As part of an exercise to keep me writing regularly I am going to pick out lectures (or parts of) that I have had recently and found interesting, and am going to explain them on here. Also for anyone interested you can see what around £3000, soon to be £9000, can get you in an English University.

Anyway, this first post comes to you courtesy of an Infectious Disease and Health lecture.

Vaccines can sometimes do more harm than good. There are risks associated with any vaccine, as with any medical intervention. This could involve rare allergic reactions, or even in some cases it could be an inherent property of the vaccine, such as with the oral polio vaccine. This vaccine is a live attenuated virus which has been passaged through both live monkeys and monkey cells to induce genetic changes that affect the viruses ability to cause disease. Reversion occurs inside most vaccinees, as the sequence of the virus genome reverts back to the original at a certain position; meaning that the virus can regain virulence. This can lead to vaccine associated paralytic poliomyelitis. This may sound dangerous but the benefits of vaccination far outweigh the risk. VAPP occurs in 1-2 in 1,000,000 doses given, whereas paralytic poliomyelitis occurs in around 1 in 100 polio infections.

Vaccinations can also do damage if they aren’t being given at high enough rates. Why? Well, as well as serving to protect the individual, vaccines can protect others even if they are not vaccinated. This is all because of a process known as herd immunity, as reducing the number of people who are susceptible to the disease will protect the remaining susceptibles; as with diseases that are infectious one person’s health status (immune/susceptible/infected) at a particular time point will have an impact on surrounding peoples’ health status. Immunisation reduces the rate of infection in those not immunised. So how can vaccination affect this to a point where it can be a positive thing, when the same intervention done at less coverage can have adverse effects?

Agents of infectious disease have a basic reproduction number (R_{0}) associated with them, a number which states how many secondary cases will arise from one primary case on average (in a population in which everyone is susceptible). The formulation of the basic reproduction number is shown below:

R_{0 }= pc x D

p is the probability that infection will occur when an infected individual meets a susceptible, c is the average rate of contact between susceptible and infected

individuals, and D is the duration of infectiousness. The basic reproduction number gives us some helpful insights into how diseases will progress through populations, when we take into account the proportion of susceptibles to immune.

As well as helping to define disease dynamics the basic reproduction number can also tell us what proportion of the population has to be vaccinated against a certain disease to prevent epidemics. How? Well remember that the basic reproduction number describes the average number of secondary cases from a single primary case in a completely susceptible population, if by vaccination we can create immunity so that vaccinees are no longer susceptible to the disease we will affect c, the average rate of contact between susceptible and infected individuals. Imagine that we have 10 individuals, 1 of whom is infected, 8 of which are immune and 1 who is susceptible. The one who is susceptible is likely to be protected from transmission of the disease to him/her due to the dead-end the disease will meet in the immune individuals, compared to the easy spread that would occur through all 9 being susceptible. This is all contained in the formula of the effective reproduction number (R) which takes into account the proportion of susceptibles in the population and tells us how many secondary cases will arise from a primary case in that population:

R = *x*R_{0}

In this case *x* represents the proportion of the population susceptible. The effective reproduction number (R) can help us to define disease dynamics. An R of <1 will obviously result in a disease that eventually dies out, an R of >1 will result in epidemics whereas R of 1 will result in endemic dynamics, where the disease always maintains a low prevalence in the population but is never eradicated. It becomes quite clear if we can reduce the susceptible proportion to a low enough number to cause the effective reproduction number to become <1 we can prevent epidemics and even eliminate/eradicate disease. For example the measles virus has an R_{0} of 15, so what proportion of the population have to be vaccinated (*p*_{v}) to prevent epidemics i.e. reduce the effective reproduction number to equal to or less than 1? Well:

*p*_{v} = >94% = 1 – 1/15

So greater than 94%, as we need the proportion susceptible (*x*) to equal 1/R_{0 }(in this case <0.06) to reduce the effective reproduction number (R) to less than 1. But don’t take my word for it, check out the data in the UK for measles notifications since the 1950s:

As the measles vaccine is introduced coverage of vaccination begins around 50% and gradually increases until it reaches a plataeu at >90% in the 90s. Notice the epidemic dynamics as coverage increases, the peak occurrences become smaller and the time between each epidemic is widened, due to a falling R number as the proportion of people susceptible decreases with increasing vaccination coverage. As the vaccine coverage reaches the >90% mark the disease dynamics enter into a more endemic state. Worryingly the vaccination coverage falls below this mark from 1998 into a point at which problems could arise once again; most likely associated with an erroneous paper published by a very silly, silly ~~doctor~~ man claiming that MMR caused autism.

Anyway enough of the epidemiology 101. How can an intervention that reduces the number of people susceptible and reduces the effective reproduction number then have a negative effect?

This is the part where we turn our heads to Greece and the curious case(s) of congenital rubella. Rubella infections are caused by the rubella virus, and are normally fairly trivial childhood infections that cause a rash and flu-like symptoms, earning it its common name German measles. In contrast congenital rubella, that which is acquired by the fetus whilst it is still in the womb of the mother in the first trimester of pregnancy, can lead to serious birth defects.

In the 1960s before any rubella immunisation was introduced to Greece the average age of infection was 8.5 years of age (around which it remained up until the late 80s). Immunisation was introduced in 1975 in children aged 1 but was never implemented with sufficient policies to obtain vaccination rates above 50%. This resulted in an increase in the average age of infection, increasing the prevalence of infections in women aged 15 to 19, with an average age of infection at 17, in a 1993 epidemic. This puts infections in a range close to women of childbearing age and subsequently caused an epidemic of congenital rubella in 1993, with 25 cases per 100,000 births (Although this is the data given in the study, they accept that inherent with the shoddy implementation, was also poor surveillance).

The shift in prevelence of rubella infection at specific age groups in two epidemics, 1986 and 1993

This occurred because a low vaccination rate reduced the number of susceptibles down to a point to create a low effective reproduction number; as vaccination reduces the rate at which new susceptibles enter the population through births. However over time the susceptibles builds up again, but much slower than if vaccination had not occurred, and a point occurs upon which an epidemic can break out; but at this point susceptible women who were not immunised are now much older than they would have been if vaccination had not occured.

The 1993 epidemic followed by cases of congenital rubella syndrome.

This worrying pattern has not only been seen with rubella but also with measles. In France in the early 2000s the vaccination coverage was stable but at the sub-optimum of 84%. This again leads to an increased average age of infection for the same reason as rubella, which is problematic as older people are more likely to have complications. Worryingly, the similar drop in UK vaccination coverage for measles could also have the same effect.

What has been shown here is what is known as perverse effects of vaccination. But vaccination is one of the greatest advances in human health if implemented properly, saving countless lives and reducing disease burden. It’s such a shame that some people spread mis-information about vaccines and their risks, either because of partisan interests or genuine ignorance. Or because some people are just simply unaware of the effect they can have on the rest of the population by having a simple medical intervention. In essence they really do ruin it for the rest of us.

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*Panagiotopoulos T, Antoniadou I, Valassi-Adam E. Increase in congenital rubella occurrence after immunisation in Greece: retrospective survey and systematic review. British Medical Journal (1999) Dec 4;319(7223):1462-7. Review.*
*Bonmarin & Levy-Bruhl. Measles in France: the epidemiological impact of suboptimal immunisation coverage. Eurosurveillance **(2002)* 7 (4), 55-60