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

Contents

• FERG: objectives and organization

• Methods, DALYs

• Source attribution

• Selected results from global reviews

• Outputs and timelines

• Discussion

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

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

FERG structure

Enteric hazards considered and outcomes

Norovirus diarrhealdiseaseCampylobacterspp. diarrhealdisease,Guillain-BarrésyndromeEnteropathogenicE.coli(EPEC) diarrhealdisease

EnterotoxigenicE.coli(ETEC) diarrhealdiseaseShigatoxin-producingE.coli(STEC) diarrhealdisease,hemolyticuremicsyndrome,end-stagerenaldisease

Non-typhoidalSalmonellaenterica

diarrhealdisease,invasivesalmonellosisShigellaspp. diarrhealdisease

Vibriocholerae diarrhealdiseaseCryptosporidiumspp. diarrhealdisease

Entamoebahistolytica diarrhealdiseaseGiardiaspp. diarrhealdisease

HepatitisAvirus hepatitisBrucellaspp. acutebrucellosis,chronicbrucellosis,orchitis

Listeriamonocytogenes perinatal:sepsis,CNS2infection,neurologicalsequelae

acquired:sepsis,CNSinfection,neurologicalsequelae

Mycobacteriumbovis tuberculosisSalmonellaParatyphiA paratyphoidfever,liverabcessesandcysts

SalmonellaTyphi typhoidfever,liverabcessesandcystsBacterialtoxins diarrhealdisease

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Parasitic hazardsconsidered and outcomes

Cryptosporidiumspp. diarrhealdiseaseEntamoebahistolytica diarrhealdiseaseGiardiaspp. diarrhealdisease

Toxoplasmagondii congenital:intracranialcalcification,hydrocephalus,CNSabnormalities,chorioretinitisearlyinlife,chorioretinitislaterinlife

acquired:chorioretinitis,acuteillness,post-acuteillness

Echinococcusgranulosus pulmonary,hepatic,CNScysticechinococcosisEchinococcusmultilocularis abdominopelvicproblemsduetoalveolarechinococcosis

Taeniasolium epilepsyAscarisspp. ascariasis,ascariasis-relatedmildabdominopelvicproblems,ascariasis-related

severewasting

Trichinellaspp. acuteclinicaltrichinellosisClonorchissinensis abdominopelvicproblemsduetoheavyclonorchiasis

Fasciolaspp. abdominopelvicproblemsduetoheavyfascioliasisIntestinalflukes

abdominopelvicproblemsduetoheavyintestinalflukeinfection

Opisthorchisspp. abdominopelvicproblemsduetoheavyopistorchiasis

Paragonimusspp. pulmonaryproblemsduetoheavyparagonimiasis,cerebralparagonimiasis

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Chemical hazards considered and outcomes

Aflatoxin hepatocellularcarcinomaCassavacyanide konzoDioxin infertility,hypothyroidyduetoprenatalandpostnatalexposure

Peanuts allergyMethylmercury intellectualdisabilities

Lead intellectualdisabilities,cardiovasculardiseaseArsenic

skincancer,bladdercancer,lungcancer

Cadmium kidneydisease

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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)

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

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

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

FERG computational approach

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)

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)

Global Causes of 7.6 Million Under-Five Deaths in 2010

Liu et al., Lancet 2012;379:2151-2161

4% in Europe and Americas

Global trends in burden of childhood deaths in 2000–10

Liu et al., Lancet 2012;379:2151-2161

Attributing diarrheal deaths in children under 5 years of age

Adapted from Lanata et al., PLoS ONE 2013;8:e72788

Pathogen Nstudies(inpatients) Ageadjustedmedian%(95%CI)Rotavirus 242 38.3(35.5-40.3)Calicivirus 36 13.8(11.8-17.6)

Campylobacterspp. 32 4.3(3.1-5.8)EnteropathogenicE.coli(EPEC) 11 15.3(7.8-27.6)

EnterotoxigenicE.coli(ETEC) 21 8.2(4.8-12.2)Non-typhoidalSalmonellaenterica

34 3.5(2.9-5.2)

Shigellaspp. 36 5.4(2.9-7.9)VibriocholeraeO1 19 1.8(0.0-6.1)

Cryptosporidiumspp. 25 2.7(0.6-5.6)Entamoebahistolytica 17 0.3(0.0-3.5)

Giardiaspp. 15 3.1(0.0-14.2)

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Diarrheal deaths by pathogen in children under 5 years of age

Adapted from Lanata et al., PLoS ONE 2013;8:e72788

Pathogen Restrictedmedian% Deathsx1000(95%CI)Rotavirus 27.8 197(110-295)Calicivirus 9.9 71(39-113)

Campylobacterspp. 3.2 22(11-50_EnteropathogenicE.coli(EPEC) 11.1 79(31-146)

EnterotoxigenicE.coli(ETEC) 6.0 42(20-76)Non-typhoidalSalmonellaenterica

2.5 18(10-30)

Shigellaspp. 3.9 28(12-53)VibriocholeraeO1 1.3 9(0-37)

Cryptosporidiumspp. 2.0 14(3-31)Entamoebahistolytica 0.2 16(0-19)

Giardiaspp. 2.3 16(0-66)Unknownetiology 24.5 176(56-304)

Total 100.0 712(491-1,049)

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Norovirus prevalence in gastroenteritis

Ahmed et al., Lancet Infect Dis. 2014;14(8):725-30

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

Disease model for toxoplasmosis

Torgerson et al., Bull WHO 2013;91:501-508

Global burden of toxoplasmosis

Torgerson et al., Bull WHO 2013;91:501-508

Global burden of trichinellosis

Devleesschauwer et al., Int J Parasitlo 2015;45:95-99

Total burden in 2010: 523 (263-882) DALYs

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%)

Global distribution of aflatoxin-related HCC

Liu et al., EHP 2010;118:818-824

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

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

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

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

FERG symposium

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

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

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

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