October 1784, Thomas Jefferson (known as the Founding Father of the United States and author of the Declaration of Independence) was serving as Minister to France. His late wife’s relatives were looking after his two daughters, Polly and Lucy, as well as their own children, when horror struck both the families.
Thomas received the following news: "I am sorry to inform you that my fears about the welfare of our children, which I mentioned in my last, were too well founded. Yours, as well as our dear little Lucy, have fallen sacrifices to the most horrible of all disorders, the whooping-cough. They both suffered as much pain, indeed more than ever I saw two of their ages experience.”
Sadly, Thomas’ loss was commonplace in the 18th century. Many children’s lives were claimed by the highly contagious whooping cough (sometimes referred to as the 100-day cough), caused by a bacteria called Bordetella pertussis.The 1940s saw the discovery of the first effective vaccine against whooping cough and it was quickly adopted globally, drastically reducing the number of whooping cough cases and deaths. However, despite widespread national vaccination programmes, rates of whooping cough have been climbing since the 1980s.
New research from University Hospital Southampton and Europe, led by Professor Robert Read, published in Clinical Infectious Disease in September, shows that people can silently carry Pertussis bacteria with no symptoms. And this could explain in part how the disease continues its stealthy spread and keeps re-emerging.
The mysterious re-emergence of whooping cough
Whooping cough can last for two to three months or more and affects around 24 million people every year worldwide, particularly in developing countries, causing around 200,000 preventable deaths in children. Adults usually experience an unpleasant and persistent cough, but the disease is much more dangerous for infants, who can be vulnerable to life-threatening complications.
In the UK alone, there were 25,891 cases between 2012 and 2018; this was a four-fold jump compared to the period between 2005 and 2011 (6,216 cases).
This is surprising, because nearly all of the population in the UK has been vaccinated against Pertussis and this should provide ‘herd immunity’ and stop the disease spreading.
Uptake of the vaccine – normally given to infants and children as a combination with diphtheria and tetanus (called DTaP) – hasn’t decreased significantly over the last 20 years. But it doesn’t give people lifelong protection and is now less effective than it was 15 years ago.
One of the researchers who carried out the work, Dr Hans de Graaf, explains what they set out to investigate.
“Research has suggested that the formulation of the vaccine we use, called the acellular pertussis (aP) vaccine, protects people against the severe symptoms of the disease, but it doesn’t prevent the bacteria from colonising the airway.
“It’s important we find out if this occurs, because if people are carrying the bacteria in their airways without getting sick, it could explain why we are seeing these modern-day outbreaks and how the infection is being passed on to those at high risk of getting dangerously ill, including infants.”
Studying Pertussis infection in volunteers
The team at University Hospital Southampton used a human challenge infection model to answer this important question; asking volunteers to take part and be purposefully exposed to the bacteria so they could study the infection in detail.
“We made sure all volunteers were healthy, non-smoking adults who had been vaccinated against whooping cough at some point, and who would not come into close contact with any vulnerable people or infants during the study,” says Dr De Graaf.
The 34 volunteers had a dose of the bacteria via nose drops. The Pertussis bacteria used in the study are a well-characterised strain that’s highly sensitive to antibiotic treatment.
“The volunteers stayed in a unit so we could keep a close eye on them for 17 days,” says Dr De Graaf. “We monitored them for signs of disease such as a cough, sore throat, nasal congestion, or generally feeling unwell – if anyone became sick, we had antibiotics on hand to treat them. And all volunteers were given antibiotics at the end of the study to ensure the Pertussis infections were fully cleared up.”
During the study doctors took numerous types of samples, including blood tests, swabs and washings from volunteers’ noses and throats, and droplets in exhaled air to determine whether the Pertussis had gained a foothold.
Importantly, the study proved very safe and no volunteers needed to be given antibiotics during the study – not even those given the highest doses of Pertussis. And the antibiotics at the end of the study were effective, clearing up any detectable signs of the bacteria within 48 hours.
19 of the 34 volunteers tested positive for Pertussis infection, despite the fact they had received vaccines in their lifetime. But although the tests were positive, they didn’t experience any obvious symptoms of having the disease.
“This is the first time anyone has shown that people can carry Pertussis infections without becoming unwell,” says Dr De Graaf. “The infection was effectively silent, even in volunteers who mounted an immune response to the bugs.”
According to Professor Robert Read, director of the NIHR Southampton Biomedical Research Centre, this has serious implications for how we try and eliminate the disease.
“Healthy adults who have been vaccinated can still carry round the bacteria without realising it. And this pool of silently lurking bacteria could explain why we are seeing episodic outbreaks of whooping cough throughout the world, with serious consequences for infants and unvaccinated people.”
It’s important information for the development of better vaccines too.
“We need more information about what protection different forms of Pertussis vaccines offer against silent colonisation later in life and whether more regular boosters in adulthood could reduce the pool of silent carriers,” says Professor Read.
Another potential strategy to tackle whooping cough is to find out whether carrying a silent infection is protective against severe disease, and whether Pertussis bacteria engineered to be harmless could act in the same way as a vaccine and protect infants and other vulnerable people.
The hope is that one day, like smallpox, vaccinations can eliminate whooping cough altogether, and the findings from this study could provide important clues to help achieve this.
The £2.3 million study forms part of a wider £24 million European project, PERISCOPE, funded by the Bill & Melinda Gates Foundation and the Innovative Medicines Initiative (IMI), involving experts from 22 institutions across 11 countries. For more information email UHS.recruitmentCRF@NHS.net.