Why a return of scarlet fever?

Medical authorities in England are reporting a sharp increase in scarlet fever. This disease, which tends to affect children rather than adults, was once common. Many great-grandparents can recall being admitted to “fever hospitals” when they contracted it in the 1930s and 40s. These were special isolation units set up to nurse and isolate children who were suffering from infectious diseases.

It starts with a sore throat caused by a bacterium. The infection then becomes more widespread in the body, causing the rash of scarlet fever. Scarlet fever is potentially dangerous because it can develop into rheumatic fever, a complication that can infect and permanently damage heart valves. It was named “rheumatic” because inflamed joints are often involved. In my copy of the John Bull Family Doctor (first owned Ivor J Rees, in 1933) the page that describes how to nurse a sufferer is the only one with the corner turned down. Aspirin, for the joint pain, was the only medicine available.

Both my parents had rheumatic fever and my father’s heart was so badly damaged that he died at 34. I was only four at the time so I have few memories of him. My mother-in-law also had rheumatic fever, which caused heart problems throughout her life. She was admitted to hospital with rheumatic fever as a small girl (“I couldn’t understand why my mother had left me there.”) and, while there, she contracted diphtheria as well.

In the 1950s and 60s rates of scarlet fever declined sharply, probably because antibiotics became available as a fast and effective treatment for infected throats.

People have been asking why there is a resurgence of this disease, which has been so rare in recent generations. Several possibilities occur to me:

GPs are, quite rightly, trying not to prescribe antibiotics for sore throats, saying things like "come back in 7 days if it’s not better". Most sore throats are viral and do clear up. But some bacterial sore throats might be missed as an unintended consequence of this change in GP behavior and could, in a week, develop into scarlet fever.

Children are getting the antibiotics but the bacteria are becoming resistant. The prescription does not work and the throat develops into scarlet fever.

In some areas GP services are under such pressure that parents may be having difficulty getting an appointment. Again a delay in seeing a doctor may result in a bad throat becoming scarlet fever.

Another factor may be an increase in poverty. Other bacterial diseases, notably TB, were steadily declining in the years before antibiotics were discovered. There is a link between TB and overcrowded, impoverished living conditions. Could the same apply to Scarlet Fever? For instance it may be that (due to changes to housing benefit) there is an increase in families living in bad quality, overcrowded housing. It could also be that there is an increase in families who don't have enough to eat (indicated by the growth of food banks). I remember a few years ago being quite shocked to read that rheumatic fever was not rare in New Zealand. The incidence is higher in Maoris and Pacific Islanders. These groups tend to suffer significantly more poverty and overcrowding, and worse health, than the white population. I wondered if the same picture might be found in Australia, where indigenous ethnic groups do even worse than in New Zealand and, blow me down, I was right.

It is possible that several factors are coming together to cause an upsurge in this unpleasant and potentially dangerous disease. If the incidence continues to rise, UK health officials could do worse than look to Australia and New Zealand to see what could be learned.

BBC article on increase

Rheumatic fever in New Zealand
Rheumatic fever in Australia

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

Nature's best cold cure

It’s been years since I suffered from a “flu like illness”, years since I’ve had a cold at all in fact. But this week my luck has run out and I’m distracting myself by writing about the way the immune system reacts to viral infections.

As soon as a virus starts invading your respiratory membranes the innate division of your immune system detects the problem and swings into action. It produces chemicals known as cytokines that cause the symptoms we associate with a cold: mucus production, sneezing, stuffy nose and cough. Cytokines also affect your brain, making you feel lethargic. The body’s temperature control centre (also in the brain) may be affected, causing a  “temperature”. Inflammation is another feature of the innate immune system, hence the sore throat and pink eyes. It’s not the virus itself that causes all these effects – it’s the innate immune system reacting to it. In some viral diseases, such as pandemic flu, the immune system reaction can be so severe as to cause death.

While all this is going on and you’re struggling to carry on working, or flopped around apathetically watching daytime TV, the adaptive branch of the immune system is also working hard in the background. A swollen gland or lymph node can accompany this activity. A production line is being set up for B lymphocytes that will release antibodies against this particular virus along with a flood of uniquely-targeted T lymphocytes that will destroy the virus-infected cells. The process of getting this second-wave attack off the ground takes 4 - 7 days.

Sometimes the innate system does the trick and you “shake off the cold” quite quickly. On other occasions you just have to wait until the adaptive system is in full swing and has cleared the virus from your system.

Ibuprofen and paracetamol are helpful for relieving many of the symptoms. They are not cures however - nothing is, apart from the immune system itself.

Doctors call these viral infections “self-limiting illnesses”. Sit them out and your immune system will make you better. The body in this case is its own healer, rolling out an incredibly sophisticated dual-phase 100% successful cold cure.

In a few cases there are complications caused by bacteria which like to breed in the soggy, congested corners of the respiratory system. Babies and toddlers are more susceptible and chest infections are the most worrying. The immune system changes throughout life and as people move into their 60s and beyond they too also more likely to get a chest infection.

A bacterial chest infection that needs antibiotics is something more than just a cough. For symptoms, when to worry and other vulnerable groups see:

http://www.nhs.uk/conditions/Chest-infection-adult/Pages/Introduction.aspx 

http://www.nhs.uk/conditions/pregnancy-and-baby/pages/spotting-signs-serious-illness.aspx#close

The adaptive immune system remembers each virus it has encountered and will deal with it swiftly in future. However there are many viruses that can cause these annoying infections and because they keep mutating you will never, however long you live, be able to fend off every one.

The one I’m grappling with this week is rather persistent – but 5 days in now and I’m beginning to feel a slight lifting of the inertia that has consumed my week. I have, at least, finished writing this blog. But my patience is wearing thin, so do your stuff now, adaptive immune system, bring on those lymphocytes and bring me relief.

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.