ec01

Introduction (EC01)

Module: EPM301 Epidemiology of Communicable Diseases Course: PG Diploma/ MSc Epidemiology

This document contains a copy of the study material located within the computer assisted learning (CAL) session. The first three columns designate which page, card and screen position the text refers to. If you have any questions regarding this document or your course, please contact DLsupport via [email protected]. Important note: this document does not replace the CAL material found on your module CDROM. When studying this session, please ensure you work through the CDROM material first. This document can then be used for revision purposes to refer back to specific sessions. These study materials have been prepared by the London School of Hygiene & Tropical Medicine as part of the PG Diploma/MSc Epidemiology distance learning course. This material is not licensed either for resale or further copying.

London School of Hygiene & Tropical Medicine September 2013 v1.0

Section 1: EC01 Introduction Aims

To introduce the important concepts of infectious disease epidemiology. Objectives By the end of this session, you should be able to:

explain what infectious diseases are and why they are important. describe the characteristics of infectious agents that influence transmission. describe the characteristics of host populations that influence transmission.

This session should take you between 2 and 2.5 hours to complete. Section 2: Why study infectious diseases? An infectious disease can be defined as: "An illness due to a specific infectious agent (or its toxic products) that arises through transmission of that agent (or product) from an infected person, animal or reservoir to a susceptible host." This transmission can occur directly, or indirectly through an intermediate host, vector or the environment. You have already considered some of the concepts and measures of infectious disease epidemiology in session FE07 and you may wish to review this.

Interaction: Hyperlink:specific infectious agent: output (appears on RHS)

Interaction: Hyperlink: person, animal or reservoir: output (appears on RHS)

Interaction: Hyperlink: susceptible host: output (appears on RHS)

Interaction: Hyperlink: susceptible host: output (appears on RHS)

2.1: Why study infectious diseases? Infectious diseases have always existed and have had a major impact on human development. It is widely believed that our immune systems and genetic makeup have evolved over many years under the selective pressure of potentially fatal diseases, such as malaria (Haldane 1948; Weatherall 1996).

In addition, epidemics of infectious diseases have decimated entire communities, and have sometimes changed the course of history.

Examples In Europe in the 14th Century, there were about 25 million deaths from bubonic plague out of a population of approximately 100 million. In 1520 the Aztecs lost about half of their population of 3.5 million from smallpox, introduced by the more immune invading Spaniards. This has been proposed as an important feature in the defeat of the Aztecs by the

Spanish invaders. In 1919, after the First World War, the global epidemics of influenza killed an estimated 20 million people during one year - more than died as a result of the

war. 2.2: Why study infectious diseases? During the 20th century, important advances in the prevention and control of many infectious diseases were achieved with the development of vaccines and antibiotic drugs. This has sometimes created the impression that infectious diseases are no longer a major threat to public health. However, this is far from being the case. The following is a quote from Dr Gro Harlem Brundtland, the Director-General of the World Health Organization:

"Illness and death from infectious diseases can be, in most cases,

avoided at an affordable cost. It is in everyone's interest that these obstacles to development be removed. Because of drug resistance, increased travel and the emergence of new diseases, we may only have a limited time in which to make rapid progress."

In the following cards, you will see some of the reasons why infectious diseases are still an important challenge to public health at the beginning of the 21st century. 2.3: Why study infectious diseases?

Mortality Infectious diseases are a leading cause of global mortality, causing more than 13 million deaths a year. They are still the main cause of death among children under 5 and the main single cause of premature death in persons under the age of 45. Click below to see pie charts of the main causes of death in each of these groups. You can use the 'swap' button in the graph viewer to switch between the two charts.

Note: On this plot, and others in the study module, you can click on the small symbol in the corner of the diagram to see information about the source of the image.

2.4: Why study infectious diseases?

Morbidity Infectious diseases are also a major cause of global morbidity. They are responsible for a huge amount of disability and suffering in the world as measured in DALYs. Click below for an example.

Interaction: Hyperlink: DALYs: output (appears in new window)

DALY Disability Adjusted Life Years, a measure of disease burden. It includes years of life lost due to premature death, and years of healthy life lost due disability or illness.

Recurring episodes of illness and long-term disability have a major economic impact on the developing countries most affected by infectious diseases.


Role in chronic disease Infectious diseases are increasingly being implicated in the pathogenesis of many important diseases that were previously thought to have a non-infectious origin.

Interaction: Tabs: Example 1 : output Cervical cancer is now known to be associated with human papillomavirus infection. Cervical cancer is the sixth most common cancer worldwide and the most common cancer in women in many developing countries.

Interaction: Tabs: Example 2 : output In the past two decades, evidence has grown on the role of Helicobacter pylori infection in gastritis, duodenal ulcer, gastric ulcer, gastric cancer and gastric-mucosa-associated lymphoid tissue (MALT) lymphoma.

Interaction: Tabs: Example 3 : output Chronic infection with hepatitis B or C can cause primary hepatocellular carcinoma (HCC). HCC is among the most common cancers in many parts of Africa and Asia.

2.6: Why study infectious diseases? Potential for epidemic spread A specific feature of infectious diseases is their ability to be transmitted between individuals. This can result in the occurrence of large outbreaks.

Between 19972000 there were more than 600 outbreaks of disease considered by the WHO to be of 'international importance'. Click below to see a world map of some of these _on the map you can click the location of each outbreak for details.

Interaction: Hyperlink: outbreaks: output (appears in new window) Outbreak The term used to describe a localised epidemic, e.g. in a village, town or city.

The term 'large outbreak' is increasingly being used instead of 'epidemic', as it is less emotive.

Interaction: Button: Show: output


Potential for epidemic spread (continued)

With increasing urbanisation and international travel, the world is becoming a smaller place, and the routes for transmission of infection are increasing. Aeroplane journeys enable individuals to travel within the incubation period of most infectious diseases.

This allows infections to spread to distant places within very short periods of time. An example of this is the annual global dispersal of meningococcal meningitis by pilgrims returning from the Haj Muslim religious festival (Saudi Arabia). Click below for an illustration of this.


Newly emerging diseases Over the past three decades, over 30 new infectious diseases and pathogens have been identified for the first time in humans. These include diseases with a very high case-fatality rate, such as new variant Creutzfeldt-Jacob disease (nvCJD) and Ebola haemorrhagic fever. Some of these new infections are highly prevalent, for example Hepatitis C and rotavirus. Other infections, such as HIV, have rapidly spread around the world. (Click on each of the terms above to view details about each one opposite.)

Interaction: Hyperlink: nvCJD: output (appears on RHS)

New variant Creutzfeldt-Jacob disease (nvCJD)

A new variant of Creutzfeldt-Jakob disease was described in the United Kingdom in 1996. The agent is considered to be the same as that causing bovine spongiform encephalopathy, a disease that emerged in the 1980s and affected thousands of cattle in the United Kingdom and other, mainly European countries. http://www.hpa.org.uk/Topics/InfectiousDiseases/InfectionsAZ/CreutzfeldtJakobDisease/ for more information.

Interaction: Hyperlink: Ebola: output (appears on RHS) Ebola The first outbreaks of Ebola haemorrhagic fever occurred in 1976 and the discovery of the virus was reported in 1977. Cases reported to WHO up to June 1997 indicated a case-fatality rate of over 70%. A major outbreak in Uganda in 2000 was thought to be associated with spread of the virus by soldiers moving across the country. http://www.who.int/csr/disease/ebola/en/index.html for more information.

Interaction: Hyperlink: Hepatitis C: output (appears on RHS) Hepatitis C

This virus was identified in 1989, and is now known to be the most common cause of post-transfusion hepatitis worldwide. So far, up to 3% of the world population are estimated to be infected, among whom 170 million are chronic carriers at risk of developing liver cirrhosis and/or liver cancer. http://www.who.int/vaccine_research/diseases/viral_cancers/en/index2.htm for more information.

Interaction: Hyperlink: rotavirus: output (appears on RHS) Rotavirus

First recognised in 1973, rotavirus is the most common cause of childhood diarrhoea worldwide. 20% of all diarrhoeal deaths and 5% of all deaths in under-5 year olds are due to rotavirus. http://www.cdc.gov/vaccines/pubs/pinkbook/rota.htm for more information.

Interaction: Hyperlink: HIV: output (appears on RHS) HIV Although the Acquired Immune Deficiency Syndrome (AIDS) was recognised in 1981, the causal virus, HIV, was first isolated in 1983. It is estimated that, since the start of the epidemic, 30.6 million people worldwide have become HIV-infected and nearly 12 million have died from AIDS or AIDS-related diseases. UNAIDS Global Report http://www.unaids.org/globalreport/Global_report.htm for more information.

Click below to see the global distribution of HIV/AIDS.

Interaction: Button: Show: output

2.9: Why study infectious diseases? Re-emerging diseases

In addition to the emergence of new infectious diseases, many old diseases that had previously been under control are starting to appear in increased numbers or in previously unaffected populations.

Resurgence of infectious diseases can occur because of any of the following reasons: changes in social or environmental conditions, failure to maintain immunisation programmes (click for an example), increased drug resistance (click for an example.

Drug resistance is currently an increasing problem for a number of diseases worldwide, and we are often in a race to develop new treatments faster than the pathogens can develop resistance. Click below to see some examples.

Interaction: Hyperlink: example: output Example Since the mid-1980s there has been a major resurgence of diphtheria in several countries of Eastern Europe, which had previously been progressing towards elimination of the disease. In 1993, 15,211 diphtheria cases were reported in

Russia and 2,987 cases in Ukraine. The main reason for the return of diphtheria in these countries was a decreased immunisation coverage due to an irregular supply of vaccines and large-scale population movements

(Galazka et al 1995).

Interaction: Hyperlink: example: output Example Mortality and morbidity rates from tuberculosis (TB) in industrialised countries declined during most of the 20th century. However, from the mid-1980s onwards, many of these countries have seen an important increase in the incidence of TB. This is mainly due to a decline in TB control programmes, the increased incidence of multi-drug resistance TB and the effect of the HIV epidemic (Grange 1998).

Interaction: Button: Show: output (appears in new window)


Potential for prevention and control

The mechanisms involved in many infectious diseases are well understood, from the molecular aspects of the infectious agent to the demographic characteristics of host populations. This level of understanding has enabled potentially very effective prevention and control measures to be developed for some infectious diseases. With efficient intervention strategies and the advent of national public health agencies, elimination of specific infectious diseases has become feasible. In some cases, there has even been the possibility (or reality) of global eradication.

Following the successful WHO programme for the global eradication of smallpox through vaccination, the last naturally acquired case of this disease occurred in October 1977 in Somalia. The countries of the Western Hemisphere have set a target for the elimination of measles by the end of the year 2005. The Global Polio Eradication Initiative was established in 1988 following a resolution of the World Assembly to eradicate poliomyelitis. Strategies to immunise millions of children on the same day have resulted in few countries now reporting cases due to wild poliovirus. Dracunculiasis (guineaworm) is now also on the verge of eradication. After intensive, globally co-ordinated programmes, the number of reported cases has dropped from almost 3.5 millions in 1986 to less than 2000 in 2010, and the disease remains endemic only in 4 countries (Ethiopia, Ghana, Mali and Sudan). Click below for an illustration of this.


Infectious disease epidemiology In epidemiology, we are interested in describing and explaining the distribution of diseases in populations. The distribution of an infectious disease depends on the transmission of the infectious agent within the host population.

This is a dynamic process, which is influenced by characteristics of the specific infectious agent, characteristics of the host population and characteristics of the relationship between the infectious agent and the host. In the next few pages we will look at how these different factors act together to influence the transmission of infectious diseases in populations.

Section 3: Infection and disease What are infectious agents? An infectious agent is an organism that is capable of producing infection or infectious disease in a larger host organism. These organisms are also known as parasites because they derive their nourishment from the organism that they live in or on. Those that cause disease are known as pathogens. There are two main classes of parasite: microparasites macroparasites Click on each of these for details.

Interaction: Hyperlink: microparasites: output (appears on RHS) Microparasites include prions, viruses, bacteria, protozoa and fungi.

Microparasites are able to multiply within the host organism, although some protozoa also undergo some of their development outside the definitive host.

Microparasites are so small that they are invisible to the naked eye. They are usually present in the host in such large quantities that epidemiologists usually count the number of infected hosts (prevalence of infection) rather than the number of parasites (intensity of infection). However, intensity can be measured for protozoans, which lie at the boundary of microparasites and macroparasites.

Interaction: Hyperlink (from above): prions: output (appears in new window) Prion

An infectious agent that is believed to have no genetic material. It is an abnormal form of a normally occurring protein of the central nervous system. It is thought to spread by inducing a change in the shape of the normal protein.

Interaction: Hyperlink: microparasites: output (appears on RHS)

Macroparasites include helminths and arthropods (the latter are usually ectoparasites). Macroparasites are not able to directly multiply within the host, and often need to leave the host to complete their life cycle. Macroparasites can usually be seen by the naked eye. This means that the number of parasites can be counted, and this has revealed that macroparasites are usually unevenly distributed within the host population. Often, many hosts are infected by a few parasites, and a few hosts are infected by many parasites. The effect on the host and the reproductive potential of the macroparasite often depends on the intensity of the infection.

Interaction: Hyperlink: helminths: output (appears in new window) Helminth

A helminth is any parasitic worm, though it usually refers to one living in the intestines of a vertebrate animal.

Interaction: Hyperlink: arthropods: output (appears in new window) Arthropod The largest phylum of the animal kingdom, containing several million species. Arthropods are characterised by a rigid external skeleton, paired and jointed legs and a fluid-filled cavity in which most of the major organs are found.

Interaction: Hyperlink: arthropods: output (appears in new window) Ectoparasite A parasite that lives on the skin of the host and obtains nourishment by sucking blood. Included in this category are ticks, lice, fleas and mites.

The term 'infestation' is used to refer to an infection with ectoparasites. 3.1: Infection and disease

Exercise Classify each of the following according to the category in which the causative infectious agent belongs, by dragging the white boxes into the blue bays opposite.

If you are unfamiliar with these examples, look-up the disease in on the CDC website http://www.cdc.gov/DiseasesConditions/az/m.html .

Interaction: Drag and Drop:

Correct response: Drag to Microparasite box That's correct, the infectious agent of malaria is a protozoan parasite and is classified as a microparasite. Incorrect response: Drag to Macroparasite box In fact the infectious agent of malaria is a protozoan parasite and is classified as a microparasite

Interaction: Drag and Drop: Correct response: Drag to Macroparasite box That's correct, tapeworms are intestinal helminths, and are classified as macroparasites. The adult worms live within the host, but the eggs are shed with faeces, so multiplication does not occur within the host. Incorrect response: Drag to Microparasite box In fact tape worms are intestinal helminths, and are classified as macroparasites. The adult worms live within the host, but the eggs are shed with faeces, so multiplication does not occur within the host.

Interaction: Drag and Drop: Correct response: Drag to Microparasite box That's correct, hepatitis C is caused by a virus, which is a microparasite. The virus multiplies within the host in numbers that cannot be quantified. Incorrect response: Drag to Macroparasite box In fact hepatitis C is caused by a virus, which is a microparasitic infectious agent. The virus multiplies within the host in numbers that cannot be quantified.

Interaction: Drag and Drop: Correct response: Drag to Microparasite box That's correct, the infectious agent of cholera is a bacterium, and is therefore a microparasite.

Incorrect response: Drag to Macroparasite box In fact, the infectious agent of cholera is a bacterium, and is therefore a microparasite.

3.2: Infection and disease

Course of infection You have previously been introduced to the concept that an individual passes through different stages of infection and different stages of disease (session FE07). In this section you will review these stages and consider their implications for the spread of infection. You may remember that the stages of infection pass from susceptible to latent to infectious and finally to non-infectious. Similarly, the stages of disease pass from being well to incubation of the infection to being symptomatic and usually to being well again.

Interaction: Hyperlink: susceptible: output (appears in new window) Susceptible adj. Able to be infected. In the infection process, the susceptible period is the period prior to infection. n. A susceptible individual, i.e. an individual that is not protected by any genetic or immune mechanism.

Interaction: Hyperlink: latent: output (appears in new window) Latent period

The time in the infection process between becoming infected and being able to transmit the infection.

Interaction: Hyperlink: infectious: output (appears in new window) Infectious An infectious individual is one that is able to transmit an infectious agent to another individual.

The infectious period, also known as the period of communicability, is the period of the infection process during which the infected individual is infectious.

Interaction: Hyperlink: non-infectious: output (appears in new window) Non-infectious period

The final stage in the infection process when an individual is no longer able to transmit the infectious agent, either because they have cleared the infection through an effective immune response or intervention treatment, or because they have died.

Interaction: Hyperlink: incubation: output (appears in new window) Incubation period

The time from initial infection to the onset of symptoms and/or signs of clinical illness.

Interaction: Hyperlink: incubation: output (appears in new window) Symptomatic period The time during which symptoms and/or signs of the disease are evident.

Symptoms refer to characteristics associated with feeling unwell, such as fever, coughing, etc., while signs refer to measurable characteristics of being unwell, such as body temperature, mean haemoglobin level, etc. 3.3: Infection and disease The diagram opposite represents the typical time course of an acute viral or bacterial infection in an individual. It shows the progression through the different stages of infection and disease. Drag and drop the appropriate stages (on the right) into the spaces on the diagram.

'Suscept.' means 'susceptible'. Interaction: Drag and Drop: Immune (decades) Correct response (drag to bottom RHS box):

That's correct. The immune state is that which occurs after the individual has cleared the infection, is no longer infectious and no longer susceptible to future infection with the same infectious agent. Incorrect response (drag to all other boxes) Incorrect

Interaction: Drag and Drop: Suscept. (years) Correct response (drag to bottom LHS box):

That's correct. An individual is susceptible prior to becoming infected. Incorrect response (drag to all other boxes) Incorrect

Interaction: Drag and Drop: Infectious (days) Correct response (drag to bottom centre RHS box):

That's correct. The infectious period occurs after the individual has become infected and the infectious agent has had some time to develop and reproduce. It partially overlaps with the appearance of clinical illness. Incorrect response (drag to all other boxes) Incorrect

Interaction: Drag and Drop: Latent (days) Correct response (drag to bottom centre LHS box):

That's correct. The latent period is the interval between getting infected and becoming infectious. Incorrect response (drag to all other boxes) Incorrect

Interaction: Drag and Drop: Incubation (days) Correct response (drag to top centre box):

That's correct. The incubation period is the interval between the point of infection and the onset of symptoms (illness). Incorrect response (drag to all other boxes) Incorrect

3.4: Infection and disease Interaction: Tabs:

As you can see, for an acute infection the average duration of the latent and infectious stages is short when compared with the susceptible and immune stages.

For chronic infections, such as Hepatitis B and HIV and most helminth infections, the infectious period can last for many years. You will see later in this session, how patterns of infection vary between infections.

Interaction: Tabs:

The abundance of the infectious agent is relatively low at the time of infection, but increases with time. This is only the case for microparasites, which multiply within the host.

Often, the onset of illness (symptoms) is associated with the occurrence of large numbers of the infectious agent. This is because the symptoms are due to toxins produced by the infectious agent, or due to the immune response to the infection (e.g. fever), both of which will be proportional to the abundance of the infectious agent._ Interaction: Tabs:

Note that the latent period overlaps with the incubation period, but they are not identical. An individual may be infectious before displaying any symptoms of disease, and may remain infectious after the symptoms have gone. In fact, for some

infections, the individual may remain asymptomatic throughout the infection, but still be infectious. This inability to identify all sources of infection makes it more difficult to measure the transmissibility of infectious diseases (as you will see in session EC03), and to target appropriate control measures.

Interaction: Hyperlink: asymptomatic: output (appears in new window) Asymptomatic

An asymptomatic individual is one that is infected and potentially infectious, but does not exhibit any symptoms of the disease. In fact the individual may not suffer any obvious adverse effects from the infection, and can be quite healthy. (back to tabs)

Interaction: Tabs: Finally, you can see that the end of the symptomatic period is associated with a decline in abundance of the infectious agent and with the build-up of specific antibody. This represents the development of an effective specific immune response, which eliminates the infection and therefore the disease.

For some infectious agents, this immune response is associated with subsequent protection from infection with the same agent and this is known as the immune state.

Interaction: Hyperlink: immune: output (appears in new window) Immune

An immune individual is one that is resistant to infection with a particular infectious agent due to a biological mechanism of defence.


Immune response to infection When an infectious agent enters its host, it has the potential to cause a lot of harm and potentially to kill. Because of this the body has evolved a defence mechanism called the immune system.

The immune system is made up of many organs and cells, which defend the body against infection, disease and foreign substances. The immune system is able to recognise that the infectious agent is foreign, and will initially mount a non-specific immune response to control the infection and limit the amount of damage caused.

Interaction: Hyperlink: non-specific immune response: output (appears in new window) Non-specific immunity Refers to the body's natural immunity, which provides an immediate defence against infection. This is mostly a cell-mediated response. Also known as innate immunity.

This is followed by a specific immune response, which is responsible for clearance of the infection. The specific response involves the development of antibodies that recognise specific antigens. For example, by reacting with surface antigens, antibodies can: prevent viruses from entering cells neutralise the effects of bacterial toxins coat bacteria to make them more recognisable to cellular responses (such as phagocytosis and lysis).

Interaction: Hyperlink: specific immune response: output (appears in new window) Specific immunity This involves the gradual development of an immune response to a specific recognised part of the infectious agent during the infection. Also known as acquired or adaptive immunity.

Interaction: Hyperlink: antibodies: output (appears in new window) Antibody

A soluble protein that is able to react specifically with foreign material.

Interaction: Hyperlink: antigens: output (appears in new window) Antigen A molecule that induces a specific antibody or cell-mediated immune response.

Interaction: Hyperlink: phagocytosis: output (appears in new window) Phagocytosis

When material, such as a bacterial cell, is engulfed by white blood cells called phagocytes, and the material is digested within the phagocytes to render it harmless.

Interaction: Hyperlink: lysis: output (appears in new window) Lysis The rupture of the cell membrane, causing the cell contents to be expelled.

3.6: Infection and disease Immune response to infection (continued) Because antibodies develop in response to infection, they are good markers of previous infection with a specific infectious agent. Measurement of the presence of specific antibodies is known as seroprevalence, and this allows epidemiologists to develop a profile of infection experience. The graph opposite shows what an age-seroprevalence profile might look like for a typical childhood viral or bacterial infection. The vertical axis represents the proportion of individuals that are seropositive.

Interaction: Hyperlink: seroprevalence: output (appears in new window) Seroprevalence

The percentage of the population that are seropositive (produce antibodies in response to a specific antigen).

Interaction: Hyperlink: seropositive: output (appears in new window) Seropositive

Seropositive means that the individual or sample tested did have specific antibodies to the antigens tested.

Source

Immune response to infection (continued) Because antibodies develop in response to infection, they are good markers of previous infection with a specific infectious agent. Measurement of the presence of specific antibodies is known as seroprevalence, and this allows epidemiologists to develop a profile of infection experience. The graph opposite shows what an age-seroprevalence profile might look like for a typical childhood viral or bacterial infection. The vertical axis represents the proportion of individuals that are seropositive.

Interaction: Hyperlink: Source: output (appears in new window)

Source:

Modified from figure 8a in: Nokes DJ and Anderson RM. The use of mathematical models in the epidemiological study of infectious diseases and in the design of mass immunization programmes. Epidemiology and Infection 1988; 101(1): 1-20.


Immune response to infection (continued) Measurement of antibodies can also be used to indicate whether an individual has produced a specific immune response to a vaccine, and how strong that response has been. However, this is not necessarily an indication of protection.

The specific immune response can have a memory component that enables the immune system to recognise an infectious agent that has caused infection previously. This immunological memory is stimulated by recognition of the specific antigens involved, by circulating antibodies, and may result in the immune system preventing re-infection with the same infectious agent.

Measurement of these antibodies can sometimes indicate whether an individual is protected from re-infection, if the specific antibodies are known to be correlated with protection against infection.

Interaction: Hyperlink:immunological memory: output (appears in new window): Immunological memory

The enhanced immune response that occurs following re-infection with the same infectious agent. 3.8: Infection and disease Exercise 1 To help you check that you have understood what each of these terms mean, complete the following exercises. Match three of the terms on the left to the definitions on the right Interaction: Drag and Drop: Specific Correct response: (drag to drop 4 on RHS) That's right. Incorrect response: Sorry, that's not correct. Check the definitions on the previous cards and try again.

Interaction: Drag and Drop: Non-specific Correct response: (drag to drop 1 on RHS) That's right. Incorrect response: Sorry, that's not correct. Check the definitions on the previous cards and try again.

Interaction: Drag and Drop: Antibodies Correct response: (drag to drop 3 on RHS) That's right. Incorrect response: Sorry, that's not correct. Check the definitions on the previous cards and try again.

Interaction: Drag and Drop: Antigens Correct response: (drag to drop 2 on RHS) That's right. Incorrect response: Sorry, that's not correct. Check the definitions on the previous cards and try again.

When you first become infected with an infectious agent your body has never seen before, your immune system will mount a drop 1 immune response to bring the infection under initial control. Then in response to drop 2 that can be recognised on the infectious agent, the immune system will produce drop 3 that will mediate a drop 4 immune response.


Exercise 2 Match three of the definitions on the left to the terms on the right, by clicking on the term and dragging an arrow across to the corresponding definition. Feedback will appear below:

drop 1

An individual who produces antibodies in response to a specific antigen drop 2

The proportion of individuals in a sample that do not produce antibodies to a specific antigen. drop 3

An individual who does not produce antibodies in response to a specific antigen. drop 4

The proportion of individuals in a sample that produce antibodies to a specific antigen. drop 5

An individual who produces a non-specific reaction in response to a specific antigen. Interaction: Drag and Drop: Seroprevalance Correct response: (drag to drop 4) That's right, the "sero-" refers to antibodies, and this is a type of prevalence. Incorrect response Incorrect Interaction: Drag and Drop: Seropositive Correct response: (drag to drop 1) That's right, the "sero-" refers to antibodies, and positive means that they are produced. Incorrect response Incorrect Interaction: Drag and Drop: Seronegative Correct response: (drag to drop 3) That's right, the "sero-" refers to antibodies, and negative means that they are not produced. Incorrect response Incorrect


Patterns of infection Because of the different types of immune response elicited by different infectious agents, the course of infection may differ. Click below to view a diagram showing five different patterns of infection, as listed below: 1. Acute, self-limited infection 2. Persistent infection with shedding (production of infectious material) 3. Latent infection 4. Persistent slow infection following an acute infection 5. Persistent slow infection (no acute stage)

Interaction: Button: Show: output (appears in new window)

Interaction: Tabs: 1 : output

Acute, self-limited infections are generally viruses and bacteria that induce lasting immunity to re-infection. Can you think of some examples of infections that show this pattern? The duration of infection can usually be measured in days, and protective immunity is often lifelong.

Interaction: Hyperlink: source: output (appears in new window) Source:

Mims CA, Playfair JHL, Roitt IM, Wakelin D and Williams R. Medical Microbiology. London, St Louis: Mosby; 1993. Interaction: Tabs: 2 : output

Persistent infections are those that produce a chronic asymptomatic 'carrier' state, which is a source of infection for others. More button

Think of at least one macroparasite and one microparasite that induce this type of infection pattern. Cloud button


Mims CA, Playfair JHL, Roitt IM, Wakelin D and Williams R. Medical Microbiology. London, St Louis: Mosby; 1993.

Interaction: Button: More: output (appears in new window) After an initial acute infection, which may or may not be associated with detectable symptoms, the infectious agent is 'controlled' by the immune system, but is not eliminated. The agent is able to persist at low levels that do not cause disease, but continues to multiply and release infectious material (e.g. virus particles, eggs). However, immune control can subsequently fail, resulting in severe symptoms.

Interaction: Button: Cloud: output (appears in new window) This category includes helminth infections, such as tapeworms and schistosomes, and the Hepatitis B virus.

Interaction: Tabs: 3 : output

Latent infections induce an initial acute infection with subsequent recovery and persistence in a non-infectious latent form that 'hides' from the immune system for years. This latent form can then be reactivated at a later stage, when it multiplies causing disease and producing infectious material. The causes of reactivation are unclear, but have been associated with immunosuppression

(e.g. stress-induced, HIV infection). Examples button


Mims CA, Playfair JHL, Roitt IM, Wakelin D and Williams R. Medical Microbiology. London, St Louis: Mosby; 1993.

Interaction: Button: Examples: output Examples Examples of latent infections are herpes simplex virus, causing cold sores on reactivation, and varicella-zoster virus, causing chicken pox initially and shingles on reactivation. Tuberculosis and vivax malaria can also produce latent infections.

Inter action: Tabs: 4 : output

Persistent slow infection following an acute infection refers to infections that are initially suppressed by the immune system, but are then able to slowly build-up again to levels that cause disease. These infections persist for long-periods and gradually 'over-power' the immune system. Can you name a well-known example of this type of persistent infection? Cloud button

Interaction: Hyperlink: source: output (appears in new window) Source: Mims CA, Playfair JHL, Roitt IM, Wakelin D and Williams R. Medical Microbiology. London, St Louis: Mosby; 1993.

Interaction: Button: Cloud: output The most common example in this category is the HIV virus, which can be infectious without causing symptoms for many years. Another example is the HTLV1 virus that causes leukaemia. Infection is thought to occur early in life, primarily through breast milk, but the tumour develops in late adulthood. Interaction: Tabs: 5 : output

Persistent slow infections with no acute stage are rare, and refer to long-term infections that multiply and build-up over many years. The best example of this is the spongiform encephalopathy, Creutzfeld-Jakob disease, which is thought to be caused by a prion infection of the central nervous system. The disease only becomes apparent after many years, and is often confused with other forms of dementia.

Interaction: Hyperlink: source: output (appears in new window) Source: Mims CA, Playfair JHL, Roitt IM, Wakelin D and Williams R. Medical Microbiology. London, St Louis: Mosby; 1993. Section 4: Transmission of the infectious agent

Infectivity and infectiousness The infectivity of an infectious agent is its ability to enter, survive and multiply in the host once a potentially infective contact has occurred. The infectiousness of an infectious agent is the ease with which it is transmitted to another host and this is closely associated with the mode of transmission. However, there is a lot of overlap between the usage of these two terms, as the infectiousness of an agent is usually dependent to some extent on its ability to multiply and to survive.

Interaction: Tabs: Infective dose : output Enough infectious material must be produced to provide a sufficient infective dose for subsequent transmission. It is often difficult to quantify this, and the infective dose is likely to vary according to the immune status of the host. All parasites tend to multiply in very large numbers to increase the likelihood that the infection will be transmitted.

Interaction: Hyperlink: infective dose: output (appears in new window) Infective dose The amount of infective material that is necessary to establish an infection in a susceptible host. (back to main card) Interaction: Tabs: Duration of infection : output An individual can be infected without being infectious, and therefore the duration of infectiousness is an important determinant of transmissibility, as you will see in session EC06. Example button The duration of infectiousness is therefore a characteristic of the infectious agent that determines whether there is sufficient opportunity for transmission to occur.

Interaction: Button: Example: output (appears in new window) Example The malaria parasite has an asexual phase of multiplication that is responsible for the disease. However it is the sexual stages that are infectious to a biting mosquito and these are not easily detectable in the circulating blood throughout an infection. 4.1: Transmission of the infectious agent

Virulence and transmissibility Virulence is the amount of pathogenicity that an infectious agent causes, that is, the severity of the disease that may result from an infection. Biologists previously believed that parasites should evolve towards being less virulent, because more virulent parasites are more likely to drive their hosts, and themselves, to extinction. On an individual scale, a parasite that rapidly kills its host has less chance of being successfully transmitted to the next host, than one that co-exists with its host for many years. This theory was also initially supported by the introduction of a highly virulent strain of viral myxomatosis into Australia in 1950 to control the rabbit population. Successively less virulent strains of the virus rapidly appeared over the following years. However, the predominant strain was eventually found to be of an intermediate virulence. Subsequent mathematical models of this idea have indicated that parasites do not necessarily need to evolve to be less and less virulent. Their evolution will depend on the relationship between virulence and transmissibility of the parasite (May & Anderson 1983). 4.2: Transmission of the infectious agent (Centre top remains static) If virulence increases the parasite's probability of being transmitted to another host, then this characteristic will be selected for. That is, parasites with this characteristic will be more likely to become widespread, than parasites without this characteristic. For example, the virulence of the rabies virus may cause rabid dogs to bite, therefore increasing transmission of the virus. Such an influence on the behaviour of an infected host is beneficial to the transmission of the infectious agent. In recent years, molecular techniques have identified a number of 'virulence genes'. It is thought that these genes are linked to improved survival in the host. For example, the adherence of malaria infected red blood cells to blood vessels is involved in the development of cerebral malaria, which can be fatal, but also allows the parasites to evade the spleen where they would be removed. 4.3: Transmission of the infectious agent Modes of transmission The mode of transmission of an infectious agent is the mechanism by which it is transmitted from a source or reservoir to a host. There are two main modes of transmission of an infectious agent (shown opposite). However, a specific infectious agent may have more than one mode of transmission.

1. Direct transmission this is the direct and essentially immediate transfer of the infective agent and can occur by direct contact or droplet spread. 2. Indirect transmission this involves an intermediate means of transfer of the infective agent between an infectious and susceptible host, and can occur by vehicle-borne,vector-borne or airborne transmission. These will be considered in more detail on the following cards. 4.4: Transmission of the infectious agent Direct transmission Direct transmission can occur by means of direct contact, such as touching, biting, kissing or sexual intercourse. Click below for examples.

Interaction: Button: Example: output (appears in new window) Examples Neisseria gonorrhoeae, the bacteria that causes gonorrhoea, are transmitted from one person to another by secretions from the mucus membranes during sexual intercourse. The rabies virus is transmitted to a human host when saliva from a rabid animal is introduced in the peripheral nervous system by a bite or scratch. Another form of direct transmission is droplet spread, in which the infectious agent is transferred by direct projection (over a distance of less than 1 metre) of a droplet spray onto the mucous membranes of the host. This can occur by sneezing, coughing or talking - words containing the letter 'F' are perfect for such transmission!

Interaction: Button: Example: output (appears in new window) Example The influenza virus is transmitted from one person to another either by droplet spread or by direct physical contact. 4.5: Transmission of the infectious agent Indirect transmission

Airborne transmission includes the dissemination of microbial aerosols that may remain suspended in the air for long periods of time. Depending on the time, some infections will retain their infectivity and others will lose it. These are distinct from the droplets mentioned previously, which are too large to remain suspended in the air.

Interaction: Hyperlink: microbial aerosols: output Microbial aerosols Suspensions in the air of particles consisting partially or wholly of micro-organisms. Back to main card Interaction: Button: Example: output (appears in new window) Example

The herpes zoster virus, which causes chickenpox, can be transmitted from person to person by airborne spread. 4.6: Transmission of the infectious agent Vehicle-borne transmission refers to the involvement of a contaminated, inanimate material or object (sometimes called a fomite) such as food, water, a surgical instrument or eating utensil. Examples i Vibrio cholera is transmitted from one person to another via contaminated water or food. The infective stages of the schistosome parasite, which causes bilharziasis, are acquired from water after having undergone development in freshwater snails. The infective stages penetrate through human skin when the person is swimming or wading in water. Sharing of contaminated needles transmits HIV between intravenous drug users. 4.7: Transmission of the infectious agent Indirect transmission Vector-borne infections are transferred to the host by an invertebrate vector (e.g. insects, lice, fleas, ticks). A mechanical vector is one that simply carries the infectious agent on or in its body.

Interaction: Button: Example: output (appears in new window)

Example Houseflies can act as mechanical vectors of Entoamoeba histolytica, which causes the intestinal illness amoebiasis. The fly lands on a contaminated surface where it picks up infected material on its legs. It can then transport this infective matter to food. A biological vector is one in which the infectious agent undergoes multiplication or a necessary stage of development.

Interaction: Button: Example: output (appears in new window) Example The female Anopheles mosquito is a biological vector of Plasmodium falciparum, the protozoan parasite that causes malaria. The mosquito ingests the sexual stages of the parasite when she feeds on an infectious person. The parasite then undergoes sexual reproduction and a period of development and multiplication, before the infectious sporozoites are injected into the person on whom the mosquito next feeds. 4.8: Transmission of the infectious agent Exercise Click and drag on each of the infections below to connect it with its mode of transmission from the list opposite. Remember that some infections have more than one mode of transmission. If you are unfamiliar with any of these infections, refer to the CDC website http://www.cdc.gov/DiseasesConditions/az/m.html for more information. Interaction: Drag and Drop: Hepatitis B virus Correct response: (drag to direct contact button on RHS) That's correct, hepatitis B can be transmitted by direct contact, for example by sexual intercourse and from mother-to-child at birth. Note that there are two possible modes of transmission. Incorrect response: (drag to all other buttons on RHS) Incorrect Interaction: Drag and Drop: Dengue virus Correct response: (drag to biological vector borne button on RHS) That's correct, dengue viruses are transmitted only through the bite of the Aedes spp. mosquito. As the virus multiplies within the mosquito, this is a biological vector. Incorrect response: (drag to all other buttons on RHS) Incorrect Interaction: Drag and Drop: Polio virus

Correct response: (drag to droplet spread button on RHS) That's correct. Poliovirus can be transmitted by droplet spread. Throat secretions are infectious, and in areas of high sanitation, this droplet spread becomes relatively more important than faecal-oral spread. Note that there are two possible modes of transmission. Incorrect response: (drag to all other buttons on RHS) Incorrect

4.9: Transmission of the infectious agent Effective contact The mode of transmission of the infectious agent dictates the type of exposure that could result in transmission of infection. It therefore determines what constitutes an effective contact between an infective person and a susceptible person, which is contact that will enable transmission. The quantification of potentially infectious contacts between infective persons and susceptible persons is important in infectious disease epidemiology. You will look at this concept in more detail in session EC03.

Interaction: Button: Example: output (appears in new window) Neisseria gonorrhoea is transmitted from one person to another by secretions from the mucus membranes during sexual intercourse. This means that only sexual contact between an infective person and a susceptible person constitutes a potentially infectious exposure. Other forms of direct contact (such as touching hands) and indirect contact (such as sharing eating utensils) do not constitute a potentially infectious exposure. Duration

For an infection that is directly transmitted, there will be many opportunities for effective contact, while for a sexually transmitted infection the opportunities will be fewer. Because of this, the duration of infectiousness is likely to differ between infections according to the mode of transmission.

Interaction: Button: Example: output (appears in new window) Example Individuals with influenza will only be infectious for a number of days, while those with HIV will be infectious for many years. This is necessary to ensure that there are sufficient opportunities of effective contact so that the infection can be transmitted. 4.10: Transmission of the infectious agent Reservoirs Like all living organisms, each infectious agent has a natural habitat, or reservoir. A reservoir is the habitat in which an infectious agent normally lives, on which it depends for survival and in which it reproduces. There are 3 main types of reservoir, and some infectious agents require more than one type of reservoir to complete their life cycle. Inanimate reservoir Animal reservoir Human reservoir

Interaction: Hyperlink: Inanimate reservoir: output (appears on RHS) Inanimate reservoir Some infectious agents live and multiply in inanimate reservoirs such as water or soil. Click below for an example:

Interaction: Button: Example: output (appears in new window) Example Clostridium botulinum is a spore-forming bacillus that causes food borne botulism. C. botulinum spores live and multiply in the soil from where they can be transmitted to a susceptible host. Back to LHS Interaction: Hyperlink: Inanimate reservoir: output (appears on RHS) Animal reservoir Arthropods, reptiles, amphibians, birds and mammals all act as reservoirs for a number of different infectious agents of humans.

Click below for some examples:

Interaction: Button: Example 1: output (appears in new window) Example The rabies virus normally lives and reproduces in a number of biting mammal species, such as dogs, foxes, skunks and bats. The virus can be transmitted from any of these reservoirs to a susceptible host.

Interaction: Button: Example 2: output (appears in new window) Example The leishmania parasite can be maintained in a number of mammals including wild rodents and domestic dogs. The parasites are transmitted to humans from this reservoir host through the bite of an infective sandfly vector. Back to LHS Interaction: Hyperlink: Human reservoir: output (appears on RHS) Human reservoir Many infectious agents have humans as their reservoir. Click below for an example:

Interaction: Button: Example: output (appears in new window) Example Humans are the natural reservoir of the hepatitis B virus. Many individuals have chronic asymptomatic infections that act as a source of infection to susceptible individuals. 4.11: Transmission of the infectious agent Reservoirs The distribution of the reservoir(s) of an infectious agent will influence the distribution of the infectious disease caused by the agent. For example, monkeypox virus is a sporadic infection that clinically resembles smallpox. Most cases have occurred either singly or in small clusters in remote villages bordering the tropical rainforest, where the population has frequent contact with wild animals. Studies have indicated that wild squirrels may be a significant reservoir host. Human-to-human transmission usually dies out quickly, therefore frequent contact with the reservoir host is necessary to maintain the disease among humans. The disease has only been reported from Central and West African rainforest countries.

Section 5: Host population characteristics For an infectious agent to be transmitted within a human population, susceptible individuals must be exposed to a source of infection. The continued transmission of an infectious agent in a population is dependent on the number of infective and susceptible individuals present, and on the effective contact between these individuals. You have seen that the susceptible status of the host is dependent on the likelihood of previous infection, and on whether a protective immune response is produced. However, for an infectious agent to persist in a host population there must be an adequate number of susceptible hosts in the population. This is because the probability of making effective contact will be dependent on the abundance of susceptible individuals. You will learn in session EC06 that there is a critical number of susceptible individuals required for the continuous transmission of an infectious agent in a population. If sufficient individuals are immune to a particular infectious agent, the remaining susceptible individuals may be protected by this population characteristic, known as herd immunity. 5.1: Host population characteristics While the mode of transmission determines the probability of effective contact, population size and behaviour determine the rate at which such potentially infective contacts may occur. If people in a population mix randomly, each person will have an equal chance of making contact with any other and so every susceptible person will have an equal chance of being exposed to infection. However, in most populations people do not mix at random, but have complex contact patterns.

Interaction: Tabs: Example 1 : output In small rural communities, the frequency of effective contact for even directly transmitted infections may be low, but once the population has been infected and is immune, the infection will die out. In large urban communities, such infections will spread rapidly through a population, and there will be sufficient influx of newborn susceptible individuals to maintain transmission. Persistent infections will be better able to circulate in small communities, as the infection will remain long enough to infect subsequent generations of susceptible individuals.

Interaction: Tabs: Example 2 : output What type of contacts people make, and with whom, has an important influence on the transmission of an infectious agent in a population.

For a sexually transmitted infection, transmission may be maintained by small groups of individuals with high rates of sexual partner change, such as commercial sex workers. The majority of the population may make insufficient effective contact to be involved in transmission. Section 6: Overview of study module In this session, you have been introduced to the concepts of infectious disease agents, patterns of infection, modes of transmission, and characteristics of host populations. These are the basic characteristics of infectious diseases that you need to be aware of when thinking about measuring, describing or controlling infectious diseases. 6.1: Overview of study module In session EC02, you will see that infectious diseases often have particular distributions in relation to whom they infect, and when and where they occur. These can sometimes be used to identify whether or not a disease has an infectious cause. Session EC03 considers the different methods of measuring the transmissibility of an infection. It introduces you to the methodology behind the secondary attack rate for measuring transmissibility in the context of a household contact study. You will also review the concept of the basic reproduction rate. 6.2: Overview of study module Session EC04 describes the process and methodology necessary to investigate an outbreak of disease. It describes how to identify an outbreak and how to collect and analyse data for an outbreak investigation. You will use these skills in the assessed work for this unit, which you can undertake after completing sessions 14. Session EC05 contains information on the assessed work, which is a simulated outbreak investigation. You will consider important issues relating to group work, and will be introduced to the problem at hand. The timing of this session will depend on the allocation of groups. 6.3: Overview of study module In Session EC06 you will be introduced to mathematical modelling in epidemiology. This is a field of growing importance and is increasingly being used to make predictions that inform public health policy. This session includes some mathematics, but stresses the importance of understanding the concepts, rather than the mathematics underlying them. Finally, Session EC07 considers the subject of estimating vaccine efficacy. Vaccines are fairly unique to infectious diseases, as they use the body's immune system to protect an individual from infection. However, measuring the benefit of this is a complex topic and this session aims to identify the current issues of interest.

Section 7: Summary This is the end of EC01. When you are happy with the material covered here please move on to session EC02. The main points of this session will appear below as you click on the relevant title. Importance of infectious diseases 1 Infectious diseases are responsible for a large amount of the disease, suffering and mortality worldwide, and this is recognised by the World Health Organisation. Infectious disease epidemiology is a growing field. In recent years infectious agents have been shown to be responsible for chronic diseases such as many cancers. A number of new infections and diseases have been identified. Diseases previously thought to be under control are re-emerging due to failing control programmes or drug resistance. Importance of infectious diseases 2 (link takes you to relevant page) Due to their particular characteristics, infectious diseases can lead to large outbreaks of disease, and this is especially evident in urban settings. With the increasing urbanisation and globalisation of recent and coming years, infectious diseases will be causing problems on a world-scale for many years to come. Because infectious agents do not recognise political boundaries, global alliances to combat infectious diseases are on the increase in the form of collaborative research and global eradication programmes. Infectious agents (link takes you to relevant page) Infectious agents can be categorised as microparasites (prions, viruses, bacteria, protozoa and fungi) and macroparasites (helminths and arthropods). These categories have implications for modes of transmission, duration of infection, and measurement of infection in epidemiological studies. Course of infection (link takes you to relevant page) During the course of an infection, an individual passes through recognisable stages: Susceptible able to be infected

Infected and latent infected but not able to transmit the infection Infected and infectious infected and able to transmit the infection Uninfected clear of infection and either immune or susceptible once more Course of disease (link takes you to relevant page) During the course of disease, an individual passes through recognisable stages: Well uninfected and well Incubation infected but not exhibiting symptoms or signs of disease Symptomatic infected and showing symptoms and/or signs of the disease Well not showing symptoms of disease (either clear from infection or asymptomatic) Patterns of infection (link takes you to relevant page) Five different patterns of infection can be described according to the immune response elicited and the characteristics of the infectious agent relating to transmission: Acute, self-limited infection Persistent infection with shedding (production of infectious material) Latent infection Persistent slow infection following an acute infection Persistent slow infection (no acute stage) Methods of transmission (link takes you to relevant page) Infectious agents can be transmitted either directly, by direct contact or droplet spread, or indirectly, by vector-borne, vehicle-borne or airborne transmission. The mode of transmission determines what constitutes effective contact between a susceptible and infectious person. It may also determine the duration of infectiousness for a specific infectious agent.

Reservoirs (link takes you to relevant page) A reservoir is the natural environment of an infectious agent. Reservoirs can be inanimate, animal or human. Reservoirs are important when aiming to control or eradicate an infectious disease. The distribution of a reservoir may determine the geographical distribution of an infectious agent. Characteristics of the host population (link takes you to relevant page) In addition to characteristics of the infectious agent, characteristics of the host population can also determine transmission. Because hosts can develop protective immunity against an infectious agent, the effect of herd immunity may enable susceptible individuals in a highly immune population to be protected from infection. If insufficient susceptible individuals are available, the infection will die out. In addition to population size, host behaviour will also determine the probability and frequency of effective contact, and therefore transmission.

2.1: Why study infectious diseases?2.2: Why study infectious diseases?2.3: Why study infectious diseases?2.4: Why study infectious diseases?2.5: Why study infectious diseases?2.6: Why study infectious diseases?2.7: Why study infectious diseases?2.8: Why study infectious diseases?2.9: Why study infectious diseases?2.10: Why study infectious diseases?2.11: Why study infectious diseases?3.1: Infection and disease3.2: Infection and disease3.3: Infection and disease3.4: Infection and disease3.5: Infection and disease3.6: Infection and disease3.7: Infection and disease3.8: Infection and disease3.9: Infection and disease3.10: Infection and disease4.1: Transmission of the infectious agent4.2: Transmission of the infectious agent4.3: Transmission of the infectious agent4.4: Transmission of the infectious agent4.5: Transmission of the infectious agent4.6: Transmission of the infectious agent4.7: Transmission of the infectious agent4.8: Transmission of the infectious agent4.9: Transmission of the infectious agent4.10: Transmission of the infectious agent4.11: Transmission of the infectious agent5.1: Host population characteristics6.1: Overview of study module6.2: Overview of study module6.3: Overview of study module

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