Food-borne viruses. Marion Koopmans. Professor of public health virology
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1 Food-borne viruses Marion Koopmans Professor of public health virology 1 9 januari 2012
2 Virus group Families Foodborne Z = zoonoses dsdna African swine fever-like viruses Hepadnaviridae Papovaviridae Iridoviridae Herpesviridae Poxviridae Adenoviridae Z ssdna Circoviridae Parvoviridae dsrna - strand RNA Rhabdoviridae Bunyaviridae Arenaviridae Reoviridae Birnaviridae Orthomyxoviridae Paramyxoviridae Filoviridae Z Z Z Z + strand RNA Arteriviridae Togaviridae Flaviviridae Hepeviridae Coronaviridae Caliciviridae Picornaviridae Astroviridae Z Z Z Z Z
3 Microbial risk assessment series: Viruses in food, WHO 2008 Grouping of (potential) food-borne viruses by most likely route of exposure Group 1 Food handler End of chain High incidence Human pathogens Local, endemic Fecal oral transmission Agents: Norovirus, Hepatitis A Products: Berries, ready to eat foods Group 2 Production Early in chain High incidence Human and animal pathogens Globalisation Mixed infections > risk Fecal oral transmission Agents: Norovirus, rotavirus, Hepatitis A hepatitis E, enterovirus Products: shellfish, irrigated produce Group 3 Zoonotic Early in chain Rare Globalisation Emerging infections Oral transmission and food handling Agents: Hepatitis E, Avian influenza, SARS, Nipah, Ebola Products: meat, animal products
4 Underascertainment of food-borne viruses Group 1: No systematic surveillance Lack of knowledge in food sector Current regulations based on bacterial pathogens Indicator organisms poor predictive value for detecting virus problems Group 2: Inequity in surveillance capacity No standardisation in laboratory and epidemiological data collections Group 3: No surveillance at human animal interface
5 percentage positive 18,0 16,0 14,0 12,0 10,0 8,0 6,0 4,0 2,0 0,0 De Wit et al, Am J Epidemiol 2001; EID 2003 ; Vinje et al, 1996, 1997; JID; Sethi et al., 1999
6 The typical diagnostic work-up of a stool specimen in patients with gastro-enteritis: strong bias for bacterial pathogens hosp phys hosp phys hosp phys hosp phys Friesema et al., 2007
7 Lab considers food source Physician considers food source (viral) Patient thinks about possible food source Notification of FSA Patient remembers menu Leftovers available Analyses positive Foodnet CDC, 1997
8 patients HCW visitor Environmental surfaces Health care institution Drift recombination Factors to consider when discussing nosocomial norovirus General community New introductions? Animals New introductions? Drift, recombination Food water Environmental contamination
9 Estimated nr FB cases Per Estimated nr hospitalisations Estimated nr deaths 95% norovirus 95% hepatitis A 99% norovirus Scallan et al., 2011
10 Participants of noronet Vironet Calicinet Japan network Europe: Established in 1999 as Integrated lab and epi project study trends and their relevance Central databases for reporting outbreaks Since 2006 global, lab-based Australia/NZ network
11
12 Nr reported outbreaks II4 non II4 ~80% Mostly health care associated outbreaks Limited virus diversity Winter seasonality ~20% More diverse settings Higher proportion foodborne greater virus diversity Limited seasonality Kroneman et al., 2008
13 Steep increase in number of reported outbreaks in recent years Rapid evolution of dominant through drift strains Increased mortality High impact and chronic disease in immunocompromised Siebenga et al., 2010, van Asten et al. 2011
14 Aantal gemelde outbreaks II4 non II Nieuwe recombinanten duiken op in 9 landen via besmette oesters New recombinants introduced in 9 countries via GGIIb outbreaks contaminated shellfish Continued circulation, additional recombination, 4 different capsids nd most common infection in hospitalised children
15 NoV phylogenetic lineages in Genogroups I and II ORF 2 ORF 1 ORF 2 ORF 1 Genotypes Genotypes Genotypes Genotypes I.c1 I.p1 II.c1 II.p1 I.c2 I.p2 II.c2 II.p2 I.c3 I.p3 II.c3 II.p3 I.c4 I.p4 II.c4 II.p4 I.c5 I.p5 II.c5 II.p5 I.c6 I.p6 II.c6 II.p6 I.c7 I.p7 II.c7 II.p7 I.c8 I.p8 II.c8 II.p8 I.pa II.c9 II.p9 I.pb II.c10 II.p10 2 Established NoV genotypes Orphan capsid Orphan polymerases > new introductions? I.pc 1 II.c11 II.p11 I.pd 1 II.c12 II.p12 I.pe 1 II.c13 II.p13 2 I.pf 1 II.c14 II.p14 2 II.c15 II.c16 II.c17 II.c18 II.c19 II.c20 II.c21 II.p15 II.p16 II.p17 II.p18 II.p19 II.p20 II.pa II.pb II.pc 1 II.pd II.pe II.pf 1 II.pg II.ph 1 II.pj II.pk 1 II.pm
16 N Analysis of FBVE NoV outbreak database, capsid data Sequences 623 USTs < Agreed methods Automated 109 clusters 37 FB clusters Molecular approach: Define seq clusters Compute probability of clustering for given genotype Analyse seq clusters for association with food Compute P value for food-borne association Verhoef et al., 2011
17 Nr of outbreaks Characteristics of source contaminated outbreaks (FBVE network ) multiple countries single country Nr of countries Reporting cases Increase Foodborne (source) 20% Foodhandler 211% Person-to-person 117% Verhoef et al., 2010
18 Surveillance as information for action
19 Prevalence of Antibodies to Hepatitis A Virus, 2006 Endemic Children Asymptomatic Epidemic Adults; May be severe CDC slide, accessed at
20 Clinical Illness Problem for food investigation: Major challenge for people to remember what they ate 30 days ago
21 INFOSAN notification: November Australian authorities notified WHO, under the IHR, of a multi-jurisdictional outbreak of hepatitis A affecting over 250 people linked to semi-dried tomatoes Epidemiological evidence implicated semi-dried tomatoes Traceback investigation was complex but tomatoes imported frozen (!! Shelf-live!!) tested positive Action: Alert posted on IHR and INFOSAN closed sites
22 Cluster in France, Nov 2009 Feb 2010 Epi link to semidried tomatoes Source unknown Institute de Veille Sanitaire patite_a/point_vha_ htm
23 Count Unusual sequence cluster of HAV cases, no increased reporting Cases of hepatitis A contracted in the Netherlands between 10 December April 2010 (n=66) week 50 week 51 week 52 week 53 week 1 week 2 week 3 week 4 week 5 week 6 week 7 week 8 week 9 week 10 week 11 week 12 week 13 week 14 week 15 Nonrelated case Secondary case not confirmed Secondary case confirmed Cases unknow n Primary case confirmed Onset of disease per week Petrignani et al., 2010
24 Analysis of viral sequences Exact source not identified Complex distribution chain FAO field inspection Recent update: cases in UK and NL Identical strain Both trace back to common supermarket chain No definitive evidence > no action
25 GENOTYPE 3 HEV in swine herds (pigs 1 to 5 mo of age) 55% 17 / 44% 35 / 71% 18 / 46% 50 / 55% 23 / 40% 39 / 57% 27 / 54% Samples: Avg = 32% Herds: Avg = 52%! Over pigs raised in Europe each year! GENOTYPE 3 HEV in acute hepatitis patients 5.6% 7.2% 6.1% 4.8% 6.9% 8.4% Average 7.1% 8.5% Widdowson et al ; Boomkens et al., 2005; Rutjes et al., 2009; Herremans et al, 2007
26 Geographical clustering of human AND animal strains Sources of infection remain unclear International agreement of protocols needed
27 Oyster herpes virus Massive die-out Market shift Top producers: China, Japan, Korea
28 Country (source) Samples analyzed % positive Reference Asia 11 countries % NoV* Cheng et al., 2005 China % NoV Kou et al., 2006 Europe Netherlands 42 17% NoV Boxman et al., 2006 Italy 235 6% HAV, 14% NoV, 2 % both Groci et al., 2007 Italy % HAV Macaluso et al., 2006 Netherlands 64 22% EV Lodder et al., 2005 France 52 40% EV Dubois et al., 2004 Spain 60 47% AdV,19% EV, 24% HAV Muniain-Mujika et al., 2003 France, Netherlands, Ireland 87 9% NoV,5% EV Beuret et al., 2003 Spain? 27% HAV, 44% EV Romalde et al., 2002 Italy 100 before depuration 90 after depuration 100 market 20% (34%***) HAV 11% HAV 23% HAV Chironna et al., 2002 Italy % (13%) De Medici et al., 2001 France % AV, 23% NoV, 19% EV, 27% RV LeGyader et al., 2000 South America Brazil 27 22% HAV Coelho et al., 2003 South America 17 24% HAV Romalde et al., 2001 * NoV = norovirus, HAV = hepatitis A virus, EV = enterovirus, AdV = adenovirus, AV = astrovirus, RV =
29 Genetic profiles of enterovirus type 71 in different geographic regions > risk of introduction? Netherlands UK B0 B1 B2 B2 C1 C2 C1 C2 C1 C2 C1 C2 Europe Austria C1 C4 Bulgaria Hungary Norway USA B1 B1 C1 B1 B2 C1 C2 C2 Australia B2 C1 C2 B3 B4 C4 Vietnam C1/C4/C5 China C3 C4 Asian Pacific region Singapore Malaysia B3 B4 B3 B4 C1 B5/C1 Japan B2 B4 C2 B4 C4 B5 Taiwan B2 C2/C3 B4 C4 B5 C Van der Sanden et al., 2010
30 Key messages Food-borne virus transmission is common, but rarely diagnosed Substantial proportion relates to sewage contamination with multiple human and animal pathogens; sources of food (and sewage) global Toolbox for early detection depends on source of virus Nr of illness incidents overwhelms PH system, selection needed Internationally agreed criteria for detection needed > risk based surveillance?
31 Ackowledgements Foodborne Viruses LIS VIROLOGY Marion Koopmans Harry Vennema Annelies Kroneman Bas van der Veer Joukje Siebenga Sanela Svraka Linda Verhoef Era Tuladhar Food Borne Viruses in Europe Network and global noronet Epidemiology Yvonne van Duynhoven Ingrid Friesema Food and water microbiology Ana Maria de Roda Husman Saskia Rutjes Martijn Bouwknecht FBVE Network 31 9 januari 2012
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