Bird flu – the pandemic clock is ticking
http://www.science.org.au/nova/090/090print.htm
Diseases caused
by viruses from animals are an ongoing threat to people's health. With
the number of deaths in Asia from bird flu rising, scientists say it is
only a matter of time before the next flu pandemic strikes.
Key text
Emerging and re-emerging diseases
Every year for the past thirty years a
new infectious agent, or an old one thought to be under control, has
emerged to cause disease in humans. Nearly two thirds of infectious
diseases in humans come from animals, and they are known as zoonoses or
zoonotic infections. Viruses are particularly good at jumping the
species barrier because they are able to infect a wide range of animals,
including humans. Some notable examples of viruses that cause zoonoses
include rabies, Ebola, Marburg, Lassa, hanta, morbilli and influenza.
So why do known viral diseases continue
to cause problems? The answer is that whenever there is a change in the
environment or the virus, a new opportunity is created to cause disease
in humans. The trigger could be localised increases in human
population, removal of forests, climate change, humans settling in new
geographic areas or humans encountering exotic animals and the viruses
they carry.
Viruses that cause colds and flu
The influenza virus is an example of a
zoonotic infection that re-emerges year after year. In humans, 'the flu'
is caused by either influenza A or B viruses. Influenza B viruses
infect only humans and although they can cause flu epidemics, do not
cause pandemics (world-wide epidemics). Influenza A viruses can infect
birds – including chickens, ducks and wild birds – and mammals,
including humans, pigs, cats, horses and whales to name a few. ‘Avian
flu’ or ‘bird flu’ is caused by avian influenza A viruses that can also
infect humans.
We tend to think of colds and flu as the
same thing – an infection that makes you suffer from a running nose,
sore throat, fever, aches and pains. Although the symptoms are similar,
a head cold and the flu are caused by different viruses. About half of
all cases of the common cold are caused by Rhinovirus, the rest being
caused by Coronavirus or Respiratory Syncytial Virus (RSV).
For most of us, the flu causes
irritating symptoms for about a week. But it can be a very dangerous
disease. World wide, the flu infects between 3 and 5 million people
every year, causing 300,000 to 500,000 deaths. In Australia, up to 3500
cases of the flu are confirmed every year, mostly in the very young, the
old, or people with underlying medical conditions.
Why can you get the flu more than
once?
The influenza virus infects cells of the
nose, throat and bronchi of the upper respiratory tract. Once inside a
cell, the virus takes control of the function of the cell to make more
copies of itself. Eventually, the cell loaded with virus particles dies
and the virus is released to spread to other cells.
During an infection, the immune system
only ‘sees’ the outside surface of the virus particle. If the immune
system doesn’t recognise the virus from previous infections, the virus
multiplies and spreads to other cells, and you get another dose of the
flu. The reason the immune system doesn’t recognise the virus is
because its outer surface is constantly changing in subtle ways. New flu
types come along every year as minor variants of existing viruses. A
slightly different vaccine is made each year to try to keep up with the
changing virus. This is why doctors recommend that particular groups of
people in the population are vaccinated each year for the flu.
The H5N1 bird flu story – so far
Occasionally, a radically different
virus emerges which has the potential to cause a pandemic (Past flu
pandemics).
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Past flu pandemics
There were three influenza
pandemics in the 20th century, the most deadly being the Spanish
flu of 1918-19, which occurred immediately after World War I.
At the time, it was not known what caused the flu. We now know
that the Spanish flu was caused by a H1N1 type Influenza A
virus, which killed between 20 and 50 million people world wide.
Human influenza viruses are
normally types H1, 2 or 3 and N1 or 2. The Asian flu of 1957-58
was caused by a H2N2 virus and the 1968-69 Hong Kong flu was
caused by a H3N2 type influenza virus. Both were created by the
genetic rearrangement of human flu virus and avian flu virus. In
the past, pandemics have occurred every 30 years or so. The
last pandemic was in 1968, so scientists predict that another
pandemic could occur any time soon, if given the right
conditions. There is the added concern that the worlds' ageing
population and others with a poor immune system are especially
vulnerable to the flu.
The 1918-19 flu pandemic
in Australia
The following article from
A History of the Pharmacy Board of New South Wales by Dr
Gregory Haines, published by the Pharmacy Board of New South
Wales and the Australian Pharmaceutical Publishing Company
(1997), is reproduced with the kind permission of Dr Haines and
the Pharmacy Board of New South Wales.
Before the emergency of the
Great War had passed, a new crisis which would fully engage
pharmacists had already begun to show itself. The winter of 1918
saw a sudden increase in the incidence of influenza in New South
Wales. This was the prelude to the 1919 influenza pandemic which
was to claim 6387 lives in the state. The death rate was about
to frighten and generate enormous alarm: for each 100,000 people
in the population, 319 were going to die.
Just over half of all
Australian deaths due to the 1919 influenza pandemic were
recorded in New South Wales. The state government took initial
steps in 1918 to try to prevent the spread of the anticipated
outbreak of the disease. Health authorities had been aware of
the influenza outbreaks in Europe and Britain from July 1918. At
that stage, what became known as Spanish Influenza was not
exhibiting unusual virulence, though its spread was anticipated.
The government made the
wearing of masks compulsory in shops, hotels, churches, theatres
and on public transport in the populous parts of the state.
Those who had become infected were to be isolated and quarantine
rules were tightened. Price control on treatments for influenza
was enforced and one Sydney pharmacist was severely fined in
October 1918 when he was found to have overcharged. In December
1918, representatives of the Pharmaceutical Society and the
medical association met and formulated a stock mixture and a
solid inhalation for use should the disease spread into Sydney
from North Head Quarantine Station.
Early in 1919 the government
strengthened its public health measures. It insisted on the use
of masks. Libraries, reading rooms, theatres, music halls,
auction rooms and billiard rooms and indoor or outdoor church
services within the County of Cumberland were prohibited. Space
regulations limited the number of people able to gather in
shops, hotels, tea rooms and restaurants. Shops were forbidden
to hold crowd-attracting bargain or clearance sales. Travel on
long-distance trains was restricted and quarantine regulations
were further tightened. Troops returning from the war were
quarantined at North Head and the Sydney Cricket Ground.
The epidemic peaked in the
winter of 1919 and abated by the February of the following year.
While it lasted, the influenza pandemic increased work and risk
for those engaged in pharmacy. It also prevented or limited the
activities of pharmacy organisations, either by preventing their
meetings or by robbing erstwhile participants of energy. The
Australasian Pharmaceutical Conference, which had not met since
1913, thanks to the war, did not gather until 1921, due to the
pandemic.
Related sites
-
Estimating the impact of the next influenza pandemic:
Enhancing preparedness (World Health Organisation)
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Information about influenza pandemics (Centers for
Disease Control and Prevention, US)
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Flu vaccine (The Science Show, 7 February 2004)
-
Alberta pandemic response (Health And Wellness, Alberta
Government, Canada)
-
Chronology of the 1918 Spanish influenza epidemic in Georgia
(University of Georgia)
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It all started in Kansas (Relevance: The Quarterly
Journal of The Great War Society, USA)
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In search of an enigma: The 'Spanish lady' (MRC,
National Institute for Medical Research, UK)
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Stanford University, USA
-
The 1918 Spanish flu pandemic, and the Hong Kong incident
(NinthDay.com)
-
Global epidemiology of
influenza: Past and present (Annual
Review of Medicine, 2000, 51: 407-421)
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In December 2003, an outbreak of bird
flu known as H5N1 occurred in poultry in eight Asian countries at the
same time. Like other influenza A viruses, H5N1 is able to infect
humans that have close contact with infected birds or water. The disease
in humans is particularly virulent, causing death in about half of the
adults and children who show symptoms of the flu, although the number is
decreasing with time.
Some of the symptoms caused by H5N1 bird
flu are unlike those of other types of flu. Notably, a sore throat, a
runny nose and other symptoms we usually associate with the flu are not
always seen. Indeed, some children in Vietnam who were thought to have
died from encephalitis (brain inflammation) probably died from H5N1 bird
flu. A growing number of people are infected by the virus but show no
signs of illness, becoming instead carriers of the disease. The variety
of symptoms – including the unusual or none at all – means that cases of
bird flu could go unnoticed for some time, giving the virus a chance to
spread.
Why is H5N1 bird flu such a concern?
Three conditions need to be met for a
pandemic to occur. Firstly, we need the presence of a new virus to
which the population has little or no immunity. The second condition is
that the virus has the ability to infect humans and to be passed on to
other humans. And the third condition is that there is no effective
vaccine to prevent the spread of the disease in humans. If all of these
conditions are met by a flu virus, or any other type of virus,
conditions are perfect for a pandemic to occur. Authorities are worried
about H5N1 because it has many of the characteristics of a virus that
can cause a pandemic.
Most cases of bird flu are caused by
people being infected by birds or water contaminated with the H5N1
virus. Authorities have reported a number of cases where infection is
likely to have occurred due to close contact between family members with
the flu. So far, H5N1 has not shown signs of being very easily
transferred from one person to the next via casual contact. However, a
more infectious virus may be created if a person with the flu also
catches bird flu H5N1. The different strains may recombine to create a
more infectious virus. The concern is that you might get a virus like
H5N1, that is already lethal, becoming extremely contagious, which would
make it easier for it to spread from person to person.
Fighting the flu
Because H5N1 is so widespread, a global
reporting system is required to limit the spread of outbreaks of the flu
in humans (Controlling an outbreak).
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Controlling an outbreak
Once a virus with the ability
to cause a pandemic exists, then control of an outbreak of the
virus becomes very important in preventing its spread. This is
true not only of the flu, but of any virus that can cause a
zoonotic infection.
Surveillance, development of
vaccines, preparedness for an outbreak and planning for a
pandemic are all important means of controlling an outbreak.
The behaviour of H5N1 virus is being monitored by researchers
from the World Health Organization (WHO) and the United States
Centers for Disease Control, looking for early signs that it has
changed or altered its ability to infect people, particularly
from other people.
Limiting the number of
infected animals that are the source of disease in people is
important in controlling outbreaks of the flu in people. For
this reason, authorities in Asian countries have culled millions
of infected poultry. A number of Asian countries also vaccinate
poultry against bird flu. Some scientists are concerned that
widespread vaccination will allow the virus to remain in the
bird population without causing disease and would put further
pressure on the virus to change.
However, it is not feasible
to vaccinate all poultry in Southeast Asia. In Vietnam for
example, 90 per cent of chickens are from ’backyard farmers’ who
live in close proximity to the animals. Some countries are
simply too poor to vaccinate their poultry. Such countries are
relying on public awareness campaigns to prevent the spread of
H5N1 from animals to people. People are being urged to modify
traditional practices so that chickens, ducks and pigs are
separated on farms and in market places.
On a broader scale, countries
can prevent the export and import of infected animals, products
or people. Australia does not import products from countries
known to have H5N1, but airline passengers need to be checked by
quarantine inspectors for bird products in their luggage.
Medical professionals need to be alert to the disease in
patients and poultry farmers need to recognise signs of the
disease in birds. |
In 1999, WHO published a world
preparedness plan, which includes a network of 112 influenza centres,
constantly monitoring reported cases of the flu to determine likely
sources of infection and to contain potentially pandemic strains.
Australia has the ‘Australian Action Plan for Pandemic Influenza’ and
‘Ausvetplan’ in place to respond to a potential flu pandemic reaching
Australia.
There are two approaches to fighting the
flu in humans. They are prevention of infection by vaccination (Vaccines
for pandemics)
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Vaccines for pandemics
Vaccination against the flu
is, in theory, the best way to prevent a flu pandemic. Usually,
vaccines are about 70 per cent effective in preventing the flu.
However, there are problems associated with widespread
vaccination. Knowing which vaccine to stockpile before the
outbreak of a pandemic is a major problem, because you don't
know which virus will cause the pandemic. It takes months to
make enough vaccine for all potential victims, and flu vaccines
only last about 12 months in storage. Every year, companies that
make the annual flu vaccine have to throw away expired or unused
vaccine, so there is little incentive for them to stockpile. Who
pays for the stockpiled vaccine if it isn't used?
There are also some technical
problems with making a H5N1 vaccine. H5N1 kills chickens, so the
usual way of making a vaccine that relies on chicken eggs
doesn't work very well. An alternative genetically engineered
virus may need to be used to produce enough vaccine in a short
period of time.
When vaccinating, it is usual
to have at least two shots, one to prime the immune system and
the other to boost immunity. Because of the limited availability
of a vaccine, the number of shots might have to be limited to
one per person. Even with only one shot, the immune system will
respond better to the virus or to another vaccine specifically
targeted to the strain causing the pandemic. Adults have some
resistance to H1 and H3 type viruses from previous cases of the
flu , but have no previous exposure to a H5 virus. Trials to
test the effectiveness of a vaccine take some months to complete
and assume that the vaccine is effective.
In Australia, with a limited
supply of vaccine, not everyone can be vaccinated. If the
priority is to minimise the number of deaths, then the aged
should receive it. But if you want to keep society running, then
priority goes to health care workers and other essential
personnel. If the priority is to keep economic losses to a
mimimum, then children and working adults should get the
vaccine.
The people at greatest risk
of infection directly from animals live in Southeast Asia. But
individuals and governments are too poor to pay for widespread
vaccination in these countries. Decisions need to be made at a
global and a local level for effective pandemic control.
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and antiviral medications. People in
direct risk of infection from animals include workers in the poultry
industry and farmers and their families in Asian countries. Medical
professionals or family members nursing infected people are also
potentially at risk.
Flu vaccines are not normally stockpiled
because, until a pandemic starts, you don’t know exactly which one to
make. But for H5N1, the WHO is recommending that vaccines that are an
imperfect match of flu be made because it is seen to be a serious
threat. An imperfect vaccine could give some protection, so although
you might fall ill, you are unlikely to die from the infection.
Antiviral drugs could be used in the
early stages of a pandemic, until vaccines are available. While H5N1 is
resistant to the
antivirals called amantadine and rimantidine, it is sensitive to
neuraminidase inhibitors such as Relenza and Tamiflu (Antivirals bring
hope).
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Antivirals bring hope
The influenza virus has found
an ideal strategy – one that makes it difficult for the body's
immune system to deal with. The surface of the virus is
constantly changing, making it difficult for the immune system
to 'recognise' the virus and fight off the infection. But the
flu virus does have a 'weak spot'. The enzyme
neuraminidase is needed for the virus to get to the site of
infection and to release new viruses from infected cells. Both
of these activities are associated with a pocket-shaped
structure on neuraminidase that does not change shape. A group
of Australian researchers thought that if the unchanging pocket
was blocked by a dummy molecule, then the virus would be unable
to increase in number and spread to other cells. The compound
they found is called zanamivir, and is now marketed by the name
Relenza. Three researchers – Peter Colman, Graeme Laver and Mark
von Itzstein – shared the 1996 Australia Prize for excellence in
the field of pharmaceutical design for their work on Relenza.
Based on the Australian
research, another compound that worked in a similar way was
found by overseas researchers, and that compound is now marketed
as Tamiflu.
Relenza is used as a nasal
spray, whereas Tamiflu is taken orally as a tablet. They are
both very effective at preventing the flu in human volunteers.
If taken within 48 hours of the first signs of the flu, they
decrease the number of people who get the flu, the severity of
the symptoms and the duration of the infection. Importantly,
they also work against H5N1 viruses in laboratory tests.
Although vaccination is the
preferred option to prevent the flu, Tamiflu and Relenza also
have the ability ability to prevent the flu when taken as a
prophylactic, before exposure to the virus. The combination of
vaccination and prevention with Tamiflu or Relenza can also be
used.
One question still remains.
Will pressure on the virus, arising from widespread use of
Relenza or Tamiflu select virus resistant to the drugs? Work to
date indicates that the virus is having a difficult time
changing the pocket structure and still being able to multiply
in cells. But that may be a matter of time and opportunity. New
forms of drugs similar to Relenza and Tamiflu are being made and
tested, to add to the number of drugs available to prevent and
treat the flu.
Related sites
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Tests for the effectiveness of
antiviral drugs show that they need to be taken in the early stages of
infection and they tend to decrease the severity and duration of the
infection.
Most health officials believe that a
pandemic is due to occur some time soon, and that it is a case of when,
not if. In which case, it would be wise to be ready for it.
Related
Nova
topic:
Immunisation –
protecting our children from disease
Glossary
antibiotic.
A substance produced by bacteria or fungi that destroys or prevents the
growth of other bacteria and fungi.
antibody.
A protein produced by the body’s immune system in response to a foreign
substance (antigen). An antibody reacts specifically with the antigen
that induced its formation and inactivates the antigen. Our bodies fight
off an infection by producing antibodies.
antigen.
Any foreign substance, usually a protein, that stimulates the body's
immune system to produce antibodies. (The name antigen reflects its role
in stimulating an immune response – antibody generating.)
antivirals.
Drugs that are used to prevent or cure a disease caused by a virus, by
interfering with the ability of the virus to multiply in number or
spread from cell to cell.
carrier.
Is a person who is infected with an agent that causes a disease who
shows no sign of illness. Asymptomatic carriers shed the causative
agent, such as a virus or bacteria, and so can pass the disease on to
others. The most famous asymptomatic carrier was Mary Mallon, or Typhoid
Mary.
contagious.
A contagious disease is easily spread from one person to another by
contact with the infectious agent that causes the disease. The agent may
be in droplets of aerosols made by coughing or sneezing, contaminated
food utensils, water or food.
cytokine.
A hormone-like molecule, produced by one cell, that has an effect on
another cell. Some types of cytokines are normally produced in low
concentration by the immune system as part of the body’s defence
mechanism. Some cytokines are toxic at high concentrations and cause
disease symptoms such as fever.
enzyme.
A protein that acts as a catalyst. Every chemical reaction in living
organisms is facilitated by an enzyme.
epidemiology.
The study of diseases or conditions in human populations and the factors
that influence their incidence and prevalence.
gene.
The basic unit of inheritance. A gene is a segment of DNA that specifies
the structure of a protein or an RNA molecule.
genetic mutation.
A change in the genetic material (DNA, or RNA in the case of some
viruses) resulting in new or rearranged hereditary determinants.
Mutations are rare, random events in which the base sequence of the
nucleic acid molecule is changed. The frequency of mutations may be
increased by chemicals or radiation.
haemagglutinin.
A protein which forms a rod-shaped spike on the surface of influenza
virus. The name haemagglutinin is given because the spikes are capable
of adhering to red blood cells, causing them to be agglutinated
(clumped).
host.
An organism on or in which a parasite lives.
immune system.
The cells, tissues and organs that assist the body to resist infection
and disease by producing anitbodies and/or altered cells that inhibit
the multiplication of the infectious agent.
neuraminidase.
An enzyme which forms a mushroom-shaped projection on the surface of an
influenza virus particle. The enzyme assists in the release of
newly-formed virus particles from the surface of an infected cell.
nucleic acid.
A large molecule made up of a sequence of phosphorylated
nitrogen-containing bases. DNA and RNA are both nucleic acids.
pandemic.
The worldwide outbreak of a disease.
prophylactic.
A medical procedure or practice that prevents or protects against a
disease or condition (eg, vaccines, antibiotics, drugs).
protein.
A large molecule composed of a linear sequence of amino acids. This
linear sequence is a protein's primary structure. Short sequences within
the protein molecule can interact to form regular folds (eg, alpha helix
and beta pleated sheet) called the secondary structure. Further folding
from interaction between sites in the secondary structure forms the
tertiary structure of the protein.
Proteins are essential to the structure
and function of cells. They account for more than 50 per cent of the dry
weight of most cells, and are involved in most cell processes. Examples
of proteins include enzymes, collagen in tendons and ligaments and some
hormones. For more information see Protein structure and diversity
(Molecular Biology Notebook, Rothamsted Research, UK).
public health.
The aspect of medical activity directed towards improving the health of
the whole community.
species.
Living things of the same kind that are potentially capable of breeding
and producing fertile offspring. Theoretically, plants or animals of
different species cannot interbreed. However, occasionally this does not
hold true.
vaccine.
A preparation consisting of antigens of a disease-causing organism
which, when introduced into the body, stimulates the production of
specific antibodies or altered cells. This produces an immunity to the
disease-causing organism. The antigen in the preparation can be whole
disease-causing organisms (killed or weakened) or parts of these
organisms.
virulent.
Highly lethal; causing severe illness or death.
virus.
A submicroscopic infectious agent consisting of a nucleic acid (DNA or
RNA) molecule surrounded by a protein coat. Viruses cannot replicate
outside a living cell. More information can be found at How viruses work
(How Stuff Works, USA).
zoonoses.
Diseases that are transferable to humans from animals.
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