a 19A serotype became an increasingly important cause of disease post-PCV7. Whole genome sequencing was used to characterize the recent evolution of 173 pneumococci of, or related to, PMEN14. This suggested that PMEN14 is a single lineage that originated in the late 1980s in parallel with the acquisition of multiple resistances by close relatives. One of the four detected serotype switches to 19A generated representatives of the sequence type (ST) 320 isolates that have been highly successful post-PCV7. A second produced an ST236 19A genotype with reduced resistance to β-lactams owing to alteration of pbp1a and pbp2x sequences through the same recombination that caused the change in serotype. A third, which generated a mosaic capsule biosynthesis locus, resulted in serotype 19A ST271 isolates. The rapid diversification through homologous recombination seen in the global collection was similarly observed in the absence of vaccination in a set of isolates from the Maela refugee camp in Thailand, a collection that also allowed variation to be observed within carriage through longitudinal sampling. This suggests that some pneumococcal genotypes generate a pool of standing variation that is sufficiently extensive to result in “soft” selective sweeps: The emergence of multiple mutants in parallel upon a change in selection pressure, such as vaccine introduction. The subsequent competition between these mutants makes this phenomenon difficult to detect without deep sampling of individual lineages.

Changes in the composition of the pneumococcal population and in IPD incidence in The Netherlands after the implementation of the 7-valent pneumococcal conjugate vaccine

The implementation of nationwide pneumococcal vaccination may lead to alterations in the pneumococcal population due to selective pressure induced by the vaccine. To monitor such changes, pneumococcal isolates causing invasive pneumococcal disease (IPD) before (2004–2005, n=1154) and after (2008–2009, n=1190) the implementation of the 7-valent pneumococcal vaccine (PCV7) in 2006 in the national immunization program (NIP) of The Netherlands were characterized by molecular typing using multiple-locus variable number tandem repeat analysis (MLVA) and capsular sequence typing (CST).The IPD incidence after the implementation of PCV7 in children <5 years of age declined, mainly due to an impressive reduction of cases caused by vaccine serotypes. In the age group of patients ≥5 years of age, the overall IPD incidence remained constant, but the IPD incidence due to vaccine serotypes declined in this age cohort as well, indicating herd immunity. IPD incidence of non-vaccine serotypes 1 and 22F isolates increased significantly and a shift in genetic background of the isolates belonging to these serotypes was observed. In general the composition of the pneumococcal population remained similar after the introduction of PCV7. Both before and after introduction of the vaccine several possible capsular switch events were noticed. We found 4 isolates from the pre-vaccination period in which the serotype 19F capsular locus had been horizontally transferred to a different genetic background. Remarkably, none of the 5 post-vaccination isolates in which we observed possible capsule switch belonged to the 19F serotype, possibly due to vaccine induced pressure. In the post-vaccine implementation period we found no evidence for capsular switch of a vaccine serotype to a non-vaccine serotype, indicating that capsular switch is not the main driving force for replacement. This study provides insights into the effects of nationwide vaccination on the pneumococcal population causing IPD.

Méningite à pneumocoque de sérotype 19F chez un enfant immunocompétent ayant reçu 3 injections du vaccin pneumococcique conjugué heptavalent Prevenar®

Seven cases of pneumococcal meningitis caused by serotypes covered by the available vaccine occurred in France in vaccinated children, 4 of which were caused by serotype 19F. A 3-year-old child, who had received 3 doses of the 7-valent pneumococcal conjugate vaccine Prevenar but not the 4th injection, presented with bacterial meningitis after acute media otitis. The identified bacterium was a 19F serotype of Streptococcus pneumoniae. This vaccine failure was characterized by an immune memory installation defect and underscores the necessity of the booster dose of vaccine during the 2nd year of life to acquire rates of protective and lasting antibodies. Serotype 19F of S. pneumoniae is particular since, despite good immunogenecity, it induces antibodies with weak avidity. We describe a case of pneumococcal meningitis caused by 19F serotype S. pneumoniae, which is included in the vaccine, in an immunocompetent child. Such events should be inventoried. They can reveal rates of antibodies that are very weak defenders, in spite of the vaccination, reflecting the absence of implementation of immunizing memory. Furthermore, an underlying immune deficit must be ruled out.

High carriage rate of high-level penicillin-resistant Streptococcus pneumoniaein a Taiwan kindergarten associated with a case of pneumococcal meningitis

BackgroundThe Taiwan19F-14 Streptococcus pneumoniae clone and its variants are being found with increasing frequency in the Asia-Pacific region. A 5-year old child with S. pneumoniae meningitis caused by a high-level penicillin resistant strain (MIC = 4 μg/ml) was admitted to a hospital in southern Taiwan. We carried out a study to determine the potential source of this strain.MethodsNasopharyngeal cultures were obtained from all children attending the same kindergarten as the index case. To determine their relatedness all isolates were compared by serotype, antimicrobial susceptibility profile and pulsed field gel electrophoresis (PFGE).ResultsA high proportion of the children including the index case (32/78, 41.0%) carried S. pneumoniae in their nasopharynx (NP). The most common serotype was 19F (13/32, 40.6%). The PFGE types of the 19F serotype isolates obtained from the patient's blood, CSF and NP were identical and were related to 11 other serotype 19F NP isolates including 10 that were indistinguishable from the Taiwan19F-14 clone. All 14 isolates had similar high-level penicillin and multi-drug resistance. The serotypes of the other 19 NP isolates included 6A (2), 6B (10), 23F (5), 9V (1) and 3 (1). The overall rate of penicillin resistance in these S. pneumoniae from these children was 87.5% (28/32), with an MIC50 of 2 and MIC90 of 4 ug/ml. In addition, multi-drug resistant-isolates (isolates resistant to 3 different classes of antimicrobials) accounted for 87.5% (28/32) of all isolates.ConclusionThe high carriage rate of high-level penicillin- and multi-drug- resistant S. pneumoniae in a kindergarten associated with a case of pneumococcal meningitis emphasizes the need for restraint in antibiotic use and consideration of childhood immunization with conjugate pneumococcal vaccine to prevent the further spread of resistant S. pneumoniae in Taiwan.

Binding and agglutination of Streptococcus pneumoniae by human surfactant protein D (SP-D) vary between strains, but SP-D fails to enhance killing by neutrophils.

Recombinant human surfactant protein D (SP-D) expressed in Escherichia coli, consisting of the head and neck regions of the native molecule, bound to all strains of Streptococcus pneumoniae that were tested, but the extent of binding varied between strains of differing capsular serotypes. The recombinant protein expressed in the yeast Pichia pastoris did not bind. Full-length native SP-D aggregated pneumococci in a calcium-dependent manner that was inhibited by maltose acting as a competitive sugar. The ability of SP-D to modulate the uptake and killing of pneumococci by human neutrophils was also addressed. Neither recombinant truncated SP-D nor native full-length SP-D enhanced the killing of pneumococci by human neutrophils. Aggregation of pneumococci varied not only between strains of the same multilocus sequence type and different serotypes but also between strains of the same serotype. However, use of recombinant strains in which the serotype had been changed showed that the degree of aggregation was influenced by the capsular type. Indeed, a 19F serotype strain which was not aggregated by SP-D did exhibit aggregation when the original isogenic strain was capsule switched to capsular serotype 3. However, although our results show that SP-D is capable of aggregating most pneumococci, no correlation between the degree of aggregation and the capsule or multilocus sequence type of the pneumococcus was clearly apparent. Therefore, although the capsule serotype is not the only determinant of aggregation by SP-D, the data presented here indicate that it does have a role to play.