Microbial Risk Assessment -1

1. Microbial Risk Assessment -1 ENVR 421 Mark D. Sobsey Spring, 2008

2. WHO Health-Risk Based Framework: Application to WHS These principles apply to all types of WSH activities

3. WHO Health-Risk Based Framework: Application to WHS • A risk-based framework • Source-to-consumer management approach to protection from exposure to environmental agents • Establishes health based-targets for control (specific microbes and chemicals) • Sets acceptable level of risk appropriate to setting and population • Helps establish and carry out Management Plans (Safety Plans) to achieve control • Includes independent surveillance • Is an integrated, proactive approach • Consistent across, compatible with and applicable to all WSH measures

4. Quantitative Microbial Risk Assessment: The Definition Applications of the principles of risk assessment to the estimation of the consequences from anticipated or actual exposure to infectious microorganisms

5. Exposure, Level of Protection and Microbial Risk: The Relationship = Confidence Region or Interval Risk  Exposure   Level of Protection (e.g., technologic control)

6. A single microbe (one unit) is infectious and can cause dramatic effects; magnitude of effects not always related to exposure level Microbes multiply in a host (increases adverse effects) Can spread to different compartments (organs & tissues) in host Microbes multiply in environmental media (some microbes) Microbes are capable of secondary spread Can first infect a host from an environmental route of exposure (water, food, etc.) Can then spread to other hosts by person-to-person transmission Some microbes cause a wide range (spectrum) of adverse effects Microbes can change: mutate, evolve, adapt, change gene expression, etc. Important Differences Between Microbial & Chemical Risks: The Microbial

7. Unique and specific structures that define (predict) activities Many molecules may be required for an effect; gradation of effects Do not multiply/reproduce No secondary spread Accumulation and compartmentalization Metabolism and chemical reactivity Detoxification Threshold (no adverse effect level) Cumulative effects Magnitude of exposure influences magnitude of adverse effects and their appearance/manifestation Distinctive health effects based on chemical reactions with specific molecules, tissues and organs Important Differences Between Microbial & Chemical Risks: the Chemical

8. Quantitative Risk Assessment for Agents from Environmental Sources: a Conceptual Framework Risk Communication Adapted from: National Academy of Sciences - National Research Council framework by US EPA and the International Life Sciences Institute (ILSI)

9. RISK ASSESSMENT FOR ENVIRONMENTALLY TRANSMITTED PATHOGENS: ILSI/EPA PARADIGM PROBLEM FORMULATION: HAZARD IDENTIFICATION CHARACTERIZATION OF EXPOSURE EFFECTS CHARACTERIZATION OF HUMAN HEALTH EFFECTS RISK CHARACTERIZATION Risk Management and Communication

10. ILSI/EPA Risk Assessment Framework and Steps: Analysis Phase

11. QRA for Agents from Environmental Sources: Steps in the Conceptual Framework

12. Conducting Hazard Identification for Microbes • Identify microbe(s) that is (are) the causative agent(s) of disease • Develop/identify diagnostic tools to: • identify symptoms • identify infection • isolate causative microbe in host specimens • identify causative microbe in host specimens • Understand the disease process from exposure to infection, illness (pathophysiology) and death • Identify transmission routes • Identify transmission scenarios

13. Conducting Hazard Identification for Microbes • Assess virulence factors and other properties of the microbe responsible for disease, including life cycle • Identify and apply diagnostic tools to determine incidence and prevalence in populations and investigate disease outbreaks • Develop models (usually animals) to study disease process and approaches to treatment • Evaluate role of immunity in overcoming/preventing infection and disease and possible vaccine development • Study epidemiology of microbe associated with exposure scenarios

14. QRA for Agents from Environmental Sources: Steps in the Conceptual Framework

15. Exposure Assessment Purpose: determine the quantity or dose Dose = number, quantity or amount of microorganisms corresponding to a single exposure (e.g., by ingestion) • Average or typical dose • A measure of central tendency (mean or median) • Distribution of doses • microbe quantity varies in time and space • described as a probability or frequency distribution • a probability density function

16. CHARACTERIZATION OF EXPOSURE - ELEMENTS INCLUDED IN PATHOGEN CHARACTERIZATION: OCCURRENCE • Temporal distribution, duration and frequency • Concentration in food or environmental media • Spatial distribution • clumping, aggregation, association with particles, clustering • Niche • ecology and non-human reservoirs: Where are they in the environment and what other host harbors them? • potential to multiply/survive in specific media

17. CHARACTERIZATION OF EXPOSURE - ELEMENTS INCLUDED IN PATHOGEN CHARACTERIZATION: OCCURRENCE • Survival, persistence, and amplification • Seasonality • Meteorological and climatic events • Presence of control or treatment processes • reliability and variability of processes • Indicators/surrogates for indirect evaluation • predictive of pathogen

18. ELEMENTS CONSIDERED IN PATHOGEN CHARACTERIZATION • Virulence and pathogenicity of the microorganism • Pathologic characteristics and diseases caused • Survival and multiplication of the microorganism • Resistance to control or treatment processes • Host specificity • Infection mechanism and route; portal of entry • Potential for secondary spread • Taxonomy and strain variation • Ecology and natural history

19. Pathogen Characteristics or Properties Favoring Environmental Transmission KEY: Multiple sources and high endemicity (continued presence) in humans, animals and environment • High concentrations released into or present in environmental media (water, food, air, etc.) • High carriage rate in human and animal hosts • Asymptomatic carriage in non-human hosts • Ability to proliferate in water and other media • Ability to adapt to and persist in different media or hosts • Seasonality and climatic effects • Natural and anthropogenic sources

20. Microbe Levels in Environmental Media Vary Over Time Occurrence of Giardia Cysts in a Water: Cumulative Frequency Distribution

21. Pathogen Characteristics or Properties Favoring Environmental Transmission • Ability to persist or proliferate in environment • Ability to survive or penetrate treatment processes • Stable environmental forms • spores, cysts, oocysts, stable outer viral layer (protein coat), bacterial capsule (outer polysaccharide layer), etc. • Resistance to biodegradation, heat, cold (freezing), drying, dessication, UV light, ionizing radiation, pH extremes, etc. • Resists proteases, amylases, lipases and nucleases • Possesses DNA repair mechanisms and other injury repair processes • Colonization, biofilm formation, resting stages, protective stages, parasitism • Spatial distribution • Aggregation, particle association, intercellular accumulation, etc.

22. Virulence Properties of Pathogenic Bacteria Favoring Environmental Transmission Virulence properties: structures or chemical constituents that contribute to pathophysiology • Outer cell membrane of Gram negative bacteria: an endotoxin (fever producer) • Exotoxins: release toxic chemicals • Pili: for attachment and effacement to cells and tissues • Invasins: to facilitate cell invasion • Effacement factors • Spores • highly resistant to physical and chemical agents • very persistent in the environment • plasmids, lysogenic bacteriophages, etc.

23. Pathogen Characteristics or Properties Favoring Environmental Transmission Genetic properties favoring survival and pathogenicity • Double-stranded DNA or RNA • DNA repair • Ability for genetic exchange, mutation and selection • recombination • plasmid exchange, transposition, conjugation, etc. • point mutation • reassortment • gene expression control • Virulence properties: expression, acquisition, exchange • Antibiotic resistance

24. Role Emergence and Selection of New Microbial Strains on Exposure Risks • Antigenic changes in microbes can create changes that overcome immunity, increasing risks of re-infection or illness • Antigenically different strains of microbes appear in hosts or are created in the environment; are selected for over time and space • Constant selection of new strains by antigenic shift and drift • Genetic recombination, reassortment , bacterial conjugation, bacteriophage infection or bacteria and point mutations • Antigenic Shift in viruses: • Major change in virus genetic composition by gene substitution or replacement (e.g., reassortment); Influena A viruses (e.g., H?N?)

25. Role Emergence and Selection of New Microbial Strains on Exposure Risks • Antigenic Drift: • Minor changes in genetic composition, often by mutation involving specific codons in existing genes (point mutations) • A single point mutation can greatly alter microbial virulence • Microbial mimicking of host antigens; e.g. malaria • Antigens expressed by pathogen resemble host antigens; they can change

26. Other Pathogen Characteristics or Properties Favoring Environmental Transmission • Ability to Cause Infection and Illness • Low infectious dose • High probability of infection and illness from exposure to one or a few microbes • Infects by multiple routes • Ingestion: gastrointestinal (GI) • Inhalation: respiratory • Cutaneous: skin • eye • Other routes

27. CHARACTERIZATION OF EXPOSURE:ELEMENTS CONSIDERED IN EXPOSURE ANALYSIS • Identification of water, food or other media/vehicles of exposure • Units of exposure (e.g number of cells) • Routes of exposure and transmission potential • Size of exposed population • Demographics of exposed population • Spatial and temporal nature of exposure (single or multiple; intervals) • Behavior of exposed population • Treatment (e.g. of water), processing (e.g., of foods), and recontamination

28. QRA for Agents from Environmental Sources: Steps in the Conceptual Framework