Why's my virus lingering?

In my previous post, written while in the gloomy grip of a viral illness I was eagerly awaiting the arrival of legions of lymphocytes and antibodies, all perfectly honed to deal with this particular virus. I am now at the “lingering” phase.

Disabling lassitude and gloom receded as my innate immune system retired from the field. My energy levels are nearly recovered but my sinuses are sensitive and my nasal passages and larynx are still decidedly damp.  And everyone I speak to who has had a winter virus seems to have the same complaint – it’s gone, in the main, but not yet forgotten. “It’s lingering” seems to be the common theme.

We should nod with respect to the complex interaction that helps us move into phase two. The innate system obviously “knows” when it can let up with those darn cytokines and let the adaptive system do its work. Hence the big leap forward after 4-7 days.

But why does the miraculous and ultimately effective adaptive immune system take so long to finally get rid of coughs and catarrh?

We have to imagine a numbers game. Viruses “breed” by invading cells and using material in those cells to make a new batch of viruses. The numbers produced are very, very large. Every time an infected cell bursts open they are releasing many thousands of virus particles with the potential to infect nearby cells.

The lymphocytes and antibodies are numerous too, but as they start to do their work, the virus production line is well-established so there is a massive amount of catching up to be done. It’s a bit like weeding a large patch of land on which the weeds are already producing seeds and the seedlings are sprouting almost as fast as the gardener can work. In the end the adaptive immune system always eliminates the last few viral particles. And the bonus prize is that it remembers the unique signature of the virus, so if you encounter it again next year it will be despatched without causing a single symptom.

I have just read a long and detailed account of the interaction between the immune system and the virus during flu (see link, below). As I sit here coughing I am slightly cheered by the thought that the sticky cough-inducing mucus in my larynx is the result of the wholesale death of infected cells.

This little episode has reminded me that influenza and other flu-like illnesses do nothing to enhance life. They can wipe out a week, or three while you wait for them to go. At least when it comes to influenza itself it’s easy to reduce the chances of picking it up by having a flu jab every autumn. It won’t prevent every possible virus – but it increases your chances of having a flu-free winter, and that’s worth having.
http://bit.ly/19yZ5jr

Ebola and the immune system

I’ve often wished the immune system had a different name. One that sounded a lot more grand and complicated. It slips easily off the tongue and gulls people into thinking that it’s no more complicated than their central heating system. And that the equivalent of a tweak of the thermostat (in the form of a pill or a foot massage) can give “it” a quick boost. When researching my book I realised that it’s a system of a very different kind – more like, say, the complexity of a city like London with its workers, businesses, buildings and transport networks.

There are two main divisions to the immune system. The emergency “innate” division kicks in the minute you have a wound. On a much slower timescale the “adaptive” division learns about all the bacteria, viruses and proteins in your environment – which to ignore and which to attack with antibodies the next time they crop up. There are many different types of immune cell (“white blood cells”) and new sub-types are discovered regularly. They produce a vast array of complex proteins called cytokines that also play a role in attacking pathogens. Part of what we mean by “immune system” is this interacting mass of cells and proteins that flow through blood and tissues during health and illness. But there is more. The permanent structures of the immune system are the bone marrow, which is the production unit for replacement immune cells, and the lymphatic system that monitors threats throughout the body.

As in cities, balance is important. You don’t need a rail system that varies its timetable unpredictably. Neither do you need an immune system that is over- or under-active. Everything has to be modulated to keep things running smoothly so as to prevent not only infection but also self-damage. Diseases associated with an over-active immune system include all the auto-immune diseases, allergies and inflammatory conditions. Toxic shock, sepsis and the cytokine storm (which can occur in pandemic flu) are more sudden and much more deadly over-reactions.

Some illnesses are not just attacked by the immune system – they directly infect immune cells and interact with them in complex ways. It’s well known that the HIV retro-virus directly attacks immune cells, using them as a base and slowly undermining their work. TB, caused by a bacterium, also infects immune cells – the ones that normally engulf and destroy bacteria entering the lungs. Ebola too infects immune cells, and progresses far more swiftly than HIV or TB. It does so by using infected immune cells to spread the virus throughout the body. Ebola is also able to damp down aspects of the immune function. But that is not all. The high fever and inflammation of the later stages of the disease are part of a massive immune over-reaction that contributes to death. 

There are various scientific initiatives attempting to tackle this unusual virus but the solutions are not simple.

There are some anti-viral drugs undergoing accelerated trials but it would be surprising if they make a significant impact. The might of the pharmaceutical industry has yet to produce a range of wonder-working anti-virals for other diseases. Anti-retrovirals, used for HIV, are probably the biggest success, despite all their limitations. Vaccine development is a long and difficult road and vaccines in current development are a while away from any prospect of a  mass roll-out. The experimental biological treatment ZMapp is a product of immunological research. It’s a combination of artificially produced antibodies that lock on to specific targets on the Ebola virus, disabling it. It is to be hoped that ZMapp works, and that one day it can be produced in large enough quantities to be useful in bringing outbreaks under control. However production methods are complex involving a lot of careful work by technicians and the growth of cloned cells in laboratory conditions. This process is not at all like the factory production line that produces conventional chemical drugs. My feeling is that science is very unlikely to come up with any quick answers, with mass impact, in the next few months.

In the meantime though, simple nursing measures like infection control and putting up a drip can save lives. As Christmas looms we are asked to contribute to a wide range of charities but this year many of us will perhaps consider that paying for some nursing supplies for Ebola stricken areas is the most urgent call on our generosity.

http://www.bbc.co.uk/news/health-30217573

Tuberculosis and smoking - a lethal combination

I recently succumbed, in the Oxfam book department, to four hefty volumes of The People’s Physician, written in the mid 1930s. As I staggered up the street clutching them to my chest, I briefly regretted my purchase. However they are providing a mine of interesting insights into health and illness when today’s 90 year olds were children. The issues were very different then compared to those we worry about today. Pulmonary tuberculosis (TB) was the second biggest cause of adult death (after cancer) and its victims were predominantly in the earlier part of adult life rather than old age. It is a horrible way to die as lung tissue is slowly destroyed.

TB is unique in the way it interacts with the immune system because many of those infected never develop the full-blown illness. Instead, the bacillus slowly creates a small focus of infection, destroying lung tissue, before the immune system gains the upper hand and literally walls off the area of infection. This virtually eliminates the chances that the infected person will pass TB to others. The immune system, in this instance, consists primarily of immune cells known as macrophages. These large “white blood cells”, patrol the cavities of the lungs engulfing bacteria. The way they interact with TB is complex. They may hold the line, ensuring that the dormant (or latent) stage of TB lasts a lifetime. In other patients a dip in their performance allows the disease to break out and proceed on its destructive path.The BCG vaccination gives only partial protection from infection.

Recently a team of immunologists in Dublin has expanded understanding of how the macrophages interact with TB and how smoking impairs their performance and does so in a number of specific ways, disturbing on the fine balance of resistance to this unusual disease.This serves to remind us that smoking has multiple damaging effects in cells throughout the body. 

In the 1930s the causes of TB were thought to be to be lack of fresh air, infected milk and poor nutrition along with overcrowded housing, which made transmission more likely.  

The only treatments were rest, preferably in a room awash with fresh air, and, if possible, exposure to plenty of sunshine. Sufferers from affluent families were sometimes sent to alpine sanatoria, where semi-clad exercise in the sunshine was a key feature of the regime. In the People’s Physician there are photos of boys wearing only underpants, skiing, ice-skating and sitting at their desks outdoors and girls (in knickers and bonnets) exercising on sunny alpine meadows.

In the 1940s antibiotics became available and streptomycin proved to be an effective cure for TB. I have a relative who received the new drug in the nick of time and, with only half a lung remaining, went on to lead a long, active life. It is still the case though, that a very long course of antibiotic treatment is required to bring about a complete cure.

Although TB is now quite rare in wealthier nations it still kills around 1.5 million people a year, mainly in poorer parts of the world, making it the biggest bacterial killer of our time. There are some 9 million new infections every year. 

It is common knowledge that the damage inflicted on the immune system by HIV is one of the driving factors of this slow-burn epidemic. Drug resistant TB is on the rise, which also contributes to the spread of infection. It was news to me that smoking, too, significantly increases the chances that an infection will become active rather than lying dormant which means that this also makes a contribution to the spread of this horrible illness.

An Indian statistical study predicts that the effects of smoking on those infected will result in an additional 40 million deaths from TB between 2010 and 2050.

Back in the mid 1930s smoking was not considered damaging to health. It was considered as normal as eating and drinking. We now know that it causes lung and other cancers and that it contributes to coronary heart disease. TB, it seems, is yet another way in which tobacco claims victims. As smoking declines in the more wealthy parts of the world it is increasing in many poorer regions, where TB is also common. If drug resistant TB spreads, and there is no reason to suppose that it will not, we could see it returning to Europe as a frequent and indiscriminate killer. This is yet another reason why governments around the world need combat the use of cigarettes with all the determination they can muster.

Here’s the link to more information about the Dublin research:

http://bit.ly/1xKmXIH

And the Indian modeling:

http://bit.ly/11rOYbn

'Flu update

It's that time of year again. Doctors are planning their 'flu vaccine clinics and posters are appearing reminding us to get our annual dose. Since last year there have been several interesting new developments in ‘flu research.

Over a hundred cases of H7N9 'flu in humans, probably contracted from poultry, have been seen in China. The high death rate emphasises the importance of influenza research. It's a race against time before a variant emerges that can easily be transmitted between humans. When it does it could cause a lethal pandemic with catastrophic death rates.

Even the usual winter 'flu sometimes causes serious illness and up to half a million people die of it, every year.

Some of this year's new information is based on analysis of existing data.

A systematic review of a large number of studies highlighted that new mums (but not pregnant ones) and obese individuals seem to be at an increased risk of dying of the complications of 'flu. These two risk groups have not been previously identified. Good quality research in this area is rather thin and more is needed so vaccination programmes can be targeted appropriately.

Another analysis found that in the 2009 outbreak of swine 'flu, pregnant women who had been vaccinated were less likely to go into premature labour than the non-vaccinated. It seems then that 'flu vaccines during pregnancy may protect both babies, from the dangers of being born too soon and mums from becoming seriously ill with 'flu, or even dying, in the month following delivery.

An Australian study looked at links between heart attacks and 'flu, using data on middle-aged people admitted to hospital. It found that having a 'flu vaccination seemed to have a protective effect against heart attacks. If other research confirmed this result it would, again, lead to a change in the recommendations for priority groups.

One of the most interesting, and surprising, findings of the year is that 'flu vaccines are not as specific as everyone thought. Immunology theory is clear - that the immune system develops antibodies, one virus at a time. So every variant of the virus requires a vaccine to match it. Each year the vaccine is a cocktail of the three types that are currently most common worldwide. This new study found that the vaccine gives significant protection against types of 'flu that are not included as well as those that are. This highlights the fact that there is a lot more to the immune system than just antibodies - and that there is still a great deal to learn about how it works.

Finally, for the needle-shy, there is hope on the horizon. Nasal spray 'flu vaccines are being introduced, (initially for use with children in the UK) and research on mice has revealed that a micro-needle patch can deliver 'flu vaccine effectively. I imagine this would be a bit like pressing a bit of Velcro or sandpaper against your skin.

In the UK the 'flu vaccine is free to priority groups and the rest of us have to pay. I always think that £10 spent on a 'flu jab is fantastically good value if it means I can get through another winter without a bout of this debilitating illness.

New risk groups

http://bit.ly/15ZLtuK

Vaccine in pregnancy

http://bit.ly/14PbZpK

Heart attacks

http://bit.ly/19e7dz6

Wider protection

http://bit.ly/158W4my

Micro patches

http://bit.ly/1geayRr

Immune System Even Cleverer Than We Thought

In any branch of science there are moments when conventional wisdom is overturned. One of those moments has just occurred in immunology as a result of research at Stanford University. Our previous understanding was too simplistic. Things are even more complicated than we thought.

For years now everyone has believed that lymphocytes can learn to recognise specific molecules but that each type of lymphocyte can only learn a single lesson. One kind of lymphocyte can learn to recognise measles virus, another can learn to spot whooping cough bacterium on sight and another can only be activated by a particular protein made by prawns. Once a lymphocyte has had its initial exposure it will produce memory lymphocytes (CD4 cells) that will hang around for the rest of your life, waiting patiently to deal with a second encounter. This is how adaptive immunity and, of course, vaccination works. 

But the one lymphocyte = one lesson theory has just been blown out of the water. It seems that lymphocytes can generalise their learning.

The human brain can generalise easily. Learner drivers are taught to negotiate road junctions. Once the basic skill is there, they will be able tackle all kinds of road junctions. No two junctions are identical but nevertheless the competent driver tackles them all confidently. The learning has been generalised.

Now it seems that memory lymphocytes have some ability to do the same kind of thing. They are even cleverer than we thought. They can recognise not only the microbe that first activated them, but some other types as well.

We knew the immune system was magnificently complicated and now we have to acknowledge the existence of a whole new level of complexity. This new knowledge may shine a light several aspects of how the immune system learns about its environment, such as how benign bacteria help the immune system to develop in childhood.
http://www.sciencedaily.com/releases/2013/02/130207131602.htm

Should 'Flu Vaccination be a Condition of Employment for Health Workers?

A recent editorial in the Canadian Medical Association Journal makes the case for mandatory flu vaccinations for health care workers.

There are a number of arguments for requiring health care workers to take up this vaccine.

Health workers in many settings tend to be exposed to flu sufferers during an epidemic and if they fall ill, services are likely to be impaired. Absence rates amongst NHS staff are high when compared to most other UK employment sectors, which puts a significant pressure on hard pressed hospital budgets.

Even more persuasive is the argument that health professionals are in contact with vulnerable patients and could infect them. Individuals sometimes argue that they do not need the flu vaccine because they "never get ill" or that, if they do get 'flu, they will stay at home. The Canadian article points out that flu can be infectious before symptoms appear. We also know that not all those infected with a virus exhibit obvious symptoms.

Age, pregnancy, injury, surgery and acute illness can all suppress the immune system. So imagine your vulnerable relative, entering a health care setting, minus a flu infection this winter. Would you want them cared for by an unvaccinated doctor or nurse?

There is a very strong argument that those who work in health and care settings should be required to have this vaccination.

Employers in the UK have traditionally been wary of imposing health-related rules on their employees. Smoking bans at work, for instance, were slow to take hold. Some would argue that imposing the requirement for vaccination would be discriminatory or an infringement of human rights.

A requirement on health workers would not be discriminatory if applied to all. It does not fall under any section of anti-discrimination law. As far as human rights are concerned, exemptions could be allowed in certain circumstances - if, for instance, someone had a religious objection to vaccination or was advised against it for medical reasons.

Otherwise there would seem to be nothing wrong in saying: It is a requirement of employment that all our staff are up to date with their vaccinations, including annual flu vaccine.

Make it part of the contract of employment when people join, so that new employees are clear that it is a requirement. Use peer pressure to encourage existing staff to comply. To prioritise employee rights over the safety of patients, would seem to be perverse logic.

http://bit.ly/VyUxzX

Could flu be stopped in its tracks?

During a 'flu epidemic vaccination helps. It reduces the pool of susceptible individuals and reduces infection rates in groups most likely to need hospital treatment. The big limitation is that it does not work very quickly. It takes the adaptive division of the immune system a week or two to respond to the vaccine and by that time someone could have contracted flu and become seriously ill. So it would be very handy if there were some means of protecting those who have been exposed to the disease - family members, carers, patients in hospital wards and residents in residential settings spring to mind. Not to mention people with weakened immune systems who may be vulnerable to both 'flu and secondary infections.

The other limitation is that flu vaccines are currently strain-specific. When swine flu started to spread in 2009 it took months before an effective vaccine was in full production. Too late to nip the pandemic in the bud. Too late to prevent some quarter of a million deaths, worldwide. These numbers are far higher than original estimates according to a recent analysis published in The Lancet Infectious Diseases last month

Exciting then, that an American research team have identified a protein that, when administered to mice that had just been deliberately infected with 'flu virus, seems to have a significantly protective effect. It works by stimulating the innate division of the immune system into action - something that is slow to happen in normal 'flu infection. Furthermore this protein is already approved for use in humans, as an immune-stimulating adjuvant in vaccines. This means that translating the research into human trials will be easier than if it was an untried substance. One of the benefits might be that it is generic, rather than strain-specific, which could be a real life saver next time a new pandemic strain emerges.

This would be an unusual treatment - something that truly "boosts" part of the immune system - as opposed to a wide range of ineffective vitamins, potions and herbs.

Sam D. Sanderson, Marilyn L. Thoman, Kornelia Kis, Elizabeth L. Virts, Edgar B. Herrera, Stephanie Widmann, Homero Sepulveda, Joy A. Phillips. Innate Immune Induction and Influenza Protection Elicited by a Response-Selective Agonist of Human C5a. PLoS ONE, 2012; 7 (7):