Enhanced molecular-based (MLST/whole genome) surveillance and source attribution of Campylobacter infections in the UK

Abstract

This human campylobacteriosis sentinel surveillance project was based at two sites in Oxfordshire and North East England chosen (i) to be representative of the English population on the Office for National Statistics urban-rural classification and (ii) to provide continuity with genetic surveillance started in Oxfordshire in October 2003. Between October 2015 and September 2018 epidemiological questionnaires and genome sequencing of isolates from human cases was accompanied by sampling and genome sequencing of isolates from possible food animal sources. The principal aim was to estimate the contributions of the main sources of human infection and to identify any changes over time. An extension to the project focussed on antimicrobial resistance in study isolates and older archived isolates. These older isolates were from earlier years at the Oxfordshire site and the earliest available coherent set of isolates from the national archive at Public Health England (1997/8). The aim of this additional work was to analyse the emergence of the antimicrobial resistance that is now present among human isolates and to describe and compare antimicrobial resistance in recent food animal isolates. Having identified the presence of bias in population genetic attribution, and that this was not addressed in the published literature, this study developed an approach to adjust for bias in population genetic attribution, and an alternative approach to attribution using sentinel types. Using these approaches the study estimated that approximately 70% of Campylobacter jejuni and just under 50% of C. coli infection in our sample was linked to the chicken source and that this was relatively stable over time. Ruminants were identified as the second most common source for C. jejuni and the most common for C. coli where there was also some evidence for pig as a source although less common than ruminant or chicken. These genomic attributions of themselves make no inference on routes of transmission. However, those infected with isolates genetically typical of chicken origin were substantially more likely to have eaten chicken than those infected with ruminant types. Consumption of lamb’s liver was very strongly associated with infection by a strain genetically typical of a ruminant source. These findings support consumption of these foods as being important in the transmission of these infections and highlight a potentially important role for lamb’s liver consumption as a source of Campylobacter infection. Antimicrobial resistance was predicted from genomic data using a pipeline validated by Public Health England and using BIGSdb software. In C. jejuni this showed a nine-fold increase in resistance to fluoroquinolones from 1997 to 2018. Tetracycline resistance was also common, with higher initial resistance (1997) and less substantial change over time. Resistance to aminoglycosides or macrolides remained low in human cases across all time periods. Among C. jejuni food animal isolates, fluoroquinolone resistance was common among isolates from chicken and substantially less common among ruminants, ducks or pigs. Tetracycline resistance was common across chicken, duck and pig but lower among ruminant origin isolates. In C. coli resistance to all four antimicrobial classes rose from low levels in 1997. The fluoroquinolone rise appears to have levelled off earlier and among animals, levels are high in duck as well as chicken isolates, although based on small sample sizes, macrolide and aminoglycoside resistance, was substantially higher than for C. jejuni among humans and highest among pig origin isolates. Tetracycline resistance is high in isolates from pigs and the very small sample from ducks. Antibiotic use following diagnosis was relatively high (43.4%) among respondents in the human surveillance study. Moreover, it varied substantially across sites and was highest among non-elderly adults compared to older adults or children suggesting opportunities for improved antimicrobial stewardship. The study also found evidence for stable lineages over time across human and source animal species as well as some tighter genomic clusters that may represent outbreaks. The genomic dataset will allow extensive further work beyond the specific goals of the study. This has been made accessible on the web, with access supported by data visualisation tools.

Emerging patterns of fluoroquinolone resistance in Campylobacter jejuni in the UK [1998–2018]

“…Fluoroquinolone resistance in C. jejuni is part of the World Health Organization (WHO) high-alert watch list and it is increasing, threatening global antibiotic efficacy [ 12, 13 ]. A single-point mutation in the C257T at the gyrA gene within the quinolone resistance-determining region (QRDR) leads to Thr86Ile amino acid substitution, which can cause phenotypic resistance to fluoroquinolone in C. jejuni [ 14–17 ]. This amino acid change can be maintained stably in Campylobacter populations without antibiotic selection pressure and in vivo chicken colonization studies have shown that fluoroquinolone-resistant Campylobacter mutants do not carry a fitness burden [ 18 ].…”