# Presentation: 142723

## PERSPECTIVES ON THE SCIENCE:  WHAT DO WE KNOW AND WHAT DO WE NEED TO KNOW ABOUT MICROBIOLOGICAL RISKS OF FOOD ANIMAL PRODUCTION? 

- Ellen K. Silbergeld
- Professor, Environmental Health Sciences, Epidemiology, and Health Policy
- Johns Hopkins Bloomberg School of Public Health
- Baltimore MD USA

- EPA REGIONAL SCIENCE WORKSH on AFOs December 2004

## TOPICS 

- WHAT ARE THE CRITICAL ISSUES?
- DO WE KNOW ALL THE RISKS?
- CAN WE DO RISK ASSESSMENTS?
- WHAT INFORMATION DO WE NEED?
- DO WE HAVE THE METHODS WE NEED?
- WHAT INFORMATION DO WE HAVE
- SOURCES -- OPERATIONS
- RELEASES – WASTES, DISCHARGES, FUGITIVES
- FATE AND TRANSPORT – TRANSFORMATIONS?
- ROUTES OF EXPOSURE – ENVIR, PERSON-PERSON, ANIMAL-HUMAN, ANIMAL-ANIMAL
- MONITORING

- EPA REGIONAL SCIENCE WORKSH on AFOs December 2004

## WHAT ARE THE CRITICAL ISSUES

- FOOD SAFETY
- ANIMAL WELFARE
- SUSTAINABILITY
- ECOLOGICAL IMPACTS
**HEALTH IMPACTS**
**FOCUS ON HUMAN, BUT ZOONOSES ALSO IMPORTANT!**

- EPA REGIONAL SCIENCE WORKSH on AFOs December 2004

## HEALTH IMPACTS OF CAFOs

- MEDIA
- AIR
- WATER – SURFACE, GROUNDWATER
- SOILS and DUSTS
- AGENTS
***PARTICULATES*** and VAPORS
- CHEMICALS and ***DRUGS***
- ALLERGENS and ***BIOTOXINS***
***BACTERIA and VIRUSES***

- EPA REGIONAL SCIENCE WORKSH on AFOs December 2004

## ANTIBIOTICS, ANIMALS and BIOSOLIDS:  A NEXUS of CONCERN

- All uses of antibiotics inevitably select for resistance
- Antibiotic resistant infections are an increasingly serious clinical problem
- The same classes of drugs are used in food animal production as in clinical medicine

- EPA REGIONAL SCIENCE WORKSH on AFOs December 2004

## ANTIBIOTIC USE IN FOOD ANIMAL PRODUCTION – United States, 2002

- Growth Promotion
- 3.1 million lbs/yr (AHI)
- 27.6 million lbs/yr (UCS)
- “Prophylaxis” and Disease Treatment
- 14.7 million lbs/yr (AHI)
- 2.0 million lbs/yr (UCS)
- COMPARED TO Human Uses
- 32.3 million lbs/yr (AHI)
- 4.5 million/lbs yr (UCS)

- EPA REGIONAL SCIENCE WORKSH on AFOs December 2004

## Conditions Promoting Resistance in Agriculture

- a) Failure of Infection Control
- 	-Crowding
- 	-Often sub-optimal hygiene
- b) Exposure to Antibiotics
- 	-Widespread
- 	-Prolonged
- 	-Sub-lethal doses
- 	-Often little dose control
- c) Stress Reaction
- 	-Increases Bacterial Shedding

- EPA REGIONAL SCIENCE WORKSH on AFOs December 2004

## Changes in Agriculture Promoting Dissemination of Pathogens and AR

- Increases in Factory Farms
- Concentrated, high volume slaughter
- Broad food distribution
- Methods of waste management

- http://www.hsus.org/programs/farm/factory/life_on_factory.html

- EPA REGIONAL SCIENCE WORKSH on AFOs December 2004

**Notes:**
The increasing trend toward factory farming and high speed, high volume slaughter along with globalization of food distribution has created conditions which promote dissemination of resistant organisms by increasing the need to use antibiotics prophylactically, the economic drive for faster food production and the failure to maintain the hygiene which is one of the primary components of decreasing resistance in human systems.

Renders some infection control strategies impotent
	No possibility of identifying and isolating sick animals
	Fecal contamination inevitable in growth and slaughter phase

## Why are we concerned?

- More biosolids applied                    than land can handle
- Contributes to surface and groundwater contamination
- Increased nutrient runoff into surface waters
- Detectable presence of drugs and resistance determinants in groundwater

- EPA REGIONAL SCIENCE WORKSH on AFOs December 2004

## Releases after storms – hog farms, US

- EPA REGIONAL SCIENCE WORKSH on AFOs December 2004

## Quinolone-resistance in Human Isolates of C. jejuni/coli in Spain

- Smith in CAMPYLOBACTER
- ASM Press, 2000

- EPA REGIONAL SCIENCE WORKSH on AFOs December 2004

**Notes:**
Now let’s switch gears to a story of the therapeutic use of a critical human drug for livestock.  These data from Spain show very dramatically the temporal relationship between introduction of fq into livestock use and the development of resistant human isolates of campylobacter (95% foodborne).
< 3% before 1990, to 83% resistant in 1996
Most isolates from children in which Fq are not used and who should have had no prior exposure to the drug to drive resistance.
50% of sampled poultry products resistant to Fq in 1993

These are good ecological epidemiologic data supporting a causal relationship.

The sad news is that in 1995-6 the US FDA licensed two fq for therapeutic use in poultry.  The drug is administered in the drinking water of the whole flock (30,000 birds per house) in which individual birds with disease are found.  We are starting to see a rise in domestically acquired fq resistant campylobacter according the the NARMS surveillance data.  Do we really need to repeat this experiment in the US?

## What is the problem:  pathogens, antimicrobial resistant pathogens, or antimicrobial resistance?

- http://www.sciam.com/1998/0398issue/0398levybox3.html

- EPA REGIONAL SCIENCE WORKSH on AFOs December 2004

**Notes:**
Bacteria have been around for 3.5 billion years longer than we have.  They’ve gotten good at genetic engineering and they can do it with a generation time of 20 minutes under optimum circumstances..

Bacteria can alter their genetic material in many more ways than higher animals.  Unlike higher animals, bacteria posses both chromosomal and plasmid DNA.  Resistance can be acquired by:
	Chromosomal Mutation with vertical transmission to progeny
	Horizontal Transfer of Resistance Genes by plasmids, integrons, bacteriophages and scavenging into either plasmid or chromosomal DNA.
	Resistance genes often travel in cassettes on integrons or in clusters on plasmids, so selection driven by the presence of a single antibiotic can simultaneously select for resistance to multiple antibiotic classes.

## AMR is not a drug/bug problem – Flow of Resistance Genes among Species

- Gene Transfer in the Environment.  Levy & Miller, 1989

- EPA REGIONAL SCIENCE WORKSH on AFOs December 2004

## WHAT SHOULD WE STUDY?

- PATHOGENS OF CLINICAL IMPORTANCE?
- HUMAN COMMENSALS AND PATHOGENS?
- AMR PATHOGENS? COMMENSALS?
***RESISTANCE DETERMINANTS? ***

- EPA REGIONAL SCIENCE WORKSH on AFOs December 2004

## Many Routes of Exposure/Transfer

**rivers and streams**

**FARMS**

**Sheep**

**Pigs**

**Poultry**

**Cattle**

**HUMANS**

**Urban**

**Rural**

**Institutions**

**Animal**
**feeds**

**Slaughter**
**Harvesting**
**Processing**

**Handling**
**Preparation**
**Consumption**

**Offal**

**Irrigation**
**Drinking water**

**Manure spreading**

**Farm effluents**

**Sewage**

**Swimming**

**Sea**

**Contact**

**High Risk Populations**
** ****Children**
** ****Elderly**
** ****Immunocompromised**

**Adapted from Dr. Ruth Etzel USDA**

***Many Routes of Exposure/Transfer***

**Fish**

**Crops**

- EPA REGIONAL SCIENCE WORKSH on AFOs December 2004

**Notes:**
The point of these five examples of salmonella—a known human pathogen– is to demonstrate that the links in the causal chain are made when people look for them, and that the routes of exposure are multiple and complex.  The more we look the more we find.  Now early data is showing both antibiotics and resistant organisms in the environment—in waste lagoons and surface waters.  The more we look, the more we find.

## CASE STUDY IN REGION III: DELMARVA POULTRY INDUSTRY

**600-800 million broiler chickens produced annually.**
**5,729 broiler chicken houses**
**2,492 chicken growers **
**13,795 poultry employees**
**Total annual gross income of Delmarva broiler industry: exceeds 1.3 billion dollars.**

- EPA REGIONAL SCIENCE WORKSH on AFOs December 2004

## THE OTHER PRODUCT OF CAFOs

- EPA REGIONAL SCIENCE WORKSH on AFOs December 2004

## Slide 18

- EPA REGIONAL SCIENCE WORKSH on AFOs December 2004

## WHO IS AT RISK FOR EXPOSURE?

- _WORKERS and GROWERS_ WHO WORK IN BROILER HOUSES
- _WORKERS WHO HANDLE LIVE CHICKENS_ AT PROCESSING PLANTS
- _HOUSEHOLD_ MEMBERS OF THESE PERSONS
- _COMMUNITY RESIDENTS_

- EPA REGIONAL SCIENCE WORKSH on AFOs December 2004

## OCCUPATIONAL AND PERI-OCCUPATONAL EXPOSURES

- WORKERS IN POULTRY PRODUCTION
- Chicken catchers and live hangers; no protective clothing; no wash area; direct contact with birds, feces etc
- HOUSEHOLD CONTACTS
- Crowded living conditions; poor housing; little access to health care

- EPA REGIONAL SCIENCE WORKSH on AFOs December 2004

## Catching chickens – occupational risks

- EPA REGIONAL SCIENCE WORKSH on AFOs December 2004

## STUDY RESULTS

- WORKERS HANDLING LIVE CHICKENS ARE AT RISK OF EXPOSURE TO BACTERIA FROM POULTRY
- THESE BACTERIA ARE OFTEN DRUG RESISTANT
- HOUSEHOLD MEMBERS ARE ALSO AT RISK

- EPA REGIONAL SCIENCE WORKSH on AFOs December 2004

## Environmental dispersal of AMR

*FISH –*
* **study of anglers and fish in Delmarva* – contact with AMR pathogens
*BIRDS - Denmark*
*Migratory birds likely to carry AMR Campylobacter* – Swedish and Danish surveillance

- EPA REGIONAL SCIENCE WORKSH on AFOs December 2004

## Drugs in the environment: CAFOs

- Antimicrobials fed to animals pass into wastes
- Detectable levels of antimicrobials measured in waste lagoons
- Antimicrobials measured in surface water – sources unclear
- Arsenic...

- EPA REGIONAL SCIENCE WORKSH on AFOs December 2004

## Arsenic sources - US

- EPA REGIONAL SCIENCE WORKSH on AFOs December 2004

## ARSENIC – THE FORGOTTEN ANTIBIOTIC

- EXTENSIVE USE OF ARSENICALS IN BROILER FEEDS
- CONVERSION INTO iAS
- DOCUMENTED CONTAMINATION OF WASTE AND AMENDED LAND
- PERCOLATION INTO GROUNDWATER LIKELY
- UPTAKE INTO CROPS KNOWN TO OCCUR

- EPA REGIONAL SCIENCE WORKSH on AFOs December 2004

## ARSENIC and POULTRY

- ROXARSONE, ARSANILIC ACID USED IN POULTRY AS COCCIDIOSTATS AND GROWTH PROMOTERS – 45 g/ton feed
- GP – CONTINUOUS LIFELONG EXPOSURE IN FEEDS
- ARSENICALS EXCRETED (>70%)
- 100-200 mg/BIRD (900 million/yr)
- 50,000-90,000 mt/YEAR ARSENIC
- ARSENICALS      INORGANIC ARSENIC
- LEACH INTO GROUNDWATER

- EPA REGIONAL SCIENCE WORKSH on AFOs December 2004

## Can we use population based surveillance?

- NARMS, FOODNET
- Incomplete coverage
- High risk areas usually not covered
- Bias in sampling and analyses

- EPA REGIONAL SCIENCE WORKSH on AFOs December 2004

## Epidemiology:  why don’t we know more?

**Epidemiology:  ****why don’t we know**** more?**

**Reported AMR infections are the tip of the iceberg**
**NARMS etc assume food borne route, do not fully explore other pathways**

- EPA REGIONAL SCIENCE WORKSH on AFOs December 2004

## Do we have the tools for risk assessment?

- FDA – approval and removal of AB drugs requires risk-based findings
- WTO – risk assessment is the implied method for international agreement on standards and guidelines
- CODEX – development of guidance for risk assessment

- EPA REGIONAL SCIENCE WORKSH on AFOs December 2004

## RISK ASSESSMENT AND AMR

- WHAT WE CANNOT DO
- Cannot use chemical RA methods
- Cannot evaluate multidrug resistance
- Cannot account for fact that AMR is a characteristic of living organisms
- Cannot account for horizontal gene transfer of the hazard
- WHAT WE NEED TO DO
- Incorporate molecular understanding from theoretical population microbiology
- Understand reservoirs, compensatory mutations, etc
**	****	**

- EPA REGIONAL SCIENCE WORKSH on AFOs December 2004

## ACKNOWLEDGEMENTS

- STUDENTS
- Jon Furuno, Amy Chapin, Lance Price, Jay Graham, Amira Roess
- COLLEAGUES
- Carol Resnick, Sam Joseph, Polly Walker, Kellogg Schwab, Rolf Halden, Pat Breysse, Tim Buckley, John Bourgeois, Pat Charache, Steve Harvey, Yvette Johnson, Rocio Vailes
*Carole Morison, Patrick Harmon, Jim Lewis, Pilar Perez,* et alia
- FUNDING
- CDC, US FDA, CLF, HHMI, R W Johnson, Winslow, Baker Foundations, MD CRF-NCI

- EPA REGIONAL SCIENCE WORKSH on AFOs December 2004