Catching the Travel Bug

Girl SunbathingLong gone are the days of a summer break where the biggest health risks were stepping in donkey droppings on the beach or being sick on a fairground ride. These days, trips abroad provide the traveller with a whole range of diseases, so what’s our defence?

Our first line of defence against many of these diseases is our immune system. Unfortunately the immune system is not perfect and cannot always mount an effective attack against invading viruses, bacteria, and parasites. This is where vaccination often comes into play.

Vaccines were essentially discovered by Edward Jenner in the late 18th century. They are based on the idea that the immune system can be stimulated by components of a pathogen — i.e. the virus or bacterium. Proteins or protein fragments (antigens) produced by pathogens alert white blood cells to their presence, which then engulf the pathogen and destroy it. The cells also start to produce Y-shaped protein molecules (antibodies). The tips of the Y match the antigens produced by invaders like a lock to a key.

The antibodies travel through the blood stream and every time they bump into an antigen that they recognise, they lock on to it. This labels other pathogen particles for attack by yet more white blood cells which see the antibody signal and digest the invaders or infected body cells. The immune system retains the chemical blueprints for making the same antibodies again for the next encounter. This is why if you survive childhood diseases such as chicken pox you are unlikely to catch it again in adulthood, although this example belies the fact that chicken pox apparently lies dormant and can re-emerge later in life as shingles.

Vaccination tricks the immune system into thinking a pathogen is attacking by using dead or a deactivated version of the virus or bacterium. The white blood cells respond, creating antibodies against the antigens but without you having to catch the disease first. The blueprints for the antibodies are stored chemically ready for a real invasion of the disease. You need a different vaccine for each disease you might encounter and if you are travelling in the Tropics or the developing world there are quite a few diseases you need protection against.

Diphtheria

Among the diseases for which a vaccine is available is diphtheria. This highly infectious disease is caused by the bacterium Corynebacterium diphtheriae, which affects the upper respiratory tract. Symptoms include a severe sore throat and fever which is followed by the formation of a lethal sticky coating in the nose and throat. The bacteria also release a toxic molecule into the blood — a chain of 535 amino acids, which penetrates cells and kills them.

In the 19th century, scientists discovered a serum that neutralises the diphtheria toxin. This ‘antitoxin’ is made by extracting antibodies and other molecules from the blood of horses that have been vaccinated against diphtheria. To work, the potion has to be administered as soon as symptoms appear because it cannot undo the damage caused by toxin that has already entered body tissues.

During the past 10 years, researchers have been trying to find drugs that can kill the diphtheria bacterium. Researchers at Brandeis University in the USA discovered the switch that starts production of diphtheria toxin, a protein called DtxR. They have determined the exact atom-by-atom structure of this protein and drug designers are now looking for compounds that can deactivate the switch before the toxin is released and so save the lives of diphtheria victims that would otherwise die.

Hepatitis B

Another serious illness you may encounter when travelling the globe is hepatitis B. It is caused by the hepadnavirus but the source in half of all cases is not known. However, sexual transmission, needle sharing among drug users, tattoos and transmission from mother to unborn child cause the other half of cases. The virus incorporates itself into the DNA of liver cells, leading to chronic liver damage and potentially liver cancer. Fortunately, vaccination before exposure provides lifelong protection.

Researchers have also discovered antiviral drugs to treat hepatitis B. These drugs resemble the nucleotide molecules that act as the natural building blocks of viral DNA (the virus’ genetic code). The fake building blocks have unreactive fluoro groups instead of hydrogen atoms at strategic positions. So, once the virus starts to use these fake molecules the duplication mechanism is jammed because unreactive fluoro groups cannot be removed to attach the next nucleotide in the chain. Viral replication is significantly slowed down, giving the immune system a chance to overwhelm the disease.

Unfortunately, the viral DNA is prone to damage, or mutations, which lead to changes in its genetics. Most mutations stop the virus working but occasionally one will benefit the virus. If, for instance, the mutation changes the virus so that it ignores the fake building block, then the antiviral drug will fail and the virus continues to replicate, passing on the mutant genes (DNA fragments) to its offspring.

Some strains of hepatitis have already evolved resistance to antiviral drugs, so scientists are desperately trying to discover replacements that might work together to defeat viral resistance.

Rabies

If you are bitten by a dog or other mammal — notably a bat — when travelling, the wound itself is the least of your worries. Rabies is yet another viral disease best avoided. Its name derives from the Latin word for madness or rage, and it leads to a fear of water (hyrophobia), foaming at the mouth, a swelling of the victim’s brain, and ultimately death. Louis Pasteur and Emile Roux developed a vaccine in 1885, but it only works if administered before symptoms appear.

In 2006, scientists in Brazil investigated the potential of a group of natural plant compounds, phenolic compounds, as antiviral drugs to treat rabies. They discovered that just three of a whole range of compounds tested had some antiviral activity. The structures of these three compounds — 3,4,5-trimethoxybenzoic acid, 3,4,5-trimethoxyacetophenone, and 3,4,5- trimethoxybenzoic acid ethyl ester — could provide a starting point for designing more effective compounds. There is no way of predicting how long that might take and any potential drug would have to go through safety tests and clinical trials before it could be used in medicine, which might take up to 10 years. In the meantime, vaccination remains the only defence, that and avoiding rabid animals.

Typhoid

The disease that killed Alexander the Great, typhoid fever is alive and well across the globe. The Salmonella typhi bacterium multiplies in the blood and spreads by ingestion of food or water contaminated with infected faeces. The bacterium causes a high fever, headache, aching muscles, and death in severe cases.

Previously, antibiotics, such as ampicillin and chloramphenicol, were the standard treatment and saved many lives. However, like so many other diseases, typhoid has evolved resistance, particularly in India and South East Asia. Vaccination, if you’re travelling in affected areas, is therefore essential.

Tuberculosis

Tuberculosis, or TB, a disease once consigned to the history books is now carried by a third of the world’s population. TB is a bacterial infection and as with viruses the bacterial DNA, its genetic code is susceptible to mutations that can help it evolve resistance to antibiotics. This has already happened in many parts of the developing world and among certain sections of society such as the homeless, drug users, and HIV sufferers.

However, the issue of resistance is more complicated than it at first appears. A study published in March 2007 in the Journal of Infectious Diseases suggests that most cases of drug-resistant TB may be due to new infections rather than acquired resistance to the antibiotics. If this research is confirmed it might help scientists devise a new strategy for stopping the spread of this disease.

Malaria

Malaria kills up to three million people each year. Malaria is caused by the Plasmodium parasite carried by infected mosquitoes. The parasites are carried into a person’s bloodstream by a bite from an infected mosquito, they then multiply in the liver and the blood causing a lethal fever.

There is no vaccine against malaria, but there are drugs that protect you from infection. Plasmodium, like many viruses and bacteria, has also evolved resistance to some of these drugs. However, a novel drug derived from Chinese medicine, known as qinghaosu, works well in treating the disease and so far has staved of resistance.

There is a great deal of research underway to find novel drugs to defeat malaria. Scientists at the Toronto General Research Institute and Ontario Cancer Institute recently, for instance, discovered a synthetic compound that targets and kills malaria parasites, including one drug- resistant strain. In January 2007, researchers at Northwestern University in the US worked out how the parasite tricks red blood cells into engulfing it and so perpetuating its lifecycle. New drugs aimed at blocking this process might beat malaria.

Today, most of the diseases we have discussed are confined to the developing world where they pose an enormous public health problem and one that usually affects privileged Westerners only when they travel to such places. However, if climate change occurs some of these could spread to the developed world. Unless we can halt global warming, the time may come when you could catch some of these diseases just by staying at home. Stepping in donkey droppings will then be the least of your worries.

Where in the world?

A selection of souvenirs you might pick up on your travels

Diphtheria – bacterium: former USSR, South America, Northern Africa
Hepatitis B – virus: Africa, parts of Asia, China
Rabies– virus: global, except Australia, New Zealand, UK, Norway, Sweden, Japan,
Singapore, Guam, Taiwan, Fiji, Hawaii
Malaria– mosquito-borne parasite: Africa, Asia, South America
Tuberculosis– bacterium: global, common in Southern Africa, Asia, South America, former USSR
Typhoid – bacterium: Africa, Asia, South America

You can obtain specific advice on diseases via the WHO and CDC sites. Your doctor or national health organisation may also produce online information. For those in the UK that can be found here.

Linked In Questions

Linked In QuestionsRecently, I did a little blogging experiment on the business networking site LinkedIn (inspired by a post on Copyblogger). I was writing a feature article for Sciencebase about risk and the public perception of trust in science and technology. As an alternative route into the opinions of lots of members of the community, I posted an open question asking rhetorically why the public no longer trusts science and told potential respondents to let me know if they didn’t mind being quoted in the article.

The question was worded very loosely with the aim of eliciting the strongest responses possible. It’s not something I would usually do, I’d simply approach independent experts and contacts and ask their opinions directly in a more traditional journalistic way. But, like I say, this was an experiment.

Replies poured in quite quickly. One respondent thought I was crazy for imagining that the public does not trust science. “People do trust science and scientists," he said, "Anyone who doesn’t, please stand up and be allowed to fall immediately victim to polio, the Black Death, measles, chronic sinus infection, prostate cancer, and on on and on.” Others were in a similar vein.

They were not the kind of responses I was expecting. As if by listing the various things that many people take for granted somehow measures their trust of science. In fact, one can make a similar list of the kinds of science-related topics that are alluded to in the research about which I was writing in the original post – GMOs, nuclear, cloning, mobile phone radiation, stem cells, cancer risk, adverse drug reactions, superbugs, vaccines, environment, pollution, chemical weapons, biological agents, military technology.

These are all science subjects, in some sense, and are considered seriously problematic in the eyes of the public. Of course, the solutions to all those problems also lies with science, but that doesn’t detract from the fact that the public commonly distrusts.

The article itself looked at how the public respond to such issues, specifically cancer clusters, and delved into how trust in such matters is actually coloured by the particular organisation or entity that is offering the information about the topic. Moreover, the study showed that the way people assess risk when faced with such information differs greatly depending on the source of the information. Their thinking seems to change in working on such a risk-benefit equation depending on the source, whether it’s come from an official organ or a pressure group, for instance.

Strangely, another respondent accused me of bias in my writing, as if somehow the placement of a deliberately provocative question in a public forum was somehow the writing itself rather than simply an enquiry.

I could not understand why he thought that my posing a question journalistically would preclude me from writing a neutral piece? It was his response to my initial broad question that has led me to write this post, however, so maybe I should thank him for the inspiration.

As I explained, I put the question with a deliberate and strong inflection in order to provoke the strongest response from the community. That’s pretty much a standard approach to getting useful opinions from people on both sides of an argument in journalism. If you don’t believe me listen to the way people like the BBC’s Jeremy Paxman and John Humphrys posture through their questioning in order to get the best response out of their interviewees. They often hint at a strong statement through their question one way or the other and people will either support what you say and offer their positive opinions or else argue against you.

It’s usually best to lean away from them (not only to avoid the blows but to inspire them to give the strongest argument for their case, and I’m not referring to Paxman or Humphrys here). Either way, you get useful comments on both sides that will provide the foundations for the actual writing and so allow you to produce a neutral article that reveals the pros and cons of an issue without personal bias.

Anyway, as an experiment, it didn’t work too well, initially. However, once the community had warmed to the question and I’d added a clarification some quite useful answers that weren’t simply an attack on the question itself began to emerge.

As it turns out, none of the responses really fit with what I wanted to report in the original post, which you can read in the Sciencebase blog under the title In What We Trust, by the way, and so I intend to write another post discussing the various points raised and namechecking those members of the LinkedIn community who were happy to be quoted.

Flu Clinic Widget

Flu shot

Is flu vaccination a shot in the dark? Regular readers will recall the recent debate on multiple vaccines, statistics, and risk we had here in September. I also have rather close personal experience of one of the risks associated with having the annual flu vaccine – Guillain-Barré Syndrome (GBS). This autoimmune disorder is purportedly associated with a respiratory or gastrointestinal tract infection although there is a statistical risk that connects it to the flu vaccine. A close relative of mine developed GBS symptoms about six weeks after having the flu jab last December and has not yet fully recovered. GBS support groups recommend she not have the vaccine again.

So, it is with mixed feelings that I read an email from Charles Forsyth (a public relations professional at www.btstrategies.com apparently working for the American Lung Association). Charles is helping the ALA raise awareness of the importance of getting an influenza vaccination at this time of year. He explains that part of the campaign involves persuading bloggers and other website owners to add a widget to their site. The widget helps readers find a local flu clinic quickly and easily where they can be vaccinated.

You can try the widget here http://www.flucliniclocator.org and download it to add to your site. Just enter your zip code to find clinics in your area and make an appointment. You could use it to find a clinic for elderly or infirm friends or relatives too or others in high-risk categories, such as asthma sufferers, and those on immunosuppressant drugs.

Tragically, influenza kills about 36,000 people each year in the US, Charles tells me, and requires another 200,000 to be hospitalized. Most of these deaths are preventable by getting a simple flu shot each fall.

The following groups are considered at higher risk than the general population

  • People who are 50 years of age and older
  • Women who will be pregnant during influenza season
  • Young children 6 to 59 months of age [Not sure what changes at 59 months, presumably they just mean under fives]
  • People with chronic medical conditions such as asthma, emphysema, chronic bronchitis, TB, CF, heart disease, kidney problems, diabetes, and severe anaemia
  • People who have diseases or having treatments that depress immunity
  • Caregivers of those at risk

Charles suggested I add the widget to the Sciencebase bird flu symptoms page, but I think that would be a little irresponsible, given that a vaccine against human influenza will most likely provide absolutely no protection against an impending bird flu epidemic. Instead, I’ve added it to my seasonal page on how to avoid colds and flu in the first place. This page rears its ugly head at this time of year on an annual basis, so it’s as good a place to slot the widget as any. I should emphasize though, that if you have any concerns about the protective efficacy of vaccination or the risks associated with the flu jab you should discuss them with your GP.

Oh, and if you think you have flu or a bad cold, don’t spread it around, stay at home.

MMR and Statistical Manipulation

Measles virus

When I was still at high school, way back in the late 1970s, there was a health scare that got a lot of media attention. Apparently, there was a perceived risk that the whooping cough vaccine could cause brain damage. The fall off in vaccination for this disease is claimed to have led to the widespread outbreaks of whooping cough in 1979 and 1982, there having previously been almost zero annual cases. At the peak there were some 60,000 cases.

Fast forward to the near present and you will recall similar scare stories about the combined measles-mumps-rubella vaccine, the MMR, and claims by researcher Andrew Wakefield (Lancet, 1998) that MMR could cause autism in some children. It’s a topic guest blogger Michael Marshall covered on Sciencebase in November 2004. It seemed that, at the time, the debate was pretty much over. However, despite repeated demonstrations of the apparent inadequacies of the original research into a link between MMR and autism, the issue is resurrected on a regular basis. Most recently in a cover story in The Observer, which drew much flack, but also left the chattering classes once more in a flap.

Right now, I’m looking at an article from the print edition of The Times offering an answer to the Question of the Week – “Measles or vaccine?” – the article talks of how measles has reappeared and it is apparently all down to many parents’ reluctance to have their children vaccinated with the MMR jab. The article talks of “herd immunity” and how enough children have had a double dose of MMR which should stave off an epidemic. The emergence of herd immunity, of course, will be little comfort for a parent whose child experience any of the potentially severe side-effects of vaccination.

In the article, pictured alongside a blow-up of the measles virus and an image of a nasty-looking hypodermic needle, are two charts, one showing the number of cases of measles in the UK from 1940 to the present day and the other showing the number of deaths over the same period. Incidence of the disease ebbed and flowed during the period up to the early 1970s whereupon cases began to fall rapidly from a peak of 800,000 a year in the early 1960s to just one or two hundred a year by the mid-1970s.

The MMR vaccine was introduced in the US in 1971 and later in the UK, thereafter incidence of measles has pretty much fallen to levels close to zero. It seems that the pre-vaccine drop had another cause, presumably reduced overcrowding, improved nutrition, better hygiene and healthcare. No one knows at what point this fall would have reached a plateau.

In contrast, the second chart of death rates shows an exponential decline in measles deaths since the 1940s, by about 1970 measles deaths were also close to zero. The risk of getting measles is about one in three, assuming no vaccination coverage at all. The risk of serious consequences to this disease, which personally I had in 1972 or thereabouts, is somewhere between 1 in 5000 and 1 in 15,000. Compare that to the risk of death in a road accident. According to Transport2000 , the UK’s national environmental transport body, each of us has a 1 in 17 chance of being killed or seriously injured in a road crash during our lives. Such figures damn the disease statistics somewhat. Of course, vaccination does come with some risks, but adverse reactions, such as seizures with an associated risk of brain damage, exist at the 1 in 10,000 level.

There has been one UK death from measles since 1992 (as opposed to the several hundred each year during the 1940s). The unfortunate victim was apparently suffering an underlying lung disease for which he required long-term immunosuppressant drugs. He was very unfortunate to be exposed to the measles virus, and when he contracted the disease he was very unlikely to have recovered. This is one fatal case. Even with near 100% vaccination, there would still be a finite risk of any random member of the population contracting the disease. Unfortunate, but true. The statistics would not lie surely?

Possums, horses, and pigs do it

Brushtail possums, photo by wollombi http://www.flickr.com/photos/wollombi/I just received an early publication alert from the Australian research organisation CSIRO announcing the imminent publication of volume 19 of their journal on reproductive science, fascinating I thought as I opened the attachment.

First up in the list of contents was a paper that sounded rather intriguing from FC Molinia and colleagues entitled: “Uterine and vaginal insemination optimised in brushtail possums (Trichosurus vulpecula) superovulated with pregnant mare serum gonadotrophin and porcine luteinising hormone”.

So, let us just dissect what that convoluted title actually means. Basically, they stimulated brushtail possums with hormones from a horse and a pig to make it produce more eggs than normal and then artificially inseminated the females, with brushtail possum sperm, obviously. I am pretty sure it is all standard procedure for getting those little brushtails up the duff, and it is not so odd that they used horse hormones in the process, after all, one form of human hormone replacement therapy uses equine estrogen.

Something worries me a lot about this particular EarlyAlert. The abstract says that artificial insemination of brushtail possums (Trichosurus vulpecula) is being developed as an assisted breeding model for endangered marsupials, as well as a bioassay for testing fertility control vaccines to manage overabundant populations.

Hmmm…humans do not have a strong record on “assisting” animals in this way, and particularly not in Australia, I am thinking rabbits and mixomatosis, feral camels, and the infamous cane toad, to name but three. Why is it that we feel we can intervene and manage ecosystems in this way? The end results are usually disastrous and given the purportedly fragile nature of Australia’s ecosystems, should we not leave well alone?

The full paper can be accessed here.

Eradicating polio

Researchers hope to revise the vaccine strategy for inocculating people in certain parts of the world against the crippling disease polio. Their approach could eradicate this endemic disease once and for all, they report, in this week’s Science magazine.

The new study, by researchers from Imperial College London and
international collaborators explains why the disease continues to afflict people in northern India. Poor sanitation and overcrowded living
conditions in Uttar Pradesh and Bihar pose a dual challenge to the
eradication effort because they encourage poliovirus to spread via infected faeces contaminating drinking water, they explain. This coupled with other infections and diarrhoea interfere with the efficacy of the
oral polio vaccine.

The researchers argue that the simple measure of using a ‘monovalent’
form of the polio vaccine alongside the standard ‘trivalent’ form in
these areas could sufficiently increase the effectiveness of vaccination
programmes to wipe out the poliovirus where it persists.

The trivalent vaccine currently in use contains weakened strains of all
three types of poliovirus, unlike monovalent vaccines, which are
strain-specific. The trivalent vaccine is typically used when more than
one strain of the poliovirus is at large in the population. The problem
with trivalent vaccines is that the three strains can interfere with
each other inside the body, producing immunity to one strain but not
another.

The researchers argue that as the type 1 strain of the virus is now the
dominant one in India, it would be more effective to focus on the
monovalent form of the vaccine.

Lead author Nick Grassly says, “The global polio eradication programme has achieved a great deal. As expected, the last remaining pockets of transmission are the biggest challenge. These pockets of transmission act as sources for all the outbreaks we see around the world today. Our research shows that in northern India the efficacy of the trivalent vaccine is compromised.”

Needle free bird flu vaccine

A needle-free, DNA-based, vaccine against avian influenza strain H5N1 has been developed by UK company Powder Med Ltd and will soon enter clinical trials.

This new vaccine is based upon PowderMed’s proprietary system for delivering DNA
vaccines — it is a needle-free injection device that fires gold particles coated with DNA
(encoding genes specific to the flu strain) at supersonic speed into the immune cells of
the skin. This first-time-in-man clinical trial will examine the ability of a vaccine based
upon the Vietnam H5N1 avian influenza strain to protect against a potential pandemic
form of flu.

A previous study, conducted by PowderMed in the United States, demonstrated that this
vaccine technology was able to produce 100% protective immune responses in adult
volunteers to a vaccine which encoded an annual influenza strain

Of course, who’s to say H5N1 will be the cause of the imminent bird flu epidemic or indeed that any avian influenza strain will be the next big viral attack on the human race. There are also sorts of terrifying possibilities lying dormant in exotic hosts the world over…think SARS…think HIV…think ebola…

This is my report from the Royal Society on emerging viral infections

Britain unprepared for flu pandemic shock

Reuters is reporting that general practitioner Steve Hajioff warns that the UK’s preparations for a bird flu pandemic are inadequate.

The UK is on high alert for bird flu following the dead swan incident in Scotland and is stockpiling vaccine. Hajioff, however, suggests that the impact on infrastructure of an avian influenza epidemic would be like a thousand 9/11’s. “In the present day, you are talking about five million people across Europe and hundreds of thousands in the UK. It’s like 1,000 September 11ths all at once,” he said.

The insensitivity of such a phrase aside, Hajioff went on to tell BBC radio: “I’m a GP and I can prepare my surgery, but if the electricity company that supplies my power has not prepared, then I am not going to be able to treat patients.”

What worries me, is whether or not Dr Hajioff is qualified to offer a new thread to the scare-mongering surrounding bird flu in this way. Maybe he is. His website tells us he “is a broadcaster, a healthcare informatics consultant, a public health physician, and a writer.” It goes on to say that he has a particular interest in international health systems, communicable disease control and electronic data security.” Interestingly(?), “For fun, he paints, skis, cooks and drives his MG. He is also a keen MIDI musician.”

And, seeing as the reporting on his offering to BBC Radio suggests he didn’t actually tell the audience anything that isn’t fairly obvious then perhaps he is qualified after all.

Just for the record, despite the continued scaremongering for almost every H5N1 is yet to mutate into a human transmissable form and the evidence points to the likelihood that such a mutant would have less virulence among humans than H5N1 has among birds.

We’ll see.

H5N1 Vaccine Available

cockerelElena Govorkova and colleagues at St. Jude Children’s Research Hospital in Memphis, Tennessee, have developed a vaccine against the potential lethal H5N1 strain of avian influenza. The vaccine protects, it seems, without triggering antibody production as is normally the case.

While lab tests show the vaccine to be effective, there is a problem with this preliminary study. It was not carried out on humans, so we shall not know whether it would be of any use should a pandemic arise. But, at least the laboratory ferrets, will be protected.

Preventing the Spread of Bird Flu

cockerelIn the week that the H7 variant of avian influenza has led to the culling of 35000 chickens in England, scientists at Imperial College London have simulated the spread of a “human” bird flu epidemic and say that rapid treatment and isolation of infected individuals not only from the public but their household contacts will be essential to prevent thousands of deaths. They also suggest that vaccine stockpiles should be gathered together in readiness for a pandemic, even if the vaccine is not very potent. However, it is strict border controls and travel restrictions that will be needed to slow an outbreak and prevent a global pandemic.

Neil Ferguson and colleagues used computer modelling to evaluate the influence of a range of anti-pandemic measures, such as treatment and prophylaxis with antiviral drugs, household quarantine, vaccination and restrictions on travel. They found that with a policy of giving antiviral drugs both as treatment to infected cases and prophylactically to the patient’s families coupled with early closure of schools hit by the outbreak, rates of disease could be cut by almost a half.

However, for this policy to be feasible, antiviral stockpiles would need to be sufficient to treat 50% of the population – twice what many countries are planning. Combining such a policy with targeted immunization of children with a stockpiled trial vaccine might reduce illness rates by two-thirds, even if the vaccine was not particularly effective in its protection. Even greater drug coverage would have a correspondingly larger protective impact. Ferguson provides more details in this week’s Nature.