Germ theory of disease
Robert Koch (1843-1910)
German physician
Identified the causes of anthrax (1876); TB (1882), and Cholera (1884)
Posited that the disease organism is always present in infected animals, but not in healthy ones
Viruses
Although viruses have been known for about 100 years, they are so small that they were not
seen until electron microscopy was invented
Viruses are particles consisting of a protein coat, viral enzymes, and nucleic acid material in the
form of DNA or RNA
In some cases they will possess an envelope, which is derived from the host cell
Viruses are obligate intracellular parasites
They possess heredity, but lack the means for metabolism and self-reproduction
They must enter and “hijack” host cells in order to reproduce
Viral Reproduction
In order to gain entry into (that is, infect) a host cell, viruses must attach themselves to a
receptor on the host cell’s surface
The receptor is typically something that the potential host cell cannot “hide” from the virus,
such as receptors for specific hormones or growth factors
As such, viruses are able to enter only those cells that possess its target receptors
Once inside the host cell, the virus uses the cell’s “machinery” of reproduction to produce
copies of its nucleic acid and protein
mRNA contains the information required to produce viral proteins
In the case of viruses with DNA, they can transcribe their DNA into mRNA, which is typical of
most cells
Virsus with RNA can either use their own RNA directly or, in the case of retroviruses, copy their
RNA “backwards” into DNA, and then into mRNA the “normal” way
Viral reproduction happens very rapidly, and can literally fill a cell with virus within hours
The mechanisms of viral reproduction are critical in the development of methods to treat viral
illness
Leaving the Host Cell
Viruses leaving host cells in order to infect another can do so by rupturing the cell, or by
“budding”
Viruses that rupture the host cell cause cytolysis, and move to adjacent cells
The resultant death of the host cell can explain the pathology associated with viruses such as
those that cause the “common cold”
Viruses that “bud” possess a lipid envelope that they derive from the host cell; the envelope
allows them to survive longer outside host cells
Viral replication can go on indefinitely in cells, since they survive viral exit
Effects of Infection
Viral infection can have a number of effects:
No pathology
Lytic infections
Carrier status – the overt pathology of the infection is no longer apparent, but the host remains
infectious
Latency – the viruses persist in a non-infectious form and are later reactivated
Transformation – viral DNA (or RNA) becomes integrated into the host cell’s DNA
Bacteria
The fossil record suggests that single-celled organisms similar to today’s bacteria have existed
for about 3,500,000,000 years
Most bacteria are not pathogenic, and many are helpful if not outright vital
Probiotic bacteria aid in our digestion
Bacteria in the gut of ruminants break down cellulose through fermentation
Bacteria in the roots of legumes fix nitrogen
Bacteria are used in making cheese, etc.
Unlike viruses, most bacteria are capable of self-sustained existence
They contain both RNA and DNA
They possess the means for metabolism, and specific bacteria have evolved to do so in oxygenrich environments, while others thrive in oxygen-depleted environments; some form spores
that allow them to persist in hostile environmental conditions for extended periods of time
Bacteria reproduce through simple binary fission; cell division can occur as rapidly as every 20
minutes, and as slowly as every two weeks
The rapid reproduction of bacteria allows for mutations to occur as genetic information “drifts”
from generation to generation
Bacteria are prokaryotic – “pre-nucleated” – while all other living organisms are eukaryotic –
“well-nucleated”
Some atypical bacteria are, like viruses, obligate intracellular parasites (e.g., Rickettsiae and
Chlamydiae) that require host cells to survive
These are often seen as being somewhere between bacteria and viruses
Fungi
Fungi are eukaryotes, with cellular structures similar to that of animals (though fungal cells are
smaller than their mammalian equivalent)
Fungi that are parasitic on humans are quite small, but still visible under the microscope or with
the naked eye
Single-celled fungi are yeasts, while multicellular moulds take the form of filaments
There are approximately 70,000 species of fungi, around 300 of which are zoonotic mycoses;
very few fungi are of significance for human disease
There are many useful fungi, including those used in making bread, beer, and antibiotics; more
recently they have been used in producing vaccines for viral illnesses such as Hepatitis B
Types of Mycoses
Cutaneous and superficial mycoses
Grow on the hair, skin, and nails
Do not cause serious disease (e.g., the moulds that cause ringworm and athlete’s foot),
or normally live commensally (such as candida albicans) but can overgrow (causing
thrush of the mouth or vagina)
Subcutaneous mycoses
Systemic mycoses
Inhaled spores that may lead to (potentially fatal) pneumonia
Mycoses pose the greatest risk to those who are immunocompromised
Control of mycotic infections is limited; a few anti-fungal drugs exist, but no vaccines have been
developed
Protozoa
Protozoans are single-celled eukaryotes
They are large enough to be see though a compound microscope
In addition to a nucleus, they possess a variety of structures that help them move, attach
themselves to their prey, and consume their prey
There are a wide variety of protozoa, but only a few are of significance for human disease
The ones that are of significance, however, are amongst the most important infections globally,
and are found primarily in the tropics
The geographical distribution of such diseases tends to be fairly concentrated, reflecting the
habitat of their arthropod vectors and, in some cases, their animal reservoir population
In addition to the challenges posed to the immune system due to the fact that they are
eukaryotic, protozoa have also developed mechanisms for eluding the immune response (e.g.,
through antigen shifts and/or immune suppression)
As with some mycoses, protozoan infections are often opportunistic – that is, a threat to the
immunocompromised
The lifecycles of some protozoa are simple, and for others wildly complex
The difficulties posed in vaccine development, the development of drug resistance, and
potential habitat shifts due to climate change highlight the ongoing significance of protozoal
infections
Helminths
Helminths represent the most significant infectious burden of our species
4,000,000,000 people worldwide have one or more intestinal worm infection
400,000,000 have worms in blood, liver, lung, or other tissues
Worm infections are most serious in tropical countries
Helminths can vary in size from almost invisible to the naked eye, to >1m in length
Worms do not reproduce in our bodies; they complete their lifecycle in part outside of our
bodies; therefore the number of worms that we contain is in direct proportion to the number
that enter our body (through the faecal-oral route, ingestion of contaminated water or soil,
penetration of the skin, or through an arthropod bite)
Worms can evade the human immune system by camouflaging themselves with human tissues
The size and number of worms involved in some infections represents a tremendous amount of
foreign material in the body
Overstimulation of the immune system can result, causing tissue damage
Helminths have found an infectious “home” in our lymph vessels, small intestine, colon,
caecum, rectum, liver, heart, lungs, gut, skin, blood, bladder, and eyes
Prions
A relatively recent discovery, prions are infectious proteins
There is some debate about the nature of prions, including that some fragment of nucleic acid
may some day be found
Prions appear to disrupt the normative formation and function of proteins
Prions in brain tissue are “protected” from the immune system by the blood-brain barrier (BBB)
Exposure control is the only known method to prevent infection and spread of prions
It has been suggested that prions may be responsible for Alzheimer’s disease, Parkinson’s
disease, and other degenerative diseases – perhaps even aging itself
An Introduction to Disease Diffusion
The diffusion of disease, and its eventual ‘fade-out,’ is a function of the characteristics of the
disease agent itself (e.g. virulence, incubation period, mode of transmission, etc.), and the
population that it affects
This ‘at risk’ population consists of three groups:
Infectives (infecteds) – those with the disease
Susceptibles – those without the disease
Immunes – those with immunity to the disease
The cycle of infection, with respect to its endemicity, is a function of population size. For
example, 19 British towns were classified on the basis of their ability to support a measles
outbreak:
Type 1(A): Population > 250 000; generates sufficient susceptibles to maintain the presence of
the disease; measles remains endemic
Type 2(B): Population > 10 000; insufficient susceptibles to maintain an outbreak; experiences
regular epidemics, but measles is not endemic
Type 3(C): Population < 10 000; insufficient susceptibles to maintain an outbreak; measles is not
endemic, nor are enough susceptibles generated to experience every epidemic
Types of Diffusion
The spread of infectious agents can occur as a result of three spatial processes:
Contagious Diffusion - the disease spreads from one location to nearby places, taking on a
wave-like form which moves over space; the diffusion process is determined by distance
Hierarchical Diffusion (i.e. cascading diffusion) - the disease enters a country or region at a
particular location (e.g. a port), and diffuses down the central place hierarchy until all of the
country or region is affected
If the disease begins at a smaller central place, it will spread to lower-order centres nearby,
‘jump’ to the primate city, and ‘trickle’ down the hierarchy from there
Migrant Diffusion - the disease is spread following the movement of an infected individual over
space, thus exposing potential infectives (‘susceptibles’)
Diseases can (and do) spread as the result of a combination of these processes
The Changing Nature of Disease Diffusion
Whether a disease spreads primarily as a result of contagious diffusion or hierarchical diffusion
is to a large degree dependent on the degree of development of the spatial economy, with
respect to the interconnectivity of the settlements in the country or region in question
Contagious diffusion will dominate when settlements are not well connected (the resulting
spread of disease will be relatively slow and a function of distance)
Hierarchical diffusion will facilitate rapid disease diffusion in those countries or regions with a
well-developed transportation network
Case Study:
Cholera in the United States
Time from source as a linear function of distance and/or population for the epidemics of 1832,
1848-49 and 1886:
1832 Time = 34.9 + 0.77Distance
Time = 44.3 + 0.71Distance - 8.5Pop
1848-49
R2=0.78
R2=0.79
R2=0.40
Time = 21.7 + 0.98Distance
R2=0.60
Time = 78.0 + 0.99Distance - 50.1Pop
1886 Time = 149 - 29.5Pop
Time = 155 - 0.03Distance - 31.4Pop
Disease Transmission Systems
R2=0.44
R2=0.44
Diseases can be passed in a number of ways:
From Human to Human - no intermediate organism is required; transmission may occur
through direct skin to skin contact (e.g. fungal infections), contact with bodily fluids (e.g. STDs),
or through the inhalation of aerosols expressed through the sneezing or coughing of an
‘infective’
From Animal to Human - no intermediate organism is required; transmission may occur through
direct contact (e.g. rabies), or through the consumption of contaminated animal tissues (e.g.
parasites, vCJD??)
Through Human-Vehicle Contact - no intermediate organism is required, though mechanical
transfer may occur through the actions of insects (e.g. flies). Contact with, or consumption of
the vehicle facilitates exposure to the disease agent (e.g. cholera, small pox, salmonellosis, etc.)
From Human to Human with an Intermediate Host - an intermediate organism is required to
complete the disease cycle; the disease agent spends an important life stage in the
intermediate host prior to re-infecting humans (e.g. snails for schistosomiasis)
‘Vectored’ from Animal to Human or from Human to Human - an intermediate organism (e.g.
fly, mosquito, flea) facilitates disease transmission by spreading the disease agent from an
infected individual to a potential infective (e.g. plague)
Disease Ecology
Jacques May described the requirements for the existence of disease foci:
AGENT - the ‘attacking’ biological organism (bacteria, virus, etc.) which results in disease
pathology
RESERVOIR - the animal population within which the disease is continuously cycled (for those
diseases which are not vectored in a strictly human to human manner)
VECTOR - the intermediate organism
HOST - the potential human infective
For a disease to exist, the first three factors must share common territory (i.e. their spatial
distributions intersect)
May advanced the concept of a ‘silent zone’ of disease for those instances where no humans
are available to be infected
Human infection may result when human activities coincide with the ‘silent zone’