UPDATE: Assessment of the UPDATE: Assessment of the Relative Risk to Public Health Relative Risk to Public Health

from Foodborne from Foodborne Listeria Listeria monocytogenesmonocytogenes Among Selected Among Selected

Categories of Ready-to-Eat Categories of Ready-to-Eat FoodsFoods

Robert L. Buchanan Robert L. Buchanan

Sherri DennisSherri Dennis

Richard C. WhitingRichard C. Whiting

U.S. DHHS FDA CFSANU.S. DHHS FDA CFSAN

The The Listeria Listeria “Problem”“Problem”

Improve public Improve public health by health by determining determining which foods which foods should receive should receive the most the most regulatory regulatory attentionattention

FDA/FSIS Draft FDA/FSIS Draft L. L. monocytogenesmonocytogenes Risk Risk Assessment – Jan 2001Assessment – Jan 2001

Carried out in a manner consistent Carried out in a manner consistent with the guidelines established by with the guidelines established by Codex Alimentarius, NACMCF, Codex Alimentarius, NACMCF, and ICMSF for the conduct of a and ICMSF for the conduct of a microbial risk assessment:microbial risk assessment: TransparencyTransparency Broad scientific and stakeholder Broad scientific and stakeholder

inputinput Extensive peer reviewExtensive peer review

Sources and Types of Sources and Types of DataData Consumption surveysConsumption surveys Contamination data Contamination data Growth, survival and thermal Growth, survival and thermal

inactivation data -- refrigeration, inactivation data -- refrigeration, storage and cooking/reheating storage and cooking/reheating

Animal studies -- virulence of Lm Animal studies -- virulence of Lm strains and susceptibility in strains and susceptibility in subpopulationssubpopulations

Epidemiological Epidemiological investigations/listeriosis investigations/listeriosis surveillancesurveillance

Selection of Food Selection of Food CategoriesCategories Potential for Lm ContaminationPotential for Lm Contamination Ready-to-eat (with one Ready-to-eat (with one

exception, foods cooked just exception, foods cooked just prior to consumption not prior to consumption not included)included)

History of causing listeriosisHistory of causing listeriosis Food contamination and Food contamination and

consumption dataconsumption data Individual foods grouped into Individual foods grouped into

categoriescategories

Exposure AssessmentExposure Assessment

Number of Number of L. monocytogenesL. monocytogenes ingestedingested Frequency of contamination of Frequency of contamination of

foodfood Extent of contaminationExtent of contamination Growth before consumptionGrowth before consumption Frequency that food is consumedFrequency that food is consumed Amount of food consumed at a Amount of food consumed at a

servingserving

Exposure AssessmentExposure Assessment

Additional variables considered Additional variables considered to determine the amount of to determine the amount of L. L. monocytogenesmonocytogenes consumed consumed Home refrigerator temperaturesHome refrigerator temperatures Percent of frankfurters reheatedPercent of frankfurters reheated Effect of temperature on growth Effect of temperature on growth

raterate Effect of temperature on extent of Effect of temperature on extent of

growthgrowth

Hazard CharacterizationHazard Characterization Probability of illness/mortality as Probability of illness/mortality as

a function of number of a function of number of L. L. monocytogenesmonocytogenes ingested ingested Dose-response curve “shape” from Dose-response curve “shape” from

micemice Variation in virulence of Variation in virulence of L. L.

monocytogenesmonocytogenes isolates isolates Accounting for differences in Accounting for differences in

susceptibility of mice and men - susceptibility of mice and men - “anchor to health statistics”“anchor to health statistics”

Variation in susceptibility within age Variation in susceptibility within age groupsgroups

Variation in susceptibility between Variation in susceptibility between age groups age groups

Populations StudiedPopulations Studied

Perinatal:Perinatal: 16 weeks after 16 weeks after fertilization to 30 days after birthfertilization to 30 days after birth

Elderly:Elderly: 60 or more years of age60 or more years of age Intermediate-age:Intermediate-age: General General

population less than 60 years old, population less than 60 years old, includes healthy people and people includes healthy people and people more susceptible to listeriosismore susceptible to listeriosis

Risk CharacterizationRisk Characterization

Combine exposure assessment Combine exposure assessment and hazard characterizationand hazard characterization Frequency of death (mortality)Frequency of death (mortality) Convert to severe cases of Convert to severe cases of

listeriosis by multiplying by 5listeriosis by multiplying by 5 Characterize variability and Characterize variability and

uncertaintyuncertainty

Risk CharacterizationRisk Characterization

Number of Lm Number of Lm consumed per consumed per

servingserving

Mortality cases per servingMortality cases per serving

Dose -response model Dose -response model (mortality)(mortality)

Listeriosis cases Listeriosis cases per annumper annum

Listeriosis cases per Listeriosis cases per servingserving

Frequency of Frequency of servingsservings

++Exposure Exposure

assessmentassessmentHazard characterizationHazard characterization

X 5X 5

X 5X 5

[30,000 + 300] [30,000 + 300] iterationsiterations

Repeat 4,000 Repeat 4,000 times!times!

Risk CharacterizationRisk Characterization

Examined results in light of:Examined results in light of: Quantitative resultsQuantitative results

Data variabilityData variability Model uncertaintyModel uncertainty

Consideration of qualitative Consideration of qualitative factorsfactors Epidemiological historyEpidemiological history Food characteristicsFood characteristics

Extensive discussion of each food Extensive discussion of each food categorycategory

Initial (2001) Risk Ranking--Per ServingInitial (2001) Risk Ranking--Per Serving

SubpopulationFood Categoriesa Intermediate

Ageb Elderlyb Perinatalb

SEAFOODSmoked Seafood 3 3 3Raw Seafood 14 14 14Preserved Fish 7 7 6Cooked Ready-to-Eat Crustaceans 6 5 5

PRODUCEVegetables 17 17 17Fruits 18 18 18

DAIRYSoft Mold-Ripened & Blue-Veined Cheese 9 9 9Goat, Sheep, and Feta Cheese 16 16 16Fresh Soft Cheese (e.g., queso fresco)c 2 1 1Heat-Treated Natural/Process Cheese 15 15 15Aged Cheese 19 19 19Fluid Milk, Pasteurizedd 10 10 10Fluid Milk, Unpasteurizedd 11 11 11Ice Cream and Frozen Dairy Products 20 20 20Miscellaneous Dairy Products 12 13 13

MEATSFrankfurters All frankfurterse 8 8 7 Only reheated frankfurtersf [15] [15] [15] Only non-reheated frankfurtersf [1] [2] [2]Dry/Semi-Dry Fermented Sausages 13 12 12Deli Meats 4 4 4Pâté and Meat Spreads 1 2 2

COMBINATION FOODSDeli Salads 5 6 8

Listeriosis: Predicted Relative Risk Listeriosis: Predicted Relative Risk per Serving–Total Population (2001) per Serving–Total Population (2001)

0

5

10

15

20

25

P SS FS DM CR PF DS FF SC PM UM DFS MD RS PC GC V F AC IC

Food Category

Med

ian

Pred

icte

d Ca

ses

per 1

00 m

illio

n Se

rvin

gs

Initial (2001) Risk Ranking - Per Initial (2001) Risk Ranking - Per Annum Annum

SubpopulationFood Categoriesa Intermediate

Ageb Elderlyb Perinatalb

SEAFOODSmoked Seafood 6 6 7Raw Seafood 17 20 17Preserved Fish 13 13 13Cooked Ready-to-Eat Crustaceans 9 8 9

PRODUCEVegetables 11 9 11Fruits 16 14 14

DAIRYSoft Mold-Ripened and Blue-Veined Cheese 14 15 15Goat, Sheep, and Feta Cheese 18 17 18Fresh Soft Cheese (e.g., queso fresco)c 7 11 6Heat-Treated Natural Cheese and Processed Cheese 10 10 10Aged Cheese 19 18 19Fluid Milk, Pasteurizedd 3 2 2Fluid Milk, Unpasteurizedd 15 16 16Ice Cream and Frozen Dairy Products 20 19 20Miscellaneous Dairy Products 5 4 5

MEATSFrankfurterse 4 5 4Dry/Semi-Dry Fermented Sausages 12 12 12Deli Meats 1 1 1Pâté and Meat Spreads 8 7 8

COMBINATION FOODSDeli Salads 2 3 3

Listeriosis: Predicted Relative Risk Listeriosis: Predicted Relative Risk per Annum – Total Population (2001)per Annum – Total Population (2001)

0

200

400

600

800

1000

1200

1400

1600

Med

ian

Cases p

er

An

nu

m

DM PM DS FF MD SS P FS CR PC V

DFS PF F SC UM RS GCAC IC

Initial (2001) Conclusions Initial (2001) Conclusions and Interpretationand Interpretation

Broad themes reemphasized:Broad themes reemphasized: Disease primarily impacts Disease primarily impacts

specific “at-risk” specific “at-risk” subpopulationssubpopulations

Disease is rare but severeDisease is rare but severe Substantial difference in risk Substantial difference in risk

among different food among different food categoriescategories

Initial (2001) Initial (2001) Conclusions and Conclusions and InterpretationInterpretation Major factors that affect risk:Major factors that affect risk:

Amount and frequency of Amount and frequency of consumptionconsumption

Frequency and levels of Frequency and levels of contaminationcontamination

Ability of food to support growthAbility of food to support growth Refrigerated storage Refrigerated storage

temperaturetemperature Refrigerated storage timeRefrigerated storage time

Technical and Scientific Technical and Scientific Reviews of the FDA/FSIS Risk Reviews of the FDA/FSIS Risk AssessmentAssessment

R evised D ocum ent

D raft for Public C om m ent

Internal and External R eviewD ata and Assum ptions

M odelD raft D ocum ent

Request for Data and In form ationFederal R egister N otice

Public M eetingsAdvisory C om m ittee (N AC M C F)

Process For Finalizing Process For Finalizing FDA/FSIS LM Risk FDA/FSIS LM Risk AssessmentAssessment Draft RA for public comment (Jan 2001)Draft RA for public comment (Jan 2001) Public comment period closes (July 2001)Public comment period closes (July 2001) Review comments and newly available Review comments and newly available

datadata Develop changes to the modelDevelop changes to the model Develop revised documentDevelop revised document Internal review and approvalInternal review and approval Issue revised risk assessment and model Issue revised risk assessment and model

(planned June/July 2003)(planned June/July 2003) Public meeting (TBA)Public meeting (TBA) Future updates of LM RA (as needed)Future updates of LM RA (as needed)

Public commentsPublic comments

Submissions to the docket Submissions to the docket representedrepresented Consumer groups, industry, trade Consumer groups, industry, trade

associations, expert modelers, associations, expert modelers, manufacturers of food processing manufacturers of food processing equipment, food retailers, equipment, food retailers, marketers for food producers/ marketers for food producers/ processors, and processors, and education/scientific societieseducation/scientific societies

Public CommentsPublic Comments

Revise food categoriesRevise food categories Reorganize cheeses according to Reorganize cheeses according to

percentage moisturepercentage moisture Split frankfurters into two separate Split frankfurters into two separate

categories (reheated and not reheated)categories (reheated and not reheated) Move vegetable and fruit salads to deli Move vegetable and fruit salads to deli

salads food categorysalads food category Weight contamination data Weight contamination data

according to geographic location, according to geographic location, year collected, study sizeyear collected, study size

Some of the New Data Some of the New Data

AMI surveyAMI survey Home storage of deli meats and Home storage of deli meats and

frankfurtersfrankfurters

Example: Average storage time Example: Average storage time for pre-packaged deli meats and for pre-packaged deli meats and hot dogs:hot dogs:

– 1 to 3 days (32%)1 to 3 days (32%)– 4 to 7 days (37%)4 to 7 days (37%)– 8 to 10 days (6%)8 to 10 days (6%)– 11 to 14 days (4%)11 to 14 days (4%)– Don’t eat these foods (13%)Don’t eat these foods (13%)

Some of the New Data Some of the New Data (2)(2) NFPA retail studyNFPA retail study

Frequency and prevalence of LM in deli meats, Frequency and prevalence of LM in deli meats, deli salads, vegetable salads, seafood salads, deli salads, vegetable salads, seafood salads, smoked seafood, soft cheese, and Hispanic-style smoked seafood, soft cheese, and Hispanic-style cheesecheese

Total samples: 31705 tested (MD and CA) Total samples: 31705 tested (MD and CA) Example: Deli MeatsExample: Deli Meats

9,199 tested: 82 positive (0.9%)9,199 tested: 82 positive (0.9%)1 sample 101 sample 1033 to 10 to 104 4 cfu/gcfu/g7 samples 100-1000 cfu/g7 samples 100-1000 cfu/g2 samples 10-100 cfu/g2 samples 10-100 cfu/g10 samples >1-10 cfu/g10 samples >1-10 cfu/g20 samples >0.1 –1 cfu/g20 samples >0.1 –1 cfu/g42 samples 0.04 – 0.1 cfu/g42 samples 0.04 – 0.1 cfu/g

Pre-packed: 77% of the samples (0.4%) Pre-packed: 77% of the samples (0.4%) Deli-packed: 23% of the samples (2.7%)Deli-packed: 23% of the samples (2.7%)

Dose-Response Changes Dose-Response Changes Separate mortality to hospitalization Separate mortality to hospitalization

ratios calculated for each populationratios calculated for each population An additional year of FoodNet data An additional year of FoodNet data

(2000) was included (slightly reduced the (2000) was included (slightly reduced the total number of predicted cases)total number of predicted cases)

Scaling factor was selected to adjust the Scaling factor was selected to adjust the median value for the predicted number median value for the predicted number of cases to the FoodNet estimatesof cases to the FoodNet estimates A different scaling factor is used to adjust the A different scaling factor is used to adjust the

exposure assessment to the FoodNet exposure assessment to the FoodNet estimates. estimates.

As a result, the scaling factor is a distribution; As a result, the scaling factor is a distribution; the total number of predicted cases is not.the total number of predicted cases is not.

Comparison of DR 2001 and Comparison of DR 2001 and Revised –Elderly PopulationRevised –Elderly Population

1.0E-10

1.0E-09

1.0E-08

1.0E-07

1.0E-06

1.0E-05

1.0E-04

1.0E-03

1.0E-02

1.0E-01

1.0E+00

1.00E+00 1.00E+02 1.00E+04 1.00E+06 1.00E+08 1.00E+10 1.00E+12 1.00E+14

Dose (cfu/serving)

Mor

talit

y (R

ate

per S

ervi

ng)

Lower Bound Median Upper Bound

1.0E-10

1.0E-09

1.0E-08

1.0E-07

1.0E-06

1.0E-05

1.0E-04

1.0E-03

1.0E-02

1.0E-01

1.0E+00

1.0E+00 1.0E+02 1.0E+04 1.0E+06 1.0E+08 1.0E+10 1.0E+12 1.0E+14

Dose (Log10 cfu)

Morta

lity (R

ate p

er M

eal)

20012001 RevisedRevised

Comparison of 2001 and Comparison of 2001 and Revised Results – Deli meats, Revised Results – Deli meats, ElderlyElderlyListeriosiListeriosiss

MedianMedian 55thth ‘ile ‘ile 9595thth ‘ile ‘ile

Per Per annumannum

20012001 650650 99 32,09232,092

RevisedRevised 850850 165165 1,1061,106

Per Per servingserving

20012001 2.2x102.2x10-7-7 3.0x103.0x10-9-9 1.1x101.1x10-5-5

RevisedRevised 3.0x103.0x10-7-7 5.8x105.8x10-8-8 3.9x103.9x10-7-7

SummarySummary

The revised model is completed and The revised model is completed and undergoing scientific and undergoing scientific and management reviewmanagement review

The revised risk assessment report The revised risk assessment report is being prepared for scientific and is being prepared for scientific and organizational reviewsorganizational reviews

Deli meats remain among the Deli meats remain among the “highest risk” foods on a per “highest risk” foods on a per annum and per serving basisannum and per serving basis

WebsiteWebsite

http://http://www.foodsafety.govwww.foodsafety.gov