Melissa Murphy

Are we on the edge of a global pandemic? What does H5N1 mea? Why do so many new viruses emerge from Asia? Is the UK government prepared and what can we do to protect ourselves? Melissa Murphy uncovers some stark realities behind the avian influenza headlines.

As human beings have evolved and moved about the planet, disease has spread and appeared as if out of nowhere. However, it seems as if every 30 years or so, a disease appears which has the ability to wipe out millions of people, destroying societies, natural habitats and economies in just months. At the moment, the world is watching one particular virus, a strain of influenza called H5N1, which has made the big leap from birds into humans. It is the first time in human history that we are watching; monitoring and analysing a potential pandemic unfold before us. Whether the H5N1 virus does turn into a pandemic remains to be seen but what is certain is that as long as mankind exists so will our virulent companion – the virus.

What is a virus?

The word ‘virus’ comes from Latin meaning poison. A virus is a microscopic organism which invades and takes over biological cells in other organisms. Viruses lack the cellular machinery for reproduction and can only reproduce by using the host’s cells. Once the virus begins reproducing it is secreted out of the host cell into the surrounding cells. It is because a virus uses the host cells to reproduce that it is so difficult to kill. The most effective approach so far is vaccination, where a weakened or dead virus is injected into a person to produce antibodies which kill off that type of virus. However, a virus can mutate into different forms making a vaccination ineffective.Every year, small mutations in the flu virus give it a new power to affect us. Normally, these changes are small enough that our bodies still recognize the virus and fight it off. Scientists can also predict these changes and update vaccinations yearly. The danger is when an influenza virus dramatically changes. It then becomes so foreign to our immune system that we are powerless to fight it. This is precisely what experts fear may happen will the current H5N1 avian flu virus.

Understanding influenze viruses

There are three main types of influenza virus: A, B and C. All three types can affect humans and types B and C only appear in humans. Neither type B or C is divided into sub-types and neither cause severe epidemics. Influenza type A virus is divided into fifteen different sub-types. They are named according to the protein types on the surface, glycoproteins hemagglutinin (HA) and neuraminidase (NA). There are 16 known HA subtypes and 9 known NA subtypes, all of which can infect birds. So H5N1 means influenza A subtype that has an HA 5 protein and an NA 1 protein.

Influenza type A viruses infects people, birds, pigs, horses, and other animals, but wild birds are the natural hosts. All known subtypes of influenza A viruses can infect birds. Typically, wild birds do not become sick and often act as carriers. However, domestic poultry can become very sick and die from avian influenza.

Avian influenza A virus strains are further classified as low pathogenic or highly pathogenic. Low pathogenic strains cause mild disease and affect humans very infrequently. In contrast, highly pathogenic strains cause severe illness and high mortality in poultry.

Although humans can be affected by influenza type A viruses, there is a substantial genetic difference between viruses that infect birds and those that infect both people and birds. Three subtypes of the avian influenza A viruses are known to do this, types A H5 (from which H5N1 is derived), A H7 and A H9.

Why are experts so concerned about H5N1?

H5N1 is one of the highly pathogenic forms of the influenza A virus. The first outbreak was in Hong Kong during 1997, 18 human cases coincided with an outbreak of highly virulent avian influenza in poultry. Extensive studies showed that direct contact with diseased poultry was the source of infection in humans. Studies found very limited evidence of the virus spreading from one person to another. Human infections ceased following the rapid destruction of Hong Kong’s entire poultry population, estimated at around 1.5 million birds.

A second outbreak began in south-east Asia in mid 2003, the largest and most severe on record. The World Health Organization (WHO) stated that: “Never before in the history of this disease have so many countries been simultaneously affected, resulting in the loss of so many birds. Despite the death or destruction of an estimated 150 million birds, the virus is now considered endemic in many parts of Indonesia and Vietnam and in some parts of Cambodia, China, Thailand, and possibly also the Lao People’s Democratic Republic. Control of the disease in poultry is expected to take several years.”

Experts are particularly concerned because the H5N1 virus can make the leap into humans. Of the few avian influenza viruses that have crossed the species barrier, H5N1 has caused the largest number of severe cases and deaths in humans. Unlike normal seasonal influenza, which causes mild respiratory symptoms in most people, H5N1 follows an unusually aggressive course, with rapid deterioration and high fatality.

At the time of going to press, there had been 152 cases of human H5N1 since the current outbreak started in 2003. Of these, 83 have been fatal. Hong Kong has experienced two outbreaks in 1997, where the first recorded instance of human infection with H5N1 infected 18 people and killed 6 of them. Since then there have been cases in Cambodia, Indonesia, Thailand and Vietnam. Most recently, an outbreak in Turkey infected 21 people, killing four.

Experts are concerned that the virus could adapt to become more suitable to humans. They are also concerned that it could exchange genes with a human flu virus, producing a new virus capable of spreading easily between people. Very few people, if any, would have natural immunity to such a virus. This change could mark the start of a global pandemic. To date, investigations have not shown any major mutations or human to human transmission of the virus.

What is a pandemic?

The word pandemic is derived from the Greek “pan” meaning all, and “demos” meaning people. According to WHO, a pandemic can start when three conditions have been met:
1. A new infectious disease emerges
2. It infects humans, causing serious illness
3. It is highly infectious and spreads easily among humans.

The only condition that H5N1 does not meet is human-to-human transmission. The risk that this will happen remains while human infections of H5N1 occur. WHO has also identified six phases of a pandemic, our current situation means we are at phase three of a pandemic alert.

The six phases of a pandemic

The World Health Organization has defined six stages of a pandemic and has made recommendations for each stage. The phases are:

Interpandemic period

Phase 1: No new influenza virus subtypes have been detected in humans
Phase 2: No new influenza subtype detected in humans but an animal variant threatens human disease

Pandemic alert period

Phase 3: Human infection(s) with a new subtype but no human-to-human spread
Phase 4: Small cluster (s) with limited localized human-to-human transmission
Phase 5: Larger cluster(s) but human-to-human spread still localized

Pandemic period

Phase 6: Pandemic reached - increased and sustained transmission in general population

Reference: The WHO global influenza preparedness plan, World Health Organization, March 2005.

So what is the real risk? Pandemics appear approximately every 10 - 40 years and experts believe we are overdue a new one. Experts at WHO and elsewhere believe that the world is now closer to another influenza pandemic than at any time since 1968, when the last pandemic occurred.

It is a view that the British government shares: “Most experts believe that it is a matter of when, not whether, another influenza pandemic strikes,” says Sir Liam Donaldson, Chief Medical Officer and which has led to the government reviewing its plans to cope with a pandemic.

What are the UK’s plans for dealing with an avian flu pandemic?

The UK was one of the first countries in the world to develop a pandemic plan and it focuses on two main strategies: vaccination and anti-viral drugs. The government will be purchasing two million doses of a H5N1 vaccine. This stockpile would be used as a first line of defence for priority groups, such as essential workers, while a vaccine against the exact flu strain is manufactured. The government has also announced their intention to purchase approximately 120 million doses of a pandemic vaccine, enough for two doses for all residents in the UK.

The major problem with relying on a vaccine is that it can only be developed once a pandemic starts and would take several months to produce. If a human pandemic occurs it means that the current H5N1 virus would have mutated, so any vaccine developed for H5N1 will be useless. The other issue is that vaccines use hen’s eggs to incubate the virus. If a pandemic occurs, there will be a mass cull of poultry meaning there could be a shortage of eggs. Britain’s supply of vaccines for seasonal flu comes from companies across Europe and there is only one major UK manufacturer, Chiron Vaccines. To supply vaccines for the UK population, 15 million doses would need to be produced every week for eight weeks. At the moment, manufacturers only supply 12 million doses for the entire winter flu season.

On 1 March 2005, the Department of Health ordered 14.6 million courses of Tamiflu from manufacturer Roche. This allows for the treatment of 25 per cent the UK population, this figure is based on previous pandemics in the 20th Century which had a clinical attack rate of 25 per cent. Roche is on track to fulfill this order by the end of September 2006.

Tamiflu is not a cure, but would be used to protect those most at risk of serious illness. Tamiflu is one of two neuraminidase inhibitors (NAIs) which have been shown in studies to reduce the severity, duration and hospitalisations caused by seasonal influenza. To maximize the chances of working, Tamiflu must be taken within 48 hours after symptoms begin. Tamiflu has been tested by the WHO and has been proven effective against the avian H7 and H9 strains of influenza. Recent animal data has also shown Tamiflu is effective against the current H5N1 avian virus.

The priority for both vaccines and Tamiflu would be key workers and high risk groups such as the elderly and the young. The main dangers on relying on Tamiflu is that if the pandemic affects more than 25 per cent of the population then there will be a serious shortage. If health services are overwhelmed then it could prove difficult to administer Tamiflu within 48 hours of the symptoms starting. Finally, the virus could become resistant to Tamiflu rendering the drug ineffective.

These problems affect every country and experts believe that the UK’s plans are the best they can be in the circumstances. “This is a high quality plan, which shows that the UK continues to be at the forefront of preparations internationally for pandemic influenza. We hope that every country will develop their preparations to the same high degree,” said Dr Asamoa-Baah, Assistant Director-General - Communicable Disease, World Health Organization.

Not all experts share this optimistic view, however. Dr Alexandra Concorde, who is a leading British virologist has been researching alternative methods of treatment. She believes that “the reason the government is hedging their bets on Tamiflu is because there is no alternative.” Dr Concorde is also concerned about the effectiveness of Tamiflu: “The problem with any anti-viral is that they are geared towards a very singular element of a singular virus. This particular element may not exist in a new pandemic strain and if Tamiflu is effective against it, in a very short time it is likely to mutate, making Tamiflu ineffective.”

Dr Concorde also believes that only purchasing Tamiflu for 25 per cent of the population is risky. “They assume that this is the number at risk. But they have no idea who that 25 per cent will be.”

Why are new viruses emerging from Asia?

Avian flu was first identified in Guangdong, the southern Chinese province which borders Hong Kong in 1996. Both the 1957 Asian flu and the Hong Kong flu of 1968 are thought to have originated from this region. In 2002, Severe Acute Respiratory Syndrome (SARS) also emerged from the same area. Why is this particular corner of the globe the breeding ground for so many deadly viruses?

Experts believe it is due to the conditions of farms in this region. Traditionally, Chinese farms were made up families living close to their animals on tiny plots of land. However, in the region of Guangdong, farming has become semi-industrialised with thousands of ducks, geese and chickens living in cramped quarters over fish farm ponds. It has been reported that the fish live on the waste from the birds and the pigs are tightly packed into rat-infested pens. Pigs are also one of the few animals that can pick up both human and avian flu viruses. This means that pigs can become a mixing vessel, creating a new virus deadly to both species.

These conditions highlight two powerful moral issues which western societies ignore at their peril. Firstly, global poverty is an underlying issue behind these farming practices and these economic issues need to be addressed. Secondly, animals were not designed to live in such cramped and unhygienic conditions. Can we really question why deadly viruses emerge when animals are kept in this way?

What can I do to protect myself and my family?

If a flu pandemic occurs, information will be released through leaflets, websites and the media. However, the Department of Health recommends the following measures to prevent the chances of catching or spreading any type of flu:

• Cover your nose and mouth when coughing or sneezing, use a tissue when possible.
• Dispose of dirty tissues promptly and carefully, bag and bin them.
• Avoid non-essential travel and large crowds whenever possible.
• Wash your hands frequently with soap and water to reduce the spread of the virus.
• Cleaning hard surfaces frequently, using a normal cleaning product.
• Make sure your children follow this advice.
• If you do catch flu, stay at home and drink plenty of fluids.

The main risk of catching bird flu is close contact with infected poultry, such as inhaling dried faeces or through plucking birds. People cannot catch bird flu from eating cooked chicken but the Food Standards Agency advises that all chicken is cooked thoroughly. Travelers to countries affected by bird flu are also advised to avoid places where live poultry are raised or kept, such as poultry farms and bird markets and to avoid contact with sick or dead poultry.

History of pandemics

Peloponnesian War – 430 BC
The first recorded pandemic killed a quarter of the population of Athens in four years. Symptoms included fever, inflammation, coughing, diarrhoea, vomiting, skin covered in ulcers, unquenchable thirst, dehydration followed nearly always by death. Scientists have speculated that this was smallpox.

Antoine Plague – AD165 and AD251-266
Possible smallpox plague, killed a quarter of those infected and up to five million in total. At the height of a second outbreak 5,000 people a day were said to be dying in Rome. Symptoms included fever, diarrhoea, and inflammation of the pharynx, along with dry or pustular eruptions of the skin after nine days.

Plague of Justinian - AD541 to 542
The first recorded outbreak of the bubonic plague. It started in Egypt and reached Constantinople the following year. It killed 10,000 people a day at its height and roughly 40 per cent of the city’s inhabitants. It went on to destroy up to a quarter of the human population of the eastern Mediterranean.

The Black Death – 1347 to 1350
This bubonic plague was named ‘the Black Death’ due to blackening of the victim’s skin. The Black Death killed at least a quarter of Europe’s population, an estimated 25 million people. There were similar bubonic plague outbreaks in Asia and the Middle East at the same time, indicating that it was a global pandemic. Bubonic plague outbreaks occurred repeatedly in Europe, gathering strength with each generation, until the 1700s. By then the estimated worldwide death toll for the bubonic plague had reached a 137 million.

Cholera – 1816
The world has experienced seven cholera pandemics, six of them starting in the 19th Century, with every continent except Antarctica suffering outbreaks. The most recent occurred in 1961, starting in Indonesia, and while modern sanitation has curbed the disease, it is still a killer today.

Asiatic Flu – 1889 to 1890
First reported in Bukhara, Russia and spread to Tomsk and the Caucasus. It then rapidly traveled west to hit North America in December 1889, then South America, India and Australia in 1890. It was caused by the H2N8 virus and had a very high attack and mortality rate.

The Spanish Flu – 1918
Caused by the H1N1 virus it was first identified in March 1918 in US troops in Kansas. By October 1918 it had spread to a world-wide pandemic on all continents. Unusually deadly and virulent, it vanished completely within 18 months. The disease had a very high mortality rate and unusually people aged 20-40 were its victims rather than the vulnerable. It killed 25 million people in six months; a fifth of the world’s population was infected. Recent research has shown that the virus strain originated from birds. It was nicknamed ‘Spanish Flu’ due to the Spain’s extensive media coverage of the sickness during the First World War.

Asian flu – 1957 to 1958
This outbreak was caused by the H2N2 virus and was responsible for 70,000 deaths in the United States.

Hong Kong flu – 1968
The H3N2 virus caused around 34,000 deaths in the United States. This virus is still in circulation today.

Useful organisations

World Health Organization – www.who/int/en
Health Protection Agency – www.hpa.org.uk
Department of Health – www.dh.gov.uk