13.4.2015 Understanding Campylobacter infections Mirko Rossi DVM, PhD Ass. Professor in Environmental Hygiene, Faculty of Veterinary Medicine www.helsinki.fi/yliopisto 13.4.2015 1 Ulla-Maija Kärkkäinen ISLAB, Kuopio Tamara Tuuminen ISLAB, Mikkeli Jaakko Uksila CFHC, Jyväskylä Hilpi Rautelin Uppsala University Human studies Hakkinen Marjaana EVIRA Chicken study Jukka Corander UH Sam Sheppard University Swansea Ann-Katrin Llarena Chicken study Professor Marja-Liisa Hänninen Conceived and designed the studies Dr. Ji Zhang developing GeP Dr. Rauni Kivistö Sara Kovanen Human studies 13.4.2015 2 Campylobacter • The most commonly reported gastrointestinal bacterial pathogen in humans in the European Union (EU) – estimated 9 mil/year infections • C. jejuni/ C. coli – 95% infections (~90% of C. jejuni) • The cost (public health systems and to lost productivity) in the EU is estimated to be around EUR 2.4 billion/year • Acute self-limiting enteritis and severe post-infections sequelae www.helsinki.fi/yliopisto 13.4.2015 3 1 13.4.2015 Campylobacteriosis in Finland and EU – incidence Reported cases over 100 000 pop. 140 120 ~ 80 100 80 Uusima FI (Aver - SD w/o Uusimaa) 60 Finland 40 ~ 60 20 0 2009 2010 2011 2012 2013 Source THL - 2015 2014 www.helsinki.fi/yliopisto 13.4.2015 4 Campylobacteriosis in Finland and EU – incidence Reported cases over 100 000 pop. 140 120 100 80 Uusima FI (Aver - w/o Uusimaa) Finland 60 EU 40 20 0 2009 2010 2011 2012 2013 Source THL, EFSA - 2015 2014 www.helsinki.fi/yliopisto 13.4.2015 5 Summer peak – risk factors (Schönberg-Norio et al. 2004) No of cases Finland Total (Source THL) 1000 June-Sept July 800 600 400 200 0 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 Tasting or eating raw or undercooked meat Drinking water from a dug well Swimming in lakes and rivers www.helsinki.fi/yliopisto 13.4.2015 6 2 13.4.2015 Diversity of C. jejuni in Finland (De Hann et al., 2012) 898 isolates (1996-2010) 1 2 3 4 P < 0.05 1 = Chicken and Human 2 = Bovine, wild birds, Helsinki zoo 3 = Bovine 4 = Natural water www.helsinki.fi/yliopisto 13.4.2015 7 Defining the source of infection Wild birds Natural water 1 2 3 4 1 2 3 4 Poultry Bovine www.helsinki.fi/yliopisto (De Hann et al., 2012) 13.4.2015 8 Defining the source of infection Similar results in UK PIG ENVIRONMENT WILD BIRD Wilson et al., 2008 PLoS Genetics CATTLE CHICKEN SHEEP Eläinlääketieteellinen tiedekunta / Henkilön nimi / Esityksen nimi www.helsinki.fi/yliopisto 13.4.2015 9 3 13.4.2015 EFSA-BIOHAZ estimation ¯Campylobacter spp. positive flocks = most costeffective measure in controlling human infections ↑ broiler production/consumption ↑ campylobacteriosis 50–80% of all campylobacteriosis cases are associated with the chicken reservoir as a whole www.helsinki.fi/yliopisto 13.4.2015 10 Does this strategy have the same impact in all the EU countries? Prevalence in Broiler Human notification rate • UK 80 % • UK • Denmark 13 % • Denmark 67.3 • Finland 74.9 • Finland 5 %* 104.0 * (Jun-Sept) Values notificated for 2013 (EFSA, 2015) Eläinlääketieteellinen tiedekunta / Henkilön nimi / Esityksen nimi 13.4.2015 www.helsinki.fi/yliopisto 11 Overlapped dominant sequence types of human and avian C. jejuni Human 1996 - 2012 Broiler 2004 - 2012 De Hann et al., 2010; AEM Kovanen et al., 2014; JCM Llarena et al, 2015; PLoSONE ST-45 27 % ST-45 33 % Others (<2%) 34 % others (< 4%) 39 % ST-677 11 % ST-50 11 % ST-137 4% ST-677 9% ST-267 ST-230 2 % 6% ST-11 4 % ST-50 3 % ST-451 ST-230 5% 6% ST-267 6% www.helsinki.fi/yliopisto 13.4.2015 12 4 13.4.2015 Seasonality of prevalence of the dominant sequence types in poultry Llarena et al, 2015; PLoSONE Broiler 2004 - 2012 ST-45 33 % Others (<2%) 34 % ST-677 9% ST-11 4 % ST-50 3 % ST-451 ST-230 5% 6% ST-267 6% www.helsinki.fi/yliopisto 13.4.2015 13 ”Cryptic outbreaks”: common source in sporadic cases? Kovanen et al, 2014; JCM Whole genome analysis using ~70% of total loci (~1200 vs 7 loci of MLST) Human domestic cases 2012 from three hospital districts 1 to 8 allele differences www.helsinki.fi/yliopisto 13.4.2015 14 No overlapping between avian and human genotypes Kovanen et al., submitted www.helsinki.fi/yliopisto 5 13.4.2015 Temporary shift in the summer peak in poultry vs human at ST level Kovanen et al., submitted www.helsinki.fi/yliopisto Decreased impact of chichen meat Kovanen et al., submitted www.helsinki.fi/yliopisto Calibrating genetic diversity: more complex than expected Rossi & Zhang, unpublished www.helsinki.fi/yliopisto 13.4.2015 18 6 13.4.2015 Spatial-temporal evolution of ST-45cc: introgression or clonal expansion? Rossi & Zhang, unpublished www.helsinki.fi/yliopisto 13.4.2015 19 Spatial-temporal evolution of ST-45cc: introgression or clonal expansion? Rossi & Zhang, unpublished www.helsinki.fi/yliopisto 13.4.2015 20 Conclusion • The use of genomics in our recent studies has revealed more complex epidemiological scenarios and ecological dynamics than previously believed • It is still unclear how and through which routes different populations and sub-populations of C. jejuni circulating in animals might impact the incidence of Finnish campylobacteriosis • Will a ¯Campylobacter spp. positive flocks in Finland significantly affect the incidence of campylobacteriosis? www.helsinki.fi/yliopisto 13.4.2015 21 7
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