Dario De MediciDepartment of Veterinary Public Health and Food Safety

Istituto Superiore di Sanità

on behalf of the National Task Force on Hepatitis A

Hotel Muhlenwaldhoff, Naz‐sciaves, BZ (1 cases, German) 

Hotel Miramonti, Stava, TN (5 cases, German) 

Hotel Belvedere, Moena, TN (1 case, German) 

Hotel Avisio, Soraga, TN (5 cases, Polish) 

Hotel Garnì Ladin, Vigo di Fassa, TN (1 cases, Dutch) 

Tschenn ,BZ (1 cases, German) 

Time 0: Alerts from EPIS‐FWD and EWRS 

On 23 May 2013, the MoH designated amultidisciplinary task force to coordinate atnational level the investigation of the 2013 HAVoutbreak in Italy

A MULTIDISCIPLINARY TASK FORCE FOR THE NATIONAL INVESTIGATION OF HAV OUTBREAK

AIMS: Epidemiological investigation on human cases Microbiological testing of food specimens Genotyping of viruses isolated in human and

food specimens Traceability of suspected lots or brands of

potential vehicles in all cases

THE TASK FORCE MEMBERS: • public health and veterinary epidemiologists, • virologists and food safety microbiologists • national RASFF contact point • experts in trace-back activities

Outbreak HAV strain: genotype 1AGenBank accession number KF182323

12/05/2013 Urgent inquiry: Hepatitis A caseswith travel history to northern Italy

HAV surveillance in Italy

• Routine surveillance system, as part of Italian National Surveillance System of ComunicableDiseases 

• Sentinel surveillance system for acute viral hepatitis (SEIEVA‐Integrated Epidemiological System of Acute Viral Hepatitis), aimed to monitor the potential risk factors associated with the disease.

Data source: Integrated Epidemiological System for Acute Viral Hepatitis (SEIEVA)  70% of LHU *provisionaldata 

Distribution of HAV cases by month of onset, Italy 1Jan 2010‐ Feb 2014

0

20

40

60

80

100

120

140gen‐10

feb‐10

mar‐10

apr‐10

mag

‐10

giu‐10

lug‐10

ago‐10

set‐10

ott‐10

nov‐10

dic‐10

gen‐11

feb‐11

mar‐11

apr‐11

mag

‐11

giu‐11

lug‐11

ago‐11

set‐11

ott‐11

nov‐11

dic‐11

gen‐12

feb‐12

mar‐12

apr‐12

mag

‐12

giu‐12

lug‐12

ago‐12

set‐12

ott‐12

nov‐12

dic‐12

gen‐13

feb‐13

mar‐13

apr‐13

mag

‐13

giu‐13

lug‐13

ago‐13

set‐13

ott‐13

nov‐13

dic‐13

gen‐14

feb‐14

numero di ca

si

mese inizio sintomi

2010 2011 2012 2013

2014

1,463 cases

Data source: SEIEVA‐Integrated Epidemiological System of Acute Viral Hepatitis

Retrospective matched case control study

Incidence <3 x 100000

Incidence 3‐6 x 100000

Incidence 6‐9 x 100000

Incidence >9 x 100000

Data not available for seieva

Friuli Venezia Giulia

Apulia

Emilia Romagna

Province ofTrento

Province ofBolzano

HAV incidence by region, Jan‐Jun 2013

Retrospective matched case control study

o Case definition: a symptomatic person, positive for HAV IgM with onset of symptoms between the 1st of January 2013 and the 31st May 2013 and resident in the Regions selected. 

o Case definition for Apulia: only the cases presenting the outbreak strain sequence Gen bank number KF182323. 

o The study included  119 cases and 419 controls

o Potential risk factors explored were consumption of berries and other food items described as potentialsources of HAV infection in the literature 

Results

ECDC:The final case definition

An EU/EEA (European Economic Area) resident with laboratory confirmed HAV genotype IA and date of symptom onset (or date of testing if onset date was not available) on or after 01/01/2013 and at least one of the following conditions: 

1. identical sequence (i.e. 100.0 %) to the 2013 HAV genotype IA outbreak strain (GenBank accession  number  KF182323)  based  on  a  fragment  of  460  nucleotides  at  the  region  of VP1‐2A 

2. 99.8 % similarity to this sequence (i.e. one nucleotide difference in 460 nucleotides) 3. identical sequence (i.e. 100.0 %) on a shorter fragment of at least 174 nucleotides at 

the region of VP1‐2A

RIVM protocol for HAV typing

http://www.rivm.nl/dsresource?type=pdf&disposition=inline&objectid=rivmp:262126&versionid=&subobjectname=

Genotype distribution of availablesequences from Italian cases (n = 352) 

91 cases:genotype IA 

sequences (severalstrains unrelated to the "outbreak"  sequence) 

234 cases:genotype IA

"outbreak" sequence

26 cases:genotype IB sequences1 case:

genotype IIIA  sequence

66.5%

25.8%

7.4%

0.3%

Strong evidence

Distribution of HAV strains in 8 Italian Regions

VENETO (n=35)

LOMBARDY (n=74)

PIEDMONT (n=18)

LAZIO (n=28)

EMILIA ROMAGNA (n=52)

17.6%

13.5% 68.9%

1.4%

3.6%

27.8%

22.2%

50.0%

2.9%17.1%

80.0%

17.9%

78.6%

IA "outbreak" strain

IA strains unrelated to the outbreak

IB

IIIA

TUSCANY (n=42)2.4%

19.0% 76.2%

2.4%

84.6%

72.5%

26.1%

All IA non outbreakcases were due to 2strains only

PUGLIA (n=69)

5.8%

9.6%

90.0%

10.0%TRENTINO (n=20)

•1310 samples of soft fruits were examined for HAV, including : 

o 15 lots positive for HAVo 45 suspected lots o 11 different manufacturing companies mostly Italiano recalls of the all the confirmed lots were done on the 

market

Data source: European Food Safety Authority, 2014. Tracing of food items in connection to the multinational hepatitisA virus outbreak in Europe. EFSA Journal 2014;12(9):3821, 186 pp. doi:10.2903/j.efsa.2014.3821 

Hot‐spot: Poland (100% of the italian lots containing redcurrants)

Bulgaria (50% of the italian lots)

• Trace‐back data collection has being enlarged to better investigate hypotheses of cross‐contamination of frozen berries.

Data source : Veterinary PH and Food Safety Department, ISS

All the companies adopted strictly GMP and own HACCP systems. Laboratory testing services to assess bacteriological contamination of the food supply were correctly applied.In the company where the production of the frozen berries was on-going five samples of frozen berries and 18 surface swabs were also collected and submitted to the laboratory. All the samples tested by regional veterinary laboratory resulted negative for presence of HAV.

Methods for detecting viruses in Food

Orig

inof th

e ou

tbreak: P

hylogene

tic ana

lysis o

f the

 strains 

circulating du

ring the ou

tbreak

Action Taken• Recall of the confirmed lots and 

advice to the population regarding the use of the leftover frozen mixed berries (e.g. advice in supermarket and shops)

• Guidelines for HACCP procedures for HAV testing in frozen berries at the processing level including sampling procedures

• Risk communication to the population through MoH and ISS website (leaflet, press releases, stakeholder ‐ National Chef Association) concerning the consumption of frozen berries (i.e. cook frozen berries for 3’ min).

Conclusions

• An interdisciplinary approach is the only way to guarantee the correct management of the outbreaks at the national and international levels

• Data as of February 2014 showed a decreasing trend from Nov 2013 (decreased demand of the frozen mixed berries at retail level since Sept 2013). However, attention remains high. 

• The last positive lot of frozen mixed berries has been confirmed in October 2013• Several options of possible HAV contamination might be suspected  trace back of 

confirmed lots might reveal only primary contamination  • No single point source of contamination ("hotspot") linking all cases and contaminated lots 

(starting points) identified during the multinational outbreak could be determined. • Frozen mixed berries should be considered at risk food items if consumed raw: 

– long shelf life – complex supply chain

• Importance of molecular characterization in absence of any epidemiological link.

Acknowledgements

Central Task Force on Hepatitis A– ISS: C Rizzo, V Alfonsi, R Bruni, L Busani, A Ciccaglione, D De Medici, S

Di Pasquale, M Escher, M C Montaño‐Remacha, L Ricotta, G Scavia, ME Tosti (Istituto Superiore di Sanità),

– Ministry of Health, DG for Prevention, V Office: MG Pompa, V Martini– Ministry of Health, DG for Hygiene, Food Safety and Nutrition): M

Massaro, B Cappelletti, P Noè, A Menghi, S Guizzardi, G Plutino, DMonteleone, S Borrello

– National Reference Centre for Emerging Risks in Food Safety, IstitutoZooprofilattico Sperimentale di Lombardia e Emilia Romagna: MNLosio, G Varisco, E Pavoni

Thank you