RAINA MACINTYRE: The next concept that’s really important for you to grasp is the concept of R– the reproductive number. R is simply the number of secondary cases generated from one index case. So for example, if I have measles and I said in a room with 100 students, and I infect 15 students, then the R zero of measles, assuming that nobody there had any immunity to measles, is 15. I infect 15 people, the R zero is 15. So the lower the R zero, the easier it is to eradicate or control a disease.
Now, the R zero is affected by characteristics of the organism itself, how infectious it is, how long it stays infectious for, and whether there’s a period of asymptomatic transmission, where a person can transmit to someone else without having any symptoms. And that certainly is the case for influenza, for example. And then it depends on population demographics, social mixing patterns, and population density. So in general, the R zero will be higher in big cities than in country towns. There, schematically I’ve shown you a disease with an R zero of three.
You can see your index case at the beginning of the tree, which gives rise to three more cases and each one of those gives rise to three more, and you get this branching chain epidemic. And the graph on the right shows you the epidemic curve that arises from an infection like this. In terms of disease control, if you vaccinate one third of the population, then you’ve reduced the R zero or you reduce the R from three to two, effectively. So the effective R becomes two. And this is what we do in terms of disease control. We aim to reduce the R to below one.
So in terms of interpreting R, if R is greater than 1, the number of cases increases and the conditions for an epidemic of present. If R is less than 1, the number of cases decreases and an infection cannot be sustained and dies out. So R equals 1 is called the epidemic threshold. The other concept that’s really important to understand is the patterns of infectious diseases. There can exist three or four patterns. The first is endemic diseases– a disease that exists permanently in a particular region or a population, and malaria is a classic example of an endemic disease. So is diabetes or heart disease. So is antibiotic resistance– it’s an endemic disease.
Epidemic disease, on the other hand, is an outbreak of disease that attacks many people at about the same time. And it may spread through one or several communities, and it’s defined by the rate of growth of the epidemic curve. So classically, this is seen with diseases with an R zero that’s well above one that’s spread person to person. Although you can see an epidemic occur from a point source outbreak such as food poisoning. A pandemic is simply an epidemic that has spread all around the world. So otherwise, the pattern is similar to an epidemic. Sporadic disease is the last pattern, and that is diseases that do not occur in high enough numbers to be either endemic or epidemic.
They occasionally cause cases– usually these are zoonotic diseases– diseases that spread from animals to humans occasionally. And human cases of avian influenza H5N1 are an example. So pandemic, as I said, is simply a global epidemic where the epidemic threshold of one is exceeded. And depending on how high the R zero is, that defines how rapidly the pandemic spreads. You’ll often hear the term epidemic. There’s an epidemic of obesity, an epidemic of diabetes, an epidemic of heart disease, an epidemic of eye sore cocaine, an epidemic of malaria. These are not epidemic diseases, even if the train is increasing over decades or years, as is the case with diabetes and heart disease. This is not epidemic disease.
You’ve got to see the rise happening within days or weeks for it to be an epidemic. That’s what an epidemic curve looks like. And it’s defined mathematically in the case of person to person infections based on the R zero. It’s not defined by the total number of cases. You have to see this rapid rise over time, and classically epidemics require surge capacity in the response in your health system. So just to sum up then those patterns of disease– at the top there is an endemic disease that’s got more or less a constant raid of infection, maybe slightly increasing. Very high numbers of cases– but the rate is constant over time or very slowly changing over time.
The red shows you the epidemic curve rise up at a peak and down, and at the bottom, the blue line is a sporadic disease that occasionally occurs. . Now Herd immunity is another concept. It applies to vaccination. It’s when the entire population is protected whether or not they’ve been immunised because the number of susceptible people is too small for the infection to spread because you’ve vaccinated enough people to stop transmission in the community. The higher the R, the higher the Herd immunity required to control the disease. And this is quite a key concept for vaccine preventable infections.
This just shows you mathematically the relationship between R zero on the x-axis horizontally, and the percentage of Herd immunity required on the y-axis vertically. And you can say for a disease like smallpox, at the time it was eradicated, the R zero was estimated to be around three. So you needed to have about 60% of the population vaccinated to eradicate it. Measles on the other hand, has a very high R zero, about 15. So you need to have in excess of 93% of the population immune in order to control, eliminate, or eradicate measles. So eradication of measles is much, much more difficult than eradication of smallpox. So what is an emerging or re-managing infection? we hear this term commonly.
It means a new evolving or re-emerging infection. And as long as microorganisms have the capacity to mutate genetically, emerging infectious diseases will remain a threat to humans. One study estimated over 335 emerging infectious disease events since 1940, 72% originating in wildlife, about half are viral and the rest are bacterial or reckiettsial. Another important concept to understand is dose response relationship. Basically, if you’re thinking about bio-terrorism and someone being infected with an unnatural dose of infection, the higher the dose of exposure, the shorter the incubation period becomes. That’s the period from becoming infected to developing symptoms and the more severe the symptoms and the illness. So in general, a deliberate attack would likely involve much higher doses than natural exposure.
Therefore you would expect to see much more severe illness and quicker onset of illness. So for any infection, there’s an expected distribution of severity from asymptomatic at one end, to death at the other end. When you say classed as an infection that show higher than expected rate of severe infection, a shorter mean incubation period then you’d expect, or recurrent severe infections in a single individual who’s otherwise got a normal immune function, this could flag the use of a potential bio weapon. The incubation period, as I said, is the time from being exposed to the infection to developing symptoms. It’s usually a range and it’s specific for each disease. So for example, smallpox is thought to be 12 to 14 days.
Infections have a mean incubation period and then a range around that. Anything that’s outside the range that’s known should be investigated because there has to be a reason why it’s outside the range. A short outlier that’s occurring quicker than you would expect it based on the range could be explained by an abnormally high dose of exposure, such as what you’d expect with a bio weapon. And a longer outlier that’s occurring outside of the expected incubation is either explained by a mischain of transmission, so you’ve just failed to identify a person in the chain of transmission, or deliberate infection because it’s not following person to person transmission. There is unnatural release of infection that’s continuing to infect people.
So in summary, infectious diseases are still a major global burden of disease. What you need to understand is the capacity for emergence and reemergence of infectious diseases, understand the types of infectious agents and the basic differences, understand the basic principles of transmission and the routes of transmission because that tells you how bio weapons can be used, and understand patterns of disease– epidemic versus endemic– and understand the dose response relationship, and the incubation period. Control and prevention of infectious diseases is a challenge but if you understand these principles, it becomes easier to put in place mitigation and prevention strategies. Thank you.