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.