SEZIONE LOMBARDA
SOCIETA` ITALIANA NEFROLOGIA
32° Congresso
Star Hotels ECHO MILANO
Milano, Sabato 25 Ottobre 2014
Come prevenire le infezioni in
dialisi:
epatite B e C
Dr. F. Fabrizi
Divisione di Nefrologia, Ospedale Maggiore
Fondazione IRCCS
Milano
Control of transmission of HBV infection
among patients on chronic haemodialysis in
the developed world has been a major goal
in the management of end-stage renal
disease
US
Reference
Year
1976
7.8%
1980
3.8%
1999
0.9%
2002
1.0%
Prevalence of HBsAg positive patients in maintenance haemodialysis
Centers for Disease Control and Prevention, Atlanta, Georgia, US
Infection control procedures against
blood-borne pathogens in HD
1) Universal precautions
2) Other precautions unique to the
HD setting:
2a) No sharing of supplies, instruments,
or medications between patients including
ancillary supply equipment
(trays, clamps, scissors, blood
pressure cuffs) and
other non-disposable items
Infection control procedures against
blood-borne pathogens in HD
2) Other precautions unique to the
HD setting:
2b) Clear separation within HD units
between clean
(where handling and storage of medications
is possible) and contaminated
areas (handling of blood specimens
and dialysis equipment after use)
Infection control procedures against
blood-borne pathogens in HD
2) Other precautions unique to the
HD setting:
2c) Cleaning and disinfection of
non-disposable items,
environmental surfaces, and dialysis
machines between use
Infection control procedures against
blood-borne pathogens in HD
2) Other precautions unique to the
HD setting:
2d) Serological testing for HBsAg
and anti-HCV antibody of
all susceptible patients
Infection control procedures against
blood-borne pathogens in HD
2) Other precautions unique to the
HD setting:
2e) Vaccination against HBV
of all susceptible patients
Universal Precautions
1) Hand washing after contact
with body fluids
2) Glove-wearing when touching
blood or other potentially
infectious material
3) Wearing of face shields,
gowns, and glasses when
exposure to
blood or body fluids is anticipated
Additional recommendations to
prevent
HBV spread within HD units
-additional HD procedures:
physical separation of HBsAg -positive from
HBsAg –negative susceptible patients
-cohorting of separate dialysis machines,
instruments, supplies, and staff
Vaccination is an important tool
for prevention
of transmission of hepatitis B
virus within dialysis units
Since early 1980s, recombinant
vaccine against hepatitis B
virus is available
The response to hepatitis B virus is
lower in patients on maintenance
dialysis compared with patients with
normal kidney function
Patients on maintenance dialysis
after hepatitis B vaccination show:
1) a lower rate of responders, i.e., those
patients who develop protective
antibody response
(antibodies against hepatitis B surface
antigen [anti-HBs]>10 UI/L)
Patients on maintenance dialysis
after hepatitis B vaccination show:
2) responders have low levels of antibody
against hepatitis B surface antigen (anti-HBs)
3) the anti-HBs antibody levels
decline logarithmically over time
The CDC currently suggest to
vaccinate susceptible dialysis
patients for hepatitis B
Recommendations for Preventing Transmission of
Infections Among Chronic Haemodialysis Patients
MMWR 2001; 50: RR-5
The frequency of responders
to HB vaccine in dialysis population
is around 50%
(versus >90%
in general population)
Poor response to Hepatitis B vaccine: reasons
• Immune compromise due to uremia
• Age
• Nutritional status
• Diabetes mellitus
• Dialysis adequacy
Fabrizi F, et al. AP&T 2011
Various approaches have been
tried in order to improve the
immunological response against
HB vaccine in dialysis population
1) I.M. (intramuscular) administration of
additional vaccine doses
2) I.M. administration of double doses of vaccine
3) I.M. administration of vaccine with adjuvants
Additional approaches to improve
the response
rate of dialysis patients
after HB vaccination exist
1) the intra-dermal administration
of recombinant HB vaccine
2) the vaccination of patients with
chronic renal failure at pre-dialysis stage
Despite these efforts, the
response rate
of dialysis patients to hepatitis B
vaccine remains lower compared
to immuno-competent populations
Infections in patients with CKD and ESRD:
Preventive strategies
Hepatitis B vaccination:
Generally underused in this population
1) Patient concerns on safety
2) Inadequate reimbursement
3) Suboptimal rates of provider
recommendations
4) Incomplete immunization history
CJASN 2008
Anti-HBV vaccines currently licensed in Italy
ENGERIX-B
Recombinant vaccine containing
20 mcg HBsAg adjuvanted with Aluminium Hydroxide
(GlaxoSmithKline)
Vaccine schedule:
40 mcg (double dose) IM months 0,1,2, and 6
Anti-HBV vaccines currently licensed in Italy
HBVAXPRO
Recombinant vaccine containing
40 mcg HBsAg adjuvanted with Aluminium Solphate
(Sanofi Pasteur)
Vaccine schedule:
40 mcg (single dose) IM months 0,1 and 6
Anti-HBV vaccines currently licensed in Italy
FENDRIX
Recombinant vaccine provided with
new adjuvant system (AS04)
composed of aluminium salt
and 3-0-desacycl-4’-monophosphoryl lipid A (MPL)
(GlaxoSmithKline)
Vaccine schedule:
20 mcg (single dose) IM months 0,1,2 and 6
Recombinant hepatitis B vaccine (Engerix-B)
Double dose (40 mcg) at months 0,1,2
Month 3: seroprotection rate 67% (79/118)
Months 24: seroprotection rate 78% (40/51)
Fabrizi F, et al. Recombinant HB vaccine use in chronic
dialysis patients. Long-term evaluation and cost-effectiveness analysis
Nephron 1996; 72: 536-543
L’adiuvante AS04
 Il MPL amplifica la risposta immunitaria mirata verso l’antigene
con il quale è co-somministrato
sangue/tessuti
Linfonodi
APCs
cellule B di
memoria
APC
Cellule T helper
MPL
TLRs
Cellule B naive
Plasmacellule
Toll-Like Receptors (TLR 4) legge
il “codice a barre” molecolare
IgG
T. Seya, T. Akazawa, T. Tsujita, M. Matsumoto, Evid Based Complement Alternat Med 3, 31 (2006)
B. Pulendran, R. Ahmed, Cell 124, 849 (2006)
C. Janeway, Immunobiology, the immune system in health and disease. (Garland Science, 2004)
-
Randomized controlled clinical trial (RCT)
Recombinant adjuvanted vaccine (n=82; Fendrix)
versus
standard recombinant vaccine (n=83; Engerix)
Kong N, et al. Immunogenicity and safety of an adjuvanted hepatitis B
vaccine in pre-hemodialysis and hemodialysis patients
Kidney Int 2005; 68: 2298-2305
Seroprotection rate:
Recombinant adjuvanted
vaccine 90.9% (95% CI, 96.3; 82.2)
Standard recombinant
vaccine 84.4% (95% CI, 91.7; 74.4)
Kong N, et al. Immunogenicity and safety of an adjuvanted hepatitis B
vaccine in pre-hemodialysis and hemodialysis patients
Kidney Int 2005; 68: 2298-2305
Seroprotection rate 80% (65/81)
HBV vaccine schedule: Fendrix 20 mcg
intramuscular administration
(deltoid muscle) at 0,1, 2, and 3 months
81 patients on long-term dialysis (three times
weekly)
Fabrizi F, Messa P. Vaccinazione anti-HBV nei pazienti in dialisi
periodica con vaccino adiuvato AS04: studio prospettico di coorte
47o Congresso Nazionale Società Italiana Igiene
(SItI) 1-4 Ottobre 2014 Rimini
Responders,n
(n=65)
Nonresponders,n
(n=16)
P
Age, yrs
67.2+14
74.5+13
0.05
Time on
dialysis, mo
40.3+42
34.5+32.9
NS
Female, n
37 (88%)
7 (43%)
NS
Caucasian, n
57 (88%)
16 (100%)
NS
Diabetes
mellitus, n
14 (21%)
3 (18%)
NS
Fabrizi F, Messa P.
47o Congresso Nazionale Società Italiana Igiene
(SItI) 1-4 Ottobre 2014 Rimini
Responders,n
(n=65)
Nonresponders,n
(n=16)
P
KT/V
1.3+0.2
1.2+0.3
NS
Naive, n
55 (85%)
13 (81%)
NS
HBcAb pos, n
5/58 (86%)
2/13 (15%)
NS
HD, n
59 (91%)
16 (100%)
NS
HCV pos, n
6 (7%)
1 (6%)
NS
Albumin, g/dL
3.9+0.3
3.8+0.4
NS
Fabrizi F, Messa P.
47o Congresso Nazionale Società Italiana Igiene
(SItI) 1-4 Ottobre 2014 Rimini
Preliminary evidence supports use of HBAS04 vaccine instead of standard
recombinant vaccine in patients on
maintenance haemodialysis
Fabrizi F, Messa P.
47o Congresso Nazionale Società Italiana Igiene
(SItI) 1-4 Ottobre 2014 Rimini
Seroprotection from HBV vaccine
1) HBV control in HD units
2) Protection for HBsAg negative pts in
the waiting list for RT from anti-HBV
core positive donors
3) Appropriate use of rooms/areas for
HBsAg positive patients on HD
‘’To isolate HBsAg-positive patients, designate
a separate room for their treatment and
dedicate machines, equipment, instruments,
supplies, and medications that will not be used
by HBV-susceptible patients’’
Recommendations for Preventing Transmission of
Infections Among Chronic Haemodialysis Patients
MMWR 2001; 50: RR-5
‘’Most importantly, staff members who are
caring for HBsAg-positive patients should not
care for susceptible patients at the same
time, including during the period when dialysis
is terminated
on one patient and initiated on another’’
Recommendations for Preventing Transmission of
Infections Among Chronic Haemodialysis Patients
MMWR 2001; 50: RR-5
‘’Newly opened units should have isolation rooms
for the dialysis of HBsAg-positive patients. For
existing units in which a separate room is not
possible, HBsAg-positive
patients should be separated from HBVsusceptible patients in an area removed from the
mainstream of activity and should undergo dialysis
on dedicated machines’’
Recommendations for Preventing Transmission of
Infections Among Chronic Haemodialysis Patients
MMWR 2001; 50: RR-5
Studies are in progress to
evaluate the protection rate
after vaccination with HBVAS04 vaccine in greater cohorts
of patients on long-term dialysis
and over long-term follow-ups