Presentation of the EFSA's second scientific conference, held on 14-16 October 2015 in Milan, Italy. MICROBIOLOGICAL RISK ASSESSMENT

1. World Health Organization estimates
of the global burden of foodborne
disease, 2010
Arie Havelaar
WHO Foodborne Disease Burden
Epidemiology Reference Group (FERG)
EFSA’s 2nd Scientific Conference
Milan, Italy, 14-16 October 2015

2. Contents
• FERG: objectives and organization
• Methods, DALYs
• Source attribution
• Selected results from global reviews
• Outputs and timelines
• Discussion

3. Introduction
• Foodborne diseases (FBD) are common
throughout the world
• Food contamination events and
outbreaks capture widespread attention
• FBD are closely linked to poverty and
development
• The full extent of FBD is unknown
• The epidemiology of FBD is highly
complex

4. WHO Initiative to Estimate the
Global Burden of FBD
• Launched in 2006, external expert group:
Foodborne Disease Burden Epidemiology
Reference Group (FERG)
• FERG objectives
– To provide epidemiological estimates on the global burden of
all relevant foodborne diseases (according to age, sex and
(WHO) regions)
– To assist WHO to strengthen the capacity of countries to
conduct burden of foodborne diseases and policy context
studies
– To assist WHO in bridging the gap between collection of
scientific evidence and food safety policy making

5. FERG structure

6. Enteric hazards considered and
outcomes
Norovirus diarrheal disease
Campylobacter spp. diarrheal disease, Guillain-Barré syndrome
Enteropathogenic E. coli (EPEC) diarrheal disease
Enterotoxigenic E. coli (ETEC) diarrheal disease
Shiga toxin-producing E. coli (STEC) diarrheal disease, hemolytic uremic syndrome, end-stage renal disease
Non-typhoidal Salmonella enterica diarrheal disease, invasive salmonellosis
Shigella spp. diarrheal disease
Vibrio cholerae diarrheal disease
Cryptosporidium spp. diarrheal disease
Entamoeba histolytica diarrheal disease
Giardia spp. diarrheal disease
Hepatitis A virus hepatitis
Brucella spp. acute brucellosis, chronic brucellosis, orchitis
Listeria monocytogenes perinatal: sepsis, CNS
2
infection, neurological sequelae
acquired: sepsis, CNS infection, neurological sequelae
Mycobacterium bovis tuberculosis
Salmonella Paratyphi A paratyphoid fever, liver abcesses and cysts
Salmonella Typhi typhoid fever, liver abcesses and cysts
Bacterial toxins diarrheal disease
1

7. Parasitic hazardsconsidered and
outcomes
Cryptosporidium spp. diarrheal disease
Entamoeba histolytica diarrheal disease
Giardia spp. diarrheal disease
Toxoplasma gondii congenital: intracranial calcification, hydrocephalus, CNS abnormalities,
chorioretinitis early in life, chorioretinitis later in life
acquired: chorioretinitis , acute illness, post-acute illness
Echinococcus granulosus pulmonary, hepatic, CNS cystic echinococcosis
Echinococcus multilocularis abdominopelvic problems due to alveolar echinococcosis
Taenia solium epilepsy
Ascaris spp. ascariasis, ascariasis-related mild abdominopelvic problems, ascariasis-related
severe wasting
Trichinella spp. acute clinical trichinellosis
Clonorchis sinensis abdominopelvic problems due to heavy clonorchiasis
Fasciola spp. abdominopelvic problems due to heavy fascioliasis
Intestinal flukes abdominopelvic problems due to heavy intestinal fluke infection
Opisthorchis spp. abdominopelvic problems due to heavy opistorchiasis
Paragonimus spp. pulmonary problems due to heavy paragonimiasis, cerebral paragonimiasis

8. Chemical hazards considered and
outcomes
Aflatoxin hepatocellular carcinoma
Cassava cyanide konzo
Dioxin infertility, hypothyroidy due to prenatal and postnatal exposure
Peanuts allergy
Methylmercury intellectual disabilities
Lead intellectual disabilities, cardiovascular disease
Arsenic skin cancer, bladder cancer, lung cancer
Cadmium kidney disease
1

9. Summary metrics of population
health
• Integrate morbidity and mortality
• Incorporate age and health status of
those affected
• Address incidence, severity and duration
of adverse health consequences
• Disability Adjusted Life Years (DALYs)
– Years of Life Lost (YLL)
– Years Lived with Disability (YLD)

10. DALY = YLL + YLD
Mortality: years of life lost (YLL)
YLL = Sall outcomes ( D x e)
D: number of deaths
e: life expectancy of fatal cases
Morbidity: years lived with disability, weighted for
severity of illness (YLD)
YLD = Sall outcomes ( N x t x w)
N: number of non-fatal cases
t: duration
w: disability weight

11. DALYs: example
10 50
Age
DW
0
1
0
80
40 × 0.25
= 10 YLDs
30 × 1
= 30 YLLs
0.25
10 + 30 = 40
DALYs

12. Methodological choices
• Hazard- and incidence based approach
• By five-year age group when data available
• No age-weighting and discounting
• WHO life table (projected for 2050; life
expectancy at birth 92 years)
• GBD 2010 disability weights with WHO
modification
• Probabilistic assessment to quantify uncertainty
• Presentation at subregional level

13. FERG computational approach

14. Source attribution (SA)
• Foodborne hazards can also be
transmitted by other pathways including
the environment (e.g. water, soil, air),
direct contact between humans or by
direct human-animal contact
• Definition of food as used by FERG
‘any substance, whether processed, semi-processed or raw,
which is intended for human consumption, and includes drink,
chewing gum and any substance which has been used in the
manufacture, preparation or treatment of food but does not
include cosmetics or tobacco or substances used only as drugs’
(Codex Alimentarius Commission)

15. SA methodology
• Data for attribution at global scale are
not available
• Twelve hazards are considered 100%
foodborne
• Structured expert elicitation (Cooke’s
classical method) for nineteen hazards
• Specific estimates for each subregion
(regional panels for diarrheal pathogens,
global panels for all other hazards)

16. Global Causes of 7.6 Million
Under-Five Deaths in 2010
Liu et al., Lancet 2012;379:2151-2161
4% in
Europe and
Americas

17. Global trends in burden of childhood
deaths in 2000–10
Liu et al., Lancet 2012;379:2151-2161

18. Attributing diarrheal deaths in
children under 5 years of age
Adapted from Lanata et al., PLoS ONE 2013;8:e72788
Pathogen N studies (inpatients) Age adjusted median % (95% CI)
Rotavirus 242 38.3 (35.5-40.3)
Calicivirus 36 13.8 (11.8-17.6)
Campylobacter spp. 32 4.3 (3.1-5.8)
Enteropathogenic E. coli (EPEC) 11 15.3 (7.8-27.6)
Enterotoxigenic E. coli (ETEC) 21 8.2 (4.8-12.2)
Non-typhoidal Salmonella enterica 34 3.5 (2.9-5.2)
Shigella spp. 36 5.4 (2.9-7.9)
Vibrio cholerae O1 19 1.8 (0.0-6.1)
Cryptosporidium spp. 25 2.7 (0.6-5.6)
Entamoeba histolytica 17 0.3 (0.0-3.5)
Giardia spp. 15 3.1 (0.0-14.2)
1

19. Diarrheal deaths by pathogen in
children under 5 years of age
Adapted from Lanata et al., PLoS ONE 2013;8:e72788
Pathogen Restricted median % Deaths x 1000 (95% CI)
Rotavirus 27.8 197 (110-295)
Calicivirus 9.9 71 (39-113)
Campylobacter spp. 3.2 22 (11-50_
Enteropathogenic E. coli (EPEC) 11.1 79 (31-146)
Enterotoxigenic E. coli (ETEC) 6.0 42 (20-76)
Non-typhoidal Salmonella enterica 2.5 18 (10-30)
Shigella spp. 3.9 28 (12-53)
Vibrio cholerae O1 1.3 9 (0-37)
Cryptosporidium spp. 2.0 14 (3-31)
Entamoeba histolytica 0.2 16 (0-19)
Giardia spp. 2.3 16 (0-66)
Unknown etiology 24.5 176 (56-304)
Total 100.0 712 (491-1,049)
1

20. Norovirus prevalence in
gastroenteritis
Ahmed et al., Lancet Infect Dis. 2014;14(8):725-30

21. Global burden of foodborne
diarrheal illness
• 582 million cases, 351,000 deaths
• Over 40% of cases in children aged
under 5 years
• Most deaths by Salmonella Typhi (52,000
deaths), enteropathogenic E. coli
(37,000) and norovirus (35,000)
• Highest disease burden in the African
and South-East Asian regions

22. Disease model for toxoplasmosis
Torgerson et al., Bull WHO 2013;91:501-508

23. Global burden of toxoplasmosis
Torgerson et al., Bull WHO 2013;91:501-508

24. Global burden of trichinellosis
Devleesschauwer et al., Int J Parasitlo 2015;45:95-9
Total burden in 2010: 523 (263-882) DALYs

25. Global incidence of aflatoxin-related
hepatocellular carcinoma (HCC)
Liu et al., EHP 2010;118:818-824
• Risk assessment approach
– Aflatoxin levels and consumption in contaminated
foods
– Prevalence of hepatitis B virus
– Cancer potency factors (30x higher in HBV+ than in
HBV- individuals)
• Annually, 550,000 - 600,000 new cases of HCC
• 25,000 – 155,000 may be attributable to
aflatoxin (4.6 – 28.2%)

26. Global distribution of aflatoxin-
related HCC
Liu et al., EHP 2010;118:818-824

27. Bottom-up or top-down approach?
• Risk assessment (bottom-up) approach assumes that
– Risks are additive or
– HCC background rate (i.e. due to all risk factors not in the model, e.g.
HCV) is the same in all global populations
• Background risk in Guangxi population (basis for cancer
potency factor) higher than in other known regions
• May lead to overestimation of global HCC incidence
• Top down approach: estimate population attributable risk,
apply to HCC incidence – default in global burden studies
• Approx. 4x lower estimates of aflatoxin-associated HCC
incidence and deaths; particularly in Africa
• Validity of either method difficult to assess
• Similar considerations for other cancer endpoints and
cardiovascular disease associated with arsenic and lead

28. Country studies
• Objectives
– Strengthen capacity of countries to conduct burden
of foodborne disease assessments
– Encourage countries to use burden of foodborne
disease estimates
• Tools
– National burden of foodborne disease study
– Hazard selection tool
– Guidance on data collection
– Situation analysis, knowledge translation and risk
communication guidance

29. Pilot country studies
• Albania, Japan, Thailand, and Uganda
• Main data gaps
– Etiology of major syndromes (e.g. diarrhea)
– Incidence to chemicals
– Attribution
• Use of private data (diagnostic labs, food
industry
• Differentiation between foodborne and
waterborne exposures difficult

30. Outputs and timelines
• WHO launch – December 2-3, 2015,
Geneva
– WHO report
– PLOS collection
– On-line interactive tool
– Country study toolkit
– Communication materials
• FERG symposium – December 15-16,
2015, Amsterdam

31. FERG symposium
http://rivm.nl/media/nieuwsbrief/Ferg-symposium/

32. Discussion (1)
• Foodborne hazards cause a wide variety of
diseases, ranging from relatively mild to severe
and life-threatening
• The global burden will be quantified for the
first time
• Many data gaps were identified, creating the
need for imputation, assumptions and expert
elicitation
• Food production is linked to human disease via
mechanisms other than direct transmission of
pathogens through food – One Health
approach

33. Discussion (2)
• FERG results will help to focus control activities
to reduce the burden of foodborne disease
• Burden and priorities vary by region
• Current results are a basis for strategies at the
global, regional and national levels
• National studies are needed to refine current
regional insights
• Concerted effort is needed by all stakeholders
in the food chain, from primary production to
consumers

34. Acknowledgements
• FERG members and resource advisors
• FERG Core group: Fred Angulo, David
Bellinger, Brecht Devleesschauwer, Herman
Gibb, Tine Hald, Martyn Kirk, Rob Lake, Paul
Torgerson
• WHO : Amy Cawthorne, Claudia Stein, Tanja
Kuchenmüller, Colin Mathers, Philippe Verger,
Yuki Minato, Natsumi Chiba, Tim Corrigan
• SA expert elicitation: Willy Aspinall, Roger
Cooke, Sandra Hoffmann
• Sponsors: Netherlands, Japan, CDC, FDA,
USDA