As deadly whooping cough makes an unwelcome comeback, scientists are working on new ways to prevent and treat it.
The return of whooping cough epidemics, even in countries where vaccines are freely available, is concentrating minds on the need for a vaccine that offers long-lasting protection.
Globally, around 85 % of children are immunised against whooping cough, yet there are still 20 to 40 million cases per year worldwide, and an estimated 200 000 to 300 000 deaths, according to the EU-funded CHILD-INNOVAC project, which is working on a new vaccine for the disease.
In Europe, vaccination rates are higher than ever before and the number of reported cases is just under 20 000 per year, according to the European Centre for Disease Prevention and Control. Yet the disease, also known as pertussis, appears to be on the way back, and has reached a 50-year high in many parts of the world.
Part of the problem, say experts, could be that the protection offered by existing vaccines wears off over time. This means adolescents and adults could be at risk of infection and, much more seriously, in danger of passing the bacteria to babies.
Whooping cough, caused by the Bordetella pertussis bacteria, produces intense bouts of coughing and vomiting and can kill very young babies. However, they generally do not begin the three-jab course of vaccines until they are two months old, and thus are not fully protected against the disease until around six months.
This problem is one that Dr Camille Locht has been wrestling with for a quarter of a century.
‘Our approach represents a totally new concept.’
Dr Camille Locht, from the CHILD-INNOVAC project
‘Rising rates of whooping cough in adolescents and young adults is not a huge issue – they may be coughing for weeks but they rarely die. The problem is that they can transmit this to newborns,’ he said. ‘We need to do something about this.’
As part of the CHILD-INNOVAC project, Dr Locht has been working on a way to protect babies with a nasal vaccine he hopes could provide faster immunity that would last for longer.
The vaccine would work by giving babies a dose of the actual bacteria, after it has been modified to render it harmless. ‘The current acellular vaccines are composed of purified components of the bacterium which causes the disease,' Dr Locht said. 'What we have done is genetically modify the bacterium so that it does not cause disease and then deliver it via a drop of liquid in the nose.’
Not to be sniffed at
Not only does he expect this to be a more effective vaccine, but a nasal vaccine would be painless and probably preferred by patients and their parents who shudder at the sight of syringes.
If the vaccine makes it from the lab to public health clinics, another bonus would be that the drops will be relatively cheap to produce and would not require any administration device – no syringes, no disposable needles, no inhalers.
‘Our approach represents a totally new concept. We found in clinical studies that, although the immune responses of newborn babies are immature, the live vaccine we are developing can induce strong prevention which lasts a long time.’
It’s already been tested in a small safety trial of 48 adult men, and now researchers need to do more work to fine-tune the ideal dose and volume of the modified bacteria that the nasal drops should contain.
The next step will be collaboration with a company and more trials in young adults. It will then be tested in children before it is ready to be trialled in babies.
‘It is impossible to predict the precise timeline but the results have been encouraging and we think it could offer something new in the fight against whooping cough,’ said Dr Locht, who is based at the INSERM Institut Pasteur de Lille in France.
Hunting for new drugs
Prevention is better than cure, but if a baby does get infected with Bordetella pertussis, antibiotics can give the immune system a valuable helping hand. However, the spread of antibiotic resistance means that existing drugs are losing their power, so new drugs which could take on the infection faster would save lives.
Dr Raz Zarivach, from the EU-funded T3SSBTEA project, believes better understanding of the basic molecular structure of harmful bacteria can be part of the solution.
He has been studying small molecules on the surface of Bordetella pertussis known as effectors. These proteins can influence how foreign bacteria interact with our immune system, essentially making the bacteria more infectious.
‘If we understand how proteins manage to change the cellular response to the bacteria, and if we can block such interaction inside the human cell, maybe we can then design antibiotics or a new way to stop the pertussis bacteria from being so dangerous,’ he said.
Dr Zarivach, a senior lecturer at Ben-Gurion University of the Negev, in Israel, has worked out the 3D structure of an effector protein found on Bordetella pertussis so that the team can better understand how it interacts with humans. This basic biology work could eventually identify new targets for drug companies, he said.
‘If we can figure out how the effectors do what they do then we may be able to understand how to design a molecule to block it.’
With tens of thousands of new cases diagnosed in Europe every year, the battle to outsmart the whooping cough bacteria looks set to intensify.
Even diagnosing whooping cough can be challenging for doctors, particularly in infants as the early symptoms can resemble other less-serious respiratory infections and, in some cases, diagnosis comes only when it is too late to intervene effectively.
The EU-funded RESPOC research consortium aims to develop a simple one-hour test for the disease by the time it finishes in 2016. Their ‘lab on a chip’ device would allow hospital staff to rapidly diagnose whooping cough without having to send samples away for specialist laboratory analysis.
‘If the disease is detected as soon as possible, a proper treatment can begin, and this is crucial in a disease that can be very serious, especially in young children,’ said Ruben Ventura of Ateknea Solutions, a firm that helps companies to develop technology, which is leading the project.
The test would work by extracting and amplifying DNA, and researchers expect it will be able to identify someone who is infected with the bacteria behind pneumonia, as well as the one that causes whooping cough.
For more information: www.respoc.eu/
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