ABSTRACT
The presence of the bird flu virus in Europe is giving rise to
some alarm in public opinion. It is the most extensive and severe
bird flu we can recall. In the history of this disease, never
in the past were so many countries struck at the same time, involving
such a high animal mortality rate. The causal agent, the H5N1
virus, has proved to be particularly tenacious. Despite the destruction
of 150 million birds, the virus is now considered endemic in many
parts of Indonesia, Vietnam, parts of Cambodia, China, Thailand
and Laos. From the close of 2003 to the spring of 2004 the disease
has also been reported in Korea and Japan. The bird flu epidemic
is a risk for human beings due to the fact that in a few cases
this virus has proved that it can also infect man very aggressively
with a high mortality rate, besides the virus could undergo changes
and easily spread from person to person. The WHO has feared the
risk of an influenza pandemic for at least ten years on the basis
of data that influenza viruses periodically change all their antigenic
features subsequently finding the human population partly or totally
unprepared from an immune perspective. This possibility occurred
thrice in the past century: in 1918-19 during the socalled “Spanish
flu”, which counted 40-50 million dead, in 1957-58 and in
1968-69. The risk of the emergence of a virus pandemic depends
on the possibility of human exposure and infections. This risk
persists as long as the virus circulates in animals. The fight
against the disease in poultry and other birds is hence the main
measure to reduce the possibility of human infection and the outbreak
of a viral pandemic. Interhuman transmission – which would
start the pandemic – could occur through genetic reorganisation
in case of a co-infection with a seasonal virus and the H5N1 virus.
This could occur both in man and in pigs or through the H5N1 virus’
gradual adjustment to bind human cells in the respiratory system.
The WHO’s strategic plan envisages
the following goals. The current pre-pandemic phase’s main
goals are: 1 - reduce the opportunities of human infection, and
2 - strengthen the surveillance system to provide an early alert.
During the next emergency phase of a viral pandemic the priority
lies in restraining or delaying the spreading of the virus. During
the declared pandemic phase efforts will focus on reducing morbidity,
mortality and the subsequent social disruption.
Concerning Italy, our country has concretely taken steps to rapidly
detect the infection’s hotbeds in birds and to book the
purchase of 36 million vaccines and adequate supplies of antiviral
drugs.
The world is facing the risk of an influenza pandemic. In a context
of economic globalisation the health risks of a country or of
an international region are quickly shared by other countries
and continents. Concerning bird flu, the risk of the disease spreading
among birds and hence the risk of a pandemic is created by another
category of travellers: migratory birds. Faced with a global threat,
all countries’ governments realise the importance of technical
and scientific collaboration, health policies and collaboration
with the pharmaceutical industry.
Bird Flu
Bird flu is a contagious animal disease, which is caused by viruses
that normally infect only birds and less commonly pigs. Bird flu
viruses are highly species-specific, but on rare occasions they
cross species barriers and infect human beings. In domestic poultry
the viral infection causes forms of disease that vary depending
on the degree of virulence. The low pathogenic forms only cause
mild symptoms and can even pass undetected. The highly pathogenic
form is instead extremely serious. It spreads very quickly through
poultry causing a disease, which involves many internal organs
and whose mortality rate can reach 100% of the poultry in just
48 hours. The influenza A virus has 16 subtypes H and 9 subtypes
N. We know that the virus’ subtypes H5 and H7 can cause
highly pathogenic forms of the disease. However neither all H5
and H7 subtype viruses are highly pathogenic nor do all cause
a severe disease in poultry.
To judge by what we know the H5 ad H7 viruses are introduced in
poultry in their low pathogenic form to then be transformed through
mutations into their highly pathogenic form. This is why the presence
of H5 or H7 viruses are a reason for concern even when the initial
signs of infection are those typical of the low pathogenic form.
The H5N1 infection in poultry is rapidly spreading in Europe too
through migratory birds. Wild water fauna is considered the natural
reserve of the influenza A virus. Probably they have spread flu
viruses for centuries without causing any alarm for international
public health till now. We know that they carry the H5 and H7
virus types’ low pathogenic form. Now instead it seems clear
that certain types of migratory birds also carry these viruses’
highly pathogenic form. The current epidemic of highly pathogenic
flu, which started in South East Asia in mid 2003, is the most
extensive and severe one we recall. Never in the past were so
many countries involved at the same time nor were so many infected
birds counted. From mid December 2003 to early February 2004,
the poultry epidemic caused by the H5N1 virus has been reported
in Vietnam, Thailand, Cambodia, Laos, China, Indonesia, Korea
and Japan. In August 2004 even Malaysia reported cases of infection.
Russia reported the first poultry epidemics late in July 2005,
followed by Mongolia and Kazakhstan. In October 2005, the H5N1
virus’ presence was confirmed in poultry also in Turkey
and Romania. In countries like Vietnam, Cambodia, Indonesia, China
and Thailand the epidemic is acquiring such endemic features as
to make us think that the virus will circulate in those countries
for still many years.
Implications for Human Health
Such an extensive spreading of the virus and its persistence in
bird populations gives rise to certain risks for human health.
The first, which causes a serious disease, is the transition of
the virus directly from poultry to man. In rare cases when there
was a species leap and hence the direct transition from poultry
to man, the H5N1 virus caused serious forms of disease involving
the death of over sixty people on a total of about 150 cases.
Unlike the normal seasonal miflu, when the infection only causes
moderate respiratory symptoms in most people, the disease caused
by the H5N1 virus has a serious clinical progress and a high mortality
rate due to primary viral pneumonia and the involvement of many
systems. Most cases so far have involved children and adults who
are in good health. 
It
is currently believed that the route of infection for human beings
is direct contact with infected poultry or surfaces or objects
that are contaminated by animal faeces. Currently most cases have
occurred in rural or periurban areas where there are farmyard
animals and the poultry moves freely even entering houses and
sharing the same spaces where children play. Since birds expel
large quantities of virus in their faeces, the possibilities of
contact with poultry faeces or with the environment that is contaminated
by the virus are many. Besides since most family budgets depend
on poultry, they sell or destroy them, thus eating infected birds.
Even the destruction of poultry flocks or their slaughtering are
considered as high risk operations for the contagion of man. A
second risk, which is far more important, is that the virus can
change into a highly contagious form for human beings and that
it can spread from person to person. This situation can mark the
start of an international epidemic, an influenza pandemic.
The Risk of a Pandemic
A pandemic can start when there emerges a new subtype of virus,
when it infects human beings causing a serious disease and when
it spreads easily and in a lasting manner among human beings.
The H5N1 virus is a new virus for human beings, which has never
circulated before among the population. It has infected over one
hundred people with a very high mortality rate. Nobody would certainly
be immune if the H5N1 virus emerged in the international population.
The
prerequisite, which is lacking to start a human pandemic, is the
established, efficient and lasting interhuman transmission of
the virus. The risk that this situation may occur depends on the
opportunities given to the virus to change. The lasting circulation
of the virus in the population and the extension of the same to
such a large number of countries are favourable conditions in
this sense. The virus can improve its transmissibility through
a genetic reorganisation process during which genetic material
is exchanged between human viruses and bird viruses during an
infection either in a human being or in a pig. In this case the
pandemic seems to have had an explosive start and spread quickly.
The second process that could produce a virus with the feared
characteristics is a gradual adjustment process, which increases
the virus’ skill to bind human cells during the following
infections, thus damaging humans. In this second mode, which could
initially appear through small clusters of human cases where the
infection could seem to be transmitted in the same family nucleus,
the contagion would spread more slowly, thus giving health authorities
more time to intervene with defensive actions. A probable case
of transmission from person to person associated with close contact
occurred in Thailand in 2004 and probably in Vietnam in February
2005, but it is not certain whether the infection was transmitted
from person to person or rather from the same source of contagion.
The threat of an influenza pandemic has long been reported by
the World Health Organization as we know that one of the influenza
virus’ features is mutation. But while yearly mutations
are not very relevant (antigenic drift), periodically they involve
a radical change in antigenic features, thus finding the international
population unprepared from an immune perspective (antigenic shift).
In the 20th century new subtypes of influenza virus emerged thrice
causing three pandemics. In 1928-29 the so-called “Spanish
flu” caused by the H1N1 virus counted the highest number
of deaths ever recorded for an epidemic during the last century
(50 million). Many of them died during the early days of the infection,
while others died following complications. About half the deceased
were youth or healthy adults. The high death rate of people was
caused by three successive waves of epidemic; the second of these
was the most terrifying. The 1957-58 “Asian flu” caused
by the H2N2 virus was identified in China in February 1957. The
third pandemic occurred in 1968-69 and was caused by the H3N2
virus. On the basis of genetic studies conducted on deceased individuals
during the “Spanish flu”, it has of late been possible
to establish that the “Spanish flu” was caused by
a bird virus, while in 1957-58 and in 1968-69 pandemics were caused
by a combination of genes from bird flu and human flu viruses.
The WHO’s reparatory Plan
The WHO has developed a preparatory plan and an answer
for pandemic flu, the Global Influenza Preparedness Plan, which
defines the phases of a pandemic, stresses the WHO’s role
and provides instructions to member states concerning measures
to be adopted before and
during a pandemic. According to that scale today we are experiencing
a pre-pandemic red alert phase; to be precise we are in phase
3 during which human infections occur with a new subtype, but
they involve no transmission from man to man or at most rare episodes
of interhuman transmission resulting from close contact. We envisage
that during phase 4 there will be small clusters with a limited
transmission from man to man but the disease will spread in a
highly localised manner, which suggests that the virus does not
as yet adjust well to humans. Phase 5 envisages more extensive
clusters, which lead us to think that the virus is adjusting to
humans but that it cannot be fully transmitted. In phase 6 instead
we enter the pandemic period during which there is a lasting transmission
in the entire population. In view of the threat of a pandemic,
the WHO recommends all countries to implement urgent actions to
get ready for a pandemic. To assist countries in this commitment
the WHO is developing a model to establish priorities. The goals
of the pre-pandemic phase we are currently experiencing focus
on:
- reducing the opportunities for a human infection; and,
- strengthening the active surveillance system.
The risk of a possible virus pandemic depends on the opportunities
for human exposure. These opportunities will persist in the measure
in which the virus H5N1 will continue to circulate in animals.
Disease control in birds is hence the chief manner to reduce the
opportunities of human infection, thus reducing the opportunities
for a pandemic virus to emerge. Hopes that the virus could be
quickly eliminated from poultry have not been concretised and
the situation seems to develop in the opposite direction involving
an increasing number of countries. 
The
virus’ highly pathogenic form is endemic in many Asian countries
and the factors that are responsible for such a long persistence
have not been entirely explained. We know that domestic geese
can secrete large quantities of virus without showing any signs
of the disease. Despite these difficulties disease control in
poultry remains a concrete goal, which involves significant changes
in intensive poultry farming systems. In Europe it involves quick
reporting and diagnosis of every infected animal to prevent the
circulation of the virus in small and large poultry farms. Bird
flu can cross borders and involve other countries both through
international trade of live poultry and through migratory birds,
which can carry the virus for long distances, thus spreading the
infection to birds in the countries they reach. The WHO, the FAO
and the WOAH (World Organization for Animal Health) have jointly
established a Global Warning and Response System (GLEWS) for animal
diseases. It combines the three agencies’ existing red alert
systems, disease ascertainment methods and response capacity.
The system formalises the sharing of epidemiological information
and envisages an operational structure for field missions in the
areas that have been struck. The WHO also means to improve its
understanding of links between animal diseases, human behaviour
and the risk of contracting the H5N1 infection. High risk behavioural
patterns on the part of inhabitants in rural areas in South East
Asia are well known but they are constantly repeated with a high
risk of protracting the infection, thus bringing death to an increasing
number of people. Every new case of human infection gives the
virus the opportunity to adjust to man; hence it is an event that
must be actively prevented even through mass education campaigns.
Asian countries where the bird flu epidemic still persists lack
epidemiological surveillance systems and efficient veterinary
and laboratory services. Few of the countries that have been struck
have the personnel and resources required to study human cases
and especially to detect and study case groups in a small family
or social context, which are a warning signal of a possible transmission
from man to man.
The WHO, the FAO and the WOAH will make use of their research
network to facilitate the quick development of new methods to
detect the virus in environmental samples. Concerning human infection,
it is particularly important to detect every cluster (group of
cases in the same family or community such as schools or hospitals)
to monitor the possible development of an epidemic. Epidemiological
surveillance conducted in close contact with patients, communities
where there have been cases and high risk groups like health operators
also provides information on the virus’ behaviour. In the
same manner information on the clinical progress of cases is also
highly relevant because we expect the better transmissibility
of the virus to coincide with a reduction in the mortality rate.
Studies on H5N1 viruses isolated from patients who have been affected
by the disease are also absolutely relevant in paving the way
for work towards an effective vaccine.
International Travellers
To date there have been no cases of human infection in Europe
because the hotbeds of bird flu have been extremely limited. One
risk could result from travellers.
Travellers visiting South East Asian countries must avoid all
contact with chicken, geese, ducks, pigeons and all types of wild
animals. They must possibly avoid staying in rural areas, attending
markets, which trade in live animals, or places where cock fighting
is practiced. They must also avoid eating poultry meats or poultry
products such as eggs that are not well cooked.
As occurs with other infectious diseases, one of the simplest
and most effective measures of prevention against the transmission
of the disease is to wash hands often and correctly with soap
and water to remove infecting material such as bird faeces. If
the traveller were to cook his own meals, he should:
- Separate raw meat from cooked meat and pre-cooked food items.
Neither the same chopping board nor the same knife should be used
for raw meat and cooked or precooked food;
- Do not prepare raw or cooked food without first washing hands
before one operation or the other;
- Do not replace the cooked meat on the same dish it was in before
being cooked;
- All food derived from poultry meats including eggs and chicken
blood must be entirely cooked; the influenza virus is destroyed
by heat, hence cooking temperature must reach at least 158 °F
(70 °C);
- Wash the egg shell thoroughly with plenty of soap and water
before handling it for cooking purposes; wash hands soon after;
- Do not use raw poultry meats or eggs that are not well boiled
in food that will not be cooked later;
- After handling raw poultry meats or eggs, wash hands and all
surfaces and utensils with soap and water.
Vaccines and Antiviral Drugs
During the pre-pandemic phase the WHO’s primary goal is
to restrain or delay the spreading of the contagion. A decisive
role for this purpose must be performed by the specific vaccine
and by antiviral drugs. Concerning Italy, the government has made
the right moves by booking the purchase of 36 million doses of
vaccine and an adequate quantity of antiviral drug supplies. The
problem – if at all – will be faced by producing firms
concerning their capacity to nationally and especially internationally
provide quantities of vaccines and drugs that can meet the requirements
of the spreading pandemic virus. The production of drugs like
Tamiflu (oseltamivir) and Relenza (zanimivir) has been extremely
limited so far considering the limited market request. In the
same manner the producing firms should extend their production
facilities and thus make important investments to meet an order
that could theoretically never be made.
Vaccines are universally considered as frontline defence. Their
production will start when the WHO officially declares that the
pandemic has started and specifies the features of the virus against
which the vaccine must be prepared. It is envisaged that the production
times of the same will range from 4 to 6 months. This interval
will be an important critical factor just as the difficulty to
produce adequate quantities of vaccine at an international level
especially in developing countries, which are densely populated
and lack health facilities and services appointed to vaccinations.
The epidemic will most likely break out in Asia, but the time
required for it to reach Europe and other continents will doubtless
be short considering international mobility, the density of air
traffic and international flights. It has been calculated that
international arrivals throughout the world exceed 800 million
a year. Hence since their quantity will be inadequate at the start
of the pandemic, antiviral drugs play a key role in reducing morbidity,
mortality and the subsequent social disruption related to the
situation.
Though neither the date nor the severity of the next epidemic
can be predicted, history shows us how these events lead to a
number of deaths and sick people that can disrupt the public life
of countries, overloading the work of hospitals, causing an economic
crisis in many sectors and
chaos in trade, tourism and air and sea transport. In a context
of global risk it is essential for all countries in the world
to closely cooperate to agree on a common strategic plan directed
by the World Health Organisation. A global threat must be met
with an action plan that is organised on an international scale.
Walter Pasini
Director of The World Health Organization
Collaborating Center for Tourist Health
(WHOCC)
Translated by interpres sas
