Information about the Coming Avian Influenza Pandemic

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Information about the Coming Avian Influenza Pandemic

 

A highly virulent and deadly new influenza virus strain is emerging in

Southeast Asia that is of great concern to health administrators and

infectious disease specialists. The new virus is called H5N1 avian

influenza virus type A. Many infectious disease experts think we are

on the verge of a major worldwide influenza pandemic of similar

severity to the 1918 Spanish Flu.

 

 

Infectious Disease Mortality, US 20th Century*

 

The impact of 1918 flu pandemic can be clearly seen as a spike up in

US mortality. *Armstong, etal. JAMA 1999;281:61-66

 

 

 

Pandemics are simply worldwide epidemics. During flu pandemics, a

higher than usual percentage of the population becomes infected and

more people die from these infections than during the usual annual flu

season. Pandemics occur because a new influenza virus makes its way

from birds or swine to humans resulting in a strain for which we have

very little immunity.

 

 

 

There are major pandemics and minor ones. Minor ones are more common

and much less severe than major ones, but still a lot worse than

routine flu outbreaks we experience each winter. All pandemics infect

many times more people than happens with the seasonal flu but during

major pandemics the death rates also soar into the tens of millions or

even higher.

 

 

 

I became aware of the potential threat of an avian influenza pandemic

last year. One of the most surprising things I learned was that

influenza pandemics are regular events. They have an almost

predictable periodicity of 3 per century. In fact, over the last 400

years there have been 12 flu pandemics recorded. Every 100 years or

so a major pandemic occurs that is so severe it dwarfs everything else

by comparison. The last one of these events was the Spanish flu in

1918.

 

 

 

During that pandemic, 5 to 10 times as many people as usual became

severely ill with flu, and many millions died from their infection.

The percentage of the population that becomes ill with flu symptoms is

known as the clinical attack rate. It is interesting to me that

studies of influenza antibody levels in people before and after

influenza epidemics reveal that the percentage of patients with blood

evidence of having had the flu is twice as high as the reported

clinical attack rate for the epidemic. In other words, for every

person who gets sick with the flu there is another person who

contracts the virus but has no or very few symptoms of the illness.

 

The medical term for the percentage of those who become ill who then

die is the case fatality rate. The case fatality rate hovers around

0.2% to 0.35% during the usual winter flu season. During minor

pandemics, this rate can increase up to 3 or 4 times but during a

major pandemic the case fatality rate is increased by 10 to 50 times.

 

 

 

Most flu experts predict that it is only a matter of time before the

virus becomes communicable between people, so that is really not the

burning question. According to the World Health Organization

guidelines for pandemics, as of September 2005 we are in Phase 3.

This places us in the Pandemic Alert Period and just one step away

from human-to-human spread that will be followed by a worldwide

pandemic.

 

 

Epidemics and Influenza Pandemics

 

 

 

An epidemic is defined as an infectious illness that spreads so

quickly that the number of new cases rises in an exponential manner

rather than just increasing linearly. This means that during

epidemics, the number of new cases doesn't just go up by ones or twos

each day. During an epidemic, the number of new cases doubles every

few days.

 

 

 

A pandemic is an epidemic that spreads across the globe affecting

every continent rather than being confined to one geographic area.

One of the most important reasons for influenza's success as a human

invader is its infectivity. The infectivity of an organism is

determined by how easily it is transmitted from one person to another.

Infecting agents that can cause illness after a small exposure are

more contagious than ones that require a larger exposure. Infectivity

is increased when infection can be passed between people without any

direct contact.

 

 

 

The most common way for flu to be transmitted is by breathing air

contaminated with virus. Coughing is how the virus gets into the air

in the first place. Flu can also be transmitted by direct contact

with someone ill with the disease. This includes shaking their hand

or even touching something that the sick person previously touched.

Under the right conditions, flu can remain infectious for days outside

of the human body, living on surfaces like counter tops or doorknobs.

Transfer of the virus can occur when a susceptible person touches a

contaminated surface.

 

 

 

After the virus is spread from one person to another, it can infect

the new person only if that person is susceptible or vulnerable to it.

With respect to influenza, virtually 100% of the human population is

susceptible to a new strain. However, fully half the susceptible

patients who contract the flu have no or few symptoms.

 

 

 

Influenza causes pandemics because it scores so highly in all these

causes of infectivity. These characteristics of influenza help

explain why this organism can quickly spread from one region of the

globe to another. Even during the relatively primitive travel

conditions existing in 1918 it only took 6 weeks for epidemic

influenza to spread from the US to Europe and Africa. Imagine how

fast the next pandemic virus will move across the globe given the many

thousands of passengers traveling internationally by air every day!

Taking this into account, the British Government's Health Protection

Agency predicts in their Influenza Pandemic Contingency Plan that once

the first case of pandemic flu reaches Hong Kong it will take only 2

to 4 weeks for the pandemic strain to arrive in the United Kingdom.

WHO Pandemic Phases May 2005

Interpandemic Period

 

 

 

Phase 1. No new influenza virus subtypes detected in humans although

there are some endemic in animals that have infected humans.

 

Phase 2. No new influenza virus subtypes detected in humans although

there are some subtypes that pose a substantial risk to human health

 

 

 

Pandemic Alert Period

 

Phase 3. Human infection confirmed with new sub-type but no or only

minimal human to human spread among close contacts only confirmed.

 

Phase 4. Small clusters with limited human-to-human transmission but

spread are highly localized, suggesting that virus is not well adapted

to humans.

 

Phase 5. Larger clusters but human-to-human spread still localized,

suggesting that the virus is becoming increasingly better adapted to

humans, but may not yet be fully transmissible (substantial pandemic

risk).

 

 

 

Pandemic Period

 

Phase 6. Pandemic: increased and sustained transmission in general

population.

 

 

 

Source: The WHO

http://www.who.int/csr/resources/publications/influenza/WHO_CDS_CSR_GIP_2005_5.p\

df

 

 

 

A feature of influenza pandemics not well appreciated generally is

that they occur in waves. The 1918 Spanish flu (H1N1) was associated

with three waves, while the 1957 Asian flu (H2N2) and 1968 Hong Kong

flu (H3N2) pandemics had two distinct waves each. The reason for this

wave behavior is not known, but some have speculated that it is due to

a change in the season of the year. The timing of a wave may also be

related to a genetic change or mutation in the new strain of influenza

virus. In past pandemics, the time between two waves was 3 to 9

months. A point to keep in mind about pandemic waves is that the

second wave can be much more severe than the first or third wave of

the series. During the 1918 pandemic, the deadly second wave was

responsible for > 90% of the deaths for the entire pandemic.

 

 

 

While the typical flu season predictably occurs from November through

March, during pandemics, flu can vary from this script. The first

wave of the 1918 flu occurred in the spring of that year ending in

March. That flu was very severe by usual standards but the second

wave beginning 6 months later in September was the most fatal. The

third wave occurred during the following winter/spring and was the

mildest of all. It is of note that pandemics end simply because all

or most susceptible persons within the population have contracted the

infection and have either died or developed immunity.

 

 

 

During pandemics, a major difference compared with seasonal flu that

is the highest death rates are among the healthy 20 to 30 year old

adults. This is in contrast with the seasonal flu that strikes the

very old, the young, and the infirm the hardest. Of course, the usual

victims of seasonal flu are not spared during pandemics. On the

contrary, death rates are much higher for every age and risk group

during pandemics compared with seasonal flu. The point here is that

the age 20 to 30 year group, usually immune to the ravages of seasonal

flu, experiences the highest death rates of any group during pandemic

years. Ironically, one possible explanation for this pandemic

observation may relate to the increased health and vigor of this

group's immune system.

 

 

 

 

What Makes the H5N1 Avian Flu so Fearsome?

 

 

 

The reason for the present state of alert among world health

authorities is the belief that we are witnessing the development of a

1918-type major flu pandemic in Southeast Asia - a once in a 100-year

major flu pandemic - due to the emergence of a H5N1 Influenza virus

type A.

 

 

 

On average there are two minor pandemics for every one major pandemic.

The minor pandemics are associated with lower clinical attack and

case fatality rates than in major pandemics. For instance, the 1957

pandemic was associated with three times as many deaths than seen for

seasonal flu but during the 1968 flu pandemic, there were only a few

more deaths than would be expected. It has now been 37 years since

the last flu pandemic, which suggests we may be due for another one soon.

 

 

 

What makes avian influenza H5N1 so troubling to the medical community?

It is its stunning killing ability, a statistic known as the

lethality of the disease. The 1918 flu, like most pandemics,

infected 40% to 50% of the world's population or approximately 640

million persons at the time. If we assume that approximately 80

million people died during the 1918 influenza pandemic[1], this

results in a case fatality rate of about 12.5% of those infected.

What is so worrisome to the influenza experts at the US CDC and WHO is

the case fatality rate for humans that become infected with the strain

presently brewing in Southeast Asia has been about 50%. This

overstates the true lethality to an unknown extent, as there may well

be a number of milder cases who have not come to the attention of the

health authorities. Nevertheless, these fatalities show what kind of

casualties the virus can cause.

 

 

 

Right now, the virus is confined mostly to birds, but has adapted to

tigers and pigs. Almost all the humans infected have had contact with

infected birds during processing, cooking, eating, caring for them, or

visiting the zoo in Jakarta, Indonesia. However, a few people are

thought to have caught the bird flu from close contact with infected

relatives. Close attention is being given for any sign that H5H1

avian influenza has become more efficient in person-to-person spread,

either from mutation or from swapping genes with another flu variety

in an infected person or animal. When this event occurs, a

development that influenza experts predict is imminent, the new viral

offspring would gain the ability to spread directly from

person-to-person. This development would signal the beginning of the

pandemic.

 

 

 

What was believed to be the first documented case of person-to-person

transmission of avian flu last year in Thailand was reported in the

New England Journal of Medicine.[2] That strain did not spread

further in people. However, as this is being written, in early fall

2005, a number of troubling cases of family clusters are being

reported in Indonesia.

 

 

 

If and when a bird flu virus that spreads well between people emerges,

we cannot be certain how lethal this new virus will be. It is not

likely to be as lethal as native H5N1 avian flu has been to the people

who have caught it from birds, but will probably be a lot worse than

routine seasonal flu. While no one can predict this in advance, it

seems logical to assume that there is 1 in 3 chance that the offspring

virus will have a worldwide clinical attack rate of 35% and 50% and a

case fatality rate of 3% to 10%. If this proves to be the case, the

effect on humanity and society will be traumatic in ways thought

impossible today in light of advances in technology and medicine since

1918.

 

 

 

In the opinion of Dr. Michael Osterholm, PhD,[3] writing in the New

England Journal of Medicine, the most likely scenario if we have a

major pandemic, is for an event that approximates the death toll seen

during 1918 Spanish Flu.[4] On the other hand, if reassortment of

H5N1 avian flu with human influenza results in a pandemic of the minor

variety this would not represent a dire threat to humanity or lead to

any significant disruption in our social or economic life.

 

 

 

Right now, we are dealing with probabilities and expert estimates. It

seems there is a 1 in 3 chance the next pandemic will be of the major

variety. Estimates by government agencies tend to focus on the hoped

for 2 in 3 chance that the next pandemic will be of the minor

variety.[5],[6] No doubt these sanguine estimates are affected by

government policies, politics, and fears of upsetting the public.

 

 

 

These influences may explain why the government prediction for the

clinical attack rate is at the low end for pandemics, and why the

predicted case fatality rates are the same as those seen during

seasonal influenza. Higher and more realistic morbidity and mortality

estimates are beginning to emerge in the press and in television and

radio interviews of influenza experts. Tommy Thompson, then Secretary

of the US Department of Health and Human Services, made an interesting

comment at a news conference he gave just before departing his office

in early December 2004. He said that one of the things he was very

concerned about was a worldwide influenza pandemic that could result

in the deaths of 30 to 70 million people. Officially, however, the

government is standing by their rosy scenarios.

 

 

A Comparison of Estimates for Influenza Pandemic Mortality and Morbidity

 

 

 

When trying to project the effect of a pandemic, the key statistics to

predict are the case fatality rate and the clinical attack rate. This

is because the death rate during a pandemic is the simple arithmetic

product of these two rates. The formula for the number of deaths due

to a pandemic is:

 

 

 

Number of Deaths = Case Fatality Rate x Clinical Attack Rate x

Population Size

 

 

 

Where: Deaths is the number of people who die, the Case Fatality Rate

is the percent of patients with the illness who die from the illness,

and the Clinical Attack Rate is the percentage of the population who

develops influenza with symptoms of infection. The number of deaths

increases as either one of these key pandemic statistics increases.

 

 

 

Pandemic years are associated with many more cases of influenza and a

higher case fatality rate than that seen in seasonal flu outbreaks.

It is common to encounter clinical attack rate ranges for seasonal flu

of 5% to 15% in the literature. For pandemic flu, clinical attack

rates are reported in the range of 25% to 50%. Case fatality rates

are more difficult statistics to come by. They are available for

recent pandemic and seasonal flu in the developed nations, but

unavailable for past pandemics and present seasonal flu in undeveloped

nations. The most reliable pandemic statistic is the number of deaths

for the developed nations. The number of worldwide dead due to the

1918 pandemic was initially reported as 20,000,000. The most recent

estimate of worldwide deaths during the 1918 pandemic is 60,000,000 to

100,000,000. It is of interest that despite being replaced by

estimates using improved epidemiologic methods and better data, the

discredited earlier statistics are often used in modern day

publications on pandemics and even within otherwise authoritative

government or scientific reports.

 

 

 

In the US, the Department of Health and Human Services has prepared a

draft US Pandemic Influenza Preparedness and Response Plan that was

published in August 2004. In this planning document, the DHHS also

provides predictions on flu morbidity and mortality that they state

are likely to occur during the next pandemic.5 These estimates can

be extrapolated to the world as a whole.

 

US DHHS Mortality and Morbidity Estimates for the US and Worldwide for

the Next Pandemic*

 

US Population 2005 = 296,000,000

 

World Population 2005 = 6,600,000,000

 

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*Adapted from the US Pandemic Influenza Preparedness and Response

Plan: - DRAFT Aug 2004

 

 

 

Inspection of the US DHHS projections reveals that these calculations

have used the case fatality rates seen during seasonal influenza in

the US, which are far lower than those seen in either minor or major

pandemics. In my opinion, this greatly weakens the credibility of

the US estimates. If the US DHHS is actually using these predictions

as the basis for their pandemic planning, I fear that we will be

woefully unprepared.

 

 

 

For comparison, let's turn to Osterholm's recent New England Journal

of Medicine article on influenza. Using a range of estimates of case

fatality and attack rates, he calculates the number of deaths the US

and world could expect from the next pandemic if it is equal in

severity to the 1918 pandemic.4

 

 

 

Osterholm used the simple expedient of extrapolating the same death

rates observed during the 1918 pandemic to the present adjusted for

the increase in population. For the worldwide death number, his range

of 180 million to 360 million is based on the current best estimate of

world deaths during the 1918 event of 60 to 100 million deaths.

 

 

 

 

Osterholm's Pandemic Case Fatality Rate Prediction for the US

 

To see chart go to:

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Osterholm's Pandemic Case Fatality Rate Prediction Worldwide

 

World Population 2005 = 6,600,000,000

 

Case Fatality Rate

 

Prediction

 

To view chart go to:

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I conclude that the method used by Osterholm provides a more reliable

estimate of the likely impact of the next pandemic than those provided

by the government sources. Therefore it makes more sense to rely on

Osterholm's predictions as the best guide for what to expect if we

experience a major pandemic. If the next pandemic is of the minor

variety, then there is little chance for any major disruption of civil

society or any of its institutions. This is not to say that the

number of deaths will be inconsequential, or that the medical systems

worldwide will not experience temporary overcapacity and shortages.

But this is not the issue and never has been. The critical issue is

not how to cope with a minor pandemic but rather how to cope with a

major event. That is the focus of this guide. Preparing you for this

possibility is my goal.

 

 

 

In my view, the gross underestimate of the impact of the next pandemic

on the US by the Department of Health and Human Services suggests a

number of unsavory possibilities. Since they have access to the

best-educated and brightest epidemiologists and medical scientists,

the reason for their less than robust prediction is not for lack of

information or analytic ability. Suffice it to say that their

performance so far does not bode well for them being a reliable source

of information as the pandemic progresses.

 

 

 

It is likely that the forces and motives operating within the US

Government that lead to this treatment of the truth are shared by

other national governments as well.