Lesson learned from one of the largest community-wide outbreak of Hepatitis A in Italy between 2013 and 2014.

1. Recurring hepatitis A outbreaks in the
EU/EEA: a national perspective
Gaia Scavia (DVM)
Istituto Superiore di Sanità
Dep. Veterinary Public Healyh
and Food Safety
Rome, Italy
gaia.scavia@iss.it
ESCAIDE – European Scientific Conference on Applied
Infectious Diseases Epidemiology 2015
Stockholm, 12 November 2015

2. Incidence <3 x 100000
Incidence 3-6 x 100000
Incidence 6-9 x 100000
Incidence >9 x 100000
Data not available for seieva
Provinceof
Trento
Outbreak of Hepatitis A in Italy, 2013-2014:
The final numbers (1) - Epidemic cases 0f Hepatitis A
• 1438 cases of HAV infection reported continuosly
between 1 January 2013 and 31 August 2014, all
over the country
•369 cases (25% of the cases reported) with
sequencing of HAV performed
•247 confirmed cases (67% of all sequenced cases)
with HAV outbreak strain (HAV gen IA, KF182323)
•Characteristics of cases:
Median age: 33 yrs
 54,8%: Males
86,3%: hospitalized (median duration 7 days)
 1 death
•Consumption of frozen berries reported by 52,6%
of possible cases and by 78,2% of confirmed cases
Incidence <3 x 100000
Incidence 3-6 x 100000
Incidence 6-9 x 100000
Incidence >9 x 100000
Data not available for seieva
FriuliVenezia
Giulia
Apulia
Emilia
Romagna
Provinceof
Trento
Province of
Bolzano
Frozen berries was the suspect vehicle

3. 161 outbreak sequences
(100% nt intragroup identity
460 base pairs at the region
of VP1/2A)
genotype IA
86 sequences genotype IA
highly related to the outbreak
sequence (a shorter fragment of 174
base pairs at the region of VP1/2A)
90sequences unrelated to
the "outbreak" sequence
(93-96% nt identity)
genotype IA
29 sequences
(89.4-93.4% nt identity)
genotype IB
Data source: National Reference Laboratory, ISS
Strong
evidence
1 frozen berry mix
outbreak sequence
(100% nt identity region
VP1/2A) genotype IA
Strong microbiological evidence:
Genotyping and sequencing of HAV (VP1/2A region)
from 369 patients with HA (April 2013 – Jan 2014)

4. Probable + confirmed cases (n=119) Confirmed cases only (n=24)
Montano-Remacha C. et al. Eurosurveillance 2014;19(37):pii=20906.
Strong epidemiological evidence:
Matched Case-Control Study: 119 cases and 419 control
Strong
evidence

5. Ministry of Health (MoH):
•Dir. Public Health and Prevention
•Dir. Veterinary Public Health and Food Safety
National Public Health Institute (ISS)
•ECDC contact point for FWD – EFSA Focal Point
•Hepatitis A dedicated surveillance SEIEVA
•Monitoring of outbreak cases of HAV
•Coordination of case control study
•Molecular characterization of HAV (National Ref. Lab for
Hepatitis)
•Development of guideline for frozen berry sampling and
testing for HAV
•Validation of method ISO/TS 15216-1:2013 for detection of
HAV in food
•Tracing-back analysis on the food supply chain
•Inspection to the food processing plants
• Food Safety Laboratory (IZSLER)
• Testing food for HAV contamination
• Molecular characterization of HAV from berries
The National Task force for the Hepatitits A
Support to the Local Health Authorities (ASL) which are the competent
authorities at the territorial level (See Reg. EC/178/2002)

6. Outbreak of HA in Italy: how it all began
EPIS - 8 May: Urgent Inquiry
posted by Germany in EPIS
ISS - April: national alert about
HA outbreaks in North Europe
and tourists from Egypt
EWRS - 9 May: Alert
posted by Poland
ISS - 8 May: EPIS Alert
forwarded to MoH and regions
RASFF (Italy) - 17 May: HAV
detected in frozen mixed berries
ASL-TN- 10 May: Mixed frozen
berries were suspected as vehicle
of HAV- tracing-back; sampling
ASL 13 May : other clusters
of HA cases reported
ISS - 14 May: Italy reply
posted in EPIS
ISS – 13, 16 May: Joint
report to the MoH
ECDC – EFSA 23 May:
First Hepatitits A
Rapid Outbreak
Assessment, Italy
IZSLER - 22 May: Two lots of
frozen mixed berries
connected with cases in TN
province positive for HAV
ISS - 22 May:
Case-Control
study drafted
MoH - 23 May: National
outbreak declared:
- Joint enhanced
molecular-based
surveillance launched.
- Start of berries tracing
back activities
RASFF (Italy) – 30
May: (756 - 757)
HAV detected in
frozen mixed berries
connected with the
German tourists
NumberofcasesofHepatitisA
Strong evidence that
frozen berries were the vehicle
of HAV infection
was obtained in 14 days !

7. Outbreak of Hepatitis A in Italy, 2013-2014:
Control measures adopted during the outbreak
• All the contaminated frozen berry lots were
withdrawn and recalled from the market
• Communication to consumers on the risk of
consuming frozen berries raw
• Guidance to frozen berry sampling
• Testing for HAV soon introduced in HACCP control
plans
• Trace-back of the frozen berries suppliers
The preliminary trace-back analysis of the HAV
contaminated lots (RASFF 694-756-757) showed
that all the ingredients had been imported,
indicating the potential for a multinational
dimension of the outbreak !

8. The Food Safety Legal Framework
• Regulation (EC) 178/2002:
Article 14: Unsafe food shall not be placed on the market
Article 53: Where it is evident that food is likely to constitute a serious risk
to human health, suspension of the placing on the market or use of the
food in question
Case-by-case risk assessment
Outbreak of HA in Italy: how it continued
• Regulation (EC) No 882/2004:
Safeguard Measure, Article 56
Conditions for application of Art.53
of Reg. (EC)/178/2002 within the EU
How to adopt more robust control measures against the risk of
HAV contamination in the frozen berry chain?

9. RASFF 694
756, 757 880, 1087
1229
1134, 1350
1350 1403
Start of EFSA tracing back
EFSA tracing-back published
20142013
SamplesoffrozenberrytestedforHAV
Weekly distribution of frozen berry tested for HAV in Italy, 2013-2014 (n=1982)
Frozen berry food chain:
characterization of the risk of HAV contamination
•Testing frozen berries at retail and at processing
•Tracing-back of frozen berry suppliers
16 months to complete the tracing back exercise!

10. Frozen berry food chain: prevalence of contamination
with HAV and lots connected with the outbreak
•1982 samples of frozen berries
tested for HAV between April 2013
and October 2014
• 62 lots from 13 packaging
companies (brands) located in 5
countries were connected with the
outbreak
15 lots contaminated with HAV
(0,8% of total samples tested)
47 suspect lots: identified only
based on cases’ interviews only
•34 lots with investigation of the
supplying chain traced-back

11. •34 lots traced-back
•1691 transactions traced-back
• 57 transactions on average, per lot
(range: 3–103)
• 406 suppliers from 19 countries
• Only 1 Italian primary supplier
• Explored hypotheses:
 Pre-harvest primary
contamination
 Post Harvest: Cross
contamination across the
food supplying chain
Tracing back in Italy: characterization of the food supply chain

12. Numberoflots
20132012 2014 2015
Lots of frozen berry connected with the outbreak, by date of packaging (n=62)
Shelf Life of frozen berries 24 months
Frozen berry food chain: estimated period of presence of HAV
contaminated lots on the the Italian market
 contamination present on the market from 2012 to 2015!!

13. • Frozen berries are associated with an important public health risk:
• Very high risk profile: when consumed raw, frozen berries are ready-to-eat
products
• When contamination occur in the preharvest phase there are no points for
risk mitigation before the consumers
• Once frozen they have a prolonged shelf-life, are easily traded with the
potential of spreading infectivity worlwide
• Need for improving tracing back timeliness and compliance by MSs
• Several pieces of evidence concerning the risk profiling of frozen berries have
been produced through the investigation of the HA outbreak in Italy
• Update of the Risk Assessment of food of non animal origin (including NoV
and HAV in frozen berries) carried out by EFSA (EFSA Journal 2014:12
(6):3706)  preliminary and necessary step for the adoption of a
microbiological criterion according to general EU food safety regulations
• Close multidisciplinary collaboration, prepardness and harmonization
across sectors are the key-tools for facing foodborne outbreak crisis
Conclusions

14. Acknowledgments
The Italian National Task Force for Hepatits A
Istituto Superiore di Sanità (ISS)
Dep. Veterinary Public Health and Food Safety
M Escher, L Busani, D De Medici, S Di Pasquale, G Scavia,
National Centre for Epidemiology, Surevillance and Health Promotion
C Rizzo, V Alfonsi, L Ricotta, MC Montaño-Remacha, E Tosti Maria
Dep. of Infectious Diseases
AR Ciccaglione, S Taffon, R Bruni, M Equestre
Ministero della Salute (MoH)
Dir. Public Health and Prevention
V Martini, MG Pompa
Dir. Veterinary Public Health and Food Safety
S Guizzardi, B Cappelletti, R Lena, V Martini, M Massaro, A Menghi, D
Monteleone, S Borrello
Istituto Zooprofilattico della Lombardia e Emilia Romagna (IZSLER)
MN Losio, E Pavoni, G Varisco
E Severi, J Takkinen, L Tavoschi (ECDC-FWD)
J Richardson, O Mosbach-Schulz (EFSA)
J. Baele, K Kostenzer (EU Commission)
L Verhoef (RIVM, Bilthoven, The Netherlands),
L De Castelli (IZSPLV, Turin, Italy)
G Squintani, M Friedel (Regione Emilia-Romagna, Bologna, Italy)
F Lo Monte (USL3 Toscana, Pistoia, Italy)