Things you really should know about: bird flu

Do you know your H5N1 from your H3N2? Laura Halpin, Farah Janmohamed and Sanjay Patwardhan consider some of the commonly asked questions about bird flu

Bird flu has recently received extensive media coverage, with escalating concerns surrounding a potential influenza pandemic. Despite the availability of many information sources, ranging from newspapers to guidance from the Department of Health and the chief medical officer, medical students and junior doctors may not have a satisfactory understanding of the key facts.

What is avian influenza?

Bird flu is a highly infectious viral disease caused by influenza A viruses, which normally infect birds and, less commonly, pigs. All birds are thought to be susceptible, but some species are more resistant than others. There are 16 H-types of influenza A, two of which affect birds—the H5 and H7 subtypes. The H5N1 subtype is responsible for the current ­outbreak.

What is the current situation?

The current outbreak emerged in poultry in South East Asia (in Korea) in December 2003 and has been documented as the most severe. The sudden spread of avian influenza in birds, with outbreaks occurring in numerous continents simultaneously, is historically unprecedented. Despite the extermination of more than 150 million birds worldwide, 176 human cases have been recorded in Vietnam, Thailand, China, Indonesia, Cambodia, Iraq, and Turkey by the World Health Organization. As of 10 March 2006, 97 people have died.

In Turkey, there have been 12 confirmed human cases, with four deaths. This has resulted in the Turkish government launching an intensive public awareness campaign.

Has an outbreak in humans ever happened before?

Avian influenza typically only affects birds and pigs, but has been known to infect humans. Human infection with the H5N1 subtype of avian influenza was first reported in Hong Kong in 1997, when 18 cases (six fatal) were identified. Ten human cases were then reported in Vietnam and Thailand in 2004, of which eight were fatal. Cambodia reported four cases in the first half of 2005, all fatal; and Indonesia reported the first of its cases in July 2005.

How does bird flu differ from normal human influenza?

Influenza viruses come in three types—A, B, and C. Although humans are at risk of infection from all three, they are not typically at risk from the H5N1 subtype of influenza A, which causes avian influenza infection. Birds, however, are only at risk of infection from type A, and hence the H5N1 subtype.

Then why should we be concerned?

All subtypes of influenza A viruses, including those from different species, can undergo reassortment of genetic material and merge. Consequently, these viruses show high levels of genetic variation due to antigenic shift, enabling subtypes such as H5N1 to jump the species barrier, as seen in the 1997 and 2003 outbreaks. Great concern therefore surrounds the tenacious nature and deaths associated with H5N1.

Influenza A viruses also mutate rapidly, resulting in permanent on-going alterations to their genetic material. This is known as antigenic drift. Influenza viruses have no mechanisms for repairing genetic errors while replicating, hence their constantly changing genetic compositions; in this way, existing strains are replaced by novel antigenic variants.

The current outbreak is the largest and most severe ever recorded, consequently, there is the obvious concern that the situation could lead to a human avian influenza pandemic. Despite the severity of the outbreak in South East Asia, incidences worldwide are, so far, sporadic and remote. Infected people may also become infected with the normal human influenza simultaneously, hence act as “mixing vessels.” This may enable the exchange of genomic material, giving rise to a novel subtype to which populations will have no immunity.

Experts predict that the avian influenza strain may also evolve into a pandemic strain by the acquisition of sufficient human genes to facilitate human to human transmission. Although scientists cannot foresee when it will occur, it is not expected to begin until there is increased and sustained human to human transmission. The United Kingdom was one of the first countries to put a contingency plan into place in preparation for a potential human influenza pandemic, details of which can be found on the Department of Health's website (www.dh.gov.uk).

How can humans become infected with avian influenza?

Surviving birds excrete the virus for up to 10 days in their droppings and saliva, hence promoting the spread of infection between birds through inhalation or consumption. The virus is usually transmitted to humans directly from infected birds or their environments. Most cases occur among people in close contact with poultry.

Who is at greatest risk?

People who live in close proximity to domestic pigs and wild and domestic birds, as in some South East Asian countries, are at greatest risk. Cases to date seem to have affected all age ranges. Young children, however, seem to be more vulnerable to the infection, although this may be because of their increased risk of contact with infected birds or through playing in environments potentially ­contaminated with bird excretions.

Within the UK, poultry farm workers are believed to be particularly susceptible to the infection as they are potentially involved with the slaughtering, defeathering, and butchering of infected birds. All of these activities are considered by WHO to be especially risky behaviours.  Veterinarians and others concerned with disease control are also considered to be highly suspectible to avian influenza.

Can humans infect each other?

Limited evidence shows that the possibility of human to human transmission does exist, but there is no evidence to date that the avian influenza virus can spread easily in humans. Transmission has only occurred in association with outbreaks in poultry. The virus has not been known to spread beyond a first generation of close contacts or into a community, implying that close contact with a severely ill person is needed. Although there have been a number of cases in which avian influenza has spread between family members, it is unknown whether or not they were exposed to the same original source as well as to one another.

Are poultry and game safe to eat?

According to the UK Food Standards Agency, avian influenza does not pose any risk for UK consumers. The risk associated with catching avian influenza is associated with being in close contact with infected live poultry, and not related to eating cooked poultry or eggs. No incidence of infection as a result of handling poultry meat has been recorded.

What are the symptoms of avian influenza infection in humans?

Symptoms are likely to occur between three to five days after exposure, although they may present as late as seven days. Early symptoms are likely to be similar to those associated with normal human influenza (fever, cough, sore throat, and myalgia). Other reported symptoms include rhinorrhoea and watery diarrhoea. Pneumonia, acute respiratory distress, and viral pneumonia are just a few examples of the fatal complications which may ensue. The median time to death after the onset of symptoms has so far been 13 days.

How is avian influenza diagnosed in humans?

You may suspect avian influenza if the patient meets the Health Protection Agency's criteria (box 1).

When taking a clinical history from a patient with suspected avian influenza, it is important to take a thorough travel and contact history to help assess the risk. Clinical investigations should always include rapid tests for normal human influenza, as this is a likely differential diagnosis.

Investigations recommended by the Health Protection Agency include a chest x ray (abnormal findings are usually non-specific), total and differential counts for lympho­penia, and liver function tests. If these are normal, a diagnosis of avian influenza is very unlikely. Only once the risk of avian influenza is assessed by the history and above investigations should respiratory specimens be collected for investigation (box 2).

Respiratory specimens (such as nasopharyngeal aspirates/swabs, nasal swabs or throat swabs) should be collected from patients with suspected infection, ideally within three days of symptoms starting (but within five days is usually adequate). Useful investigations include the polymerase chain reaction, immunofluoresence tests, and viral culture.

How are infected patients treated?

Oseltamivir (Tamiflu) and zanamivir are both selective neuroaminidase inhibitors currently used to treat normal seasonal influenza. Neuro­aminidase is a glycoprotein with enzymatic activity, found on the surface of influenza A and B viruses. It is essential for the replication of these viruses as it breaks the bonds that hold viral particles to the outside of an infected cell. The breakage of such bonds releases the virus with resulting spread of infection. Neuroa­minidase inhibitors block the replication of influenza A and B virions (inert carriers of viral genome), preventing their release from the surface of infected cells. Infection of new host cells and further spread of infection within the respiratory tract are thereby halted. As all neuro­aminidase inhibitors are effective against strains of influenza, they are thought to increase patients' prospects of survival from avian influenza. They should be given early (within 48 hours), with their aim being to shorten symptom duration, reduce infectivity, and restrict complications.

Oseltamivir is predicted to be vital should a pandemic occur as it can be given orally, compared with zanamivir, which can only be inhaled. Therefore the UK government is expanding its stockpile (with an estimated 14 million courses to date—enough to treat a quarter of the population). But concerns surround the current limited manufacturing production as well as the high purchasing costs for some developing countries.

Amantadine and rimantadine are both M2 inhibitors. These drugs work by inhibiting the M2 ion channel protein in influenza A viruses, thus halting a key step in the replication process. Such drugs may also be used during a human avian influenza pandemic, but there is concern that there may be rapid resistance to these drugs, thereby limiting their effectiveness. It is already known that some H5N1 strains are resistant to this class of drugs; however, some strains are believed to have stayed susceptible.

Adequate supplies of antibiotics will be needed to prophylactically manage secondary bacterial infections of the lungs in high risk patients. The most fatal pneumonia seen to date, however, is resistant to available antibiotics.

Is there a vaccine?

Although no vaccine against the H5N1 strain has been available to date, several potential vaccines have been developed and are currently being tested. However, no vaccine is expected to become widely available unless a pandemic begins because the circulating virus will change because of antigenic drift.

Can the normal influenza vaccine prevent people catching bird flu?

The vaccine currently used for normal seasonal influenza will not protect against avian influenza, but may offer the best protection against illness and potential death should a pandemic occur. If the current vaccine was given to people at high risk of exposure to the virus, the protection provided against normal human influenza would reduce the subsequent risk of simultaneous infection with avian influenzas.

What travel advice should be given to patients?

Currently travel is not restricted to any countries, including those that have reported human cases of avian influenza. But patients should be advised to avoid live ­animal markets, poultry farms, and infected environments when visiting affected areas. People should also ensure that any poultry, game, or egg products that they consume or handle are properly cooked. No live poultry or poultry products should be brought into the UK from affected areas.

Even if patients have visited areas with known cases of avian influenza and are experiencing flu-like symptoms, they are unlikely to be infected unless they have been in close contact with birds in an affected area. They are more likely to have normal human flu because this will also probably have a high incidence in these areas. If a patient develops a severe respiratory condition, however, has ­visited an area known to be affected by avian influenza, and has had contact with live poultry or pigs within seven days of the onset of symptoms, human avian influenza should be suspected.

What precautions should exposed healthcare workers take?

Avian influenza is a notifiable disease, and therefore any suspected case should immediately be referred to a consultant in communicable diseases control at the local health protection unit.

The Health and Safety Executive's advice for healthcare staff in such an event are summarised in box 3. A risk assessment should be carried out on all suspected human avian influenza cases so that the appropriate precautions can be put into place to minimise risk to healthcare workers.

On a final note

Although it is not yet known if or when a pandemic will strike, it is reassuring that operational measures have been outlined in a number of countries, including the UK. Although the disease may not be predictable and guidelines are constantly evolving, it is certainly advantageous for medical students and health professionals to have some background knowledge, especially when dealing with anxious patients.

Competing interests: None declared.

Laura J L Halpin , final year medical student, affiliation
Email: halpin_laura@hotmail.com Farah Janmohamed , final year medical student, Barts and the London Medical and Dental School, London
Email: Sanjay Patwardhan , specialist registrar, City Hospital, Birmingham
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studentBMJ 2006;14:133 - 176 April ISSN 0966-6494