James Wood Lectures

Interpretation of diagnostic tests

Purpose of diagnostic tests 

  • reduce uncertainty in diagnosis and management
  • diagnosis is based on combination of clinical signs and test results 
  • judgement re interpretation is critical - leads to (in)action

Determinants of test usefulness 

  • Validity
  • Reliability - reproducability 
  • Effect on decision of clinical outcome - quality of test given characteristics and clinical context 
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Measures of tests

Measures of test characteristics

  • sensitivity - proportion with disease who test positive 
  • specificity - proportion without disease who test negative 
  • these are normally inversely related

Measures of test interpretation 

  • positive predictive value (PPV) - how likely is positive result to be real
  • negative predictive value (NPV) - how likely is negative result to be real 
  • test interpretation is very dependent on disease prevelance in population - both are highly impacted by prevalence 
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Calculations

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Control Programmes

  • control case numbers per unit time  - important if management can be overwhelmed 
  • minimise total number of cases occuring in an epidemic - are under curve of infecteds 
  • minimise impact of disease and associated control programme - total no. culled farms in FMD outbreak 
  • need to lower infection rate, keep it less that 1:1
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FMDV control

  • much transmission occurs prior to diagnosis 
  • key features: minimising infectious animals (early diagnosis), reduce transmission, reduce infectious animals by culling, tracing 
  • timing of controls is critical 
  • vaccination can be used to prevent or aid control 
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Bovine TB controls

  • endemic infection, dealt with by test and slaughter of individual cattle with herd level controls/movement restrictions 
  • large geographic heterogeneity, - high incidence area extending from SW to S Wales, Scotland almost free
  • complicated by - significant wildlife reservoir, poorly sensitive cattle diagnostic test 
  • much transmission occurs prior to diagnosis - sometimes symptoms never present 
  • key features - minimise infectious animals by early diagnosis, reduce transmission
  • timing of controls critical
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African Horse Sickness control

  • culicoides midge transmitted, as BTV and Schmallenberg
  • disease not found in Europe - BTV and disease modelling suggest disease could spread in summer 
  • major focus on excluding infection from Europe 
  • timing of control critical - need early diagnosis 
  • vaccination likely important if outbreak occured
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Bovine Tuberculosis Control - Disease

  • disease caused by Mycobacterium bovis infection 
  • M. bovis can infect a wide range of mammalian hosts - incl. cattle, humans, badgers, sheep, camelids, wild boar, deer etc.
  • prior to pasteurisation M. bovis killed 2,500 people a year in the UK (GI disease) - now very few cases - most people are aged >50
  • disease has been subject to statutory controls in UK since 1950s
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Bovine Tuberculosis Control - Diagnosis

  • routine slaughterhouse surveillance of all animals (meat inspection)
  • routine testing in cattle herds and slaughter of diagnosed animals - annual testing in high incidence areas, four yearly testing of breeding stock in low incidence areas 
  • pre-movement testing of cattle moved from/in high incidence areas
  • detailed follow up on herds, with movement restrictions, where infection diagnosed 
  • ante-mortem diagnostics (skin test/hypersensitivity reaction) - insensitive - leaves burden of infection, specificity ~99.98% - can be used in low incidence areas 
  • gamma interferon assay improves sensitivity but poor specificity - cost is high 
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Bovine Tuberculosis Control - Epidemiology

  • transmission by cattle to cattle contact and contact with wildlife reservoir 
  • missed infection - herd level persistence, movement of undetected infected cattle between herds 
  • significant wildlife reservoirs - badgers GB/Ireland, different densities, different species in other countries 
  • evidence for wildlife infection - shared infections locally (genotyping strain), culling trials, experimental trials
  • very heterogeneous across UK - cattle to cattle transmission in low incidence areas, heavy burden of wildlife challenge in SW England and parts of Wales - badgers infection estimated to be associated with 50% of herd breakdowns in trial areas 
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Bovine Tuberculosis Control - Control

  • still actively spreading despite controls - massive increase in disease when controls halted - eg 2001 FMDV outbreak when testing ceased 
  • very regionalised - different drivers in different regions 
  • RBCT - culling badgers can reduce incidence of new infections - ~25% in culled regions, incidence increased ~12% in peripheral regions, average rate is 16%
  • cattle vaccination slight effect on disease - massively hampered by need to continue testing vaccinated animals, lack of available DIVA, cost-benefit analysis suggests it might not be feasible to get farmer uptake 
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Bovine Tuberculosis Control - Future Prevention

  • Badgers - culling part of England government policy, but may make things worse, vaccination part of Welsh and NI policies - unclear of impact on cattle disease 
  • vaccination of cattle - partial efficacy - previously slower than test and slaughter programme in 1950s, subject to complex rules with EC, currently illegal, unclear quite how much vaccination would interfere with testing 
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