12 Background to the infectious diseases
Vertebrates have been continuously exposed to microbial infections throughout their hundreds of millions of years of evolution. Disease or death was the penalty for inadequate defences. Therefore they have developed:
The fundamental bases of these defences have been described in Chapters 9 and 10. If these defences were completely effective, microbial infections would be scarce and terminated rapidly, as microorganisms would not be allowed to persist in the body for long periods.
Microorganisms faced with the antimicrobial defences of the host species have evolved and developed a variety of characteristics that enable them to bypass or overcome these defences and carry out their obligatory steps for survival (Table 12.1). Unfortunately, microorganisms evolve with extraordinary speed in comparison with their hosts. This is partly because they multiply much more rapidly, the generation time of an average bacterium being 1 h or less compared with about 20 years for the human host. Rapid evolutionary change is also favoured in bacteria that can hand over genes (carried on plasmids) directly to other bacteria, including unrelated bacteria. Antibiotic resistance genes, for instance, can then be transferred rapidly between species. This rapid rate of evolution ensures that microbes are always many steps ahead of the host’s antimicrobial defences. Indeed, if there are possible ways around the established defences, microorganisms are likely to have discovered and taken advantage of them. Infectious microorganisms therefore owe their success to this ability to adapt and evolve, exploiting weak points in the host’s defences, as outlined in Table 12.2 and Figures 12.1, 12.2. The host, in turn, has had to respond to such strategies by slowly improving defences, adding extra features, and having multiple defence mechanisms with overlap and a good deal of duplication.
|Obligatory steps for infectious microorganisms|
|Attachment ± entry into body||Evade natural protective and cleansing mechanisms||Entry (infection)|
|Local or general spread in the body||Evade immediate local defences||Spread|
|Multiplication||Increase numbers (many will die in the host, or en route to new hosts)||Multiplication|
|Evasion of host defences||Evade immune and other defences long enough for the full cycle in the host to be completed||Microbial answer to host defences|
|Shedding from body (exit)||Leave body at a site and on a scale that ensures spread to fresh hosts||Transmission|
|Cause damage in host||Not strictly necessary but often occursa||Pathology, disease|
a The last step, causing damage in the host, is not strictly necessary, but a certain amount of damage may be essential for shedding. The outpouring of infectious fluids in the common cold or diarrhea, for instance, or the trickle from vesicular or pustular lesions, is required for transmission to fresh hosts.
Every infection is a race between the capacity of the microorganism to multiply, spread and cause disease and the ability of the host to control and finally terminate the infection (Fig. 12.1). For instance, a 24-h delay before an important host response comes into operation can give a decisive advantage to a rapidly growing microorganism. From the host’s point of view, it may allow enough damage to cause disease. More importantly, from the microbe’s point of view, it may give the microbe the opportunity to be shed from the body in larger amounts or for an extra day or two. A microbe that achieves this will be rapidly selected for in evolution.
The picture of conflict between host and parasite, usually and appropriately described in military terms, is central to an understanding of the biology of infectious disease. As with military conflicts, adaptation on both sides (Box 12.1) tends to lessen the damage and incidence of death in the host population, leading to a more stable and balanced relationship. The successful parasite gets what it can from the host without causing too much damage, and in general, the more ancient the relationship, the less the damage. Many microbial parasites, not only the normal flora (see Ch. 8), but also polioviruses, meningococci and pneumococci and others, live for the most part in peaceful coexistence with their human host.
Box 12.1 Lessons in Microbiology
Myxomatosis provides a well-studied classic example of the evolution of an infectious disease unleashed on a highly susceptible population. Myxomavirus, which is spread mechanically by mosquitoes, normally infects South American rabbits (Sylvilagus brasiliensis), but they remain perfectly well, developing only a virus-rich skin swelling at the site of the mosquito bite. The same virus in the European rabbit (Oryctolagus cuniculus) causes a rapidly fatal disease.
Myxomavirus was successfully introduced into Australia in 1950 as an attempt to control the rapidly increasing rabbit population. Initially, more than 99% of infected rabbits died (Fig. 12.2), but then two fundamental changes occurred:
1. New, less lethal strains of virus appeared and replaced the original strain. This occurred because rabbits infected with these strains survived for longer and their virus was therefore more likely to be transmitted.
2. The rabbit population changed its character, as those that were genetically more susceptible to the infection were eliminated. In other words, the virus selected out the more resistant host, and the less lethal virus strain proved to be a more successful parasite. If the rabbit population had been eliminated, the virus would also have died out, but the host–parasite relationship quite rapidly settled down to reach a state of better balanced pathogenicity, and by the 1970s only about half the rabbits died from infection. Australian rabbits have since faced a new threat, a calicivirus introduced from Europe, which spreads by contact and causes a lethal haemorrhagic disease.