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

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

"Immune Boosting" Alcohol?

Everyone wants to promote the idea of “boosting the immune system” these days. Those who sell supplements lead the charge, with a regiment of alternative practitioners following closely behind. Immune boosting is also a favourite phrase with journalists, It’s a cheap and easy way of writing headlines. Scientists and science journalists succumb to its lure as well. This reported experiment with Barbary apes and alcohol is a good example.

Eight monkeys were allowed free access to alcoholic drinks for 7 months. Four of them were deemed heavy drinkers and the other four, moderate drinkers, depending on their freely chosen intake. There was a comparison group that was allowed no alcohol. The monkeys’ response to smallpox vaccine was tracked. It is not surprising that the heavy drinkers showed impaired immune function. Alcohol is toxic and large amounts of it will damage just about any bodily function you care to name.

What was more interesting is that the moderate drinkers had a better response to the vaccine than either of the other groups. We should, though, be skeptical about the size of the groups and the fact that the comparison groups were self-selecting rather than randomly allocated. Maybe the immune systems of those drawn to heavy drinking were different in some way to the more temperate beasts. We should also, always, be skeptical about making direct inferences from animal studies to human health.

For scientists, or science journalists, to talk about “boosting the immune system” is a bit like the mayor saying that some free-to-use bikes will boost the economy of the city, just because a few more energy drinks were sold in a few local kiosks. Like a city, the immune system is an immensely complex and intricate set of interlocking sub-systems. Millions upon millions of immune cells interact with billions of immune molecules to keep a body in a finely-balanced state of health. There are many different types of these cells and molecules - they are incredibly small and incredibly numerous. Strength of response to a single vaccine does not tell us anything about how the same immune system might cope with other vaccines, with TB, MRSA or the common cold. You cannot “boost” the whole thing – it’s a crazy concept. And we should never forget that an over-active immune system can be just as harmful as an under-active one – in allergies and the many auto-immune diseases for instance.

It’s New Year’s Eve – if you drink heavily you might be more likely to get an infection of some kind in the next few days. But if you exercise restraint and only have a glass or two, there are no promises that this will serve to actively improve your health. But drunk or sober, I hope you have a happy and healthy 2014.

Moderate Alcohol Consumption Boosts Body's Immune System

'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

Immunology and Cancer

Ten years ago the author of a keynote speech on the science of immunology remarked: "The paradox of today's immunology is that tremendous progress in basic science has been matched by only a few clinical applications." At the time, he noted, a journal paper in immunology was being published every 15 minutes but little of this knowledge was translated into useful treatments for patients.

The task of trying to understand what is happening in the immune system reminds me of the Walrus and the Carpenter who wondered whether the shore could be cleared of sand: "if seven maids with seven mops swept for half a year". You could envisage those poor maids, sweeping diligently, only to discover layer beneath layer of sand. So it has been in the biological sciences with layer after layer of complexity being revealed, the deeper the scientists dig. Ten years ago only ten of the immune-based drugs known as monoclonal antibodies were in use. The list has grown rapidly since then and many of them being used to treat various forms of cancer. It has taken an astounding amount of pure research to enable these immune-based treatments to prolong lives. Herceptin is the best known example.

In the world of cancer drug development there are a two main strategies. The traditional one is to try out various chemical compounds until you find one that kills cancer cells without killing, or permanently damaging the patient. The more recent and much more sophisticated method is to pinpoint a particular cancer gene or molecular pathway, and then devise a molecule that will block the gene or disrupt the pathway. Unlike the generic weedkiller approach of chemotherapy the new drugs are very specific. They may have dangerous side effects but they are unlikely to be the ones that traditionally accompany chemotherapy: hair falling out and immune system being seriously impaired.

Some of the underpinning research is done by immunologists who are slowly starting to understand the puzzling interactions between cancers and the immune system. We have known for a long time that some immune cells can destroy cancer cells and in recent years there is increasing understanding about why they might fail to do so and how, sometimes, immune cells are deceived into promoting the spread of cancer. But the processes have to be unpicked, one molecule at a time if they are to be used by medicine.

Research published in this month's New England Journal of Medicine reveals some encouraging results for another antibody-based drug. The interesting thing about this one is that it operates directly on one of the molecular interactions between the immune system and cancer. It does not, as Science Daily implies in its headline "boost" the immune system. Instead it prevents the cancer from using one of the possible ways of defending itself against an immune attack.

The new drug was tested on 296 patients who were suffering from some of the more lethal kinds of cancer - melanoma, lung cancer and so on, who had already had other forms of treatment. The results showed that "approximately one in four to one in five patients" responded in an encouraging way. These results are exciting, given the nature of their diseases. Immunology did indeed make slow beginnings in terms of practical applications, but at last it is starting to produce benefits for patients.

  

Antonio Coutinho Immunology at the crossroads EMBO Rep. 2002 November; 3(11): 1008–1011.

Suzanne L. Topalian et al. Safety, Activity, and Immune Correlates of Anti–PD-1 Antibody in Cancer. New England Journal of Medicine, 2012 DOI

http://en.wikipedia.org/wiki/List_of_monoclonal_antibodies

http://www.sciencedaily.com/releases/2012/06/120602134835.htm

Mouse Immune System Responds to Music

It is not that surprising that music has been shown to reduce stress and distress in some human patients. But who would have thought that mice would be affected by music? But it seems that mice produce and respond to music. According to recent research, male domestic mice (and other species) sing, like songbirds, to attract a mate. Strange to think they might be warbling away beneath the floorboards. Fortunately their song is not audible to humans otherwise it might keep us awake.

Musical mice are also in the news due to recent Japanese research that involved playing opera and Enya to mice that were being subjected to heart transplants (Masateru Uchiyama et al, 2012).You would think the idea for this research might have been a bit of a wild card - but indeed someone's hunch paid off in terms of some interesting results. (But yes, this was tough on the mice and I don't think if I was on the ethics committee I'd have been talked into approving this one.)

Transplant survival increased in the mice that were treated to the non-stop opera (but not the new-age Enya) and there were significant changes in some key immune cells and molecules.

So should we conclude that music boosts your immune system? Not at all - increased transplant survival indicates less rejection - and therefore a less active immune response.

Does this research have an application in terms of human health and recovery? Again, I don't think so. The musical likes and dislikes of mice and humans might, after all, be different. Not to mention the musical preferences of their immune systems.

Should someone be trying to repeat this research on humans? Again the answer is no. You would have to persuade transplant patients to volunteer to put up with non-stop noise (classical, new-age, or just a high pitched sound) for a week before or after their operations. A bit of a non-starter I'd say. And humans are given anti-rejection drugs which would muddy the waters, to say the least. 

This is the kind of research that raises lots of questions, many of which may never be answered. But it does highlight that, even in mice, the interaction between the brain and the immune system is more complicated than we can begin to imagine.