Antibiotic susceptibility and molecular analysis of invasive Neisseria meningitidis recovered in the Republic of Ireland, 1996 to 2016.

This study examined the antimicrobial susceptibility of invasive meningococcal disease (IMD)-associated Neisseria meningitidis recovered in the Republic of Ireland between 1996 and 2016. In total, 1359 isolates representing over one-third of all laboratory-confirmed cases of IMD diagnosed each epidemiological year (EY; July 1-June 30) were analysed. All isolates were susceptible to ciprofloxacin, rifampicin and cefotaxime and 74% and 87% were susceptible to sulphonamide and penicillin, respectively. The proportion of isolates exhibiting reduced susceptibility to penicillin increased significantly during the study with no evidence of major clonal expansion or horizontal spread of a specific penA allele. Greater diversity observed among recently recovered meningococci and specifically among isolates exhibiting reduced penicillin susceptibility contributed to the overall increase in penA allele diversity throughout. The emergence and dissemination of strains with phenotypic and genotypic reduced susceptibility to penicillin increase the need for continued surveillance of antimicrobial susceptibility of meningococci in the Republic of Ireland especially in view of the recommendation of penicillin G as empiric treatment of choice for pre-hospital management.

Epidemiology of two decades of invasive meningococcal disease in the Republic of Ireland: an analysis of national surveillance data on laboratory-confirmed cases from 1996 to 2016.

We examined the epidemiology of invasive meningococcal disease (IMD) in the Republic of Ireland (ROI) between epidemiological year (EY) 1996/1997 and EY2015/2016. Over the 20 EYs, 3707 cases were reported with annual incidence rates per 100 000 peaking at 11.6 in EY1999/2000, decreasing significantly to 1.5 in EY2015/2016. The highest disease burden was in infants and children <5, whereas adults aged ⩾65 years experienced the highest case fatality ratio (CFR) of 15.7% but over the study period the median annual CFR remained low (4.4%). Meningococcal serogroup B (menB) dominated (78%), followed by menC (17%), menW (1%) and menY (1%). The incidence of menC IMD declined significantly in all age groups after menC vaccine introduction in 2000. MenB incidence also declined over the 20 EYs with decreasing trends in all age groups under 65, including an almost 50% decrease in infants over the final four EYs. IMD incidence in the ROI has declined, partly attributable to menC vaccination success, coupled with a spontaneous decline in menB. However, recent gradual increases in non-menB IMD and the introduction of vaccines targeting menB demand continued detailed surveillance to accurately monitor trends and to assess vaccine impact.

Is It Time To Review The Vaccination Strategy To Protect Adults Against Invasive Pneumococcal Disease?

Pneumococcal conjugate vaccines (PCVs) have reduced the predominant serotypes causing invasive pneumococcal disease (IPD). We assessed the impact of the paediatric 7- and 13-valent pneumococcal conjugate vaccines (PCV7 and PCV13) among older adults. We compared serotype-specific incidence rates from 2007/08 to 2016/17, expressed as incidence rate ratios (IRR). Introducing PCV7 and PCV13 into the childhood immunisation programme resulted in a decline in these serotypes in adults ≥65 years of age, with PCV7 serotypes decreasing by 85% (IRR=0.11, 95%CI: 0.05-0.22, p<0.0001) and PCV13 serotypes not included in PCV7 (PCV13-7), decreasing by 9% (IRR=0.68, 95%CI: 0.40-1.16, p=0.134). However, there was a significant increase in serotypes only found in the 23-valent polysaccharide vaccine, PPV23-PCV13: IRR=2.57, 95%CI: 1.68-4.03, p<0.0001, and non-vaccine types (NVTs), IRR=3.33, 95%CI: 1.75-6.84, p=0.0001. The decline of IPD associated with PCV7/13 serotypes and the increase in PPV23-PCV13 serotypes indicates clear serotype replacement. Increasing PPV23 uptake could still reduce the burden of disease for this population.

A retrospective assessment of the completeness and timeliness of meningococcal disease notifications in the Republic of Ireland over a 16-year period, 1999-2015.

OBJECTIVES: To assess how invasive meningococcal disease (IMD) records held by the Irish Meningitis & Sepsis Reference Laboratory (IMSRL) compare to records of IMD notifications reported on the national integrated electronic Computerised Infectious Disease Reporting (CIDR) system. STUDY DESIGN: We assessed the completeness, data quality and timeliness of IMD notifications and reference laboratory records for the period between 01 July 1999 and 30 June 2015 by identifying discrepant and/or missing data items in a matched case data set and by measuring the timeliness of case reporting. METHODS: We matched anonymised cases notified to CIDR to records based at the IMSRL using birth, reporting and onset dates with gender and laboratory parameters of meningococcal strain characteristics and method of confirmation. Completeness, data quality and the timeliness of notifications were assessed by a stratified sensitivity-based technique and by calculating the average difference between IMSRL and CIDR reporting dates. RESULTS: CIDR recorded a total of 3163 notifications, of which 2759 (87.2%) were matched to IMSRL records. Completeness of IMD case classification as confirmed was estimated to be >99%. Examining the levels of discrepant or missing data in both matched CIDR and IMSRL records as a measure of data quality, recording of demographic items and meningococcal group showed least differences, recording of laboratory case confirmation method and meningococcal strain characteristics were less well recorded, with detail on clinical presentation/diagnosis least well recorded. Overall average annual difference between CIDR and IMSRL recording dates was 3.2 days (95% confidence interval 2.6-3.8). CONCLUSIONS: A high quality of IMD surveillance in Ireland was demonstrated, but scope for improvements in timeliness and capture of enhanced surveillance data regarding date of onset and strain-specific characteristics were identified.

Low Yield of Positive Cerebrospinal Fluid (CSF) Culture and Bacterial PCR Tests In Paediatric Patients With A Normal CSF White Cell Count.

The aim was to review paediatric patients who had a positive cerebrospinal fluid culture or bacterial PCR test, yet had a normal CSF white cell count for age. Patients were included if they had a CSF sample sent for culture (between 2005 and 2015) or bacterial PCR (2010-2015), however neurosurgical and neurology patients were excluded. Of the 2,482 patients reviewed, there were 101 patients with laboratory-confirmed bacterial meningitis included, of which 27 were positive by culture and PCR, 26 by culture alone and 48 were positive by PCR only. Eighteen (18%) of these patients had CSF white cell counts within normal range. Only one case with a normal CSF white cell count, where the lumbar puncture was done after six days of antibiotics, was deemed to be clinically significant. Bacterial PCR should not be routinely requested in patients with a normal CSF white cell count, unless their blood culture is positive or unless clinically indicated based on the assessment of a senior paediatrician.

Group B streptococcal PCR testing in comparison to culture for diagnosis of late onset bacteraemia and meningitis in infants aged 7-90 days: a multi-centre diagnostic accuracy study.

The aim of this study was to compare an in-house real-time PCR assay, with bacterial culture as the reference, for the diagnosis of late onset group B Streptococcal (GBS) disease. This was a retrospective review. All children aged 7-90 days presenting to four paediatric centres that had a blood or CSF sample tested by GBS PCR were included. Of 7,686 blood and 2,495 cerebrospinal fluid (CSF) samples from patients of all ages received for PCR testing, 893 and 859 samples were eligible for the study, respectively. When compared to culture, the sensitivity of blood PCR was 65% (13/20) in comparison to the CSF PCR test which was 100% (5/5). Ten of 23 PCR-positive blood samples and 17 of 22 PCR-positive CSF samples were culture negative. The median threshold Ct values for culture-positive/PCR-positive CSF samples was lower than that of culture-negative/PCR-positive CSF samples (p = 0.08). Clinical details of 17 available cases that were culture negative/PCR positive were reviewed; seven were deemed to be definite cases, eight were probable and two were possible. The results showed that detection of GBS by PCR is useful for CSF samples from infants aged 7-90 days with suspected meningitis; however, analysis of blood samples by PCR is of limited value as a routine screening test for late onset GBS sepsis and should not replace bacterial culture.

The epidemiology of invasive pneumococcal disease in older adults in the post-PCV era. Has there been a herd effect?

The 7 and 13-valent pneumococcal conjugate vaccines (PCVs) have reduced the incidence of invasive pneumococcal disease (IPD) in children in many countries. The objective of this work was to assess the impact of PCVs and potential herd-protection in older adults in Ireland. IPD notification and typing data from adults ⩾65 years of age from July 2007 to June 2016 was assessed using national surveillance data. There was a 94% reduction in PCV7 serotypes from 2007-2008 to 2015-2016, incidence rate ratio (IRR 0·05, P < 0·0001). However, there was no decline in the additional PCV13 (PCV13-7) serotypes over the same period (IRR 0·90) nor in comparison with the pre-PCV13 period 2009-2010 (IRR 0·92). The incidence of serotypes in the 23-valent pneumococcal polysaccharide vaccine only (PPV23-PCV13) and non-vaccine types (NVTs) increased significantly (IRR 2·17, P = 0·0002 and IRR 3·43, P = 0·0001 respectively). Consequently, the overall IPD incidence rate in adults has remained relatively unchanged (from 28·66/100 000 to 28·88/100 000, IRR 1·01, P = 0·9477). Serotype 19A and NVTs were mainly responsible for penicillin resistance in recent years. The decline of PCV7 serotypes indicate that the introduction of PCV7 resulted in herd-protection for adults. However, increases in PPV23-PCV13 and NVTs suggest that changes in vaccination strategy amongst older adults are needed to build on the success of PCVs in children.

Klebsiella pneumoniae bloodstream infection, antimicrobial resistance and consumption trends in Ireland: 2008 to 2013.

This study aimed to describe the epidemiology and antimicrobial resistance trends of Klebsiella pneumoniae bloodstream infection (BSI) in Ireland, in conjunction with national antimicrobial consumption data, during the period 2008 to 2013. A retrospective cohort study of K. pneumoniae BSI cases was conducted, based on notifications from Irish microbiology laboratories to the Health Protection Surveillance Centre (HPSC). In total, 1942 K. pneumoniae BSI cases were identified over 6 years, with 310 reported in 2008 and 326 reported in 2013. From 2008 to 2013, the proportion of isolates resistant to co-amoxiclav (24 % versus 29 %), piperacillin-tazobactam (11 % versus 27 %), third generation cephalosporins (3GC) (11 % versus 21 %), fluoroquinolones (13 % versus 21 %) and gentamicin (11 % versus 17 %) increased overall, concurrent with increasing national rates of antimicrobial consumption in Ireland (acute hospitals: 35.87 versus 39.77 defined daily doses (DDD) per 100 bed days used (BDU); and community: 6.38 versus 7.85 DDD per 1000 inhabitants per day (DID)). Enhanced data on the patient's admission route was available for 735 (38 %) cases. Overall, 51 % (n = 378) were categorised as 'acquired in the reporting hospital'. The all-cause mortality was 20 %, with 115 deaths, 101 (88 %) of whom died within 30 days of blood culture sampling date. K. pneumoniae is the second most common cause of Gram-negative BSI in Ireland, with most cases healthcare-associated and an all-cause mortality of 20 % reported in this study. Annual increases in resistance to different antimicrobial classes and in a multi-drug resistant phenotype have been observed, concurrent with increasing national broad spectrum antimicrobial consumption. These trends portend a risk to patient outcomes and highlight the urgency for individual prescribers to evaluate their antimicrobial prescribing habits in hospitals, long-term care and community settings.

Reporting of Acute Flaccid Paralysis in Children under 15 years of age: Improving Surveillance, January 2009 - December 2014.

Acute Flaccid Paralysis (AFP) surveillance, including case investigation and specimen collection is a gold standard method for poliomyelitis surveillance. The expected annual non-polio AFP rate <15 years of age in Ireland is = 1/100 000 population. This study reviewed all cases of AFP reported to the Irish Paediatric Surveillance Unit and the Health Protection Surveillance Centre between January 2009 and December 2014 and compared reporting rates with the expected incidence rate annually. We assessed quality of surveillance data in terms of completeness of investigation for each case reported. Forty-three AFP cases in children <15 years were notified; 35 of which were confirmed. Guillain-Barre Syndrome (GBS) accounted for 48.6% (n=17) of AFP notifications. In 2014, the expected annual AFP target rate was reached. This study identified possible under-reporting of AFP paediatric cases in Ireland between 2009-2013. Completeness of investigations has improved over time, but requires further work.

Real-time polymerase chain reaction and culture in the diagnosis of invasive group B streptococcal disease in infants: a retrospective study.

Group B streptococcus (GBS) is a leading cause of invasive disease in infants. Accurate and rapid diagnosis is crucial to reduce morbidity and mortality. Real-time polymerase chain reaction (PCR) targeting the dltR gene was utilised for the direct detection of GBS DNA in blood and cerebrospinal fluid (CSF) from infants at an Irish maternity hospital. A retrospective review of laboratory and patient records during the period 2011-2013 was performed in order to evaluate PCR and culture for the diagnosis of invasive GBS disease. A total of 3570 blood and 189 CSF samples from 3510 infants had corresponding culture and PCR results. Culture and PCR exhibited concordance in 3526 GBS-negative samples and 13 (25%) GBS-positive samples (n = 53). Six (11%) and 34 (64%) GBS-positive samples were positive only in culture or PCR, respectively. Culture and PCR identified more GBS-positive infants (n = 47) than PCR (n = 43) or culture (n = 16) alone. Using culture as the reference standard, the sensitivity, specificity, and positive and negative predictive values for PCR on blood samples were 71.4%, 99.2%, 25% and 99.9%, and for CSF samples, they were 60%, 97.8%, 42.9% and 98.9%, respectively. The sensitivity and positive predictive values were improved (blood: 84.6% and 55%; CSF: 77.8% and 100%, respectively) when maternal risk factors and other laboratory test results were considered. The findings in this study recommend the use of direct GBS real-time PCR for the diagnosis of GBS infection in infants with a clinical suspicion of invasive disease and as a complement to culture, but should be interpreted in the light of other laboratory and clinical findings.

Infant botulism due to C. butyricum type E toxin: a novel environmental association with pet terrapins.

We describe two cases of infant botulism due to Clostridium butyricum producing botulinum type E neurotoxin (BoNT/E) and a previously unreported environmental source. The infants presented at age 11 days with poor feeding and lethargy, hypotonia, dilated pupils and absent reflexes. Faecal samples were positive for C. butyricum BoNT/E. The infants recovered after treatment including botulism immune globulin intravenous (BIG-IV). C. butyricum BoNT/E was isolated from water from tanks housing pet 'yellow-bellied' terrapins (Trachemys scripta scripta): in case A the terrapins were in the infant's home; in case B a relative fed the terrapin prior to holding and feeding the infant when both visited another relative. C. butyricum isolates from the infants and the respective terrapin tank waters were indistinguishable by molecular typing. Review of a case of C. butyricum BoNT/E botulism in the UK found that there was a pet terrapin where the infant was living. It is concluded that the C. butyricum-producing BoNT type E in these cases of infant botulism most likely originated from pet terrapins. These findings reinforce public health advice that reptiles, including terrapins, are not suitable pets for children aged <5 years, and highlight the importance of hand washing after handling these pets.

A prolonged outbreak of invasive meningococcal disease in an extended Irish Traveller family across three Health Service Executive (HSE) areas in Ireland, 2010 to 2013.

Between March 2010 and November 2013 eight laboratory-confirmed cases of serogroup B, invasive meningococcal disease (IMD) were identified in an extended Irish Traveller family across three Health Service Executive (HSE) areas of Ireland. Cases were aged between 5 and 46 months, and were either a cousin or sibling of another case. All eight cases survived. Chemoprophylaxis was given to relevant nuclear family members and close contacts on each occasion, but failed to prevent further cases. Neisseria meningitidis isolates from six cases were highly related, belonging to the ST-41/44 clonal complex, and shared the porA designation 7­2,4. In November 2013, the outbreak control team recommended that directly observed ciprofloxacin chemoprophylaxis be administered simultaneously to the extended family, and that the four component meningococcal B (4CMenB) vaccine be administered to family members aged 2 months to 23 years inclusive and relevant close contacts of the eighth case. Subsequently these recommendations were implemented at three regional clinics. Additionally pharyngeal swabs (n=112) were collected to assess carriage rates of N. meningitidis in this extended family. Pharyngeal carriage of N. meningitidis was detected in 15 (13%) family members. From the epidemiological investigation and carriage study overcrowding was the most likely risk factor identified in this outbreak. To date, the combination of directly observed ciprofloxacin chemoprophylaxis and use of 4CMenB vaccine have controlled the outbreak with no further cases diagnosed.

Pertussis in young infants: clinical presentation, course and prevention.

Pertussis is a highly contagious disease caused by the Gram negative aerobic coccobacillus, Bordetella pertussis. It may present with severe symptoms and complications in infants and can pose a diagnostic challenge. This is a vaccine preventable illness covered by the Irish Childhood Immunisation Schedule. In 2011, a retrospective review was conducted of the records of infants, under six months, with a confirmed diagnosis of pertussis, presenting to Temple Street Children's University Hospital (TSCUH). A summery of notifications of pertussis nationally, from 2001 to 2012, was also examined as part of the study. This found that the rate of reported cases of pertussis has been increasing in Ireland. This national increase corresponds with a rising number of cases identified at TSCUH. Patients commonly presented severely ill with cyanosis and apnoea, on a background of prolonged cough. We found that pertussis was diagnosed rapidly in most cases however in all cases there was a delay to commencement of appropriate macrolide therapy.

Increased incidence of invasive group A streptococcal disease in Ireland, 2012 to 2013.

Invasive group A streptococcal (iGAS) infections have been notifiable in Ireland since 2004. Incidence rates (2004-2011) have ranged from 0.8 to 1.65 per 100,000. In 2012, the iGAS rate rose to 2.66 per 100,000 and was associated with a high proportion of emm1 isolates. A further increase in January to June 2013 has been associated with increased prevalence of emm3. Public health departments and clinicians have been alerted to this increase.

Transmission of endemic ST22-MRSA-IV on four acute hospital wards investigated using a combination of spa, dru and pulsed-field gel electrophoresis typing.

The transmission of meticillin-resistant Staphylococcus aureus (MRSA) between individual patients is difficult to track in institutions where MRSA is endemic. We investigated the transmission of MRSA where ST22-MRSA-IV is endemic on four wards using demographic data, patient and environmental screening, and molecular typing of isolates. A total of 939 patients were screened, 636 within 72 h of admission (on admission) and 303 >72 h after admission, and 1,252 environmental samples were obtained. Isolates were typed by spa, dru and pulsed-field gel electrophoresis (PFGE) typing. A composite dendrogram generated from the three sets of typing data was used to divide isolates into 'dendrogram groups' (DGs). Ten percent of patients (92/939) were MRSA-positive; 7 % (44/636) on admission and 16 % (48/303) >72 h after admission (p = 0.0007). MRSA was recovered from 5 % of environmental specimens (65/1,252). Most isolates from patients (97 %, 85/88) and the environment (97 %, 63/65) exhibited the ST22-MRSA-IV genotype. Four DGs (DG1, DG4, DG16 and DG17) accounted for 58 % of ST22-MRSA-IV isolates from patients. Epidemiological evidence suggested cross-transmission among 44/92 patients (48 %) but molecular typing confirmed probable cross-transmission in only 11 instances (13 %, 11/88), with the majority of cross-transmission (64 %; 7/11) occurring on one ward. In the setting of highly clonal endemic MRSA, the combination of local epidemiology, PFGE, spa and dru typing provided valuable insights into MRSA transmission.

Isolation of NDM-1-producing Klebsiella pnemoniae in Ireland, July 2011.

We report the identification of New Delhi metallo-betalactamase 1 (NDM-1)-producing Klebsiella pnemoniae in Ireland. The organism was resistant to multiple antibiotic classes, including carbapenems, and PCR and sequencing confirmed the presence of the blaNDM-1 gene, carried on a 98 kb plasmid. The organism was isolated from an infant, who was born in India and moved to Ireland at the age of four months. This is the first reported isolation of an NDM-1-producing Enterobacteriaceae strain in Ireland.

Using genomics to examine the persistence of Streptococcus pneumoniae serotype 19A in Ireland and the emergence of a sub-clade associated with vaccine failures.

BACKGROUND: Streptococcus pneumoniae serotype 19A remains a significant cause of invasive pneumococcal disease (IPD) in Ireland despite the successful introduction of a 13-valent pneumococcal conjugate vaccine (PCV13) in 2010 which reduced the overall incidence of IPD in children. METHODS: Invasive Streptococcus pneumoniae serotype 19A isolates from the Irish reference laboratory between 2007-08 and 2017-18 were analysed using whole genome sequencing (WGS) to investigate the persistence of this vaccine-preventable serotype. We compared the entire national 19A collection to other international collections using a standardised nomenclature of Global Pneumococcal Sequencing Clusters (GPSC). RESULTS: Expansion of GPSCs and clonal complexes (CCs) may have been associated with vaccine introduction and antimicrobial prescribing policies. A sub-clade of GPSC1-CC320 (n = 25) unique to Ireland, included five of the ten vaccine failures/breakthrough cases identified (p = 0.0086). This sub-clade was not observed in a global GPSC1-CC320 collection. All isolates within the sub-clade (n = 25) contained a galE gene variant rarely observed in a global pneumococcal collection (n = 37/13454, p < 0.001) nor within GPSC1-CC320 (n = 19/227) (p < 0.001). The sub-clade was estimated to have emerged at the start of the PCV-vaccine era (ancestral origin 2000, range 1995-2004) and expanded in Ireland, with most isolated after PCV13 introduction (n = 24/25). CONCLUSIONS: The identification of a sub-clade/variant of serotype 19A highlights the benefit of using WGS to analyse genotypes associated with persistence of a preventable serotype of S. pneumoniae. Particularly as this sub-clade identified was more likely to be associated with IPD in vaccinated children than other 19A genotypes. It is possible that changes to the galE gene, which is involved in capsule production but outside of the capsular polysaccharide biosynthesis locus, may affect bacterial persistence within the population. Discrete changes associated with vaccine-serotype persistence should be further investigated and may inform vaccine strategies.

National hand hygiene campaigns in Europe, 2000-2009.

Hand hygiene represents the single most effective way to prevent healthcare-associated infections. The World Health Organization, as part of its First Global Patient Safety Challenge, recommends implementation of multi-faceted strategies to increase compliance with hand hygiene. A questionnaire was sent by the European Centre for Disease Prevention and Control to 30 European countries, regarding the availability and organisation of their national hand hygiene campaigns. All countries responded. Thirteen countries had organised at least one national campaign during the period 2000-2009 and three countries were in the process of organising a national campaign. Although the remaining countries did not have a national campaign, several reported regional and local hand hygiene activities or educational resources on national websites.

Hospital infection society prevalence survey of Healthcare Associated Infection 2006: comparison of results between Northern Ireland and the Republic of Ireland.

As part of the Third Healthcare Associated Infection (HCAI) Prevalence Survey of the United Kingdom and Ireland, HCAI point prevalence surveys were carried out in Northern Ireland (NI) and the Republic of Ireland (RoI). Here we explore the potential benefits of comparing results from two countries with different healthcare systems, which employed similar methodologies and identical HCAI definitions. Forty-four acute adult hospitals in the RoI and 15 in NI participated with a total of 11 185 patients surveyed (NI 3644 patients and RoI 7541). The overall HCAI prevalence was 5.4 and 4.9 in NI and the RoI, respectively. There was no significant difference in prevalence rates of HCAI, device-related HCAI or HCAI associated with bloodstream infection but there was a difference in meticillin-resistant Staphylococcus aureus-related HCAI (P = 0.02) between the two countries. There were significantly more urinary tract infections and Clostridium difficile infections recorded in NI (P = 0.002 and P < 0.001). HCAIs were more prevalent in patients aged >65 years and in the intensive care unit in both countries. HCAIs were also more prevalent if patients were mechanically ventilated, had had recent non-implant surgery (RoI) or had more recorded HCAI risk factors. This is the first time that HCAI prevalence rates have been directly compared between NI and the RoI. By closely examining similarities and differences between HCAI prevalence rates in both countries it is hoped that this will influence healthcare planning and at the same time reassure the public that HCAI is important and that measures are being taken to combat it.