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.

Awareness and Preventative Behaviours Regarding Toxoplasma, Listeria and Cytomegalovirus Among Pregnant Women

Aim Infection with toxoplasma, listeria and cytomegalovirus (CMV) infections can negatively affect pregnancy outcomes. Awareness of these infections, knowledge of preventive practices and pertinent behaviours was assessed. Methods A survey of patients at antenatal clinics in a Dublin maternity hospital was conducted over a six month period. Analysis was undertaken using SPSS. Results The response rate was 36% (287/800). One in two respondents were aware of toxoplasma, one in four of Listeria but only 1 in 10 of CMV. Overall, knowledge was highest among older, more educated pregnant women. Nativity had a significant effect on knowledge and behaviour, but increasing parity did not. However the majority practised key safe behaviours. Conclusion Information must be conveyed to pregnant women in a user friendly format and in a culturally sensitive way.

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.

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.

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.

Physician-led thoracic ultrasound-guided biopsy; a district general hospital perspective.

BACKGROUND: Physician-led thoracic ultrasound (TUS)-guided biopsies provide a prompt route to tissue diagnosis in pleural and peripheral lung malignancies. This retrospective study reviews the diagnostic performance and safety of this approach in a UK District General Hospital. METHODS: Time to biopsy, diagnostic yield and complication rate were analysed in a cohort of 49 patients undergoing ultrasound-guided tissue sampling between September 2019 and December 2022. RESULTS: Fifty-one TUS-guided biopsies were attempted. Mean time from decision to biopsy was 5 days. The overall diagnostic yield was 82%. Complication rate was low; 3 minor adverse effects were reported which led to no change in routine care. CONCLUSION: This single centre retrospective study shows that physician-led TUS-guided biopsy provides a safe and timely method of obtaining a tissue diagnosis in thoracic malignancy. It offers an alternative to computer tomography (CT)-guided or thoracoscopic biopsies and should be considered in selected patients where local procedural expertise exists.

Universal antenatal screening for hepatitis C.

The aims of this study were to pilot universal antenatal HCV screening and to determine the true seroprevalence of HCV infection in an unselected antenatal population. A risk assessment questionnaire for HCV infection was applied to all women booking for antenatal care over a 1-year period. In addition the prevalence of anti-HCV antibody positive serology in this population was determined. Over the course of the year, 9121 women booked for antenatal care at the Rotunda and 8976 women agreed to take part in the study, representing an uptake of 98.4%. 78 (0.9%) women were diagnosed as anti-HCV positive, the majority of whom were Irish (60.3%) or from Eastern Europe (24.4%). 73% of anti-HCV positive women reported one or more known risk factor with tattooing and a history of drug abuse the most commonly reported. 27% (n = 21) of anti-HCV positive women had no identifiable risk factors. Due to selective screening, seroprevalence of HCV is impossible to accurately calculate. However the universal screening applied here and the high uptake of testing has allowed the prevalence of anti-HCV among our antenatal population to be calculated at 0.9%. A significant proportion (27%) of anti-HCV positive women in this study reported no epidemiological risk factors at the time

Multiplex PCR to determine Streptococcus pneumoniae serotypes causing otitis media in the Republic of Ireland with further characterisation of antimicrobial susceptibilities and genotypes.

The purpose of this study was to determine the serotypes, genotypes and antimicrobial susceptibilities of Streptococcus pneumoniae causing otitis media (OM) in children in Dublin, Ireland. S. pneumoniae isolates (n = 28) from spontaneously discharging OM were studied. Serotyping was performed using a previously undescribed multiplex polymerase chain reaction (PCR) scheme in combination with serological methods. Multilocus sequence typing (MLST) was performed using standard procedures. Antimicrobial susceptibility testing was performed using the Etest method. Fourteen different S. pneumoniae serotypes were identified. The five most common serotypes were 3, 19F, 19A, 14 and 6A, which accounted for 68% of all infections. The 7-valent pneumococcal conjugate vaccine (PCV7), 10-valent pneumococcal conjugate vaccine (PHiD-CV) and 13-valent pneumococcal conjugate vaccine (PCV13) provided potential coverages of 43%, 46% and 86%, respectively. Reduced susceptibility to penicillin was evident for 25% of isolates and was associated with serotypes 14, 19A, 19F and 9V. A total of 21 different sequence types (STs) were identified. Pneumococcal Molecular Epidemiology Network (PMEN) clones or their variants represented 54% (15/28) of all isolates. Continued monitoring and characterisation of S. pneumoniae causing OM in Ireland is warranted in order to guide future vaccine and treatment policies.

Serotype distribution of Streptococcus pneumoniae causing invasive disease in the Republic of Ireland.

The 7-valent pneumococcal conjugate vaccine (PCV7) was included in the routine infant immunization schedule in Ireland in September 2008. We determined the serotype of 977 S. pneumoniae isolates causing invasive disease between 2000-2002 and 2007-2008, assessed for the presence of the recently described serotype 6C and determined the susceptibility of isolates during 2007-2008 to penicillin and cefotaxime. Serotype 14 was the most common serotype during both periods and 7·7% of isolates previously typed as serotype 6A were serotype 6C. During 2000-2002 and 2007-2008, PCV7 could potentially have prevented 85% and 74% of invasive pneumococcal disease in the target population (i.e. children aged <2 years), respectively. The level of penicillin non-susceptibility was 17% in 2007-2008. Ongoing surveillance of serotypes is required to determine the impact of PCV7 in the Irish population and to assess the potential of new vaccines with expanded valency.

HIV testing and treatment in the antenatal care setting.

Routine linked HIV antenatal screening, with "opt-out", was introduced at the Rotunda in January 1998. This paper reviews the screening and subsequent pregnancy management and outcome in HIV positive women from 1998 to 2006. During this time 225 women (280 pregnancies) were HIV positive and 194 women subsequently delivered at the Rotunda, representing 233 liveborn infants. Overall anti-HIV prevalence was 0.42%, increasing from 0.06% in 1998 to 0.57% in 2006. Of 233 livebirths, 111 (48%) were delivered by spontaneous vaginal delivery (SVD). HIV treatment was started pre-pregnancy in 14 (6%) pregnancies and antenatally in 208 (90%). The vertical transmission rate in mothers receiving >4 weeks of treatment was 0%. We conclude that routine antenatal HIV screening is effective and significantly benefits the health of mother and child.

Susceptibility of pregnant women to toxoplasma infection--potential benefits for newborn screening.

Congenital toxoplasmosis (CT) arises as a result of new acquisition of Toxoplasma infection by a susceptible woman during pregnancy. Early detection of CT through neonatal screening programmes could optimize management and improve infant outcome. This study sought to estimate the prevalence of Toxoplasma susceptibility in pregnant women. As detection of Toxoplasma antibodies in neonatal blood reflects maternal exposure history, maternal antibody seroprevalence was determined using anonymized residual blood from newborn screening cards. A total of 20,252 cards were tested in 1 year. 4,991 (24.6%) cards tested positive for Toxoplasma antibody. Results were stratified by county. Toxoplasma antibody seroprevalence rates of 25% indicated that Toxoplasma infection is common in Ireland and that up to 75% of women remain susceptible to primary infection during pregnancy. This study aimed to a) determine the seroprevalence of Toxoplasma antibody in pregnant women, and hence b) estimate the risk for acquisition of primary toxoplasmosis in pregnancy in order to support an application to fund a pilot newborn screening programme.

Impact of a rapid molecular test for positive blood cultures from neonatal intensive care patients on clinical management: a retrospective audit.

BACKGROUND: Both Staphylococcus aureus and coagulase negative Staphylococci are common causes of late-onset neonatal sepsis in the neonatal intensive care unit (NICU), usually relating to intravascular access device infections. AIMS: This project aimed to review the impact on antimicrobial treatment and clinical outcome in the NICU setting, of the introduction of the Xpert MRSA/SA BC test (Cepheid, USA) for the identification of staphylococci in blood cultures. METHODS: A retrospective audit was carried out of the pre- and post-intervention periods; the intervention was the introduction of the Xpert MRSA/SA BC test. RESULTS: In total, 88 neonates had positive blood cultures with Staphylococcus spp., comprising 42 neonates in the pre-intervention and 46 in the post-intervention groups. The pre-intervention group had a higher birth weight (1.541 kg vs. 1.219 kg, p = 0.05) and higher platelet count (288 vs. 224 × 109/L, p = 0.05). There was a trend towards a shorter duration of antimicrobial therapy in term infants and in the length of admission; however, this was not statistically significant (p = 0.2). All of the nine infants post-intervention with significant bacteraemia (S. aureus =3, CoNS =6) were changed to the optimal antimicrobial at the time the result was available. CONCLUSIONS: This study shows that the introduction of the Xpert MRSA/SA BC test can lead to a reduction in the length of admission and duration of antimicrobials in term infants; however, the difference was not statistically significant. All nine infants with clinically significant bacteraemia were treated with the appropriate antimicrobial when the Xpert MRSA/SA BC test result was available.

A case of disseminated miliary tuberculosis in a five-year-old child.

A five-year old girl was referred, by the local area medical officer, as she had a positive Mantoux test and a chest x-ray consistent with miliary tuberculosis. She had initially been identified three months previously as a contact of a case of open pulmonary tuberculosis. A CT scan of the brain at the time of presentation showed multiple intracranial tuberculomae. A CT Brain scan three months into the treatment regime showed a significant reduction in the number and size of nodules indicating a favourable response to treatment. This case emphasises the importance of rapid tracing of paediatric tuberculosis contacts, if serious complications and their consequences are to be avoided.

Tinea capitis in a paediatric population.

Tinea capitis is an increasing problem in Europe. The pattern of infection is changing with an increase in pathogenic anthropophilic dermatophytes particularly Trichophyton tonsurans. We aimed to determine the frequency of tinea capitis in a paediatric population attending dermatology outpatients and examine the clinical spectrum of disease. A retrospective analysis was performed of all laboratory proven tinea capitis cases presenting to the dermatology outpatient department at The Children's University Hospital, Temple Street over an 18-month period (1st January 2004 to 30th of June 2005 inclusive). Sixty-two children had tinea capitis of whom 53 (85.5%) were of African descent. Thirty-five (56%) were male and 27 female (44%). The average age at presentation was 4.02 years (age range 1-163 months) with five cases occurring in children less than one year of age. The most common pathogen was the anthropophilic dermatophyte Trichophyton tonsurans, accounting for 47 (75.8%) of all cases of tinea capitis. Eight (12.9%) were secondary to Microsporum ferrigineum, 2 (3.2%) secondary to Trichophyton violaceum, both Trichophyton soudanese and Trichophyton verruosum accounted for 1.6% each. The zoophilic organism Microsporum canis was diagnosed in 3 cases (4.8%). Presenting signs included scaling of the scalp (35.47%), scaling of the scalp and alopecia (53.24%), and alopecia and kerion (11.29%/o). The duration of symptoms was recorded in 52 patients with the average duration 8.38 months (range 0.5-72 months). In 20 cases an associated skin involvement on other areas of the body was recorded. All patients at diagnosis were either on no, suboptimal or inappropriate treatment. The prevalence of tinea capitis is increasing in this hospital based cohort. The main pathogen is now Trichophyton tonsurans. Children of African descent are at increased risk of infection. The diagnosis is poorly recognized and needs to be highlighted as a public health issue. There is a need for community based prevalence studies.

Low cytomegalovirus sero-prevalence in Irish pregnant women.

The aim of this study was to determine the sero-prevalence of cytomegalovirus (CMV) IgG antibody in pregnant women in Ireland and assess individual risk factors for prior acquisition of CMV. In 2002, sera from 1047 pregnant women were tested by enzyme immunoassay for CMV IgG. Age and nationality were recorded for each patient. Among Irish-born women the following additional factors were also recorded: socio-economic status, number of children and occupational exposure to children. Only 30.4% (204/670) of Irish women were CMV antibody positive compared to 89.7% (322/359) of non-Irish women (p < 0.001). Non-Irish women were mostly from Sub-Saharan Africa, Eastern Europe and Asia. Lower socio-economic group and increasing number of children were significant independent predictors of CMV sero-positivity among Irish pregnant women (p < 0.05). Irish pregnant women have one of the lowest reported CMV sero-prevalence rates worldwide, indicating low circulation of CMV within the community. However, up to 70% of Irish women are susceptible to a primary infection during pregnancy.

Cloning and characterisation of the serC and aroA genes of Yersinia enterocolitica, and construction of an aroA mutant.

A gene library of Yersinia enterocolitica 8081 was constructed in the cosmid vector pHC79. Recombinants containing the aroA gene, encoding 5-enolpyruvylshikimate 3-phosphate synthase, were identified by complementation of the aroA mutation in Escherichia coli K-12 strain AB2829. All six recombinant plasmids which complemented aroA also complemented the serC mutation in E. coli K-12 strain KL282. Tn5 mutagenesis suggested serC encoding 3-phosphoserine aminotransferase was the proximal gene in an operon with aroA. The nucleotide sequence of a 3-kb HindII-EcoRV fragment encoding the two genes was determined. The serC and aroA open reading frames contain 362 and 428 codons, respectively, and the deduced amino acid sequences share 78% and 81% homology, respectively, with the corresponding E. coli genes. Sequence inspection revealed no obvious terminators or promoters in the intergenic region. The cloned Y. enterocolitica aroA gene was inactivated in vitro and reintroduced into the parental Y. enterocolitica 8081 strain using the suicide vector pJM703.1. Stable aroA insertion mutants of Y. enterocolitica were isolated.

The effect of bile acids on the growth and adherence of Helicobacter pylori.

Bile reflux gastritis occurs in the absence of Helicobacter pylori (H. pylori). The aim of this study was to see if the bile acids cheno or ursodeoxycholic acid affected the growth or adherence of H. pylori in vitro. Twenty-seven strains growth were inhibited by 0.1% chenodeoxycholic acid whereas only 11 out of the 27 were inhibited by 0.1% ursodeoxycholic acid. Growth was totally inhibited by a combination of 0.05% chenodeoxycholic acid +0.05% ursodeoxycholic acid. Chenodeoxycholic acid was a more effective inhibitor of adherence in that the number inhibited and percentage inhibition were greater than with ursodeoxycholic acid. Bile salts might be useful in the treatment of H. pylori infection.

Timing and interpretation of tests for diagnosing perinatally acquired hepatitis C virus infection.

The diagnosis of hepatitis C virus (HCV) infection in children born to HCV-infected women is based on serologic assays and HCV RNA measurement by PCR. Interpretation of the results of these tests is hampered by uncertainty about the age distribution of loss of maternal antibody and the sensitivity and specificity of PCR at different ages. On the basis of findings from a recent vertical transmission study, we estimated the posttest probability of a child's being infected or uninfected under several test result scenarios. These estimates may assist clinicians in assessing the likelihood of infection in an individual child and in using the currently available assays cost effectively.