Chris Smith

An Introduction to Influenza

The flu, or influenza, is caused by a highly infectious virus. It spreads through the air, multiplies in cells lining the airways, and causes seasonal epidemics of respiratory infections which are sometimes life threatening.

Flu circles the globe every year. As it spreads, the virus is slowly changed by mistakes made when it copies its genetic material. These changes make it very difficult for our immune systems to recognise the infection for a second time, explaining why a previous bout of the flu does not prevent subsequent infections.

The virus gets its name from the Latin word 'influentia', meaning 'influence', because 14th century Italians thought that the 'distemper', as flu was also known, was due to the adverse influence of the stars. But records show that even the ancient Greeks, two and a half thousand years ago, recognised it. Indeed, Hippocrates, the forefather of modern medicine, clearly described the symptoms of flu in 419 BC.

Scientists originally believed that influenza was caused by a bacterium, but in 1933 three English scientists, Smith, Andrewes and Laidlaw, found that filtered (bacteria-free) nasal washings from patients with the flu could transmit the disease to ferrets, suggesting that the infection was instead caused by a virus. Subsequently three types of flu virus have been identified and are named influenza A, B and C respectively. Types A and B produce essentially identical illnesses, but influenza C infection produces milder symptoms, more like a cold.

The flu virus originally came to humans from birds. At some point in history the virus jumped the species barrier and began to infect people. We now know that the serious flu pandemics of the 20th Century (a pandemic is an epidemic affecting the whole world), in 1977, 1968, 1957 and the 1918 Spanish Flu (which killed 40 million people) were all started by a bird flu virus which got into people. This happens because Influenza A still bears a close genetic resemblance to its counterpart in birds meaning that, under the right circumstances, bird and human flu viruses can exchange genes, producing highly virulent new viruses. Because the immune system has never been exposed to this virus before, and has no ability to recognise it, the virus tends to cause very severe infections with a high fatality rate.

STRUCTURE, AND HOW FLU VIRUSES GROW
The viral particles that cause flu are tiny, measuring about one ten-thousandth of a millimetre in diameter. The virus consists of a core, containing the genetic material, surrounded by a coat studded with proteins. These proteins, which include the haemagglutinin (H) and neuraminidase (N) molecules used to identify different flu strains, work like molecular grappling hooks helping the virus to lock on to and invade its target cells. Once inside, the virus effectively hijacks the infected cell, turning it into a flu factory. Each infected cell can produce thousands of new viral particles. With every cough, or sneeze, they spray out in their millions and loiter in the air until they are breathed in by another susceptible victim.

SYMPTOMS
Flu has a short incubation period lasting 2-3 days. You become infectious about a day before you begin to feel unwell, and the symptoms last for 3-7 days in total. Thereafter follows a period of convalescence during which sufferers often continue to experience tiredness, and occasionally depression, for up to 3 weeks.

Although infection with flu is confined to the respiratory tract (nose, throat and airways) it produces generalised symptoms throughout the body as the immune system gears up to tackle the virus. Most people complain of chills and a high fever, muscle aches and pains, feeling very tired, headaches, a runny nose, sore throat and a cough.

In children 'flu can also trigger abdominal pain, nausea, vomiting and diarrhoea, although these symptoms are rare in adults. Indeed, bouts of gastroenteritis are often misleadingly referred to as "gastric flu" but are in fact caused by an entirely different class of viruses and bacteria.

IS IT THE FLU, OR SOMETHING ELSE ?
A number of other infections can produce flu-like illnesses :

• Colds, or other respiratory viral infections (these usually produce much milder symptoms than genuine flu).
• Bacterial pneumonia (can occur at any age but is more common in people with pre-existing chest problems including asthma or emphysema).
  
• 'Strep throat' - a streptococcal infection in the throat usually produces a very sore throat, a temperature, there is often pus visible on the tonsils, but no nasal congestion.
  
• Meningitis - it is always important to be vigilant for the signs of meningitis which can begin with flu-like symptoms. These include headache, neck stiffness, photophobia (dislike of bright lights), nausea and vomiting, drowsiness, fever and a non-blanching rash. If you suspect meningitis, always seek medical advice.
  
• Toxic shock syndrome - this occurs in women who use tampons and is caused by toxin-producing bacterial growth within the tampon. The risks of this condition developing can be minimised by frequently changing tampons and never leaving the same one in place for more than 8 hours.

DIAGNOSIS
In most cases, the diagnosis of flu can be made on the basis of the symptoms alone. But sometimes it is useful to confirm the diagnosis by using laboratory tests, for instance in patients who are very unwell, or when deciding whether antibiotics are required (since viral infections do not respond to antibiotics). Some GPs (general practitioners) also work as 'spotter practices' whose job it is to send in swabs from possible cases of flu to help laboratories, and the world as a whole, to monitor the strains of flu that are circulating in the community.
The techniques used in the laboratory include culturing the virus from throat or nose swabs (which takes 3 to 5 days), and using special colour-coded antibodies to look for the virus directly in mucus washed out of the lungs or sinuses. Flu infection can also be confirmed retrospectively if blood samples taken several weeks apart show a rise in antibodies to influenza.

RISK FACTORS FOR DEVELOPING COMPLICATIONS
The majority of 'flu cases resolve spontaneously and without complications (see below), but some groups of people are at much greater risk including :

• The over 65 age group, who account for over 90% of flu-related deaths. With increasing age the body becomes less robust, and the immune system less effective at responding with sufficient speed to new infections, both of which can enable the virus to gain the upper hand.
  
• The very young, who are more likely to succumb to the flu, and to develop more severe symptoms than adults, because their immune systems have not yet learned to recognise, and neutralise, the virus.
• People with chronic diseases, including heart disease, kidney disease, diabetes, asthma and other respiratory diseases.
• Pregnant women - some studies have suggested that women in mid to late pregnancy may be up to nine times more likely to die from the 'flu because pregnancy temporarily reduces the effectiveness of the immune system. Together with the increased demands placed upon the body by pregnancy itself, this effect also means that the illness can last up to three times longer than it does normally. (There is no risk to the unborn baby, however).

COMPLICATIONS CAUSED BY INFLUENZA INFECTION
Flu infection can increase the chances of developing other conditions :

• Asthma can become (temporarily) worse, requiring more frequent use of inhalers. If breathing remains difficult despite increasing inhaler use, you should see your doctor.
  
• Croup, or laryngo-tracheo-bronchitis, which produces a characteristic 'barking' cough, occurs in children and can be triggered by flu infection.
  
• Febrile convulsions. In any illness associated with a fever, children between the ages of 6 months and 5 years can occasionally experience brief fits, or seizures. This is not the same as epilepsy and resolves spontaneously once the illness passes.
  
• Secondary bacterial infections in the lungs (pneumonia), the middle ear (otitis media - common in children) and sinuses (sinusitis). Damage done to the airways by infection with the flu virus can enable bacteria to gain a foothold. The history is usually one of a preceding flu infection which begins to get better, followed by a relapse and symptoms in the affected area including earache, sinus pain or cough and sputum production. Bacterial 'superinfections' like this usually require a course of antibiotics.
  
• Viral pneumonia - this occurs when the virus itself causes damage to the lung tissue leading to worsening shortness of breath, a dry cough and, in severe cases, confusion and a bluish discolouration of the skin due to low blood oxygen levels. Viral pneumonia is less common than its bacterial counterpart but is extremely serious. The patient usually needs to be put on a ventilator, and the condition is frequently fatal.
  
• Reye's Syndrome - this condition occurs in children up to age 15 and is triggered by taking aspirin during infections with flu or chickenpox. It leads to swelling of the brain and fatty change in the liver, and produces drowsiness, inactivity or irrational behaviour, and can be fatal. Therefore, aspirin-containing remedies should not be given to children under 15 except on the advice of a doctor.
  
• Inflammation of muscles (myositis), occasionally including the heart (known as myocarditis), can sometimes follow infection with flu, particularly in children. Muscles become tender, most noticeably in the legs, and if the heart is involved there may be palpitations, shortness of breath, chest discomfort and rapid pulse. These conditions usually resolve spontaneously but can be aggravated by exercise. It is therefore advisable to rest completely until the flu symptoms resolve.
  
• Miscarriage - rarely a severe bout of flu can trigger miscarriage. But in uncomplicated cases there is no risk to the unborn baby.
  
• Neurological problems - very rarely infection with flu can lead to problems with the nervous system including viral, and post viral, encephalitis (inflammation in the brain), and a condition which causes muscle weakness known as Guillain-Barre Syndrome.
  
• Kidney failure - dehydration caused by insufficient fluid intake can be sufficient to cause kidney (renal) failure in some people, particularly if they have pre-existing kidney disease. However, this is usually reversible with re-hydration.

TREATMENT
In uncomplicated cases of flu the best treatment is bed rest, regular fluids, and simple over-the-counter pain-killing and temperature-lowering drugs like aspirin or paracetamol. It's quite safe to use aspirin and paracetamol together, but do not use aspirin in children under the age of 15 (see Reye's Syndrome above) or if you have a history of stomach ulcers. You should also avoid taking aspirin on an empty stomach, and use it cautiously if you are asthmatic.

Antibiotics are not effective against viral infections, including the flu, unless a bacterial infection, such as a pneumonia, develops subsequently.

There are, however, a number of specific anti-influenza agents available on prescription. These include amantadine (Symmetrel) and rimantadine (Flumadine) which work by preventing the virus from shedding its coat inside cells, stopping it from multiplying. These agents can be used to protect at-risk individuals from infections, and are also able to offer limited benefit to sufferers if started within 48 hours of infection. They are, however, only active against influenza A.

Two newer drugs, zanamivir (Ralenza) and oseltamivir (Tamiflu), which are active against both influenza A and influenza B, work by blocking the action of a viral enzyme called neuraminidase which is essential for the virus to spread. Both of these agents can provide useful protection against the flu (including avian flu) in at-risk individuals, and they can also shorten the duration of the symptoms if started within 2 days of infection. Oseltamivir has been noted to cause vomiting and diarrhoea in some people, however.

SERIOUS SIGNS TO LOOK OUT FOR
If, despite regular aspirin or paracetamol, bed rest and adequate fluids, there is persistent and prolonged high fever, or rapid breathing, shortness of breath, dehydration, drowsiness and confusion, chest pain, fainting, or seizures (in children - see febrile convulsions above), you should seek medical advice.

PREVENTION - FLU VACCINE
The mainstay of flu prevention is the flu vaccine which contains a cocktail of 3 killed viruses and provides protection against both flu A and flu B infections.

Because the flu virus is continually changing, two separate vaccines are now produced each year, six months apart, for the flu seasons in the southern and northern hemispheres respectively. By analysing samples of flu collected from patients the World Health Organisation (WHO) continuously monitors the strains of flu that are circulating in the community. This information helps doctors and scientists to decide which viruses should be included in the vaccine for the forthcoming year. The vaccine is produced by growing the selected strains of the virus in hen's eggs. The grown virus is harvested and chemically inactivated to prevent it from causing disease. A small amount is then administered by injection so that the immune system can learn to recognise the virus, and produce antibodies capable of neutralising it. Protective antibodies against influenza appear in the blood about 2 weeks after vaccination.

WHO SHOULD BE VACCINATED ?
Anyone can receive the flu vaccine with the exception of babies under 6 months of age, women in the 1st trimester of pregnancy, and patients with HIV and a CD4 count less than 200. Vaccination provides up to 90% protection against the flu (less in the elderly) and lasts up to 12 months. However, because the vaccine represents a 'best-guess' at what strains of the virus will be circulating in the forthcoming winter, it cannot guarantee protection, and it also needs to be repeated the following winter.

Certain groups of people, who are at increased risk of complications, are advised to undergo vaccination :

• The over 65's.
• Those with chronic diseases including heart problems, diabetes, respiratory disease (including asthma) and renal (kidney) failure.
• The immunocompromised, including patients who are on immune-suppressing drugs for diseases like rheumatoid arthritis or following an organ transplant, and individuals with HIV.
• Women in mid to late pregnancy (2nd and 3rd trimesters)
  
• Carers looking after any of the above.

ARE THERE ANY SIDE EFFECTS ?
The normal vaccine is prepared in eggs which means that individuals with an allergy to eggs should seek medical advice before immunisation. Because the vaccine kick-starts the immune response in the same way that the virus would, it can sometimes produce mild flu-like symptoms for a day or so following administration. This occurs more commonly in children than adults, but under no circumstances can the vaccine cause you to develop flu. It contains only broken-up, inactivated virus.

A NEW KIND OF VACCINE
A new live flu vaccine called has recently been introduced in some countries, including the US. LAIV (live attenuated intranasal vaccine) is a weakened flu virus than can be administered in the form of nose drops and encourages the body to develop a more powerful protective immune response to the virus. It also has fewer side effects than the existing vaccine and, because there are no needles involved, it is painless.

- June 2005

About the Author

Chris Smith is a clinical lecturer in virology at Cambridge University and the founder and managing editor of the Naked Scientists