Gonorrhoea: time for a culture shift

1
Gonorrhoea time for a culture shift?
2
Contents

• Introduction and Background
• Attendees
• Total Numbers
• Male attendees
• Female attendees
• Summary and implications

3
Background 1

• Poorly performing EIA for chlamydia leads to
  introduction of new testing method, which also
  detects gonorrhoea
• Decision to run this new GC test (Gen-Probe
  Aptima Combo 2) alongside existing test (GC
  culture) for trial period
• Sensitivity of existing test 95

4
Brief overview of B1 NAATS
5
The Tests (B1 NAATs)

• Roche Cobas Amplicor PCR assay limited
  specificty Cytosine DNA Methyltransferance
  gene
• LCx probe system (abbot) OPA gene
• BD Probe tec Target gene?
• TMA Combo 2 assay target 16S rRNA

6
BD Probe Tec

• BD Probe Tec in the UK
• Urethral swabs in men 25/152 GC ve men
• 5 cases cult neg, 2 microscopy positive
• Urethral/cervical swabs in men/women Slater et
  al
• Rectal swabs in men high concordance
• Urines difficult for Lab centrifugation needed

7
Slater et al BAASH poster 2005

• BD probe Tec introduced without local evaluation
• Culture was not performed unless high risk or
  microscopy positive
• Men 49 ve urethral culture NAAT detected 48,
  one missed was also micro ve also
• Sensitivity 97.9
• Females 29 ve cervical NAAT detected all

8
Slater et al cont BAASH poster 2005

• Specificity
• Men 48/50 NAAT ve also cult positive
• 2 NAAT ve cult negative
• Both cultures several days post GC tx and one
  symptomatic GC contact
• PPV 96

9
Slater et al cont BAASH poster 2005

• Specificity Females
• 43/55 NAAT positives had cultures done
• 14 NAAT ve cervical cult Neg
• 3 ve other sites
• 6 Abx prior to cult (include one B1 contact)
• 4/14 possible false Positives
• PPV 74

10
TMA

• Transcription Mediated Amplification
• Target ribosomal RNA
• Urine sample do not require a centrifugation step

11
Aptima Combo 2

• American Multicentre Study female endocervical
  and urines
• GC Prevalence about 8
• Gold standard cult positive or LCx positive
  (two sites)
• 126/1479 Combo 2 positive
• Sens 99.2 Spec 98.7 PPV 90
• No data on PPV as culture gold standard

12
First published UK study of TMA NAAT

• Identify GC prevalence amongst chlamydia
  screening population
• To monitor culture and partner findings in those
  GC NAAT positive
• 47 (1) of 4680 females F/up 38
• 8 (1.7) of 473 men F/up 5

13
TMA study cont

• Supportive evidence
• Females 37/38 34 culture ve
• 3 B1 contacts
• Males 5/5 Cult ve
• Low prevalence Population (1) excellent PPV

14
Reasons for culture Negative GC

• Recent Antibiotic (dental etc)
• Selective medium
• Failure to sustain or clearance (immunity)
• Organism perishes on culture plate
• Non Neisseria Species

15
Background (2)

• Simultaneous B1 NAAT testing commences 6th June
  2005
• Endocervical swab for women
• Urethral swab then First Catch Urine for men
• Expectation that NAAT will have higher
  sensitivity (detect more cases) than culture, but
  are these true or false positives?
• Decision to perform in house comparison of NAAT
  vs Culture

16
Methods of Audit

• Positive gonorrhoea results from H.As list (from
  lab)
• G.C proforma for a period of 10 months (June 05
  to March 06) supposed to be completed at B1 Tx
• Case notes were reviewed and data collected using
  excel.

17
Total Cases in Audit
18
Male Positive Results
19
Sensitivity and Specificity

• Sensitivity the proportion of patients with a
  disease who have a positive test (ie how well
  does it identify cases)
• Specificity the proportion of patients without
  the disease who have a negative test (ie how well
  does it identify healthy subjects)

20
Positive and Negative Predictive Values

• Positive Predictive Value the proportion of
  people with a positive test who actually have the
  disease (i.e if theyre NAAT ve, have they got
  it?)
• Negative Predictive Value the proportion of
  people with a negative test who really dont have
  the disease (i.e. if theyre NAAT ve, do they
  really not have it?)

21
Male
Sensitivity (Both/Cult) 100
Specificity (Both-/Cult-) 98.9
Positive PV (Both/NAAT) 68.6 Negative
PV (Both-/NAAT-) 100
22
Male discrepant results
23
Male adjusted Positive PV

• Assume all previous indicators are true positives
  with failure of culture
• Positive PV Both ve (with all high risk
  included)/NAAT ve (72/86)
• So PPV might 83.7

24
Equivocals
25
Male equivocals any reason?
26
Female Positive Results
27
Female
Sensitivity (NAAT/Cult) 98.1
Specificity (Both-/Cult-) 98.9
Positive PV (Both/NAAT) 54.2 Negative
PV (Both-/NAAT-) 99.98
28
Female Culture Pos/NAAT Neg

• One case
• Positive on 2 runs in Mayday but control failed
  negative when sent of site
• ? Sample degradation

29
Age distribution
30
Racial distribution
31
Female NAAT Pos/Culture Neg
32
Female adjusted Positive PV

• Assume all previous indicators are true positives
  with failure of culture
• Positive PV Both ve (with all high risk
  included)/NAAT ve (80/96)
• So PPV might 83

33
Female Equivocals
34
Female equivocals any reason?
35
Community Experience

• Dual testing for GC and C4a introduced by
  microbiology for all GP/FP specimens

36
COMMUNITY SPECIMENS IN FEMALES
37
COMMUNITY GENTIAL SWAB CULTURES
38
How do we compare?
39
Summary

• NAAT appears very sensitive compared to culture
  in local population. Excellent NPV.
• PPV acceptable. Occasional false positives
  possible if relying on NAAT alone. Poor cross
  referencing.
• No information on sensitivities need to
  continue culture for NAAT positive cases when
  return for treatment. 3rd generation
  cephalosporin
• Equivocal results in men are most likely to be
  true negative

40
Summary - cont

• The high NPV allows routine abandoning of B1
  microscopy and culture with significant cost
  savings
• Allow abandoning of screening for asymptomatic
  NSU
• This can be reinvested in another aspects of GU
  diagnostics e.g HSV NAAT testing
• Future Compare self taken vaginal with cervical
  in women.
• TV incorporate into NAAT testing system