Risk Wise

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Influenza: how to blunt the Damocletian sword

Professor Albert Osterhaus, DVM, PhD, Head, Department of Virology, Erasmus MC, Rotterdam

nfluenza in humans comes in three different forms: seasonal,

avian, and pandemic influenza. Although these three human

disease entities are all caused by infection with an influenza

virus, there are principle differences in their causative agent,

disease manifestation and degree of spreading from human to

human.

Annually recurring seasonal influenza is caused by an influenza virus

of the A or B type and besides being responsible for a huge burden of

disease, causes the deaths of about 400,000 people worldwide every

year. Avian influenza in humans is caused by sporadic zoonotic trans-

missions of avian influenza A viruses from birds to humans. The highly

pathogenic avian influenza A virus of the H5N1 subtype (HPAI-H5N1),

that currently circulates in many areas of Eurasia and Africa in an

unprecedented way, has caused the deaths of more than 60 per cent of

the more than 400 reported sporadic human cases to date. Avian

influenza is not or very rarely transmitted from human to human. If

however an avian influenza A virus does acquire the possibility to effi-

ciently spread from human to human, it becomes a real human

pandemic virus and an influenza pandemic becomes reality: the virus

spreads worldwide within a relatively short period of time.

Influenza pandemics in the 20th century varied from

severe to moderate with the 1918-1919 pandemic

(‘Spanish flu’) alone killing more than an estimated 50

million people. The subsequent influenza pandemics of

1957 (‘Asian flu’) and 1968 (‘Hong Kong flu’) were less

severe, but still have each killed millions of people.

Although the three influenza pandemics of the last

century together have cost the lives of 50 to 100 million

people, it should be realized that the cumulative number

of deaths caused by the annually recurring seasonal

influenza epidemics worldwide is in the same order of

magnitude. So, it may be estimated that the different

forms of influenza have cost the lives of more than 100

million people in the past century.

Probably the most intriguing question today is

whether the world will face another influenza pandemic

and if so, when will it happen, what avian influenza

virus will be at its basis, and how severe will it be? The

answer to the first question is that the re-emergence of

an influenza pandemic is just a matter of time and

should therefore rather be considered a matter of when

than of if. This is based on the current knowledge of the

mechanisms underlying the development of pandemic

influenza viruses.

To become a pandemic virus, an avian influenza A

virus should not only be pathogenic to humans, but

should also transmit efficiently from human to human.

The pathogenicity of a future pandemic virus will to a

large extent be determined by the avian virus that will

be at its basis. After crossing the species barrier to

humans, an avian influenza virus may acquire trans-

missibility between humans by either of two

mechanisms. The first is the result of combining genetic

material of the avian and a mammalian influenza virus

that is already present in humans or other mammalian

species. The second mechanism is the result of sequen-

tial mutation of an avian influenza virus that repeatedly

crosses the species barrier from birds to humans. The

former mechanism was at the basis of the last two

pandemics, the Asian flu and the Hong Kong flu,

whereas the latter was probably involved in the gener-

ation of the Spanish flu virus. There is absolutely no

reason to believe that the generation of yet another

pandemic influenza virus by either of these two mech-

anisms will not happen again, and the frequently

reported zoonotic transmissions of avian influenza A

viruses of different subtypes to humans in the last

decade, often with fatal consequences, clearly highlights

Vaccination is the most cost-effective medical intervention to combat

seasonal influenza