EQA for Tests Sexually Transmitted Infections

Slide1: 

Quality Assurance of Tests for Sexually Transmitted Infections Michael A. Noble MD FRCPC CDC Quality Assurance Meeting, November 29, 2000

Slide2: 

In North America The most commonly submitted sample is urine from women with acute or recurrent urinary tract infection. The most common cause of urinary tract infections in women is recent sexual activity. Tests for sexually transmitted infections are the second most commonly submitted samples send to medical laboratories. Sexual activity directly accounts for 60-70 percent of microbiology laboratory activity.

In North America: 

In North America Sexually transmitted infections cycle with a periodicity of 10-20 years. Peaks in 1920s, 1940s, 1960s, 1980s Progressive decreasing detection and reporting rates throughout 1990s Rate of sexually transmitted infections lower now compared to the last 20 years. Diagnostic assays for sexually transmitted infections continuously improves. North America experience does not necessarily reflect world-wide experience.

Why STI Diagnosis is Important: 

Why STI Diagnosis is Important STIs rapidly spread throughout communities. STIs can be associated with acute illness. STIs can be associated with chronic illness. STIs can be associated with remote illness. Ulcerative STI associated transmission of other illnesses, especially HIV. Syphilis Chancroid LGV

Sexually Transmitted Infections: 

Sexually Transmitted Infections Bacterial Neisseria gonorrhoeae Chlamydia trachomatis Treponema pallidum Haemophilus ducryei (chancroid) Lymphogranuloma Mycoplasma Viruses Herpes simplex II Hepatitis B Hepatitis C HIV Papillomavirus Yeasts and fungi Candida albicans Candida glabrata Candida tropicalis Parasites Trichomonas vaginalis Entamoeba histolytica

Sexually Transmitted Infections: 

Sexually Transmitted Infections Neisseria gonorrhoeae Chlamydia trachomatis Treponema pallidum

Slide7: 

Urethritis Acute tenosynovitis Neonatal Conjunctivitis P.I.D. Urethral Strictures Chronic Arthritis Infertility Gonorrhea F.H.C.-Hepatitis Sepsis

Slide8: 

Urethritis Acute Arthritis Neonatal Conjunctivitis P.I.D. Chronic Arthritis Infertility Chlamydia trachomatis Hepatitis

Slide9: 

Chancres Cardiovascular Gumma Neurosyphilis Meningitis Tabes dorsalis General paresis HIV Transmission. Congenital Transmission Chronic Arthritis Hepatitis Syphilis Lymph- adenopathy

Test Procedures Requiring EQA(Those with Readily Available EQA Programs): 

Test Procedures Requiring EQA (Those with Readily Available EQA Programs) Neisseria gonorrhoeae Gram stain Culture PCR Chlamydia trachomatis DFA EIA PCR Culture Treponema pallidum Serological tests for Syphilis VDRL, RPR, FTA-abs, MHA-tp

What is available for international guidance for Quality Assessment forMedical Laboratory Tests?: 

What is available for international guidance for Quality Assessment for Medical Laboratory Tests?

Standards for Consideration (1): 

Standards for Consideration (1) ISO 17025/ISO 15189 and NCCLS GP17A 5.6.5 The laboratory shall participate in organised inter-laboratory comparisons, such as external quality assessment and proficiency testing schemes, that encompass the extent and complexity of analytical and diagnostic procedures used by the laboratory. The laboratory director and management shall monitor the results of external quality assessment and proficiency testing and participate in the implementation and documentation of corrective actions. Schemes should be consistent with ISO Guide 43.

Slide13: 

Standards for Consideration (2) . ISO Guide 43 These programmes should, as far as possible, provide clinically relevant challenges that mimic patient samples and that check the entire examination process including pre- and post-analytical procedures

Slide14: 

The Laboratory Cycle Bartlett ‘80 The Patient Report Creation Report Transmission Report Interpretation Collection Transport Accession Analysis Test Selection P r e A n a l y t I c P o s t A n a l y t I c

When was the last time a clinical laboratory commonly received samples in the form of a small glass vial that contained a small amount of white powder that required rehydration?: 

When was the last time a clinical laboratory commonly received samples in the form of a small glass vial that contained a small amount of white powder that required rehydration? Mimicing patient samples

What constitutes a Guide 43“clinically relevant challenge that mimics patient samples” : 

What constitutes a Guide 43 “clinically relevant challenge that mimics patient samples” Gram stain with host elements and proportionate microbial elements DFA material with host elements and proportionate microbial elements. EIA material with bacterial contaminants and proportionate microbial elements. PCR material that may contain inhibitors. Antibody challenges in fresh human serum.

Standards for Consideration (3): 

Standards for Consideration (3) ISO 17025/ ISO 15189 (2) 5.6.6 Whenever a formal inter-laboratory comparison program is not available, the laboratory shall develop a mechanism for determining the accuracy of those procedures not otherwise evaluated. Whenever possible, this mechanism shall utilise externally derived challenge materials such as exchange of samples with other laboratories. The laboratory director and management shall monitor the results of this mechanism proficiency testing and participate in the implementation and documentation of corrective actions. 

Alternatives to formal EQA(In decreasing order of acceptability): 

Alternatives to formal EQA (In decreasing order of acceptability) Self-initiated peer-group inter-laboratory comparison. (    ) Self-initiated inter-laboratory comparison. (   ) Challenge review of known positive-negative clinical material ( ) Challenge review of control material ()

Challenges with many Proficiency Tests currently available: 

Challenges with many Proficiency Tests currently available Gram stain: usually with bacteria only Culture usually lyophilyzed material only EIA/DFA assay and brand specific PCR Does not contain host material VDRL/RPR/FTA (blood) frozen human serum VDRL (csf) csf not commonly available

Challenges of compliance with Guide 43 requirements: 

Challenges of compliance with Guide 43 requirements Making relevant materials requires considerable research and development. Non-lyophilized material tends to degenerate rapidly with time. Fresh human serum degrades quickly. Samples require temperature and time control in transportation.

Proficiency Testing of Neisseria culture assays: 

Proficiency Testing of Neisseria culture assays Challenges (and some solutions) Dies quickly in transport medium 50 percent die-off in 24 hours Improved (7 day) survival with 5% CO2 Unstable recovery from lyophylization Bacterial identification should be challenged Neisseria cinerea (low virulence commensal) Colonies larger, Gluocse negative, Enzyme substrate false positive DFA negative Agglutination false positive

Slide22: 

Gram stain challenge containing gram negative diplococci (intra- and extracellular) with human neutrophils.

Syphilis Serology: 

Syphilis Serology

Proficiency Testing for Syphilis Serology: 

Proficiency Testing for Syphilis Serology Fresh human serum. Test across the range of dilutions typically found in the clinical samples. Clinical Interpretation of VDRL and RPR is based on both qualitative (positive/negative) and quantitative (low titre/high titre) results.

Slide25: 

The Laboratory Cycle Bartlett ‘80 The Patient Report Creation Report Transmission Report Interpretation Collection Transport Accession Analysis Test Selection P r e A n a l y t I c P o s t A n a l y t I c

Slide26: 

Pre-analytic phase testing Can the laboratory transport samples quickly and safely? Analytic phase Testing Can the laboratory identify organisms when present? Can the laboratory distinguish between contaminants and positives? Can the laboratory recognize true negative samples? Post-analytic phase testing Post-analytic phase testing Can the laboratory provide information that is accurate, clinically relevant, unambiguous and interpretable?

Quality Control of PT materials: 

Quality Control of PT materials Are you providing really providing what you are saying you are providing? Pre-test sampling: MIL STD 105E based random sampling charts for acceptance sampling (5-15% sampling for 98-99% confidence) Same-time sampling: Program and reference laboratory testing Post-test sampling: Sample call-back and review

Programs that comply with Guide 43 requirements: 

Programs that comply with Guide 43 requirements Programs with some compliance C.A.P. - USA UK-NEQAS – UK QMPLS – Ontario, Canada CMPT – British Columbia, Canada Note this list should not be considered complete or comprehensive

Goal of PT Program Assistance: 

Goal of PT Program Assistance Assist with establishment of program core Assist with program start-up and provision of training and start-up materials Serve as reference resource for regionally based local program Timeframes vary with situation

In Summary: 

In Summary Sexually Transmitted Infections are commonly associated with fastidious or non-growing organisms, making laboratory diagnosis challenging. Tests for Sexually Transmitted Infections are critical for diagnosis and documentation and need critical quality control. Development of PT materials can be expensive and challenging, but many issues have been addressed. Quality materials are available existing programs.