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VHPB - Prevention of Viral Hepatitis in Italy: Lesson Learntand the Way Forward - Catania, November 7-8, 2002
MOLECULAR TRACING OF HCV:OPTIONS FOR CONTROL OF HOSPITAL TRANSMISSION
FILIPPO ANSALDI, GIANCARLO ICARDIDipartimento di Scienze della Salute
UNIVERSITA’ DEGLI STUDI DI TRIESTEDipartimento di Scienze della Salute
UNIVERSITA’ DEGLI STUDI DI GENOVA
MOLECULAR EPIDEMIOLOGY
LABORATORY AND ANALITICAL TOOLS
Emerging Infectious Disease CharacterizationDetectionDiagnosis
Disease Emergence OriginsEcology
SURVEILLANCE OF IN
FECTIOUS AGENTS
DETERMIN
ING SOURCE O
F INFECTIO
N
NOSOCOMIAL TRANSMISSION OF HCV
HOW•Trasfusion of contaminated blood or blood products•Invasive diagnostic or therapeutic procedures•Organ transplantation
“Neither the magnitude of nosocomial transmission … nor the mechanisms involved in HCV transmission are well understood”
Sanchez-Tapias JM, 1999
WHO•Donor-to-patient transmission•Patient-to-patient transmission•Trasmission from health care workers to patients
NOSOCOMIAL TRANSMISSION OF HCV
HOW•Trasfusion of contaminated blood or blood products•Invasive diagnostic or therapeutic procedures
- endoscopy- use of non-disponsable needle- hemodialysis
PREVALENCE OF ANTI-HCV AMONG HEMODIALYSIS:1st AND 2nd GENERATION TESTS
Investigator Year Percentage of positive Difference1° Gen. 2° Gen.
Sheu 1992 32.2 47.2 +15%Huang 1993 38.6 58.8 +22.2%Chan 1993 11.8 21.6 +9.8%Sakamoto 1993 10.7 21.9 +11.2%Hayashi 1994 31.7 55.5 +23.8%Irie 1994 30.1 38.6 +8.5%
PREVALENCE OF ANTI-HCVAMONG HEMODIALYSIS PATIENTS IN THE WORLD
United KingdomScandinavia
North AmericaWestern Europe
MediterraneanSouth AmericaEastern Europe
Hong KongJapan
TaiwanSouth Africa
Egypt
0 10 20 30 40 50 60
Weste
rnA
sia
Afr
ica
Percentage of anti-HCV positive
PREVALENCE OF ANTI-HCV AMONGHEMODIALYSIS PATIENTS IN ITALY
Investigator Year Percentageof positive
Mondelli 1990 28 1° generation testGilli 1990 17.3Calabrese 1991 52 2° generation testSilini 1993 46.8Aucella 1995 35Pelleray 1996 32.6 3°generation testDi Lallo 1999 28.6Biamino 1999 13.5Petrosillo 2001 30
INCIDENCE AMONG HEMODIALYSIS PATIENTS
Investigator Country Year Incidence/1000 pts years
Jadoul Belgium 1993 17Fabrizi USA 1998 7.3Schneeberger The Netherlands 2000 5Saab USA 2001 2Petrosillo Italy 2001 9.5Valtuille Argentina 2002 4-5
Italian surveillance with small study population (<100)Incandela Italy 1994 0Aucella Italy 1995 24Biamino Italy 1999 0
RISK FACTORS
•History of blood transfusion•Time of hemodialysis•Multiple medical, surgical or endoscopic procedures (?)•High prevalence of HCV infected attending the unit•Understaffing
Critical control point: Touch to the two needle holes used for the
shunt(1000 times per year)
Surface cleaning and prevention of surface contamination
Contamination of ultrafiltrate
UNRESOLVED QUESTIONS
?•Exact mode of transmission•Efficacy of some preventive measures
Isolation of positive patients ?
• 78 patients• three times a week in 4 shifts:
Monday/Wednesday/Friday Morning (MWF/M), Monday/Wednesday/Friday Afternoon (MWF/A), Thursday/Tuesday/Saturday Morning (TTS/M) and Thursday/Tuesday/Saturday Afternoon (TTS/A).
• Two patients underwent treatment six times a week(one patient TTS/A and MWF/A and the other TTS/M and MWF/A).
• 5 rooms and everyone contained 4 consoles.• The dialysis machines were chemically disinfected
with standard procedure and the dialyzers were never re-used.
• No patients were intravenous drug users and no risk behavior were identified when patients were outside the dialysis unit.
• 21 out of 78 (26%) were anti-HCV reactive and they were treated preferentially in dedicated areas
THE HEMODIALYSIS UNIT, MAY ‘96
EPIDEMIOLOGICAL SURVEILLANCE PROGRAM
Each month•Anti-HCV screening •ALT, if abnormal
•HCV-RNA
EPIDEMIC CURVE OF 23 INCIDENT CASES
MAJ JUN JUL AUG SET OCT NOV DEC JAN FEB MAR APR
Thursday/Tuesday/Saturday Morning (TTS/M)
Monday/Wednesday/Friday Morning (MWF/M)
Monday/Wednesday/Friday Afternoon (MWF/A)
Thursday/Tuesday/Saturday Afternoon (TTS/A)
Shift:
3
4
1§
2§
2
1
1
3
3
5
5
2
2
2
2
1
3
2
4
2
2
4
5
55
Room number
Newly infected patients that were HCV-RNA positive and viremic patients already infected on May ’96 were retrospectively investigated by sequencing the 5’ untranslated region of the viral genome to identify
the route of the virus andthe mechanisms of
transmission.
AIM
STUDY POPULATIONOF THE MOLECULAR INVESTIGATION
26 HCV-RNA positive patients14 were anti-HCV positive on May ’9612 seroconverted in the period June ’96 –
May ’97Anti-HCV positive Seroconvertedpatients on May ‘96 patients
Age mean +/- s.d. 65,4+/-12,6 66,8+/-16,2Sex: Male 10 (71%) 5 (42%)Length of time on dialysis:mean+/- s.d. (months) 125,9+/-70,2 50,9+/-56,9History of
blood transfusion 4 (29%) 5 (42%)Persistent abnormal
ALT value 0 0
HD3A HD3B
HD2C HD2A HD2B
HD4A HD19
M62321
0.01 Genetic distanceMean S.E.
HD3 vs HD19 0.060.03HD19 vs M62321 0.060.03
RangeFrom a single patients at different timepoint 0 - 0.08From a cluster 0 – 0.11
(Grethe S et al., 2000)
METHODSSEQUENCING OF THE 5’ UTR: WHY ?
MWF/A SHIFT ON MAY ‘96
Room 1 Room 2 Room 3 Room 4 Room 5
2a/c, M84833 - + 1b, D31602 2a/c, M84833
1b, D31602 - 2a/c, M84833 - +
+ - + 4cd, L28058 -
+ - 2a/c, M84833 1b, L38345 -
MWF/A SHIFT ON APRIL ‘97
Room 1 Room 2 Room 3 Room 4 Rooo 5
2a/c, M84833 1b, D31602 1b, D31602 2a/c, M84833
1b, D31602 1b, D31602 2a/c, M84833 1b, D31602
4cd, L28058 4cd, L28058
2a/c, M84833 1b, L38345
TTS/M SHIFT ON APRIL ‘97
Room 1 Room 2 Room 3 Room 4 Rooo 5
1b, D31602 1b, D31602 1b, D31602 1b, D31602
2a/c, M84833
1b, D31602
2a/c, M84833
4, L296003a, D177632a/c, M848332a, D009441b, U517621b, D458661b, D316021a, D316011a, D29818
4c/d, L28058
GENOTYPE AND STRAIN DISTRIBUTION IN HEMODIALYSED PTS, IN UNTREATED PTS, IN TREATED PTS AND ASYPTOMATIC SUBJECTS
HEMODIALYSED PTSOTHERS
No = 26 No = 62
To investigate the occurrence of monitor contamination, strains infecting the new cases and those infecting the patients who were already anti-HCV positive who dialysed in the same console and during the previous shifts were compared. No correlation was observedThe epidemiological investigation included collection of information on the use of multi-dose medication vials, staffing training and patterns, glove use, environmental decontamination or other methods of infection control. Infectious control practices were substantially observed. Exposure to blood and potentially contaminated items could not be anticipated in every condition and opportunities for cross-contamination from chronically infected patients were rarely observed…BUT SOME HEALTH WORKERS WERE ENGAGED ON APRIL ‘96 AND OUR INVESTIGATION ON PERSONNEL BEHAVIOR WAS MADE ON DECEMBER ‘96...
•The molecular data of our study strongly suggest the patient-to-patient transmission of HCV in a haemodialysis unit by sequence analysis of a high conserved region of the virus genome
•In our study we performed a sequence analysis of highly conserved 5’UTR of the virus, this region being less susceptible to mutation under immunological pressure. We believe that the sequence of a high conserved region represent the fingerprint of infecting virus. The main pitfall of the 5’UTR sequence analysis is that only 5 different isolates were found in haemodialysis patients. Despite this limitation, evidence was found for nosocomial transmission and the route of HCV was evident in 2 shift
•Molecular investigation showed that measures to treat anti-HCV positive patients in dedicated areas failed.
•The sequencing data allowed us to exclude console contamination.
MAIN POINTS (I)
•The evidence that 3 different strains and no cases of co-infection caused new cases testifies in favour of no blood or blood product contamination
•Our data underlined the importance of the strict enforcement of standard precautions to prevent HCV transmission in haemodialysis units: during the process of haemodialysis exposure to blood can be routinely anticipated and gloves are required whenever caring for a patient or touching the equipment. The medications should be prepared in a separate room to that for the treatment of the patient and common trolleys should not be used to distribute medication. Training and educational program for all health workers and patients should be improved to decrease the risk and to prevent transmission of infections among chronic haemodialysis patients.
MAIN POINTS (II)
WORKING GROUP
Dipartimento di Scienze della SaluteUNIVERSITY OF GENOA
Pietro CrovariGiancarlo IcardiAnsaldi Filippo
Bianca BruzzoneDaniela de Florentiis
Paola Marasso