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Guideline Summary
Guideline Title
Chlamydia trachomatis: UK testing guidelines.
Bibliographic Source(s)
Clinical Effectiveness Group. Chlamydia trachomatis: UK testing guidelines. London (UK): British Association for Sexual Health and HIV; 2010. 17 p. [18 references]
Guideline Status

This is the current release of the guideline.

This guideline updates a previous version: Carder C, Mercey D, Benn P. Chlamydia trachomatis. In: Ross J, Ison C, Carder C, Lewis D, Mercey D, Young H. Sexually transmitted infections: UK national screening and testing guidelines. London (UK): British Association for Sexual Health and HIV (BASHH); 2006 Aug. p. 26-32. [9 references]

Scope

Disease/Condition(s)

Chlamydia trachomatis infection

Guideline Category
Diagnosis
Evaluation
Screening
Clinical Specialty
Family Practice
Infectious Diseases
Internal Medicine
Obstetrics and Gynecology
Urology
Intended Users
Advanced Practice Nurses
Clinical Laboratory Personnel
Nurses
Physician Assistants
Physicians
Public Health Departments
Guideline Objective(s)

To make recommendations regarding sampling and diagnostic testing for chlamydia

Target Population

Individuals in the United Kingdom with or at risk for Chlamydia trachomatis infection

Interventions and Practices Considered
  1. Nucleic acid amplifications tests (NAATs) following potential exposure
  2. Retesting equivocal (unconfirmed reactive) test results using NAAT assay
  3. Use of appropriate specimens
    • First catch urine
    • Cervical specimens
    • Urethral specimens
    • Pharyngeal specimens
    • Rectal specimens
    • Vaginal specimens
    • Conjunctival specimens
    • Specimens from the glans penis (considered but not recommended)
  4. Special considerations for sexual assault victims
  5. Re-screening if patient re-presents
  6. Test of cure, if indicated
Major Outcomes Considered
  • Test sensitivity and specificity
  • Test of cure

Methodology

Methods Used to Collect/Select the Evidence
Searches of Electronic Databases
Description of Methods Used to Collect/Select the Evidence

Search Criteria

A search using the terms Chlamydia trachomatis, diagnosis and genital was undertaken using EMBASE from January 2004 until the end of 2008. The journals Sexually Transmitted Infections, Sexually Transmitted Diseases and the International Journal of STDs and AIDS were hand searched for relevant articles. A total of 98, 201 and 100 references were identified respectively. The most relevant references (those providing additional or new evidence) were included after reviewing titles and abstracts.

Number of Source Documents

Not stated

Methods Used to Assess the Quality and Strength of the Evidence
Weighting According to a Rating Scheme (Scheme Given)
Rating Scheme for the Strength of the Evidence

Levels of Evidence

Level Type of Evidence
Ia Evidence obtained from meta-analysis of randomised controlled trials
Ib Evidence obtained from at least one randomised controlled trial
IIa Evidence obtained from at least one well-designed controlled study without randomisation
IIb Evidence obtained from at least one type of well-designed quasi-experimental study
III Evidence obtained from well-designed, non-experimental descriptive studies, such as comparative studies, correlation studies and case control studies
IV Evidence obtained from expert committee reports or opinions and/or clinical experience of respected authorities
Methods Used to Analyze the Evidence
Systematic Review
Description of the Methods Used to Analyze the Evidence

Not stated

Methods Used to Formulate the Recommendations
Expert Consensus
Description of Methods Used to Formulate the Recommendations

Clinicians and scientists from the Bacterial Special Interest Group of the British Association of Sexual Health and HIV (BASHH) have been involved in the development of this guideline. Patient involvement was not attempted but the authors drew on their experience as practising clinicians.

Rating Scheme for the Strength of the Recommendations

Grades of Recommendation

Grade Recommendation
A (Evidence levels Ia, Ib) Requires at least one randomised controlled trial as part of the body of literature of overall good quality and consistency addressing the specific recommendation
B (Evidence levels IIa, IIb, III) Requires availability of well-conducted clinical studies but no randomised clinical trials on the topic of recommendation
C (Evidence level IV) Requires evidence from expert committee reports or opinions and/or clinical experience of respected authorities. Indicates absence of directly applicable studies of good quality
Cost Analysis

A formal cost analysis was not performed and published cost analyses were not reviewed.

Method of Guideline Validation
External Peer Review
Internal Peer Review
Description of Method of Guideline Validation

These guidelines have been posted for comment on the British Association for Sexual Health and HIV (BASHH) website for 3 months for consultation.

Recommendations

Major Recommendations

Definitions for the level of evidence (I-IV) and grade of recommendation (A-C) are provided at the end of the "Major Recommendations" field.

Summary of Recommended Tests for Chlamydia trachomatis

Use of Tests with Appropriate Specimens

  Specimens
First catch urine Cervix Vulval-vaginal Urethra Glans penis Pharynx Rectum Conjunctiva
NAAT 1 1 1 1* 3 2# 2# 2
Tissue Culture 3 (No longer recommended)

NAAT: nucleic acid amplification test

Key:

  1. Test of choice
  2. Test of choice, not licensed
  3. Not recommended

*Men and women with persistent urethral symptoms where tests from other sites are negative or women who have undergone a hysterectomy

#Men who have sex with men (MSM) and commercial sex workers (CSW)

Appropriate Specimens for Men and Women

  Specimen
Men First catch urine (specimen of choice) or urethral swab
Men who have sex with men (MSM) First catch urine (specimen of choice) or urethral swab
and
Pharyngeal and rectal swab
Women undergoing speculum examination Endocervical swab
Women not requiring speculum examination Self taken lower vaginal swab (specimen of choice) or first catch urine*

*Please note first catch urine samples may be less sensitive than endocervical or self taken lower vaginal swabs for the detection of C. trachomatis.

A variety of different tests are available to detect C. trachomatis in the genital tract. Their appropriate use depends on the characteristics of the test itself, the correct choice of sample and the clinical presentation of the patient. Currently there are no enzyme immuno-assays (EIAs), point of care tests (POCT) or deoxyribonucleic acid (DNA) probe technology that can be recommended for use in the diagnosis of C. trachomatis as they show inferior sensitivity and specificity to that of the recommended tests, the nucleic acid amplification tests (NAATs).

Nucleic Acid Amplification Tests

The role of nucleic acid amplification technology in the routine diagnosis of C. trachomatis infections has evolved over the last decade. There are a number of commercial assays currently available for routine use. The four (listed) below are commonly used in clinical practice:

  • Abbott RealTime PCR assay (Abbott m2000, Abbott Diagnostics)
  • BD ProbeTec ET, Strand displacement amplification (SDA, Becton Dickinson)
  • COBAS Taqman, Polymerase chain reaction assay (Real-time PCR, Roche Diagnostics)
  • GenProbe Aptima assay, Transcription mediated amplification assay (TMA, GenProbe)

These commercial assays all detect both viable and non-viable organisms but differ in their target sequence and their method of amplification. These assays also offer dual detection of C. trachomatis and Neisseria gonorrhoeae from a single specimen. For further information regarding the detection of N. gonorrhoeae using NAATs please see the National Guideline Clearinghouse (NGC) summary of the British Association of Sexual Health and HIV (BASHH) guideline UK national guideline for the management of gonorrhoea in adults, 2011 and BASHH/Health Protection Agency (HPA) guidance at www.hpa.org.uk External Web Site Policy.

Recommendation

NAATs are the tests of choice for urethral, cervical, vaginal (self-taken and clinician-obtained) and first catch urine specimens because of their superior sensitivity and high specificity (Ib, Grade A). All of the above commercial NAATs show adequate sensitivity and specificity. The testing platform selected must have a positive predictive value (PPV) over 90% and detect all known variants (IV, Grade C).

It is beyond the remit of these guidelines to recommend any one NAAT above another. The choice of testing platform will depend on a variety of factors including:

  • The volume of samples to be processed
  • Reproducibility
  • Hands-on-time/automation
  • Cost of reagents/equipment
  • The relative sensitivity and specificity of the individual tests for different clinical specimens
  • Whether the test is used to detect C. trachomatis alone or as a combined test for C. trachomatis and N. gonorrhoeae

No single test provides 100% sensitivity and specificity. Test problems include inhibitors, contamination, reproducibility and hormonal factors, which can lower sensitivity.

Although not licensed for these sites, NAATs may be used and potentially give valid results from pharyngeal and rectal specimens (IIa, Grade B). This should be validated locally for the individual platform used.

Confirming Positive NAATs by Another Technique

Only another NAAT is sensitive enough to confirm a positive result. (IIa, Grade B). Currently the HPA guidelines recommend that every positive chlamydia result should be confirmed using a NAAT, preferably with an assay of equal sensitivity but with a different target.

However recent data suggests that confirmatory testing may be unnecessary given that >90% of positive NAAT results will be confirmed. (III, Grade B) The data are available for genital specimens and for some platforms only. Further work is required to validate this strategy for extra-genital specimens. Regardless of the site tested, clinicians need to be aware of the potential for false positive results, particularly when using the test in a low prevalence population.

When the test result is equivocal (unconfirmed reactive), arrangements should be made to re-test the original sample and request a further sample. Where possible this sample should be tested using a NAAT assay of equal sensitivity but with a different target. (IIa, Grade B)

Inhibition

Inhibitors can be identified in specimens from all sites, in particular first-void urine. An internal amplification control to identify inhibition should be used and is available using some commercial kits. Not all NAATs include an internal control (see individual manufacturer's instructions).

Transport, Storage and Handling of Samples

Requirements for the transport, storage and handling of samples vary between commercial assays and the manufacturer's instructions should be followed. It is recommended that results should be available within seven working days of the specimen being taken. If supplementary testing of a sample is required then the results should be available within 14 working days of the specimen being taken.

Quality Assurance

All efforts need to be made to ensure all staff adhere to the correct test procedures, avoid sampling errors and environmental contamination. Participation in an External Quality Assurance (EQA) programme needs to be encouraged (essential in an accredited laboratory) to minimise common errors and ensure that reproducibility of testing is maintained.

New Variant Chlamydia trachomatis

In November 2006 a C. trachomatis strain with a deletion in the cryptic plasmid was discovered in Sweden (new-variant – nvCT). The deletion, 377bp in length, affected the target sequence of some commercial tests resulting in false negative results. Isolated cases were found in Norway, Ireland, Denmark, France and Scotland. It is uncertain why this strain appears here and only enhanced surveillance will show whether it will be found elsewhere.

The target sequence of some commercially available kits has since been modified, but not all kits are capable of detecting the nvCT. Current NAATs are being modified and withdrawn so it is important that clinicians and microbiologists are aware of the status of the test they use. Further variants could occur and may not be detected by current commercial assays.

Lymphogranuloma Venereum

Lymphogranuloma venereum (LGV) is caused by the more invasive L serovars (L1, L2, L2a, and L3) of C. trachomatis. Since the end of 2003, an ongoing outbreak of LGV proctitis has been reported in Europe and North America among men who have sex with men (MSM), which has been strongly associated with human immunodeficiency virus (HIV) infection. It is recommended that all MSM with a positive rectal chlamydia NAAT who report rectal symptoms or who are a contact of someone with LGV should have a sample sent to the Sexually Transmitted Bacteria Reference Laboratory (STBRL), Health Protection Agency Centre for Infections, London, United Kingdom [UK] or the Scottish Bacterial Sexually Transmitted Infections Reference Laboratory (SBSTIRL). A real-time polymerase chain reaction (PCR) assay is now available at STBRL and SBSTIRL which performs well for the detection of LGV, non-LGV or dual infections from rectal specimens (IV, Grade C). Further information regarding the LGV enhanced surveillance protocol is available at http://www.hpa.org.uk/Topics/InfectiousDiseases/InfectionsAZ/LGV/EnhancedSurveillanceSystem/ External Web Site Policy and the LGV guideline is available at http://www.bashh.org/documents/92/92.pdf External Web Site Policy.

Tissue Culture

The traditional method of diagnosing C. trachomatis was by cell culture. Although chlamydiae are bacteria, they cannot be cultivated in non-living or cell free media. However, few laboratories in the UK still offer this service. Cell culture procedures are expensive, labour intensive and time consuming. Cell culture allows viable isolates to be obtained from cases where therapeutic failure is suspected, to test for antimicrobial resistance. At best the sensitivity of cell culture is probably no more than 75%, although specificity should be 100% if a C. trachomatis major outer membrane protein (MOMP) specific stain is used. Cell culture is no longer required for medico-legal purposes (IV, Grade C).

Appropriate Specimens for Testing for Chlamydia trachomatis

The performance of different tests for C. trachomatis can be influenced by the test specimen used.

First Catch Urine (FCU)

First catch urine comprises the first 15-50 mls of urine passed at any time of the day (see individual pack inserts). The patient must not have urinated for at least one hour (or 2 hours for some kits). FCU is licensed in both men and women for most NAATs, FCU in women is less sensitive than using endocervical or self taken lower vaginal specimens. FCUs are the preferred specimens for men (IIa, Grade B).

Cervical Specimens

Cervical samples are suitable for all tests. Specimens should be taken during a speculum examination with the swab inserted into the cervical os using the manufacturers swab collection packs and rotated for a few seconds (IIa, Grade B).

Urethral Specimens

Both male and female urethral samples are suitable for all tests. For men either a urethral specimen or first catch urine are ideal specimens although a urethral specimen may cause discomfort. For a male urethral specimen the swab is inserted into the urethra 2-4 cm and rotated one or more times (Grade C). A urethral sample may be required in women with persistent urethral symptoms in whom specimens for C. trachomatis at other sites are negative or in those who have undergone a hysterectomy (IV, Grade C). For a female urethral specimen introduce the swab 1 cm into the urethra and rotate one or more times (IV, Grade C).

Pharyngeal Specimens

A cotton tipped swab should be rubbed over the posterior pharynx and tonsillar crypts.

Pharyngeal samples are licensed for use with the tissue culture technique (IIa, Grade A).

NAATs are not licensed for use with pharyngeal specimens but accumulating evidence suggests they perform well (IIa, Grade B). Pharyngeal specimens should be taken and tested for C. trachomatis in MSM (IIa, Grade B) and commercial sex workers (CSW) reporting sexual behaviours which may result in pharyngeal infection (IV, Grade C). There is insufficient evidence to recommend testing for pharyngeal C. trachomatis using NAATs in heterosexual men and women (IV, Grade C).

There is limited data regarding self taken pharyngeal specimens among MSM but what there is suggests similar sensitivity and specificity to samples obtained by healthcare workers.

Rectal Specimens

A cotton tipped swab should be rubbed against the rectal wall. This should ideally be taken at proctoscopy but data suggests that rectal swabs taken without proctoscopy have similar sensitivity.

Tissue culture is validated for detecting C. trachomatis from rectal specimens (IIa, Grade B). There are no licensed NAATs for the detection of C. trachomatis in rectal specimens but data is available supporting the validity of these tests for use here. Routinely available NAATs for C. trachomatis will detect all serovars including LGV (IIa, Grade B). Rectal specimens should be taken and tested for C. trachomatis in MSM (IIa, Grade B) and CSWs (IV, Grade C) reporting sexual behaviours which may result in rectal infection. There is insufficient evidence to recommend testing for rectal C. trachomatis using NAATs in heterosexual men and women (IV, Grade C).

There is limited data regarding self taken rectal specimens among MSM but this suggests similar sensitivity and specificity compared to samples obtained by healthcare workers via proctoscopy.

Vaginal Specimens (VS)

Insert the swab into the vagina, about two inches and gently rotate the swab for 10 to 30 seconds.

Some commercially available NAATs are licensed for use with vaginal samples, either clinician obtained or self-taken (further information is available from each manufacturer's kit insert). Vaginal specimens have been demonstrated by a number of workers to produce similar sensitivity to cervical testing (IIa, Grade B). Vulval specimens are not recommended for testing for C. trachomatis.

Conjunctival Specimens

A cotton tipped swab should be used to for C. trachomatis from the conjunctiva. NAATs have a higher sensitivity to detect infection from the conjunctiva than other methodologies.

Specimens from the Glans Penis

NAATs have poor sensitivity to detect C. trachomatis from clinician and self-taken specimens from the glans penis and cannot be recommended (IIa, Grade B).

Factors Which May Alter Recommended Tests or Test Sites

Recommendations for testing are unaltered for:

  • Sexual contacts of known chlamydia infection
  • Sex workers – pharyngeal and rectal specimens should be taken and tested for C. trachomatis in CSWs (IV, Grade C) reporting sexual behaviours which may result in infection at these sites.
  • Pregnant women
  • Presence or absence of symptoms

However testing in women who have undergone a hysterectomy should be undertaken using either a FCU, vulval-vaginal (VV) specimen or a urethral swab (IV, Grade C).

Sexual Assault Victims

Culture is no longer recommended for detecting C. trachomatis at all exposed sites following sexual assault in adults because of its low sensitivity. It is recommended that a NAAT be taken from all exposed sites. (IIa, Grade C). Confirmation of a positive NAAT for C. trachomatis should be undertaken using a NAAT with a different target in medico-legal cases. This is available in some laboratories and the Sexually Transmitted Bacterial Reference Laboratory or the SBSTIRL.

Frequency of Repeat Testing in an Asymptomatic Patient

Re-exposure to a possible source of chlamydia should lead to re-screening if the patient re-presents. However there is no evidence currently to guide the frequency of repeat testing in those without a clear history of re-exposure to chlamydia. The Department of Health (DoH) Chlamydia Screening Programme for under 25's recommends repeat testing annually or every time someone has a new sexual partner.

When to Test Following Potential Exposure to Infection

Individuals should be advised to have a test for chlamydia with a NAAT when they first present and, if potential exposure occurred within the last two weeks, they should also be asked to return for a repeat NAAT two weeks after the exposure (IV, Grade C). (http://www.bashh.org/documents/1743/1743.pdf External Web Site Policy)

Test of Cure (TOC) Following C. trachomatis treatment

TOC (repeat testing to confirm clearance of infection) is not routinely recommended if:

  • Standard treatment has been given
  • There is confirmation that the patient has adhered to therapy
  • There is no risk of re-infection

However, if these criteria cannot be met or if the patient is pregnant a TOC is advised. This should be taken using the same technique and sample type as used for the initial testing. Few data are however available regarding the optimal time to undertake a TOC. It is recognised that NAATs will detect residual DNA/ribonucleic acid (RNA) even after successful treatment of the organism four to six weeks after treatment (IIb, Grade B).

Definitions:

Levels of Evidence

Level Type of Evidence
Ia Evidence obtained from meta-analysis of randomised controlled trials
Ib Evidence obtained from at least one randomised controlled trial
IIa Evidence obtained from at least one well-designed controlled study without randomisation
IIb Evidence obtained from at least one type of well-designed quasi-experimental study
III Evidence obtained from well-designed, non-experimental descriptive studies, such as comparative studies, correlation studies and case control studies
IV Evidence obtained from expert committee reports or opinions and/or clinical experience of respected authorities

Grades of Recommendation

Grade Recommendation
A (Evidence levels Ia, Ib) Requires at least one randomised controlled trial as part of the body of literature of overall good quality and consistency addressing the specific recommendation
B (Evidence levels IIa, IIb, III) Requires availability of well-conducted clinical studies but no randomised clinical trials on the topic of recommendation
C (Evidence level IV) Requires evidence from expert committee reports or opinions and/or clinical experience of respected authorities. Indicates absence of directly applicable studies of good quality
Clinical Algorithm(s)

None provided

Evidence Supporting the Recommendations

Type of Evidence Supporting the Recommendations

The type of supporting evidence is identified and graded for selected recommendations (see the "Major Recommendations" field).

Benefits/Harms of Implementing the Guideline Recommendations

Potential Benefits

Accurate diagnosis of Chlamydia trachomatis infection

Potential Harms
  • Regardless of the site tested, clinicians need to be aware of the potential for false positive results, particularly when using the test in a low prevalence population.
  • No single test provides 100% sensitivity and specificity. Test problems include inhibitors, contamination, reproducibility and hormonal factors, which can lower sensitivity.

Qualifying Statements

Qualifying Statements
  • This guideline makes recommendations regarding sampling and diagnostic testing for chlamydia and does not discuss the utility or indications for chlamydia population screening.
  • These guidelines are intended to be used in combination with the following guidelines:
  • This guideline has been designed for use in sexual health clinics in the United Kingdom (UK) but its principles are also applicable to other healthcare settings where screening or testing for C. trachomatis is undertaken.

Implementation of the Guideline

Description of Implementation Strategy

An implementation strategy was not provided.

Implementation Tools
Audit Criteria/Indicators
For information about availability, see the Availability of Companion Documents and Patient Resources fields below.

Institute of Medicine (IOM) National Healthcare Quality Report Categories

IOM Care Need
Getting Better
Staying Healthy
IOM Domain
Effectiveness

Identifying Information and Availability

Bibliographic Source(s)
Clinical Effectiveness Group. Chlamydia trachomatis: UK testing guidelines. London (UK): British Association for Sexual Health and HIV; 2010. 17 p. [18 references]
Adaptation

Not applicable: The guideline was not adapted from another source.

Date Released
2006 Aug (revised 2010)
Guideline Developer(s)
British Association for Sexual Health and HIV - Medical Specialty Society
Source(s) of Funding

British Association for Sexual Health and HIV

Guideline Committee

Clinical Effectiveness Group (CEG)

Composition of Group That Authored the Guideline

Authors: Caroline Carder, Biomedical Scientist, University College London Hospitals NHS Foundation Trust; Danielle Mercey, Consultant in GUM, University College London; Paul Benn, Consultant in GUM, Mortimer Market Centre, Camden PCT

Editors: Jonathan Ross, Whittall Street Clinic, Birmingham. GUM Professor, Chairman, Bacterial Special Interest Group; Mark FitzGerald, Musgrove Park Hospital, GU Physician, Clinical Effectiveness Group

Financial Disclosures/Conflicts of Interest

Each of the authors has declared that they have no conflicts of interest.

Guideline Status

This is the current release of the guideline.

This guideline updates a previous version: Carder C, Mercey D, Benn P. Chlamydia trachomatis. In: Ross J, Ison C, Carder C, Lewis D, Mercey D, Young H. Sexually transmitted infections: UK national screening and testing guidelines. London (UK): British Association for Sexual Health and HIV (BASHH); 2006 Aug. p. 26-32. [9 references]

Guideline Availability

Electronic copies: Available from the British Association for Sexual Health and HIV Web Site External Web Site Policy.

Availability of Companion Documents

The following are available:

  • British Association for Sexual Health and HIV: framework for guideline development and assessment. British Association for Sexual Health and HIV; 2010. 18 p. Electronic copies: Available in PDF from the BASHH Web site External Web Site Policy.
  • Testing for chlamydia: the "window period." British Association for Sexual Health and HIV; 2008 May 20. 1 p. Electronic copies: Available in PDF from the BASHH Web site External Web Site Policy.

In addition, auditable outcomes are provided in the original guideline document External Web Site Policy.

Patient Resources

None available

NGC Status

This NGC summary was completed by ECRI Institute on June 19, 2008. The information was verified by the guideline developer on October 20, 2008. This NGC summary was updated by ECRI Institute on June 6, 2012.

Copyright Statement

This NGC summary is based on the original guideline, which is subject to the guideline developers and/or BMJ Publishing Group's copyright restrictions. Reproduction and use of this guideline is permitted provided that (a) the original content is not changed or edited; and, (b) any content derived from the original guideline is acknowledged as that of the author(s) and responsible organizations.

Readers wishing to download and reproduce material for purposes other than personal study or education should contact BMJPG to seek permission first. Contact: BMJ Publishing Group, BMA House, Tavistock Square, WC1H 9JR, UK.

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