Transcript Microbial Risk Assessment -1

Microbial Risk Assessment -1
ENVR 421
Mark D. Sobsey
Spring, 2008
WHO Health-Risk Based Framework:
Application to WHS
These principles apply to all
types of WSH activities
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
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
Exposure, Level of Protection and
Microbial Risk: The Relationship
= Confidence Region or Interval
Risk 
Exposure 
 Level of Protection (e.g., technologic control)
Important Differences Between Microbial &
Chemical Risks: The Microbial
• 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 Chemical
• 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
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)
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
ILSI/EPA Risk Assessment Framework and
Steps: Analysis Phase
QRA for Agents from Environmental Sources: Steps in
the Conceptual Framework
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
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
QRA for Agents from Environmental Sources: Steps in
the Conceptual Framework
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
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
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
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
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
Microbe Levels in Environmental Media Vary Over Time
Occurrence of Giardia Cysts in a Water: Cumulative Frequency Distribution
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.
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.
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
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?)
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
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
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
QRA for Agents from Environmental Sources: Steps in
the Conceptual Framework