When colds kill

Section:
Features
Colds are usually just a nuisance but last year a new strain killed at least 140 people. Is the common cold getting
nastier?
IN APRIL last year, Paige Villers was finishing basic training at Lackland Air Force Base in Texas when she came
down with a cold. She struggled to shake it off. Then came a prolonged battle with pneumonia, followed by an
immune over-reaction that killed her.
"She had symptoms that just looked like a cold or the flu," Villers's mother told reporters. "You hear of people dying of
pneumonia, but it's usually older people. Not a 19-year-old in the prime of her life."
It turned out that Villers had been infected by an adenovirus, a family of viruses that normally causes no more than a
common cold. But this virus was a nasty new strain called Ad14, which killed at least 140 people in the US in 2007.
The real toll may well have be much higher, as the viruses behind such deaths are rarely diagnosed.
The emergence of Ad14 - and the surprising turn it took this year - is a sharp reminder that a harmless cold is not the
only possible outcome of the constant battle between people and respiratory viruses. There can be others.
Even before the discovery of Ad14, interest in cold viruses had revived, partly thanks to new technologies that make it
much easier to study them. What biologists have been uncovering is both surprising and disturbing. "It is increasingly
clear that these viruses can kill," says Sebastian Johnston of Imperial College London.
The common cold is just that: common. We breathe in 15,000 litres of germ-laden air every day, says Ron Eccles,
head of the Common Cold Centre at Cardiff University in the UK. "The respiratory system is constantly under attack."
While the respiratory system does have formidable immune defences, a slew of viruses are staying one step ahead in
the arms race. They cause acute upper respiratory tract infections, aka the common cold. Adults typically have two to
four colds a year, while young children have six to ten.
Astonishingly, we have no idea how many viruses lie behind such infections. More than 200 members of nearly a
dozen families of viruses are known to cause colds, but it is becoming clear that many more are out there.
The reason for our ignorance is that the traditional method for identifying cold viruses is to grow them in culture.
Doctors take a sample of mucus - snot - and add it to a thin layer of human cells in a dish to see what virus replicates.
This is how rhinoviruses, thought to cause up to half of all colds, were discovered in the 1960s. However, live viruses
often do not survive sampling and culturing, and the method can fail to identify which virus is behind a cold in a third
of cases.
Now, however, researchers don't need to grow viruses to identify them. With the help of PCR, which amplifies the
amount of DNA in a sample, they can look directly for viral DNA or RNA sequences. To everyone's surprise, this is
turning up cold viruses that are completely new to science, but whose genetic diversity and worldwide distribution
suggest they have been circulating in humans for a long time.
In 2001, for instance, Ab Osterhaus of Erasmus University in Rotterdam, Netherlands, discovered human
metapneumovirus. In adults, hMPV causes no more than a cold, but in babies it can be lethal - like the respiratory
syncytial virus (RSV), identified decades earlier.
In 2006, researchers investigating an outbreak of upper respiratory tract infections in New York found that a third were

due to a previously unknown rhinovirus - and they couldn't identify the rest. Last year, a team in California used
especially sensitive PCR to investigate colds in 37 people and found "remarkable and unanticipated diversity": 30
varieties of rhinovirus, including some previously unknown ones, and two unexpected coronaviruses.
"There are probably more cold viruses out there we haven't discovered," says Osterhaus, whose group is launching a
wide search for viruses in general in humans and animals.
Finding the viruses is fast becoming the easy part - establishing what they do is harder. In years gone by, researchers
used to stick samples of new viruses up people's noses to see what happened. "No one puts novel viruses
deliberately into human volunteers any more," says Kenneth McIntosh of Harvard Medical School - thanks both to
liability laws and a healthier respect for the unexpected properties of viruses.
In 2005, for instance, random PCR on children in Swedish hospitals turned up a complete novelty, bocavirus, which
has now been found worldwide. Last year two new polyomaviruses turned up in Australia, the US and Sweden. These
viruses may well have caused the respiratory tract infections from which they were taken, but no one has yet been
able to prove it.
Part of the reason we are so amazingly ignorant about the causes of the world's most common disease, says Eccles,
is that research funding has focused, understandably, on nastier germs. That said, the impact of colds is not trivial:
they cost the US economy alone some $40 billion a year.
The reason why colds are usually little more than a nuisance is that it's not in their interest to make us any sicker than
they do. "For a cold virus to spread, the host must be able to walk around shedding mucus on people," says Eccles.
"Any virus that stops you doing that has to become milder, or die out."
Most cold symptoms are actually caused by the immune system's response to infections. A virus well adapted to its
host provokes the immune system just enough to cause symptoms that help it pass from person to person. For a cold,
that means lots of mucus, coughing and sneezing without making you too ill to move. Turning nasty For instance,
when the bat coronavirus that caused the SARS outbreak jumped to humans in 2002, it was frequently lethal. By
2004, the few SARS cases detected were mild.
Surprisingly, being too contagious can also be a disadvantage for a virus. In populations made up of separate groups
that have only occasional contact - villages, say - a virus that very rapidly infects everyone in one village could die out
before getting a chance to spread to other villages.
If there is little chance of running out of susceptible hosts, though, nasty viruses can spread. Last year, a team at the
University of Sheffield in the UK demonstrated this in live animals for the first time by showing that in moth larvae that
had more contact with other larvae, a virus became more communicable - and more virulent.
The analogy with our modern, globalised society is worrying. There are more people than ever before, and more
contact between far-flung communities. Does this mean that respiratory viruses could evolve to become more
contagious, and thus more likely to cause serious illness?
"In principle, yes," say epidemiologist Angus Buckling of the University of Oxford. "But it is complex." There will also
be increased mixing of viruses, he says, and competition between viruses within hosts can also affect virulence.
So does increased global travel explain Ad14? "This was a true emergence, the first appearance of this virus in our
nation," says David Metzgar of the US Naval Health Research Center in San Diego, who tracks adenoviruses in their
favourite victims, military recruits.

This year, New Scientist can reveal, Metzgar has found that exactly the same Ad14 virus that went on a killing spree
in 2007 is still circulating - except that now it is only causing ordinary colds. How is this possible? Because we
humans have changed. Frozen blood samples show almost no immunity to Ad14 in 2006, so it spread like wildfire. As
it spread, a few people who were unusually sensitive to it died. Now most of us have encountered it and have at least
partial immunity.
So the state of our defences is just as important to the outcome as the nature of the virus. If a virus is unlike anything
we've encountered before, or if our defences have been weakened, cold viruses can kill. This is why viruses such as
RSV and hMPV that are mild in adults can kill babies.
Few cold viruses damage respiratory tissue directly. Instead, they can kill by unleashing inflammation, which can
trigger heart attacks and even multiple organ collapse, and open the way for bacterial infections.
The more widespread use of PCR in hospitals has revealed how often supposedly benign cold viruses can turn nasty.
Last winter, researchers in the US discovered that ordinary rhinovirus put toddlers in hospital as often as RSV,
especially those with asthma.
Such studies show that cold viruses can be very nasty indeed in people with asthma. That's significant because
asthma is rampant in rich countries, especially in children, for reasons we still don't understand. Asthma involves
inflammation of the airways, and cold viruses make this worse by triggering additional inflammatory responses.
The same is true of chronic obstructive pulmonary disease, which constricts the lungs in a similar manner to asthma
but on a constant basis, whereas people with asthma have intermittent attacks. The incidence of COPD is rising in
developing countries as smoking spreads and average ages rise: it is the world's fifth most common cause of death
now, but the World Health Organization predicts it will be third by 2030.
So people with asthma and COPD are most at risk from cold viruses - unless you count the impact of colds on
another kind of pathogen altogether. When people go to their doctor with a cold, up to a third are prescribed
antibiotics even though the drugs have no effect on any of the viruses that cause colds. In the absence of any reliable
tests, doctors often assume - wrongly - that if cold symptoms last more than a week the cause must be bacterial.
Doctors also give antibiotics to prevent bacterial complications of a viral cold, but a review in 2005 found that unless
you have a history of complications, the practice is usually useless. Some doctors also prescribe antibiotics just to
placate patients, knowing full well they will make no difference. All these misuses of antibiotics are contributing to the
rise of antibiotic-resistant superbugs, which are a massive threat. Put it all together, and the message is clear: we
ignore the common cold at our peril.
Will there ever be a cure? Debora MacKenzie
The realisation that colds can kill (main story) has renewed interest in finding vaccines and treatments. The trouble is
that the common cold is caused not by one virus but by hundreds of different ones.
This means a vaccine or drug that works against one of these viruses, or one family of viruses, is usually ineffective
against all the others. What's more, because colds are usually so mild, if treatments cause even minor side effects
they can be worse than the disease. Such treatments will never get approval for general use, which is why most
companies instead focus on drugs that relieve symptoms.
Nevertheless, some drugs and vaccines are being developed against the cold viruses most likely to turn nasty. A
vaccine against RSV, which can cause serious illness in young children and the elderly, is going through clinical trials.
It consists of a weakened strain of the virus given as a nasal spray.

A treatment for RSV infections, based on RNA interference, is also in development, as are several conventional drugs
that target rhinoviruses. The most advanced is pleconaril, which keeps the surface proteins of rhinoviruses from
binding to cells. It reduces both the symptoms and duration of a cold.
However, treatments for specific viruses are useless unless your cold is caused by the virus in question - and doctors
have no quick way to work out which virus is to blame for a cold. Systems to do this are under development, mostly
based on looking for specific DNA or RNA sequences, but none are near to reaching the market.
An alternative approach would be to keep taking drugs that prevent infection throughout the cold season, such as a
derivative of the anti-smallpox drug cidofovir which has been shown to prevent infection with adenoviruses. But again,
as adenoviruses are only responsible for a few per cent of colds, the benefits hardly justify the expense and risk of
side effects from remaining on a drug permanently. An exception is preventing RSV in premature babies, who may die
if infected: two kinds of monoclonal antibodies to RSV are available for them.
Short of everyone on the planet isolating themselves for two or three weeks, so existing cold viruses run out of hosts
and die out, it is hard to see how we can ever defeat the common cold. Even then, new cold viruses would evolve in
time from animal viruses.
Some even question whether it is desirable to try to eliminate colds. "It's blind speculation," says Joel Weinstock of
Tufts University in Boston in the US, "but the common cold may protect us from more serious viruses." An occasional
sniffle might be a price worth paying if it keeps our immune defences primed.
It's not the snot Debora MacKenzie
How can 200 or more viruses all cause the same disease, the common cold? The answer is that they don't - cold
symptoms are in fact caused by our immune system's response to the virus.
Viruses that break through our defences usually start replicating in the cells lining the throat, which is why you feel
irritation and pain there first. Sore throats often feel as if the very tissue is being destroyed, but this seldom happens
with a cold. Rather, the symptoms are caused by the chemical alarm signals released by immune cells when they
detect viruses. The alarm molecules trigger local inflammation and also stimulate sensory nerves, producing the
feeling of pain and sneezing.
The most important of the immune signals, or cytokines, is called interferon. It triggers headaches, fatigue, loss of
appetite, malaise, nausea, depression and even muscle pain, caused by wastage, which happens a little even with a
mild cold.
A day or two later, these early symptoms are followed by a runny nose as the inflammation response spreads. It starts
as watery discharge due to tiny blood vessels exuding the watery part of blood. Then glands in your nose starting
producing mucus to wash out virus particles. If the mucus turns green, it's a sign not of bacterial infection - as some
doctors think - but that there are lots of white blood cells in it, which carry green iron-containing catalysts for
destroying germs.
During this process, the veins in the nose lining dilate. This, not snot, is the main reason for the congestion that
makes breathing difficult. Autonomic nerves ensure that the veins in each nostril dilate alternately, about every three
minutes, to prevent complete blockage. The tear ducts and sinus passages also become inflamed, making your
sinuses hurt and your eyes water.
If the inflammation reaches deep parts of your throat, it triggers coughing. It's the same response as if something

were stuck in your throat. In this case, though, coughing serves no useful purpose, unless the inflammation spreads
even deeper to the bronchi, and you cough up the mucus.
It is still not clear whether treatments for cold symptoms slow your recovery or not. Some cold researchers think the
typical symptoms help clear infections, but others think they are merely a useless side effect of cytokines. It seems
the body's own cure for a cold is not so much worse than the disease, it is the disease.
How to avoid colds Debora MacKenzie
Does cold cause colds? In the 1950s and 1960s scientists put cold viruses in people's noses and chilled them, or not,
afterwards. It seemed to make little difference, so the belief has been dismissed as folklore.
But in 2005 Ron Eccles of Cardiff University in the UK found that more students develop colds naturally after their feet
are chilled. Chilling anywhere on the body prompts a reflex cut in blood flow to the nasal lining, a major site of heat
loss, which may lower our defences against viruses.
Kids are the other big cause of colds. Cold viruses spread in snot, either sneezed out into airborne droplets or, more
often, smeared onto hands which then touch surfaces or other hands, from where they get into people's noses and
eyes.
Children pass on viruses better than adults because they get more snot on hands, wash them less often, and have
more physical contact with peers and caregivers. That said, in classic experiments in the 1950s, researchers stained
the snot of adults with a fluorescent dye before they engaged in normal activity - and watched in awe as the dye
turned up all over the room and its other occupants.
So if you want to avoid catching a cold, keep your nose warm, wash your hands a lot and stay away from children.
~~~~~~~~
By Debora MacKenzie

Flu spreads via airborne particles

Section:
IN THE NEWS
Health & Illness
Hand washing goes only so far in retarding transmission
Half of flu cases arise when people inhale tiny particles that float in the air, an international group of researchers
reports June 4 in Nature Communications. The finding flies in the face of conventional wisdom, which holds that
nearly all influenza spreads by large droplets that sick people release when they sneeze or cough. Those large
droplets, the theory went, get on people's hands and transmit the virus from there.
While scientists knew that small particles called aerosols represent possible routes of disease spread, many thought
that cases almost never arise that way.
Public health officials say that knowing how often flu transmits via the air is important for controlling
outbreaks,especially when dealing with pandemic strains for which no vaccine exists.

Benjamin Cowling, an infectious disease epidemiologist at the University of Hong Kong, and his colleagues studied
how flu spread among 782 families in Bangkok and Hong Kong during regular outbreaks from 2008 through 2011.
Some families received liquid soap and instructions about proper hand hygiene. Some also got surgical masks.
Together, washing hands and wearing surgical masks should block transmission of the virus through the large-droplet
route.
But surgical masks don't block airborne flu. So the researchers assumed that people who got sick even though they
wore the masks and washed their hands probably caught the flu by inhaling small particles. And to work out how the
families without soap and masks caught the flu, the researchers further assumed, based on previous lab studies, that
people who got sick through the airborne route were more likely to develop classic flu symptoms such as fevers and
coughs. People who catch flu via large droplets typically get milder symptoms.
Aerosol transmission caused 33 percent to 92 percent of cases in Hong Kong and 55 percent to 98 percent in
Bangkok, the team calculated.
"There's a lot of uncertainty in that data," says Donald Milton, an environmental health scientist at the University of
Maryland's School of Public Health in College Park. But the exact proportion of cases due to airborne spread doesn't
matter as much as the evidence that aerosols are an important route of transmission, he says. "What it really says is
you can't rule out aerosols."

Washing your hands can be the key to good health

Contents
Time to get in a lather
Soap or sanitizer?
Practice your bedside manner
Section:
Healthy You
Want to take your health into your own hands? Try washing them. According to the Centers for Disease Control and
Prevention, keeping your hands clean is one of the most important steps you can take to stay healthy and avoid
spreading germs to others.
You can pick up germs when you touch surfaces like elevator buttons or keyboards and then touch your own eyes,
nose or mouth before washing your hands. According to CDC, some viruses and bacteria can live two hours or longer
on surfaces like !, doorknobs and desks.
"When it comes to preventing infections, what we want to do is keep bacteria and viruses away from the places where
they can start an infection, and those places are our mucus membranes, such as our eyes, nose or mouth," says
Michael Bell, MD, associate director for infection control at CDC. "The thing that is most likely to come into contact
with your eyes, your nose or your mouth are your fingers, so our own hands are a really big delivery mechanism for
bacteria and viruses."
Think about what happens when you go into an airport, a school or any public place. You have to touch things. You
have to touch the railing on the escalator, the handle on the grocery cart, the tabletop at the cafeteria. All of those
things can be dirty, but if you wash your hands before you touch your own face, then you aren't going to deliver the

germs that can cause an infection.

As to how often you wash, there's no magic number, but you should always wash your hands before eating, after
using the toilet, after blowing your nose, after coughing or sneezing into your hands, after handling garbage, before
and after preparing food, after changing a diaper, after touching animals or animal waste, before and after treating
wounds or cuts, before and after touching a sick or injured person, and before inserting or removing contact lenses.
"As a very rough guide, if you aren't washing your hands at least 10 times a day, you probably aren't washing your
hands enough," Bell says. "If you think about it, you are probably visiting the restroom three or four times a day, and
you are probably having three meals a day, and that alone gets you up to seven times, and I guarantee you the other
three add up very quickly."
So roll up your sleeves and grab some soap. There's more to hand-washing than meets the eye -- or nose or mouth.
Time to get in a lather
"Practically speaking, you can spend a long time washing your hands and do a poor job or you can be quick and do a
thorough job of cleaning all the parts of your hands," Bell says.
If you're using soap and water, wet your hands with clean running water -- warm water works best -- and apply soap.
Rub your hands together to make a nice lather and scrub all the surfaces. Don't forget to wash between your fingers
and under your nails, as well as the backs of your hands, which people frequently miss, Bell says. Keep rubbing your
hands together for about 20 seconds, then rinse them well under clean running water and dry them with a paper
towel.
When it comes to safe food handling, neglecting to wash up is the most common mistake people make. Poor hand
hygiene contributes to food-related illnesses such as salmonella and E. coli infection, and the bugs can spread
through your kitchen and get on your hands, cutting boards and other surfaces. Washing your hands often will help
prevent bacteria spreading from raw meat and poultry to the vegetables you're chopping for your salad:
So go ahead and spend all day in the kitchen whipping up that souffl, but remember to wash your hands frequently,
including before and after handling food.
Soap or sanitizer?
When it comes to washing your hands, any kind of soap and water will do the trick, and the soap doesn't have to be
antibacterial.
"It can be plain old soap and water," says CDC's Bell. "For most things that we might be carrying on our hands, the
combination of the detergent action of soap and the physical action of rinsing after you wash do a great job of
removing or inactivating the germs on our hands."
Soap and water not handy? Pack some alcohol-based hand sanitizer in your purse or pocket. It's a terrific option if
you don't have soap and water nearby. According to Bell, hand sanitizers don't have the mechanical action of
removing germs from your hands, but they can do a good job of inactivating most germs in a pinch.
Practice your bedside manner
If you've visited someone in the hospital recently, you might have noticed a hand sanitizer dispenser on the wall just
outside or inside the room. Aaron Glatt, MD, a spokesman for the Infectious Diseases Society of America, says you
should use it to clean your hands prior to entering the room and again when you leave.
If you happen to see a doctor or nurse come from another patient's room without washing their hands, you have every

right to speak up and ask them to wash up. Glatt, who is president and chief executive officer of New Island Hospital
in Bethpage, N.Y., says many hospitals post signs saying: "Ask your doctor, ask your nurse, 'Did you wash your
hands?'"
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By Teddi Dineley Johnson
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