Emerging Infectious Diseases

Lecture 1 & Sample Questions

François Elvinger

Lecture Objectives: The concept of emergence. Definitions of emerging infectious diseases. Qualification and quantification of emerging disease. Factors influencing propagation of disease agents in populations.

This course will concentrate on emerging infectious diseases. The phrase ‘emerging infectious diseases’ was recently introduced by microbiologist and Nobel Prize winner Joshua Lederberg, and can be applied to infections that newly appear in a population, or have existed but are [rapidly] increasing in incidence or geographic range. We should not ignore the changing exposures of populations to toxic substances or environmental and occupational challenges that not only cause newly emerging diseases and public health challenges, but also may change the susceptibility of populations to infectious agents.

Human and animal populations throughout history have been afflicted by major outbreaks of infectious disease that swept through the ‘known’ world mostly in the wake of conquering armies or following trade routes. The plague in the 14^th century decimated the population of Europe and Asia, with a third of the population from southern to northern Europe dead within 4 years of introduction of the disease. The Spaniards in their conquest of the very powerful nations of Central America were aided by the smallpox virus which was introduced in naïve populations by Spanish troops and decimated the opposing leadership and armies. The first veterinary schools in Europe were founded in the 18^th century primarily to study and control recurring epidemics of rinderpest.

Emerging diseases today, as in the Middle Ages and beyond, are cause for popular alert and concern, as shown by the fears generated by bovine spongiform encephalitis and acquired immunedeficiency syndrome. Highly infectious and lethal diseases now may appear to be controllable, and emerging infectious diseases today have to be considered in the context of decreasing infectious disease induced mortality during most of the 20^th century and the recent increased recognition of novel diseases in human and animal populations, partly due to improved diagnostic capabilities. Emerging diseases can be attributed to either true emergence (i.e. a newly appearing disease agent that had not been present), increased recognition (i.e. a disease agent was present in a population but has only recently been recognized due to improved diagnostic tests / capabilities), increased incidence of previously recognized disease (because of greater human and animal traffic, greater population densities, increased susceptibility of the host population). Those factors responsible for disease emergence can often be recognized, although intervention altering any of these factors may prove to be difficult, even impossible: for example, recognition of emergence of new influenza strains in Asia will not lead to travel reduction or limitation (although, as I am editing these notes on 11/25/00 I just read in the newspaper that 137 delegates from Uganda to a conference on regional security in Kenya were expelled from Kenya because of fears of exposure to the Ebola virus).

We will start out by analyzing some proposed definitions for emerging infectious diseases, and some of the underlying terms:

Emerging [infectious] disease

Disease whose incidence has increased or is expected to increase
in a defined time period and location.

Infection that has newly appeared in [a] population or has existed but is rapidly increasing in incidence or geographic range.

(S.S. Morse, Emerg.Infect.Dis., 1996;1(1))

Emerging infectious diseases are diseases of infectious origin whose incidence in humans has increased within the past two decades or threatens to increase in the near future.

(Institute of Medicine. Emerging Infections: Microbial Threats to Health in the United States. Washington, D.C.: National Academy Press, 1992)

These three definitions are similar, however I would like to point out some distinctions:

The first two definitions differ in the sense that the first considers disease, the second infection as the primary operator. Both however, at this state of knowledge, may be insufficient as we may have to consider circulation of potentially infectious / disease agents that neither cause infection nor disease, however are a threat to plant, animal and public health.

The 1992 Institute of Medicine definition is too restrictive for our purpose when treating emerging infectious disease with regard to animal and zoonotic diseases, and their impact on public health. This definition may just reflect the state of knowledge in 1992 and a misunderstanding of the scope of what constitutes the global and interspecies, intergenus, interkingdom and other transmission of disease agents: we cannot restrict ourselves to just considering disease agents as infecting one end host, i.e. the human (as the chief organism), but we have to consider that even transmission of infectious particles among bacterial and viral agents, or agents that affect plant health ultimately may affect human health and has to be considered in any definition of emerging infectious disease agents.

As a consequence, any definition of emerging disease, emerging infectious disease, emerging infectious disease agent has to be broad, and although it ultimately has to be defined as related to public health, all intermediate organisms and populations that are affected have to be factored into the concept of emergence.

Health health is a state of complete physical, mental, and social well-being and not merely the absence of disease or infirmity.

(World Health Organization, http://www.who.int/aboutwho/en/definition.html)

Disease absence of health, or non-compensated perturbation of one or several functions of a host, or pathological condition occurring in a susceptible population (Toma et al.,1999)

Incidence new cases of disease in a population in the course of a defined period of time

Determinants of Health / Disease

Host – Agent – Environment Triad

Health dynamics in a population are affected by host, agent and environmental factors. For a disease to be introduced and maintained in a population, the host has to be susceptible to colonization and infection, the agent has to be infective for the host, and the environment in which host and agent are interacting has to be conducive to providing effective contact between host and agent for colonization and infection of the host to take place, and for assurance of propagation of the agent across the host population.

(Host factors in animal populations are genotype, species and breed, gender, age, size and conformation, use and behavior; agent factors are virulence & pathogenicity, gradient and outcome of infection, transmission mode; environmental factors are location, climate, husbandry, stress affecting both host and agent. Modified from Thrusfield, Veterinary Epidemiology, 1995)

How do we qualify and quantify emergence?

Emerging disease is commonly recognized with regard to its impact on populations: high morbidity, mortality or case-fatality of a syndrome, and / or ‘dramatic’ clinical disease signs. Emergence cannot be uniformly defined for all hosts and agents. A condition / agent may be emerging for a population, a subpopulation, a single host or group of hosts. An agent endemically present in one species may emerge in another species. A disease that has been successfully controlled in a population may reemerge. Given the non-precise definitions of emerging disease listed above, in animal populations we may bypass quantification in terms of incidence (i.e. numbers of new cases, time period, ‘rapidity’ of spread) in favor of assessment in terms of impact on production economics in animal populations. In order to qualify and quantify emergence we have to clearly identify all host and agent components, and their interaction:

qualitative

Host: who / what is the target population?

Agent: what is the agent and how do we recognize it?

Interaction: what are the mechanisms of infection, transmission and what is the mode of propagation?

quantitative

Incidence: magnitude of increase?

Time: temporal pattern of increase, duration of outbreak?

Space: location, area affected?

Assessment of severity of disease, in terms of clinical signs and mortality, and answering the questions above is essential for the evaluation of the impact of an emerging agent in a population, and for the development and implementation of control measures. For example, on qualitative components, outdoor activities, either occupational (farming) or recreational (hunting, fishing, golf, ...) predispose individuals [the target host / population] for exposure to arboviral agents like the equine encephalomyelitides in the United States and the more recently introduced West Nile virus infections. Recognition of that latter virus was delayed due to similarities in case presentations with other arboviral diseases like St.Louis virus encephalitis, and studies on reservoir and vector species for West Nile virus are ongoing. Regarding quantitative components of emergence of West Nile encephalitis, the incidence increase was from non-existent, with greater incidence in late fall, and propagation of disease across northern Atlantic States within 2 years with likely endemicity across eastern U.S. within 3 to 4 years.

Disease maintenance and propagation

What are the conditions for an entering disease agent to be propagated among a population with a given susceptibility in an environment altered by climatologic changes and human activity and thus be recognized as a newly emerging or reemerging disease agent? The basic case reproduction number, R₀, must be 1 or greater for a pathogen to persist in a host population (Anderson and May, 1991). That is, each newly infected host has to be the source of infection for at least one other host to maintain a disease in a population, and has to be the source of infection for more than one host for a disease to expand. In other words, each infected host has to be in an environment that facilitates one or more effective contacts with susceptible hosts. Emergence of a disease may not be recognized for a long period of time in the case of disease outbreaks that are spatially or temporally separated and appear as sporadic in the host population, with R₀ appearing as less than 1 in each temporal and spatial location.

Disease propagation and magnitude of a disease outbreak in a population depends on multiple spatial and temporal factors. In the Reed-Frost model, disease propagation varies depending on probability of effective contact between infective and susceptible animals. This probability is influenced by population density, time point and duration of contact, host susceptibility and host infectiousness (amount of infectious agent that a host can transmit), agent transmissibility (how well can I transfer this organism), agent infectivity (how much organism do I need to infect?) and agent virulence (how much disease does this agent cause?). That is, in the Reed-Frost model, similarly to the explanation for R₀ above, infected individuals have to have the opportunity to interact with susceptible individuals in a manner sufficient for disease agents to be transmitted effectively, that is in a quantity sufficient to cause disease in the non-infected individual. For a susceptible individual to be exposed to an infectious dose he has to be in contact with one or more infective individuals for a sufficient amount of time for sufficient agent “amounts” to be transmitted. For the disease to be maintained in the population, this newly infected individual has to contribute to the infection of one or more susceptible individuals and so on.

Population density and probability of effective contact are very much dependent on spatial characteristics in which a population evolves. Spatial components that affect disease transmission are distance of susceptible to infectious individuals, terrain that separates those individuals, vegetation, soil types, climate that may affect survival and / or transport of agents or their vectors, topography, roads that may allow contact between susceptible and infectious individuals. Diseases in livestock and poultry may be transmitted easier 2 miles down a road in a valley than to a farm half a mile away across a mountain ridge.

Temporal components also play into the Reed-Frost model and the likelihood of an infectious animal to transmit disease to a susceptible animals: an infected animal / individual may move across space following exposure but prior to shedding of an agent (latent or prepatent period, or eclipse phase), due to trade and travel, and has to come into contact with susceptible animals while being infectious.

Sample Questions

1) The following statements relating to the definition of emerging infectious disease are correct except:

a)      Disease emergence is defined by an increase in prevalence of a disease agent in a population in which the disease had not been detected.

b)      There is no clear distinction in the definitions between emergence of novel disease agents, recognition of disease agents that had been present in a population but were not recognized because they caused minimal problems or could not be recognized because of diagnostic limitations, and reemergence of disease agents.

c)      Reemergence of disease agents refers to emergence of disease agents that had disappeared from a population due to natural decline (R₀<1) or control measures by public, animal or plant health authorities.

2) Determinants of health / disease often are categorized in the ‘disease triad’. The following statements are correct except:

a)      There are 3 participants in the development and propagation of infectious disease in a population: the host, the agent and the environment.

b)      The environment may increase host susceptibility through environmental stressors.

c)      Environmental stressors can contribute to disease in a resistant host.  

3) R₀ is called the basic case reproduction number (basic reproduction ratio, basic reproductive rate) and can be represented by:

                 Number of susceptible hosts being infected                              
     Number of infected hosts being the source of infection for susceptible hosts

All of the following statements are true except:

a)      for a novel disease agent to be maintained and propagated in a population, R₀ for the agent has to be equal or exceed 1

b)      if 0 < R₀ < 1, then the disease agent will disappear from a population 

c)      if R₀ < 1, then the disease agent becomes endemic

4) The following statements related to the Reed-Frost model are correct except: 

a)      The Reed-Frost model is applicable to point-source (common source) epidemics.

b)      The progression of disease (increase and decrease in incidence) is dependent on time period t (generally incubation or latent period of the agent), numbers of infectious cases and susceptible hosts during each time period, and probability of effective contact p (which is also dependent on population density d) during that time period. The simplest form of the model maintains p and d constant.

c)      The number of susceptibles relative to the number of infectious individuals at some point during a propagating disease outbreak decreases to a point where effective contact is not likely anymore. By that time point R₀ is below 1 and the disease is halted in its rogression in the population.