The definition of infectious disease

Infectious diseases are so termed because they are contracted by transmission of the infectious agent from a person, animal or even an inanimate object (termed the ‘carrier’). This also explains the use of the term ‘communicable’.

Not all infections can be classified as infectious diseases. For example, an infection can arise when a person succumbs to microorganisms that naturally live within the body, but which do not usually cause disease in a state of healthy balance. A bladder infection, also called ‘cystitis’, is an example of such a disease, in that the bacteria which cause a person to develop cystitis usually originate from the person’s own natural bowel bacteria.

The impact of infectious disease

The description of infectious disease can often be found to be the subject of one of the first chapters in general textbooks about pathology and clinical medicine. This is a reflection of the importance of infectious disease. In terms of causation of disability and death, infections are the single most important cause of disease worldwide. However, in developed countries, infections do not cause as much death and disability as they do in developing countries. In the developed world the most important causes of death and disability are now the non-communicable diseases, and most importantly disease of the cardiovascular system, cancer and, in young people, accidents (see Q.2.4a-1).

The modern developments of vaccination and drug treatment for infections are widely acknowledged in conventional medicine to have led to the decline in infectious disease in developed populations. However, it is increasingly understood that the provision of basic needs, such as clean water and removal of sewage (sanitation), good housing and adequate diet, are also important factors which account for the reduction in infectious disease. The provision of these basic needs contributes to the attainment of a basic level of health, and in health the body is better able both to withstand contracting some infections, and also to overcome those infections that do develop.

The study of the epidemiology of diseases such as tuberculosis, rheumatic fever and diphtheria supports this theory that healthy populations resist infectious disease. All these diseases have declined dramatically in well-nourished western populations, and yet are major causes of ill-health in developing countries. For all three, the decline preceded the introduction of vaccinations or antibiotic treatment, and relates more to improvements in nourishment and sanitation. The reports that tuberculosis is on the increase again in western countries reflect an increase largely confined to marginalised groups, such as the homeless, who do not have access to good nutrition and housing.

Measles is an infectious disease from which most well-nourished children make a full recovery, with less than 0.1% developing long-term serious consequences. However, measles is still one of the major causes of infant death and blindness in developing countries, causing death in up to 30% of infants who contract it in some impoverished localities. This illustrates the fact that infectious disease has much more impact in populations who are more susceptible as a result of malnutrition and poor living conditions.

Nevertheless, there are many infections that cause serious disease within healthy populations. Examples of such diseases include bacterial meningitis, certain types of pneumonia, certain types of food poisoning (including Escherichia coli serotype O157), human immunodeficiency virus (HIV) infection and many of the tropical diseases (e.g. malaria and typhoid). Although it is true that these diseases often tend to have a greater impact on those who are more susceptible, such as the very young and the elderly, these infections are nevertheless also well recognised to be the cause of significant ill-health and mortality in previously fit young people. This is an indication that some infections can ‘take hold’ and cause damage even when the individual does not appear obviously to be particularly susceptible to a severe illness.

Immunity and infectious disease

The topic of immunity was introduced in Chapter 2.1d. The general level of immunity to a disease in a population is another major factor that affects the impact of the disease. Diseases that are very common in a population are termed ‘endemic’. Chickenpox and the common cold are diseases that are endemic in the UK, whereas malaria is endemic in a tropical country such as Uganda. It is common for a population in a locality which has been exposed from birth to an endemic disease to have less marked reactions to that disease than visitors to that locality. This is why travellers to foreign countries frequently succumb to infections that do not seem to affect the locals, leading to symptoms such as fevers and food poisoning.

The resistance of a population to an endemic disease is attributed in part to ‘herd immunity’. This term describes the immunity that results from the fact that a large proportion of the population have already encountered that infection, often in early life. For this reason, they will not thereafter easily contract the disease. If herd immunity exists, the disease is less likely to take hold in the population because there are fewer people to whom it can be passed on. This is one of the principles of vaccination campaigns which aim to ensure that a large proportion of the population is immune. The end result of a successful vaccination campaign is an increase in the herd immunity to a specific disease such as measles.

However, acquired herd immunity is not the whole story. Local people who have not yet experienced endemic diseases still generally appear to be able to fight off these infections when they do experience them more efficiently than travellers to the area. A striking example of this is the impact that was made by minor infections taken by the first explorers to the New World. Diseases such as the common cold and chickenpox caused serious consequences in communities to whom they were totally new infections. It seems as if the immune system of a person in a locality is prepared in some way to deal with an endemic disease, but is seriously challenged by one that is not a normal part of the local pattern of infections. This extra level of protection may possibly be the result of a genetic adaptation of the local population over generations of exposure to endemic diseases (an example of ‘natural selection’).

If a disease suddenly appears to be on the increase in a population, then the term ‘epidemic’ is used. An epidemic disease is not necessarily severe, but is occurring much more often than expected. Epidemics occur either because a new type of infectious agent has emerged for which there is no pre-existing herd immunity, or because over the course of time the herd immunity has diminished so that the disease can rapidly take hold once again.

Transmission of disease

The three examples of infectious diseases described above also illustrate the diversity of ways in which infections can be transmitted. Tonsillitis is transmitted by inhalation of droplets, the cold sore virus through infected saliva penetrating the mucous membranes of the mouth, and HIV is transmitted via infected body fluids (commonly blood and semen) penetrating the usual skin barriers (see Q2.4a-3).

There is an enormous number of possible routes of infection, illustrating the complex ways by which infectious agents have adapted themselves to find their way into their human hosts. Modes of transmission can be broadly considered in two categories: person-to-person spread and animal-to-person spread. Examples of these are listed in Table 2.4a-II.

Table 2.4a-II The different modes of transmission of infectious agents

Emerging infections

For each of the known infections, the causative infectious agent has adapted to target particular human tissues and causes damage in a characteristic way. The conventional view is that such adaptation is the consequence of evolution over the course of many years. Evolution is believed to be the result of mutation that is ‘beneficial’ to the infectious agent. As a species of microbe replicates, occasionally mutation leads to daughter microbes that are better able to reproduce than are their parents. In the case of infectious disease, this successful adaptation is often one that leads the daughter microbes to be more efficient at infecting human cells. This is because it is through infection that microbes obtain the nutrients necessary for survival and replication.

Evolution in complex species such as humans is believed to occur very gradually over many thousands of years. However, evolution of simple species such as viruses and other microbes may lead to a dramatic change in a species over a much shorter time. This is because the microbes replicate at a very rapid rate.

HIV is an example of an infection that seemed to emerge, probably originally in Africa, within the last 50 years, before which time it was completely unknown. HIV currently appears to be perfectly adapted to thrive in the human body through having a protein on its coat that connects exactly with the proteins on the human leukocyte. One theory is that HIV previously existed as a monkey virus, and through chance mutation acquired this protein that enables it to survive and replicate in humans.

It is now recognised that new microbes are emerging in this way all the time, as they change in form through replication. Over the past quarter of a century, more than 30 new or newly recognised infections have been identified around the world (see Q2.4a-4). The newly emerging infectious diseases include hepatitis C and E viruses, Lyme disease, staphylococcal toxic shock syndrome, H5N1 avian influenza (bird flu), SARS (sudden adult respiratory distress syndrome) virus and nvCJD (new variant Creutzfeldt–Jakob disease) virus.

Mutation does not only give rise to new species of infectious organism; it also can lead to subtle changes in existing organisms. These changes, which lead to new ‘strains’, can mean that the organism is no longer recognised by the immune system of someone who had previously had immunity to that disease.

This type of mutation appears to occur more readily in some infectious organisms than others. For example, the influenza virus rapidly changes its characteristic coat through mutation. This gives rise to the frequent epidemics of influenza that are experienced in the UK. Each influenza epidemic reflects a wave of infections by a new strain of the virus. This explains why people can contract influenza repeatedly during their life, and why a new vaccine for influenza needs to be developed on an annual basis.

In contrast, the chickenpox virus appears not to mutate significantly, reflected in the fact that most people retain their immunity to chickenpox for life.

Diseases caused by viruses

Viruses and prions are so small that, unlike bacteria and human cells, they cannot be seen using a simple microscope. Instead, a more powerful microscope, called an ‘electron microscope’, is required to produce images of these particles. Figures 2.4b-I and 2.4b-II show electron micrographs of two different viruses: the envelope-bounded DNA herpes simplex virus, and the icosohedral (20-sided) RNA rotavirus. The size of these viruses is measured in nanometres (nm), which are an unimaginable one-billionth of a metre (1 × 10⁻⁹ m) in size. These viruses are 160 and 80 nm in diameter, respectively.

Figure 2.4b-I • Electron micrograph of the herpes simplex virus.

Figure 2.4b-II • Electron micrograph of the human rotavirus.

Viruses contain some genetic material that is similar in structure to that found within human chromosomes, together with additional proteins that form a surrounding coat. Prions are composed of a single complex protein alone. Because of their simplicity, viruses and prions often have a structure that resembles a geometric crystal. This is in contrast to the complex and unique rounded structures found in each living cell.

Viruses cause damage because they have adapted to be able to penetrate living cells, and then to utilise the nutrients within those cells to replicate. Viruses cannot replicate, obtain nutrients or respond to environmental changes without living

Viruses can damage human cells in different ways: some simply cause cell death, as for example does the cold sore virus. This can have many consequences, depending on which tissue is affected. The death of human cells and release of cellular contents leads to inflammation, so the familiar features of redness, heat, swelling and pain are commonly found when a part of the body is affected by a virus.

Other consequences include:

An excessive immune response to viruses can also be damaging. Possible consequences include:

The much reported ‘postviral syndrome’, which describes depression and exhaustion following a viral infection, has also been attributed to delayed immune damage to the nervous system following a viral infection.

Viruses are classified into groups (families and subfamilies) according to their structure. Some of the major families of viruses are listed in Table 2.4b-I, and some of the diverse diseases that result from viral infections are listed in Table 2.4b-II (see Q2.4b-1).

Table 2.4b-I Some different families of virus

Table 2.4b-II Various viral diseases

Diseases caused by prions

Prions have only recently been discovered and described as infectious agents. They are known to be even more simple in structure than a virus in that they consist of a single protein. Prions are believed to cause disease by mimicking the structure of essential proteins in the nervous system of their animal hosts. They seem to induce an irreversible change of these proteins into more prion proteins. This leads the host cells to degenerate, and enables the prion to increase in quantity. Creutzfeldt–Jakob disease (CJD) and the new variant form (nvCJD) are two prion diseases that have been shown to affect humans. As far as it is known, prion diseases can only be transmitted when infected animal tissue or blood enters the body of another animal, either by the ingestion of infected flesh, or through surgery and possibly through blood transfusion.

Diseases caused by bacteria

Bacteria (singular is bacterium) are microorganisms that consist of a single simple cell. The structure is far less complex than the typical animal cell described in Chapter 1.1b. Bacteria do not have nuclei or mitochondria, for example, but instead the copying of the genetic material and the energy-generating processes all take place around large molecules that are situated free within the cell cytoplasm. Nevertheless, the bacterium still uses basic nutrients and reproduces in a similar way. For this reason a bacterium is considered a life form. Bacteria are, on average, about one-tenth of the size of human cells, but can be seen through a simple microscope.

Figure 2.4b-III shows a simplified drawing of a rod-shaped bacterium, Escherichia coli (E. coli). The size of bacteria is generally measured in micrometres (μm), which are one-millionth of a metre (1 × 10⁻⁶ m) in size. An E. coli bacterium is 3 μm in length, which is 20 times longer than the diameter of the complex herpes simplex virus.

Figure 2.4b-III • Simplified diagram of a coliform bacterium (E. coli).

If a bacterial disease is suspected, a doctor might take a ‘swab’ of the infected site, for example an inflamed tonsil. The swab is taken to the laboratory, where it is swept across a glass slide, stained with a dye that is absorbed by bacteria, and the ‘smear’ then viewed through a microscope.

In the examination of a smear from an inflamed tonsil resulting, for example, from infection by the Streptococcus bacterium, the microscope might reveal clumps of large epithelial cells from the tonsil, and chains of tiny darkly stained circular forms, the streptococcal bacteria (also known as ‘streptococci’).

Bacteria are classified according to their shape, ability to absorb stains, and other properties that can be tested in the laboratory, and have been given Latin names that often reflect these characteristics. Very often bacteria are classified as Gram-negative or Gram-positive. This simply indicates the way that a bacterium reacts to a stain first used by an early pathologist called Gram, and is a reflection of the nature of the protective coat around the bacterium. More recently, bacteria have been classified according to their genetic makeup. This has led to reclassification of some groups, because genetic analysis reveals similarities and differences that are not apparent from their morphological characteristics.

Bacteria may also be classified according to their morphology. The two broad categories of cocci (spherical cells) and bacilli (rod shaped cells) are morphological categories.

Important Gram-positive bacteria include species of Staphylococcus, Streptococcus, Bacillus, Clostridium (including tetanus), Mycobacterium (including tuberculosis), Corynebacterium (including diphtheria) and Listeria.

Important Gram-negative bacteria include species of Chlamydia, Escherichia (e.g. E. coli), Salmonella, Vibrio (e.g. cholera), Helicobacter, Neisseria (e.g. gonorrhoea and meningococcus), Bordetella (e.g. whooping cough), Legionella (e.g. Legionnaire’s disease) and Treponema (e.g. syphilis) (see Q2.4b-2).

Some infectious diseases, for example tonsillitis and pharyngitis, can be caused by both bacteria and viruses. Other examples include meningitis, encephalitis, pericarditis, bronchitis and pneumonia. Although in these conditions there are various possible infectious agents, the end result of the infection is similar in terms of the development of inflammation within a particular organ (see Q2.4b-3).

Many infectious diseases are described by terms that end with the suffix ‘-itis’. However, this suffix refers only to the fact that an organ is inflamed, but not what the cause might be. This is true also for the term ‘pneumonia’. In fact, some inflammatory conditions, including bronchitis, pneumonia, cystitis, pericarditis and meningitis, can also be the result of damage by chemicals, radiation and autoimmune disease. They are, therefore, not always infectious diseases.

Diseases caused by protozoa, flukes and worms

Protozoa are single-celled animals and they share all the characteristics of the typical animal cell. Protozoa multiply by simple binary fission (mitosis).

Flukes, tapeworms and worms are more complex multicellular animals that possess a rudimentary nervous system and gut. They multiply by producing eggs that develop through an immature stage to the adult form. Often an additional animal host to the human is required for the life cycle to complete itself. For instance, the eggs of the pork tapeworm have to mature in the flesh of pigs before the parasite can be passed on to humans (as a result of eating infected meat).

Collectively, protozoa, flukes, tapeworms and worms are considered to be parasites when they infect human beings. The scientific definition of a parasite is a plant or an animal that lives in or on another animal and lives at the expense of that animal. In medical usage this term does not apply to bacteria or viruses. Nevertheless, the damage done by parasites is similar to that wreaked by infection with bacteria and viruses, including inflammation and an excessive immune response.

Protozoal diseases include giardiasis and amoebiasis (both causes of diarrhoea), malaria and sleeping sickness (tropical disease), and Trichomonas infection (a sexually transmitted disease). Most worm and fluke infections are tropical diseases, although threadworms and toxocariasis are worm infections that can be contracted in the UK.

Diseases caused by fungi

Fungi are a large class of life forms that includes the familiar mushrooms and toadstools, but also moulds and yeasts. Strictly speaking, they are classified as part of the plant kingdom.

Fungi are different from all other plants in that they do not contain the green pigment called ‘chlorophyll’. Because of this they cannot use sunlight to manufacture energy. Instead, fungi require living or rotting animal and plant tissue to survive. Therefore, many have evolved to be parasites, obtaining nutrients from other living organisms, including humans.

In general, fungi do not cause serious disease in humans unless there is depletion of the immune system. In people with immunodeficiency, fungal disease can become a significant and sometimes life-threatening problem. However, minor fungal skin and mucous-membrane infections are very common in healthy people. These include athlete’s foot, ringworm and thrush.

Athlete’s foot is generally a mild fungal infection that targets damp skin. The most common site for the infection to start is the skin between the fourth and fifth toes. It rarely spreads beyond this area, although it can affect the growing nails, resulting in thickening and discolouration.

Ringworm is a fungal skin infection that forms an itchy, spreading ring of redness and scaling on the skin in a way that can be compared to the ‘fairy ring’ produced by some mushrooms. This mild but very contagious rash is often contracted from handling animals.

Thrush is due to a yeast called Candida albicans, which is a natural resident (commensal) of the bowel and genital tract of healthy human beings. It becomes problematic when the natural balance of the microorganisms in the body becomes disturbed. The Candida then becomes too dominant, akin to overgrowth of one plant species in a poorly tended garden. Excessive Candida leads to thick white patches and discharge, and can cause inflammation of the mucous membranes of the genital tract and the mouth.

Candida syndrome is recognised by some complementary health practitioners as a complex constellation of symptoms that include digestive problems, such as diarrhoea, irritable bowel syndrome and bloating, other fungal problems, such as athlete’s foot, and mental problems, such as exhaustion and depression. Thrush may or may not be present in Candida syndrome. The symptoms of chronic fatigue syndrome (also known as ‘myalgic encephalomyelitis’ (ME)) have also been attributed to Candida. Excessive sugars and yeasts in the diet are claimed to be one of the causes of the Candida syndrome, and so the treatment involves a strict diet and the use of antifungal preparations. The use of preparations of the natural bacterium Lactobacillus acidophilus is recommended to help regain a healthy natural balance of microorganisms.

Candida syndrome is not recognised in conventional medicine. For this reason, patients who believe that they have Candida syndrome will not routinely be offered antifungal treatment by conventional doctors unless they have the white discharge, soreness and itching characteristic of thrush. The clinical evidence supporting the benefits of Lactobacillus supplementation in chronic fatigue and minor digestive disturbance is also not believed to be strong. Nevertheless, many doctors will recommend Lactobacillus supplementation to treat depletion of these bacteria resulting from antibiotic treatment or for the treatment of thrush.

Fungal infections are very problematic for someone with immunodeficiency. For example, patients with AIDS commonly experience severe thrush, which can affect the whole oesophagus and mouth as well as the genital mucous membranes. In severe immunodeficiency, Candida can spread to invade the lining of the bowel and other deep parts of body, and this can be life-threatening. Many AIDS patients develop a skin condition called ‘seborrhoeic dermatitis’, which is also due to overgrowth of a usually harmless skin fungus. Unusual fungal infections, such as cryptococcosis and histoplasmosis, are common causes of death in patients with immunodeficiency syndromes such as AIDS.