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M Cafferkey

Publications and source records attributed to M Cafferkey.

At least 19 recordsLinked to original sources

Haemolytic uraemic syndrome associated with interfamilial spread of E. coli O26:H11.

In September 2000, haemolytic uraemic syndrome (HUS) was diagnosed in a 10-month-old child with a prodromal history of vomiting and diarrhoea (non-bloody). Investigation revealed that a self-limiting gastrointestinal illness (mean duration 48 h) had occurred among immediate and extended family in the 2 weeks prior to the child's admission. The epidemiology of the illness suggested person-to-person spread. Five children (close family contacts) had E. coli O26 verocytotoxin (VT1 and VT2) isolated from stools. Stool culture and serology from the index case were negative for shiga toxin-producing E. coli (STEC) organisms. Control measures in accordance with the Public Health Laboratory Service (PHLS), verocytotoxogenic organisms (VTEC) guidelines were applied to prevent further spread among the extended family and contacts. Despite detailed food and environmental exposure histories, the source of the illness was not identified. This incident highlights the importance of investigation of cases of post-diarrhoeal HUS, for potential shiga toxin E. coli aetiology.

Diarrhea↗

Molecular epidemiology of group B streptococci in Ireland: associations between serotype, invasive status and presence of genes encoding putative virulence factors.

Group B streptococcal isolates (n = 159) from the three Dublin maternity hospitals, were serotyped and analysed for the bac, bca, hylB, pepB, and rib genes. The serotype distribution of the isolates was Ia, 19.5%; Ib, 18.9%; II, 10.7%; III, 29.5%; IV, 1.9%; V, 15.1%; non-typeable, 4.4%. There was a statistically significant association between the serotype and invasive status (carriage or infection) of isolates (P < 0.005), but no significant association between serotype and degree of invasiveness was demonstrated. The presence or absence of each analysed gene was not associated with the invasive status of isolates. Statistically significant associations were revealed between bca and hylB (IS1548) (P = 0.0004) and between bac and bca (P=0.014). The bac, bca, hylB (IS1548) and rib genes and the numbers of tandem repeats in the bca gene showed significant associations with serotype. Almost 50% of serotype III isolates possessed at least one of the bac and bca genes and 55-65% of strains of serotypes Ia, Ib and II possessed the rib gene. Most serotype III isolates had IS1548 in their hylB genes. Serotype Ib was the only serotype in which more than half of the strains contained more tandem repeats in the bca gene than the overall mean for the GBS population studied of 7.4 repeats. These findings indicate that some previously reported associations between putative virulence factors and GBS disease require further study and clarification.

Chi-Square Distribution↗

Genomic polymorphic profiles in an Irish population with meningococcaemia: is it possible to predict severity and outcome of disease?

Patients with meningococcal disease have increased plasma levels of proinflammatory cytokines IL-6, IL-1beta, and TNF-alpha, with higher levels associated with fatal outcome. This study investigated whether polymorphisms in genes encoding these cytokines, and in those encoding anti-inflammatory IL-10 and IL-1Ra, are associated with the outcome in patients with meningococcal disease. Seven polymorphisms were genotyped in 183 meningococcal disease patients and 389 controls. The IL-6 -174 G/G and IL-10 -1082 A/A genotypes were more frequent in nonsurvivors compared with survivors (P=0.023 IL-6, 0.25 IL-10), and in patients with severe disease compared to those with mild disease (P=0.037 IL-6, 0.0078 IL-10). An association was also found between meningococcal disease and the IL-1RN VNTR polymorphism, but no association was observed with the LTA +252, TNF -308, IL-10 -592, or IL-1B +3953 polymorphisms. We conclude that genetic variability in the IL-6, IL-10, and IL-1RN genes is associated with a poor outcome in meningococcal disease.

Adult↗

Employment of broad-range 16S rRNA PCR to detect aetiological agents of infection from clinical specimens in patients with acute meningitis--rapid separation of 16S rRNA PCR amplicons without the need for cloning.

AIMS: The aim of this study was to develop a polyacrylamide gel electrophoresis (PAGE) method for the rapid separation of 16S rRNA PCR amplicons from aetiological agents of acute meningitis. METHODS AND RESULTS: Blood samples from 40 patients with suspected acute meningococcal meningitis were examined for the presence of causal agents, including Neisseria meningitidis employing two methods: (i) broad-range 16S rRNA PCR in conjunction with PAGE and automated sequencing and (ii) species-specific PCR employing ABI TaqMan technology for N. meningitidis. Analysis of clinical specimens employing 16S rRNA PCR yielded 33/40 (82.5%) positive for the presence of bacterial DNA. Species-specific PCR yielded 30/40 (75%) clinical specimens positive for N. meningitidis. Prior to separation by PAGE, only 6/33 (18.2%) amplicons were able to be identified by sequence analysis, the remaining amplicons (n=27) did not yield an identification due to the presence of mixed 16S rRNA PCR amplicons. Following separation, amplicons were re-amplified and sequenced, yielding 24/27 (88.9%) positive for N. meningitidis and three specimens positive for Acinetobacter sp., Staphylococcus aureus and Streptococcus pneumoniae. One specimen was positive for both N. meningitidis and Streptococcus spp. and another specimen was positive for N. meningitidis and Pseudomonas sp., by broad-range PCR. Seven clinical specimens were negative for N. meningitidis and other eubacteria using both detection techniques. CONCLUSIONS: Clinical specimens including blood and cerebrospinal fluid from patients with suspected acute bacterial meningitis, may become contaminated with commensal skin flora, resulting in difficulties in downstream sequencing of pathogen plus contaminant DNA. This study allows for the rapid separation of amplified pathogen from contaminant DNA. SIGNIFICANCE AND IMPACT OF STUDY: This study demonstrated the usefulness of the rapid separation of multiple 16S rRNA PCR amplicons using a combination of PAGE and automated sequencing, without the need of cloning. Adoption of this technique is therefore proposed when trying to rapidly identify pathogens in clinical specimens employing broad-range 16S rRNA PCR.

Acinetobacter↗

Penicillin susceptibility and epidemiological typing of invasive pneumococcal isolates in the Republic of Ireland.

A national study was undertaken to investigate the incidence of invasive pneumococcal disease in the Republic of Ireland and to examine the associated isolates. In 1999, 144 S. pneumoniae isolates, all recovered from cases of invasive disease, were received from 12 microbiology laboratories. The incidence of invasive pneumococcal disease was estimated to be 6.6/100000 population. All isolates were analyzed for serotype, penicillin susceptibility, chromosomal relatedness (by using pulsed-field gel electrophoresis [PFGE]), and penicillin-binding protein (pbp) fingerprinting. Several findings of note were observed regarding the pneumococcal population in Ireland. First, isolates of 25 different serotypes were represented, with serotypes 14, 9V, 8, 5, 4, and 3 being the most common. This finding, together with the pbp fingerprinting and PFGE typing results, indicated the clonal spread of strains of these serotypes in Ireland. Second, 27 (18.7%) isolates had reduced susceptibility to penicillin, and 74% of these were serotype 9V. Of these, 80% appeared to belong to the same clone. This could suggest the spread of the international Spanish/French 9V penicillin-resistant clone into Ireland. Third, nine different pbp genotypes were identified, four of which were new. Two pbp genotypes accounted for the majority of isolates dividing them according to their penicillin susceptibility status but irrespective of serotype and PFGE type. This is strong evidence for the occurrence of horizontal transfer of pbp genes between strains, observed with both penicillin-susceptible and penicillin-nonsusceptible isolates. Fourth, there was evidence of serotype transformation since isolates, indistinguishable by pbp fingerprinting and PFGE typing, expressed different capsular types.

Base Sequence↗

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.

Age Factors↗

Mother-to-child transmission of hepatitis C virus: evidence for preventable peripartum transmission.

BACKGROUND: Little information is available about the timing of mother-to-child transmission of hepatitis C virus (HCV), and no interventions to decrease transmission rates have been identified. We examined the effect of risk factors, including mode of delivery, on the vertical transmission rate. METHODS: Data from HCV-infected women and their infants from three hospitals in Ireland and from a British Paediatric Surveillance Unit study of infants born to HCV-infected mothers were used to estimate the vertical transmission rate and risk factors for transmission. We used a probabilistic model using methods that simultaneously estimated the time to HCV-antibody loss in uninfected infants and the diagnostic accuracy of PCR tests for HCV RNA. FINDINGS: 441 mother-child pairs from the UK (227) and Ireland (214) were included. 50% of uninfected children became HCV-antibody negative by 8 months and 95% by 13 months. The estimated specificity of PCR for HCV RNA was 97% (95% CI 96-99) and was unrelated to age; sensitivity was only 22% (7-46) in the first month but rose sharply to 97% (85-100) thereafter. The vertical transmission rate was 6.7% (4.1-10.2) overall, and 3.8 times higher in HIV coinfected (n=22) than in HIV-negative women after adjustment for other factors (p=0.06). No effect of breastfeeding on transmission was observed, although only 59 women breastfed. However, delivery by elective caesarean section before membrane rupture was associated with a lower transmission risk than vaginal or emergency caesarean-section delivery (odds ratio 0 [0-0.87], p=0.04, after adjustment for other factors). INTERPRETATION: The low sensitivity of HCV RNA soon after birth and the finding of a lower transmission rate after delivery by elective caesarean section suggest that HCV transmission occurs predominantly around the time of delivery. If the findings on elective caesarean section are confirmed in other studies, the case for antenatal HCV testing should be reconsidered.

Age Factors↗

Measurement of serum antigen concentration by ultrasound-enhanced immunoassay and correlation with clinical outcome in meningococcal disease.

The distribution of Neisseria meningitidis serogroup B and C polysaccharide antigen in blood and the prognostic significance of antigen concentration was examined by ultrasound-enhanced immunoagglutination of coated microparticles. Specimens (169 sera/plasma from 145 patients with confirmed meningococcal disease) were tested retrospectively. The ultrasonic immunoassay detected serum antigen in 136 samples from 112 patients. Titration of antigen-positive specimens allowed estimation of blood antigen concentration. The modal blood antigen titre was 1/16, corresponding to an estimated polysaccharide concentration of 0.85 microg/ml. The lowest mean blood antigen concentration found ultrasonically was 0.05 microg/ml; compared to the 1.98 microg/ml found by conventional latex agglutination, this represents an approximately 30-fold improvement in sensitivity. Three grades of outcome were correlated with the presenting antigen titre in 83 patients: (i) <2 weeks hospitalisation, (ii) > or =2 weeks hospitalisation and (iii) mortality. High polysaccharide concentrations correlated with mortality. Nine of 15 patients with a serum antigen titre of 1/64 or greater (> or =3.4 microg/ml polysaccharide) died, whereas no patient with titres equal to or less than 1/4 (< or = 0.21 microg/ml) died, including those patients in whom antigen was undetectable by ultrasonic immunoassay. Increasing antigen concentration significantly correlated with severity of outcome (P<0.001). Ultrasound-enhanced agglutination provides a rapid prognostic indicator by sensitive measurement of serum antigen level.

Humans↗

Antibiotic prophylaxis post-tonsillectomy: is it of benefit?

The decision to prescribe antibiotics post-tonsillectomy still remains controversial. However, recent changing trends in the tonsillar tissue microflora have been widely reported, with Haemophilus influenzae, Staphylococcus aureus and anaerobic organisms all being implicated. All of the above are beta-lactamase producers and thus render lactamase prone antibiotics inactive. We compared two groups of children, one on Amoxycillin and clavulanic acid (a lactamase stable antibiotic with anaerobic cover) for 1 week post tonsillectomy--Group A (N = 44), and another group on no treatment--Group B (N = 34). We compared tonsillar core, surface and postoperative tonsillar fossae bacteriological profiles in the two groups. The tonsil core pathogens included H. influenzae (64%) of which 9.5% were beta-lactamase producers, Streptococcus viridans (55.9%), S. aureus (37%) of which 86% were beta-lactamase producers, and anaerobes which were found in 25% of samples. We found that there was considerably less morbidity in those children receiving postoperative antibiotics compared to those who did not, as judged by the amount of analgesia consumed (p = 0.379), time to resumption of normal diet (p = 0.0072) and pain analogue scores (p = 0.0006). We feel that treating children who have undergone tonsillectomy with amoxycillin and clavulanic acid significantly reduces postoperative morbidity.

Amoxicillin↗

Meningitis antigen detection: interpretation of agglutination by ultrasound-enhanced latex immunoassay.

Detailed instructions for performance and interpretation of ultrasound-enhanced latex agglutination tests for the rapid identification of bacteria causing meningitis are described. This recently developed technique, which enhances the sensitivity of most latex immunoagglutination assays, has been studied mainly in the context of detection of antigens of meningitis-causing bacteria. The test concentrates on the Wellcogen bacterial antigen kit (Murex Diagnostics Ltd) that contains five latex suspensions specific for Haemophilus influenzae type b, Neisseria meningitidis ACYW135, N. meningitidis B/Escherichia coli K1, Streptococcus group B and Streptococcus pneumoniae. Light photomicrographs of positive agglutination are shown. Particular attention is paid to the appearance of the latex in negative control samples following exposure to ultrasound. Guidance is given on interpretation and assessment in clinical samples.

Antigens, Bacterial↗

Current use of the TORCH screen in the diagnosis of congenital infection.

The aim of the study was to determine the number of congenital infections detected in Dublin with the current use of the TORCH screen. A review of all laboratory results was undertaken with subsequent review of relevant medical charts. A total of nine cases were documented in a 5-year period from January 1991 to December 1995. Six of these had already been suspected. There was a failure to follow up 47% of positive screens. TORCH screening in Ireland has an unacceptably low yield, and in the opinion of the authors should be abolished.

Animals↗

Comparison of sevoflurane and halothane for outpatient dental anaesthesia in children.

In a prospective, randomized, double-blind clinical study, we have studied 100 children, aged 2-12 yr, to compare halothane and sevoflurane in outpatient dental anaesthesia. All patients were unpremedicated and received inhalation induction using nitrous oxide in oxygen supplemented with either halothane (maximum inspired concentration 5%) or sevoflurane (maximum inspired concentration 8%). Time to loss of the eyelash reflex was more rapid using sevoflurane although time to adequate anaesthesia (to allow insertion of a mouth prop) was slower in the sevoflurane group. The incidence of cardiac arrhythmia was higher during halothane (62%) than during sevoflurane anaesthesia (28%) (P < 0.005) and the arrhythmias were more often ventricular in origin. The two agents were comparable in terms of ease of use and quality of anaesthesia, and times to eye opening and satisfying discharge criteria were similar. We conclude that sevoflurane has qualities that have made halothane the most used inhalation agent for children, and that it is superior to halothane in dental outpatients where cardiac arrhythmias are a particular problem.

Ambulatory Surgical Procedures↗

Community study of toxoplasma antibodies in urban and rural schoolchildren aged 4 to 18 years.

To estimate the prevalence of toxoplasma antibodies in schoolchildren and their association with clinical and environmental data, antibody titres were measured in 1276 children aged 4 to 18 years attending primary and secondary schools. Environmental and clinical data were obtained by questionnaire. Altogether 12.8% (163/1276) of children had antibodies to Toxoplasma gondii with no difference between the sexes. Seroprevalence was higher in country children (16.6% (50/302)) than town children (10.2% (75/737)). The proportion testing positive increased with age in both town and country children. No association with cat ownership was found. Toxoplasma seropositivity was associated with a positive toxocara titre, having had a bitch whelp in the past two years, and having an unwormed dog at home. Lack of energy or tiredness in the last 12 months were the only clinical features associated with a positive titre.

Adolescent↗

Microbial contamination in an in vitro fertilization-embryo transfer system.

OBJECTIVE: To determine sources and transmission of microorganisms in IVF-ET and efficacy of in-place controlling systems. DESIGN: Prospective study. SETTING: In Vitro Fertilization-Embryo Transfer Unit at a university teaching hospital. PATIENTS: Twenty-eight couples undergoing 30 completed IVF-ET cycles. INTERVENTIONS: Gamete and embryo processing in a penicillin and streptomycin-rich medium. MAIN OUTCOME MEASURES: Presence of microorganisms at various stages of IVF-ET. Fertilization, cleavage, and pregnancy rates. RESULTS: In 50% of cycles no microorganisms were isolated and in the other 50% microbes were cultured from various loci. Cultures of four preprocessed semen samples were positive and corresponding postprocessed samples negative. Microbes were detected in 27% of needle washes after oocyte collection; in 40% and 32% of follicular fluids from left and right ovaries, respectively; and in two culture media from egg-sperm incubations at 20 hours after insemination. No microorganisms were grown from media from zygote incubations. Fertilization, cleavage, and pregnancy rates were independent of microbial presence. CONCLUSION: Seminal fluid and transvaginally collected oocytes are potential sources of microbial contamination of the IVF-ET culture system. A penicillin- and streptomycin-rich culture medium is effective in removing contaminating microbes. End point measures are not affected by commensal contamination.

Culture Media↗

The incidence and role of actinomyces in recurrent acute tonsillitis.

Although actinomyces has been identified in between 1.77% and 37% of resected tonsils its possible role in recurrent acute tonsillitis has received little attention. A histological and bacteriological study of 129 pairs of tonsils from patients with recurrent acute tonsillitis showed actinomyces to be present in 29.5%. The organism, however, was also present in 40% of tonsils from 10 patients with no history of tonsillar disease. In neither of these groups was there any specific evidence of tissue reaction to actinomyces nor was there a male preponderance as in clinical actinomycosis. The presence of actinomyces in the tonsil was not favoured by the concurrence of beta-lactamase producing bacteria. These data indicate that actinomyces does not have a causal role in recurrent acute tonsillitis.

Actinomyces↗