Norovirus - latest news

Winter vomiting (noro) virus is usually a brief, illness that lasts for a few days. For the vulnerable though diarhoea and vomiting can be more serious and if it spreads in institutional environments it can cause big problems. It transmits very easily – just a few viral particles are all that is required to infect someone.

We don’t know a great deal about why it is more common in winter or why an outbreak can appear “out of nowhere”. There is a suspicion that some individuals can carry the virus in their bodies for a long period. This happens with some other pathogens that use the faecal-oral route, such as the one that causes typhoid. In the notorious case of “Typhoid Mary” a cook passed the infection to a number of people, over a number of years.

A paper published this week has shed new light on the biology of norovirus. Researchers used a strain of mice that were infected with the virus.

One surprising discovery is that certain antibiotics, if given before infection, seem to have a protective effect against noro. This has led to the suspicion that certain gut bacteria can live in symbiotic partnership with the virus and sustain a long-term infection. This mechanism could facilitate a reservoir of infection in the community. Kill the bacteria with antibiotics and you might prevent long term noro infection.

This discovery seems unlikely to lead to antibiotic treatment for the average case of norovirus. The immune system brings about its own cure, within a few days. It’s a classic example of a self-limiting illness. Also, trying to eliminate specific bacteria in the gut is a tricky business – you can kill off friendly bacteria and leave the field clear for the much more persistent Clostridium difficile infection. Any headines suggesting a prospect of antibiotic treatment for noro are misleading.

The other discovery is that there is a specific immune chemical, a fairly recent discovery, that can attack this virus. The immune system’s armoury of chemical weapons is vast and there is still a lot to learn about how individual chemicals interact with specific pathogens. Interferons are a category that have formed the basis for drug development. As drugs they tend to be used for serious illnesses. A fairly newly discovered interferon seems to have had success in eliminating noro infection in mice.

Again this is contributing to the understanding of the virus and the detailed operation of the immune system. In the long term, dosing “carriers” of norovirus, who are not ill, with a potent interferon-based drug, is unlikely to prove to be a practical proposition.

The best defence agains noro virus is hygiene. Wash hands regularly during the winter and if anyone in the family is ill, use diluted bleach to swab down bathroom surfaces.

http://bit.ly/14CQc50

http://www.nhs.uk/conditions/Norovirus/Pages/Introduction.aspx

What is plasma treatment?

It’s reported in the press that a health care worker, recently diagnosed with Ebola, is being offered plasma treatment in a London hospital. This involves a transfusion of plasma from patients who have recovered from Ebola.

Plasma (blood with the cells removed) is a rich broth, full of antibodies and other immune proteins. The treatment should perhaps be re-named “antibody transfusion”.

When there's a new, unfamiliar infection the adaptive division of the immune system takes a while to set up a production line for the appropriate antibodies. First, a wandering immune cell detects the presence of a virus or bacterium and carries it to a lymph node where it's examined by passing lymphocytes. If a lymphocyte identifies it as a new threat it settles down in the lymph node, cloning a huge number of identical self-copies. These are then released (into the plasma) with the capacity to flood the body with millions of copies of the newly minted antibody. It is this lymphocyte-cloning process that takes several days.

The danger is, that in a disease like Ebola, a patient could die before their own antibodies can be produced in sufficient quantities to eliminate the virus. An infusion of antibodies from a recovered patient has the potential to keep them alive until their own production gets up to speed.

From the late 1890s plasma has been used to treat infections. Often the donor was a horse, which had been inoculated with a virus or bacterium causing it to form ample quantities of the antibody. The technique saved many lives but had its disadvantages – the need to keep large stables of horses and the risk of developing immune reactions to equine plasma proteins to name but two. The practice declined rapidly with the discovery of antibiotics and other modern drugs.

Plasma donated by human Ebola survivors has proved useful in previous outbreaks and is probably the best treatment currently available. As with any type of blood transfusion donors should be screened for viruses such as HIV. WHO has recently issued guidelines.

I’m sure we all hope that in this current UK case it will prove successful.

http://apps.who.int/iris/bitstream/10665/135591/1/WHO_HIS_SDS_2014.8_eng.pdf

Scientists synthesise antibodies

This week scientists at Yale University have announced one of those game-changing achievements that could change the future of medicine. And, probably, win a Nobel prize. They have synthesized mini-antibodies that can function within the body and attack both cancer cells and disease-causing agents.

An antibody is a highly complex macro-molecule, produced by the adaptive division of the immune system. It’s a powerful bespoke weapon that will only attack a single type of bacterium, a particular strain of virus or a cancer cell with a particular genetic signature. They lock on to receptors on the surface of the pathogens and disable them. Imagine them as tiny wheel clamps that are individually designed for each new make of car that comes on the market. One of the problems with antibody production is that it is not instant. It takes the immune system several days or weeks to get its production line up to speed and in a serious disease like Ebola, the patient can die before enough antibodies are produced. Once the antibody template has been produced, it can be used more swiftly whenever the particular threat re-appears.To work on cancer cells the immune system first has to identify them as alien.

Antibodies are tiny and these new synthetic antibodies even smaller. Picture a bespoke wheel clamp on a jumbo jet. But that might make them easier to produce.

Currently there are just a few ways in which medicine can use antibodies:

Vaccines – in which the body is induced to create a new type of antibody without becoming ill. New vaccines are hard to develop.

Extracting antibodies from blood of those previously infected. This is being tried currently to treat Ebola.

Snake bite serum – produced by injecting animals with small amount of venom and then extracting antibodies from blood serum.

Monoclonal antibodies – producing an individual antibody type in the lab, using a complex biological system.

If simpler synthetic antibodies could be produced by a less laborious process than monoclonal antibodies it would open the door to a wide range of options in treating infectious diseases and cancers.

A ground breaking moment in immunology without a doubt.

http://bit.ly/13kPg4T

The immune system cleans up

The immune system is a teeming mass of interacting cells and complex organic chemicals that enable our bodies to deal with microbes. Immunologists have been toiling away for decades now and their research is, these days, at the level of individual molecular pathways. There are millions of these pathways – the circuit diagrams in an unimaginably complex computer.

One of the less well-known roles of the immune system is to identify and remove faulty, worn out or cancerous body cells. In other words it doesn't just fight off intruders, it declutters the house as well. It is fundamental to the immune system that it must, every day, make millions of judgements about what is ‘self’ and ‘not self’ so that it knows whether or not action is needed. It seems that cells that don’t pass its quality control process become re-classified as no-longer-self and dispatched for recycling.

Research into the molecular mechanisms of this decluttering process is beginning to lead to new medical treatments. 

In one recent report, a drug has been used (on a small group of patients) to block a molecule that enables bladder cancer cells to prevent an immune attack. The results are looking promising. The cancer cells disguise themselves as ‘self’ and the immune system ignores them. But the compound whips away the disguise and enables the malignant cells to be identified and destroyed. Treatments based on discoveries like this could eventually replace chemotherapy, which uses cytotoxic chemicals that inevitably damage healthy tissues.

http://bbc.in/1HQDMGv

In another study, a potential new treatment for malaria has been discovered and is ready to progress to safety trials in humans.

The malaria parasite makes its home inside healthy red blood cells. A couple of million red blood cells are produced every second by the bone marrow, so an equivalent number of worn out cells must be efficiently destroyed and removed from circulation. After detailed research into the genetics and cellular mechanisms of the parasite and into the way the immune system disposes of blood cells, a compound has been discovered that seems to hasten the disposal of malaria-infected cells and clear the parasite from the blood of mice. This is hopeful news when you consider the toll that malaria takes, particularly on young children.

http://bit.ly/1yovBcB

There is an enormous amount of fundamental research that has brought immunology to this point - mountains of Ph D theses and thousands of careers bent over the laboratory bench. This kind of research is not funded by drug companies and the fact that it is now, finally, beginning to produce treatments highlights the need to maintain public funding for pure science.

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