快猫短视频

London

鈥淭his little piggy went to market,

This little piggy stayed at home鈥︹��

More likely than not, the little piggy that stayed at home had not reached a
marketable size.

For nearly fifty years, farmers have been adding low doses of antibiotics to
their livestock鈥檚 food because this improves their feeding efficiency so the
animals need less food to reach marketable weight. But now, there is heated
debate over whether these additives pose a real risk to human health.

Some medical microbiologists want to ban antibiotics from being used as
growth promoters on the grounds that they encourage the development of
antibiotic-resistant bacteria which could threaten human health. But most
scientists who have studied growth promoters and their links to antibiotic
resistance in humans say that there is no evidence that they are causing
problems. They argue that banning antibiotic growth promoters could increase
risks to human health and put poultry, pigs and cattle at risk of disease and
death. And on the farms, many are reluctant to forgo the benefits of using
antibiotic growth promoters without compelling evidence for a ban.

Although there are commercial, economic and ethical aspects to the debate,
these need to be carefully separated from scientific assessments of evidence for
real risk.

Growth-promoting antibiotics are believed to work in animals by
controlling low-level diseases which divert energy the animals would otherwise
spend putting on weight (See 鈥淗ow antibiotics work鈥�, p 26). But the concern is
that they could also promote the emergence of bacterial strains which have
genetic resistance to antibiotics. As genetic material can be transferred
between bacteria, there is every reason to suspect that any genes carrying
resistance to antibiotics could also be transferred. Since bacteria with
resistance genes would have an obvious advantage over bacteria that succumbed to
antibiotics, intense selective pressure would cause resistance to spread
throughout bacterial populations. Antibiotic-resistant bacteria could then cause
diseases in humans that would be untreatable with conventional antibiotics.

In theory, diseases could be contracted directly if animal bacteria get into
human food, as happens with food poisoning caused by Salmonella,
Campylobacter and Escherichia Coli. But most livestock bacteria
can鈥檛 survive in humans and so are not a threat. Diseases could also be
contracted indirectly by the transfer of resistant genes from animal to human
bacterial strains. But so far, no natural transfers have been clearly
demonstrated.

Since the 1960s, public health officials and scientists worldwide have tried
to quantify the risks of resistance arising from antibiotic growth promoters,
and frame appropriate responses. The first attempt was the 1969 report of the
Swann Committee to the British Parliament. Its recommendation鈥攖o prevent
antibiotics used in human medicine being given as animal growth
promoters鈥攚as incorporated into British law. A directive from the European
Commission requiring similar restrictions to be enacted by the governments of
European Community states was agreed in 1970.

In 1986, Sweden considered the issue and decided to ban all antibiotic growth
promoters. This decision is one reason why growth promoters have hit the news
again recently. When Sweden joined the EU in 1995, it was allowed to keep its
ban, but was given until the end of 1998 to either convince the rest of the EU
states to join its ban, or to drop the ban and fall into line with the other
members.

The other reason why growth promoters are a hot topic again is controversy
over a veterinary antibiotic called avoparcin, which is closely related to an
important medical antibiotic called vancomycin. Denmark and Germany banned
avoparcin early last year. (Australia followed suit a few months later.) But
then, last summer, the EU鈥檚 Scientific Committee on Animal Nutrition rejected
the scientific basis for the ban (This Week, 27 July 1996, p7). Last month this
tale took an unexpected turn when the European Commission chose to ignore the
SCAN鈥檚 advice and called for avoparcin to be banned right across the EU.

Compelling evidence

Other investigations, such as those by the US Office of Technology Assessment
in 1979 and the US National Academy of Sciences in the 1980s did not find
compelling evidence that fears over antibiotic growth promoters have been
realised. The US still allows antibiotics such as penicillin and
chlortetracycline to be given as growth promoters even though they are routinely
used to treat humans.

Victor Lorian, head of the department of epidemiology and infection control
at the Bronx-Lebanon Hospital in New York, rejects claims that giving animals
low levels of antibiotics compromises human health. Over fifty years in the US,
there has been only one compelling case of resistance in a bacterial strain that
infects livestock causing disease in humans. That was in 1983 and involved an
outbreak of food poisoning caused by a strain of Salmonella that was
resistant to a number of antibiotics. The strain was linked to hamburgers made
from cattle fed on low doses of chlortetracyline.

But even in this case, the evidence was contested: many of the affected
people had been dosing themselves with antibiotics which could also have
promoted resistance, and because all the cattle had been slaughtered by the time
health officials tracked down the source of the outbreak, the resistant
Salmonella could only be traced to a neighbouring farm, not to the herd in
question. 鈥淐onsidering the millions, if not billions of cattle fed with
antibiotics and eaten by man it is clear that the one case is not statistically
significant and certainly does not justify banning antibiotics from the food of
meat animals,鈥� says Lorian.

Yet, in Britain, Laura Piddock of the department of infection at the
University of Birmingham believes that the American case and a few other cases
of possible transmission justify her suspicions that there is a link between
resistance in animals and people. She admits that 鈥渆vidence showing beyond doubt
that antibiotic-resistant bacteria arising in animals cause subsequent infection
in man which is difficult to treat is difficult to find鈥�. She adds that, 鈥渙nly
for Salmonella has a natural pathway of transfer of antibiotic
resistant bacteria鈥攆rom animals to foodstuffs to man and subsequent
infection鈥攂een clearly recorded.鈥�

But even allowing this slender evidence of transmission, it looks as
though鈥攁t least in Europe鈥攇rowth promoters cannot be blamed for
Salmonella resistance. The growth promoters used in Europe only work
against a particular class of bacteria, known as Gram-positive bacteria.
Salmonella strains belong to a different class, the Gram-negative
bacteria.

According to David Taylor, a microbiologist at Glasgow veterinary school,
鈥渘one of the currently registered growth promoters has any effect on
Salmonella鈥攁ny argument for a ban based on the risk of inducing
resistance is entirely spurious鈥�. Although growth promoters affecting
Gram-negative bacteria have been used in the US and Australia, there is no
substantial evidence of an increase in resistance among Salmonella
strains.

Instead, Taylor blames the high doses of veterinary antibiotics used to treat
infections in livestock for the resistant Salmonella and
Campylobacter that are being found in increasing numbers of food poisoning
cases in humans. Antibiotics at these concentrations鈥攗p to a
hundred times those used for growth promotion鈥攌ill normal bacteria. And
this means that they operate, in evolutionary terms, as a strong selective force
on resistant bacteria. Piddock cites the example of a fluoroquinolone antibiotic
called enrofloxacin, which vets use in Europe. There is growing evidence, she
says, that enrofloxacin is selecting for strains of Campylobacter in
poultry that can enter the food chain, and which are resistant to a medical
fluoroquinolone called ciprofloxacin.

Gene shuffling

Salmonella (and Campylobacter) are among the few bacteria
that can survive in both animal and human hosts. For the majority of strains
that cannot, the key issue is whether resistant strains that are specific to
animals can transfer their resistance genes to strains that infect humans. There
is no clear evidence of natural transfer, but under lab conditions Bill Noble
and his colleagues at St Thomas鈥檚 Hospital, London, reported transferring
resistance to the antibiotic vancomycin from Enterococcus faecalis
to Staphylococcus aureus. E. faecalis can be transferred to
humans in meat products and has been found in human faecal samples. According to
Noble, the data show that 鈥渋t is feasible for resistance genes to transfer
between different bacterial strains, but it doesn鈥檛 show it will happen. It
could occur next week, or in 2020, but there are other situations where
resistance has not transferred when it could have done.鈥�

The complex issues of transfer of resistance and risks of cross-resistance to
antibiotics have been most widely discussed in debates over avoparcin. This
commonly used growth promoter is known to confer cross-resistance to related
glycopeptides, including vancomycin. In recent years, vancomycin has become a
鈥渓ast resort鈥� antibiotic in humans, used to treat serious infections caused by
the 鈥渟uperbug鈥�, methicillin-resistant S. aureus (MRSA). Cases of this
resistant bacterium are now being reported from increasing numbers of hospitals
worldwide.

Increases in MRSA are probably due to the heavy use of antibiotics in
hospitals and ease of transmission between patients. But the possibility of
farmyard resistance to avoparcin eventually promoting resistance to vancomycin
in hospitals has been seized on by opponents of growth promoters. Initial
research by Frank Aarestrup of the Danish Veterinary Laboratory found evidence
of widespread glycopeptide resistance on farms where avoparcin was used and was
heavily relied on in justification for the Danish and German bans.

In July 1996, the EU鈥檚 SCAN considered the scientific foundation for the
German and Danish bans. Its members wanted hard evidence for a natural and
sustainable transfer of resistance from livestock to humans, but did not get it.
Their report said that Aarestrup had obtained contradictory results in later
studies鈥攁nd that, in any event, he found only small numbers of resistant
bacteria which were unable to grow without assistance.

The members of SCAN also weighed other evidence for and against the risk of
transmission, although it did not publish details of the studies involved. They
concluded that early research which had suggested vancomycin resistance could be
transferred between bacterial species was contradicted by later, more sensitive
studies showing that the genes responsible for vancomycin resistance in human
E. faecalis were different from those conferring resistance in strains
isolated from pigs and poultry.

The SCAN report notes that 鈥渋t is customary in science to require proof of
the positive鈥�, and this may be why it recommended monitoring the avoparcin
situation and holding a further review within two years. The recent
recommendation by the European Commission to ban avoparcin is apparently also
based on 鈥渟cientific opinion鈥� (This Week, 21/28 December 1996, p 6). But so far,
details of any further positive evidence of a risk has not been forthcoming from
the Commission.

鈥淏laming animal use of antibiotics is a soft option,鈥� says Steve McOrist of
the Edinburgh Veterinary School. 鈥淢edics should be looking at the infection
control procedures in hospitals that allow the spread of resistant strains
between patients.鈥� The American experience supports his stance: although
avoparcin has never been used as a growth promoter in the US,
vancomycin-resistant bacteria are reported from 15 per cent of American
intensive care units.

Richard Lacey, a microbiologist at Chapel Allerton Hospital, Leeds, and an
outspoken critic of the agricultural industry, says he is also not convinced
that using antibiotics as growth promoters is a risk to human health. 鈥淚 am not
bothered about agents which are chemically different from those used in human
medicine鈥攖here is virtually no possibility of them being a major factor in
human disease.鈥� But he is strongly opposed to growth promoters and what he
regards as other artificial inputs to farming on ethical grounds.

Others are also worried about the complex ethical and animal welfare
dimensions to the arguments. If Europe decides to side with Sweden and impose a
ban on all growth promoters, the immediate costs would fall on farm livestock in
increased death and disease. McOrist says that in the year following the Swedish
ban, an extra 50 000 pigs died of 鈥渟cours鈥濃�攐r diarrhoea. Whether we like
it or not, the health of many farm animals now depends on low doses of
antibiotics. Taylor feels that banning the remaining growth promoters used in
Europe 鈥渨ill cause problems in the treatment and management of disease which
will lead to animals suffering鈥�.

There are also economic and consumer considerations. Any ban on growth
promoters will be at a cost. In late 1995, a report for the European Commission
by researchers at the universities of London and Munich estimated that if growth
promoters were banned throughout the EU, reduced efficiency and higher treatment
costs would increase food costs by 1 billion Ecus (拢750 million) a
year.

Trade war

This would inevitably be passed on to the consumers. The report also included
a survey of housewives in France, Germany and Britain. Although this found that
more than 60 per cent opposed the routine use of antibiotic growth promoters
while fewer than 20 per cent actually approved, there is no evidence that these
opinions would translate into a ready acceptance of higher prices.

A further, less easily measured cost would be the potential for provoking a
trade war with other countries that still allow the use of antibiotic growth
promoters. This could result in a repeat of problems caused in 1987 when the
European Commission banned growth hormones and the US and other countries found
they could no longer export meat to Europe. Similar rumblings emerged last year
before the Commission鈥檚 controversial decision, last month, to approve imports
of genetically modified maize from the US.

Herbert Lundstr枚m of the Swedish Veterinary Association still maintains
that 鈥渁ll unnecessary use of antibiotics 鈥攗se that is not to prevent or
cure disease鈥攕hould be stopped in the interests of both animals and
consumers鈥�. He says that Sweden will fight to keep its ban on antibiotic growth
promoters. Yet Swedish farmers now have to control many diseases previously kept
in check by growth promoters by other methods, including increased reliance on
higher doses of therapeutic antibiotics. Their use of tetracyclines doubled
between 1988 and 1994. In an ironic twist, it is even possible that a ban on
antibiotic growth promoters might inflame the situation that it is supposed to
calm.

* * *

How antibiotics work

FARMERS have given their livestock antibiotic growth promoters since the
1940s, when their effects were discovered by accident. 快猫短视频s were feeding
chickens vitamin B12, produced by fermenting bacteria, and found that the birds
grew faster than expected. They then realised that the bacteria also produced
the antibiotic chlortetracycline. Farmers began using it and other antibiotics
to improve weight gain in their animals, reducing the amount of food needed to
bring them to market.

Exactly how antibiotics enhance performance has never been properly
explained. But evidence is now accumulating to show they work by knocking out
low-level infections.

Therapeutic or preventative doses of antibiotics kill bacteria. By contrast,
antibiotics given as growth promoters seem to work at levels which don鈥檛 affect
the ability of beneficial gut bacteria to grow and reproduce but can stunt
growth of disease-causing bacteria or tone down the damage they do.

In 1995, Lilian Ishida and colleagues from Tohoku University medical school
in Japan showed that low doses of antibiotics stop bacteria sticking to cell
surfaces in the host, blocking an essential first step in the infection process.
Around that time, Mario Jacques of the University of Montreal found that low
doses of the antibiotics tylosin and apramycin in livestock prevent bacteria
from absorbing the iron needed for growth and reduce the amount of toxic
chemicals they release into the host. Tylosin and apramycin are both used as
therapeutics, but tylosin is also used as a growth promoter.

Victor Lorian of the Bronx-Lebanon Hospital in New York reported that, under
laboratory conditions, a number of low-dose antibiotics improve the ability of
human and animal white blood cells to recognise and destroy bacteria. Research
on how growth promoters work promises a tantalising new angle on the debate over
their use. If low-dose antibiotics disable bacteria in different ways from
higher, therapeutic doses, it seems likely that the two regimens will also
generate different selective pressures for developing resistance.