MODULE 2

DISEASE IN POPULATION
Learning objectives:
This topic will enable students to:
 Define and classify a case
 Define and discuss the natural history of infectious disease
 Describe the chain of infection and ways to interrupt the transmission chain
 Define infectivity, pathogenicity and virulence
 Explain the concept of herd immunity and its role in the prevention of disease spread
 Outline the factors affecting disease spread in animal populations

INTRODUCTION

Describing disease or other health-related outcomes is essential to its identification, and

characterization with respect to its natural history, transmission, distribution in relation to
the specific population, time and place of occurrence. The characterization must be done
in a manner that will refine the hypothesis developed regarding its origin, causes and
spread.

1. CASE DEFINITION, CLASSIFICATION AND COUNTING

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1.1 Case Definition

In the conduct of studies such as clinical trials, case series, and diagnostic test evaluation,
establishing a case definition is necessary in the selection of patients which will be
included in the study. In a disease outbreak, identifying sick animals is more difficult
since exposure of the animals is unknown and the disease can be complex, unusual and
unrecognized. Formulating a case definition is thus an essential initial procedure.

A case definition is a set of diagnostic criteria for identifying and

reporting an animal, premise, outbreak or any other unit of
interest to have the disease or other outcome under investigation.

Case definition should be uniform to ensure that every case is identified in the same
manner and allows the veterinarian to distinguish true cases from those that are not. With
an agreed, standardized case definition, cases are identified and reported by other
veterinarians investigating similar outbreaks occurring in other places. Thus, a standard
case definition would improve the comparability of cases of a disease or other outcome
reported from different geographic areas, time periods or diverse sources.

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A case is defined based on the following criteria:

1) Clinical criteria (signs and symptoms)

2) Pathologic criteria (lesions)
3) Laboratory criteria (test results)
4) Epidemiologic criteria (animal, time and place)

The animal producer is usually alerted by the presence of a disease in his farm based on
the symptoms he recognizes. When a veterinarian is called in to investigate the problem,
he makes an initial diagnosis of the condition using a set of distinct clinical signs.
However, clinical signs and symptoms are not reliable because of similarity with other
conditions, and mild and atypical cases may be misclassified as non-cases. Moreover,
few animals exhibit clinical signs or the whole range of signs, and inapparently infected
animals are missed (see Box 1). Thus, clinical signs alone are not adequate to distinguish
true cases from non-cases or unrelated cases of a suspected disease. Additionally, for
some diseases like Postweaning Multisystemic Wasting Syndrome (PMWS), detection of an
infectious agent does not establish the presence of disease (see Example 1). In these
situations, the epidemiologic criteria such as animal characteristics, time, place and
animal behavior are included in the case definition (see Example 1).

There are instances when disease is evident only by noting the suboptimal performance
of animals in the herd or flock. Here, clinical signs are not relevant and therefore
excluded in the diagnostic criteria. For example, in identifying risk factors for lower
conception rates, a case may be defined as a cow with a body condition score below 2 at
breeding (Noordhuizen et al., 1984). Thus, performance criteria can be used, when
relevant, in defining a case.

Case definition may start from loose to strict or broad to narrow. For potentially severe
contagious diseases, where it is vital to identify every possible case, it would be useful to
initially use a “loose” case definition. On the other hand, a “strict” case definition is
chosen in establishing the etiology of disease, when there is a need to be certain that any
animal or other unit of interest included in the investigation really had the disease.

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 EXAMPLE: Case definition and category of Postweaning Multisystemic Wasting
Syndrome (PMWS)

1 Clinical criteria
 Growth retardation and wasting in 6-12 week old pigs, with a high case fatality
 At least 15% mortality rate in the target age groups;
 Commonly with dyspnea, enlarged inguinal lymph nodes, diarrhea, pallor and
jaundice
2 Pathological criteria
 Lymphocyte depletion
 Botryoid inclusion bodies in areas of lymphocyte depletion
 Granulomatous interstitial pneumonia
 Histiocytic infiltration and hepatocellular changes
 Inflammatory lesions and vascular changes in kidneys
 Enteritis
3 Laboratory criteria
Detection of abundant porcine circovirus 2 (PCV2) antigens by
immunohistochemistry within characteristic lesions in lymphoid tissues (tonsils, lymph
nodes, ileum, spleen) of affected pigs
4 Epidemiological criteria
Movements of potential fomites onto the property from high risk sources at the time
prior to clinical onset

Case category
Confirmed: a case that meets the clinical description and which is confirmed by a
combination of histopathology and detection of PCV2 within characteristic lesions

Sources: New Zealand. 2004. PMWS case definition. Draft Joint Regional Pest Management
Strategy /2/06/04.pdf; Sorden (2000).

1.2 Case Classification

In disease investigation, identified cases can be further categorized according to the level
of diagnostic certainty. Examples of a case classification with several categories are
shown below:
1. Possible, Probable, Definite
2. Suspect, Probable, Confirmed
3. Suspect, Possible, Probable, Confirmed
4. Probably unaffected, Probably affected, Certainly affected, Clinical, Laboratory
confirmed
5. Non-outbreak associated, Outbreak associated

A case can be tentatively classified as suspect/probable/possible until additional

information such as laboratory results becomes available. Depending on the laboratory
findings, the suspect/probable/possible case can be reclassified as either
confirmed/definite/certainly affected/ or “not a case”.

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1.3 Converting Case Counts into Rates or Proportions

Following case identification, cases that occurred in one time or place are counted under
each case category and the number compared with the number that occurred at another
time or another place.

When the populations at risk to be compared vary in size, comparisons should be made
using rates or proportions to determine the risk of becoming a case (incidence) or being
a case (prevalence) (Smith, 2005).

BOX 1. Consider the iceberg and spectrum concepts of disease in case definition and
classification

Iceberg concept – In a population, animals

with clinical disease and symptoms are
easily recognized and counted. However,
these clinical cases only represent a small
proportion of infected animals, i.e., the tip
of the iceberg. A large proportion of
infected animals in the same population
are subclinical, i.e., do not show signs and
symptoms and therefore not likely to be
included as cases unless identified by
definitive diagnostic test or a battery of
auxiliary tests. In addition, categorizing
cases according to levels of diagnostic
certainty is desirable at least at the
beginning of a disease investigation or
surveillance.

Spectrum of disease – Similar to iceberg concept, the spectrum of disease complicates case
definition. Animals in a herd exhibit a range of disease manifestations from inapparent to
subclinical to clinical to fatal (see Figure 1). There will always be animals with inapparent
infections. Some clinical cases will also be excluded from the case group to enter the
noncase group. Both these groups of animals will not be counted as cases, if the standard
criteria used are based on a set of clinical signs or symptoms. Even with the use of a
diagnostic test, inapparently infected, subclinical cases and some cases may be missed.
Hence, those likely to be identified are those with clinical signs and symptoms, particularly
the severely affected. A diagnostic test or a battery of auxiliary tests done later will improve
the initial clinical diagnosis and case classification made.

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2. NATURAL HISTORY OF DISEASE

2.1 Definition and Importance

Natural history of disease refers to the natural, uninterrupted progression of a disease

process in the individual animal over time. Knowing the natural history of disease is
essential to:
 Determine the real burden of disease;
 Assess the need for and timing of disease prevention and control measures;
 Evaluate disease control strategies and options;
 Inform animal producers of disease consequences;
 Predict the probable outcome of disease

Figure 1. The natural history of infectious disease. It consists of a continuum of distinct

stages beginning with host’s exposure to the agent and ending with recovery
or death.

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2.2 Stages of Natural History of Infectious Disease
The natural history of an infectious disease is a continuum of distinct stages beginning
with host’s exposure to the pathogen and ending with any of three possible outcomes:
recovery or death (Figure 1).

2.2.1 Host Susceptibility

Host susceptibility to disease depends on genetic factors, innate resistance and specific
acquired immunity (Figure 4). Factors which increase susceptibility such as malnutrition,
pre-existing illness, stress, co-infections, immunosuppressive agents and genetic defects
in immunity favor infection of animals by infectious agents.

2.2.2 Subclinical Stage

Usually, a period of subclinical or inapparent pathologic changes follows exposure,

ending with the start of symptoms. For infectious diseases, the period between exposure
and occurrence of clinical signs is called the incubation period. A part of the incubation
period is the latent period, the time interval form infection to shedding of the agent and
in which the agent is dormant but with potential to become active. This latent period is
the prepatent period for parasites (Figure 1). During the incubation period, symptoms
are not apparent, although some biochemical and pathologic changes may be detectable
with laboratory tests. A screening test that can detect early infection can be applied
during the incubation or latent period, thus minimize the harmful effects of disease from
occurring, reduce treatment costs, or prevent disease spread. It is essential that disease
control authorities be familiar with the incubation period of the “major” diseases present
in the country and in their areas of responsibility. The maximum incubation period of a
disease agent is used as a basis for determining postarrival quarantine holding time for
animals that originated from an infected herd or geographic area. For FMD, animals are
held in an approved isolation facility and observed for development of clinical signs and
symptoms and/or tested for antibody within 28 days, which is twice greater than the maximum
incubation period of this disease due to the high infectivity of the virus. If the animals do not
develop clinical signs and symptoms of the disease of interest and/or antibody to the agent within
this time, the animals are then allowed to mix with the importing farm or the general population

2.2.3 Clinical Stage

The appearance of clinical signs indicates onset of clinical stage. Most diagnoses are
made during the clinical stage. The natural history and spectrum of disease present
challenges to the veterinarians since the clinical cases of illness often represent only the
“tip of the iceberg” (see Box 1). Many additional cases may be too early to diagnose or
may remain inapparent. The animals with inapparent or undiagnosed infections may be
able to transmit the infection to other animals within the population or to other
populations.

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2.2.4 Outcome

Disease can either end in death or recovery. Sometimes, relapsing infections occur
following recovery because some infectious agents are capable of changing their antigens
to escape host defenses.

3. CHAIN OF INFECTION

Disease occurs as a result of interplay of the host, agent and environment in a process
called chain of infection (Figure 2). Transmission occurs when the pathogen leaves its
source through a portal of exit, and is conveyed by some mode of transmission, and
enters through an appropriate portal of entry to infect a susceptible host. The
components of chain of infection are described in the following sections.

Figure 2. Chain of infection showing transmission of a disease agent from its source to
susceptible hosts. It consists of several components which are linked
together. Each link must be present and in sequential order for an infection
to occur. Understanding the characteristics of each link provides the
veterinarian with methods to prevent the spread of infection.

3.1 Disease Agent and Sources of Infection

The sources of a particular disease agent for susceptible animals are the clinical cases,
reservoirs, contaminated vehicles and the environment. Among these sources, clinical
cases are less important epidemiologically because they are likely to be recognized and
consequently, have less contact with the healthy animals in the herd as a result of
separation, treatment or removal from the rest of the healthy herd.

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Inapparently infected animals/ humans, carriers, intermediate hosts and vectors that
harbor and capable of transmitting disease agents are called reservoirs (Smith, 2005).
Identification of these reservoirs and their role in maintaining infection on farms or
spreading infection, are essential to the control of any disease. Certainly, diseases with
multiple reservoirs are difficult to control compared to diseases with single reservoirs.
To prove that an animal species is a reservoir of infection for another, there must be
conclusive evidence(s) that the animals concerned transmit the disease agent to the host
under natural conditions. Several criteria must be fulfilled (Halpin,1975):

1) The disease agent must be isolated from the tissue(s) of that animal species;
2) The animal species, host and disease agent must be present in the same
geographical area at the same time period of the year;
3) Infection of the animal species by disease agent should be long enough so that
the agent can be transmitted to the host. Animal species where infection is only
short-lived is only a dead-end host for that disease agent.
4) Animals concerned must easily transmit the disease agent to susceptible hosts in
the natural condition. To be an efficient transmitter, a large proportion of the
animal species must be infected by the disease agent so that the same species
can transmit the agents to susceptible hosts. Clearly, the disease agent should
multiply in the animal species.

The mere detection of antibodies against the disease agent in an animal species is not
proof that the animal concerned is the reservoir for that particular agent. Thus, suspect
animal reservoirs for FMD virus in the Philippines need to be assessed using the above
criteria.

Carriers are asymptomatic animals that shed infectious agents either intermittently or
continuously before clinical signs develop (incubatory carriers), following recovery to
infection despite an immune response (recovered carriers) or lifelong infection
(persistent or chronic carriers). FMD-infected animals, for example, excrete the virus
12 to 24 hours before the appearance of clinical signs. True carriers, on the other hand,
harbor the infectious agents but never show clinical signs. True carriers occur in such
diseases as salmonellosis. Latently infected animals may also be called true carriers.
They do not show clinical signs while the disease agent is in a dormant state, and only a
few do so when the agent multiples and are excreted in response to stressors. Carrier
animals disseminate the infectious agents and therefore, must be detected by a screening
test to remove these animals from the susceptible population. Knowing which diseases
have carrier states would be helpful in implementing disease control measures.

Vectors are invertebrate animals that transmit the disease agent to susceptible animals.
Proof that an arthropod is a vector of a disease agent is not an easy task - the same criteria
mentioned for reservoirs also apply. Disease agents can also be transmitted to susceptible
animals through inanimate objects, called vehicles. Examples of vehicles are hairs and
semen of animals, food, water, beddings, equipment and veterinary drugs. Salmonella
typhimurium and Escherichia coli O157:H7 can multiply in food, and can result to

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contamination of a whole lot of food or feeds. This information has implications in
developing quarantine protocols on animal products imported or derived from an infected
area.

Intermediate hosts are animals where part of the disease agent’s life cycle is spent.
Intermediate hosts and vectors should also be eliminated where possible to interrupt
disease transmission.

The environment where the disease agent multiplies, can also be a source of infection for
susceptible animals. An infected animal is not required for dissemination of disease
agents. Cryptococcus neoformans can be transmitted to humans through inhalation of
airborne yeasts, which grow in pigeon feces.

3.2 Portals of Exit and Entry

The portals of exit are the means in which infectious agents exit the infected hosts
(Figure 3). The agent enters the host via portals of entry, usually in the same route that
it uses for leaving the sources of infection. Although infectious agents may use more than
one route, there is a preferred route for most agents. For instance, Salmonella may enter
the respiratory system but the preferred route is the mouth.

Figure 3. Portals of entry and exit for infectious agents

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3.3 Modes of Transmission

The mode of transmission is the means by which infectious agents are transmitted to
other animals. An agent can be transmitted to susceptible hosts in several ways:
vertically from parents to offsprings, or horizontally between animals of more or less
the same generation, either by direct and indirect means (Figure 2). An agent can have
more than one mode of transmission.

3.3.1 Direct Transmission: Direct contact and Droplet spread

In direct transmission, the infectious agent is immediately conveyed to a susceptible

animal either through direct contact and droplet spread. Direct contact is through biting,
licking, touch, mating or contact with soil and vegetation containing infectious agents.
Contagious diseases require very close contact for transmission. Droplet spread is one
where large infectious aerosols (> 100 µm) are transmitted through sneezing, coughing,
sniffing or bellowing directly onto mucous membranes of the nose, mouth or conjunctiva
of susceptible animals. These expiratory droplets settle to the ground rapidly, hence, do
not travel far from the source, i.e., within 1 meter from the source. Infection by droplet
infection is of less significance in open air and does not usually result to epidemics even
in animals kept in confinement.

3.3.2 Indirect Transmission: Vector, Vehicle and Airborne

Infectious agents can also be transmitted indirectly to susceptible animals using an

intermediary such as vectors for vector-borne diseases, vehicle for vehicle-borne diseases
or agents can be airborne prior to transmission to susceptible animals.

Vectors carrying the disease agents on their feet, mouthparts or in their gut can pass on
these agents mechanically during their feeding in animal hosts. Since the agent does not
multiply, neither develop in the vector, mechanical transmission must be completed
quickly, particularly if the agent has a short survival time on the body, appendages or
mouthparts of the vector. Mechanical transmission is favored when vector density is high
and the susceptible and infected animals are in close proximity to each other.
Transmission by vectors can also occur biologically, if part of the non-sexual stage of
development of the agent is spent in vectors before transmission. Such vectors can
transmit the pathogen transtadially between development stages of the same generation,
or transovarially between generations of the vector. In transovarial transmission, the
vector population is a continuing source of infection to susceptible animal hosts since
reinfection of the vector population is not required. Infection between different species
of animals can occur when several development stages of the vector feed on different
animal species.

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Vehicle transmission can occur over long distances such as when imported fresh beef
contaminated with Listeria monocytogenes is consumed as undercooked. In airborne
transmission, microorganisms suspended in particles of air (< 100 µm) for long periods
are transmitted to susceptible animals, usually via respiratory route, either by droplet
nuclei or dust. Infection by droplet nuclei may lead to epidemics in animals raised under
intensive production but of less importance in open air.

3.4 Susceptible Hosts

Following exposure, animals may either succumb to disease or not. The proportion of
susceptible animals that become infected following exposure is called infectivity. In
epidemiology, infectivity is measured as secondary attack rate. Not all infected animals
however, develop clinical disease. The proportion of infected animals that develop
clinical disease is called pathogenicity. For those that develop clinical disease, the
outcome may be mild to severe or fatal. The proportion that developed severe to fatal
infections is called virulence, measured as case fatality in epidemiology.

The ability of the animal to ward off infection is called immunity. Immunity can be
innate or acquired (Figure 4). Innate immunity refers to resistance to an infection for
reasons other than previous natural exposure or vaccination. An example of innate
immunity is the resistance of Bos indicus breeds of cattle to tick infestation. Specific
acquired immunity can either be naturally or artificial. Natural acquired immunity
involves the acquisition of protective antibodies as a result of infection, i.e., active
acquired immunity or by passive transfer of antibodies form dam to offspring. Artificial
ways of acquiring immunity involve the administration of vaccines, toxoids, antitoxins or
immune serum globulin.

Innate Immunity Acquired immunity

Natural Artificial

Active Passive Active Passive

follows colostral vaccination, antitoxin

infection antibodies toxoid
infection

Figure 4. Types of immunity.

Similar to individual animals, population groups can also be immune. Herd immunity is
the resistance of a group of animals to invasion and spread of an infectious agent. This
concept of herd immunity is taken advantage by vaccinating less than 100% of the
population to be able to eliminate or prevent the entry of infectious agent into the

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population. In general, yearly vaccination coverage of at least 70% probably would be
required and have to be sustained until risk of reinfection from others could be safely
guaranteed and further measures instituted locally. To be effective, mass vaccination
should be coordinated among at least all infected areas of the country, rather than upon
vaccination in only one of the endemic areas.

4. BREAKING THE CHAIN OF INFECTION

Knowledge of the chain of infection allows the timely application of appropriate and
realistic control and preventive measures. Interrupting the sustained transmission
chain from infected to susceptible hosts is the goal of infectious disease control. In
general, control measures should be directed against the weakest link in the infection
chain that is most susceptible to intervention and cost-effective, unless not feasible, and
socially or psychologically unacceptable.

Obviously, control measures directed to eliminate the source animals excreting the
disease agent would be the most effective. An example of such measure is slaughter.
Although effective, slaughter-based control is either socially and psychologically
unacceptable because of the animal welfare issue, or economically unjustifiable in many
developing countries. It is also a non-viable option when compensation is not offered to
animal producers. Control can also be directed against the pathogen. Thus, bacteria are
destroyed by bactericidal drugs, fungi controlled using anti-fungal agents, etc.
Interventions can also be applied to interrupt the mode of transmission of infectious
agents such as through isolation of sick animals, vector control, disinfection of milking
machines and air sterilization.

Another way of breaking the chain of infection involves the identification of the major
risk factors for disease and/or its manipulation. Selection of resistant breeds of animals is
also a rational preventive measure. Finally, measures can be applied at the susceptible
hosts such as via vaccination and adequate nutrition to increase host resistance.

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5. FACTORS THAT INFLUENCE SPREAD OF DISEASE IN
POPULATIONS

Several factors affect the formation of the chain of infection in populations.

5.1 Host’s Factors: Susceptibility, Immunity

The presence of large number of infective animals and susceptibles within a population
favor the dissemination of disease agents. Susceptibility of animals to infection and
disease varies between and within animal species, regardless of their immune status. In
general low herd immunity increases the spread of disease agents, the reasons being that
1. There are more susceptible than immune individuals that become available to
acquire the disease agent;
2. The proportion of effective contact is increased;
3. Environmental contamination is increased

Conversely, high herd immunity restricts the spread of disease agents. A highly
infectious animal infects many susceptibles because of the prolonged shedding of the
disease agent. Infectious period refers to the time period in which disease agent is
transmitted from infected to susceptible animals.

5.2 Effective Contact

Effective rate of contact refers to the frequency of contact between individual animals in
the population. It depends on a number of factors:
 Low herd immunity decreases the distance between infected and susceptibles;
 Increased animal movement increases probability of contact of susceptibles with
infected animals;
 Increased congregation of animals such as during pregnancy testing, dipping of
animals for tick removal, crowding of animals at transport, assembling in livestock
auction markets and communal grazing;
 Biting, sneezing, coughing, and coitus directly transmit disease agents to
susceptible;

5.3 Disease Agent Characteristics: Infectivity, Stability and Virulence

Infectivity, stability and virulence of disease agent affect spread of disease agent.
 Highly infective disease agent requires low minimum infective dose for
transmission. With low minimum infectious dose, disease agents are easily
transmitted. The minimum infective dose refers to the minimum amount of
infectious particles needed to set off an infection. For vector-transmitted diseases,
the threshold level of vectors must be reached for effective transmission. The
threshold level refers to the minimum amount of agent needed for transmission to
vertebrate host.

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  Excreted disease agents must survive long enough in external environment to be
transmitted to susceptible hosts. Stability is made possible either by the organism’s
structures such as spores (e.g., Bacillus anthracis) or by protection against the
destructive effects of direct sunlight, chemicals, inappropriate pH and temperature
(e.g., skin scabs for sheep pox virus).

 Highly virulent pathogens tend to spread faster, thus infecting many susceptible
animals in any given time.

5.4 Environment Factors: Climate, Topography, Reservoirs, Management

Climate, soil, water and other environmental factors govern the survival, distribution and
dispersal of animal reservoirs, insect vectors and of the disease agents they transmit.
Wind, water and man can facilitate the transport of disease agents over long distances.
An example was the spread of Bovine Ephemeral Fever within an Israeli village in 1991
(Yeruham and Braverman, 2007). Actively flying mosquito vectors, assisted by long
prevailing night winds transported the BEF virus from infected to non-infected areas in
the Israeli village in two weeks time.

Today, most of the pathogens spread through (legal or illegal) international trade in in
animals and their products. Factors such as topography, farm management long-distance
movements of animals, and biosecurity are all important elements in the spread of
infection. Farm management factors that increase risk of spread include low level of
biosecurity, increase stocking rate, open and mixed herds, poor sanitation, pasture
grazing, poorly designed housing, among others. Sourcing replacement animals from
infected herds or countries endemic for the disease of interest can introduce the disease
agent to disease-free herds and geographic areas.

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Health and Production Service on Dairy Farms. V. Index List on
Metabolic/Nutritional Diseases, Body Condition Score and Ration Composition.
Preventive Veterinary Medicine 3:289-300.
Putt SNH, Shaw APM, Woods AJ, Tyler L and James AD. 1988. Veterinary
Epidemiology and Economics in Africa. 2nd edition. Addis Ababba, Ethiopia:
ILCA. 129 pp.
Schwabe CW, Riemann HP and Franti CE. 1977. Epidemiology in Veterinary Practice.
Philadelphia: Lea and Febiger. 303 pp.
Segalés J, Calsamiglia M and Domingo M. 2003. How We Diagnose Postweaning
Multisystemic Wasting Syndrome. 4th International Symposium on Emerging and
Re-emerging Pig Diseases – Rome June 29 – July 2.
Smith RD. 2005. Veterinary Clinical Epidemiology. 3rd ed. Illinois: Taylor and Francis.
259 pp.
Sorden SD. 2000. Update on Porcine Circovirus and Postweaning Multisystemic
Wasting Syndrome. Swine Health Production 8: 133-136.
Thrusfield MV. 2007. Veterinary Epidemiology. 3rd ed. London: Butterworths:
Blackwell Publishing Co. 610 pp.
Yeruham I, Gur Y, Braverman Y. 2007. Retrospective epidemiological investigation of
an outbreak of ephemeral fever in 1991 affecting dairy cattle herds on the
Mediterranean coastal plains. The Veterinary Journal 173: 190-193.

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