Previous Page Table of Contents Next Page


Descriptive hazard characterization serves to structure and present the available information on the spectrum of human illness associated with a particular pathogen, and how this is influenced by the characteristics of the host, the pathogen and the matrix, as indicated in Figure 3. This is based on a qualitative or semi-quantitative analysis of the available evidence, and will take the different pathogenic mechanisms into account.

5.1 Information related to the disease process

When a hazard characterization is being undertaken, one of the initial activities will be to evaluate the weight of evidence for adverse health effects in humans in order to determine, or confirm, the ability of the pathogen to cause disease. The weight of evidence is assessed on the basis of causality inferences appropriately drawn from all of the available data. This entails examination of the quantity, quality and nature of the results available from clinical, experimental and epidemiological studies; analyses of pathogen characteristics; and information on the biological mechanisms involved. When extrapolating from animal or in vitro studies, awareness of the biological mechanisms involved is important with respect to assessment of relevance to humans.

Undertaking hazard characterization for waterborne and foodborne microbial pathogens, the biological aspects of the disease process should be considered. Each of these steps is composed of many biological events. Careful attention should be given in particular to the following general points:

The information related to the disease should provide detailed - qualitative or quantitative, or a combination - insights into the disease process. In most cases, this would be based on the available clinical and epidemiological studies. Narrative statements are helpful to summarize the nature of and confidence in the evidence, based on limitations and strengths of the database. Each source of information has its advantages and limitations, but collectively they permit characterization of potential adverse health effects. The analysis should include evaluations of the statistical power of the studies, and appropriate control of possible bias, while identifying what is uncertain and the sources of uncertainty.

Characterization of the adverse human health effects should consider the whole spectrum of possible effects in response to the microbial hazard, including asymptomatic infections and clinical manifestations, whether acute, subacute or chronic (e.g. long-term sequelae), or intermittent (see Table 1). Where clinical manifestations are concerned, the description would include consideration of the diverse clinical forms, together with their severity, which may be variable among pathogens and among hosts infected with the same pathogen. Severity may be defined as the degree or extent of clinical disease produced by a microorganism, and may be expressed in a variety of ways, most of which include consideration of possible outcomes. For mild gastrointestinal symptoms, severity may be expressed as duration of the illness, or as the proportion of the population affected (morbidity). Where the gravity of the distress requires medical care or includes long-term illness, or both, severity may be expressed in terms of the costs to society, such as the proportion of workdays lost or cost of treatment. Some pathogens and the related clinical forms may be associated with a certain degree of mortality and therefore severity may be expressed as mortality rate. For pathogens that cause chronic illness (i.e. the disease leaves long-term sequelae) it may be desirable to include, in the characterization of the human health effects, considerations related to quality of life as it may be affected by the disease. Quality of life may be expressed in a variety of ways, depending on the nature of the illness. For instance, human life expectancy may decrease, chronic debilitation may occur, or quality of life may be affected by episodic bouts of disease. Increasingly, concepts such as Quality Adjusted Life Years or Disability Adjusted Life Years are being used to integrate and quantify the effects of different disease end-points on the health of individuals or populations (for examples, see WHO, 2000a; Havelaar et al., 2000).

Table 1. Elements that might be included in characterization of adverse human health effects.

Clinical forms

Duration of illness

Severity (morbidity, mortality, sequelae)


Epidemiological pattern

Secondary transmission

Quality of life

SOURCE: Adapted from ILSI, 2000.

In addition to a description of the human adverse health effects, information on the disease should include consideration of the epidemiological pattern and indicate whether the disease may be sporadic, endemic or epidemic. The frequency or incidence of the disease or its clinical forms, or both, should be addressed, together with their evolution with time and possible seasonal variations. The description should include consideration of the repartition of clinical forms according to specific groups at risk. Finally, the potential for, extent of or amount of transmission, including asymptomatic carriers, as well as secondary transmission, should also be characterized. Information collected on these aspects is important to guide the risk characterization phase of the risk assessment.

In all cases, and with particular regard to further modelling, it is important that the characterization includes a definition of possible end-points to be considered. Thought needs to be given to the appropriate criteria when defining "infection" of the host by the pathogenic agent, and the criteria of what constitutes a clinical "case". In addition, a definition of the severity scale should be provided, specifying the indicator chosen (e.g. disease end-point or consequences) and how it can be measured. The description should also include information on uncertainties and their sources.

To the extent possible, the characterization should incorporate information on the physiopathology of the disease, i.e. on the biological mechanisms involved. Depending on the information available, this would include consideration of elements such as:

The "natural history" of the disease needs to be completed by specific consideration of factors related to the microorganism, the host and the food matrix, insofar as they may affect development of health effects, their frequency and severity.

5.2 Information related to the pathogen

Basically, this information is analysed with a view to determining the characteristics of the pathogen that affect its ability to cause disease in the host. The analysis will take the biological nature of the pathogen into account (bacterial, viral, parasitic, prion) as well as the relevant mechanisms that cause illness (infectious, toxico-infectious, toxigenic, invasive or not, immune-mediated illness, etc.). In principle, the descriptive hazard characterization is applicable to all types of pathogens and all associated illnesses. In practice, by nature of the data collected, the focus will be on acute effects, associated with single exposures rather than long-term effects associated with chronic exposure. Note that the possible interaction between repeated single exposures (e.g. the development of acquired immunity) is an integral part of the descriptive characterization.

The ability of a pathogen to cause disease is influenced by many factors (Table 2). Some of these factors relate to the intrinsic properties of the pathogen, such as phenotypic and genetic characteristics that influence virulence and pathogenicity, and host specificity. The characteristics of the pathogen that determine its ability to survive and multiply in food and water, based on its resistance to processing conditions, are critical components of MRA, with reference to both exposure assessment and hazard characterization. Ecology, strain variation, infection mechanisms and potential for secondary transmission may also be considered, depending on the biology of the microorganism and on the context of the hazard characterization, such as the scenario that has been delineated during the problem formulation stage of a full risk assessment.

Table 2. Elements that might be included in characterization of the pathogen

Intrinsic properties of the pathogen (phenotypic and genetic characteristics)

Virulence and pathogenicity mechanisms

Pathological characteristics and disease caused

Host specificity

Infection mechanisms and portals of entry

Potential for secondary spread

Strain variability

Antimicrobial resistance and its effect on severity of disease

SOURCE: Adapted from ILSI, 2000.

When not already included in the characterization of the pathogen, specific consideration should be given to the intrinsic properties of the pathogen that influence infectivity, virulence and pathogenicity; their variability; and the factors that may alter the infectivity, virulence or pathogenicity of the microorganism under consideration. As a minimum, elements to be included in hazard characterization with regard to the pathogen are summarized in Table 2.

5.3 Information related to the host

Host-related factors are the characteristics of the potentially exposed human population that may influence susceptibility to the particular pathogen, taking into account host intrinsic and acquired traits that modify the likelihood of infection or, most importantly, the probability of illness and its severity. Host barriers are multiple in number and pre-existing (innate); they are not all equally effective against pathogens. Each barrier component may have a range of effects depending on the pathogen, and many factors may influence susceptibility and severity. These are identified in Table 3.

Not all of the factors listed in Table 3 would be relevant, or important, for all pathogens. In all cases, however, an important issue in hazard characterization is to provide information on whom is at risk and on the stratification of the exposed population for relevant factors that influence susceptibility and severity.

Table 3. Factors related to the host that may influence susceptibility and severity


General health status, stress

Immune status

Underlying conditions, concurrent or recent infections

Genetic background

Use of medications

Pertinent surgical procedures


Breakdown of physiological barriers

Nutritional status, bodyweight

Demographic, social, and behavioural traits

SOURCE: Adapted from ILSI, 2000.

5.4 Information related to the matrix

The factors related to the food matrix are principally those that may influence the survival of the pathogen through the hostile environment of the stomach. Such effects may be induced by protection of the pathogen against physiological challenges, such as gastric acid or bile salts. These are related to the composition and structure of the matrix (e.g. highly buffered foods; entrapment of bacteria in lipid droplets). Alternatively, the conditions in the matrix may phenotypically affect the ability of the pathogen to survive the host barriers, such as increased acid tolerance of bacteria following pre-exposure to moderately acid conditions, or induction of stress-response by starvation in the environment. Stress conditions encountered during the processing or distribution of food and water may alter a pathogen's inherent virulence and its ability to resist the body's defence mechanisms. These potential matrix effects can be important elements in hazard characterization. The conditions of ingestion may also influence survival by altering the contact time between pathogens and barriers, e.g. initial rapid transit of liquids in an empty stomach. These factors are summarized in Table 4.

Table 4. Elements that may be included in characterization of the effect of the matrix on the pathogen-host relationship

Protection of the pathogen against physiological barriers

Induction of stress response

Effects on transport of pathogen through the gastrointestinal tract

5.5 Dose-response relationship

The final - and essential - element in the descriptive hazard characterization is the relationship, if any, between the ingested dose, infection and the manifestation and magnitude of health effects in exposed individuals.

Description of the dose-response relationship involves consideration of the elements or factors related to the pathogen, the host and the matrix, insofar as they may modulate the response to exposure. Where appropriate information is available, it also involves a discussion about the biological mechanisms involved, in particular whether a threshold, or a collaborative action of the pathogens, may be a plausible mechanism for any harmful effect, or whether a single pathogen may cause adverse effects under certain circumstances. Elements to be considered are listed in Table 5.

Table 5. Elements to be considered in describing the dose-response relationship

Organism type and strain

Route of exposure

Level of exposure (the dose)

Adverse effect considered (the response)

Characteristics of the exposed population

Duration – multiplicity of exposure

SOURCE: Adapted from ILSI, 2000.

Where clinical or epidemiological data are available, discussion of the dose-response relationship will generally be based on such data. However, the quality and quantity of data available will affect the characterization. The strengths and limitations of the different types of data were addressed in Chapter 4. A specific difficulty is of obtaining data to characterize infection, or to characterize the translation of infection into illness and illness into different outcomes. In many cases, the analysis may only be able to describe a relationship between a dose and clinical illness. Other difficulties arise from several sources of variability, including variation in virulence and pathogenicity of the microorganisms, variation in attack rates, variation in host susceptibility, and type of vehicle, which modulates the ability of pathogens to affect the host. Therefore, it is essential that the dose-response analysis clearly identify what information has been utilized and how the information was obtained. In addition, the variability should be clearly acknowledged and the uncertainties and their sources, such as insufficient experimental data, should be thoroughly described.

Previous Page Top of Page Next Page