Back to the future – our journey back in time to investigate the present and future behaviour of pertussis

Here, Albert Jan van Hoek and Elizabeth Miller, co-authors of an article published in BMC Medicine, tell us more about their team’s “back to the future” journey to understand causes of the recent resurgence in whooping cough (pertussis) and how their findings may help us deal with it in the future.

The counterfactual scenario is a long-established device used by historians to explore the significance of historical events by hypothesizing “What would have happened if…?” a particular historical event had not occurred.

Even the great Winston Churchill, an individual who himself shaped the course of history, succumbed to the lures of virtual history in his contribution to a volume of essays published in 1931 entitled “If it had happened otherwise”. Sir Winston speculated thus The quaint conceit of imagining what would have happened if some important or unimportant event had settled itself differently has become so fashionable that I am encouraged to enter upon an absurd speculation. What would have happened if Lee had not won the Battle of Gettysburg.”

In our article in BMC Medicine we use the counterfactual approach to try and understand the cause of the recent resurgence in whooping cough (pertussis) in England and to help predict its future behavior.

For most of us lesser mortals our flirtation with virtual history is more mundane. Which of us hasn’t at one time thought “What would have happened if I hadn’t done such and such”, like going to that party that night where I met … .

The “what if” scenario is so intriguing that it is now an established film genre as in the “Back to the Future” films where, with the aid of a time machine, an individual travels back in time to change the future course of events (despite the fact that the events being influenced have already happened – a logically impossible scenario that requires a high tolerance of cognitive dissonance on the part of the filmgoer, but nevertheless seems to work for most of us).

In our article in BMC Medicine we use the counterfactual approach to try and understand the cause of the recent resurgence in whooping cough (pertussis) in England and to help predict its future behavior.

Unfortunately, unlike the characters in the “Back to the Future” films who were aided by a DeLorean car, electric guitars and plenty of charisma, we had to rely on mathematical equations, computer programming and the laborious collection of data.

Two counterfactual scenarios in pertussis history

We investigated two counterfactual scenarios; what would have happened if there had not been a dramatic drop in pertussis vaccine coverage in the UK in the 1970s and 80s and what would have happened if we hadn’t changed to an acellular pertussis vaccine but continued to use whole cell vaccine from 2004 onwards.

The whole cell vaccine contains hundreds of bacterial antigens, as well as some toxins, and generates both protective antibodies (B cell immunity) and activates cellular defenses (T cell immunity).

In contrast the acellular product contains just a few purified bacterial antigens and is therefore less reactogenic than the whole cell – which was the main rationale for its development. However, it is more limited in terms of its protective armory as it predominantly induces B cell immunity.

While antibodies may protect against disease, T-cell responses are usually involved in bacterial clearance and reduction in infectivity as elegantly illustrated in the baboon challenge experiments conducted by Todd Merkel’s group in the US.

Mathematical model of pertussis transmission dynamics

To investigate our “what if” scenarios we parameterized a mathematical model that was designed to mimic in silico the transmission dynamics of pertussis infection in England. In this computer model we recreated the English population over time starting from 1955 onwards – the year before the introduction of pertussis vaccine and coincidentally the same year into which Marty McFly launched himself in the DeLorean.

Our model was fitted to the pertussis notification data in 1955, and so starts with the simulation of natural transmission of pertussis before any vaccination. From 1955 onwards we simulate the impact of introduction of the whole cell vaccine, and re-run history investigating our two counterfactual scenarios.

Pertussis resurgence was probably caused by acellular vaccine use

Our results suggest that it was the introduction of the acellular vaccine, rather than the collapse in vaccine coverage a generation ago, that likely played an important causative role in our recent pertussis resurgence.

By varying the parameters used to define how well the whole cell and acellular vaccines protect against infection we were able to identify the values that produced the model outputs most closely fitting the observed epidemiological trends.

Gratifyingly we show that the effect of the vaccines on British children is likely to be similar to that on Todd Merkel’s baboons – better protection against infection induced by whole cell than acellular vaccines.

What’s there for the future?

There will therefore be a continuing need for the maternal pertussis vaccination program. (…) Countries still using a whole cell vaccine should stay with it.

Our observations have implications for the future. Our model predicts that the elevated transmission of pertussis that resulted from the transition from whole cell to acellular vaccines will continue. There will therefore be a continuing need for the maternal pertussis vaccination program that was introduced in the UK in 2012 as an outbreak control measure and has been so successful in preventing infants dying from whooping cough.

Together with other analyses, our model findings contributed to the recent recommendation by the World Health Organisation that countries still using a whole cell vaccine should stay with it. For countries that have already made the transition, our model predicts that reduction in pertussis transmission in the future requires a vaccine that provides better all-round protection than the acellular vaccine, in fact one with some of the properties of whole cell vaccine – a true case of “Back to the future”.

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