Science: Small, deadly, likes to travel

An age-old pig virus in Malaysia has begun killing humans. So what has provoked it to jump species now? By Charles Arthur
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Killing pigs in a pen may sound like a piece of simile, akin to shooting fish in a barrel. Except that in Malaysia and Singapore, killing pigs has become a necessary precaution to try to stop people dying. So far, the Malaysian army has killed almost 800,000 pigs as part of an eradication programme that takes in 1.2 million animals nationally.

The aim is to prevent the human death toll - 117 since 29 September - from mounting further. The cause is what the US Centers for Disease Control and Prevention (CDC) in Atlanta calls "a virus that is not like any we have ever seen before".

As with so many before it, the cause of the outbreak is a zoonosis - a disease passed from animals to humans. Zoonoses include the most deadly illnesses known to humans, a roll-call including Aids, the Black Death and the Ebola virus, to name only the most famous.

So does that mean that the new virus causing the deaths in Malaysia is equally deadly? So far, the answer seems to be no. Though the CDC is still studying it, it appears that human beings are, in the scientific term, a "dead-end host" for the virus - that is, it is not transmitted between people. (Unfortunately, the use of this term early in the outbreak of mad cow disease, or BSE, when cattle were termed dead-end hosts, led people to conclude, wrongly, that BSE could not be transmitted to people. Though it is not caused by a virus, BSE is a zoonosis.)

What intrigues scientists is why a virus will emerge from an animal carrier - known as a "reservoir" - to infect a human being at one time rather than another, and, more importantly, working out a way to predict or measure the likelihood of people infected with the virus then passing it on to others.

The Malaysian virus, dubbed "Nipah" (pronounced "nee-pa") after a badly affected pig-rearing village where it was first detected, is related, but not identical, to the Hendra virus. That was identified only in 1994, when an outbreak in Australia led to the death of 13 racehorses and a trainer. In both cases, the reservoir is thought to be fruit bats, but the entire genetic blueprint (genome) of Nipah differs from that of Hendra by about 20 per cent.

"It is quite different from the Hendra virus," says Dr Brian Mahy, director of the division of viral and rickettsial diseases at the CDC. "So we have to assume that if it has been in a reservoir, then it has been there a long time."

Dr Mahy is one of the CDC team who are investigating the new virus, having been called in by the Malaysian government three weeks ago. They have already established that it affects not just human beings and pigs, but also dogs and goats; a dog was found dying from the infection. That fact alone makes the virus remarkable. "Infecting several different species is unusual; we don't see many that do that," he says.

Even so, the likelihood is that since Nipah is so different from Hendra it must be very old, so people must have fallen ill with it in the past, according to David Onions, one of Britain's leading experts on zoonoses, who has spoken to the CDC team. "It has probably occurred before," he says, "but hasn't been noticed."

Indeed, zoonoses are nothing new. Ever since humans began domesticating animals such as cattle and dogs thousands of years ago, viruses have had increased opportunities to jump from one species of host to another. In many cases they cannot do so, or our defences fight them off easily. But in a few cases the reservoir animals (which may not even develop symptoms) can pass on viruses that acquire lethal effect in human beings.

Research published earlier this year showed that HIV, the human immunodeficiency virus that leads to Aids, has for thousands of years crossed and re-crossed between humans and primates (where it exists as SIV, simian immunodeficiency virus) in the central African jungles. The critical difference is that in this century international travel has allowed viruses to spread rapidly around the globe. In addition, rising populations have put increasing pressure on people in the Third World to encroach on tropical forests. This has inevitably brought them closer to the viruses of wild animals.

"There are two kinds of zoonosis," explains Professor Onions. "The first is where the human is a dead-end host - an infected person cannot pass it on to another. The worrying other kind is where we can transmit it to other people. If you want a nightmare scenario, and for some reason some people do, the most dangerous kind of zoonosis would be from somebody going on an exotic holiday, catching a new disease with a long incubation period, and then becoming a blood donor. However, it is not very likely."

Other examples of zoonoses include influenza, in which the more virulent forms (including the one that swept Britain earlier this year) often result from a "recombination", or mixing, of the virus genome within the reservoir population. "The thing about the influenza virus is that it has a segmented genome," says Dr Mahy. "It is broken up into eight parts, which can recombine in different orders in the reservoir animal to give more or less virulent forms. We can then catch it back, as in the case of `Asian flu'."

Pigs are almost the ideal host for viruses on the path towards zoonosis; they have many human-like characteristics, and even at the genetic level they share with human beings some strong similarities in their immune system. "They have [cell] receptors for both bird and human viruses," explains Dr Mahy.

Professor Onions points out that certain types of virus are well-adapted to changing or mutating rapidly, notably those that use RNA - a close cousin of DNA - as their genetic material. "The RNA viruses will change about one in every 10,000 nucleotides each time they reproduce. They also recombine very frequently. For flu [an RNA virus], pigs act like a mixing vessel for producing new forms of a virus."

The phrase for this phase is "amplification"; having recombined, the virus can then pass between different animals, until its infectivity and virulence are sufficient for it to make the hop to a new species, whose cell receptors and machinery will differ in various ways from their existing host. The crucial question then becomes: how effectively can the newly infected human being's immune system cope with the threat from this new invader?

In the case of Nipah, those who have so far died or been infected have all been adult men who were in close contact with pigs. It has also infected 11 abattoir workers in Singapore - all of whom had handled imported pig meat from Malaysia. Killing the pigs is thus seen as the simplest means of wiping out the infection - even though the primary reservoir is the fruit bat.

Zoonoses often have serious knock-on effects besides the illnesses they cause; the Nipah epidemic has wrecked Malaysia's pounds 250m pork trade, and hit the tourism industry - though the CDC advises that visitors are unlikely to be endangered as long as they stay away from pig-breeding regions.

But what about the future? Should we expect more deadly zoonoses to spring up as international travel comes to more and more countries, and humans push further into previously untouched jungle, and live closer to animals?

"[The idea of] zoonosis is a very anthropomorphic view of life," says Professor Onions. "There are diseases that pass from cattle to sheep; there are some that pass from humans to animals. There's a tendency to think that what happens to us is special. But from an evolutionary viewpoint there's nothing special about this time. The fact is that most diseases we see now were probably zoonoses at some stage in their development - and we're still here."

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