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• Cases of polioencephalitis and polioencephalomyelitis in cows and sheep – conclusions of expert meeting
• Laboratory detection of bacteria with extended-spectrum beta-lactamases
  

Cases of polioencephalitis and polioencephalomyelitis in cows and sheep – conclusions of expert meeting

A meeting was convened on the 21 June 2004 by the Health Protection Agency involving representatives from the fields of both animal and human health including the Department of the Environment Food and Rural Affairs (DEFRA), Veterinary Laboratories Agency (VLA), the Department of Health, independent experts, and observers from the Food Standards Agency (FSA). This expert group considered the likely cause and public health implications of cases of polioencephalitis and polioencephalomyelitis in cattle and sheep in which, after routine investigation by the VLA, an aetiological agent (ie, organism responsible) was not identified.

Details of a recently published and publicised case in a heifer, another unrelated case in a bull, and 20 other cases in sheep were reviewed. In all cases, investigations have eliminated a diagnosis of louping ill, an endemic disease which could produce these pathological features. These cases, which occurred over a period of ten years, were considered against the background of a fluctuating but not increasing rate of sample submissions to the VLA for the investigation of non-notifiable nervous diseases in cattle and sheep. In addition, a further seven adult cattle with similar neuropathological changes, submitted under BSE Orders between 2000 and 2003 were brought to the attention of the group. These animals were examined for bovine spongiform encephalopathy (BSE) with negative results. They had also been examined in the last two weeks for louping ill with negative results.

Although all of the animals had features characteristic of neurotropic viral infections, review of the clinical and pathological findings revealed that the two cattle in the initial series had different clinical features and distribution of brain lesions. This suggested that they may represent different conditions. The group also considered that the cases in sheep presented several clinical and pathological variations and may have been caused by more than one agent. The clinico-pathological observations in the seven additional cattle cases submitted for statutory BSE diagnosis are limited by virtue of the focus of the submission, but warrant further investigation. In no cases were the pathological changes consistent with those of a transmissible spongiform encephalopathy. The group considered that it was not unexpected to find this type of inflammatory lesion in a small proportion of animals from which tissues are submitted for diagnostic examinations.

Recent virological testing identified an enterovirus in brain samples from the heifer and this is the likely cause of its condition. It was decided to proceed with virological testing for enteroviruses in the other cases in cattle and sheep.

The expert group considered that these cases were unlikely to pose a significant risk to human health because:

• there is no apparent link between the low number of cases identified over the past ten years
• l there is no increasing trend in samples submitted from cows or sheep with neurological disease or the proportion diagnosed as having encephalitis
• l none of the 29 animals in question would have entered the food chain
• l if the aetiological diagnosis of enterovirus infection were substantiated for the other cases, the species specificity of such viruses would, almost certainly, rule out any pathogenicity for man based on currently available evidence. In addition, as enteroviruses are easily destroyed by heat, pasteurisation and cooking provides additional safeguards if milk or meat from affected animals were to have entered the food chain.
  
  The risk to public health will be reviewed in future as more information on the other cases becomes available.

Laboratory detection of bacteria with extended-spectrum beta-lactamases

Extended-spectrum beta-lactamases (ESBLs) are plasmid-mediated enzymes that hydrolyse and confer resistance to second and third generation cephalosporins, eg, cefuroxime, cefotaxime, and ceftazidime – the most widely used injectable antibiotics in many hospitals.

Until around 2001/2002, most ESBL-producing bacterial isolates in the United Kingdom (UK) were Klebsiella species, often from specialist units. Their ESBLs were cephalosporin-hydrolysing mutants of TEM and SHV – the common ‘old’ plasmid mediated penicillinases of Enterobacteriaceae. Laboratory methodology, therefore, evolved to detect these TEM and SHV variants, which mostly confer obvious resistance to ceftazidime with variable resistance to cefotaxime.

On this basis, it was recommended that ceftazidime should be used to screen for ESBL-mediated cephalosporin resistance in Enterobacteriaceae, with further confirmatory tests done on isolates found to be resistant. Since 2000, however, bacteria producing a new class of ESBL, CTX-M types, have emerged in the UK. The majority of producer isolates to date are Escherichia coli, often from patients at the hospital/community interface (eg, urinary infections in outpatients with a history of recent hospitalisation), although some patients do not appear to have had contact with hospitals. Isolates producing CTX-M ESBLs show obvious resistance to cefotaxime, with variable resistance to ceftazidime. Thus,
screening with ceftazidime alone will fail to detect many producers. In view of this change the recommendations for screening Enterobacteriaceae have now been amended. Full details are available at
<http://www.hpa.org.uk/srmd/div_nsi_armrl/ESBL_advice_June_2004.pdf>, but the minimum recommendations can be summarised as:

Enterobacteriaceae from infections in hospitalised patients

• Test both cefotaxime and ceftazidime on first-line panel, or test cefpodoxime.
• Perform ESBL confirmatory tests (see grey box below) on isolates found resistant to any of cefotaxime, ceftazidime, or cefpodoxime

Enterobacteriaceae from community patients

• Test cefpodoxime as an indicator on first-line panel (one possible first-line panel for community urinary tract infection specimens comprises cefpodoxime, nitrofurantoin, trimethoprim, a fluoroquinolone, and two out of cephalexin, coamoxiclav, and ampicillin/amoxycillin).
• Perform ESBL confirmatory tests (below) on isolates found resistant to cefpodoxime.
  
  
  Identification to genus/species level is highly desirable for the interpretation of resistance patterns and, as a minimum, should be undertaken on all isolates found resistant to cefotaxime, ceftazidime, or cefpodoxime in the above tests.
  
  To confirm ESBL production in isolates found resistant to cefotaxime/ceftazidime or cefpodoxime: examine for synergy between cefpodoxime and clavulanate using combination discs (a 5-mm larger zone to the clavulanate-containing disc indicates the presence of an ESBL). For Enterobacter spp. and C. freundii use cefpirome/clavulanate combination discs.
  
  The detection of ESBL-producing organisms should be reported as a matter of urgency to clinicians, with all cephalosporins indicated as resistant, irrespective of original laboratory results, to ensure that appropriate therapy is given, usually a carbapenem.
  
  The Health Protection Agency’s Antibiotic Resistance Monitoring and Reference Laboratory would be pleased to further investigate the following ESBL producers and advise on further testing, as appropriate:
  
  
• Representatives from outbreaks
• ESBL-positive E. coli from any laboratory where these have not been encountered previously
• Anysuspected ESBL-producers from a patient without recent hospital contact.
  
  
  If in doubt, please contact David Livermore (tel: 020 8327 7223) email: <david.livermore@hpa.org.uk> or Neil Woodford (tel: 020 8327 7255) email: <neil.woodford@hpa.org.uk> to ask for advice.