Epidemiology of Haemophilus influenzae in the Republic of Ireland, 2010-2018.

The purpose of this study was to investigate H. influenzae epidemiology in the Republic of Ireland. We performed serotyping, multi-locus sequence typing (MLST) and susceptibility testing on H. influenzae isolates received by the Irish Meningitis and Sepsis Reference Laboratory from 2010 to 2018. Three hundred sixty-seven invasive and 41 non-invasive infection (NII) isolates were received. Invasive isolates were mostly recovered from paediatric (21%) and elderly (42%) populations. Invasive disease was more prevalent in females of childbearing age (72%) compared with males the same age (28%). Non-typeable H. influenzae (NTHi) predominated among invasive (83%) and NII (95%). Invasive Hib disease isolates were infrequent (4%, n = 15). Among invasive disease, Hif was the commonest encapsulated serotype (10%, n = 37), and the only encapsulated serotype detected in NII (5%, 2/41). The first PCR-confirmed serotypes d and a in Ireland were characterised among invasive disease in 2017 and 2018, respectively. MLST revealed a diverse NTHi population, while encapsulated serotypes were clonal. Sequence type (ST) 103 (n = 14) occurred exclusively in invasive NTHi disease. Ampicillin resistance (AmpR) was 18% among invasive isolates and 22% in NII. ß-Lactamase production was the main source of ampicillin resistance in invasive and NII isolates. We detected ß-lactamase negative ampicillin resistance (BLNAR) among invasive isolates. We report an NTHi fluoroquinolone-resistant clone: ST1524 among invasive (n = 2) and NII isolates (n = 2). The Hib vaccine has positively impacted on Hib disease in Ireland, given the low frequency of Hib. The dominance of NTHi, emergence of serotypes a and d and BLNAR suggest a changing H. influenzae epidemiology in Ireland.

Noninvasive pneumococcal clones associated with antimicrobial nonsusceptibility isolated from children in the era of conjugate vaccines.

Carriage and noninvasive pneumococcal isolates frequently have a higher prevalence of antimicrobial nonsusceptibility than invasive isolates. From 2009 to 2014, we determined the associated clones in 169 pediatric noninvasive nonsusceptible pneumococci from a total of 506 isolates collected after 7- and 13-valent conjugate vaccine introduction (PCV7/13) to the Irish childhood immunization schedule in 2008 and 2010, respectively. We compared our results to those from 25 noninvasive pediatric pneumococcal isolates collected in 2007, the year before introduction of conjugate vaccines. In 2007, England(14)-9 and Spain(9V)-3 accounted for 12% and 32% of nonsusceptible clones, respectively, but in 2009 to 2014, their prevalence fell to 0% and 2.4%. Furthermore, there was a significant decline in Spain(6B)-2 and its variants from 2009 to 2014 (P = 0.0024). Fluctuations occurred in clonal complex 320 associated with serotype 19A. The prevalence of Sweden(15A)-25 and its variants and ST558 (a single-locus variant of Utah(35B)-24) associated with nonvaccine serotypes (NVT) 15A and 35B increased from 0% and 8% in 2007 to 19% and 16% in 2013 to 2014, respectively. Pilus locus 1 (PI-1) is associated with the spread of some nonsusceptible pneumococcal clones. PI-1 was more frequently associated with PCV7/13 serotypes than NVT (P = 0.0020). Our data highlight the value of surveillance of noninvasive pneumococci following conjugate vaccine introduction. Importantly, emerging clones associated with NVT may limit the effectiveness of PCV7/13 in reducing the high rate of nonsusceptibility among pediatric noninvasive pneumococci, with implications for empirical treatment strategies.

Haemophilus influenzae type f in the post-Haemophilus influenzae type b vaccination era: a systematic review.

Since the introduction of Haemophilus influenzae (Hi) serotype b (Hib) vaccination, reports of increasing incidence rates of non-Hib serotypes have emerged. A systematic review was performed to investigate whether the Hi serotype f (Hif) incidence rate has increased globally and to describe its associated disease burden. In the post-Hib vaccine era, evidence shows that the incidence rate of Hif infection is increasing worldwide. In total 94 studies including 2 701 patients reported Hif infections. The estimated pooled incidence rate of Hif infection was 0.15/100 000 population per year (range: 0.05-0.40/100 000), with a median case fatality ratio of 14.3 %. Invasive infections most frequently presented as pneumonia (45 %), septicaemia (34 %) and meningitis (20 %). Of 191 Hif isolates, 87 % were ampicillin-susceptible. Multi-locus sequence typing revealed that Hif were relatively clonal, with the majority belonging to clonal complex 124. Hif causes invasive infections of significant variance in both severity and presentation. Globally, the Hif population shows little genetic variability and currently appears to possess low resistance to antimicrobials.

Phylogenetic Structure and Comparative Genomics of Multi-National Invasive Haemophilus influenzae Serotype a Isolates.

Recent reports have indicated a rise of invasive disease caused by Haemophilus influenzae serotype a (Hia) in North America and some European countries. The whole-genome sequences for a total of 410 invasive Hia isolates were obtained from 12 countries spanning the years of 1998 to 2019 and underwent phylogenetic and comparative genomic analysis in order to characterize the major strains causing disease and the genetic variation present among factors contributing to virulence and antimicrobial resistance. Among 410 isolate sequences received, 408 passed our quality control and underwent genomic analysis. Phylogenetic analysis revealed that the Hia isolates formed four genetically distinct clades: clade 1 (n = 336), clade 2 (n = 13), clade 3 (n = 3) and clade 4 (n = 56). A low diversity subclade 1.1 was found in clade 1 and contained almost exclusively North American isolates. The predominant sequence types in the Hia collection were ST-56 (n = 125), ST-23 (n = 98) and ST-576 (n = 51), which belonged to clade 1, and ST-62 (n = 54), which belonged to clade 4. Clades 1 and 4 contained predominantly North American isolates, and clades 2 and 3 predominantly contained European isolates. Evidence of the presence of capsule duplication was detected in clade 1 and 2 isolates. Seven of the virulence genes involved in endotoxin biosynthesis were absent from all Hia isolates. In general, the presence of known factors contributing to ß-lactam antibiotic resistance was low among Hia isolates. Further tests for virulence and antibiotic susceptibility would be required to determine the impact of these variations among the isolates.

Colonisation of Irish patients with chronic obstructive pulmonary disease by Streptococcus pneumoniae and analysis of the pneumococcal vaccine coverage: a non-interventional, observational, prospective cohort study.

OBJECTIVES: To characterise the pattern of colonisation and serotypes of Streptococcus pneumoniae among patients with chronic obstructive pulmonary disease (COPD) who currently receive the 23-valent pneumococcal polysaccharide vaccine (PPV-23) according to vaccination status, use of antibiotics and steroids. To investigate the prevalence of PPV-23 and 13-valent pneumococcal conjugate vaccine (PCV-13) serotypes within the study cohort. DESIGN: A non-interventional, observational, prospective cohort study with a 12 -month follow-up period inclusive of quarterly study visits. SETTING: Beaumont Hospital and The Royal College of Surgeons in Ireland Clinical Research Centre, Dublin, Ireland. PARTICIPANTS: Patients with an established diagnosis of COPD attending a tertiary medical centre. PRIMARY OUTCOME MEASURE: Colonisation rate of S. pneumoniae in patients with COPD and characterisation of serotypes of S. pneumoniae with correlation to currently available pneumococcal vaccines. Sputum and oropharyngeal swab samples were collected for the isolation of S. pneumoniae. SECONDARY OUTCOME MEASURE: Seasonality of colonisation of S. pneumoniae and its relationship with the incidence of exacerbations of COPD. RESULTS: S. pneumoniae was detected in 16 of 417 samples, a colonisation incident rate of 3.8% and in 11 of 133 (8%) patients at least once during the study. The majority of S. pneumoniae isolates were identified in spring and were non-vaccine serotypes for either the PPV-23 or PCV-13 (63%). The colonisation incident rate of S. pneumoniae fluctuated over the four seasons with a peak of 6.6% in spring and the lowest rate of 2.2% occurring during winter. Antibiotic use was highest during periods of low colonisation. CONCLUSIONS: There is seasonal variation in S. pneumoniae colonisation among patients with COPD which may reflect antibiotic use in autumn and winter. The predominance of non-vaccine types suggests that PCV-13 may have limited impact among patients with COPD in Ireland who currently receive PPV-23. TRIAL REGISTRATION NUMBER: NCT02535546; post-results.

Non-invasive pneumococcal serotypes and antimicrobial susceptibilities in a paediatric hospital in the era of conjugate vaccines.

To evaluate the effects of 7-valent pneumococcal conjugate vaccine (PCV7) introduction to the routine childhood immunisation schedule in 2008 and its replacement by PCV13 in 2010 in Ireland, we surveyed the serotypes and antimicrobial susceptibilities of 339 pneumococci associated with carriage and non-invasive infection (NII) in a Dublin paediatric hospital from 2009 to 2012. Furthermore, we compared the distribution of pneumococcal serotypes collected from 2009 to 2012 to 105 NII pneumococci isolated in 2007, the year before conjugate vaccine introduction. PCV7 serotypes declined from 2007 to 2012 as follows: carriage, 67-23% (p=0.0004); conjunctivitis, 58-0% (p<0.0001); non-bacteraemic lower respiratory tract infection, 50-19% (p=0.0363) and otitis media 54-27%. Notably, antimicrobial resistant (AMR) PCV7 serotypes showed a significant decrease by the end of the study period (i.e. 2012) (p<0.0001). Compared with 2007 the overall occurrence of serotype 19A increased from 1.9 to 10% in 2010 (p=0.0132) and to 15% in 2011 (p=0.0005). Importantly, serotype 19A declined significantly from 2011 levels to an overall prevalence of 4.8% in 2012 (p=0.0243). Most striking was the significant reduction of AMR 19A (p=0.0195). Conversely, increases were observed in non-vaccine type (NVT) pneumococci in 2009-2012, of which serotypes 11A (n=30), 15B/C (n=17), 22F (n=14), 35Bn=13), non-typeable pneumococci (n=13) and 23A (n=12) were the most prevalent. Moreover, an increase in NVT non-susceptible to at least one antimicrobial in 2009-2012 was noted, attributable to serotypes 35B (n=10) and 15A (n=7). In summary, this study has shown that PCV7 and PCV13 introduction has had a positive impact on their target serotypes and antimicrobial resistance amongst pneumococci within a paediatric hospital within a short time period. However, the increase in NVT prevalence highlights the need for continued surveillance.