Noel D McCarthy

University of Oxford, Oxford, England, United Kingdom

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Publications (49)300.35 Total impact

  • American journal of epidemiology. 07/2014;
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    ABSTRACT: Patients born outside the UK have contributed to a 20% rise in the UK's tuberculosis incidence since 2000, but their effect on domestic transmission is not known. Here we use whole-genome sequencing to investigate the epidemiology of tuberculosis transmission in an unselected population over 6 years. We identified all residents with Oxfordshire postcodes with a Mycobacterium tuberculosis culture or a clinical diagnosis of tuberculosis between Jan 1, 2007, and Dec 31, 2012, using local databases and checking against the national Enhanced Tuberculosis Surveillance database. We used Illumina technology to sequence all available M tuberculosis cultures from identified cases. Sequences were clustered by genetic relatedness and compared retrospectively with contact investigations. The first patient diagnosed in each cluster was defined as the index case, with links to subsequent cases assigned first by use of any epidemiological linkage, then by genetic distance, and then by timing of diagnosis. Although we identified 384 patients with a diagnosis of tuberculosis, country of birth was known for 380 and we sequenced isolates from 247 of 269 cases with culture-confirmed disease. 39 cases were genomically linked within 13 clusters, implying 26 local transmission events. Only 11 of 26 possible transmissions had been previously identified through contact tracing. Of seven genomically confirmed household clusters, five contained additional genomic links to epidemiologically unidentified non-household members. 255 (67%) patients were born in a country with high tuberculosis incidence, conferring a local incidence of 109 cases per 100 000 population per year in Oxfordshire, compared with 3·5 cases per 100 000 per year for those born in low-incidence countries. However, patients born in the low-incidence countries, predominantly UK, were more likely to have pulmonary disease (adjusted odds ratio 1·8 [95% CI 1·2-2·9]; p=0·009), social risk factors (4·4 [2·0-9·4]; p<0·0001), and be part of a local transmission cluster (4·8 [1·6-14·8]; p=0·006). Although inward migration has contributed to the overall tuberculosis incidence, our findings suggest that most patients born in high-incidence countries reactivate latent infection acquired abroad and are not involved in local onward transmission. Systematic screening of new entrants could further improve tuberculosis control, but it is important that health care remains accessible to all individuals, especially high-risk groups, if tuberculosis control is not to be jeopardised. UK Clinical Research Collaboration (Wellcome Trust, Medical Research Council, National Institute for Health Research [NIHR]), and NIHR Oxford Biomedical Research Centre.
    The lancet. Respiratory medicine. 04/2014; 2(4):285-92.
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    ABSTRACT: A free-range broiler breeder flock was studied in order to determine the natural patterns of Campylobacter colonisation over a period of 63 weeks. Campylobacter STs were not mutually exclusive and on average colonised only 17.7% of the birds tested at any time. Campylobacter STs typically reached a peak in prevalence upon initial detection in the flock before tailing off, although the ST and antigenic flaA short variable region in combination were stable over a number of months. There was evidence that, with a couple of exceptions, the ecology of C. jejuni and C. coli differed, with the latter forming a more stable population. Despite being free-range, no newly colonising STs were detected over a 6 week period in autumn and a 10 week period in winter, towards the end of the study. There was limited evidence that those identified amongst broiler chicken flocks on the same farm site were likely to colonise the breeder flock earlier (R2 0.16, p 0.01). These results suggest that there is natural control of Campylobacter dynamics within a flock which could potentially be exploited in designing new intervention strategies, and that the two different species should perhaps be considered separately.
    Environmental Microbiology 02/2014; · 6.24 Impact Factor
  • American journal of epidemiology 01/2014; 179(2):262-3. · 5.59 Impact Factor
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    ABSTRACT: Multilocus sequence typing (MLST) was proposed in 1998 as a portable sequence-based method for identifying clonal relationships among bacteria. Today, in the whole-genome era of microbiology, the need for systematic, standardized descriptions of bacterial genotypic variation remains a priority. Here, to meet this need, we draw on the successes of MLST and 16S rRNA gene sequencing to propose a hierarchical gene-by-gene approach that reflects functional and evolutionary relationships and catalogues bacteria 'from domain to strain'. Our gene-based typing approach using online platforms such as the Bacterial Isolate Genome Sequence Database (BIGSdb) allows the scalable organization and analysis of whole-genome sequence data.
    Nature Reviews Microbiology 09/2013; · 22.49 Impact Factor
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    ABSTRACT: Campylobacter- spp.-related gastroenteritis in diners at a catering college restaurant was associated with consumption of duck liver pâté. Population genetic analysis indicated that isolates from duck samples were typical of isolates from farmed poultry. Campylobacter spp. contamination of duck liver may present a hazard similar to the increasingly recognized contamination of chicken liver.
    Emerging Infectious Diseases 08/2013; 19(8):1310-3. · 6.79 Impact Factor
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    ABSTRACT: Antimicrobial resistance is increasing among clinical Campylobacter cases and is common among isolates from other sources, specifically retail poultry - a major source of human infection. In this study the antimicrobial susceptibility of isolates from a UK-wide survey of Campylobacter in retail poultry in 2001 and 2004--5 was investigated. The occurrence of phenotypes resistant to tetracycline, quinolones (ciprofloxacin and naladixic acid), erythromycin, chloramphenicol and aminoglycosides was quantified. This was compared with a phylogeny for these isolates based upon Multi Locus Sequence Typing (MLST) to investigate the pattern of antimicrobial resistance acquisition. Antimicrobial resistance was present in all lineage clusters, but statistical testing showed a non-random distribution. Erythromycin resistance was associated with Campylobacter coli. For all antimicrobials tested, resistant isolates were distributed among relatively distant lineages indicative of widespread acquisition. There was also evidence of clustering of resistance phenotypes within lineages; indicative of local expansion of resistant strains. These results are consistent with the widespread acquisition of antimicrobial resistance among chicken associated Campylobacter isolates, either through mutation or horizontal gene transfer, and the expansion of these lineages as a proportion of the population. As Campylobacter are not known to multiply outside of the host and long-term carriage in humans is extremely infrequent in industrialized countries, the most likely location for the proliferation of resistant lineages is in farmed chickens.
    BMC Microbiology 07/2013; 13(1):160. · 3.10 Impact Factor
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    ABSTRACT: Sequence-based typing is essential for understanding the epidemiology of Campylobacter infection, a major cause of bacterial gastroenteritis world-wide. We demonstrate the practical and rapid exploitation of whole genome sequencing to provide routine definitive characterisation of C. jejuni and C. coli for clinical and public health purposes. Short-read data from 384 Campylobacter clinical isolates collected over four months in Oxford, United Kingdom, were assembled de novo. Contigs were deposited on the pubMLST.org/campylobacter website and automatically annotated for 1667 loci. Typing and phylogenetic information were extracted and comparative analyses performed for various subsets of loci, up to the level of whole genome, using Genome Comparator and NeighborNet algorithms. The assembled sequences (for 379 isolates) were diverse, and resembled collections from previous studies of human campylobacteriosis. Small subsets of very closely related isolates mainly originated from repeated same patient samples, and in one case, a likely laboratory contamination. Much of the within patient variation occurred in phase variable genes. Clinically and epidemiologically informative data can be extracted from WGS data in real time with straightforward, publicly available tools. These analyses are highly scalable, transparent, do not require closely related genome reference sequences, and provide improved resolution: (i) among Campylobacter clonal complexes; and, (ii) between very closely related isolates. Additionally, these analyses rapidly differentiated unrelated isolates, allowing the detection of single strain clusters. The approach is widely applicable to human bacterial pathogens in real time in clinical laboratories with little specialist training required.
    Journal of clinical microbiology 05/2013; · 4.16 Impact Factor
  • Noel D McCarthy, Iain A Gillespie, Sarah J O'Brien
    American journal of epidemiology 05/2013; 177(9):1022. · 5.59 Impact Factor
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    ABSTRACT: In November, 2012, a 28-year-old man, presented with a 4-day history of fever, shivers, sweating, and vomiting. He had type-2 diabetes, which was being treated with sitagliptin and metformin. On admission he had evi dence of a systemic infl ammatory response (temperature 39·3°C, pulse 160 bpm, respiratory rate 30 per min, white cell count 15·0×10⁹ per L, with 12·3 neutrophils and 0·2 mye locytes), abnormalities of blood clotting (INR 1·6, PTT 57 s, fi brinogen 0·99 g/L (normal range 1·5–4·5); plate lets 19×10⁹ per L), multi-organ failure (creatinine 167 μmol/L, raised alanine aminotransferase 511 U/L and bilirubin 87 μmol/L), progressive hypoxia, hyperglycaemia glucose 20·6 mmol/L), and lactic acidosis (PH 7·29, lactate 7·5 mmol/L). He was diagnosed with overwhelming sepsis and transferred to the intensive care unit. Initial treatment was with piperacillin-tazobactam, insulin, oxygen, and aggressive fl uid replacement, including platelet infusions, fresh frozen plasma, and cryo-precipitate. Ventilatory support was required 15 h after admission, at which time he was anuric. Renal replace-ment therapy was needed for 21 days and ventilatory support for 38 days, partly because of pseudomonas superinfection of the chest that was diagnosed on day 17. Tests for legionella and leptospira and initial blood cultures were negative. Serum taken 30 days after admission had a high IgG titre to Seoul hantavirus (1:10 000 by IFA, Euroimmun, Medizinische Labor-diagnostika AG), although serum from 1 month before admission (sent for hepatitis screening because of a mild transaminasaemia) was negative. Hantavirus RNA was not detected in either sample. We learnt that he kept two pet agouti rats (Rattus norvegicus) that he had acquired from a larger pack bred in England. Seoul hantavirus RNA was detected by RT-PCR 1 in blood taken from these two rats and from seven of the larger group. In November, 2011, one of the English owners had been hospitalised with fever, renal impairment, spleno megaly, and thrombo cytopenia that was secondary to an unidentifi ed viral illness. Retrospective Seoul hantavirus serological Lancet 2013; 381: 1070 Rare and Imported Pathogens Department (S
    The Lancet 03/2013; 381:1070. · 39.06 Impact Factor
  • Noel McCarthy
    The Lancet Infectious Diseases 02/2013; 13(2):104-5. · 19.97 Impact Factor
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    ABSTRACT: Zoonotic pathogens often infect several animal species, and gene flow among populations infecting different host species may affect the biological traits of the pathogen including host specificity, transmissibility and virulence. The bacterium Campylobacter jejuni is a widespread zoonotic multihost pathogen, which frequently causes gastroenteritis in humans. Poultry products are important transmission vehicles to humans, but the bacterium is common in other domestic and wild animals, particularly birds, which are a potential infection source. Population genetic studies of C. jejuni have mainly investigated isolates from humans and domestic animals, so to assess C. jejuni population structure more broadly and investigate host adaptation, 928 wild bird isolates from Europe and Australia were genotyped by multilocus sequencing and compared to the genotypes recovered from 1366 domestic animal and human isolates. Campylobacter jejuni populations from different wild bird species were distinct from each other and from those from domestic animals and humans, and the host species of wild bird was the major determinant of C. jejuni genotype, while geographic origin was of little importance. By comparison, C. jejuni differentiation was restricted between more phylogenetically diverse farm animals, indicating that domesticated animals may represent a novel niche for C. jejuni and thereby driving the evolution of those bacteria as they exploit this niche. Human disease is dominated by isolates from this novel domesticated animal niche.
    Molecular Ecology 01/2013; · 6.28 Impact Factor
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    ABSTRACT: OBJECTIVE: To quantify and determine factors associated with delay in initiation of tuberculosis (TB) treatment in the Thames Valley area, South East England, and the proportion of this delay that could be attributed to patient care-seeking or to delay within the National Health Service (NHS). STUDY DESIGN: Retrospective analysis study reviewing medical notes and enhanced TB surveillance data. METHODS: Demographic and clinical information was collected from medical notes and the Enhanced TB Surveillance database for patients who were diagnosed with TB and resident in the Thames Valley. Treatment delay was defined as the period between the onset of symptoms and the start of treatment. Patient delay was defined as the period between the onset of symptoms and the first presentation to the NHS. Health service delay was defined as the period between the first contact with the NHS and the start of treatment. Univariate and multivariate linear regression analyses were used to assess the association between delays and explanatory variables (age, gender, place of birth, ethnicity, disease site, sputum smear, culture, primary care trust of residence). RESULTS: The study included 273 patients with TB. The median time between symptom onset and initiation of treatment was 73 days [95% confidence interval (CI) 65-89], of which the contributions of health service, patient and referral delays were 39 (95% CI 34-55), 29 (95% CI 22-36) and 16 (95% CI 12-24) days, respectively. On multivariate analysis, extrapulmonary TB (P = 0.010), female (P = 0.003) and UK-born (P = 0.008) patients were associated with longer health service delay. Age (P = 0.001) and extrapulmonary TB (P = 0.010) were associated with longer overall treatment delay. CONCLUSION: Treatment delay for TB, especially delay after first presentation to the NHS, remains a public health concern. Differences in health service delay, for example by gender and country of birth, highlight that some of this should be open to health service intervention.
    Public health 01/2013; · 1.26 Impact Factor
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    Euro surveillance: bulletin europeen sur les maladies transmissibles = European communicable disease bulletin 01/2013; 18(9). · 5.49 Impact Factor
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    ABSTRACT: Hybridization between distantly related organisms can facilitate rapid adaptation to novel environments, but is potentially constrained by epistatic fitness interactions among cell components. The zoonotic pathogens Campylobacter coli and C. jejuni differ from each other by around 15% at the nucleotide level, corresponding to an average of nearly 40 amino acids per protein-coding gene. Using whole genome sequencing, we show that a single C. coli lineage, which has successfully colonized an agricultural niche, has been progressively accumulating C. jejuni DNA. Members of this lineage belong to two groups, the ST-828 and ST-1150 clonal complexes. The ST-1150 complex is less frequently isolated and has undergone a substantially greater amount of introgression leading to replacement of up to 23% of the C. coli core genome as well as import of novel DNA. By contrast, the more commonly isolated ST-828 complex bacteria have 10-11% introgressed DNA, and C. jejuni and nonagricultural C. coli lineages each have <2%. Thus, the C. coli that colonize agriculture, and consequently cause most human disease, have hybrid origin, but this cross-species exchange has so far not had a substantial impact on the gene pools of either C. jejuni or nonagricultural C. coli. These findings also indicate remarkable interchangeability of basic cellular machinery after a prolonged period of independent evolution.
    Molecular Ecology 12/2012; · 6.28 Impact Factor
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    ABSTRACT: Case-control studies are important in infectious disease epidemiology for rapidly identifying and controlling risks, but challenges, including the need for speed, can place practical restrictions on control selection and recruitment. The biased comparisons that result can hamper or, worse, mislead investigators. Following a 2009 outbreak of Shiga-like toxin-producing Escherichia coli O157 infection associated with a petting farm in southeast England, it was hypothesized that case behavior alone could be used to identify risks. Case-patients' exposures were randomized on a case-by-case basis, and the resulting permuted data were compared with the actual events preceding illness by conditional logistic regression analysis. There was good agreement between the risks identified by using our new method and the risks elicited in the original outbreak case-control studies. This was also the case in analysis of 2 further historical outbreaks. These initial findings suggest that the technique, which we have called the "case-chaos" technique, appeared to be useful in this setting. Analysis of simulated data supports this view. Circumventing the need for traditional control data has the potential to reduce outbreak investigation lead times, leading to earlier interventions and reduced morbidity and mortality. However, further validation is necessary, coupled with an awareness of limitations of the method.
    American journal of epidemiology 08/2012; 176(6):497-505. · 5.59 Impact Factor
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    ABSTRACT: We sought to explain seasonality and other aspects of Campylobacter jejuni epidemiology by integrating population genetic and epidemiological analysis in a large 3-year longitudinal, two-centre, population-based study. Epidemiological information was collected for 1505 isolates, which were multilocus sequence-typed. Analyses compared pathogen population structure between areas, over time, and between clinical presentations. Pooled analysis was performed with published international datasets. Subtype association with virulence was not observed. UK sites had nearly identical C. jejuni populations. A clade formed by ST45 and ST283 clonal complexes showed a summer peak. This clade was common in a Finnish dataset but not in New Zealand and Australian collections, countries with less marked seasonality. The UK, New Zealand and Australian collections were otherwise similar. These findings map to known in-vitro differences of this clade. This identifies a target for studies to elucidate the drivers of the summer peak in human C. jejuni infection.
    Epidemiology and Infection 02/2012; · 2.87 Impact Factor
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    ABSTRACT: An outbreak of gastroenteritis affected at least 240 persons who had eaten at a gourmet restaurant over a period of 7 weeks in 2009 in England. Epidemiological, microbiological, and environmental studies were conducted. The case-control study demonstrated increased risk of illness in those who ate from a special 'tasting menu' and in particular an oyster, passion fruit jelly and lavender dish (odds ratio 7·0, 95% confidence interval 1·1-45·2). Ten diners and six staff members had laboratory-confirmed norovirus infection. Diners were infected with multiple norovirus strains belonging to genogroups I and II, a pattern characteristic of molluscan shellfish-associated outbreaks. The ongoing risk from dining at the restaurant may have been due to persistent contamination of the oyster supply alone or in combination with further spread via infected food handlers or the restaurant environment. Delayed notification of the outbreak to public health authorities may have contributed to outbreak size and duration.
    Epidemiology and Infection 12/2011; 140(9):1695-701. · 2.87 Impact Factor
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    ABSTRACT: Identifying the Campylobacter genotypes that colonize farmed and wild ducks will help to assess the proportion of human disease that is potentially attributable to the consumption of duck meat and environmental exposure to duck faeces. Comparison of temporally and geographically matched farmed and wild ducks showed that they had different Campylobacter populations in terms of: (i) prevalence, (ii) Campylobacter species and (iii) diversity of genotypes. Furthermore, 92.4% of Campylobacter isolates from farmed ducks were sequence types (STs) commonly associated with human disease, in contrast to just one isolate from the wild ducks. Only one ST, ST-45, was shared between the two sources, accounting for 0.9% of wild duck isolates and 5% of farmed duck isolates. These results indicate that domestic 'niche' as well as host type may affect the distribution of Campylobacter, and that husbandry practises associated with intensive agriculture may be involved in generating a reservoir of human disease associated lineages.
    Environmental Microbiology Reports 10/2011; 3(5):574-580. · 3.26 Impact Factor

Publication Stats

940 Citations
300.35 Total Impact Points

Institutions

  • 2005–2014
    • University of Oxford
      • Department of Zoology
      Oxford, England, United Kingdom
  • 2012–2013
    • Swansea University
      • Institute of Life Science "ILS"
      Swansea, Wales, United Kingdom
  • 2011
    • Princeton University
      • Department of Ecology and Evolutionary Biology
      Princeton, NJ, United States
  • 2008
    • Oxford University Hospitals NHS Trust
      Oxford, England, United Kingdom
    • University of Southampton
      Southampton, England, United Kingdom
  • 2004
    • Norwegian Institute of Public Health
      • Division of Infectious Disease Control
      Kristiania (historical), Oslo County, Norway