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.

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.

Invasive pneumococcal disease in children in Ireland--the anticipated benefit of conjugate pneumococcal vaccination.

BACKGROUND: Streptococcus pneumoniae is an important cause of childhood illness. Recently a safe and effective 7-valent conjugate pneumococcal vaccine for children has been licensed in the EU. AIMS: To calculate the incidence of invasive pneumococcal disease (IPD) in children in Ireland, to estimate the burden of disease and to anticipate the protective effect of the conjugate vaccine. METHODS: Retrospective review of data from children with IPD. RESULTS: Ninety-six cases of IPD in 95 children including two related deaths were identified. All childhood IPD incidence was estimated at 10.6/100,000. We anticipate that the 7-valent conjugate vaccine could prevent up to 90% of sepsis and up to 82.5% of meningitis cases. CONCLUSIONS: IPD is an important cause of mortality and morbidity in children in Ireland. Routine use of conjugate pneumococcal vaccine would have a significant impact on pneumococcal disease, especially in vaccinated children but also in unvaccinated children and older adults.

Screening for Chlamydia trachomatis in asymptomatic women attending outpatient clinics in a large maternity hospital in Dublin, Ireland.

BACKGROUND: Chlamydia trachomatis can cause a sexually transmitted infection, which, untreated, may result in considerable morbidity. METHODS: A prevalence study was conducted for C trachomatis using nucleic acid amplification technology in asymptomatic women, and certain risk factors that may be used to direct future screening strategies were assessed. RESULTS: The study population comprised 945 asymptomatic women, of whom 783 were attending antenatal clinics, 91 were attending infertility clinics and 71 were attending family planning clinics. An overall C trachomatis prevalence of 3.7% (35/945) was found, with the highest prevalence of 11.2% (22/196) in Irish single women aged <25 years. Logistic regression analysis showed that single status and age <25 years were independent, statistically significant predictors of C trachomatis infection. CONCLUSION: These results support routine screening of asymptomatic women who are sexually active and aged <25 years. An opportunist active screening of all sexually active women independent of age should be additionally considered if resources permit.

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.

Susceptibility to infectious rash illness in pregnant women from diverse geographical regions.

Varicella-zoster (VZV), rubella (RV) and parvovirus B19 (B19V) infections are important causes of rash illness in pregnancy, due to their potential adverse impact on both mother and fetus. We determined susceptibility to these infections in pregnant women attending our hospital in 2002. Age and nationality were recorded. Sera were tested for VZV, RV, and B19V antibody by enzyme immunoassay. Of 7,980 women screened for VZV IgG, 11.3% were seronegative and therefore susceptible to infection. Across different worldwide regions, 6.9% of Irish and other Western European women were susceptible to VZV, compared to 19.7% of other women tested (p < 0.001), most of whom were from Central and Eastern Europe, sub-Saharan Africa and Asia. Of 7,872 women screened for RV IgG, 2.3% were seronegative. Few Irish (0.6%) or other Western European women (0.7%) were rubella non-immune, but 5.5% of women from other regions tested were susceptible to rubella (p < 0.001). A random subset of 1,048 women were tested for B19V IgG. About 38% were susceptible, varying from 22% to 63% across the different regions studied. There are important differences in immunity to these infections and so of potential risk of an adverse outcome in indigenous and immigrant pregnant women in Ireland.

Irish strains of Neisseria meningitidis: characterisation using multilocus sequence typing.

A total of 56 Neisseria meningitidis strains are analysed using multilocus sequence typing (MLST). Twenty-nine distinct sequence types (STs) were identified, eight of which were new. Four known hypervirulent clones--ST-11 (electrophoretic type [ET]-37) complex, ST-44 complex (lineage 3), ST-32 (ET-5) complex and ST-8 complex (cluster A4)--were identified by MLST in 35 disease-associated and four carrier strains. Two other clones (ST-22 complex and ST-269 complex) were identified in nine disease-associated and one carrier strain. The remaining strains were heterogeneous. Additional sequencing within the FumC gene further distinguished the ET-15 clone within the ST-11 (ET-37) clonal complex. This resolution of isolates into genetic clones by MLST enhances the more traditional techniques of serotyping and serosubtyping. The data obtained established that hyperendemic meningococcal disease in Ireland could be attributed to strains belonging to four major hypervirulent clones, all of which account for elevated levels of disease worldwide. The extra information provided by MLST will be used to study the population structure and epidemiology of N. meningitidis and will allow a comparison of Irish strains with those circulating globally.

Outcome of infants born to hepatitis C infected women.

BACKGROUND: Hepatitis C virus (HCV) can be transmitted vertically from mother to infant, either late in pregnancy or at delivery. AIMS: To determine the outcome of infants born to HCV infected women, to characterise epidemiology and to design an appropriate infant monitoring schedule. METHODS: Three hundred and fourteen infants, born to 296 HCV positive women between 1994 and 1999 were monitored for a median of 18 months (range 1-52). RESULTS: Forty per cent of infants were small for age and 46% had neonatal abstinence syndrome (NAS). Of 173 infants of defined status, 11 were infected (vertical transmission rate [VTR] 6.4%, 95% CI 2.8-10). Infected infants were diagnosed at a median of three months (range 0.5-10). Liver transaminases elevation was documented in 8% of uninfected infants. A negative HCV PCR test before one month of age did not exclude infection but all infected patients had detectable HCV RNA when next tested (range 2-10 months). CONCLUSIONS: 94% of infants born to HCV antibody positive women are not HIV infected. Liver transaminase elevation in exposed infants is not always indicative of infection. A minimum monitoring schedule of testing (PCR and antibody) at six to eight weeks, six and 18 months allows early diagnosis while detecting late seroconversions.

Antenatal hepatitis B screening - is there a need for a national policy?

Routine antenatal testing for hepatitis B carriage with maternal consent was introduced at the Rotunda in January 1998. The uptake of testing has been excellent; 99.98% of women presenting for antenatal care accepted hepatitis B (HBV) screening in the 30-months from January 1998 through June 2000. The prevalence of HBV carriage was 0.35% (58 pregnancies of 16,222 tested) increasing from 0.25% in 1998 (16 of 6227) to 0.45% in the first six months of 2000 (16 of 3484). Fifty-five women had 58 pregnancies (three women had two pregnancies). Two of these were e-antigen positive. HBV carrier status was previously unknown in 48 (87%). Two additional women had acute HBV infection in pregnancy. Forty-five infants have been born to mothers included in this screening programme. Audit of infant outcome reveals excellent compliance with immunisation and follow-up: 29 (64%) have completed the 3 dose HBV vaccination schedule to date. Thirteen infants (31%) are still attending; three are lost to follow-up including one whose family has emigrated. Routine antenatal screening for hepatitis B carriage is cost-effective and should be considered a standard of care in maternity practice.

Hepatitis C infection in an Irish antenatal population.

BACKGROUND: Hepatitis C infection (HCV) has an estimated seroprevalence of 1-2% in women of child-bearing age and vertical transmission rate of 5-15%. AIMS: To characterise the current trends of HCV in an Irish antenatal population. METHODS: Infants of HCV seropositive women, born 1994 to 1999, were referred to the Paediatric Infectious Diseases service. Maternal details were collected retrospectively. RESULTS: 296 HCV seropositive women were studied. 244 (82%) were infected through intravenous drug use (IVDU), 25 (8%) through heterosexual contact and 13 (7%) via blood products. Nine women had no identifiable risk factors. Coinfection with other blood borne viruses was uncommon (4.7% HIV, 3.4% hepatitis B). Of 84 women tested for HCV-RNA, 46 (55%) were positive. Eighty three (26%) delivered prematurely; the caesarean section rate was 11%. CONCLUSIONS: HCV is increasingly detected in antenatal clinics. Heterosexual contact is a mode of spread. Maternal HCV viraemia can be variable in pregnancy. Further study of HCV in pregnancy is needed to define the impact of pregnancy on HCV, accurately predict infant outcome and selectively target interventions to women at greatest risk of transmission.

Bacteriology of normal and diseased tonsils assessed by fine-needle aspiration: Haemophilus influenzae and the pathogenesis of recurrent acute tonsillitis.

The pathogenesis of recurrent tonsillitis is largely unknown. Selection of appropriate antibiotic therapy for patients with recurrent tonsillitis is difficult because of the limitations of traditional methods of sampling tonsillar microflora and the increasing incidence of beta-lactamase producing bacteria in the tonsil. In addition, little attention has been paid to the bacteriology of normal tonsils. The tonsil core bacteria was assessed in 124 patients with recurrent acute tonsillitis. Fifty-five of these patients were randomly selected for fine-needle aspiration which revealed a similar profile of bacteria in 85%. Fine-needle aspiration of 10 normal tonsils found few pathogens; the predominant organisms being normal flora. No Haemophilus influenzae were detected in this control group. This study demonstrates the accuracy of fine-needle aspiration in identifying tonsil core bacteriology and its suitability in the clinical setting. It reports on the flora of normal healthy tonsils and it highlights the association between H. influenzae and recurrent acute tonsillitis.

Meningococcal disease in the Republic of Ireland: 1995.

Two hundred and nine culture confirmed cases of meningococcal disease were reported in the Republic of Ireland in 1995, using a new laboratory based surveillance system. The reported rate of 5.9/100000 population is one of the highest in western Europe, but the rate differed widely between regions. Fifty-three per cent of cases were female. Half of the cases occurred in four months (January, February, March, and December). Nineteen cases (9%) died. The highest age specific incidence was in infancy (under 1 year). Infections with serogroup B accounted for 105 cases (54%) and serogroup C 87 cases (45%). We estimate that up to 30% of cases of meningococcal disease may be preventable when conjugate meningococcal group C vaccines become available, but cost benefit analyses will be required to determine how they should be employed.

The in-vitro susceptibilities of vaginal lactobacilli to four broad-spectrum antibiotics, as determined by the agar dilution and E test methods.

The minimum inhibitory concentrations (MICs) of cefaclor, co-amoxiclav, clarithromycin and ciprofloxacin for 59 strains of vaginal lactobacilli were determined by both the reference agar dilution and E test methods. With the exception of clarithromycin, there was poor correlation between the results obtained by the two techniques. This was most apparent for the beta-lactams studied, the MICs of cefaclor as determined by the E test being particularly difficult to define. The stability of antimicrobial gradients in the E test may cause problems when testing slow-growing bacteria and/or organisms which grow only under anaerobic conditions. Accordingly, only those MICs determined by the agar dilution method are reported. The percentages of susceptible isolates were as follows: clarithromycin, 100; co-amoxiclav, 100; cefaclor, 20; and ciprofloxacin, 4. The administration of antimicrobials, such as ciprofloxacin and cefaclor, which have poor activities in vitro against lactobacilli, may therefore be advantageous to the host because it allows the protective effects of the normal vaginal flora to be preserved.

Chemoprophylaxis of invasive pulmonary aspergillosis.

Invasive aspergillosis in now the second most common mycosis encountered in patients with cancer, particularly those with haematological malignancies. The present review discusses strategies for the chemoprophylaxis of invasive pulmonary aspergillosis. Recommendations for chemoprophylaxis are currently based on the particular fungal pathogens seen in individual centres and the resources available. In many units, only BMT recipients are nursed in protected environments and the majority of patients at risk of invasive mycosis, i.e. patients undergoing remission induction or consolidation therapy, are nursed on open wards. The studies so far reported have included relatively small numbers of patients and provide insufficient data for definitive recommendations. The measures used at present should be considered as ad hoc approaches for use in units in which spore-free air for profoundly neutropenic patients is lacking. Nebulized amphotericin B allows deposition of a chemical barrier throughout the airways. Intravenous low dose amphotericin B would be protective when invasion occurs and is clearly the chemoprophylaxis of choice in patients with an established diagnosis of previous invasive aspergillosis at any site. The role of surgery in removing a focus of infection before further chemotherapy, should not be overlooked. The potential role of cytokines in accelerating host defence recovery may in future also prove to be important in controlling invasive fungal infection.

Effect of pre-operative antibiotic treatment on the bacterial content of the tonsil.

The impact of 7 days pre-tonsillectomy antibiotics on the aerobic bacterial content of the tonsil was studied in 70 consecutive patients. One group received no antibiotic, one group received pre-operative amoxycillin and the final group, pre-operative cefaclor. The qualitative bacteriology was similar in the three groups Haemophilus influenzae was the predominant isolate present in the centre ('core') of the resected tonsil. Similar numbers of beta-lactamase producers including H. influenzae and Straphylococcus aureus were found in all three groups. Quantitative bacteriology of the tonsil core demonstrated that there was a significant reduction in core tonsil pathogens associated with antibiotic therapy. The most statistically significant difference was between the untreated control group and the cefaclor treated group. We conclude that in patients with established recurrent acute tonsillitis, oral antibiotics penetrate the diseased tonsil and influence the predominant core aerobic microflora.

Yersinia frederiksenii infection and colonization in hospital staff.

A diagnosis of gastrointestinal infection with Yersinia frederiksenii was made in a 24-year-old female hospital doctor, resident in hospital. An additional three of nine medical residents screened were found to be faecal carriers of Y. frederiksenii. The latter three residents denied any gastrointestinal symptoms. Screening of 25 resident nurses and 25 in-patients for carriage of Y. frederiksenii was negative. Initial investigation revealed that the medical residents frequently drank unpasteurized milk, which was supplied on the understanding that it would be used for cooking only. Counts of > 10(8) cfu l-1 were obtained from unpasteurized milk samples, including 24 species of Gram-negative bacilli. Yersinia spp. were not isolated. Residents also drank water from the cold taps in the bedrooms; this water was supplied by a holding tank on the hospital roof. Subsequent investigations revealed that three of the 21 holding tanks supplying stored water to the hospital were not covered. Y. enterocolitica was isolated from the uncovered water tank supplying the medical residence.

Bacteriology of tonsil and adenoid and sampling techniques of adenoidal bacteriology.

The value of pernasal swabs and direct adenoid swabs in chronic adenoid and adenotonsillar disease was assessed in 175 patients. Prior to adenoidectomy (53 patients) or adenotonsillectomy (122 patients), pernasal and direct adenoid swabs were taken. Adenoid currettings and tonsil tissue were cultured. Haemophilus influenzae was the bacterium most frequently isolated from adenoid currettings and from the centre (core) of the resected tonsil. There was a close relationship between the bacteriology of the pernasal swab and the adenoid tissue and tonsil core in 72 and 71% of patients, respectively. There was an identical profile of pathogens in 52 and 49%, respectively. We suggest that in children with adenoiditis or adenotonsillitis and hypertrophy of the adenoid, a pernasal swab should be used in preference to a throat swab in selecting appropriate antimicrobial therapy. Penicillin and ampicillin are not appropriate blind therapy in chronic adenoid and adenotonsillar infections because of the prevalence of beta-lactamase-producing aerobes (40%) in adenoid and tonsil core in these conditions.

Serotype F double- and triple-converting phage insertionally inactivate the Staphylococcus aureus beta-toxin determinant by a common molecular mechanism.

The precise molecular mechanism of Staphylococcus aureus beta-toxin inactivation by the serotype F triple-converting phage phi 42, phi A1 and phi A3 was investigated. Sequence analysis of the phi 42 (attP) and Staphylococcus aureus (attB) attachment sites and the left (attL) and right (attR) chromosomal/bacteriophage DNA junctions of individual lysogens, each harbouring a triple-converting phage, revealed the presence of a common 14-bp core sequence in all four sites. These findings indicate that the genomes of the triple-converting phage integrate into the 5'-end of the beta-toxin gene (hlb) by a site- and orientation-specific mechanism identical to that previously described for the serotype F double-converting phage phi 13.