杏吧原创

CHARLIE GIBBS never knew what hit him. The 56-year-old insurance claims adjuster didn鈥檛 notice when a mosquito took a drink of his blood one day last summer, but the event turned his world upside down.

鈥淚 used to walk two miles a day. I played golf. I liked to work in the garden,鈥� he recalls. These days Gibbs, who lives in Clinton, Mississippi, uses a walking frame, grateful that he can walk at all. Only nine months ago his legs and arms were completely paralysed. And for the first month he was ill, he couldn鈥檛 even recognise Kathy, his wife of 33 years.

While his frightened family stood by, doctors struggled for two-and-a-half weeks to figure out what catastrophe had befallen him. Was it a stroke? Or the mysterious Guillain-Barr茅 syndrome, an inflammation of the nervous system that can cause sudden paralysis? But both brain and body scans checked out fine. Then the results of nerve conduction tests made everyone sit up and take notice 鈥� including researchers at the CDC, the US Centers for Disease Control and Prevention in Atlanta. Neurons called anterior horn cells in Gibbs鈥檚 spinal column showed severe damage, clear evidence of poliomyelitis. Except that Gibbs didn鈥檛 have poliovirus. No one has had it in the US for years. Instead, he had West Nile virus.

It was an unexpected diagnosis, but not inconceivable. While poliomyelitis is most closely identified with poliovirus, it can be triggered by other less well-known viruses as well. When the CDC announced the first six cases of West Nile poliomyelitis last autumn, the realisation that this virus could well be the 鈥渘ew polio鈥� began to sink in.

It鈥檚 not just that West Nile can attack the same areas of the nervous system and cause paralysis soon after infection like poliovirus that is concerning. It鈥檚 what could happen years from now. Poliovirus, it turns out, can have a devastating second act. Decades after recovery, survivors 鈥� including those who suffered only mild symptoms, with no poliomyelitis 鈥� can find themselves battling the painful legacy of a ravaged nervous system. The fear now is that there could be a similar time bomb ticking away unnoticed in the bodies of West Nile victims. If West Nile is close enough to poliovirus to cause poliomyelitis, perhaps it can cause these long-term problems too.

Poliovirus infections were first described centuries ago but it is only in the past 20 years that researchers have started to understand the long-term consequences. In a typical case, 50 per cent of the neurons serving the muscles (called motor neurons), are destroyed. Another 45 per cent can suffer serious damage but will eventually rebuild themselves. Neurons producing the neurotransmitter dopamine, which is critical for brain function, also take a severe hit. Over time, the surviving neurons will sprout extra dendrites and take over the job of the lost neurons. Richard Bruno, director of the Post-Polio Institute at Englewood Hospital in New Jersey says: 鈥淭here were people who had paralytic polio who could not move a muscle 鈥� patients who were in iron lungs 鈥� and a month later they could walk out of the hospital. It just shows you the incredible amount of redundancy in the system.鈥�

Everyone starts out with far more neurons than they need, so they can handle a lifetime of loss due to normal wear, tear and ageing. Problems set in if you run out of neurons before you run out of life. It is essentially a numbers game, explains Bruno

Even when the immune system has eradicated poliovirus, the damage remains, masked by neurons doing extra duty to make up for those that were killed. But these overworked neurons will eventually begin burning out. Add that complication to normal wear and tear and decades after the initial infection, a suite of other symptoms can set in: fatigue, weakness, cognitive problems, joint and muscle pain, trouble with breathing, swallowing, and sleeping. These are dubbed 鈥減ost-polio sequelae鈥� (PPS). Since the dead neurons are gone for good, there is no cure 鈥� although physical and psychological therapy can help patients cope.

Worryingly, PPS, which can take 30 to 40 years to appear, can hit any survivors no matter how mild their original infection. According to a 1987 survey by the US Public Health Service, there were 1.63 million polio survivors in the US. Nearly one-third of those with the less severe non-paralytic polio reported late-onset symptoms. Survivors of paralytic polio are even more likely to experience PPS, so there may be hundreds of thousands of cases, just in America. Worldwide, the WHO estimates there may be as many as 20 million polio survivors, mainly in poor countries where vaccination programmes have lagged behind those in the West. So what of West Nile? Could a tussle with this virus, even a mild one, eventually lead to 鈥減ost-West Nile sequelae鈥�?

West Nile made US headlines when it was discovered in New York City four years ago. But scientists first described the virus in 1937 after finding it while screening Ugandan patients for sleeping sickness. When it appeared in Egypt 13 years later, studies showed that most adults in the region had antibodies. So did most of the camels, horses, water buffalo and birds, a sign of widespread exposure. Aside from causing mild fever and headaches in children, the virus didn鈥檛 seem much of a problem. But there are two lineages of West Nile, occurring throughout Africa, western Asia, the Middle East and parts of Europe. The strain in North America seems to come from a more virulent branch of the family tree.

Exactly how West Nile, a mosquito-borne flavivirus whose primary hosts are birds, got into North America isn鈥檛 known. But since 1999 it has raced across the continent, from the Atlantic to the Pacific, and from Canada to El Salvador (see Map), infecting nearly 200 species of birds, mammals and reptiles along the way. So complete has the invasion been that last December the US Department of Agriculture quietly changed the disease鈥檚 status from 鈥渇oreign鈥� to 鈥渆ndemic鈥�.

Like poliovirus, West Nile can cause a range of symptoms. Those worst hit get meningoencephalitis, an inflammation of the brain and spinal cord, as well as poliomyelitis, we now know. But for every meningoencephalitis patient there are 30 cases of West Nile fever, a flu-like illness causing headache, stiff neck and fever. Often there are barely any symptoms at all, and the vast majority of cases are never diagnosed.

Warning signs

As yet it is too soon to know if the long-term effects of West Nile will mimic those of poliovirus. But already there are warning signs. Recovery patterns for the two viruses are remarkably similar. A study tracking the first group of US meningoencephalitis patients in 1999 found that more than half still had problems with fatigue, weakness, memory loss or depression a year later. Denis Nash, an epidemiologist with the New York City Health Department says patients didn鈥檛 improve much between 12 and 18 months, after which the follow-up stopped. Recovery from poliovirus also tends to plateau at about a year.

What鈥檚 worse, patients who only had West Nile fever aren鈥檛 bouncing back so fast either, notes Mike Bunning, an epidemiologist with the CDC who has been studying several dozen cases from an outbreak in St Tammany Parish, Louisiana, last year. 鈥淭hey鈥檙e complaining upwards of a month later that they鈥檙e still not feeling right 鈥� they still have memory lapses and fatigue, and we鈥檙e a little surprised by that.鈥� In fact, some may be suffering from cases of mild meningoencephalitis. But the test, a spinal tap to sample nervous-system fluid, is usually only given to the sickest patients. Again, the parallels with polio are striking: not all poliovirus infections result in poliomyelitis, but all cause some brain inflammation, even the mild cases.

If it turns out that a bout of West Nile can lead to late-onset symptoms, too, then North America is sitting on a time bomb. After studies where people living in at-risk areas were interviewed and had blood tests following outbreaks researchers believe that for every case of meningoencephalitis, about 150 people are actually infected with the virus. So last year鈥檚 North American tally of 2700 confirmed meningoencephalitis cases translates to roughly 400,000 infections 鈥� including 80,000 cases of West Nile fever, which may leave people more at risk of late-onset symptoms. There are sure to be more. While trials of a vaccine are due to begin in the autumn, even if all goes well it is likely to be several years before the vaccine is licensed.

Most cases are never diagnosed. Last year, only 1162 cases of West Nile fever were reported 鈥� a little more than 1 per cent of the likely total. Because fever patients sustain at least some neurological damage, they could be at risk of late-onset symptoms. Although the incidence of West Nile infection is equal across all age groups, serious illness goes up with age, which may be due to weaker immune systems. Perhaps the most under-reported group is children, and only a handful of cases in people under 20 have been reported. Why? It could be that young people have more neurons, which may allow them to bounce back faster. A mild case of West Nile 鈥� a stiff neck and fever for a day or two 鈥� could easily be chalked up as just another childhood infection. The question is whether any damage will appear over time.

There may be a way to predict the future: bird-watching. Watching other animals works too. Veterinary pathologist Tracy McNamara, whose work on sick birds at the Bronx Zoo helped identify US West Nile in 1999, says: 鈥淚f you鈥檙e worried about diseases that can affect both animals and people, then the animal disease data is more important than the human.鈥� If you wait for the first human case to be diagnosed, you can lose critical time. Crows started dying six weeks before people began showing up at hospitals in 1999.

Likewise, the animals may be able to tell us the longer-term consequences of West Nile infection, including whether we should expect post-West Nile sequelae. Early indications are that the virus may persist for many months after the initial infection at least. Take the Indian rhino that died at Bronx Zoo in the summer of 2000. The immediate cause of death was bad aim 鈥� he鈥檇 managed to toss a log in the air, which broke his neck on the way down 鈥� but a post-mortem revealed deeper problems. Although he had recovered from a mild case of West Nile the previous autumn, his brain was riddled with inflammation. 鈥淲e should have just had evidence of a previous infection,鈥� says McNamara. 鈥淭his looked like it could have happened yesterday.鈥� And then hooded cranes, which tested positive for the virus but had never shown any symptoms, had evidence of encephalitis on post-mortem.

Unlike people, zoo animals are regularly examined and, after death, dissected, which makes it much easier to chart the complete course of their diseases. So two years ago the CDC set up the Zoo Network, now 130 institutions strong, to take advantage of this ready-made surveillance opportunity for West Nile. The researchers have found that animals may be completely asymptomatic, or may have balance problems, tremors, disorientation, impaired vision. Post-mortems reveal major neuron death in the brain, spinal cord, and peripheral nervous system.

Meanwhile, pathologist Robert Tesh at the Center for Tropical Diseases at the University of Texas in Galveston, has found evidence of persistent low-level infection in the brains of golden hamsters inoculated with the West Nile for drug and vaccine tests. After the first week, the hamsters started to look droopy, then developed tremors, balance problems and paralysis. Half the young adults died, but the other half appeared to recover, though showed signs of residual weakness. Tesh killed the survivors a few at time and examined them. Persistent infection was still evident almost two months later when the experiment ended.

It鈥檚 not the first time West Nile has been fingered as a persistent infection. According to a 20-year-old study at the then Soviet Academy of Medical Sciences in Moscow, this occurred in rhesus monkeys infected in the lab 鈥� even ones with no symptoms.

A persistent low level of infection might help explain cases of encephalitis both in zoo animals that recovered, as well as in animals that tested positive but never showed any early signs of illness, speculates McNamara. Lingering West Nile virus might trigger the immune system to go into overdrive, similar to what happens with post-measles encephalitis. And if that sort of thing happens in animals, then there is a real danger that West Nile could cause problems months after infection in people, too. A case of meningoencephalitis diagnosed in January might be due to a mosquito bite the previous August.

So can the animals also tell us whether or not North America is facing a time-bomb of West Nile sequelae 20, 30, 40 years from now? The best hope for answering this question comes from an ongoing study of 4000 baboons, rhesus macaques and pigtail macaques living in outdoor breeding colonies at the Tulane National Primate Research Center in St Tammany Parish, Louisiana. After dead birds showed West Nile was in the area in autumn 2001, the staff collected blood samples from 1700 animals. All tested negative. By next June the first mosquito carrying the virus was trapped on the property. A week later the epidemic 鈥渂asically exploded,鈥� recalls Andrew Lackner veterinary pathologist and centre director. By the end of the summer 36 per cent of the monkeys tested positive.

So far, no signs of illness have been detected in the monkeys, but a headache, mild fever or stiff neck lasting a day or two probably wouldn鈥檛 be noticed, says Lackner. Most of the monkeys in a breeding colony are young and, presumably, neuron-rich. A five-year-old macaque is equivalent to a 25-year-old human. So we will have to wait a few years to find out whether they are going to develop any late-onset symptoms.

In its first three seasons, West Nile conquered North America, attacking everything from crows to people in their tens of thousands. The question now is how deeply into the future its effects will be felt.