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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...
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