Avian influenza, or “bird flu”, is a contagious disease of animals
caused by viruses that normally infect only birds and, less commonly, pigs.
Avian influenza viruses are highly species-specific, but have, on rare
occasions, crossed the species barrier to infect humans.
In domestic poultry, infection with avian influenza viruses causes two main
forms of disease, distinguished by low and high extremes of virulence.
The so-called “low pathogenic” form commonly causes only mild symptoms
(ruffled feathers, a drop in egg production) and may easily go undetected.
The highly pathogenic form is far more dramatic. It spreads very rapidly
through poultry flocks, causes disease affecting multiple internal organs,
and has a mortality that can approach 100%, often within 48 hours.
Which viruses cause highly pathogenic disease?
Influenza A viruses have 16 H subtypes and 9 N subtypes. Only viruses
of the H5 and H7 subtypes are known to cause the highly pathogenic form of
the disease. However, not all viruses of the H5 and H7 subtypes are highly
pathogenic and not all will cause severe disease in poultry.
On present understanding, H5 and H7 viruses are introduced to poultry flocks
in their low pathogenic form.
When allowed to circulate in poultry populations, the viruses can mutate,
usually within a few months, into the highly pathogenic form. This is why
the presence of an H5or H7 virus in poultry is always cause for concern,
even when the initial signs of infection are mild.
Influenza viruses are grouped into 3 types, designated A, B and C.
Influenza A and B viruses are of concern for human health.
Only influenza A viruses can cause pandemics.
The H subtypes are epidemiological most important, as they govern the
ability of the virus to bind to and enter cells, where multiplication of the
virus then occurs.
The N subtypes govern the release of newly formed virus from the cells.
Do migratory birds spread highly pathogenic avian influenza viruses?
The role of migratory birds in the spread of highly pathogenic avian
influenza is not fully understood.
Wild waterfowl are considered the natural reservoir of all influenza A
viruses. They have probably carried influenza viruses, with no apparent
harm, for centuries. They are known to carry viruses of the H5 and H7
subtypes, but usually in the low pathogenic form.
Considerable circumstantial evidence suggests that migratory birds can
introduce low pathogenic H5 and H7 viruses to poultry flocks, which then
mutate
to the highly pathogenic form.
In the past, highly pathogenic viruses have been isolated from migratory
birds on very rare occasions involving a few birds, usually found dead
within the flight range of a poultry outbreak. This finding long suggested
that wild waterfowl are not agents for the onward transmission of these
viruses.
Recent events make it likely that some migratory birds are now directly
spreading the H5N1 virus in its highly pathogenic form. Further spread to
new areas is expected.
What is special about the current outbreaks in poultry?
The current outbreaks of highly pathogenic avian influenza, which began
in South-East Asia in mid-2003, are the largest and most severe on record.
Never before in the history of this disease have so many countries been
simultaneously affected, resulting in the loss of so many birds.
The causative agent, the H5N1 virus, has proved to be especially tenacious.
Despite the death or destruction of an estimated 150 million birds, the
virus is now considered endemic in many parts of Indonesia and Viet Nam 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.
The H5N1 virus is also of particular concern for human health.
Which countries have been affected by outbreaks in poultry?
From mid-December 2003 until early February 2004, poultry outbreaks
caused by the H5N1 virus were reported in 8 Asian nations (listed in order
of reporting): the Republic of Korea, Viet Nam, Japan, Thailand, Cambodia,
Lao People’s Democratic Republic, Indonesia, and China.
Most of these countries had never before experienced an outbreak of highly
pathogenic avian influenza in their histories.
In early August 2004, Malaysia reported its first outbreak of H5N1 in
poultry, becoming the ninth Asian nation affected.
The Russian Federation reported its first H5N1 outbreak in poultry in late
July 2005, followed by reports of disease in adjacent parts of Kazakhstan in
early August.
Deaths of wild birds from highly pathogenic H5N1 were reported in both
countries.
Almost simultaneously, Mongolia reported the detection of H5N1 in dead
migratory birds.
In October 2005, H5N1 was confirmed in poultry in Turkey and Roma¬nia.
Outbreaks in wild and domestic birds are under inves¬tigation elsewhere.
Japan, the Republic of Korea, and Malaysia have announced control of their
poultry outbreaks and are now considered free of the disease. In the other
affected areas, outbreaks are continuing with varying degrees of severity.
What are the implications for human health?
The widespread persistence of H5N1 in poultry popula¬tions poses two
main risks for human health.
The first is the risk of direct infection when the virus passes from poultry
to humans, resulting in very severe disease.
Of the few avian influenza viruses that have crossed the species barrier to
infect humans, H5N1 has caused the largest number of cases of severe disease
and death in humans.
Unlike normal seasonal influenza, where infection causes only mild
respiratory symptoms in most people, the dis¬ease caused by H5N1 follows an
unusually aggressive clini¬cal course, with rapid deterioration and high
fatality. Pri¬mary viral pneumonia and multi-organ failure are com¬mon.
In the present outbreak, more than half of those infected with the virus
have died. Most cases have occurred in previously healthy children and young
adults.
A second risk, of even greater concern, is that the virus – if given enough
opportunities – will change into a form that is highly infectious for humans
and spreads easily from person to person. Such a change could mark the start
of a global outbreak (a pandemic).
Where have human cases occurred?
In the current outbreak, laboratory-confirmed human cases have been
reported in 4 countries:
Cambodia
Indonesia
Thailand and
Viet Nam.
Hong Kong SAR has experienced 2 outbreaks in the past.
In 1997, in the first recorded instance of human infection with H5N1, the
virus infected 18 people and killed 6 of them.
In early 2003, the virus caused 2 infections, with one death, in a Hong Kong
family with a recent travel history to southern China.
How do people become infected?
Direct contact with infected poultry,
Or
Surfaces and objects contaminated by their faeces, is presently consid¬ered
the main route of human infection.
To date, most human cases have occurred in rural or periurban areas where
many households keep small poultry flocks, which often roam freely,
sometimes entering homes or sharing outdoor areas where children play.
As infected birds shed large quantities of virus in their faeces,
opportunities for exposure to infected droppings or to environments
contaminated by the virus are abundant under such condi¬tions.
Moreover, because many households in Asia depend on poultry for income and
food, many families sell or slaughter and consume birds when signs of
illness appear in a flock, and this practice has proved difficult to change.
Exposure is considered most likely during slaughter, defeathering,
butchering and preparation of poultry for cooking.
There is no evidence that properly cooked poultry or eggs can be a source of
infection.
9. Does the virus spread easily from birds to humans?
ANS. No. Though more than 100 human cases have occurred in the current
outbreak, this is a small number compared with the huge number of birds
affected and the numerous associated opportunities for human exposure,
especially in areas where backyard flocks are common.
It is not presently understood why some people, and not others, become
infected following similar exposures.
What about the pandemic risk?
A pandemic can start when 3 conditions have been met:
1. A new influenza virus subtype emerges;
2. It infects humans, causing serious illness; and
3. It spreads easily and sustain ably among humans.
The H5N1 virus amply meets the first 2 conditions:
It is a new virus for humans (H5N1 viruses have never circulated widely
among people), and
It has infected more than 100 humans, killing over half of them. No one will
have immunity should an H5N1-like virus emerge.
All prerequisites for the start of a pandemic have therefore been met save
one: the establishment of efficient and sustained human-to-human
transmission of the virus.
The risk that the H5N1 virus will acquire this ability will persist as long
as opportunities for human infections occur.
These opportunities, in turn, will persist as long as the virus continues to
circulate in birds, and this situation could endure for some years to come.
What changes are needed for H5N1 to become a pandemic virus?
The virus can improve its transmissibility among humans via 2 principal
mechanisms.
The first is a “re-assortment” event, in which genetic material is exchanged
between human and avian viruses during co-infection of a human or pig.
Reassortment could result in a fully transmissible pandemic virus, announced
by a sudden surge of cases with explosive spread.
The second mechanism is a more gradual process of adaptive mutation, whereby
the capability of the virus to bind to human cells increases during
subsequent infections of humans.
Adaptive mutation, expressed initially as small clusters of human cases with
some evidence of human-to-human transmission, would probably give the world
some time to take defensive action.
What is the significance of limited human-to-human transmission?
Though rare, instances of limited human-to-human transmission of H5N1
and other avian influenza viruses have occurred in association with
outbreaks in poultry and should not be a cause for alarm. In no instance has
the virus spread beyond a first generation of close contacts or caused
illness in the general community.
Data from these incidents suggest that transmission requires very close
contact with an ill person.
Such incidents must be thoroughly investigated but – provided the
investigation indicates that transmission from person to person is very
limited – such incidents will not change the WHO overall assessment of the
pandemic risk.
There have been a number of instances of avian influenza infection occurring
among close family members. It is often impossible to determine if
human-to-human transmission has occurred, since the family members are
exposed to the same animal and environmental sources as well as to one
another.
How serious is the current pandemic risk?
The risk of pandemic influenza is serious. With the H5N1 virus now
firmly entrenched in large parts of Asia, the risk that more human cases
will occur will persist.
Each addi¬tional human case gives the virus an opportunity to improve its
transmissibility in humans and thus develop into a pandemic strain.
The recent spread of the virus to poultry and wild birds in new areas
further broadens oppor¬tunities for human cases to occur.
While neither the timing nor the severity of the next pandemic can be
predicted, the probability that a pandemic will occur has increased.
Are there any other causes for concern?
Yes. Several.
Domestic ducks can now excrete large quantities of highly pathogenic virus
without showing signs of ill¬ness and are now acting as a “silent” reservoir
of the virus, perpetuating transmission to other birds. This adds yet
another layer of complexity to control efforts and removes the warning
signal for humans to avoid risky behaviors.
Compared with H5N1 viruses from 1997 and early 2004, H5N1 viruses now
circulating are more lethal to experi¬mentally infected mice and to ferrets
(a mammalian model) and survive longer in the environment.
H5N1 appears to have expanded its host range, infecting and killing
mammalian species previously considered resistant to infection with avian
influenza viruses
The behavior of the virus in its natural reservoir, wild waterfowl, may be
changing
The spring 2005 die-off of upwards of 6000 migratory birds at a nature
reserve in central China, caused by highly pathogenic H5N1, was highly
unusual and probably unprecedented.
In the past, only 2 large die-offs in migratory birds, caused by highly
pathogenic viruses, are known to have occurred: in South Africa in 1961
(H5N3) and in Hong Kong SAR in the winter of 2002–2003 (H5N1).
Why are pandemics such dreaded events?
Influenza pandemics are remarkable events that can rapidly infect
virtually all countries.
Once international spread begins, pandemics are considered unstoppable,
caused as they are by a virus that spreads very rapidly by coughing or
sneezing.
The fact that infected people can shed virus before symptoms appear adds to
the risk of international spread via asymptomatic air travelers.
The severity of disease and the number of deaths caused by a pandemic virus
vary greatly, and cannot be known before the emergence of the virus.
During past pandemics, attack rates reached 25-35% of the total population.
Under the best circumstances, assuming that the new virus causes mild
disease, the world could still experience an estimated 2 million to 7.4
million deaths (projected from data obtained during the 1957 pandemic).
Projections for a more virulent virus are much higher.
The 1918 pandemic, which was exceptional, killed at least 40 million people.
In the United States, the mortality rate during that pandemic was around
2.5%.
What will be its immediate impact?
Pandemics can cause large surges in the numbers of people requiring or
seeking medical or hospital treatment, temporarily overwhelming health
services.
High rates of worker absenteeism can also interrupt other essential
services, such as law enforcement, transportation and communications.
Because populations will be fully susceptible to an H5N1-like virus, rates
of illness could peak fairly rapidly within a given community. This means
that local social and economic disruptions may be temporary.
They may, however, be amplified in today’s closely interrelated and
interdependent systems of trade and commerce.
Based on past experience, a second wave of global spread should be
anticipated within a year.
As all countries are likely to experience emergency conditions during a
pandemic, opportunities for inter-country assistance, as seen during natural
disasters or localized disease outbreaks, may be curtailed once
international spread has begun and governments focus on protecting domestic
populations.
What are the most important warning signals that a pandemic is about to start?
The most important warning signal comes when clusters of patients with
clinical symptoms of influenza, closely related in time and place, are
detected, as this suggests human-to-human transmission is taking place.
For similar reasons, the detection of cases in health workers caring for
H5N1 patients would suggest human-to-human transmission.
Detection of such events should be followed by immediate field investigation
of every possible case to confirm the diagnosis, identify the source, and
determine whether human-to-human transmission is occurring.
Studies of viruses, conducted by specialized WHO reference laboratories, can
corroborate field investigations by spotting genetic and other changes in
the virus indicative of an improved ability to infect humans. This is why
WHO repeatedly asks affected countries to share viruses with the
international research community.
What is the status of vaccine development and production?
Vaccines effective against a pandemic virus are not yet available.
Vaccines are produced each year for seasonal influenza but will not protect
against pandemic influenza.
Although a vaccine against the H5N1 virus is under development in several
countries, no vaccine is ready for commercial production and no vaccines are
expected to be widely available until several months after the start of a
pandemic.
Some clinical trials are now under way to test whether experimental vaccines
will be fully protective and to determine whether different formulations can
economize on the amount of antigen required, thus boosting production
capacity.
Because the vaccine needs to closely match the pandemic virus, large-scale
commercial production will not start until the new virus has emerged and a
pandemic has been declared.
Current global production capacity falls far short of the demand expected
during a pandemic.
What drugs are available for treatment?
Two drugs (in the neuraminidase inhibitors class), oseltamivir
(commercially known as Tamiflu) and zanamivir (commercially known as Relenza)
can reduce the severity and duration of illness caused by seasonal
influenza.
The efficacy of the neuraminidase inhibitors depends on their administration
within 48 hours after symptom onset. For cases of human infection with H5N1,
the drugs may im¬prove prospects of survival, if administered early, but
clini¬cal data are limited. The H5N1 virus is expected to be sus¬ceptible to
the neuraminidase inhibitors.
An older class of antiviral drugs, the M2 inhibitors amanta¬dine and
rimantadine, could potentially be used against pandemic influenza, but
resistance to these drugs can develop rapidly and this could significantly
limit their effectiveness against pandemic influenza. Some currently
circulating H5N1 strains are fully resistant to these M2 inhibitors.
However, should a new virus emerge through reassortment, the M2 inhibitors
might be effective.
For the neuraminidase inhibitors, the main constraints – which are
substantial – involve limited production capacity and a price that is
prohibitively high for many countries.
At present manufacturing capacity, which has recently quad¬rupled, it will
take a decade to produce enough oseltamivir to treat 20% of the world’s
population. The manufacturing process for oseltamivir is complex and
time-consuming, and is not easily transferred to other facilities.
So far, most fatal pneumonia seen in cases of H5N1 infec¬tion has resulted
from the effects of the virus, and cannot be treated with antibiotics.
Nonetheless, since influenza is often complicated by secondary bacterial
infection of the lungs, antibiotics could be life-saving in the case of
late-onset pneumonia.
WHO regards it as prudent for countries to ensure adequate supplies of
antibiotics in advance.
Can a pandemic be prevented?
No one knows with certainty.
The best way to prevent a pandemic would be to eliminate the virus from
birds, but it has become increasingly doubtful if this can be achieved
within the near future.
Following a donation by industry, WHO will have a stock¬pile of antiviral
medications, sufficient for 3 million treat¬ment courses, by early 2006.
Recent studies, based on math¬ematical modeling, suggest that these drugs
could be used prophylactically near the start of a pandemic to reduce the
risk that a fully transmissible virus will emerge, or at least to delay its
international spread, thus gaining time to aug¬ment vaccine supplies.
The success of this strategy, which has never been tested, depends on
several assumptions about the early behavior of a pandemic virus, which
cannot be known in advance.
Success also depends on excellent surveillance and logistic capacity in the
initially affected areas, combined with an ability to enforce movement
restrictions in and out of the affected area.
To increase the likelihood that early interven¬tion using the WHO
rapid-intervention stockpile of antiviral drugs will be successful,
surveillance in affected countries needs to improve, particularly concerning
the capacity to detect clusters of cases closely related in time and place.
What strategic actions are recommended by WHO?
In August 2005, WHO sent all countries a document outlining recommended
strategic actions
For responding to the avian influenza pandemic threat
Recommended actions
Aim to strengthen national preparedness
Reduce opportunities for a pandemic virus to emerge
Improve the early warning system
Delay initial international spread and
Accelerate vaccine development.
Is the world adequately prepared?
No. Despite an advance warning that has lasted almost 2 years, the
world is ill prepared to defend itself during a pandemic.
WHO has urged all countries to develop preparedness plans, but only around
40 have done so.
WHO has further urged countries with adequate resources to stockpile
antiviral drugs nationally for use at the start of a pandemic. Around 30
countries are purchasing large quantities of these drugs, but the
manufacturer has no capacity to fill these orders immediately.
On present trends, most developing countries will have no access to vaccines
and antiviral drugs throughout the duration of a pandemic.
What is South Africa doing about it?
The Department of Health has held workshops on influenza pandemic at CDC
unit
There have been workshops by the NHLS.
“Viral Watch” is a programme that is ongoing by the national health
laboratory services to pick up the beginning of a pandemic in its early
stage.
The National department of health has fast tracked the process of
registering the drug Tamiflu for import into the country
The provincial CDC team has developed fact sheets, frequently asked
questions, intranet communication,
Conducted workshops for district teams as well as for EMRS.
The surveillance by the department of agriculture and veterinary sciences is
ongoing.
There are awareness articles in the newspapers on an ongoing basis.
The Disaster management team and the CDC with all stakeholders are to
develop a comprehensive plan for the influenza pandemic.
Meanwhile surveillance for early identification of cases, improved reporting
(flash reporting through operations center) and community awareness and
health education will commence.
Public are reminded to keep high personal hygiene Keep surroundings clean
and wash hands frequently.
