Scheming 鈥榮hapeshifter鈥 flu is always one step ahead
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On a March morning 100 years ago, a soldier in Kansas reported to the infirmary with a fever, muscle aches and a sore throat.
By lunchtime, records state, dozens had joined him, stricken with what would become known as the Spanish Flu.
Within months, the virus infected a third of the world鈥檚 population and killed as many as 100 million people.
It could happen again.
While the scale of the 1918-19 flu epidemic remains unparalleled, another pandemic is inevitable, experts say.
Given the limitations of available drugs, flu-triggered respiratory diseases can claim up to 650,000 lives even in a non-pandemic year.
About a third of people infected have no symptoms, but some 3 to 5 million fall severely ill with the flu every year, a heavy economic burden in terms of medical care and lost productivity.
Drift and shift
Why does this common and familiar virus remain a threat after decades of study and massive medical advances that have eradicated the smallpox virus and severely hamstrung malaria and polio?
鈥淚nfluenza A is the archetypal shapeshifter,鈥 molecular virology professor Jonathan Ball of the University of Nottingham said.
This is the species that causes most human outbreaks.
Unlike many other viruses, the flu germ exists in dozens of sub-types of which two, H1N1 and H3N2, currently circulate in humans.
Each of these can be further sub-divided into many different strains, with new ones emerging all the time 鈥 each needing its own vaccine.
Vaccines work by mimicking an infection 鈥 exposing the body to a germ, but in a weakened, non-sickening form.
When confronted by a viral intruder, the immune system takes a few days to produce an array of assault weapons, including antibodies.
After vanquishing the virus, antibodies hang around in case the same germ comes back later, prepared for a faster counterattack the second time around.
But the flu virus has evolved to evade detection by patrolling antibody 鈥渟oldiers.鈥
Its first and most common strategy is called 鈥渁ntigenic drift鈥 鈥 tiny genetic changes that occur as the virus replicates, rendering it ever so slightly different each new flu season.
The second, much rarer technique, is called 鈥渁ntigenic shift鈥 and is what causes deadly pandemics every few years or decades.
This happens when genetic material is exchanged between Influenza A subtypes 鈥 sometimes a mix between animal and human viruses 鈥 to concoct a brand-new strain to which few people, if any, have immunity.
Since the Spanish Flu, three much less deadly pandemics were caused in this way: the Asian Flu in 1957, the Hong Kong Flu in 1968 and the so-called Swine Flu outbreak in 2009.
The flu virus has another evolutionary edge too.
Unlike smallpox, polio, or measles, it has a natural home in nature 鈥 in birds which live all around us.
And it can cross the species barrier, also into pigs and horses, with relative ease.
Because they lack an animal 鈥渞eservoir,鈥 with widespread vaccination, we could eradicate polio and measles like we did smallpox, explained virologist David Evans of the University of St Andrews in Scotland.
鈥淲e will not be able to eradicate the flu because we will be continuously exposed to it. We, the human population, are going to be continuously exposed to new strains of influenza... every few years, every few decades, probably forever,鈥 said Evans.
Taken together, these factors predict that 鈥渢here will be another pandemic,鈥 according to flu expert Wendy Barclay of Imperial College London.
鈥淗ow dangerous and how many deaths (it) will cause depends on the exact virus and the way it evolves,鈥 she said.
Of course, we have antibiotics today to treat secondary infections with opportunistic bacteria that cause diseases such as bronchitis or pneumonia that were the main cause of flu-related death in 1918, and still are.
鈥淣onetheless, the outbreak could be very bad,鈥 if it happened today, said Barclay.
Could we ever conquer the flu? Probably not with any known strategy, the experts said.
Many hope for a 鈥渦niversal鈥 vaccine that could tackle the core of the flu virus, looking beyond its external disguise.
This would protect against different subtypes, and for a longer period of time.
Several universal vaccines are being tested, but 鈥渨e don鈥檛 know which, if any, will succeed,鈥 said Ball.
Antiviral drugs such as Tamiflu do exist to treat symptoms, but are expensive and not universally effective, the analysts added.
The predicament is certainly not for want of trying.
鈥淚t (the flu) is, one of the best studied of all viruses, without a shadow of doubt, and it鈥檚 one of the best understood,鈥 said Evans.
鈥淏ut partly what we鈥檝e learnt is that it鈥檚 very difficult to control.鈥
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