standards for laboratory diagnosis of tuberculosis professor brian i. duerden inspector of...
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Standards for Laboratory Standards for Laboratory Diagnosis of TuberculosisDiagnosis of Tuberculosis
Professor Brian I. DuerdenProfessor Brian I. DuerdenInspector of Microbiology and Infection Inspector of Microbiology and Infection
Control,Control,Department of HealthDepartment of Health
Guidance and StandardsGuidance and Standards
National SOPNational SOP– How to do the testsHow to do the tests
NICE guidanceNICE guidance– How to manage the patientHow to manage the patient
DH programmeDH programme– What service should be deliveredWhat service should be delivered– 3 working groups3 working groups
TB monitoring and laboratory TB monitoring and laboratory services working groupservices working group
Surveillance standardsSurveillance standards
Standards for laboratory diagnosisStandards for laboratory diagnosis– Current best practiceCurrent best practice– Simple and straightforwardSimple and straightforward– Not replicate or replace the National SOPNot replicate or replace the National SOP
Standards to coverStandards to cover
SamplesSamples
Transfer to laboratoryTransfer to laboratory
Immediate testsImmediate tests– MicroscopyMicroscopy
Culture, isolation and Culture, isolation and identificationidentification
Laboratory facilities Laboratory facilities and expertiseand expertise
Transport Transport
Susceptibility testingSusceptibility testing
Molecular Molecular fingerprinting/typingfingerprinting/typing
NotificationNotification
PCR detection of MtbPCR detection of Mtb
Immunodiagnostic Immunodiagnostic teststests
Histopathology Histopathology
SamplesSamples
Type of sampleType of sample– Sputum (resp. sample), CSF (spinal/para-Sputum (resp. sample), CSF (spinal/para-
spinal/intra-cerebral), gastric washings, lymph spinal/intra-cerebral), gastric washings, lymph nodes (tissues), urine, faecesnodes (tissues), urine, faeces
Number of samplesNumber of samples– 2 or 3 for sputum? Consecutive days.2 or 3 for sputum? Consecutive days.– Early morning or any time?Early morning or any time?– True LRT specimenTrue LRT specimen
DocumentationDocumentation
Transfer to laboratoryTransfer to laboratory
Within 24h (or 1 working day, max 48h)Within 24h (or 1 working day, max 48h)– Minimise overgrowthMinimise overgrowth– Maintain AFB characterMaintain AFB character
Potentially infected clinical samplePotentially infected clinical sample– Routine procedureRoutine procedure
Immediate testsImmediate tests
MicroscopyMicroscopy– Auramine fluorescent stainingAuramine fluorescent staining– 6-day service (not on call)6-day service (not on call)– Perform microscopy and issue result within 24h (1 Perform microscopy and issue result within 24h (1
working day) of receiptworking day) of receipt– Telephone positive result to Telephone positive result to seniorsenior member of clinical member of clinical
teamteam– Notify lead TB nurse, lead clinician, CCDCNotify lead TB nurse, lead clinician, CCDC
Accreditation; IQC programme; satisfactory EQA Accreditation; IQC programme; satisfactory EQA performance; staff CPD/peer reviewperformance; staff CPD/peer review
Culture, isolation and identificationCulture, isolation and identification
Automated liquid culture on all samplesAutomated liquid culture on all samples– Set up within 24h of receipt (6 day service)Set up within 24h of receipt (6 day service)– Plus conventional solid culturePlus conventional solid culture
Send all isolates to RCM on day found to Send all isolates to RCM on day found to be positivebe positive– Reach RCM within 24h Reach RCM within 24h
Complete identification of most Complete identification of most mycobacterial isolates within 21 daysmycobacterial isolates within 21 days
Identification and reportingIdentification and reporting
NAAT (PCR, LCR) or hybridisation gene NAAT (PCR, LCR) or hybridisation gene probe for Mtb complexprobe for Mtb complex– On the day culture shows positive OROn the day culture shows positive OR– Within 24h of receipt at RCMWithin 24h of receipt at RCM
Other probes and/or phenotypic testsOther probes and/or phenotypic tests
Report on day of test to Report on day of test to – SeniorSenior member of clinical team member of clinical team– Lead TB nurse, lead TB clinician, CCDCLead TB nurse, lead TB clinician, CCDC
Laboratory facilities and expertiseLaboratory facilities and expertise
Safety – Category 3 for cultureSafety – Category 3 for culture– HSE approvedHSE approved– Contingency plan for accidental dispersalContingency plan for accidental dispersal– Continuity plan for closureContinuity plan for closure
AccreditedAccredited– IQC programme, satisfactory EQAIQC programme, satisfactory EQA
Sufficient number – daily service, Sufficient number – daily service, competencecompetenceNamed Consultant and BMS for adviceNamed Consultant and BMS for advice
TransportTransport
SamplesSamples– Potentially infected samples (routine)Potentially infected samples (routine)
Positive culturesPositive cultures– Category A but exemption to treat as B for Category A but exemption to treat as B for
clinical and diagnostic purposesclinical and diagnostic purposesUN 3373 – marked Diagnostic or Clinical UN 3373 – marked Diagnostic or Clinical
P650 packagingP650 packaging
Do not send by Royal MailDo not send by Royal Mail
Susceptibility testingSusceptibility testing
Complete within 30 days of initial receipt of Complete within 30 days of initial receipt of clinical sample for primary agentsclinical sample for primary agents– Isoniazid, rifampicin, pyrazinamide, ethambutolIsoniazid, rifampicin, pyrazinamide, ethambutol
Takes 10-20 days by liquid proportion (automated) or Takes 10-20 days by liquid proportion (automated) or resistance ratioresistance ratio
Molecular detectionMolecular detection– Rifampicin within 24h if MDRTB suspectedRifampicin within 24h if MDRTB suspected– Isoniazid under developmentIsoniazid under development
Done at RCM with accreditation, IQC, EQADone at RCM with accreditation, IQC, EQA
Molecular fingerprinting/typingMolecular fingerprinting/typing
ALL ISOLATESALL ISOLATES– 15-loci MIRU-VNTR15-loci MIRU-VNTR
Mycobacterial Interspersed Repetitive Units – Mycobacterial Interspersed Repetitive Units – Variable Number Tandem RepeatsVariable Number Tandem Repeats
– Results to national databaseResults to national database– Other techniques as appropriateOther techniques as appropriate
Done at RCMDone at RCM
Laboratory notification Laboratory notification
HPAHPA– Via CoSurv from laboratory that identifies a Via CoSurv from laboratory that identifies a
positive culturepositive culture– Confirmation of positive from RCM within 24h Confirmation of positive from RCM within 24h
(1 working day) of receipt(1 working day) of receipt– RCM reports culture and susceptibility results RCM reports culture and susceptibility results
to MycobNET within 24h of report to clinicianto MycobNET within 24h of report to clinician
PCR detection of MtbPCR detection of Mtb
Not routineNot routine
Available from RCM for particular samplesAvailable from RCM for particular samples– High suspicionHigh suspicion– Definitive diagnosis deemed to be urgentDefinitive diagnosis deemed to be urgent– Liaise in advance – Consultany Microbiologist Liaise in advance – Consultany Microbiologist
to RCM to RCM
Immunodiagnostic testsImmunodiagnostic tests
Interferon Interferon γγ (QuantiFERON-TB Gold) (QuantiFERON-TB Gold)
Activated specific T-cells (T-SPOT.Activated specific T-cells (T-SPOT.TBTB))
– Standard under developmentStandard under developmentWhich patients?Which patients?
How long should it take?How long should it take?
Who provides it?Who provides it?
What do the results mean and who interprets What do the results mean and who interprets them?them?
HistopathologyHistopathology
Report within 3 days of receiptReport within 3 days of receipt
Inform the Microbiology service Inform the Microbiology service – Ensure same reporting as for positive Ensure same reporting as for positive
microscopy and culture resultsmicroscopy and culture results
Send autopsy samples to Microbiology Send autopsy samples to Microbiology without formalinwithout formalin!!!!
[Role of PCR to be determined][Role of PCR to be determined]
Implementation of standardsImplementation of standards
Local responsibilityLocal responsibility– What is done where?What is done where?
Microscopy; culture; identificationMicroscopy; culture; identification
– What throughput is needed?What throughput is needed?– Equipment – cost-effectivenessEquipment – cost-effectiveness– Personnel Personnel
Maintain skills; CPD; peer reviewMaintain skills; CPD; peer reviewNamed individuals for adviceNamed individuals for adviceBack-up and coverBack-up and cover
– IQC, EQAIQC, EQA