September Pre-evaluation of the External Quality Assessment Schemes in Virus Diagnostics

Transcription

1 September 2018 Corrected version: 20 November 2018 (See Table 3; page 9, program 344) of the External Quality Assessment Schemes in Virus Diagnostics Prof. Dr. Heinz Zeichhardt Dr. Martin Kammel Issued by: INSTAND Gesellschaft zur Förderung der Qualitätssicherung in medizinischen Laborarien e.v. Düsseldorf/Berlin, Germany, Virology September corr doc 1 of 16

2 INSTAND EQA schemes in virology in cooperation with: Deutsche Vereinigung zur Bekämpfung der Viruskrankheiten e.v. (DVV) Gesellschaft für Virologie e.v. (GfV) Deutsche Gesellschaft für Hygiene und Mikrobiologie e.v. (DGHM) EQAS Adviser: Prof. i.r. Dr. Heinz Zeichhardt Professor of Virology Charité - University Medicine Berlin Correspondence address: Prof. Dr. Heinz Zeichhardt Institut für Qualitätssicherung in der Virusdiagnostik - IQVD Potsdamer Chaussee 80, D Berlin, Germany Tel.: +49-(0) ; Fax: +49-(0) Heinz.Zeichhardt@iqvd.de Assistant EQAS Adviser: Dr. Martin Kammel c/o INSTAND e.v. Ubierstr. 20, D Düsseldorf, Germany Tel.: +49-(0) ; Fax: +49-(0) M.Kammel@iqvd.de Carried out by: INSTAND e.v. Ubierstr. 20 D Düsseldorf, Germany Tel.: +49 (0) Fax: +49 (0) instand@instand-ev.de Internet: Virology September corr doc 2 of 16

3 Pre-Evaluation and Mailing of Participation Documents INSTAND External Quality Assessment Schemes September 2018 Virus Immunology Virus Genome Detection by PCR/NAT Dear colleagues, You have participated in one or several of the INSTAND external quality assessment (EQA) schemes in virus diagnostics of September Today you receive the pre-evaluation. By mail, you receive the following participation documents of those EQA schemes in which you have participated this time: certificate of successful participation confirmation of participation statement of individual results Please note: Starting in September 2018, INSTAND e.v. has introduced the EQAS (RV) Online system for result entry for the following 5 EQA schemes: Virus Immunology Cymegalovirus (Ab) (351) Virus Immunology Hepatitis B Virus Program 1 (HBsAg, Anti-HBs, Anti-HBc) (344) Virus Immunology HIV-1/HIV-2 (Ab) (335) Virus Genome Detection Cymegalovirus Program 1 (365) Virus Genome Detection Parainfluenza Viruses (388) For these 5 EQA programs, data processing and generation of participation documents are now performed by the new "RV Online system". This enables you get direct access your participation documents via the butn "Evaluation" and the butns corresponding "Certificate" and "Evaluation". Please see: Annex 1 "Overview of the function and operation of RV Online", page 17. Starting with the EQA term November 2018, all EQA programs in virus diagnostics will be performed online (details will follow). For the forthcoming EQA schemes, participants having yet not used the RV Online system are kindly advised follow the information in Annex 1. The EQA schemes having been performed in September 2018 are highlighted in bold in Tables 1 and 2. For these highlighted EQA schemes, the corresponding participation documents will be sent out by mail gether with this pre-evaluation. VIRUS IMMUNOLOGY: Cymegalovirus (351) Hepatitis A virus (343) Hepatitis B virus Prog. 1 (344) Hepatitis B virus Prog. 2 (345) Hepatitis C virus (346) HIV-1/HIV-2 (335) HIV-1 p24 Ag (337) Table 1: EQA schemes performed with a frequency of four times per year VIRUS GENOME DETECTION: Cymegalovirus (365) Hepatitis A virus (377) Hepatitis B virus (361) Hepatitis C virus (362) HIV-1 (360) Parvovirus B19 (367) Legend Table 1: The EQA schemes having been performed in September 2018 are highlighted in bold (Table 1). For these highlighted EQA schemes, the corresponding participation documents will be sent out by mail gether with this pre-evaluation. The results of the 5 EQA schemes highlighted underlined in bold with colour in Tables 1 and 2 have been processed and evaluated by the new "RV Online system" for the first time in September Virology September corr doc 3 of 16

4 VIRUS IMMUNOLOGY: Table 2: EQA schemes performed twice per year or with lower frequency (EQA schemes having been performed in September 2018 are highlighted in bold) Chikungunya virus (402) Dengue viruses (Ab/NS1-Ag) (350) Epstein Barr virus (352) TBE (FSME) virus (358) Hantaviruses (355) Hepatitis D virus (347) Hepatitis E virus (348) Herpes simplex viruses (354) HTLV-1/HTLV-2 (339) Measles virus (357) Mumps virus (356) Parvovirus B19 (342) Rubella virus (341) Rabies (Tollwut) virus (336) Varicella zoster virus (353) Zika virus (338) $ VIRUS GENOME DETECTION: Adenoviruses (371) BK virus (364) Chikungunya virus (392) Coronaviruses (340) Cymegalovirus training program (368) Cymegalovirus resistance determination (349) Dengue viruses (369) Enteroviruses (372) RKI-Entero-Surveillance (every two years) (374) Epstein Barr virus (376) Hepatitis B virus training program (378) Hepatitis B virus genotyping (396) Hepatitis B virus resistance determination (397) Hepatitis C virus training program (379) Hepatitis C virus geno-/subtyping (375) Hepatitis C virus resistance determination (399) Hepatitis D virus (400) Hepatitis E virus (380)* Herpes simplex virus type 1/2 (363) HIV-1 training program (382) HIV-1 drug resistance determ. (standard progr.) (383) HIV-1 drug resistance determ. (additional progr.) (384) HIV-2 (395) Human Metapneumovirus (385) Human Papilloma viruses (373) Human Rhinoviruses (393) Influenza viruses (genome/ag) (370) JC virus (394) Measles virus (386) Mumps virus (387) Norovirus (381) Parainfluenza viruses (388) Respirary syncytial virus (Ag/genome) (359) Rotaviruses (401) Rubella virus (389) Rabies (Tollwut) virus (390) Varicella zoster virus (366) West Nile virus (391)* Zika virus (403) Legend Table 2: $ The EQA scheme virus immunology Zika virus (338) will be performed only once per year (term September) due the changed epidemiologic situation of infections with Zika virus. * INSTAND will increase the frequency for the EQA schemes for genome detection of hepatitis E virus (380) and West Nile Virus (391) from 2 4 times per year, as for Germany the Paul-Ehrlich-Institut (German Federal Institute for Vaccines and Biomedicines) plans change/changed the requirements for institutions involved in virus safety testing of certain blood products by testing with appropriate nucleic acid amplification techniques (NAT). The EQA schemes having been performed in September 2018 are highlighted in bold (Table 2). For these highlighted EQA schemes, the corresponding participation documents will be sent out by mail gether with this pre-evaluation. The results of the 5 EQA schemes highlighted underlined in bold with colour in Tables 1 and 2 have been processed and evaluated by the new "RV Online system" for the first time in September EQA schemes in Table 2 marked in italics were not performed in September Please see the following Tables 3, 4 and 5 for details on sample properties and the expected target values for this EQA scheme September You received information on sample properties already per on The reports of all EQA schemes will be released on the INSTAND homepage immediately after completion. For details please see the INSTAND homepage under "EQAS Online / Service for EQA tests / EQA area (Virus immunology / Virus genome detection)" in English language: and in German language: Virology September corr doc 4 of 16

5 Please note: RiliBAEK A compilation of the "Guidelines of the German Medical Association on quality assurance in medical laborary testing (Bundesaerztekammer / RiliBAEK = Richtlinie der Bundesaerztekammer zur Qualitaetssicherung laborariumsmedizinischer Untersuchungen)" with all Sections including Section "Qualitative medical laborary testing = Qualitative laborariumsmedizinische Untersuchungen" and Section "Direct detection and characterisation of infectious agents = Direkter Nachweis und Charakterisierung von Infektionserregern" has been published (in German language: Deutsches Aerzteblatt, Jg. 111, Heft 38, 19. September 2014, A A 1618) (please see link). An English version of the guideline translated by INSTAND e.v. with the consent of the Executive Board of the German Medical Association has been published in "German Medical Science" [in English language: Bundesaerztekammer (German Medical Association), Instand e.v., Guidelines of the German Medical Association on quality assurance in medical laborary testing. GMS Z Forder Qualitatssich Med Lab. 2015; 6] (please see link). INSTAND EQA schemes in virus diagnostics in 2019 For details please see the INSTAND brochure 2019 (please see link). Surplus samples of the current and previous EQA schemes in virus diagnostics are available for test assessment of your virus diagnostics. Please contact INSTAND e.v. for details. Thank you for your kind cooperation. Prof. Dr. Heinz Zeichhardt Dr. Martin Kammel Virology September corr doc 5 of 16

6 Table 3: EQA Schemes Virus Immunology September 2018 Program Group RiliBÄK Analyte Sample Chikungunya virus # (Ak) * plasma** 402 # anti-chikv-igg anti-chikv-igm anti-chikv-igg anti-chikv-igm anti-chikv-igg anti-chikv-igm anti-chikv-igg anti-chikv-igm The samples and are identical * *, = *, = * qualitative dilution sample source of a healthy blood donor without signs of an acute, recent or past chikungunya virus infection The samples and are identical. The sera derive from patient G-C5. N.B.: The same patient G-C5 also donated the primarily derived, which was used for sample Samples and represent the follow-up (pool ) of patient G-C5 with a past chikungunya virus infection. anamnestic details: see sample ; blood collected: 9 months and 16 months after onset of disease The sera for sample derive from patient G-C5. N.B.: The same patient G-C5 also donated the follow-up, which was used for the identical samples and Sample (pool ) represents the primarily derived from patient G- C5 with an acute chikungunya virus infection. chikungunya virus RNA ; traveler returned from French Guiana; clinical signs at onset of disease: exanthema on the legs, heavy joint paint, limb pain, fever; blood collected 7 days, 22 days and 30 days after onset of disease # The EQA program Virus Immunology - Chikungunya Virus (402) is performed in cooperation with Bernhard-Nocht-Institut, Hamburg (Nationales Referenzzentrum für tropische Infektionserreger, Abteilung für Virologie, WHO Collaborating Centre for Arbovirus and Haemorrhagic Fever Reference and Research; Prof. Dr. Stephan Günther, Dr. Petra Emmerich und Prof. Dr. Dr. Jonas Schmidt- Chanasit). Virology September corr doc 6 of 16

7 Table 3 (contd.): EQA Schemes Virus Immunology September 2018 Program Group RiliBÄK Analyte Sample Cymegalovirus (Ab) Dengue viruses* (Ab and NS1-Ag) * anti- Dengue NS 1 Ag anti-cmv-igg anti-cmv-igm anti-cmv-igg anti-cmv-igm anti-dengue-igg anti-dengue-igm Dengue NS1-Ag anti-dengue-igg anti-dengue-igm Dengue NS1-Ag anti-dengue-igg anti-dengue-igm Dengue NS1-Ag anti-dengue-igg anti-dengue-igm Dengue NS1-Ag qualitative dilution sample source avidity: no avidity/ not done avidity: high healthy blood past CMV infection (two healthy blood donors) of a healthy blood donor without signs of an acute, recent or past dengue virus infection from patient G-D26 with a recent primary dengue virus infection (DENV-3); traveller returned from Malaysia and Indonesia; clinical signs at onset of disease: diarrhea, fever; blood collected 4 weeks after onset of disease of a healthy blood donor without signs of an acute, recent or past dengue virus infection dengue virus G-D28 represents an acute primary dengue virus infection for NS1-Ag only of a healthy blood donor without signs of an acute or past dengue virus infection spiked with a cell culture propagated virus (DENV-2; heat inactivated) * The EQA program Virus Immunology - Dengue Viruses (350) is performed in cooperation with Bernhard-Nocht-Institut, Hamburg (Nationales Referenzzentrum für tropische Infektionserreger, Abteilung für Virologie, WHO Collaborating Centre for Arbovirus and Haemorrhagic Fever Reference and Research; Prof. Dr. Stephan Günther, Dr. Petra Emmerich und Prof. Dr. Dr. Jonas Schmidt- Chanasit). Virology September corr doc 7 of 16

8 Table 3 (contd.): EQA Schemes Virus Immunology September 2018 Program Group RiliBÄK Analyte Sample Hantaviruses* (Ab) 355* anti-dobrava-igg anti-dobrava-igm anti-hanta-igg anti-hanta-igm anti-hanta-igg anti-hanta-igm anti-puumala-igg anti-puumala-igm The samples and are identical = = qualitative dilution sample source from patient G-H13 detection of persisting anti- PUUV-IgM possible accepted results: / borderline/ with a past Dobrava-Belgrade virus infection, probably acquired in Brandenburg, Germany, anamnesis concerning a stay abroad outside Europe excluded, at onset of disease hospitalization necessary, characteristic sympms such as elevated creatinine, flu-like sympms and abnormal fatigue blood collected approx. 5 years after onset of disease of healthy blood donors (pool) without signs of an acute or past hanta virus infection from patient G-H9 with a past / post-acute Puumala virus infection, probably acquired in North Rhine Westphalia, Germany, anamnesis concerning a stay abroad outside Europe excluded; at onset of disease outpatient treatment, characteristic sympms such as elevated creatinine, increased liver test values and flu-like sympms; Blood collected approx. 4 months after onset of disease * The EQA program Virus Immunology - Hantaviruses (355) is performed in cooperation with Nationales Konsiliarlaborarium für Hantaviren (Charité - Universitätsmedizin Berlin, Campus Mitte, Institut für Virologie: Prof. Dr. Jörg Hofmann, Prof. Dr. Christian Drosten). Virology September corr doc 8 of 16

9 Table 3 (contd.): EQA Schemes Virus Immunology September 2018 Program Group RiliBÄK Analyte Sample Hepatitis A virus (Ab) Hepatitis B virus (prog. 1) (HBsAg anti-hbs anti-hbc) Hepatitis B virus (prog. 2) (anti-hbc- IgM HBeAg anti-hbe) anti-hav anti-hav anti-hav-igm 50 miu/ml (75 miu/ml)* 50 miu/ml (71 miu/ml)* qualitative dilution sample source (a) 1 : 150 (a) 1 : 300 anti-hav-igg healthy blood donor healthy blood anti-hav-igm : 30 acute hepatitis A HBsAg HBsAg HBsAg HBsAg anti-hbs anti-hbs anti-hbs anti-hbs anti-hbc IU/ml (4.10 IU/ml target value) IU/ml (2.10 IU/ml target value) IU/ml (7.96 IU/ml target value) IU/ml (1.06 IU/ml target value) <10 IU/l (1.66 IU/l target value) low ( 10 IU/l) not evaluated IU/l (135 IU/l target value) IU/l (117 IU/l target value) (b) 1 : (b) 1 :4 000 (b) 1 : (b) 1 : : : 25 anti-hbc (c) 1 : anti-hbc (c) 1 : 500 anti-hbc (c) 1 : acute hepatitis B healthy blood anti-hbs healthy blood donor anti-hbs healthy blood donor patient after acute hepatitis B (healed up with complete seroconversion) healthy blood chronic hepatitis B ( for HBeAg, anti-hbc-igm ) anti-hbc-igm healthy blood anti-hbc-igm : 160 acute hepatitis B HBeAg healthy blood HBeAg :800 chronic hepatitis B anti-hbe (d) 1 : 90 chronic hepatitis B ( for HBeAg) anti-hbe (d) 1 : 180 a, b, c, d: Marked samples derive from corresponding sck materials diluted in consecutive steps. * For highly concentrated samples some commercial tests for the detection of anti-hav-igg or anti-hav-tal reveal values > 60 miu/ml, which are outside the linear measurement range of the respective test system. Therefore, a final target value derived from a consensus value from all results stated in miu/ml could not be assigned highly concentrated samples. In this case a lower limit value in miu/ml is indicated in order assess a reported result of a laborary as a "correct" result. corrected on 20 November Virology September corr doc 9 of 16

10 Table 3 (contd.): EQA Schemes Virus Immunology September 2018 Program Group RiliBÄK Analyte Sample Hepatitis C virus (Ab and HCV-Ag) * plasma** HIV-1/ HIV-2 (Ab) HIV-1 p24 Ag Rabies virus* * anti-hcv HCV Ag anti-hcv HCV antigen anti-hcv HCV antigen anti-hcv HCV antigen anti-hcv HCV antigen ** ** * ** $ qualitative dilution sample source 1 : 20 1 : 20 anti-hiv (e) 1 : 50 anti-hiv (e) 1 : 100 anti-hiv (e) 1 : 50 anti-hiv-1/ p24 Ag : p24 Ag anti-rabv anti-rabv e: The marked dilutions were performed with the same sck materials. healthy blood chronic hepatitis C (subtype 4a) primarily derived plasma (before therapy) from the same patient whose followup plasma was used for sample healthy blood condition after chronic hepatitis C (subtype 4a) (successful therapy) follow-up plasma whose primarily derived plasma (before therapy) was used for sample HIV-1 infection $ Sample : Accepted target values for complementary tests (test category 20): and indeterminate. healthy blood HIV-1 infection (spiked pool of blood donors; HIV-1 heat inactivated) healthy blood healthy blood donor recent active rabies vaccination * The EQA program Virus Immunology - Rabies Virus (336) is performed in cooperation with Nationales Konsiliarlabor für Tollwut (Rabies Virus) (Universitätsklinikum Essen, Institut für Virologie, Prof. Dr. Ulf Dittmer, Prof. Dr. Stefan Ross). Virology September corr doc 10 of 16

11 Table 3 (contd.): EQA Schemes Virus Immunology September 2018 Program Group RiliBÄK Analyte Sample Zika virus* (Ab) 338* anti-zika-igg anti-zika-igm anti-zika-igg anti-zika-igm anti-zika-igg anti-zika-igm qualitative dilution sample source of patient G-Z1 (pool ) with a past Zika virus infection; stay in Sao Paulo and Ponta Negara, Brazil clinical signs at onset of disease: strong headaches, nausea, intestinal disorders, skin rash (not itchy), fever 38,5 C blood collected: 14 and 26 months after onset of disease healthy blood donor of patient G-Z4 with a post-acute Zika virus infection (Zika virus RNA not detectable anymore); stay in the Caribbean / Martinique clinical signs: diarrhea, night sweats, exanthema, swelling of the joints, conjunctivitis blood collected: 53 days after onset of disease * The EQA program Virus Immunology - Zika Virus (338) is performed in cooperation with Bernhard-Nocht-Institut, Hamburg (Nationales Referenzzentrum für tropische Infektionserreger, Abteilung für Virologie, WHO Collaborating Centre for Arbovirus and Haemorrhagic Fever Reference and Research; Prof. Dr. Stephan Günther, Dr. Petra Emmerich und Prof. Dr. Dr. Jonas Schmidt- Chanasit). Virology September corr doc 11 of 16

12 EQA Schemes Virus Genome Detection by PCR/NAT September 2018 Notices Evaluation of results for quantitative genome detection of CMV 1 Notice for German and foreign participants of EQA scheme 365: For evaluation, "IU/ml" have primarily been considered as measurement units of the quantitative results for the analyte CMV. This is in accordance the "Guideline of the German Medical Association (Bundesaerztekammer / RiliBAEK)", Specified RiliBAEK Section, Table B. 3-2a, When applying CE-marked tests, which not (yet) allow reporting of results in IU/ml, you should continue report the results as stated by the manufacturer. Evaluation of results for quantitative genome detection of HBV and HCV 2 3 Notice for German participants of EQA schemes 361 and 362: For evaluation, "IU/ml" have been considered as measurement units of the quantitative results for the analytes HBV and HCV. This is in accordance the "Guideline of the German Medical Association (Bundesaerztekammer / RiliBAEK)", Specified RiliBAEK Section, Table B. 3-2a. Statements in "copies/ml" will not be accepted anymore. Notice for foreign participants of EQA schemes 361 and 362: Please note that quantitative results in "copies/ml" for the genome detection of HBV and HCV, respectively, have not been evaluated due the low number of analyses or missing analyses. Evaluation of results for quantitative genome detection of HIV Notice for German participants of EQA scheme 360: For evaluation, "copies/ml" have been considered as measurement unit of the quantitative results for the analyte HIV-1. This is in accordance the "Guideline of the German Medical Association (Bundesaerztekammer / RiliBAEK)", Specified RiliBAEK Section, Table B. 3-2a. Statements in "IU/ml" will not be accepted anymore. Notice for foreign participants of EQA scheme 360: Please note that quantitative results in "IU/ml" for the genome detection of HIV-1 have not been evaluated due the low number of analyses or missing analyses. Virology September corr doc 12 of 16

13 Table 4: EQA Schemes Virus Genome Detection - September 2018 Program BK virus (DNA) suspension of urine Chikungunya virus & cell lysates CMV (DNA) spiked plasma HAV spiked plasma HBV (DNA) plasma HCV plasma HDV plasma HIV-1 spiked plasma Group RiliBÄK Sample & qualitative (note on geno-/subtype) dilution Target value of all methods (provisional data) copies/ml IU/ml : (a) 1 : : (a) 1 : not evaluated # (b) 1 : (S27) (inactivated) not evaluated # (b) 1 : (S27) (inactivated) not evaluated # : (Martinique) (inactivated) not evaluated # For evaluation of results in copies/ml or IU/ml: see notice 1, page : : : (c) 1 : not evaluated # not evaluated # : 500 not evaluated # not evaluated # not evaluated # not evaluated # (c) 1 : not evaluated # not evaluated # (d) 1 : Results in copies/ml: (d) 1 : not accepted (d) 1 : 700 or not evaluated (see notices 2 and 3, page 12) (subtype 1b) 1 : 675 Results in copies/ml: (genotype 3) (e) 1 : 100 not accepted or not evaluated (genotype 3) (e) 1 : (see notices 2 and 3, page 12) : not evaluated # not evaluated # (f) 1 : 100 not evaluated # not evaluated # not evaluated # not evaluated # (f) 1 : 900 not evaluated # not evaluated # (group M / subtype B) (group M / subtype B) (group M / subtype B) (g) 1 : (g) 1 : (g) 1 : not accepted or not evaluated (see notices 4 and 5, page 12) a, b, c, d, e, f, g: Marked samples derive from corresponding sck materials diluted in consecutive steps. # The quantitative results are not evaluated due the low number of analysis (without disadvantage for the certificates).. & The EQA programs Virus Genome Detection Chikungunya virus (392), Dengue Viruses (369), West Nile Virus (391) and Zika Virus (403) are performed in cooperation with Bernhard-Nocht-Institut, Hamburg (Nationales Referenzzentrum für tropische Infektionserreger, Abteilung für Virologie und WHO Collaborating Centre for Arbovirus and Haemorrhagic Fever Reference and Research: Prof. Dr. Stephan Günther, Prof. Dr. Dr. Jonas Schmidt-Chanasit und Dr. Petra Emmerich). Virology September corr doc 13 of 16

14 Table 4 (contd.): EQA Schemes Virus Genome Detection - September 2018 Program JC virus (DNA) suspension of urine Group RiliBÄK Sample 394 qualitative (note on geno-/subtype) Target value of all methods dilution (provisional data) copies/ml IU/ml : : : : Parvovirus B19 (DNA) plasma (genotype 1) 1 : (genotype 1) (h) 1 : (genotype 1) (h) 1 : Rabies virus* vaccine 390* (i) 1 : (i) 1 : (i) 1 : Quantitative results were not reported h, i: Marked samples derive from corresponding sck materials diluted in consecutive steps. * The EQA program Virus Genome Detection - Rabies Virus (390) is performed in cooperation with Nationales Konsiliarlabor für Tollwut (Rabies Virus) (Universitätsklinikum Essen, Institut für Virologie, Prof. Dr. Ulf Dittmer, Prof. Dr. Stefan Ross). Virology September corr doc 14 of 16

15 Table 5: EQA Schemes Virus Genome Detection incl. Typing September 2018 Program Group RiliBÄK Sample Dengue viruses & cell lysates HCV- Geno-/Sub typing* 369 & 375* qualitative Target value of all methods copies/ml species not evaluated # ---- type (note on dilution) DENV-3 (inactivated) 1 : 100 diluted (j) not evaluated # not evaluated # not evaluated # ** $ ** % DENV-3 (inactivated) 1 : 900 diluted (j) DENV-2 (inactivated) 1 : 300 diluted genotype 3 ** /(subtype 3a) ** 1 : diluted genotype 1 / subtype 1a 1 : 190 diluted genotype 1 $ / subtype 1b $ 1 : 52.8 diluted genotype 2 ** /(subtype 2b) ** 1 : 82.6 diluted genotype 2 % / (subtype 2a) % 1 : 95 diluted Parainfluenzaviruses cell lysate ## ## ## ## ---- PIV-3 1 : diluted (k) PIV-2 1 : diluted PIV-3 1 : diluted (k) j, k: Marked samples derive from corresponding sck materials diluted in consecutive steps. # The quantitative results are not evaluated due the low number of analysis (without disadvantage for the certificates). ## Samples , and : The target ranges for the quantitative results are set by the EQAS expert (ET). & The EQA programs Virus Genome Detection Chikungunya virus (392), Dengue Viruses (369), West Nile Virus (391) and Zika Virus (403) are performed in cooperation with Bernhard-Nocht-Institut, Hamburg (Nationales Referenzzentrum für tropische Infektionserreger, Abteilung für Virologie und WHO Collaborating Centre for Arbovirus and Haemorrhagic Fever Reference and Research: Prof. Dr. Stephan Günther, Prof. Dr. Dr. Jonas Schmidt-Chanasit and Dr. Petra Emmerich). * The EQA program Virus Genome Detection - HCV-Genotyping (375) is performed in cooperation with Nationales Referenzzentrum für Hepatitis C-Viren (Universitätsklinikum Essen, Institut für Virologie, Prof. Dr. Ulf Dittmer, Prof. Dr. Stefan Ross). ** Samples (subtype 3a) and (subtype 2b): The statement of the correct genotype will be considered for obtaining a certificate of successful participation. Sample (subtype 1a): The statement of the correct subtype is necessary for obtaining a certificate of successful participation. $ Sample (subtype 1b): In test category 30, some participants could not determine the subtype by using the test of one manufacturer (Abbott - RealTime HCV Genotype II). These inconsistent results have not been evaluated for this EQA scheme (without disadvantage for the certificate of successful participation). The Nationales Referenzzentrum für HCV (Essen) and the manufacturer have been informed. % Sample (subtype 2a): The statement on the correct genotype will be considered for obtaining a certificate of successful participation. Tests from different manufacturers were unable differentiate between subtype 2a and subtype 2c for this sample. Virology September corr doc 15 of 16

16 Table 5 (contd.): EQA Schemes Virus Genome Detection incl. Typing September 2018 Program Group RiliBÄK Sample West Nile virus & cell lysate 391 & qualitative Target value of all methods copies/ml species not evaluated # not evaluated # not evaluated # not evaluated # not evaluated # not evaluated # type (note on dilution) WNV-1 (inactivated) 1 : 3 diluted (l) WNV-2 (inactivated) 1 : diluted WNV-2 (inactivated) 1 : diluted WNV-1 (inactivated) 1 : 30 diluted (l) WNV-1 (inactivated) 1 : 300 diluted (l) Zika virus & plasma 403 & not evaluated # not evaluated # not evaluated # ---- African lineage 1 : 200 diluted Asian lineage 1 : diluted Asian lineage 1 : 30 diluted (inactivated) (inactivated) (inactivated) not evaluated # l: The marked dilutions were performed with the same sck materials. # The quantitative results are not evaluated due the low number of analysis (without disadvantage for the certificates). & The EQA programs Virus Genome Detection Chikungunya virus (392), Dengue Viruses (369), West Nile Virus (391) and Zika Virus (403) are performed in cooperation with Bernhard-Nocht-Institut, Hamburg (Nationales Referenzzentrum für tropische Infektionserreger, Abteilung für Virologie und WHO Collaborating Centre for Arbovirus and Haemorrhagic Fever Reference and Research: Prof. Dr. Stephan Günther, Prof. Dr. Dr. Jonas Schmidt-Chanasit and Dr. Petra Emmerich). Virology September corr doc 16 of 16