Meeting
Public health challenges for
controlling HCV infection
WHO informal consultation with VHPB
Geneva, May 13-14, 2002
Prof Alessandro Zanetti
Institute of Virology – University of Milan
Hepatitis C:
a major worldwide public health problem
• 170 million chronic carriers
• In developed countries the incidence has
progressively declined for:
improvment of general standard of living
and hygiene
 introduction of general public health measures (screening for safe blood, use of
disposable syringes and needles, universal
precautions in medical settings, etc)
Strategies for
primary prevention of HCV
Identification of carriers and acutely
infected individuals (counselling,
treatment)
Interruption of the viral chain of
transmission
Measures to prevent hepatitis C
transmission through:
 Transfusion
 I. V. drug use and other parenteral
 Nosocomial
 Sexual
 Household contact and daily life
 Vertical/perinatal
exposures
Blood transfusion safety:
prevention strategies
• Selection of periodic, volunteer,
unremunerated donors
• Evaluation of medical and personal history
• Confidential unit exclusion
• Implementation of donors screening
• Viral inactivation
• Proper use of blood, blood components
and derivates
Residual risk of transfusion-transmitted
viral infections
 Mostly related to the pre-seroconversion
window period.
 The probability of transmitting HCV through
transfusion of screened blood is related to the
length of the pre-seroconversion window phase
and the incidence of HCV infection among
donors.
 The magnitude of residual risk may differ
within countries depending on the sensitivity of
the assays used for screening and on the level
of HCV endemicity.
Residual risk of transfusion-associated HCV
infection in Italy (Transfusion 2002, in press)
Methods
Matematical model (incidence/
Study population
Site: Lombardy
Period: Jan 1996-Dec 2000
n° records examined for periodic,
volunteer, unpaid donors:
2, 411, 800
Mean donors per year: 223,500
Donation index: 2.1
Laboratory
3rd generation EIA
supplemental assays
window-period model)
Estimated residual risk of transmitting HCV/HIV
by transfusion of antibody-screened blood
Year
Residual risk
Estimated donations
+ve during the window
phase x 106 donations
HCV
HIV
(95%CI)
(95%CI)
HCV
HIV
1996
1997
1998
1999
2000
1: 90,909
1: 100,000
1 : 163,934
1 : 158,730
1 : 181,818
1:357,142
1:370,370
1:1,000,000
1:400,000
1:400,000
11
10
6.1
6.3
5.5
2.8
2.7
1
2.5
2.5
Total
1 : 126,582
1:434,782
7.9
2.3
(5.7-10)
(1.7-3)
(100,000-175,438) (333,333-588,235)
Estimated residual risk to the blood supply
in Europe and in the USA
Cases per 106 donations
Lombardy
18
15.03
16
14
12
10
8
9.7 2
7.9
6
4
4.48 1
2
0
2.3
0.58 3
HCV
2.03 2
1.75 1
HIV
1 Couroucé (1996); 2 Schreiber (1996); 3 Allain (1997)
Residual risk of
transfusion-transmitted HCV
• It is currently very small in developed
countries.
• The safety of blood supply remains a major
source of public concern, requiring a continous
effort to reach zero-risk.
• NAT can shorten the window period and,
consequently, further reduce the residual risk
of HCV transmission.
Declining time to detection of HCV/HIV markers
during the window phase following infection
HCV RNA HCV Ag
0
Infection
13 14
EIA 2.0
70
80
EIA 1.0
150 (days)
HCV
HIV RNA
0
Infection
EIA 3.0
11
p24 Ag
16
EIA 3.0
22 (days)
HIV
Estimated reduction of the residual risk of transfusiontransmitted HCV (7.9 x 106 donations) and HIV (2.3 x 106
donations) by using direct viral detection assays in
combination with the existing serologic assays
Estimated window Estimated window %Reduction Project yeld (infected Estimated
phase period
phase reduction
unit detected x106
Residual Risk
(days)
(days)
units)
x10 6 donations
HCV:
NAT
13
57
81.4
6.4
1.5
cAg
14
56
80
6.3
1.6
NAT
11
11
50
1.15
1.15
p24
16
6
28
0.6
1.7
HIV:
Measures to reduce risk of
transfusion-associated hepatitis C
• Solvent/detergent treatment of plasma and
derivates (utilized with success against enveloped
viruses).
• Photochemical decontamination using psoralen
and UV light (effective to inactivate a wide range
of viruses).
• The possibility to inactivate also agents whose
genomic sequences are unknown (not detectable
by NAT) offers the potential for approaching
of zero risk associated to transfusion.
HCV transmission by i.v. drug use
• In many developed countries, drug use is the
major source of HCV infection.
• In Europe up to 60-70% of IVDUs living in urban
areas of the major cities, are anti-HCV positives.
• The rate of infection depends on the lenght of
the time of drug abuse (25% of infection during
the first year of addiction, 50% after 5 years
and up to 90% for more than 5 years of use).
Prevention of HCV transmission
by i.v. drug use (1)
• Need of extensive education campaigns aimed:
 to prevent initiation of drug use
 to reduce harm-behaviours
 to avoid sharing of syringes and needles,
water or drug preparation equipments.
Prevention of HCV transmission
by i.v. drug use (2)
For IVDUs who cannot or will not stop injecting
drugs:
• Easy access to sterile syringes* (syringe exchange
program), accompanied by counselling and health
education.
• Safe disposal of used syringes (to reduce the chance
of re-use of blood-contamined syringes and to assure
the community about the risk of discarded syringes
in the neighborhoods).
* some countries have legal restrictions on the sale and distribution
of sterile syringes
Piercing, tatooing
 Education on the potential risk of acquiring
blodd-borne viruses through indequates
sterilized equipment, including needles.
 Tattoing makers must follow infection-control
procedures (i.e. using gloves, cleaning and
disinfecting surfaces, etc).
Nosocomial and occupational exposure
• Nosocomial transmission of HCV through unsafe
injections and other medical practices or through
unscreened blood remains a major problem in
developing countries.
• In developed countries, HCV spread is mainly
related to non-strict observance of universal
precaution measures (indequate disinfection/
sterilization, sharing of medication vials and supplies
and contamined equipment).
Modalities of acquiring blood-borne
viruses in health-care settings
 Nosocomial
 Occupational
from the environment to the
patient or from patient-to-patient
from an infected patient to the
HCW
 From an HCW to the patient
Nosocomial transmission of HCV
• Anedoctical cases as well as outbreaks of HCV
are documented, especially in hemodialysis
and in haematologic settings.
• Out patients facilities (i.e. endoscopic services
and dentist’s surgery) also represent high-risk
settings.
Measures to control and prevent
nosocomial transmission of HCV
• Strict observance of universal precautions.
• Education and training of HCWs to the proper use
of standard precautions including vaccination
against HBV.
Hemodialysis setting
 Precautions should be even more stringents.
 Patients should have assigned specific dialysis
stations.
 Clean and contamined areas should be separated.
 Isolation of HCV infected patients is not
recommended.
Occupational risk of acquiring HCV in healthcare settings and measures to prevent it
• Risk is low.
• Follow-up studies of needlestick from HCV+
sources indicate a 1-10% seroconversion rate in
recipients (mean risk of 1.8%).
• From an Italian study carried out on 3,795 expo-
sures to HCV, the rate of transmision was 0.4%
(0.9% in cases of exposures to hollow needles and
0.3% for conjunctival exposure)*.
• Standard barrier precautions and engineering
controls should be implemented to prevent infection.
* Eurosurveillance 1999; 4:33.
Transmission of HCV from HCWs to patients
and measures to prevent it
• Transmission can occur but is very rare.
• To date, six reports of confirmed transmission of
HCV from HCWs to patients have been published,
including a Spanish anesthesiologist addicted to
oppioids who infected nearly 200 patients.
• Look back of 2,286 women who had been operated
between January ’93 and March 2000 by an HCV
infected gynecologist, showed that only one
(0.04%) woman acquired infection by the
surgeon (Arch Intern Med 2002; 162: 805).
HCV-Provider-to-Patient Transmission
Published Cases
Case 1
An HCV-positive surgeon infected a patient during valve
replacement surgery.
Case 2
A highly viremic cardiothoracic surgeon infected five of his
patients intraoperatively between 1988 and 1993.
Cases 3 and 4
HCV provider-to-patient transmissions by two gynecologists.
Case 5
An HCV-positive anesthesiologist transmitted the virus during a
cardiothoracic operation.
Case 6
A Spanish anesthesiologist addicted to opioids infected almost
200 of his patients intentionally.
Esteban et al., 1996; Duckworth et al., 1999; UK Health Department, 2000; Bosch, 2000; Garfein, 2000
Management of HCV infected HCWs
No need to screen HCWs and no recommendations
(CDC, EASL) exist to restrict professional activities
of infected HCWs who, hovewer, must follow strict
aseptic tecniques and universal precautionary
measures.
 According to a Consensus Conference held at the
ISS in Rome*, HCV infected (RNA+) HCWs should
abstain from directly performing invasive
(exposure prone) procedures while no other
limitations in their activities are necessary.
* Digest Liver Dis 2001; 33:795.
Sexual transmission of HCV
• It occurs but the virus is inefficiently transmitted
through this route.
• Sex is a common behaviour and the existence of
a large reservoir of HCV carriers provides multiple
opportunities for exposure to potentially infected
partners.
• Adolescents and young adults, individuals with
multiple partners, prostitutes and their clients,
patients with STDs, partners of HCV and HIV coinfected persons are at the increased risk of
acquiring HCV sexually.
• No reliable HCV markers (i.e. genotype or HCV load)
can predict transmission.
Prevention of sexual transmission of HCV
 Counselling and education (especially for adolescents).
Individuals in long-term monogamous relationship
should be informed of the low risk of transmission
and encouraged to discuss the risk and the use of
barrier protections with sexual partners.
The use of condom is strongly recommended for
individuals with multiple partners, with STDs
and for IVDUs.
 There is no clear evidence that prophylaxis
 with Ig can event sexual transmission of HCV.
Prevention of HCV transmission
•
•
•
•
•
•
(Household contacts and “daily life”)
HCV can be percutaneously transmitted within families.
Infected persons should be informed on preventive
measures.
Prevention includes avoiding shared use of razors,
toothbrushers and any item that pierces the skin.
Sharing meals or eating utensiles is not a known
risk factor.
“Daily life” is not a risk factor.
There is no evidence to justify exclusion of anti-HCV +
individuals from partecipation in social, educational
or employment activities.
Hepatitis C and pregnancy
• Pregnancy is not contraindicated in women with HCV.
• Maternal infection does not appear to affect pregnancy
adversely nor does pregnancy have adverse effects on
the course of the liver disease.
• A woman with HCV infection should not be counselled
against becoming pregnant.
• The major issue raised by HCV infection during pregnancy is how to decrease the risk of viral transmission to the newborn.
• Available drugs cannot be used in pregancy since they
are teratogenic (Ribavirin) or have adverse effects on
fetal growth (Interferon).
Mother-to-child transmission of HCV (1)
• Risk is less than 5% but is higher for babies
•
•
•
born to woman with HIV co-infection.
Transmission is restricted to infants whose
mothers are viremic (RNA+).
Risk of infection increases with increasing
maternal viral load, but a specific cut-off value
which predicts transmission cannot be defined.
Transmission is not related to specific genotypes.
Mother-to-child transmission of HCV (2)
• There is no evidence to support that caesarean delivery may reduce risk of HCV transmission compared to
vaginal delivery.
The role of obstetric variables such as type of vaginal
delivery (spontaneous, induced, operative), duration of
rupture membranes and timing of caesarean section
(before, during labour) remains largely unexplored.
The safety of obstetric procedures (use of monitoring
devices and different instruments) during pregnancy
in mothers HCV+ is not well documented.
•
•
• Caution should be recommended in using any invasive
procedures (i.e. chorionic villous sampling, amniocentesis, cord blood sampling) that may expose the fetus or
the neonate to maternal blood.
Mother-to-infant transmission of HCV
 HCV can be detectable in colostrum and milk but
breastfeeding appears to be safe and is not
contraindicated.
 Factors that might modify the risk of viral transmission by breastfeeding (i.e. duration of lacta-
tion, levels of HCV-RNA in colostrum and milk,
exposure to chapped nipples) require further
studies.
Assisted reproductive techniques
• There are insufficient data on the interaction between
HCV infection and ART to make recommendations.
• If the woman is infected, the couple should counselled
on the potential risk of mother-to-child transmission.
• If the male is infected, there is a potential risk of
transmission to female if semen contains HCV.
• Over 1400 intrauterine inseminations attempts with
processed semen of males HCV+ have been performed without a case of transmission to the uninfected
partner (1).
• There is no report of HCV transmission through
heterologous gametes by individuals infected with
HCV, but is recommended to select uninfected donors.
1. Semprini AE - personal communication
Persons who should be screened
for HCV infection
• Persons who received transfusion or solid
•
•
trasplants prior to donor screening (1991)
Haemophiliacs
HCWs after percutaneous or mucosal exposure
to anti-HCV+ blood
IVDUs
•
• Hemodialyzed patients
• Donors of blood, organ or tissue transplantation
• Children born to mothers with hepatitis C
HCV screening
• Screening should be accompained by pre and
•
post-counselling.
Screening is not recommended for general population as well as for pregnant woman (or limi-
ted to woman undergoing prenatal invasive
procedures?) and HCWs (except those involved in
exposure prone procedures).
• Future availability of effective drugs to treat
infections and of a protective vaccine might
change our current strategy for screening.