National Mycobacterium Reference Service-South (NMRS-South)
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1 Public Health England National Infection Service National Mycobacterium Reference Service-South (NMRS-South) user handbook
Transcript of National Mycobacterium Reference Service-South (NMRS-South)
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Public Health England National Infection Service
National Mycobacterium Reference Service-South (NMRS-South) user handbook
National Mycobacterium Reference Service-South user manual
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Contents Introduction .................................................................................................................................. 3
Delivery address .......................................................................................................................... 5
Personnel and contact details ...................................................................................................... 6
Summary of NMRS-South services ............................................................................................. 7
NMRS-South services and turnaround times ............................................................................... 8
Key factors affecting specimen performance ............................................................................. 11
Primary service .......................................................................................................................... 12
Specimen requirements for microscopy and culture ............................................................... 12
Fastrack service ......................................................................................................................... 14
Interferon gamma release assay ............................................................................................ 15
Referral of specimens or cultures .............................................................................................. 17
Requesting additional tests ........................................................................................................ 17
Fastrack service ..................................................................................................................... 17
NMRS-South pricelist ............................................................................................................. 18
Specimen and sample submission guidelines ............................................................................ 19
Request forms to accompany specimens or cultures ............................................................. 19
Urgent specimens ................................................................................................................... 20
Guidance on packaging and transport ....................................................................................... 21
Further information ..................................................................................................................... 22
Important notes ...................................................................................................................... 24
Reports ...................................................................................................................................... 25
Quality assurance in the NMRS-South....................................................................................... 26
Tissue samples from deceased people ...................................................................................... 27
Compliance with the Human Tissue Act ................................................................................. 27
Complaints ............................................................................................................................. 27
PHE Reference Microbiology – recognition of Caldicott recommendations ............................... 28
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Introduction This user handbook is intended for use by referral laboratories to the unit. The National Mycobacterium Reference Service-South (NMRS-South) is an accredited constituent reference laboratory of the National Infection Service (NIS) of Public Health England (PHE). With its sister laboratory, the National Mycobacterium Reference Service – Central & North (NMRS-Central & North), based in Birmingham, it provides Mycobacterial Reference services to the NHS in England. NMRS works closely with Mycobacterial Reference services in the Devolved Administrations. The principal activities of the unit include: • provision of a Mycobacterial Reference Service utilising whole genome sequencing
(WGS) for identification of Mycobacterium sp isolates • prediction of drug susceptibility for M. tuberculosis and determination of relatedness
and investigation of outbreaks of M. tuberculosis Phenotypic drug susceptibility testing is carried out for selected M. tuberculosis and non-tuberculosis mycobacteria (NTM) isolates. Extended testing is carried out for M. tuberculosis complex isolates with resistance to first-line agents. The laboratory also offers a primary isolation service, including microscopy and culture, and a Fasttrack (PCR) Service for detection of M. tuberculosis complex and rifampicin resistance. Interferon Gamma Release Assays for detection of latent infection and diagnosis are also carried out. The NMRS-South provides information and advice to clinical and public health teams, assisting in the identification and investigation of TB transmission and actively supporting outbreak investigation and surveillance activity within the UK. Since January 2018 the NMRS-South has utilised WGS for the identification of all mycobacterial isolates and detection of resistance for Mycobacterium tuberculosis. The laboratory no longer provides MIRU VNTR typing as WGS provides improved discrimination based on single nucleotide polymorphism (SNP) differences between all sequenced isolates. By implementing WGS within a single management structure across both laboratories in the NMRS for England the new service improves the diagnosis, treatment and public health management of TB and plays a significant role in delivering England’s TB strategy. The NMRS-South understands that it may take some time for users to establish familiarity with report formats. Clinical and scientific support is always available from the NMRS-South to guide users through the change to WGS.
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The WGS service includes identification of mycobacterial cultures, sensitivity or resistance prediction and determination of relatedness between M.tuberculosis complex isolates (typing). Identification of NTM continues to be a core part of our service. In response to recent recommendations (2015 TB services review, BTS NTM treatment guidelines, NICE guidance for management of cystic fibrosis), we are working to standardise our testing methods and costs across the service, including drug susceptibility testing. We are monitoring turnaround times as part of the service, aiming to report full WGS results within 7 working days of the receipt of pure positive cultures. The unit is a World Health Organization (WHO) Supranational Reference Laboratory for M. tuberculosis DST. Together with centres in Germany, Sweden and Belgium, it co-ordinates External Quality Assurance (EQA) for DST across the EU and non-EU states in the WHO Euro region. It is also a member of the WHO Global Laboratory Initiative involved with the development of WHO/IUATLD strategies for management of mycobacterial diseases and participates in international EQA schemes receiving samples and dispatching to designated regions. The NMRS-South, with the ECDC, co-ordinates the European Reference Laboratory Network for tuberculosis. Ownership and accountability of the user manual lies with the Laboratory Manager and the Clinical Lead for the NMRS-South.
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Delivery address Address Public Health England National Mycobacterium Reference Service-South National Infection Service 61 Colindale Avenue London NW9 5HT DX Address PHE Colindale NMRS-South DX 6530016 COLINDALE NW Phone +44 (0)20 832 76957 Email [email protected] [email protected] Web National mycobacterium reference service- South (NMRS-South) Hours of service Services will be provided from 9am to 5pm, Monday to Friday (excluding Bank holidays). Establishment of service agreement Each request referred from a stakeholder to the laboratory for testing is considered to be an agreement under PHE’s terms and conditions of business.
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Personnel and contact details Email Telephone
General or clinical enquiries
[email protected] [email protected]
020 8327 6957 020 8327 7708
Name Email Telephone
Clinical Lead Dr David Wyllie [email protected] 020 8327 7708
Laboratory Manager
Mrs Norah Easy [email protected] 020 8327 7708
Clinical Scientist Dr Simon Warwick [email protected] 020 8327 7596
Safety Officer Mrs Melanie Kemp [email protected] 020 8327 7708
Quality Manager Mrs Sangita Sapkota Mrs Lucy Taylor (maternity leave)
[email protected] [email protected]
020 8327 7708
Training Officer Ms Sharmila Naidoo
[email protected] 020 8327 7708
General results enquiries are initially addressed by our administrative staff, who will direct clinical and technical enquiries to the appropriate staff. There is daily cover for clinical and technical issues. Complex cases are discussed further internally and the advice given will often be a product of this discussion, not just the opinion of the person answering the telephone call. We record the advice given for continuity and must know the identity of both the patient and the caller.
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Summary of NMRS-South services • Identification of Mycobacterium spp. Isolates – WGS based identification service from
liquid or solid culture media provided free to the NHS • Drug susceptibility testing and genotypic resistance prediction for M. tuberculosis
complex – Genotypic drug susceptibility predictions are made for all isolates. Routine phenotypic susceptibility testing for first line agents (isoniazid / rifampicin / pyrazinamide / ethambutol) is no longer performed. If WGS predicts resistance or if WGS data is not sufficiently clear to accurately make a prediction, phenotypic testing of first line agents will be performed. Testing for second and third line agents will be performed for multi-drug resistant isolates when clinically indicated
• Drug susceptibility testing for Non-Tuberculous Mycobacteria (NTM) – phenotypic culture and microtiter plate based testing for clinically significant NTM isolates
• Determination of M. tuberculosis isolate relatedness – based on SNP differences determined by WGS, provided free to the NHS and for the support of outbreak investigations, detection of laboratory cross-contamination events and so on
• Interferon gamma release assay – latent TB infection diagnosis • Primary isolation service, including microscopy and culture • Fastrack (PCR) service – molecular detection of M. tuberculosis complex and
rifampicin resistance or multi or extensive drug resistance in primary specimens only • Scientific and technical advice • Clinical advice for case and outbreak investigation and management • Archived collection of mycobacterium isolates for epidemiological analysis • Training • Research and development Further information about services or matters of interest.
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NMRS-South services and turnaround times All turnaround times are dependent upon the receipt of a pure culture containing sufficient bacteria for analysis. We will attempt to purify contaminated cultures where possible. Reference service test repertoire and turnaround times Reference service Description Turnaround time
WGS-based identification of AFB Positive Cultures and prediction of sensitivities
DNA sequencing is performed for species identification and prediction of sensitivities: WGS Isoniazid WGS Rifampicin WGS Ethambutol WGS Pyrazinamide WGS Quinolone group WGS Streptomycin WGS Aminoglycosides group
Only cultures received by 9:30am are processed the same day. All other cultures are processed the following day Reported within 7 working days of culture receipt
Phenotypic M. tuberculosis susceptibility
First Line Antibiotics
Isoniazid, Rifampicin, Ethambutol, Pyrazinamide – not performed routinely. See ‘Summary of NMRS-South Services’
Reported within 40 working days of culture receipt
Reserve Antibiotics Moxifloxacin, Levofloxacin, Amikacin, Kanamycin, Prothionamide, Capreomycin, Linezolid
Reported within 40 working days of request for reserve sensitivities, identification of rifampicin resistance or MDRTB in referred cultures
Additional Antibiotics PAS Reported within 40 working days of request for these sensitivities or identification of XDRTB
Non-Tuberculous Mycobacteria (NTM) susceptibility
Rapid growers
Amikacin, Tobramycin, Cefoxitin, Co-trimoxazole, Clarithromycin, Linezolid, Ciprofloxacin, Moxifloxacin, Doxycyline
Reported within 35 working days of culture receipt
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Reference service Description Turnaround time
Slow growers M. kansasii and M. szulgai
Rifampicin, Clarithromycin, Ethambutol
Reported within 40 working days of culture receipt
Slow growers M.avium-intracellulare complex spp. (MAC)
Clarithromycin Amikacin Linezolid Moxifloxacin.
Reported within 40 working days of culture receipt
Other slow-growing species
Clarithromycin only Reported within 40 working days of culture receipt
* Testing of further agents can be performed if clinically indicated – please contact the NMRS-South to discuss individual cases
Primary service test repertoire and turnaround times Primary service Turnaround time
Fluorescence microscopy on clinical samples
Reported within one working day of specimen receipt
Culture of clinical samples (including blood and bone marrow) on liquid and solid media
Final negative result reported after 30 working days (6 weeks) (or 40 working days [8 weeks] for blood and CSF samples) Note: Cultures that are negative at 6 or 8 weeks which were positive on either FastTrack or microscopy are incubated further for a total of 12 weeks. A report is only issued if the culture subsequently becomes positive. A further incubation comment is also added to the report for such cases.
PCR service for clinical samples Rapid detection of M. tuberculosis complex and Rifampicin resistance in pulmonary and CSF samples
Clinical Samples received by 9:30 am are analysed on the same day and results communicated to the sending laboratory within one working day. Note: A minimum CSF (NOT supernatant) volume of 0.5 ml is required for Fastrack.
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Primary service Turnaround time
If culture is specifically requested, we will also culture the residual material but the minimum volume required would be >0.5 ml, The chances of obtaining a positive smear and culture result are increased when a large volume of CSF is submitted for examination.
Detection of M. tuberculosis complex and rifampicin resistance in non-pulmonary samples
Clinical samples received before 9:30am Wednesday, results communicated to sending laboratory by end of day Friday. Note: For paraffin wax embedded samples the whole wax block must be sent. Wax shavings or shaved sections are not accepted. The block MUST always be submitted with a diagram or slide indicating the area where AFB/granuloma were see otherwise the sample will not be processed. If no diagram or slide is received within 2 weeks following initial communication, the block will be sent back to the referring laboratory.
Interferon gamma release assay Quantiferon assay
Reports sent out within 10 working days of sample receipt.
Advisory service Clinical and technical advice
Available Monday to Friday 9am to 5pm.
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Key factors affecting specimen performance The NMRS-South will endeavour to process all samples received irrespective of any delay between sample collection and arrival at the NMRS-South. However, test performance, particularly of primary culture, may well be reduced by significant delays following sample collection, and we recommend that service users make transport arrangements that minimise such delays. Note: If a specimen is submitted to NMRS-South for an investigation that we do not offer we will temporarily archive the sample or isolate and issue a report to the sender explaining the reasons for the sample’s rejection. The specimen will then be sent back to the referring laboratory or referred on, if within PHE Colindale. Reference service for positive mycobacterial cultures (identification, drug resistance testing and genomic relatedness for TB) Turnaround times for bacterial identification and drug susceptibility tests are dependent upon the receipt of viable, pure cultures. Cultures that are no longer viable will necessitate the sending of a second isolate, thus significantly increasing turnaround time. Mixed or contaminated cultures in which AFB has been seen require purification and subculture to obtain final results. The NMRS-South will undertake such processes whenever possible rather than rejecting contaminated cultures. However, this will again result in a significantly increased turnaround time. If no AFB can been seen in the submitted culture whether contaminated or not, no further work will be carried out. Submitting a second pure culture will often allow final results to be obtained more quickly and we always recommend that a second sample is sent when the first is mixed or contaminated. If an aliquot of a liquid culture is to be sent then a minimum volume of a 3 ml smear positive sample is required. Transfer 3 ml of deposit from a settled positive sample to a sterile non-glass leak proof universal for transport, and store the rest of the sample at your laboratory. If a volume of between 2 to 3ml is received the NMRS-South will attempt WGS but there will be insufficient sample volume to perform any required phenotypic testing – for this reason we strongly advise referring laboratories to send at least 3ml. Samples of less than 2ml will be not be processed. Solid cultures can be submitted when there is visible growth on the slope. Note: Leaking cultures will not be processed and a report will be issued informing the user of this. Note: Please do not submit culture plates. These will be not be processed and a report will be issued informing the user of this. Please do not submit MGIT tubes.
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Primary service Though the NMRS-South will not reject samples that are subject to significant delay between collection and receipt, clinical specimens submitted for culture should be as fresh as possible. We strongly recommend that specimens are refrigerated if any delays in submission to the NMRS-South are likely. Do not add diluent to specimens.
Specimen requirements for microscopy and culture Sample type Sample volume / sample
container Comments and special precautions
Respiratory specimens
Sputum Three samples of ≥ 5 ml. CE Marked leak proof non-glass container without preservatives.
Three samples should be collected approximately 8 to 24 hours apart with at least one from early morning shortly after waking.
Bronchial Alveolar Lavage (BAL)/ bronchial washings
>5 ml CE Marked leak proof non-glass container without preservatives.
Contamination of the bronchoscope with tap water, which may contain environmental Mycobacterium spp, should be avoided.
Sterile specimens
CSF, pleural fluid, aspirates effusions, other sterile fluids
As large a volume as can be sent, ideally at least 6ml. CE Marked leak proof non-glass container without preservatives. Submit CSF samples in a sterile 60 ml container, where possible.
Collect aseptically.
Blood And bone marrow A minimum volume of 3 ml for culture should be sent in a vacutainer containing lithium-heparin or sodium citrate NOT EDTA (Mycobacterial survival is lower in EDTA tubes).
Direct microscopy is not performed. EDTA, even in trace amounts, inhibits the growth of some Mycobacterium spp and so is not acceptable.
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Sample type Sample volume / sample container
Comments and special precautions
Skin, bone and tissue, including post mortem samples
As much as possible. CE Marked leak proof non-glass container without preservatives.
Collect aseptically. Sterile distilled water can be added to prevent desiccation. A caseous portion should be selected if possible. Tissue biopsy specimens received in formalin are unacceptable for culture.
Endobronchial Ultrasound Bronchoscopy (EBUS)
As much as possible. CE Marked leak proof non-glass container without preservatives.
Other specimens
Urine Early Morning Urines (EMU) are preferable. CE marked leak proof container that does not contain boric acid.
Direct microscopy is not performed. Should be collected in the early morning on 3 consecutive days in a CE marked leak proof container that does not contain boric acid. If there are no appropriate containers for a whole EMU sample, a midstream EMU sample is an acceptable, but not ideal, alternative.
Faeces Maximum of 20 ml in a single container. CE Marked leak proof non-glass container without preservatives.
Direct microscopy is not performed.
Gastric aspirates >5 ml CE marked leak proof non-glass container without preservatives.
Collect samples early in the morning (before breakfast) on 3 consecutive days. Aspirates should be promptly delivered and processed to avoid acidic deterioration of organisms.
Pus or pus swabs As much as possible. Pus - CE marked leak proof non-glass container without preservatives.
Collect aseptically. Pus is the sample type of choice. Swabs are less preferable.
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Sample type Sample volume / sample container
Comments and special precautions
Specimens of non-human origin
If you wish to send samples of non-human origin please contact the NMRS-South before sending.
Fastrack service This service offers rapid molecular detection of Mycobacterium tuberculosis complex and rifampicin resistance from primary specimens. If testing is required, please ensure that a decontaminated respiratory sample is sent and received at the NMRS-South by 9:30am on Wednesday for it to be included in that weeks testing, as this test is only performed once a week. Ideal specimens are smear positive primary respiratory specimens as these have the highest load of acid fast bacilli (AFBs). The assay sensitivity in smear-negative specimens is significantly lower due to the lower bacillary load. Sensitivity is lower again for fluid specimens, such as CSF, pleural fluid and ascitic fluid. The minimum volume of CSF (NOT supernatant) that can be examined is 0.5ml. The minimum volume of others fluids required is 1.0ml - however submitting the largest possible volume of CSF and other fluids will increase the sensitivity, with a volume of at least 6ml being ideal. For respiratory specimens at least 1ml of sample is required. For paraffin wax embedded samples, the whole wax block must be sent – wax shavings or shaved sections will not be accepted. The block MUST always be submitted with a diagram or slide indicating the area where AFB/granuloma were seen otherwise the sample will not be processed. If no diagram or slide is received, the NMRS-South will contact the sending laboratory by telephone to communicate this information and if they have not been received within 2 weeks the block will be sent back to the referring laboratory and a comment will be added to the report. If random sampling of the block is to be undertaken, please ensure that this is clearly stated on the request form to avoid a delay in testing. Please note that random sampling is not advised and results of such testing should be treated with caution. Wax blocks will also be returned to the referring laboratory on completion of the test. Please note that lysed blood, heavily bloodstained samples or pus-containing samples can interfere with PCR based reactions. DNA in specimens requesting molecular tests may degrade if stored for too long before referral.
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We also offer PCR-based testing for detection of resistance to isoniazid, quinolones and aminoglycosides in primary samples under certain circumstances. Please contact the NMRS-South clinicians to discuss cases where you feel this may be required. If the sample is received and requires decontamination, this will delay PCR testing and will not be tested until the following week. If resistance to isoniazid, quinolones and aminglyocsides is detected the specimen will also be cultured on solid and liquid media if this was not requested originally.
Interferon gamma release assay Blood should be collected in the tubes provided (following the provided instructions) and MUST be incubated within 16 hours of collection at 37°C for 16 to 24 hours, before sending. Samples must reach NMRS-South within 72 hours post incubation. • More information on the Interferon gamma release assay (IGRA) • Guidelines for QuantiFERON®-TB Gold Plus Blood Collection, Handling and
Transportation • QuantiFERON®-TB Gold Plus Blood Collection Tube Order Form Test reports are issued with the following comments to allow interpretation of the result. Positive Latent TB Infection QuantiFERON-TB Gold Plus Results: Positive The result of the test is that this patient is POSITIVE for infection with Mycobacterium tuberculosis as determined using the guidelines laid down by the kit manufacturer (Qiagen). The magnitude of the measured IFN-gamma level cannot be correlated to stage or degree of infection, level of immune responsiveness, or likelihood for progression to active disease. A positive QuantiFERON-TB Gold Plus result does not necessarily indicate the presence of active tuberculosis disease, but may do so in the appropriate context and appropriate symptoms. Negative Latent TB Infection QuantiFERON-TB Gold Plus Results: Negative The result of the test is that this patient is NEGATIVE for infection with Mycobacterium tuberculosis as determined using the guidelines laid down by the kit manufacturer (Qiagen). A negative QuantiFERON-TB Gold Plus result does not necessarily exclude the presence of active tuberculosis disease. Indeterminate Latent TB Infection QuantiFERON-TB Gold Plus Results: Indeterminate The result of the test is that this patient is INDETERMINATE for infection with Mycobacterium tuberculosis as determined using the guidelines laid down by the kit manufacturer (Qiagen). An indeterminate result can be as a consequence of impaired
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immune status. An Indeterminate QuantiFERON-TB Gold Plus result does not exclude the presence of active disease or latent TB infection. In addition we have introduced an additional category for indeterminate (uncertainty of measurement), which we will be using where applicable. Indeterminate (within uncertainty of measurements) Latent TB Infection QuantiFERON-TB Gold Plus Results: Indeterminate (within uncertainty of measurement) The result of the test is that this patient is INDETERMINATE (within equivocal range) for infection by Mycobacterium tuberculosis meaning that it falls very close to the cut-off value so we can’t be certain it is a true result. An Indeterminate QuantiFERON-TB Gold Plus result does not exclude the presence of active disease or latent TB infection. We recommend that you send another specimen for testing.
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Referral of specimens or cultures No specimens or cultures are referred by the NMRS-South to other laboratories. In exceptional circumstances, the NMRS-S Business Continuity Plan (BCP) may be invoked and samples will need to be referred to another laboratory. Should this occur, the work shall be placed with a competent laboratory which complies with ISO15189:2012 or other accreditation Standard as appropriate and NMRS-S will request assuarance from the referral loaboraotry about quality assurance practices for monitoring purposes. If other investigations are required at another laboratory then it is strongly recommended that a further specimen or culture is sent directly to that laboratory.
Requesting additional tests Fastrack service Additional requests for Primary Fastrack testing MUST be accompanied by a downloadable Fastrack request form (N2). Requests can be processed, on receipt of sufficient and suitable material, within the time periods specified below: 1. CSF samples: within 1 day of specimen receipt 2. Sterile samples (except CSF): within 2 weeks of specimen receipt 3. Smear negative sputum: within 1 day of specimen receipt 4. Smear positive sputum: up to 1 week of specimen receipt M. tuberculosis susceptibility testing All first isolates of M. tuberculosis have resistance prediction by WGS. Phenotypic susceptibility testing is only performed for first line agents if WGS predicts resistance or is fails to make a prediction. All new Multi-Drug Resistant isolates (MDRs) are processed for phenotypic reserve drug susceptibility testing. Repeat phenotypic testing will only be performed on isolates received more than 2 months after previous testing. Additional susceptibility testing on M. tuberculosis isolates MUST be discussed with the NMRS-South before requests are submitted. Appropriate additional susceptibility testing requests can be processed up to 6 weeks following receipt of culture. Non-tuberculous mycobacteria (NTM) susceptibility testing NTM isolates will be set up for an appropriate panel of phenotypic testing depending on the species based on the organism identification and the patient’s clinical status. Full and accurate completion of the request form aids in this process.
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Additional susceptibility testing on NTM isolates MUST be discussed with the NMRS-South before requests are submitted. All sterile site and non pulmonary site samples requesting NTM sensitivities will receive sensitivities. Appropriate additional NTM susceptibility testing requests can be processed up to 6 weeks after culture receipt.
NMRS-South pricelist For the NMRS-South pricelist, please contact the laboratory using the general enquiries contact details.
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Specimen and sample submission guidelines Specimens must be labelled with the following: 1. Surname or forename, or other unique patient identifier 2. Sender’s sample number or reference number 3. Date of birth Request forms must match the corresponding specimen and include the above information on the sample as well as details listed below. The name and contact information of the requester (a telephone number is vital for urgent requests) should also be included. 1. Tests required 2. Sample type 3. Specimen or isolation site 4. Date of dispatch 5. NHS number 6. Sex 7. Date and time of collection of specimen 8. Relevant clinical information 9. Reference number
Request forms to accompany specimens or cultures There are 3 NMRS-South request forms: 1. Mycobacterium Referral Form (primary samples and positive cultures) (N1) 2. Fastrack Request Form (N2) 3. QuantiFERON®-TB Gold PLUS test (N4) Download NMRS-South request forms. Please order pre-labelled request forms with your requestor code and address from the PHE LIMS department via e-mail – [email protected] – as this will reduce clerical errors. Please ensure the appropriate NMRS-South request from is fully completed for the sample being submitted with the required information as stated above, as well as the correct telephone number, particularly for Primary Fastrack requests.
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Each sample must be accompanied by an individual request form, even if more than one sample is submitted from the same patient. The PHE NMRS-South laboratory advises users that, where forms are poorly completed, the user will be charged. Please state clinical details when they are provided. Wherever possible the NMRS-South supports its users by not rejecting referred specimens and cultures. The space marked ‘For NMRS-South Use Only’ is intended for use by NMRS-South staff. Please do not write in this space. You can view a series of videos on various aspects of the work of NMRS-South online. These include videos about: • Filling out request forms • How does WGS identify mycobacteria? • How does WGS predict drug susceptibility? • Interpreting NMRS reports Mycobacterium tuberculosis • Phenotypic susceptibility testing for Mycobacterium tuberculosis • Unable to speciate mycobacterium – what happens next • What happens to my sample – the NMRS workflow • What is whole genome sequencing
Urgent specimens If a reference service is required urgently, please contact the NMRS-South to discuss prior to dispatch. Always mark urgent requests as ‘URGENT’ clearly on the request form.
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Guidance on packaging and transport A small but significant proportion of samples received by the PHE National Infection Services are poorly or inappropriately packaged. This often leads to samples leaking or being damaged during transport, therefore posing a serious risk to PHE staff handling them. PHE hopes to eliminate this risk by helping laboratories to understand basic packaging requirements. The following guidelines are intended to cover the transport of clinical samples from humans, or cultures of micro-organisms isolated from such samples to another laboratory for diagnostic or other clinical testing within the UK where the micro-organisms suspected of causing the disease are all either hazard groups 2, 3 or 4. The terms Category A and Category B are limited to classifying samples or microbial cultures being transported to another laboratory. These guidelines are not intended as a substitute for reading the advice provided by Department for Transport and Department of Health.
Sample description Packaging requirement
Category A samples are known or suspected to contain a microbial agent with the following definition: ‘an infectious substance which is transported in a form that if exposure to it occurs, is capable of causing permanent disability, life-threatening or fatal disease to humans or animals.’ See indicative list. The majority are Hazard Group 3 or 4.
Assign to UN2814 (Humans) Packaging Instructions PI620 Supporting documentation as per ADR. Transport as category A ADR licensed courier.
For practical reasons, to allow referral or reference services to continue, a limited number of Category A agents have been exempted from being transported as Category A. These are Vero-cytotoxin-producing Escherichia coli (VTEC), Mycobacterium tuberculosis and Shigella dysenteriae 1.
Assign UN3373 Packaging instruction PI650. Send by courier. Royal Mail will NOT accept.
Category B samples are those that do not meet the definitions of Category A.
Assign UN3373 Packaging instruction P1650. Send by Post or courier Royal Mail WILL accept.
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Further information More information can be found on the following webpages: • Shipping dangerous goods • Transporting dangerous goods • Guidance on regulations for the Transport of Infectious Substances 2013 to 2014 • International Civil Aviation Organization • The United Nations Economic Commission for Europe Reporting incidents during transportation that may affect the safety of personnel The NMRS-South will report any leaking containers and improperly packaged parcels to users. Leaking cultures will not be processed by the NMRS-South. Users will be informed and a repeat sample requested. Repeated offences will be referred to the PHE Safety Committee who may refer to the Health and Safety Executive. Label the specimen or culture bottle with the name of the patient (or unique identifier) and the laboratory number. All specimens or cultures sent to the NMRS-South must be packed in accordance with IATA regulations 650/602. Do not submit positve cultures on agar plates. These will be discarded and not processed. Specimens may be sent by Royal Mail or courier We recommend that to minimise delays specimens, especially those sent for our Fastrack molecular diagnostic service, are sent by routine courier, for example DX or other specialised courier. Please ensure that the courier is able to reach the NMRS-South before 5:00pm. Cultures can only be sent by courier The NMRS-South will endeavour to process primary material if leakage occurs. However, this is likely to compromise the chance of successful culture and we will request the user to send us an additional specimen.
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Packaging The packaging should consist of 4 components (see diagram below): 1. a leak-proof primary receptacle(s) 2. a polythene bag containing absorbent material 3. a leak-proof secondary packaging 4. an outer packaging of adequate strength
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Important notes For liquids, each leak-proof primary receptacle should be wrapped in absorbent material – sufficient to absorb all contents of the sample – and placed inside a polythene bag. One sample per bag. The use of parafilm is not recommended. The bagged samples may then be placed together inside a rigid, leak-proof plastic container. This rigid leak-proof plastic container should be placed inside a fibreboard box or approved DX plastic outer packaging. This outer packaging should be of sufficient size for its capacity, mass and intended use, and with at least one surface having minimum dimensions of 100 mm × 100 mm. Any documentation must be placed between the secondary container and the outer packaging. Please DO NOT place it inside the plastic container.
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Reports The NMRS-South issues ‘acknowledgement of receipt’ reports on the date of receipt of the samples. NMRS-South reports are routinely sent out via PHE-eLab. Printed reports will only be sent out if the referring laboratory is not registered to PHE-eLab. For details on how to register for E-lab and further information, please email: [email protected] Users can access archived reports on PHE-eLab using the search function for up to 2 years. It is our policy that reports containing patient data should not be sent by routine email. Emails cannot be relied on to guarantee security of patient data because they can be intercepted by a third party en route (unless encrypted).
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Quality assurance in the NMRS-South The NMRS-South is accredited in accordance with International Standard ISO15189:2012 – Medical Laboratories with Laboratory No.10080. All tests are in scope, with the exception of Whole Genome Sequencing, processing of wax blocks for Fastrack analysis and all test procedures associated with animal samples. ISO15189:2012 Medical Laboratories credential for NMRS-South Laboratory No.10080 The NMRS-South is seeking accreditation for the extraction and reporting of samples for Whole Genome Sequencing. The NMRS-South participates in numerous EQA schemes, including those run by the UK National External Quality Assurance Scheme (NEQAS), the World Health Organization (WHO), and the European Centre for Disease Prevention and Control (ECDC). The quality of our systems is also checked by our Internal Quality Assurance (IQA) schemes, which requires selection of referred samples for ‘blinded’ testing at a later date. After processing, the results for IQA samples are ‘unblinded’ and are assessed against the results originally reported to the sending laboratory. Any discrepancies are fully investigated as to their root cause before remedial action is implemented. Performance of IGRA is additionally monitored using Internal Quality Control specimens and Westgard rules. Any discrepancies leading from EQA or IQA are fully investigated as to their root cause before corrective action is implemented. Results of our EQA and IQA performance are discussed at departmental meetings, as appropriate.
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Tissue samples from deceased people Compliance with the Human Tissue Act PHE Microbiology Services is licensed by the Human Tissue Authority (HTA) (Licence number 12459) to store tissues from deceased people for scheduled purposes. Post mortem samples are submitted to PHE NIS by coroners or pathologists for examination to help them determine the cause of death. As part of our public health remit, we sometimes need to retain these samples for the purpose of public health monitoring, which is defined as a scheduled purpose within the Human Tissue Act 2004. Further analysis of these samples may help determine the cause of an outbreak due to an infectious disease or may allow identification of new strains of infectious agents at a later date. Obtaining consent to remove, store and use human tissues for a scheduled purpose is one of the underlying principles of the Human Tissue Act. PHE Microbiology Services receives post-mortem samples from Coroners’ post-mortems or from NHS establishments across the UK and therefore we are not in a position to either seek consent ourselves or have arrangements in place to confirm that the requirements of the Act have been complied with by the sender. We ask coroners and pathologists who send post mortem samples to PHE Microbiology Services to provide us with details of consent, and would also ask that consent includes retention of the samples for the purpose of public health monitoring. When tissue samples from deceased people are received at the PHE Microbiology Services. they are retained securely and confidentiality is maintained in compliance with Caldicott principles as are all samples received at this centre. It is normal practice for tissue samples from the deceased to be disposed of in the same way that all other clinical samples we receive are disposed of. However, we will adhere to any specific requirements regarding disposal or returning tissue samples if requested by the sending coroner or pathologist.
Complaints Please refer complaints by post, email or telephone to the Clinical Lead or Laboratory Manager of the NMRS-South using the contact details provided above. The complaint will be answered within 14 days of being raised.
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PHE Reference Microbiology – recognition of Caldicott recommendations The recommendations of the Caldicott report (1997) and the subsequent Information Governance Review (2013) have been adopted by PHE and by the NIS as a whole. These recommendations relate to the security of Patient Identifiable Data (PID) and the uses to which they are put. NMRS-South observes Caldicott guidance in handling PID and has appointed its own Caldicott Guardian. The Caldicott Guardian advises the Clinical Lead of the NMRS-South and others on confidentiality issues and is responsible for monitoring the physical security of PID in all parts of the NMRS-South site. This also applies to the transfer of results of investigations to and from the site whether by mail services, electronically or by telephone. The value of 'safe haven' arrangements or other means by which the sender and receiver of information can identify themselves to each other before data is transferred is emphasised. See the Reports section of this user manual. The NMRS-South audits the security of its PID in collaboration with its customers. Customers are invited to review our arrangements in conjunction with individual laboratory directors and/or the Caldicott Guardian. Customers are also asked to draw to the Caldicott Guardian’s attention any instances where PID security has been threatened or has broken down. Any uses that PID are put to outside the clinical diagnostic services generally allow patient identifiers to have been removed beforehand, and when PID is used for research purposes the proposals are considered first by the appropriate Ethics Committee. All enquiries about the security and use of PID should be addressed to the Caldicott Guardian at: [email protected]
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Published: February 2021 PHE gateway number: GW-1742
Website: www.gov.uk/phe Twitter: @PHE_uk Facebook: www.facebook.com/PublicHealthEngland © Crown copyright 2021
Prepared by: Julie Johnson For queries relating to this document, please contact: [email protected]
