Disease causation

In order to study the field of infectious disease modelling and dynamics, a high-level overview of disease outbreak categorisation and the process which describes disease establishment in humans are required. A short overview of the disease burden with regards to chronic and infectious diseases are presented in § 2.1.1. The terms used to contextualise the nature of a disease outbreak are mentioned in §2.1.2. To understand disease causation from a systems perspective, the process of disease establishment within an individual is discussed in §2.1.3, which is followed by a discussion on types of risk factors which contribute to disease establishment in §2.1.4. A brief overview is afforded to the required actors in the process of disease establishment in §2.1.5.

2.1.1 The disease burden

The mortality and morbidity caused by disease can be ascribed to either communicable diseases (CDs) or non-communicable diseases (NCDs).

According to the Dictionary of Epidemiology (Porta 2014), NCDs (i.e. chronic or non-transmissible diseases) are diseases “for which evidence is lacking that transmission from individual to individual is possible by contagion, a vector, biological heredity or inheritance.” These diseases tend to have long durations and result from an interaction of genetic, physiological, environmental and behavioural factors (WHO 2017b). According to the World Health Organisation (WHO) (WHO 2017b), NCDs kill 40 million people each year, equivalent to 70% of all deaths globally.

Although not an exhaustive enumeration, some prominent examples of NCDs include cardiovascular disease, heart-disease and stroke, obesity, cancer, and chronic respiratory disease (Iwelunmor et al. 2015; Piot et al. 2016; WHO 2017b).

According to the Dictionary of Epidemiology (Porta 2014), CDs (i.e. acute or transmissible diseases) are diseases “whose causal agent can be transmitted from successive hosts to healthy subjects, from one individual to another.” Furthermore, CDs may be classified as contagious or non- contagious (e.g. relying on vector transmission). There was an expectation that as countries developed socio-economically and the occurrence of NCDs increased as a result of the adoption of a western lifestyle, that NCDs would replace CDs as the primary burden of disease. Kalyani and Shankar (2016), however, state that mortality and morbidity from CDs remain the leading cause of death in developing countries. Thus, as the incidence of NCDs increase, lower and middle income countries face a double disease burden of both CDs and NCDs (Piot et al. 2016).

Although not an exhaustive enumeration, some diseases which are classified as CDs include measles, mumps, malaria, chickenpox, hepatitis, rabies, cholera, food poisoning, tetanus, pertussis (whooping cough), influenza, yellow fever and tuberculosis. (Kalyani & Shankar 2016; WHO 2017a).

It is important to characterise the difference between CDs and NCDs, as vaccines only target CDs.

2.1.2 Differentiation between epidemic, endemic and pandemic disease outbreaks

 epi (among) + demos = epidemic;  en (in) + demos = endemic; and  pan (all) + demos = pandemic.

A disease epidemic occurs when widespread occurrence of a disease is present in a community at a given time. More specifically, an epidemic disease outbreak is an outbreak which occurs outside

the normal expectancy within a specified community or region (Porta 2014). The re-occurrence of a disease outbreak in a region for which the disease was previously absent for a long time is also regarded as an epidemic outbreak.

A disease infection is considered endemic if the disease occurs habitually within a geographic region or population group (Porta 2014). In other words, a disease is regarded as endemic when it is established and expected within a particular population or geographic region.

An epidemic disease outbreak which occurs over a large geographic area, crossing country borders and infecting a large number of individuals is classified as a pandemic disease outbreak (Porta 2014).

From this brief discussion, it is clear that the disease classification as epidemic, endemic and pandemic depends on the history of previous outbreaks and the ability of the disease to cause widespread infection. Furthermore, a single disease may be classified as an epidemic in one country, but endemic in another, depending on the history of previous outbreaks. This highlights some the complexity and variability associated with disease classification.

2.1.3 An overview of the disease process

Three stages characterise disease establishment in individuals, namely the induction, promotion and expression stages (Jewell 2004).

The start of the etiological1 _{process concerns the induction or start of the disease process. For}

NCDs, this may occur at birth or as a part of a reaction to the environment, whereas for CDs this may occur once an individual comes into contact with a disease (Jewell 2004).

The promotion stage is the phase associated with the multiplication of the disease pathogen within the host to the point where the clinical symptoms of the disease start to manifest. The end of the promotion stage is usually associated with a clinical diagnosis of the disease. It is quite rare to observe the exact moment that a disease starts, thus the induction and promotion phases are usually regarded as a single phase in the disease evolution (Jewell 2004).

The latency period exists between the start of induction and the presentation of clinical symptoms. Once clinical symptoms appear, the disease process works toward the expression of the disease, which relates to the outcome of the disease. Depending on the severity of the disease and the treatment strategies employed, the outcomes may range from full recovery of the disease, renewed susceptibility to infection, full immunity or death. Public health interventions typically focus on the induction and promotion stages of diseases, whereas the expression stage of a disease is usually addressed by clinical treatment interventions (Jewell 2004).

1 _{The study of the causation or origin.}

2.1.4 Risk factors

Epidemiology relates to the study of the determinants or links between risk factors and disease outcomes (CDC 2012). The interaction of these determinants are useful to inform health-related outcomes in the presence of various risk factors. The interaction between risk factors also affects the potential of disease establishment in an individual. The risk factors are classified according to the following three categories, with an example in the context of tuberculosis (Joubert 2014):

 Necessary, a risk factor that must be present in all situations in order for a disease to be present (e.g. presence of the disease pathogen);

 Sufficient, the minimum set of a particular combination of risk factors which together are likely to result in disease establishment in some individuals (e.g. presence of the disease pathogen and low individual immunity); and

 Component, the risk factors which in combination result in establishment of disease (i.e. the sufficient set of risk factors consist of a number of component risk factors).

2.1.5 Actors in the disease cycle

One of the simplest models that capture disease causation is that of the epidemiologic triangle, the traditional model used to describe infectious disease (CDC 2012). The triangle consists of the following corners:

 Agent, refers to the micro-organisms or pathogens responsible for the disease and capable of infecting a host (CDC 2012; Mishra et al. 2011);

 Host, an entity which can become infected and transmit the disease; and

 Environment, which refers to the extrinsic factors that influence the exposure and interaction between the agent and the susceptible host (CDC 2012). These factors may include climate, biological vectors, socio-economic factors and availability and quality of healthcare services. Some of these contextual factors are discussed in more detail within §2.4.

The interaction of these three components greatly affect the establishment and propagation of disease. In the following section (§2.2) the chain of infection is discussed in greater depth, which illustrates some of the interactions of the agent, host and environment.