Measles was once one of those diseases that everyone knew closely, one of the infamous childhood diseases. Until the 1960s, it was estimated that every year an impressive 2.6 million people died worldwide from it. If today this pest is somewhat unknown, this is due to the enormous success of vaccination.
The vaccine, developed in 1963, was distributed through a global campaign that reached more than a billion people. Result: measles mortality on the planet was reduced to 73 thousand deaths in 2014. Since then, however, this number has risen due to the slowdown in vaccination.
But if the vaccine is a powerful tool with the potential to end measles history, how did it get started? Measles has been with humanity for centuries. The first clinical reports were written by the Persian physician Rhazes in the 10th century Common Era (CE) and from then onwards devastating epidemics were recorded. what the virus Measles morbillivirus (MeV), who caused the disease, can you tell us about your past?
Researchers have been helping to put this story to rest for some time. MeV is one of the most communicable infectious agents we know, infecting entire communities in the blink of an eye. As this infection produces long-lasting immunity, the virus remains in the population mainly through the birth of susceptible children. In this context, one of the classic studies of epidemiological modeling showed that there is a critical community size, around 250,000-500,000 people, below which MeV cannot remain endemic in the population. In smaller communities it quickly infects everyone and becomes extinct.
One of the richest sources of information about the identity of the virus lies in its genetic sequence. Comparisons of this sequence to those of other similar viruses identify the already eradicated as its closest relative. Rinderpest morbillivirus (RPV), responsible for a devastating disease in cattle. It is likely that at some point an ancestor of MeV broke through the species barrier, jumping from a bovine to a human due to the proximity brought by domestication.
But when would this fateful event have taken place? The answer may also lie in genetic sequences, obtained by statistical modeling of their molecular evolution.. Dating the common ancestor between MeV and RPV, which corresponds to a bovine virus that existed before the passage between the species, is a calibration problem: comparing sequences gives us an estimate of how many mutations have occurred since that ancestor, but how to calibrate what does that mean in terms of time?
Several viruses collected in different periods are used for this calibration: statistical methods contrast sampling dates with differences between sample sequences to date these ancestral events. However, for a quality calibration it is important that the time scales are compatible. This is a problem for measles: we want to date an event that occurred many centuries ago and the sample is all very new (with the exception of the strain used to make the vaccine, the sequences were all after 1990).
In a recent study examining old collections of lung samples preserved in museums, researchers looked for instances in which a person died of measles. Then they applied techniques for extracting genetic material in the hope of finding sufficiently preserved sequences. Bingo! Three new sequences were added to the sample, one from 1912 and two from 1960. With this addition and the use of the most modern statistical techniques, it was possible to improve the dating. While the ancestor was previously believed to have lived in the 9th century CE, now estimates point to the 6th century BC.
Well, how then did the history of measles begin? We still don’t have a definitive answer, and science continues to bring new findings. But one of our best guesses is this: since domestication, ancient humans and cattle lived in close proximity. Several times over the centuries some RPV lineage crossed the species barrier and infected humans, but these outbreaks did not last long. By the 4th century BCE, cities and communities with populations larger than the critical size of 250,000 people began to emerge in many parts of the ancient world..
And it was only from that moment (and after the common ancestor) that one of the events of human infection by the bovine virus permanently established itself in human populations as an ancestor of measles. It was then that our long and sad coexistence with this plague began, which hopefully one day the vaccine will help us to put an end to it.
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Gabriela Cybis is a biologist, professor of Statistics at UFRGS, works in statistical modeling for genetics.
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