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Friday 28 November 2014

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.

Monday 24 November 2014

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:
And the Indian modeling: