Version number CAT 2016/01

Transcription

1 Version number CAT 2016/01

2 Contents An Introduction to the QCMD EQA Schemes 4 Disease Groups Blood Borne Virus 5 Central Nervous System 5 Congenital Infections 6 Drug Resistance 6 Exotic/Emerging Diseases 7 Gastrointestinal Diseases 7 Immunocompromised Associated Diseases 8 Respiratory Diseases 8 Sexually Transmitted Infections 9 Transplant Associated Diseases 9 Typing 10 Viral EQA HIV-1 (RNA) 11 Hepatitis B virus 11 Hepatitis C virus 12 HIV-1 (DNA) 12 B19 virus 13 HCV Genotyping 13 HBV Genotyping 14 Varicella-Zoster virus 14 Enterovirus 15 Parechovirus 15 Herpes simplex virus 1 & 2 16 Cytomegalovirus Dried Blood Spots 16 West Nile virus 17 Dengue virus 17 JC virus 18 BK virus 18 Human Herpes virus 6 19 Human Cytomegalovirus 19 Cytomegalovirus Whole Blood 20 Epstein-Barr virus 20 Adenovirus 21 Influenza A & B virus 21 Human Metapneumovirus 22 Respiratory Syncytial virus 22 Parainfluenza virus 23 Coronavirus 23 Rhinovirus 24 Influenza Haemagglutinin Typing 24 Norovirus 25 Hepatitis A virus 25 Hepatitis E virus 26 Version number CAT2016/ Page

3 Contents HBV Drug Resistance 26 HIV-1 Drug Resistance 27 HIV-1 Drug Resistance (Integrase) 27 Human Papillomavirus 28 Bacterial EQA Chlamydia trachomatis 29 Neisseria gonorrhoeae 29 Chlamydophila pneumoniae & Mycoplasma pneumoniae 30 Legionella pneumophila 30 Methicillin Resistant S. aureus 31 Methicillin Resistant S. aureus Typing (epidemiology and outbreak studies) 31 M. tuberculosis 32 Clostridium difficile 32 Bordetella pertussis 33 Borrelia burgdorferi spp.(lyme Disease) 33 Fungal EQA Aspergillus spp. 34 Candida spp. 34 Pneumocystis jirovecii pneumonia (PCP) 35 Parasitic EQA Toxoplasma gondii 36 EQA Pilot Studies Epstein-Barr virus Whole Blood 37 CMV Drug Resistance 37 Chlamydia psittaci 38 HCV Drug Resistance 38 Hepatitis D virus 39 Measles / Mumps 39 Extended Spectrum β-lactamase and Carbapenemase 40 Vancomycin Resistant Enterococci 40 S. aureus SPA 41 Viral Gastroenteritis 41 Bacterial Gastroenteritis 42 Parasitic Gastroenteritis 42 MALDI-TOF Bacterial 43 Mycoplasma spp. (cell contamination) 44 Chikungunya virus 45 Sexually Transmitted Infections 45 Syphilis 46 Diarrheagenic Escherichia coli 46 MERS Coronavirus 47 Version number CAT2016/01 2

4 Contents Serology EQA Pilot Studies Serology Introduction 48 Blood borne virus serology 48 Viral hepatitis serology 49 Immune status serology 50 New Molecular EQA Pilot Studies for 2016 Respiratory Introduction 51 Respiratory I 51 Respiratory II 52 Enterovirus Typing 53 Herpes Simplex Virus Drug Resistance 54 Dermatophilosis 55 Helicobacter pylori 56 Bacterial Sepsis 57 Bacterial 16S Ribosomal RNA 58 Appendix Programmes in order of distribution 59 Version number CAT2016/01 3

5 An Introduction to the QCMD EQA Schemes The aim of QCMD's External Quality Assessment (EQA) programmes are to help monitor and improve laboratory quality by assessing a laboratory s use of molecular diagnostic technologies within the routine clinical setting. The EQA schemes are both educational and regulatory in application, support continuous quality improvement, as well as assist laboratory accreditation / certification to ISO15189 or equivalent. Who can participate? The QCMD EQA programmes are open to any clinical laboratory conducting molecular based tests for the routine diagnosis of infectious diseases. QCMD will undertake to provide the EQA service to any laboratory from any country who wishes to take part in an EQA programme. The QCMD EQA service is offered directly or through one of QCMD many regional QA collaborators. To register or find out more go to The EQA programme format All individual QCMD EQA programmes have their own design specifications which are defined and agreed annually by QCMD in conjunction with assigned scientific experts / expert groups. Each EQA programme consists of between 1 and 4 challenges (distributions) per year, with each challenge comprising 3-5 samples (panel members). For example, participating laboratories registering for the molecular quantitative EQA programmes for the Blood Borne Virus (BBV) pathogens such as HIV, HBV, and HCV can chose whether they want either 2 or 4 challenges per year depending upon their laboratories regulatory requirements. Whereas for other non-bbv quantitative EQA programmes including the transplantation pathogens such as CMV, EBV, etc participants will receive two challenges per year. In contrast, the respiratory and gastroenteritis EQA range will remain single challenges (distributions) per year. Pilot EQA programmes will also remain single challenges / distributions per year. The QCMD EQA programmes are provided in accordance with the QCMD Code of Practice and QCMD s accreditation to ISO17043:2010. For more details on the format of each of the EQA programmes see the individual EQA specifications within the catalogue or visit the QCMD website. QCMD EQA Reports & feedback After close of the EQA results return phase, EQA participants receive an individual report generated by the Neutral Office. Individual reports provide laboratories with an overview of their performance within an EQA challenge in relation to their method type, the technology group they are within and where appropriate the consensus from the overall participants within the EQA programme. On completion of the EQA programme, a supplementary or final report may be commissioned. The supplementary report will include any relevant additional information regarding the recent annual EQA distribution. The supplementary reports also include Scientific Expert commentary / feedback on the overall EQA results within that distribution. Where required, National EQA providers or country specific EQA groups are also provided with an additional country specific EQA report. Further information For further details register on line and visit your profile area, download the QCMD participant manual at Version number CAT2016/01 4

6 Disease Groups Blood Borne Virus The Blood-Borne Virus (BBV) group of QCMD External Quality Assessment (EQA) programmes consists of pathogens that are classically detected directly from the blood. This includes human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) B19 virus (B19V) and more recently Hepatitis A virus (HAV), Hepatitis E virus (HEV) and Hepatitis D virus (HDV). The BBV molecular quantitative EQA programmes for the pathogens HIV, HBV, and HCV consist of either 2 or 4 challenges per year, with each challenge comprising of 3-5 samples. The EQA genotyping and drug resistance programmes typically consist of 1 challenge per year and comprise between 5-12 coded samples, with different viral loads and genotypes, depending on the annual objectives of the individual BBV EQA programme. For the drug resistance BBV EQA programmes different current resistance markers are included and emphasis is placed on the determination and interpretation of these resistance markers. HIV-1 (RNA) Hepatitis B virus Hepatitis C virus HIV-1 (DNA) B19 virus HCV Genotyping HBV Genotyping Hepatitis A virus Hepatitis E virus HBV Drug Resistance HCV Drug Resistance Hepatitis D virus HIV-1 Drug Resistance HIV-1 Drug Resistance (Integrase) Central Nervous System Infections of the Central Nervous System (CNS) can occur indirectly via the blood following damage to the blood brain barrier or directly through intraneuronal routes. Encephalitis and meningitis are important CNS infections which can have viral, bacterial or parasitic origins. Viral encephalitis can occur as a result of acute infection or as the consequence of latent infection. Common viral causes include Herpes Simplex Virus (HSV), specific Enteroviruses (EV), JC and BK virus, as well as Varicella-Zoster Virus (VZV). Bacterial infections within the CNS such as meningitis can be a result of direct infection of the brain or may be due to underlying diseases which can lead to secondary CNS infection. Parasites such as Toxoplasma gondii can also cause CNS infections particularly in immunocompromised individuals. In recent years significant advances have been made in understanding CNS pathogenesis with the development of molecular technologies for the diagnosis and monitoring of disease, the introduction of effective treatment therapies and, in some cases, the development of vaccines (e.g. Japanese encephalitis & rabies). The range of QCMD EQA programmes within this area focus on pathogens known to play a significant clinical role in CNS infection. The general aim of this group of EQA programmes is to assess the laboratories ability in the detection and determination of the selected pathogen. Where appropriate pathogen load estimation is also evaluated. Varicella-Zoster virus Enterovirus Parechovirus Herpes simplex virus 1& 2 West Nile virus Dengue virus Chikungunya virus JC virus BK virus Toxoplasma gondii Measles / Mumps Herpes simplex virus drug resistance Borrelia burgdorferi spp. (Lyme Disease) Version number CAT2016/01 5

7 Disease Groups Congenital Infections The term congenital infection is used to describe those infections transmitted from mother to child either during pregnancy (Transplacental infection) or immediately after childbirth. They can be caused by viruses, bacteria and on occasion parasites. The ability of a particular pathogen to cross the placenta and infect the foetus /embryo is dependent on many factors including the mother s immune status. Primary infections during pregnancy can result in spontaneous abortion or major developmental disorders if undetected and left untreated. Cytomegalovirus Dried Blood Spots Toxoplasma gondii In recent years the diagnosis of congenital infections has been significantly improved by the ability to obtain clinical samples such as blood through chorionic villus sampling. In addition the application of molecular technologies has helped significantly in the diagnosis, monitoring, and treatment rationale. CMV Dried Blood Spots is one of the EQAs provided in this disease group. Drug Resistance The ability of microorganisms to adapt and develop resistance to antimicrobials is natural and an evolutionary trait they have been employing for thousands of years. Hence there are many examples of drug resistant strains in viral, bacterial and parasitic diseases. However it is well recognised that the over prescription of antimicrobials within clinical practice and their overuse in domestic products has helped to accelerate drug resistance, and led to the emergence of multidrug resistance. QCMD has established a range of Drug Resistance EQA programmes covering a variety of pathogen types. The primary aims of these programmes are to assess the laboratory in their ability to detect and determine the presence of drug resistance at the molecular level. In addition some of the programmes also cover drug resistance interpretation. Methicillin Resistant S. aureus CMV Drug Resistance HBV Drug Resistance HCV Drug Resistance Herpes simplex virus drug resistance HIV-1 Drug Resistance HIV-1 Drug Resistance (Integrase) Extended Spectrum β-lactamase and Carbapenemase Vancomycin Resistant Enterococci Version number CAT2016/01 6

8 Disease Groups Exotic/Emerging Diseases A complex relationship exists between the pathogen genetics, host and the environment. As a result predicting the future emergence of exotic diseases is difficult. However, globalisation coupled with rapid increases in human populations over the last 50 years has played an important role. Local environmental changes such as deforestation due to urbanisation bring humans into closer contact with potential new pathogen vectors. These factors disturb the subtle balance between pathogen, host and the environment and create the opportunity for the emergence of new disease pathogens or the re- emergence of existing pathogens. These diseases can be caused by newly identified pathogens, pathogen strains such as SARS or the mutation of existing strains such as Influenza virus. In addition, the spread of known pathogens (e.g. West Nile virus & Dengue virus) into new geographical areas leading to new potential endemics account for a large number of exotic / emerging diseases. The EQAs within this group focus on those emerging diseases that are frequently being identified within progressive geographic regions. West Nile virus Dengue virus Chikungunya virus MERS Coronavirus Gastrointestinal Diseases Gastroenteritis can be caused by a wide variety of bacteria, viruses and parasites. It is often associated with severe inflammation of the gastrointestinal tract involving both the stomach and small intestine. This results in acute diarrhoea and vomiting. Diagnosis is primarily based on clinical symptoms, but laboratory diagnosis on the etiological cause is often needed in order to support patient care. In recent years molecular diagnostic techniques such as real-time PCR have also been introduced for the laboratory diagnosis of gastroenteritis, including the ability to simultaneously screen for a wide range of enteric pathogens using multiplex assays. As a result, molecular diagnostic techniques are increasingly being used in the routine laboratory setting for detection, determination and surveillance of a wide range of enteric pathogens. Adenovirus Clostridium difficile Norovirus Viral Gastroenteritis Bacterial Gastroenteritis Parasitic Gastroenteritis Diarrheagenic Escherichia Coli Helicobacter pylori The general aim of this group of EQA programmes is to allow laboratories to assess their ability in the use of molecular diagnostic tests for a range of viral, bacterial and parasitic enteric pathogens. Version number CAT2016/01 7

9 Disease Groups Immunocompromised Associated Diseases The treatment and management of patients with compromised immune systems has seen important developments in recent years with, for example, the introduction of novel multi-drug treatment regimes. As a result the healthcare and management of immunocompromised patients has greatly improved. However, pathogen infection or viral reactivation remain significant contributors to morbidity and mortality in these patients. A number of opportunistic parasitic, fungal and viral pathogens are of concern in the management of immunocompromised patients due to both acute infection and reactivation of latent virus in the immunocompromised host. Advances in molecular diagnostics have allowed accurate pathogen assessment and quantitative monitoring, particularly of viral activity over time, which allows early and accurate pre-emptive intervention and management of antiviral drug therapy. JC virus BK virus Human Herpes virus 6 Human Cytomegalovirus Cytomegalovirus Whole Blood Epstein-Barr virus Epstein-Barr virus Whole Blood CMV Drug Resistance Toxoplasma gondii Aspergillus Candida spp. Pneumocystis jirovecii pneumonia (PCP) The range of QCMD EQA programmes within this area focus on pathogens known to play a significant clinical role in the management of immunocompromised patients. The general aim of this group of EQA programmes is to assess the ability of laboratories in the detection of the selected pathogen and where appropriate quantitative estimation is also evaluated. Respiratory Diseases Respiratory tract infections (RTIs) are common conditions, experienced by most adults and children each year. They can affect both the upper and lower respiratory tract and range from the common cold to viral and bacterial pneumonia. For the young, the elderly and the immune compromised, RTIs can be a significant health threat if not managed effectively. RTIs can be caused by a large number of bacterial, viral and fungal pathogens which have nearly indistinguishable physiological symptoms. This can increase the chances of undiagnosed or misdiagnosed infections leading to patients either not receiving critical medications, or receiving unnecessary antibiotics. The advance of molecular diagnostic techniques has improved our ability to rapidly determine the causative agents of RTIs and has the potential to improve patient management, control of nosocomial transmission and promote targeted therapy. The Respiratory EQA programmes cover 15 of the major viral, bacterial and fungal causes of RTIs, focusing on the pathogen load and allowing assessment of the laboratories ability to accurately identify the species of interest at clinically relevant levels. Chlamydophila pneumoniae and Mycoplasma pneumoniae Legionella pneumophila Adenovirus M. tuberculosis Bordetella pertussis Influenza A & B virus Human Metapneumovirus Respiratory Syncytial virus Parainfluenza virus Coronavirus MERS Coronavirus Rhinovirus Influenza Haemagglutinin Typing Chlamydophila psittaci Respiratory I Respiratory II Measles / Mumps Pneumocystis jirovecii pneumonia (PCP) Version number CAT2016/01 8

10 Disease Groups Sexually Transmitted Infections Sexually transmitted infections (STIs) remain a major public health concern throughout the world with some infections reaching epidemic proportions in sexually active groups. As a result a number of WHO and UN global strategies have been initiated in an attempt to control the spread of STIs. STIs are the main preventable cause of infertility, particularly in women. However some STIs remain asymptomatic before leading to serious reproductive complications and congenital infections, therefore appropriate diagnosis and treatment is essential. Chlamydia trachomatis Neisseria gonorrhoeae Herpes simplex virus 1& 2 Herpes simplex virus drug resistance Human Papillomavirus Syphilis Sexually Transmitted Infections Molecular diagnostic assays allow the accurate assessment of STIs in patients that present with similar symptoms or asymptomatic persons from at risk groups allowing early and accurate intervention and treatment. The range of QCMD EQA programmes within this area focus on pathogens known to be the most common cause of STIs. The general aim of this group of EQA programmes is to assess the ability of laboratories in the detection of the selected pathogen. Transplant Associated Diseases Advances in transplant medicine, including the development of immunosuppressive agents, has greatly improved the prospects of transplant recipients. However, pathogen infection and in particular viral reactivation remain significant contributors to transplant patient morbidity and mortality. A number of viruses are of particular concern, these include: human herpes virus 6 (HHV6), human cytomegalovirus (CMV) and Epstein-Barr virus (EBV) along with Human adenovirus (ADV) JC virus (JCV) and BK virus (BKV). Other opportunistic infections such as the parasite Toxoplasma gondii are also relevant. Advances in molecular diagnostics have allowed accurate pathogen assessment prior to transplant and accurate quantitative monitoring, particularly of viral activity over time, after the transplant has been performed. This in turn allows early and accurate pre-emptive intervention and antiviral drug therapy. JC virus BK virus Human Herpes virus 6 Human Cytomegalovirus Cytomegalovirus Whole Blood Epstein-Barr virus Epstein-Barr virus Whole Blood CMV Drug Resistance Adenovirus Toxoplasma gondii The range of QCMD EQA programmes within this area focus on those pathogens known to play a significant clinical role in transplant medicine. The general aim of this group of EQA programmes is to assess the ability of laboratories in the detection of the selected pathogen and where appropriate quantitative estimation is also evaluated. Version number CAT2016/01 9

11 Disease Groups Typing Advances in the treatment and management of patient infection have seen important developments in recent years. In particular the introduction of novel antiviral drug therapies has improved the medium and long term prospects of infected patients. However, the development of drug resistance pathogens is an increasing complication and remains a significant factor in the treatment of these patient groups. The use of genotyping and sequencing technologies has allowed accurate pathogen assessment and monitoring of patient samples over time. This allows early and accurate determination of pathogen status. Which in turn allows preemptive intervention and management of antiviral drug therapy. The range of QCMD EQA programmes within this area focus on pathogens known to play a significant clinical role in the management of infection. The general aim of this group of EQA programmes is to assess the ability of laboratories in the genetic determination of the selected pathogen and where appropriate the specific mutation points within the target gene. HCV Genotyping HBV Genotyping Enterovirus Typing Methicillin Resistant S. aureus Typing (epidemiology and outbreak studies) CMV Drug Resistance Influenza Haemagglutinin Typing HBV Drug Resistance HCV Drug Resistance Herpes simplex virus drug resistance HIV-1 Drug Resistance HIV-1 Drug Resistance (Integrase) S. aureus SPA MALDI-TOF Bacterial Version number CAT2016/

12 Viral EQA HIV-1 (RNA) HIVRNA16 Catalogue Number QAV To assess the proficiency of laboratories in detection and quantitation of Human Immunodeficiency Virus (HIV) RNA. To assess the proficiency of laboratories in detection and quantitation in different HIV genotypes. Total Number of Challenges 2 or 4 Number of Panel Members per Challenge 4 Units of Measurement Cultured virus and/or Clinical material Plasma The primary unit is IU/ml however other units will be accepted 1.2 ml Panel Sample Pre-treatment Requirement Ready for analysis. Treat as clinical samples and analyse accordingly & Quantitative Hepatitis B virus HBVDNA16 Catalogue Number QAV To assess the proficiency of laboratories in the detection and quantitation of Hepatitis B Virus (HBV) DNA. To assess the proficiency of laboratories in the detection and quantitation in different HBV genotypes. Total Number of Challenges 2 or 4 Number of Panel Members per Challenge 4 Units of Measurement Cultured virus and/or Clinical material Plasma The primary unit is IU/ml however other units will be accepted 1.2 ml Panel Sample Pre-treatment Requirement Ready for analysis. Treat as clinical samples and analyse accordingly & Quantitative Version number CAT2016/

13 Viral EQA Hepatitis C virus HCVRNA16 Catalogue Number QAV To assess the proficiency of laboratories in the detection and quantitation of Hepatitis C Virus (HCV) RNA. To assess the proficiency of laboratories in the detection and quantitation in different HCV genotypes. Total Number of Challenges 2 or 4 Number of Panel Members per Challenge 4 Units of Measurement Clinical material Plasma The primary unit is IU/ml however other units will be accepted 1.2 ml Panel Sample Pre-treatment Requirement Ready for analysis. Treat as clinical samples and analyse accordingly & Quantitative HIV-1 (DNA) HIVDNA16 Catalogue Number QAV To assess the proficiency of laboratories in the detection of Human Immunodeficiency Virus type 1 (HIV-1) pro-viral DNA. Total Number of Challenges 2 Number of Panel Members per Challenge 4 Cultured proviral cells Physiological Buffer 0.1 ml Panel Sample Pre-treatment Requirement Ready for analysis. Treat as clinical samples and analyse accordingly. Quantitative for information purposes only Version number CAT2016/

14 Viral EQA B19 virus B19DNA16 Catalogue Number QAV To assess the proficiency of laboratories in detection and quantitation of B19 virus DNA. Total Number of Challenges 2 Number of Panel Members per Challenge 4 Clinical material Plasma Units of Measurement The primary unit is IU/ml however other units will be accepted 1.2 ml Panel Sample Pre-treatment Requirement Ready for analysis. Treat as clinical samples and analyse accordingly & Quantitative HCV Genotyping HCVGT16 Catalogue Number QAV To assess the proficiency of laboratories in the correct genotyping of Hepatitis C Virus (HCV) RNA using molecular methods. Genotypic Variant Clinical material Various HCV subtypes Plasma 1.2 ml Panel Sample Pre-treatment Requirement Ready for analysis. Treat as clinical samples and analyse accordingly Molecular typing Version number CAT2016/

15 Viral EQA HBV Genotyping HBVGT16 Catalogue Number QAV To assess the proficiency of laboratories in the correct genotyping of Hepatitis B Virus (HBV) using molecular methods. Genotypic Variant Clinical material Various HBV subtypes Plasma 1.2 ml Panel Sample Pre-treatment Requirement Ready for analysis. Treat as clinical samples and analyse accordingly Molecular typing Varicella-Zoster virus VZVDNA16 Catalogue Number QAV To assess the sensitivity of participants' molecular assays in detecting various types and concentrations of varicella-zoster virus (VZV). To review the performance of participants quantitative VZV molecular assays. Total Number of Challenges 2 Number of Panel Members per Challenge 5 Cultured virus and/or Clinical material Transport Medium Panel Sample Pre-treatment Requirement 1.0 ml Ready for analysis. Treat as clinical samples and analyse accordingly. Quantitative for information purposes only Version number CAT2016/

16 Viral EQA Enterovirus EVRNA16 Catalogue Number QAV To assess the ability of participants' molecular assays to detect different types and concentrations of Enterovirus (EV). To review the performance of participants quantitative EV molecular assays. Total Number of Challenges 2 Number of Panel Members per Challenge 5 Cultured virus and/or Clinical material Transport Medium 1.0 ml Panel Sample Pre-treatment Requirement Ready for analysis. Treat as clinical samples and analyse accordingly. Quantitative for information purposes only Parechovirus PeVRNA16 Catalogue Number QAV To assess the ability of participants' molecular assays to detect different types and concentrations of Parechovirus. Total Number of Challenges 2 Number of Panel Members per Challenge 5 Cultured virus and/or Clinical material Transport Medium 1.0 ml Panel Sample Pre-treatment Requirement Ready for analysis. Treat as clinical samples and analyse accordingly Version number CAT2016/

17 Viral EQA Herpes simplex virus 1 & 2 HSVDNA16 Catalogue Number QAV To assess the sensitivity of participants' molecular assays in detecting various strains of herpes simplex virus (HSV). To review the performance of participants quantitative HSV molecular assays. Total Number of Challenges 2 Number of Panel Members per Challenge 5 Cultured virus and/or Clinical material Transport Medium 1.0 ml Panel Sample Pre-treatment Requirement Ready for analysis. Treat as clinical samples and analyse accordingly. Quantitative for information purposes only Cytomegalovirus Dried Blood Spots CMVDBS16 Catalogue Number QAV To assess the performance of participants in the detection of clinically relevant levels of human cytomegalovirus (CMV) from dried blood spots. Units of Measurement 2 x 50µl Cultured virus and/or Clinical material Dried Blood Spots The primary unit is IU/ml however other units will be accepted Panel Sample Pre-treatment Requirement DNA extraction from dried blood spot. Quantitative for information purposes only Ambient Version number CAT2016/

18 Viral EQA West Nile virus WNVRNA16 Catalogue Number QAV To assess the proficiency of laboratories in the detection of West Nile virus. To determine the proficiency of laboratories in distinguishing West Nile virus from other flaviviruses. Cultured Virus Transport Medium Lyophilised Panel Sample Pre-treatment Requirement Reconstitution of lyophilised material. Quantitative for information purposes only 2-8 C / Lyophilised Ambient Dengue virus DENVRNA16 Catalogue Number QAV To assess the proficiency of laboratories in the detection of dengue virus. To assess the proficiency of laboratories in distinguishing dengue virus from other flaviviruses. Cultured Virus Transport Medium Lyophilised Panel Sample Pre-treatment Requirement Reconstitution of lyophilised material. Quantitative for information purposes only 2-8 C / Lyophilised Ambient Version number CAT2016/

19 Viral EQA JC virus JCDNA16 Catalogue Number QAV To assess the sensitivity of participants' molecular assays in detecting various types and concentrations of JC virus (JCV). To assess the proficiency of laboratories in the reliable quantitation of JCV viral load. Total Number of Challenges 2 Number of Panel Members per Challenge 5 Units of Measurement Cultured virus and/or Clinical material Transport Medium and/or Plasma The primary unit is Copies/ml however other units will be accepted 1.0 ml Panel Sample Pre-treatment Requirement Ready for analysis. Treat as clinical samples and analyse accordingly & Quantitative BK virus BKDNA16 Catalogue Number QAV To assess the sensitivity of participants' molecular assays in detecting various types and concentrations of BK virus (BKV). To assess the proficiency of laboratories in the reliable quantitation of BKV viral load. Total Number of Challenges 2 Number of Panel Members per Challenge 5 Units of Measurement Cultured virus and/or Clinical material Transport Medium and/or Plasma The primary unit is Copies/ml however other units will be accepted 1.0 ml Panel Sample Pre-treatment Requirement Ready for analysis. Treat as clinical samples and analyse accordingly & Quantitative Version number CAT2016/

20 Viral EQA Human Herpes virus 6 HHV6DNA16 Catalogue Number QAV To assess the sensitivity of participants' molecular assays in the detection of various types of Human Herpes Virus 6 (HHV6). To assess the proficiency of laboratories in the reliable quantitation of HHV6 viral load. Total Number of Challenges 2 Number of Panel Members per Challenge 5 Genotypic Variant Units of Measurement Cultured virus and/or Clinical material Subtypes A and B Transport Medium and/or Plasma The primary unit is Copies/ml however other units will be accepted 1.0 ml Panel Sample Pre-treatment Requirement Ready for analysis. Treat as clinical samples and analyse accordingly & Quantitative Human Cytomegalovirus CMVDNA16 Catalogue Number QAV To assess the proficiency of laboratories in the detection and quantitation of human cytomegalovirus (CMV). Total Number of Challenges 2 Number of Panel Members per Challenge 5 Units of Measurement Cultured virus and/or Clinical material Plasma The primary unit is IU/ml however other units will be accepted 1.0 ml Panel Sample Pre-treatment Requirement Ready for analysis. Treat as clinical samples and analyse accordingly & Quantitative Version number CAT2016/

21 Viral EQA Cytomegalovirus Whole Blood CMVWB16 Catalogue Number QAV To evaluate the ability of laboratories in the detection of CMV from whole blood samples. To assess the precision of molecular assays at clinically relevant viral loads. Total Number of Challenges 2 Number of Panel Members per Challenge 5 Units of Measurement Cultured virus and/or Clinical material Whole Blood The primary unit is IU/ml however other units will be accepted 1.0 ml Panel Sample Pre-treatment Requirement Ready for analysis. Treat as clinical samples and analyse accordingly & Quantitative <-30 C / Frozen on Dry-ice Epstein-Barr virus EBVDNA16 Catalogue Number QAV To assess the proficiency of laboratories in the detection and quantitation of Epstein-Barr virus (EBV). Total Number of Challenges 2 Number of Panel Members per Challenge 5 Units of Measurement Cultured virus and/or Clinical material Transport Medium and/or Plasma The primary unit is IU/ml however other units will be accepted 1.0 ml Panel Sample Pre-treatment Requirement Ready for analysis. Treat as clinical samples and analyse accordingly & Quantitative Version number CAT2016/

22 Viral EQA Adenovirus ADVDNA16 Catalogue Number QAV To assess the proficiency of laboratories in the detection of adenovirus. To assess the proficiency of laboratories in the detection of different adenovirus serotypes including currently circulating serotypes of interest. Total Number of Challenges 2 Number of Panel Members per Challenge 5 Cultured virus and/or Clinical material Transport Medium and/or Plasma 1.0 ml Panel Sample Pre-treatment Requirement Ready for analysis. Treat as clinical samples and analyse accordingly & Quantitative Influenza A & B virus INFRNA16 Catalogue Number QAV Assess the proficiency of laboratories in detection of influenza virus RNA. Assess the proficiency of laboratories in distinguishing influenza virus A and B. Cultured virus and/or Clinical material Transport Medium 1.0 ml Panel Sample Pre-treatment Requirement Ready for analysis. Treat as clinical samples and analyse accordingly Version number CAT2016/

23 Viral EQA Human Metapneumovirus MPV16 Catalogue Number QAV To assess the sensitivity and specificity of laboratories in the detection of human Metapneumovirus (MPV). To assess the ability of laboratories in the detection of different human MPV types. Cultured virus and/or Clinical material Transport Medium 1.0 ml Panel Sample Pre-treatment Requirement Ready for analysis. Treat as clinical samples and analyse accordingly Respiratory Syncytial virus RSV16 Catalogue Number QAV To assess the specificity and sensitivity of laboratories in the detection of Respiratory Syncytial virus (RSV). To assess the ability of laboratories in the detection of different RSV types. Cultured virus and/or Clinical material Transport Medium 1.0 ml Panel Sample Pre-treatment Requirement Ready for analysis. Treat as clinical samples and analyse accordingly Version number CAT2016/

24 Viral EQA Parainfluenza virus PINFRNA16 Catalogue Number QAV To assess the proficiency of laboratories in the detection of parainfluenzavirus. To assess the proficiency of laboratories in the detection of different parainfluenzavirus types. Cultured virus and/or Clinical material Transport Medium 1.0 ml Panel Sample Pre-treatment Requirement Ready for analysis. Treat as clinical samples and analyse accordingly Coronavirus CVRNA16 Catalogue Number QAV To assess the proficiency of laboratories in the detection of coronavirus. To assess the proficiency of laboratories in the detection of different coronavirus genotypes. Cultured virus and/or Clinical material Transport Medium 1.0 ml Panel Sample Pre-treatment Requirement Ready for analysis. Treat as clinical samples and analyse accordingly Version number CAT2016/

25 Viral EQA Rhinovirus RVRNA16 Catalogue Number QAV To assess the proficiency of laboratories in the detection of Rhinovirus. To assess the proficiency of laboratories in the detection of different Rhinovirus genotypes. Cultured virus and/or Clinical material Transport Medium 1.0 ml Panel Sample Pre-treatment Requirement Ready for analysis. Treat as clinical samples and analyse accordingly Influenza Haemagglutinin Typing INFHT16 Catalogue Number QAV To assess the proficiency of laboratories in the detection of different influenza virus subtypes. To assess the proficiency of laboratories in the typing and subtyping of influenza viruses. Number of Panel Members per Challenge 5 to 10 Panel Sample Pre-treatment Requirement Cultured virus and/or Clinical material Transport Medium 1.0ml Ready for analysis. Treat as clinical samples and analyse accordingly Molecular typing Version number CAT2016/

26 Viral EQA Norovirus NVRNA16 Catalogue Number QAV To assess the specificity and sensitivity of laboratories in the detection of Norovirus. To assess the ability of laboratories in the detection of different Norovirus serogroups. Cultured material and/or Clinical material and/or Purified nucleic acid Transport Medium and/or Physiological Buffer 1.0ml VTM, 0.1ml Buffer Panel Sample Pre-treatment Requirement Ready for analysis. Treat as clinical or semi-processed samples Hepatitis A virus HAVRNA16 Catalogue Number QAV To evaluate the ability of laboratories in the molecular detection of Hepatitis A Virus (HAV) in terms of sensitivity and specificity. Number of Panel Members per Challenge 8 to 10 Panel Sample Pre-treatment Requirement Cultured virus and/or Clinical material Plasma 1.2 ml Ready for analysis. Treat as clinical samples and analyse accordingly. Quantitative for information purposes only Version number CAT2016/

27 Viral EQA Hepatitis E virus HEVRNA16 Catalogue Number QAV To evaluate the ability of laboratories in the detection of Hepatitis E virus (HEV). Number of Panel Members per Challenge 8 to 10 Panel Sample Pre-treatment Requirement Clinical material Plasma 0.6 ml Ready for analysis. Treat as clinical samples and analyse accordingly. Quantitative for information purposes only HBV Drug Resistance HBVDR16 Catalogue Number QAV To assess the performance of laboratories in the detection of drug resistance mutations in the hepatitis B virus (HBV) DNA Polymerase gene using Sequencing techniques and/or LiPA technology. Number of Panel Members per Challenge 5 to 10 Cultured material and/or Clinical material Plasma Panel Sample Pre-treatment Requirement Ready for analysis Various mutations DNA polymerase Sequence Analysis Version number CAT2016/

28 Viral EQA HIV-1 Drug Resistance ENVA16 Catalogue Number QAV To assess the performance of laboratories in the detection of drug resistance mutations in the HIV-1 protease and reverse transcriptase genes. Number of Panel Members per Challenge 4 to 7 Panel Sample Pre-treatment Requirement Cultured virus and/or Clinical material Plasma Various mutations - Reverse Transcriptase (RT) and Protease (PR) genes Lyophilised Reconstitution of lyophilised material Sequence Analysis 2-8 C / Lyophilised Ambient HIV-1 Drug Resistance (Integrase) ENVAINT16 Catalogue Number QAV To assess the performance of laboratories in the detection of drug resistance mutations in the HIV-1 integrase gene. Number of Panel Members per Challenge 4 to 7 Panel Sample Pre-treatment Requirement Cultured virus and/or Clinical material Plasma Various mutations - Integrase (INT) gene Lyophilised Reconstitution of lyophilised material Sequence Analysis 2-8 C / Lyophilised Ambient Version number CAT2016/

29 Viral EQA Human Papillomavirus HPVDNA16 Catalogue Number QAV To assess the proficiency of laboratories in the detection of different high risk Human Papillomavirus (HPV) types. Clinical material and/or Cell lines containing HPV Transport Medium (PreservCyt) C / Liquid Ambient Version number CAT2016/

30 Bacterial EQA Chlamydia trachomatis CTDNA16 Catalogue Number QAB To assess the qualitative performance of participants' molecular assays in detecting Chlamydia trachomatis (C. trachomatis) at various concentrations. To assess the ability of participants' molecular assays to correctly identify different C. trachomatis strains. Total Number of Challenges 2 Number of Panel Members per Challenge 5 Cultured bacteria and/or Clinical material Urine and/or Physiological Buffer Neisseria gonorrhoeae NgDNA16 Catalogue Number QAB To determine the qualitative performance of participants' testing for Neisseria gonorrhoeae using molecular technologies. Total Number of Challenges 2 Number of Panel Members per Challenge 5 Cultured bacteria and/or Clinical material Urine and/or Physiological Buffer Version number CAT2016/

31 Bacterial EQA Chlamydophila pneumoniae & Mycoplasma pneumoniae CP.MP16 Catalogue Number QAB To assess the proficiency of laboratories in the correct detection of Chlamydophila pneumoniae and Mycoplasma pneumoniae. Cultured bacteria and/or Clinical material Bronchoalveolar Lavage (BAL) and/or Transport Medium 0.5 ml Panel Sample Pre-treatment Requirement Reconstitution of lyophilised material 2-8 C / Lyophilised Ambient Legionella pneumophila LPDNA16 Catalogue Number QAB To assess proficiency of laboratories in the detection of Legionella pneumophila. Cultured bacteria and/or Clinical material Bronchoalveolar lavage (BAL) and/or Transport Medium 0.5 ml 2-8 C / Liquid Ambient Version number CAT2016/

32 Bacterial EQA Methicillin Resistant S. aureus MRSADNA16 Catalogue Number QAB To assess the performance of participants in the detection of Methicillin Resistant S. aureus. Cultured bacteria and/or Clinical material Microbiological Medium and/or Transport Medium 1.2 ml Panel Sample Pre-treatment Requirement Ready for analysis. Treat as clinical samples and analyse accordingly 2-8 C / Liquid Ambient Methicillin Resistant S. aureus Typing (epidemiology and outbreak studies) MRSATP16 Catalogue Number QAB To assess the proficiency of participants in the molecular typing for outbreak analysis of Methicillin Resistant S. aureus. Cultured bacteria and/or Clinical material Microbiological Medium and/or Transport Medium Genetic variants of S. aureus 0.2 ml Panel Sample Pre-treatment Requirement Culture followed by standard NA extraction Molecular typing Evaluated by various methodologies 2-8 C / Liquid Ambient Version number CAT2016/

33 Bacterial EQA M. tuberculosis MTBDNA16 Catalogue Number QAB To assess the proficiency of laboratories in the molecular detection of Mycobacterium tuberculosis (M. tuberculosis) (M. Bovis BCG). Total Number of Challenges 2 Number of Panel Members per Challenge 5 Cultured Mycobacteria tuberculosis (M. bovis - BCG) Sputum and/or Synthetic Sputum and/or Synthetic CSF 1.0 ml Panel Sample Pre-treatment Requirement Routine respiratory sample treatment 2-8 C / Liquid Ambient Clostridium difficile CDDNA16 Catalogue Number QAB To assess the proficiency of participants in the molecular detection of Clostridium difficile (C. difficile). Cultured bacteria and/or Clinical material Microbiological Medium and/or Synthetic Faecal Matrix 1.0 ml Version number CAT2016/

34 Bacterial EQA Bordetella pertussis BPDNA16 Catalogue Number QAB To assess the proficiency of laboratories in the detection of Bordetella pertussis. Cultured bacteria and/or Clinical material Physiological Buffer 1.0 ml Panel Sample Pre-treatment Requirement Ready for analysis. Treat as clinical samples and analyse accordingly Borrelia burgdorferi spp.(lyme Disease) BbDNA16 Catalogue Number QAB To assess the qualitative detection of Borrelia burgdorferi sensu stricto (B. burgdorferi s.s) at different concentrations. To assess the qualitative detection of B. burgdorferi genospecies complex at different concentrations. Cultured bacteria and/or Clinical material Microbiological Medium and/or Transport Medium Version number CAT2016/

35 Fungal EQA Aspergillus spp. ASPDNA16 Catalogue Number QAF To assess the qualitative detection of Aspergillus species at different concentrations. Cultured material and/or Clinical material and/or Purified nucleic acid Plasma and/or Physiological Buffer and/or Synthetic Sputum. Quantitative for information purposes only Candida spp. CANDNA16 Catalogue Number QAF To evaluate the ability of laboratories to use molecular techniques for detection of Candida species. Cultured material and/or Clinical material and/or Purified nucleic acid Plasma and/or Physiological Buffer Covering clinical and analytical range Version number CAT2016/

36 Fungal EQA Pneumocystis jirovecii pneumonia (PCP) PCPDNA16 Catalogue Number QAF To assess laboratories ability in the molecular detection of Pneumocystis jirovecii (P. jirovecii). To assess the sensitivity of molecular assays in routine clinical use for the detection of P. jirovecii. Cultured material and/or Clinical material Physiological Buffer & Quantitative Version number CAT2016/

37 Parasitic EQA Toxoplasma gondii TGDNA16 Catalogue Number QAP To assess the proficiency of participants in the qualitative detection of Toxoplasma gondii at different concentrations. Panel Sample Pre-treatment Requirement Cultured material and/or clinical material Amniotic Fluid and/or Plasma Lyophilised Reconstitution of lyophilised material 2-8 C / Lyophilised Ambient Version number CAT2016/

38 EQA pilot Studies Epstein-Barr virus Whole Blood EBVWB16 Catalogue Number QAV Epstein-Barr virus (EBV) is associated with a broad spectrum of epithelial and lymphoproliferative disorders which are an important cause of mortality and morbidity especially in immunocompromised hosts. As a result, the measurement for EBV viral load is an essential element in patient management and whole blood is often a common matrix when monitoring these patients. The primary aim of this EQA is to evaluate the ability of the participating laboratory in the detection of EBV from whole blood samples. The EQA will investigate quantification ranges of the molecular assays at clinically relevant viral loads. Total Number of Challenges 2 Number of Panel Members per Challenge 5 Units of Measurement Panel Sample Pre-treatment Requirement Cultured virus and/or Clinical material Whole Blood The primary unit is IU/ml however other units will be accepted 1.0 ml Ready for analysis. Treat as clinical samples and analyse accordingly & Quantitative <-30 C / Frozen on Dry-ice CMV Drug Resistance CMVDR16 Catalogue Number QAV Cytomegalovirus (CMV) is a betaherpes virus with a high prevalence (40-80%) within the population. The virus is normally latent and asymptomatic. However within subpopulation groups such as the immunocompromised and / or those on transplantation treatments CMV infection results in high rates of mortality and morbidity rates. Antiviral drug such as ganciclovir, (prodrug valganciclovir), foscarnet, and cidofovir have been shown to be effective in the treatment of early stage active CMV infection. However, drug resistance conferred by mutations within the viral DNA polymerase (pol) gene are now becoming of major concern. The aim of the CMV Drug Resistance EQA pilot study is therefore to assess the laboratories ability to detect CMV drug resistance mutations using their routine molecular diagnostic platform and procedures. Number of Panel Members per Challenge 5 to 10 Cultured material and/or Clinical material Plasma and/or Physiological Buffer Sequence Analysis Version number CAT2016/

39 EQA pilot Studies Chlamydia psittaci CPS16 Catalogue Number QAB Chlamydia psittaci is a widespread zoonotic bacterial infection that can result in severe pneumonia and other serious health problems in humans. Direct detection of Chlamydia psittaci by culture is hazardous and requires specialist facilities. Alternative sero-diagnostic procedures lack specificity at the Chlamydia species level. The development of nucleic acid amplification technology (NAT) diagnostic tests for Chlamydia psittaci that are sensitive and species specific has resulted in these tests becoming of increased practical and clinical relevance. The aim of this EQA is to assess the laboratories' ability in the molecular detection of Chlamydia psittaci. Number of Panel Members per Challenge 8 to 10 Cultured material and/or Clinical material Transport Medium HCV Drug Resistance HCVDR16 Catalogue Number QAV Hepatitis C virus (HCV) infection represents a major public health problem, affecting 170 million people worldwide. It is the main cause of acute and chronic hepatitis. The majority of infected individuals progress to chronic infection, which leads to liver cirrhosis, hepatocellular carcinoma, and ultimately the requirement for liver transplantation. At present there are no effective vaccines available. In addition, standard approaches to HCV treatment (pegylated interferon, PEG IFN) are limited and often difficult for the patient to tolerate. A number of new therapies are starting to become available. These include direct-acting antiviral (DAA) drugs such as those targeted against the HCV protease inhibitors. Two DAA drugs that target the HCV NS3 protease (boceprevir and telaprevir) have been approved for the treatment of HCV infections. Treatment success rates have been shown to improve dramatically when DAA drugs are administered in combination with PEG-IFN and ribavirin. However in vitro and in vivo studies have shown that DAA drugs may be susceptible to drug resistance. Therefore the identification of specific drug resistance mutations within the HCV virus is becoming increasingly important in the clinical management of HCV infection. The aim of the HCV Drug Resistance Typing EQA is therefore to assess the laboratories ability to detect HCV drug resistance mutations using their routine molecular diagnostic platform and procedures. Number of Panel Members per Challenge 5 to 10 Panel Sample Pre-treatment Requirement Clinical material Plasma Various mutations - Protease (PR) Ready for analysis Sequence Analysis Version number CAT2016/

40 EQA pilot Studies Hepatitis D virus HDV16 Catalogue Number QAV Hepatitis D virus (HDV) is a single stranded RNA satellite virus that can be classified into three genotypes designated I, II and III. Genotype I is considered the most prevalent and is associated with a broad spectrum of disease worldwide. Genotype II is mainly restricted to parts of Asia and is less severe than genotype I. Genotype III is found in South America and is responsible for a more severe form of delta hepatitis. As an RNA satellite virus, HDV is closely associated with hepatitis B and it relies on hepatitis B virus (HBV) for the production of envelope proteins during transmission. Therefore, co-infection with HBV or superinfection of a host already carrying HBV is required for HDV infection. As a result, HDV distribution closely parallels that of HBV. Molecular techniques are already an important diagnostic and monitoring tool for HBV and similar techniques are now being introduced for the fast and accurate diagnosis of HDV. The primary aim of this EQA pilot study is to evaluate laboratories in the detection of HDV within the routine clinical setting. Number of Panel Members per Challenge 8 to 10 Cultured material and/or Clinical material Plasma and/or Physiological Buffer & Quantitative Measles / Mumps MM16 Catalogue Number QAV Mumps & Measles are acute viral illnesses caused by RNA viruses of the paramyxovirus family. Globally, Measles remains a leading cause of morbidity and mortality with an estimated 770,000 deaths annually. In addition complications associated with Mumps include aseptic meningitis and, although less common, encephalitis which can result in death or permanent disability. In recent years, worldwide vaccination programmes have been effective in reducing morbidity and mortality rates. However inconsistences in vaccination coverage such as the health scare associated with the introduction of the trivalent form of the vaccine for Measles, Mumps, and Rubella (MMR) can lead to resurgences and outbreaks. Conventional laboratory diagnostic methods including serology or viral culture often lack sensitivity and can be time consuming especially in regions where there is a low prevalence of disease due to the high uptake of vaccination. Hence the use of molecular diagnostics plays an important role in the confirmation of acute infection. In addition, the genotyping of mumps and measles can provide information regarding the epidemiology of the viruses within an outbreak and also for differentiating vaccine strain from wild-type. The aim of this EQA pilot study is to evaluate the current use of molecular technologies for the detection, determination and genotyping of mumps and measles within the routine clinical laboratory setting. Cultured material and/or Clinical material Physiological Buffer Version number CAT2016/