September 18, 2019

2&3: Natural History of the Measles

How did humans first contract the measles virus? How has measles affected the human population over time? What is the difference between morbidity and mortality statistics?

2&3: Natural History of the Measles

In this lecture, Andrew Wakefield discusses the pathological history of the measles virus in humans. Using this foundation, the coming lectures will build upon this understanding of measles' natural history.


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So having looked at the mortality from what were historically the major killer diseases, let's look at mortality for some other infectious diseases that were considered of lesser significance. And let's look at those diseases against which we vaccinate: Measles, mumps, polio, chicken pox and rubella. Data are available for measles, mumps and polio. Here we see the decline in mortality in the UK, a graph with which we're becoming quite familiar now. Here we see a similar image from the United States of America showing exactly the same pattern of decline in mortality in advance of the vaccine being introduced. Mumps was never a major killer, but nonetheless the pattern of decline in mortality, both in the United States and the UK, is exactly the same, falling well in advance of the vaccine being introduced. And people say, "Well, what about polio? Vaccination has eliminated polio, what a wonderful thing." Well, that may be the case, but look at this graph; this is the mortality from polio, and the red line indicates the introduction of the vaccine. If you look at the peaks occurring in mortality in advance of vaccination, and the decline in the mortality rate, it's really quite dramatic well in advance of the vaccine being introduced, and continues to decline thereafter.

So polio, the whole story has yet to be told. So the mortality trends for infectious diseases, including those that were considered to be the major and minor killer diseases of mankind, show a similar decline over time, irrespective of whether or not there was ultimately a vaccine available. Why? Improved sanitation, better standard of living, easy to understand for major enteric infections that come from contaminated water, such as cholera and dysentery, but less obvious with diseases such as measles. It's not enough to simply cite improved social circumstances without further explanation. What is it about the social circumstances? What is it about the change in social circumstances that influences the outcome from a disease?

02:24 S1: Here is the World Health Organization's manual on training the world's vaccinologists. Key point, the impact of vaccination on the health of the world's peoples is hard to exaggerate. With the exception of safe water, nothing else, not even antibiotics, has had such a major effect on the reduction of mortality and morbidity on a population growth. Is that statement justified based upon what we have just seen? So what questions arise? The importance of this graph, I think, is difficult to overstate. It holds the key to so much of our understanding of man's relationship with infectious disease. Measles is becoming very rapidly a milder and milder disease. Again, what would have happened had we let nature take its course and not introduced the vaccines, and why this decline? Some explanations are clearly required.

Now we come to a very important part of the discussion; we are trying to understand the natural history of measles. We have looked at measles in the individual, now we want to look at the natural history of measles in populations; what has happened in populations over time? Again, remind you that morbidity is the state of suffering from the disease, mild to severe, and mortality, which is effectively the worst end of morbidity, death from the disease, or complications from the disease, such as secondary bacterial pneumonia. Now, measles, as I have said, is a primate virus. It doesn't exist in any animal reservoir in sub-primate species, so there's no niche for it to hide out between epidemics. So for measles to become a highly prevalent, indeed epidemic, disease in developed populations, then there had to be a continuous chain of transmission between people who were infected and susceptible individuals.

And so you can imagine that as populations grew, particularly in Europe, as populations became more dense, as people moved from rural to urban dwellings, then there was at some critical point a sufficient size of population that allowed measles to go from being just epidemic to endemic; in other words, constantly circulating within that population. Now if we look at contiguous countries such as Europe, countries with a common border, we see the emergence of measles first, and we see this classical biannual epidemic pattern. So we see epidemics occurring every two years. This allows in the inter-epidemic years the accumulation of sufficient numbers of susceptible individuals to accommodate an epidemic the following year. It's very different in countries that are isolated, such as islands. Islands tell us so much about infectious disease, and one classic example are the Faroe Islands north of Scotland, a principality of Denmark.

And it was some years ago that we learned a great deal from Peter Ludvig Panum, who went to the Faroe Islands to study measles virus, and taught us so much about what we know of measles today. One of the most important things that he observed was that a single exposure to measles produces lifelong immunity. For example, the last epidemic in the Faroes was in 1781, before Panum went, and he found that only those inhabitants who were over 64 years of age and who had experienced that last epidemic were protected from the next epidemic of measles, so a fascinating observation that one exposure to measles as a child can lead to lifelong immunity. We also looked to others who understood the natural history of measles extremely well: Dr. Axton working in what was then Rhodesia, now Zimbabwe. The outcome of natural measles infection as he studied it was, for the great majority, a mild to moderate disease that led to recovery and lifelong immunity. In some, there were severe disease that could resolve with recovery and lifelong immunity or could lead to death.

He also introduced this extremely important concept of subclinical disease, not everybody who's susceptible and exposed develops classical measles. Many actually developed such a mild disease, it never gets recorded as measles or produces no symptoms at all. Let me remind you that in the US when there were 400 to 500 thousand reported cases a year, it was estimated that there were some 5 million actual cases. So what has happened to measles mortality at the time? We've heard from political leaders, from vaccinologists, from public health doctors around the world, that measles is a killer. Now, that's a rather static view, it leads one to the impression that measles was a major killer, that we vaccinated, and measles is no longer a major killer as a consequence. What is the truth? To understand that, let's go to this graph, which is the measles death rates in children under 16 years of age in England and Wales from the '1920s onwards. And you can see that early on, there was this epidemic pattern of measles which produced a very high mortality, 1200 per million children. And there was a striking change, a striking change, a dramatic fall in the case fatality rate from measles that preempted the introduction of antibiotics to treat secondary pneumonias, for example, and certainly preempted the introduction of the vaccine.

So let's take Dr. Axton's detailed clinical observations from Africa, where he has seen the spectrum of disease from subclinical through to mild to moderate measles through to death. The bell-shaped curve shows that the great majority of those affected by measles lie in the range of a mild to moderate disease from which they recover and develop lifelong immunity. We have this concept of subclinical disease. Now, let's go back in history to a time when measles was a major killer, the curve was shifted to the right, there were a higher proportion of severe exposures with death, very few subclinical exposures, that is the historical pattern of measles. And now, what has happened is we've gone the other way, is that measles is associated... Natural measles with very few deaths. It is becoming a milder and milder disease with lower mortality, lower morbidity and indeed far more subclinical cases of measles. It's not that measles isn't infecting individuals or wasn't before the vaccine was available, it was the disease was becoming milder and vaccination began when there had already been a 99.6% reduction in the case fatality rate. And the question is, "Why?". Understanding the answer to the question why is absolutely essential, it's essential to our understanding of this notion of Herd immunity, what it really means, compared to what it's claimed to be.

It's also interesting to speculate what would have happened if this process had been allowed to continue naturally. What would have happened to that curve? And with other exponential type curves, then it gradually approaches the axis, may never reach zero. But what would have happened? Here's a key question, if we had never intervened with vaccination, would that curve have decayed toward zero? And therefore, of course we'll never know because we did intervene with vaccination. But it's a very, very interesting question. Should we have done? Should we have done just because we could? But this is something to be explored in subsequent talks.