Clinical Aspects of NAAT Testing for Neisseria Gonorrhoea

Neisseria Gonorrhoea

Second most common bacterial STI in UK Intracellular Gram-ve diplococcus Obligate human pathogen Colonises urogenital tract Uncomplicated mucosal infection Ascending infection of tract complicated Rare, invasion into blood - disseminated Conjunctivitis / Neo-natal conjunctivitis Facilitates transmission of other STIs (HIV)

Clinical Manifestations

Gonorrhoea Epidemiology

Why Bother with NAAT for GC?

-

GUM attendances year on year Many asymptomatic individuals wishing screening 48 hr waiting targets by 2008 Multiple swabs replaced by single swab/urine
time saving to see more patients increased acceptability to patients

Audit showed 38% males, 60% females to have a symptom or risk factor
halving the numbers of patients requiring GC cultures

GC NAAT as Sole Test for GC?

GRASP data 2004 showed sig. increase in resistance

- >5% ciprofloxacin resistance all England/Wales - 9% to 14% ciprofloxacin resistance 2003-2004

Sufficient sample size to detect 5% resistance level

-high quality culture methods required -need for adequate level of lab expertise

Currently unlicensed for other samples (rectum/pharynx) Most rapid diagnosis made using microscopy

Clinical Use of SDA Test for Gonorrhoea

SDA test alone is not appropriate for screening Certain individuals still need to be cultured.
- those identified as high risk for GC - those testing +ve following testing with SDA alone.

From a retrospective audit carried out on clinical data from the trial patients using the criteria of risk factors and symptoms. - only 4 individuals (all female) had no markers for possible GC (7.4% of
the GC+ve group and 0.25% of all tested patients)

A protocol for the combined SDA test was set up, and its use in clinical practice commenced 1/2/05.

Protocol for Use of the Combined SDA Test in Clinical Practice

Risk Factor* Symptom** Sign positive Full Screen
*Risk Factors GC Contact Past GC Diagnosis MSM (Men who have sex with men) MSM Contact CSW (Commercial sex worker) CSW Contact

negative

SDA only Urine (m) Cervix (f)

positive

Cultures prior to treatment

negative No further action

**Symptom Males Discharge/Dysuria Females Discharge/Abnormal bleeding/ Abdominal pain/Dysuria

Audit of the First Three Months of Clinical Practice

We wished to evaluate the test by looking at:
1.

Concordance between SDA and cultures. Adherence to the protocol. Adequacy of the protocol. ie. Low numbers of SDA +ve patients needing to be re-tested.

2.

3.

Audit of First Three Months Clinical Use

A retrospective case note review of all gonorrhoea +ve patients, on any test (at all sites) between 1/2/05 and 30/4/05. Data collected on sex, age, risk factors, symptoms, other STIs, consort data, and which tests were performed, of SDA, culture and microscopy. A further 100 sets of GC negative case notes was reviewed, picked at random from the same time period. Data was collected as to whether there were any deviations from the protocol.

3328 patients were tested for Gonorrhoea between 1/2 - 30/4 2005. 106 tested positive, (62 males and 45 females.)
Table 1. Results from GC Positive Group Mean Age Male (Total 62) Female (Total 44) 28.6 Other STIs
C4a 20 (32%) C11 1 (1.6%) A6 1 (1.6%) HIV 4 (6.5%) C4a 19 (43%) C6a 4 (9.1%)

Results

Risk Factor/ Symptoms 59 (95%)

Full Screen 59 (95%) (1 void) 39 (88.6%) (2 void)

Asympto Screen 2 (3.2%)

SDA+ve/ Culture+ve 49 (79%)

SDA+ve/ CultureCulture-ve 2 (3.2%)

SDASDA-ve/ Culture+ve 7 (11.2%)

21.6

38 (86.3%)

3 (6.8%)

33 (75%)

3 (6.8%)

3 (6.8%)

Of 98 patients tested with both SDA and culture: - SDA+ve/Culture+ve results in 82 (83.7%). 83% males/85% females. - SDA-ve/Culture+ve results found in 10. (7 males and 3 females) - All 7 males were MSM, culture positive at rectal or pharyngeal sites.
- 4 were also GC contacts. - Of the 3 women, 2 were positive at rectal site only. - 1 was culture positive at urethral site only (a false negative).

Table 2. SDA+ve/Culture-ve Results

Risk Factor Males 1. 2. * * 3. * * 4. Females 1. 2. ** 3. 4. 5. 6. MSM MSM No No Misc. No No No No No Symptom No No No No No Yes No No No No Microscopy Positive(Ur) Positive(Ur) Not done Not done Negative Positive Negative Not done Not done Negative Other Culture Info None +ve on rere-exam SDA only SDA only +ve placenta culture None None SDA only SDA only Culture +ve on rere-call Consort GC Positive Unknown Positive Negative Negative Negative Positive Negative Positive Positive Negative

10/106 results were SDA positive with cultures negative or unavailable.

Of these 10, 7 had other features that were consistent with a GC diagnosis. **3 likely false positive SDA results, 2 males, 1 female. (BUT 2 unconfirmed)

Adequacy of the Protocol

Ability of protocol to predict need for cultures in those with GC

- 5 patients with no RF/symptoms subsequently tested GC+ve on SDA - 4.7% of the +ve cases and 0.15% of the tested population - less than the projected number of re-calls (7.4% of +ves, 0.25% of all patients)

Ease of adherence to protocol GC+ve Group - all patients with RF/symptoms screened by culture/SDA
- 2 inappropriate cultures. 3 incomplete set of tests - 4/5 SDA only screens NOT cultured pre-treatment GC-ve Group 5/100 audited case notes SDA alone sent inappropriately

Urethral Only GC Infection in Females

From our study, 2 (7.4%) of 27 GC+ve women found to be culture+ve at urethral site only 1 of these women (asymptomatic/no risk factors) was cervical SDA-ve
- a false negative (In women cervix SDA replaces cervical and urethral culture)

1978 study*, 6% of 607 GC+ve women at a London GUM clinic had single site urethral gonorrhoea infection SDA picks up some of these. Urethral + cervical culture clinical standard in UK Larger studies needed to examine how many urethral GC single site infections missed? Additional urine/urethral swabs in women clinically and economically feasible?

*Barlow, Phillips. Lancet. April 1978, 761-764

Changes in Clinical Practice

Less time spent on swabbing and microscopy frees doctors and nurses to see more patients Rapid screening of asymptomatic patients in routine clinics Introduction of fast-track asymptomatic screening clinic
- maximised patient numbers, minimal staff

Audit of clinical practice May 2005 Nov 2005 48hr access improved from 24% - 40% increase in acceptability of tests (in men especially)

Summary of GC SDA

Sensitive/Specific test in our study population Low numbers of false positives in clinical practice Single site urethral GC in women, an issue? PPV is high in our population
This can vary in different populations Anxiety remains about poor PPVs in low prevalence populations

Need remains for culture alongside SDA

with a suitable protocol for the target population which can be easily followed

Can result in significant in clinical/lab workload Cost neutral in terms of lab/test costs Increased clinical efficiency greater patient throughput