The Establishing and Impact of a Laboratory Quality Assurance Program In The Central Asia Region Kalashnikova T. ( DIH, EPO, CDC/CAR) Musabaev E. (Ref. Lab.Uzbekistan) Usmanov R. (Ref. Lab. Kyrgyztan) Kovtunenko N ( RL RC AIDS Kazazhstan) Suleymenova S.(Ref. Lab Kazazhstan) Golovchenko N.I.(RL RC AIDS Kyrgyzstan) Ongarbaev A. (Ref. Lab.Uzbekistan) Kuchuk T.(Ref. Lab. Kyrgyztan) Mustafaeva E. (Ref. Lab.Uzbekistan) Jumagulova A. (DIH, EPO, CDC/CAR) Drobeniuk J. (DVH, NCID, CDC) Favorov M. (DIH, EPO, CDC/CAR)

2 Features of laboratory service in Central Asia region Absence of continuously postgraduate education for laboratory specialists Short supply with technical facilities Absence of Quality control of test kits Absence of steady monitoring for analysis quality in every single laboratory (IQCl) and state (EQC)

3 GOAL Establishing and implementation of laboratory quality assurance system for HIV and viral hepatitis diagnosis in states of Central Asia

4Objectives Training of Central Asia specialist of rules of assurance and laboratory quality control (QA) Establishment of reference-laboratories – QA centers for development and implementation of: Normative standards Biological standards Re-equipment of the leading laboratories on the republican and oblast levels Monitoring of test performance quality by implementation External quality assessment /Proficiency Testing programs National level International level

5 METHODS Training by conducting four-day workshops Methods of quality control on pre-analytical, analytical and post-analytical steps of laboratory analysis Development and application of biological standards Establishment the internal quality control Biosafety in laboratory Ethiopathogeneses and clinic-epidemiological features of HIV and viral hepatitis PRACTICE ELISA with reference samples panel in standardized conditions Teaching the principals of evaluation the reliability of results through the data of accuracy and repeatability Comparative analysis of results for detection of faults and its reasons

6 ESTABLISHING OF NATIONAL REFERENCE LABORATORIES Building Boxes for serologic researches Space for samples getting Staff space Assistant space Staff Physicians Laboratory assistants Laboratory technician Equipment RefrigeratorsRefrigerators ThermostatsThermostats PCsPCs WashersWashers ReadersReaders PipettesPipettes Stand-alone electric power supplyStand-alone electric power supply

Re-equipment of the leading laboratories of CAR 41 technical and ELISA equipment sets with 24 items in each were purchased Uzbekistan - 19 sets Kyrgyzstan– 6 sets Kazakhstan – 4 sets Turkmenistan – 6 sets Tajikistan – 6 sets

8 TRAINING 19 QA HIV and hepatitis laboratory diagnostics training courses were held in different regions of Central Asia: –Kyrgyzstan (1998, 2002, 2003) –Uzbekistan (1999, 2000, 2001, 2002, 2003(2),2004) –Kazakhstan (2000, 2001, 2002(2), 2003(2) –Turkmenia (2000,2004) 378 of participants – representatives of laboratory service system of CAR –Blood Donor Centers –Infectious diseases hospitals –Private laboratories –SSC (sanitarian surveillance centers) Lecturing in quality control have been included to workshops for epidemiologists and practitioners in Central Asia

9

10 Reference laboratories for HIV and viral hepatitis were established in four states of Central Asia Kyrgyzstan ( 1998) Uzbekistan*( 1999) Kazakhstan ( 2000) Turkmenistan ( 2000) * Joint project with Swiss agency of emergent events and CDC/USAID

11 JURAL BASIS OF NRL The principals of establishing of assurance of quality control system are fixed in «Regulation of activity of reference laboratories» and approved by Ministry of Health

12 STANDARTS FOR QUALITY ASSURANCE Methodical recommendations for pre-analytical step (RefLab of Kyrgyzstan, 2000) Instruction for preanalytical step (RefLab of Kazakhstan, 2000) Instruction for establishing of internal laboratory quality control (RefLab of Uzbekistan, 2001) Manual for the creation and implementation Standat Operating Procedure ( SOP) – NRL of Kazakhstan, Kyrgyzstan, Uzbekistan.

13 BIOLOGICCAL STANDARTS FOR QUALITY CONTROL Reference samples with markers of HIV (anti-HIV) and viral hepatitis (anti-HCV) developed by NRL of Kyrgyzstan, Kazakhstan and Uzbekistan Internal Laboratory Control ( implementation into national reference laboratories of Kyrgyzstan, Kazakhstan and Uzbekistan) Verification test-kits ( implementation in Kyrgyzstan, Uzbekistan) Program of External quality assessment on the national level (Uzbekistan, Kyrgyzstan, Kazakhstan)

MONITORING OF THE QUALITY OF TEST PERFORMANCE National EQA/PT program International EQA/PT program

15 Design of Multi -reference pattern, developed in NRL RC AIDS and NRL of Kazakhstan # of sample Type of marker 1Anti-HIV high-active (OD/OD crit. =14,5) 2Anti-HIV Moderate-active (OD/OD crit. =4,9) 3Anti-HIV low-active (OD/OD crit. =2,9) 4Anti-HCV Moderate-titered (OD/OD crit. =3,5) 5Anti-HCV high-titered (OD/OD crit. =5,1) 6HBsAg ( 5 ng/ml) 7HBsAg (1 ng/ml) 8HBsAg (0,25 ng/ml)

16 Data of evaluation of the Multi-reference panel, developed in NRL RC AIDS and NRL of Kazakhstan # of sampleantiHIV Veronostika (Organonh Teknika) antiHIV WesternBlot BioRad,США Ortho HCV 5,0,ELISA LTXE,322 HBsAg Murex (Abbott) Anti-HIV Anti-HCV HBsAg

17 Results of national EQC of anti-HIV tests in Kazakhstan and Kyrgyzstan, 2003 (the same multi-reference, created Ref.lab.of AIDS center of Kazakhstan was used)

18 Results of EQC of anti-HCV tests in Kazakhstan and Kyrgyzstan 2003 (the same multi-reference, created Ref.lab.of AIDS center of Kazakhstan was used)

19 Results of EQC of HBsAg test in Kazakhstan and Kyrgyzstan 2003 (the same multi-reference, created Ref.lab.of AIDS center of Kazakhstan was used)

20 External quality assessment /Proficiency Testing program in Uzbekistan, laboratories of Laboratory service network participated AIDS center on the republic and province level (23), Centers for sanitary and epidemiological surveillance (8), Blood banks (12) Infection diseases hospitals (6) EQA/PT program includes distribution of specimens with serological markers of HIV, HBV and HCV infections

21 Anti-HIV test results 40% ( 13/33) could achieved 100% results. Most of laboratories (29 / 33) used Peptoscreen-2 (29 из 33) Sensitivity of Peptoscreen-2 in NRL is about %, Sensitivity

22 During EQA run only 16 from 49 laboratories had anti-HCV kits and could participate 63% (10/16)labs could achieve 100% accurate results ( to compare 17% - 4/23 in 2001 ) Anti-HCV test results Sensitivity

23 26 laboratories participated 15 participants used ELISA 10 participants used hemagglutination test 1 participant used radio immune assay 33%( 5/15) laboratories, which are using ELISA kits could achieve 100 accuracy Non of the labs which are using hemagglutination test or radio immune assay could detected HBsAg in refeence panel. HBsAg test results Чувствительность Специфичность

24 Model Performance evaluation Program (MPEP) HUMAN IMMUNODEFICIENCY VIRUS TYPE ( HIV-1) ANTIBODY TESYING Program is organized by the Division of laboratory system СDC, Atlanta It is conducted two times a year 743 laboratories participated in MPEP in January, US laboratories (80%) З6 ( 4,8%) laboratories were from Asia, including 20 laboratories from Central Asia – involved in Sentinel Epidemiologic Surveillance and laboratories of Blood Banks on the republican or city level Uzbekistan -10, Kazakhstan - 6, Kirghizia - 3, Turkmenistan - 1

25 Results of CAR laboratories participation in MPEP January 2004 –19 laboratories identified correctly 6 samples with the different anti-HIV content –1 laboratory (Uzbekistan) had false- positive result July 2004 – results are presented to CDC Atlanta from 20 participated laboratories of CAR

26 Proficiency program for anti -HIV-1 in DRIED BLOOD SPOTS, DLS, CDV Atlanta Program is organized by the Division of laboratory system СDC, Atlanta It is conducted two times a year 34 laboratories USA participated in the program in laboratories from CAR involved in Integrated Sentinel Surveillance participated in the anti-HIV DBS PT program for the first time in July 2004 Kazakhstan - 6 labs Uzbekistan - 1 lab Kirgizia - 1 lab

27 Conclusion (1) Conclusion (1) The program of quality assurance of laboratory diagnosing of HIV and viral hepatitis has been developed and implemented in Uzbekistan, Kazakhstan and Kyrgyzstan The realization of the program allowed: –Training the laboratory experts of Central Asia to quality assurance rules –Establishment of the Reference Laboratories serving as methodical centers for quality assurance of the laboratory researches of infectious diseases

28Conclusion(2) It allowed: –Obtaining the objective results of viral hepatitis sentinel surveillance in Kyrgyzstan –Organizing of quality control of test kits while licensing and further using production in Uzbekistan and Kyrgyzstan –Monitor the quality of testing of anti-HIV, anti-HCV, HBsAg, using the EQC programs in Uzbekistan, Kazakhstan and Kyrgyzstan

29 Recommendation Sustainability of the QA programs in CAR could be achieved by : –Implementation of QA issuer ( SOP, IQC) in each laboratory of laboratory service network Conducting the regional and interregional EQC/PT program on the regular basis Participation in the international EQC/PT program –Development of system of laboratory certification by policy changes in laboratory management and operations

Thank your for your attention