Pre-evaluation of the EQA Schemes in Virus Diagnostics November/December 2014 INSTAND e.v. in cooperation with: Deutsche Vereinigung zur Bekämpfung der Viruskrankheiten (DVV) Gesellschaft für Virologie (GfV) Deutsche Gesellschaft für Hygiene und Mikrobiologie (DGHM) Prof. Dr. Heinz Zeichhardt doc. Dr. Oliver Donoso Mantke Issued by: INSTAND e.v. Gesellschaft zur Förderung der Qualitätssicherung in medizinischen Laborarien e.v. Düsseldorf/Berlin, 26.01.2015
EQAS Adviser: Assistant EQAS Adviser: Prof. Dr. Heinz Zeichhardt doc. Dr. Oliver Donoso Mantke Charité - Universitätsmedizin Berlin c/o INSTAND e.v. Institut für Virologie, Campus Benjamin Franklin Ubierstr. 20, 40223 Düsseldorf Hindenburgdamm 27, 12203 Berlin Tel.: +49-(0)30-688197730; Fax: +49-(0)30-688197741 Tel.: +49-(0)30-81054-300; Fax: +49-(0)30-81054-303 Email: donoso@instand-ev.de Email: Heinz.Zeichhardt@charite.de Organisation and Logistics: INSTAND e.v. Ubierstr. 20 40223 Düsseldorf Tel.: +49 (0)211-1592 13 0 Fax: +49 (0)211-1592 1330 Email: instand@instand-ev.de Internet: www.instand-ev.de Pre-evaluation Virology November December 2014 20150126a EN.doc 2 von 11
Dear colleagues, Pre-Evaluation and Mailing of Participation Documents INSTAND External Quality Assessment Schemes - November/December 2014 Virus Immunology Virus Genome Detection by PCR/NAT You have participated in one or several of the INSTAND external quality assessment (EQA) schemes in diagnostics of November/December 2014. 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 statement of participation statement of individual results The EQA schemes having been performed in November/December 2014 are highlighted in bold and italics in Tables 1 and 2. Table 1 EQA schemes performed with a frequency of four times per year VIRUS IMMUNOLOGY: VIRUS GENOME DETECTION: Cymegalo (351) Hepatitis A (343) Hepatitis B Prog. 1 (344) Hepatitis B Prog. 2 (345) Hepatitis C (346) HIV-1/HIV-2 (335) HIV-1 p24 Ag (337) Cymegalo (365) Hepatitis A (377) Hepatitis B (361) Hepatitis C (362) HIV-1 (360) Parvo B19 (367) Table 2 EQA schemes performed twice per year or with lower frequency VIRUS IMMUNOLOGY: VIRUS GENOME DETECTION: Dengue es (Ab/NS1-Ag) (350) Epstein Barr (352) TBE (FSME) (358) Hantaes (355) Hepatitis D (347) Hepatitis E (348) Herpes simplex es (354) HTLV-1/HTLV-2 (339) Measles (357) Mumps (356) Parvo B19 (342) Respirary syncytial (Ag/genome) (359) Rubella (341) Rabies (Tollwut) (336) Varicella zoster (353) Adenoes (371) BK (364) Cymegalo training program (368) Dengue es (369) Enteroes (372) RKI-Entero-Surveillance (every two years) (374) Epstein Barr (376) Hepatitis B training program (378) Hepatitis C training program (379) HCV genotyping (once a year) (375) Hepatitis E (380) Herpes simplex 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 Metapneumo (385) Human Papilloma es (373) Influenza es (genome/ag) (370) Measles (386) Mumps (387) Noro (381) Parainfluenza es (388) Rubella (389) Rabies (Tollwut) (390) Varicella zoster (366) West Nile (391) Pre-evaluation Virology November December 2014 20150126a EN.doc 3 von 11
Please see the following Tables 3, 4 and 5 for details on sample properties and the expected target values for this EQA scheme November/December 2014. 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 / Reports / Year and Category (Virus immunology / Virus genome detection)" in English language: http://www.instandev.de/en/eqas/reports/ and in German language: http://www.instandev.de/ringversuche/kommentare/. Please note: RiliBÄK A compilation of the "Guideline of the German Medical Association (Bundesärztekammer / RiliBÄK = Richtlinie der Bundesärztekammer zur Qualitätssicherung laborariumsmedizinischer Untersuchungen)" with all Sections including Section "Qualitative determinations in laborary medicine = Qualitative laborariumsmedizinische Untersuchungen" and Section "Direct detection and characterization of infectious diseases pathogens = Direkter Nachweis und Charakterisierung von Infektionserregern" has recently been published (in German language: Deutsches Ärzteblatt, Jg. 111, Heft 38, 19. September 2014, A 1583 - A 1618) (please see link). Note for German laboraries: The requirements laid down in Specified Section - effective since 01.04.2013 - should be fulfilled by 31.03.2015 at the latest (end of transition period). In this context we refer especially the requirements defined in Table -2a "External quality assurance for the detection of concentration of nucleic acids of CMV, HBV, HCV and HIV-1 in blood//" = "Externe Qualitätssicherung bei der Bestimmung der Nukleinsäurekonzentration in Blut/Plasma/Serum". Please see our information on the INSTAND EQA schemes in diagnostics and the new RiliBÄK (as of 24 January 2014) (see link, paragraph 1.3). New INSTAND EQA schemes in diagnostics and INSTAND ordering documents 2015 We may inform you that 10 new EQA schemes for genome detection will be launched in 2015 after we have introduced 19 additional EQA schemes in diagnostics in 2014. For details please see the INSTAND ordering documents 2015 incl. brochure and order form (please see link). Surplus samples of the current and previous EQA schemes in diagnostics are available for test assessment of your diagnostics. Please contact INSTAND for details. Thank you for your kind cooperation Prof. Dr. H. Zeichhardt doc. Dr. O. Donoso Mantke Pre-evaluation Virology November December 2014 20150126a EN.doc 4 von 11
Table 3: EQA Schemes Virus Immunology - November/December 2014 Program Group RiliBÄK Analyte Sample Cymegalo Epstein Barr Tick-borne encephalitis (TBE = FSME) # Hepatitis A Hepatitis B (prog. 1) (HBsAg anti-hbs anti-hbc) 351 352 358 343 344 mandary: mandary: mandary: mandary: anti-cmv-igg anti-cmv-igm anti-cmv-igg anti-cmv-igm ---- anti-tbe-igg anti-tbe-igm anti-tbe-igg anti-tbe-igm 351037 351038 352019 352020 358019 358020 qualitative dilution sample source avidity: no avidity The accepted results will be shown in the final report. anti-hav 343073 >= 60 miu/ml anti-hav 343074 >= 60 miu/ml healthy blood donor past CMV infection past EBV infection for anti-ebna-1 for anti-vca-igm past EBV infection for anti-ebna-1 for anti-vca-igm indication of a past TBE infection/vaccination indication of a past TBE infection/vaccination (a) 1 : 100 anti-hav-igg (a) healthy blood donor 1 : 200 anti-hav-igm 343075 1 : 4 acute hepatitis A infection anti-hav-igm HBsAg 344217 HBsAg 344218 HBsAg 344219 HBsAg 344220 anti-hbs 344221 anti-hbs 344222 anti-hbs 344223 anti-hbs 344224 343076 0.00-0.05 IU/ml (0.00 IU/ml target value) 1.70-3.55 IU/ml (2.40 IU/ml target value) 0.00-0.05 IU/ml (0.00 IU/ml target value) 3.40-7.10 IU/ml (4.69 IU/ml target value) 45-150 IU/l (105 IU/l target value) 0-9 IU/l (0 IU/l target value) 90-300 IU/l (205 IU/l target value) 0-9 IU/l (0 IU/l target value) (b) (b) (c) (c) healthy blood healthy blood 1 : 1 600 chronic hepatitis B healthy blood 1 : 800 chronic hepatitis B 1 : 500 1 : 250 anti-hbc 344225 (d) 1 : 1 000 anti-hbc 344226 anti-hbs healthy blood donor healthy blood anti-hbs healthy blood donor healthy blood chronic hepatitis B ( for anti-hbc-igm and HBeAg, resp.) healthy blood anti-hbc 344227 (d) 1 : 2 000 chronic hepatitis B anti-hbc 344228 (d) 1 : 500 a, b, c, d: Marked samples represent dilutions from the corresponding sck materials. # FSME = Frühsommer-Meningoenzephalitis ( for anti-hbc-igm and HBeAg, resp.) Pre-evaluation Virology November December 2014 20150126a EN.doc 5 von 11
Table 3 (contd.): EQA Schemes Virus Immunology - November/December 2014 Program Group RiliBÄK Analyte Sample qualitative dilution sample source mandary: anti-hbc-igm 345109 1 : 110 acute hepatitis B infection Hepatitis B anti-hbc-igm 345110 healthy blood donor (prog. 2) mandary: HBeAg 345111 1 : 540 chronic hepatitis B (anti-hbc-igm 345 HBeAg HBeAg 345112 healthy blood donor anti-hbe) mandary: anti-hbe 345113 healthy blood donor chronic hepatitis B anti-hbe 345114 1 : 65 ( for HBeAg) Hepatitis C (Ab and HCV-Ag) Hepatitis D Hepatitis E Herpes simplex es HIV-1/ HIV-2 346 347 348 354 335 anti-hcv mandary: anti-hcv HCV antigen anti-hcv HCV antigen anti-hcv HCV antigen anti-hcv HCV antigen anti-hdv-igg anti-hdv-igm anti-hdv-igg anti-hdv-igm anti-hev-igg anti-hev-igm anti-hev-igg anti-hev-igm anti-hsv-igg anti-hsv-igm anti-hsv-igg anti-hsv-igm anti-hiv-1/2 346073 346074 346075 346076 347019 347020 348019 348020 354019 354020 not evaluated not evaluated 335073 Pre-evaluation Virology November December 2014 20150126a EN.doc 6 von 11 (e) (e) (f) 1 : 6 000 (f) 1 : 3 000 anti-hiv-1 335074 (g) 1 : 100 anti-hiv-1 335075 (g) 1 : 50 anti-hiv-1 335076 (g) 1 : 200 1 : 100 past hepatitis C infection 1 : 15 chronic hepatitis C 1 : 50 past hepatitis C infection healthy blood chronic hepatitis D acute hepatitis E infection healthy blood donor past HSV-1 infection healthy blood donor healthy blood HIV-1 infection HCV Ag mandary: mandary: HIV-1 mandary: p24 Ag 337037 (h) 1 : 57 000 p24 Ag 337 p24 Ag 337038 (h) 1 : 76 000 HTLV-1/ anti-htlv-1 339013* (i) 1 : 240 HTLV-1 infection HTLV-2 anti-htlv-2 339014** (j) 1 : 5 339 HTLV-2 infection anti-htlv-2 339015** (j) 1 : 2.5 * ** anti-htlv-1 339016* (i) 1 : 120 HTLV-1 infection anti-measles-igg Measles 357019 357 anti-measles-igm anti-measles-igg 357020 anti-measles-igm anti-mumps-igg Mumps 356019 356 anti-mumps-igm anti-mumps-igg 356020 anti-mumps-igm e, f, g, h, i, j: Marked samples represent dilutions from the corresponding sck materials. HIV-1 infection (spiked pool of blood donors; HIV-1 heat inactivated) indication of a past measles infection/vaccination indication of a past measles infection/vaccination indication of a past mumps infection/vaccination indication of a past mumps infection/vaccination
Table 3 (contd.): EQA Schemes Virus Immunology - November/December 2014 Program Group RiliBÄK Analyte Sample Parvo B19 Respirary syncytial (antigen/ genome) Rubella Varicella zoster 342 359 341 353 mandary: mandary: anti-parvo B19-IgG 342037 = avidity: no avidity 342039 anti-parvo B19-IgM anti-parvo B19-IgG anti-parvo B19-IgM 342038 qualitative dilution sample source anti-parvo B19-IgG 342039 = avidity: no avidity 342037 anti-parvo B19-IgM anti-parvo B19-IgG anti-parvo B19-IgM 342040 RSV 59019 1 : 2.4 RSV A 359020 1 : 20 titer Hi test / HiG anti-rubella-igg anti-rubella-igm titer Hi test / HiG anti-rubella-igg anti-rubella-igm anti-vzv-igg anti-vzv-igm anti-vzv-igg anti-vzv-igm The samples 342037 and 342039 are identical. 341019 341020 353019 353020 32-512 20 IU/ml (120 IU/ml target value) 64-1 024 40 IU/ml (233 IU/ml target value) sera of healthy blood past parvo B19 infection ( of one healthy blood donor) sera of healthy blood past parvo B19 infection (sera of two healthy blood donors) RSV B infected HEp-2 cells (lysate) RSV A infected HEp-2 cells (lysate) sera of two healthy blood donors with indication of a past rubella infection or vaccination sera of three healthy blood donors with indication of a past rubella infection or vaccination past VZV infection past VZV infection Pre-evaluation Virology November December 2014 20150126a EN.doc 7 von 11
Table 4: EQA Schemes Virus Genome Detection by PCR/NAT - November/December 2014 EBV HAV spiked HBV HCV HEV * suspension of feces** HIV-1 spiked HIV-2 spiked HMPV 376 377 361 362 380 360 395 385 Program Group RiliBÄK Sample qualitative Target value of all methods (note on dilution (provisional data) geno-/subtype) copies/ml IU/ml 365073 $ = (a) 1 : 20 000 approx. 2 400 approx. 5 115 CMV 365076 mandary: 365074 (a) 1 : 313 approx. 139 530 approx. 268 994 365 365075 ------- 0 0 365076 $ = (a) 1 : 20 000 approx. 2 645 approx. 4 305 365073 CMV Global 994001 ------- approx. 97 800 approx. 121 985 Collaboration 994002 ------- approx. 8 929 approx. 13 400 994 --- 994003 ------- 0 0 994004 ------- approx. 8 963 approx. 14 055 994005 ------- approx. 116 500 approx. 175 940 376037 (b) 1 : 100 approx. 14 852 approx. 13 560 mandary: mandary: mandary: mandary: mandary: 376038 & = 376039 ------- 0 0 376039 & = 376038 ------- 0 0 376040 (b) 1 : 400 approx. 3 863 approx. 3 477 377073 = 377075 (c) 1 : 5 400 not evaluated # not evaluated # 377074 (c) 1 : 16 200 not evaluated # not evaluated # 377075 = 377073 (c) 1 : 5 400 not evaluated # not evaluated # 377076 ------- not evaluated # not evaluated # 361073 (d) 1 : 15 000 not evaluated # approx. 4 180 361074 ------- not evaluated # 0 361075 (d) 1 : 75 000 not evaluated # approx. 735 361076 ------- not evaluated # 0 362073 ------- not evaluated # 0 362074 (subtype 3a) 1 : 50 not evaluated # approx. 13 257 362075 (subtype 2a/2c) (e) 1 : 1 200 not evaluated # approx. 3 355 362076 (subtype 2a/2c) (e) 1 : 300 not evaluated # approx. 13 150 380013* ----- not evaluated # not evaluated # 380014* (f) 1 : 12.5 not evaluated # not evaluated # 380015* (f) 1 : 25 not evaluated # not evaluated # 380016** 1 : 17 not evaluated # not evaluated # 360073 (subtype B) 1 : 480 000 000 approx. 726 not evaluated # 360074 (subtype B) (g) 1 : 1 000 000 approx. 317 250 not evaluated # 360075 ------- 0 not evaluated # 360076 (subtype B) (g) 1 : 64 000 000 approx. 8 330 not evaluated # 395001 (h) 1 : 1 000 not evaluated # not evaluated # 395002 (h) 1 : 10 not evaluated # not evaluated # 395003 ------- not evaluated # not evaluated # 395004 (h) 1 : 100 not evaluated # not evaluated # 385005 % = 385008 (subtype A) (i) 1 : 1 000 not evaluated # ------- 385006 (subtype A) (i) 1 : 10 000 not evaluated # ------- 385007 (subtype A) (i) 1 : 100 not evaluated # ------- 385008 % = 385005 (subtype A) (i) 1 : 1 000 not evaluated # ------- # The quantitative results are not evaluated due the low number of analyses (without disadvantage for the certificate). a, b, c, d, e, f, g, h, i: Marked samples derive from corresponding sck materials diluted in consecutive steps. $ The samples 365073 and 365076 are identical. The samples 377073 and 377075 are identical. & The samples 376038 and 376039 are identical. % The samples 385005 and 385008 are identical. Pre-evaluation Virology November December 2014 20150126a EN.doc 8 von 11
Table 4 (contd.): EQA Schemes Virus Genome Detection by PCR/NAT - November/December 2014 Program Group RiliBÄK Sample qualitative Target value of all methods (note on dilution (provisional data) geno-/subtype) copies/ml IU/ml 386005 (genotype D4) 1 : 10 not evaluated # ------- Measles 386006 (genotype A) 1 : 10 not evaluated # ------- 386 low 386007 (genotype D8) (j) 1 : 100 not evaluated # ------- FTA cards not evaluated* 386008 (genotype D8) (j) 1 : 10 not evaluated # ------- Mumps FTA cards Parvo B19 Rubella FTA cards VZV 387 367 389 366 mandary: mandary: 387001 (genotype G) (k) 1 : 10 not evaluated # ------- 387002 (genotype G) (k) undiluted not evaluated # ------- 387003 ------- not evaluated # ------- 387004 (genotype F) undiluted not evaluated # ------- 367073 (l) 1 : 50 000 approx. 86 000 approx. 71 150 367074 (l) 1 : 12 500 approx. 346 500 approx. 263 417 367075 (l) 1 : 3 200 000 approx. 1 633 approx. 1 965 367076 ------- 0 0 389001 (genotype 2B) (m) undiluted not evaluated # ------- 389002 (genotype 1G) undiluted not evaluated # ------- 389003 (genotype 2B) (m) 1 : 10 not evaluated # ------- 389004 ------- not evaluated # ------- 366037 (n) 1 : 1 000 approx. 7 300 ------- 366038 (n) 1 : 250 approx. 29 200 ------- 366039 (n) 1 : 500 approx. 15 000 ------- 366040 ------- 0 ------- * The qualitative results for sample 386007 - low for measles - are not evaluated due inconsistent results (without disadvantage for the certificate). # The quantitative results are not evaluated due the low number of analyses (without disadvantage for the certificate). j, k, l, m, n: Marked samples derive from corresponding sck materials diluted in consecutive steps. Pre-evaluation Virology November December 2014 20150126a EN.doc 9 von 11
Table 5: EQA Schemes Virus Genome Detection by PCR/NAT - November/December 2014 incl. Typing Program Group RiliBÄK Sample qualitative dilution species type (note on dilution) Adenoes mandary: Enteroes HSV-1/ HSV-2 371 372 363 mandary: mandary: 371037 371038 Quantitative results D will be discussed in 371039 the final report. C 371040 C 372037 372038 ---- 372039 Quantitative results will be discussed in the final report. ---- 372040 ---- 372041 ---- 363055 = 363057 A ---- approx. 151 500 ---- 363056 approx. 51 298 ---- 363057 = 363055 approx. 146 175 ---- 363058 approx. 6 000 ---- 363059 approx. 7 937 ---- 363060 approx. 25 750 ---- Adeno 31 1 : 600 diluted Adeno 37 1 : 500 000 diluted Adeno 2 1 : 100 000 diluted (o) Adeno 2 1 : 4 000 diluted (o) Coxsackie B3 1 : 25 000 diluted Echo 30 1 : 100 000 diluted Echo 7 1 : 200 diluted (p) Echo 7 1 : 400 diluted (p) Entero 68 1 : 100 diluted HSV-1 1 : 5 000 diluted (q) HSV-2 1 : 450 diluted (r) HSV-1 1 : 5 000 diluted (q) HSV-1 1 : 135 000 diluted (q) HSV-2 1 : 3 600 diluted (r) HSV-2 1 : 900 diluted (r) Human papilloma es * **biopsy material Noro suspension of feces 373 381 mandary: 373046* ----- ---- ---- 373047* High Risk ----- ---- 373048** Low Risk ----- ---- 373049* High Risk ----- ---- 373050* High Risk ----- ---- 381013 & = 381015 HPV 16 1 : 40 diluted HPV 6 1 : 88 diluted HPV 16 1 : 5 diluted HPV 18 1 : 40 diluted ---- ---- genogroup I 381014 Quantitative results ---- 1 : 125 diluted will be discussed in 381015 & = the final report. ---- ---- 381013 381016 ---- genogroup II 1 : 200 diluted o, p, q, r: Marked samples derive from corresponding sck materials diluted in consecutive steps. : The samples 363055 and 363057 are identical. & : The samples 381013 and 381015 are identical. Pre-evaluation Virology November December 2014 20150126a EN.doc 10 von 11
Table 5 (contd.): EQA Schemes Virus Genome Detection by PCR/NAT - November/December 2014 incl. Typing Program Group RiliBÄK Sample Influenza A and B es* inclusive influenza A(H1N1) pdm09, avian influenza A(H5N1) and avian influenza A(H7N9) (genome/ antigen) 370* mandary: 370049 370050 and results considered as "correct" (target values) type/subtype strain origin for Influenza A(H1N1) pdm09-virus (accepted target value for rapid tests for the detection of influenza A antigen: / borderline) for seasonal influenza B (accepted target value for rapid tests for the detection of influenza B antigen: / borderline) A/California/7/2009 (vaccine strain) B/Massachusetts/2/2012 (vaccine strain) 370051 ----- 370052 # 370053 370054 for avian influenza A(H7N9) # (accepted target value for rapid tests for the detection of influenza A antigen: / borderline) for avian influenza A(H5N1) (accepted target value for rapid tests for the detection of influenza A antigen: / borderline) for seasonal influenza A(H3N2) A/Anhui/1/2013 A/Whooper swan/ Germany/R65-2/2006 A/Vicria/361/2011 (vaccine strain) infected MDCK cells (lysate) (1 : 60 diluted) infected MDCK cells (lysate) (1 : 66 diluted) non-infected MDCK cells (lysate) allanic fluid (inactivated) (1 : 330 diluted) allanic fluid (inactivated) (1 : 40 diluted) infected MDCK cells (lysate) (1 : 30 diluted) * The EQA program for influenza A and B es, incl. influenza A(H1N1) pdm09, avian influenza A(H5N1) and avian influenza A(H7N9), is performed in cooperation with Nationales Referenzzentrum für Influenza, Robert Koch-Institut, Berlin, Dr. Brunhilde Schweiger and Nationales Referenzlabor für Aviäre Influenza, Bundesforschungsinstitut für Tiergesundheit, Friedrich-Loeffler-Institut, Insel Riems, PD Dr. Timm C. Harder For samples 370049, 370050, 370052 and 370053, the reporting of "borderline" in test category 30 (Antigen detection of influenza A ) and test category 40 (Antigen detection of influenza B ) was accepted as additional correct result for tests for antigen detection of influenza A and B, respectively (in general rapid tests). Considering also the result "borderline" ensured that these samples would not have been misinterpreted as. # Sample 370052 - for avian influenza A(H7N9) : The results in test category 10 (genome detection of influenza A) obtained by a test of one manufacturer (Cepheid; GeneXpert Flu Assay) have not been evaluated due results. The affected laboraries are advised contact the manufacturer for a modified test capable detect also avian influenza A(H7N9). Pre-evaluation Virology November December 2014 20150126a EN.doc 11 von 11