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Surveillance of hepatitis C Infection in France JC Desenclos, Département des Maladies Infectieuses Institut de Veille Sanitaire Outline • Background • Ongoing Surveillance – – – – – HCV screening activity newly treated patients in reference centres blood donors & residual risk indicators of arm reduction activities nosocomial HCV infections • Repeated surveys – HIV-HCV co-infection – prevalence and % of HCV infected screened – HCV associated deaths • Other projects HCV national prevention and control plan • National plan initiated by the Ministry of Health • Planned at the regional level • Secondary and tertiary prevention – screening of at risk groups (goal : 70% in 2002) – early follow up, management and treatment • Primary prevention – blood (NAT, 2001) and organ donation safety – harm reduction policy among IV drug users – control of iatrogenic transmission • health care related (standard precautions…) • tattooing, piercing… Epidemiolgical profile • Prevalence : 1.1%; 500 000 - 650 000 with HCV antibodies of whom 80% are HCV RNA+ (1994) 1,5 • Source of past infection: Hommes • Blood transfusion : 1/3 • IV drug use : 1/3 • iatrogenic : ?? 10-15% • Genotype : 0,5 10,3 • “0bservatoire VHC” 22,5 3 • 2000-2001 • Incidence : 11,8 0,5 0 20-29 4 5 1 2 • ? Femmes 1 54,9 30-39 40-49 50-59 Prevalence of HCV serum antibodies in 4 regions, France, 1994 Fécamp : 1,9% IdF * IdF* 0,9 % Lorraine* 1,0 % Centre* 0,8 % Lyon : 1,3% PACA* 1,7 % Proportion of HCV positive subjects who knew their status when screened, Social security examination center, Région Centre, France, 1993-2000 % 80 IV drug use Transfusion <91 60 Others Total 40 20 0 1993 1995 Source : Dubois et al, Concours Médical 1997 2000 Year Objectives of HCV surveillance • Data for decision making – burden – trends – risk factors • Evaluate prevention and control programs – screening activities – blood safety – IVDU harm reduction • Disease control : outbreak detection, investigation and control • Link and interaction with public health research Surveillance of laboratory HCV antibody screening activity • RENAVHC : network of hospitals and public laboratories nationally distributed (N = 257) • Initiated in 2000 • Activity by quarter – – – – monitor screening activities number of serologic tests done and of positive test confirmation activity basic characteristics of positive tests • Analysis by quarter and region (n = 22) Screening activity by quarter, RENAVHC network (n=257), France 2000 Quater 2000 Number of tests % (ELISA, Immunoblot) Positive January - March 113 834 5,1 Aprill – June 110 327 5,2 Juilly - September 103 737 4,7 Octobrer- Décember 118 254 5,0 Total 446 152 5 Newly referred patients in hepatitis C reference centers • 30 reference centers – hepatology or gastro-enterology centers – designated by the ministry of health – coordinate a regional network of clinical care, information, treatment, prevention, training… • National surveillance network – reference centers-InVS (23 in 2000; 25 in 2001) – trend overtime in patient characteristics – case definition : newly referred hepatitis C – data : clinical, epidemiological and virological Newly referred HCV patients, “pôles de référence, 2000” : mode of discovery of HCV Mode of discovery Women N = 718 n (%) 248 (34,5) Men N = 948 n (%) 282 (29,8) Total N = 1666 n(%) 530 (31,8) Risk factor 175 (24,4) 333 (35,1) 508 (30,5) Diagnostic procedure following symptoms or biologic abnomalities (anomalie des tests hépatiques, complication de cirrhose, bilan d’un carcinome hépato-cellulaire) 170 (23,7) 186 (19,6) 356 (21,4) Others 125 (17,4) 147 (15,5) 272 (16,3) 1 modalité de découverte Systematic check up (blood donation, pre surgery check up…) Newly referred HCV patients, “pôles de référence, 2000” : clinical stage Clinical stage N = 1559 n (%) Normal ALT 317 (20,3) Chronic hepatitis 1064 (68,3) Compensated Cirrhosis 129 (8,3) Decompensated cirrhosis 24 (1,5) Carcinoma 16 (1,0) Acute hepatitis 9 (0,6) 9,8 * * 1991-1993 : 20%; F. Roudot-Thoraval et al. Hepatology 1997 ; 26 : 485-90 Newly referred HCV patients, “pôles de référence, 2000” : source of infection Suspected source of infection Transfusion IV drug use Nasal drug useHCV-HIV Professional exposure † Nosocomial exposure ‡ Other factors ¶ No risk factors Women n (%) 359 46,2 183 23,2 co-infection 37 5,1 : 35 4,5 146 18,4 146 18,7 99 12,3 Men n (%) 281 518 7%131 20 136 202 115 total >100%, > to more than 1 risk factorr; †health care related ; ‡ dialysis, surgery, endoscopy ; ¶ acupuncture, injections, piercing, sexual partner HCV+ * : in 1991-2003 : 34 and 25%, respectively 27,1 34* 49,5 38* 4,1 1,9 12,9 19,4 10,7 Surveillance of blood safety • Collaborative surveillance between blood centers & InVS • HBV, HCV and HIV markers – – – – all donors repeat donors denominators characteristics of positive patients • Incidence among repeat donors • Estimate of residual risk Incidence of HIV, HBV, HCV and HTLV among repeat blood donors, France, 1992-2000 Cases per 100 000 person year 6,0 5,0 4,0 3,0 2,0 HBV HIV HCV HTLV 1,0 0,0 1992-94 1993-95 1994-96 1995-97 1996-98 1997-99 1998-00 3 years moving period Source : GATT, InVS, INTS Residual risk of transmission of blood-borne viruses per million blood donations, 1992-2000 (Transfusion; 2002, in press) Risk per 1 000 000 9,0 8,0 7,0 6,0 5,0 4,0 3,0 HBV 2,0 HCV HIV HTLV 1,0 0,0 1992-94 1993-95 1994-96 1995-97 1996-98 1997-99 1998-00 3 years moving period Source : GATT, InVS, INTS Harm reduction activities : SIAMOIS • National data-base, stratified by district • Delivery indicators – – – – number of syringes sold number of steribox kit sold amount of subutex sold methadone • Impact indicators – overdose deaths – arrests for drug offense • National and local monitoring • Sharp drop in 1ml syringe sale in last year Notification of nosocomial infection events • Introduced in 2001 • Nosocomial sentinel events – based on criteria; no positive nor negative list – HCV and HBV infection following medical care • Notification – to local district health offices – inter-regional nosocomial coordination centers – national coordination : RAISIN-InVS Examples of notification of HCV iatrogenic transmission since July 2001 • Outbreak in an haemodialysis center, 2001 – – – – 22 new infections; incidence : 52%person years 3 genotypes major breaches in hygiene procedures case-control study: infection associated with : • care by a nurse who had just cared for an HCV+ patient • not to dialysis on a machine used previously by an HCV positive patient • Seroconversions associated with : – endoscopy (1) – inappropriate use of a glucometer (1) Surveys • Seroprevalence and behavioral surveys of IV drug users (InVS, INED, ANRS) – multi-city (5 to 6 large urban area) – cluster (multi site) probability sample – blood (finger) taken for HIV, HCV and HBV – questionnaire – pilot done in Marseille (April 2002) • Prevalence of HIV-HCV co-infection • National seroprevalence survey HIV-HCV co-infection • National probability sample of HIV wards – one day survey (June 2001) – in- and out- HIV positive patients – basic epidemiological and clinical characteristics • Results – N = 1744 – co-infecion : 28% (25-30 000 patients) • Among HCV patients, HIV infection : 7% • New survey planned in 2003 – hepatitis B markers – include hepatology wards % HCV infection among HIV patients, France, June 2001 Caractéristiques Catégories Patients % séropositifs VIH+ (N) pour VHC Région PACA Ile-de-france Autres régions 219 836 691 43 25 23 1175 569 27 26 Moins de 35 35 à 44 ans 45 ans et plus 392 821 521 18 38 15 Stade A Stade B Sida 627 400 693 25 31 25 Toxicomanes Transfusés Homosexuels Hétérosexuels 394 64 562 621 84 53 6 9 Sexe Hommes Femmes Age Stade VIH Transmission Population survey • Aim : evaluate HCV prevention plan – prevalence by age (18-80), gender, region (5 inter-regions) and social status (low vs others) – % of HCV+ subjects who knew HCV status – % of HCV+ patient that are taken in charge • Stratified probability cluster sample of social security affiliated – N = 15 000 – HCV and HBV – Planned for last quarter of 2002 Mortality associated with hepatitis C • Vital statistics • Specific viral hepatitis included in 10th ICD • Not available in the 9th ICD: – chronic hepatitis – cirrhosis – carcinoma • Survey of death certificates (CépiDC-InVS) – retrospective survey of certifiers and medical records – random sample of certificates with mention of liver conditions and HIV – done in 1997 and planned in 2003 for (HCV and HBV) Death associated with chronic hepatitis per 100 000 population, by gender, France, 1979-1998. Source : CépiDC-INSERM Taux de décès / 100 000 1,4 1,2 Hommes Femmes 1,0 0,8 0,6 0,4 0,2 98 19 97 19 96 19 95 19 94 19 93 92 19 19 91 19 90 19 89 19 88 19 87 19 86 19 85 19 84 19 83 19 82 19 81 80 19 19 19 79 0,0 Representative sample of death certificates with mention of liver disease (N = 360), France, 1997 Cause of death Viral hepatitis Other infections Liver tumor Other liver diseases Cirrhosis Total Number 140 40 50 60 70 360 Source : CépiDC Estimate of the number of deaths associated with HCV in 1997 • • • • By applying sampling fraction Deaths : 1 837, 95% CI : 1 740 - 1 930 Death per 100 000 : 3,2; 95% CI : 2,9 - 3,3 Initial versus associated cause of death : – initial : – associated cause : • major role : • not major : – Total : 630 1207 564 643 1837 Source : CépiDC Death rate associated to HCV infection by age and gender, France, 1997 Death per 100 000 25 Hommes Femmes Total 20 15 10 5 0 <25 25-44 45-64 Age Source : CépiDC >64 Tous âges Disease registries • Cancer registriy (Francim) – all cancers (liver cancer included) – covers 10 districts (12% of population) – certified, coordinated and funded jointly by InVS and INSERM – being strengthened to monitor long term trends • Cirrhosis registry – no registry in France – interaction between HCV, HBV and alcohol Public health research conducted under the auspices of ANRS • Case control study of HCV seroconversions – plan to include 70 cases and 280 controls – ongoing • Cohort study of HCV- intravenous drug users – north and east of France – one year follow up – basic incidence rate : ~ 10% person year • Sociological research : perception, barriers to screening, follow up, treatment; quality of life... • Cost-efficacy studies...