The mutating world of a killer virus
Experts worry that the virus has mutated to a higher virulence. Indeed, all the Sars viruses that have been sequenced by scientists (one each from Toronto, Hanoi, Bangkok and Singapore, and two from Hongkong) already show some differences.
The mutating world of a killer virus
By Andy Ho, The Straits Times, Singapore, April 22, 2003
LAST week, the World Health Organisation (WHO) said that Sars could become a global epidemic if it 'maintains its present pathogenicity and transmissibility'.
It hedged that predictions were problematic 'until we understand what is going on in China', but those statements nevertheless sent more jolts of fear into an already nervous world.
Pathogenicity, or the power of an organism to produce disease, is thought of as follows: If newly-infected Sars patients infect, on average, fewer than one person each, fewer and fewer people will be infected with each round of infection. If this 'basic reproductive number' is less than one, an outbreak cannot sustain itself and will burn itself out.
If the number exceeds one, however, the disease involves ever bigger numbers, as in Hongkong and Canada, where Sars is still spreading.
Still, it is of some comfort that the number of cases (outside China) is increasing arithmetically, not geometrically. So far as we know, the outbreak is not growing exponentially out of control.
How many people get infected depends on: First, how many times a Sars case comes into contact with healthy persons; second, how likely it is to be transmitted each time ('transmissibility'); and, third, when and for how long a case actually sheds the virus and so is infectious.
All these together cause the disease, but what people fear is death.
The Sars mortality rate is said to be about 5 per cent, compared to 20 per cent for the 1918 flu pandemic. Dr Henry Niman, a bioengineering professor at Harvard, has however challenged the Hongkong authorities, pointing out that this is wrong because the mortality rate is really the number who die from Sars divided by the 'population of interest' or the total number of cases with known outcomes, that is, those who either die or are discharged - not those still in hospital whose outcomes are yet unknown.
Thus, if 30 are diagnosed with Sars and three die, while seven are discharged but 20 remain hospitalised, the death rate is 3 divided by (3+7), or 30 per cent, rather than 3 divided by 30, or 10 per cent.
If so, on April 19, say, the mortality rates were actually as follows: Singapore 13.8; Hongkong 18.2 ; Canada 18.2; Vietnam 9.8 per cent.
For Singapore, between April 10 and April 19, the mortality rate fluctuated between a low of 10.7 and a high of 15.0 per cent.
What these figures show is that Sars pathogenicity is not as low as it might first appear, although transmissibility appears low since the virus is, as far as is known, not airborne like flu.
The Amoy Gardens case in Hongkong, in which 321 cases erupted almost simultaneously, is a worrying exception. Patients have a more severe illness, with more younger persons afflicted and showing more unusual symptoms, like diarrhoea. Experts worry that this might mean the virus has mutated to a higher virulence.
Indeed, all the Sars viruses that have been sequenced by scientists (one each from Toronto, Hanoi, Bangkok and Singapore, and two from Hongkong) already show some differences.
RNA viruses mutate a million times faster than human cells and, compared to DNA, there is little proof-reading and repair of RNA after duplication so this is an error-prone process.
Because coronaviruses have the largest RNA genomes, their potential for mutation is so large that no two coronavirus particles are genomically identical.
We used to be told that electrons orbited around an atom's centre like planets around the sun. Later, because we did not know for certain where electrons were at any one moment, we were told to think of them as a probability cloud around the nucleus.
In the same way, Sars' possible genomes form a cloud-like probability space around some unchanging genes.
It is this cloud of closely-related mutants that evolves rather than a single variant, so mutations that enable the virus to infect cells accumulate to reach a maximum very quickly.
Theoretically, after that point, mutations that lead to lower pathogenicity will accumulate so that the virus does not kill off its host. The virus survives in hosts that learn to carry it without becoming ill or killed.
To reduce the number of wild European rabbits that were invading farms across Australia, health authorities introduced the myxoma virus. In the early 20th century, the bug killed off the bunnies in 10 days. Fifty years later, however, the weakened virus needed four weeks.
So infected rabbits stayed infective three times longer, permitting the virus to spread further afield and, over time, become the prevalent strain.
Rabbits that developed resistance survived to have offspring with inherited resistance so that in a few generations, immune rabbits also became prevalent.
The lesson: Viruses tend to become weaker over time, for if they remain highly virulent, their hosts would be killed off and they themselves would perish too. By developing weaker strains over time, viruses ensure their own survival.
Historically, 'new' microorganisms emerge and cause an epidemic, until at some point in time when they seem to disappear. Seem to, because they linger around quietly - until mutations produce a new outbreak.
The best studied coronavirus is the one that causes infectious peritonitis in cats, which are killed in an outbreak but are otherwise carriers between epidemics.
The Sars virus could later enter that state, WHO authorities suggested last week.
For now, however, with good isolation of cases and quarantine of contacts, the number of infectious people out there will be the key in determining whether a pandemic occurs. In this respect, China is the wild card.
On April 20, when Canada shut its largest trauma unit in Toronto's Sunnybrook Hospital, its head of infection prevention control, Dr Mary Vearncombe, said: 'I have no optimism it can be contained in places like China. It will still be imported (here).'
Last week, WHO said that while Vietnam appears to have controlled Sars, it still faces the threat of massive importation from China, so their 1,130 km of shared borders might have to be sealed.
Things may be changing, though. China's Health Minister was sacked over the weekend and Beijing admitted that its case load was 10 times higher. Now that China is coming clean, experts might get a better grip on the situation.
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