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One day in late July this year, all dealers working on the exchange
floor of New York’s World Trade Center were ordered to take a tuberculin
test. Staff were told that they would be allowed onto the trading floor
only if they wore a sticker to show they had tested negative. The order
followed the discovery that two employees had developed TB. The microbe
that has long been the poor world’s biggest infectious killer had penetrated
one of the rich world’s most powerful financial institutions.

This incident, though newsworthy, is hardly typical of the deepening
TB crisis in New York. In reality, the people at greatest risk from this
old foe are those who have always been most at risk: the poorest and most
marginal groups, those with suppressed immunity, and those who care for
them – in Harlem, the Bronx, Brooklyn, and across the river in Newark, New
Jersey. By comparison, say health officials, the threat to most office workers
is low and the decision to test all staff at the World Trade Center was
an overreaction. But the dealers’ stickers are important in symbolic terms.
TB is returning on a scale that would have been unthinkable just a decade
ago and now Wall Street and the politicians know about it.

If ever there were a tale of two cities, this is it. New York has its
own ‘Third World’ of poverty, homelessness, and disenfranchisement. The
rich city and the poor city rarely collide, but the return of TB is suddenly
reminding the rich that the poor exist. In 1985 the disease had been declining
for 35 years. Since then the number of cases has increased by 18 per cent
across the US as a whole. In New York City, the climb has been much steeper,
with an increase of nearly 150 per cent since 1980.

But it is the latest twist in the TB story that has finally brought
a flurry of official action – the rapid spread during the 1980s of drug-resistant
strains of the TB bacterium, Mycobacterium tuberculosis. Multi-drug resistant
(MDR) strains are virtually untreatable: more than half of those infected
with them so far have died. Moreover, they have spread from the marginalised
groups of the homeless and the injecting drug users to infect health workers
and others with a political voice. America can no longer afford to forget
TB.

But let’s keep a sense of proportion. While industrialised countries
may have rediscovered TB, their problem is a fleabite compared with what
is happening in the developing world. The fuss in the US has focused attention
on TB worldwide. The disease continues to kill some 3 million people a
year, more than 95 per cent of them in developing countries, and numbers
are climbing. Last year there were 8 million new cases. One-third of the
world’s population, mostly in Asia, is infected with M. tuberculosis. And
while the infection is dormant in most of those people, in the coming decades
the spread of HIV is expected to reactivate TB in millions of them, causing
a sharp rise in the number of cases of disease and death.

The American problem may be small in comparison, but it is nevertheless
alarming a nation that 20 years ago was led to believe it had seen the last
of infectious diseases. And paradoxically, the emergence of drug-resistant
TB in the US could eventually help to reduce death rates from TB worldwide,
by stimulating long-overdue basic research into the disease.

Galvanised by the need to combat the drug-resistant strains, the US’s
National Institute of Allergy and Infectious Diseases is putting funds into
the neglected area of TB research and recruiting new scientists. Not before
time, say researchers: ‘The diagnostics are stone-age and the immunology
is bronze-age,’ says Barry Bloom, a leading mycobacterial researcher at
the Albert Einstein College of Medicine in New York. ‘And there has not
been a new drug for TB for years.’ Zeda Rosenberg at the NIAID, who is coordinating
the new TB research effort, adds: ‘TB research stopped before the era of
biotechnology. So none of the techniques had been applied.’ The only exception
has been in molecular genetics, which by the late 1980s had begun to produce
spectacular results in TB research. More of this later.

A TIME BOMB EXPLODES

First, what has happened to bring TB back with such a vengeance? Tom
Frieden, head of TB control for the New York City Department of Health,
sums it up. ‘This was a time bomb constructed by social and economic inequality
and ignited by the HIV epidemic.’ He believes there are four major reasons:
the inadequate public health system; the arrival of HIV, the ‘explosion’
of homelessness and the increasing number of TB-infected immigrants in New
York. HIV undoubtedly plays a big part. In New York, about 40 per cent of
the known TB patients are also HIV-positive, says Frieden. ‘HIV speeds
up the tape for TB.’ If an HIV-negative person becomes infected with TB,
they face only a 10 per cent chance of developing the disease over their
lifetime. But in any given year an HIV-positive person infected with TB
faces a risk of developing TB as high as 8 per cent.

HIV could not, however, have done this alone. Other researchers pin
the blame more squarely on the public health system. Karen Brudney and Jay
Dobkin at the Presbyterian Hospital in New York have argued that the increase
in TB was beginning before the advent of AIDS, and Bloom estimates that
immigrants are contributing only slightly more new cases than would have
been expected from their proportion of the total population.

The history speaks for itself. New York and New Jersey closed down their
TB hospitals and sanatoriums at the beginning of the 1970s. The aim was
to switch funds and staff to a much-improved outpatient service for treating
people in their homes. It did not turn out like that. By the mid-1970s,
New York City was foundering in its famous financial crisis and virtually
all the TB beds were closed; on top of this, money for outpatient care was
actually cut. By 1979, TB was on the increase. Lee Reichman, president of
the American Lung Association, from the University of Medicine and Dentistry
in New Jersey, says he testified repeatedly to Congressional committees
through the 1980s, warning of a coming epidemic. And, like others, he
could see the specific problem of drug resistance looming. ‘You have to
treat people properly to make sure drug resistance doesn’t emerge.’

CATASTROPHIC RESULTS

As Brudney and Dobkin were to show, however, patients were not treated
properly. In one study, 89 per cent of patients who were discharged from
hospital disappeared from the hospital’s follow-up and failed to complete
their treatment. More than a quarter of them were back within a year suffering
from TB again. This pattern was being repeated all over the city. Incomplete
treatment creates the ideal conditions for drug resistance, and the results
have been catastrophic.

Ten years ago, about 6 per cent of all strains of M. tuberculosis tested
were resistant to one or more of the TB drugs. In New York City today, more
than one-third are resistant to one drug; almost one-fifth to the two main
drugs, rifampicin and isoniazid; and a few fail to respond to all drugs.
Every doctor and scientist involved agrees that this could have been prevented.
‘We made them resistant by our inaction and by the fact that we do not have
a proper health care system,’ says Reichman.

In 1990 and 1991, researchers investigated three outbreaks of MDR TB
in hospitals in New York City (This Week, 9 November 1991). The outbreaks
resulted in more than 80 new cases of MDR TB, mainly in HIV-positive people.
About 70 per cent of those infected died. Another outbreak was investigated
in Miami, and news of a fifth outbreak in a major hospital in New Jersey
is now emerging. Altogether, two or three dozen health workers are known
to have been infected. There have also been outbreaks in prisons and shelters
for the homeless, and in one outbreak 28 prisoners and one guard died. The
official figures are almost certain to have underestimated the problem.

Although about 80 per cent of those known to have died of TB caused
by MDR strains have been HIV-positive, no one knows how many people with
a fully functioning immune system have been infected. Animal studies using
other bacteria suggest that drug-resistant strains tend to be less easily
transmitted than drug-sensitive strains, but with MDR TB, this does not
so far seem to be the case. MDR strains appear to have been transmitted
no more and no less readily than ordinary strains, says Bloom, although
he stresses that there are few data. The explanation could simply be that
the MDR TB bacteria are surviving longer in patients than the drug-sensitive
strains. This would mean that they make up a bigger share of the pool of
surviving bacteria, and so would have more opportunity to spread.

INEXPERIENCED DOCTORS

Drug-resistant strains have existed at least as long as the drugs themselves.
Random mutations in the genome of the bacterium occasionally throw up a
strain that happens to resist a particular drug. If a patient carrying
one of these strains is taking only one TB drug instead of several, or stops
treatment early, selection pressure will tend to favour the resistant strains.
To avoid creating such conditions, doctors are supposed to use several drugs
so that any bacteria evading one will be hit by another. And they are supposed
to make sure therapy is completed. But doctors are inexperienced in dealing
with this disease. ‘Only a couple of dozen in New York really know how to
take care of patients,’ says Frieden.

Most studies to date have shown that people of all social classes and
educational backgrounds are loath to continue taking tablets when they feel
well, whether the tablets are antibiotics, antimalarials or for high blood
pressure. With TB, it is a misconception to think that only drug abusers,
homeless people and the unemployed fail to complete treatment, says Ronald
Young, a fieldworker in the Bronx whose job is to supervise people taking
their tablets. Saundi Jenkins, nurse-manager of the University Hospital’s
TB clinic in Newark, says health workers are the worst. Of 72 staff at the
hospital who tested positively for TB last year, she says, 61 failed to
come back to the clinic for a course of TB drugs designed to prevent infection
turning to disease.

A couple of mornings spent with field workers in the Bronx and Newark
made it clear how complex are the problems of those most at risk . In the
Bronx, Young can supervise about a dozen patients, visiting all of them
every day for however many months it takes to finish therapy. He and one
colleague are the only field workers for the whole of the Bronx, which last
year had the highest rate of increase in new cases of TB for any area of
the city. He knows he can barely scratch the surface.

A pilot programme to test directly observed therapy (DOT) was set up
in New York City in 1982, and was almost immediately shown to be effective.
Yet even now, two years after the first MDR outbreak, the number of DOT
workers employed by the city is still only enough to cover 200 patients.
Last year alone, there were 3673 new cases of TB and a large number of uncured
patients from the previous year. DOT is clearly not receiving the resources
it needs. ‘We expect (the number of workers) to increase dramatically in
the next few months,’ says Frieden.

No one doubts, then, that TB in the US is once again a major threat
to public health. This is where the scientists are supposed to come in,
but a whole generation has been lost, says Bloom. After the first TB drug,
streptomycin, was licensed 40 years ago, a string of equal or better drugs
followed: isoniazid, PAS, rifampicin and others. In combination with good
control programmes in the West, these drugs appeared to have transformed
TB from a life threatening disease to an inconvenience. Research interest
fell accordingly. During the 1970s, the US National Institute of Allergy
and Infectious Diseases spent less and less on TB research. By 1979, only
eight TB grants were awarded, totalling just $514 000. The money has climbed,
but very slowly.

In 1989, when the rise in TB was already apparent, only 20 grants were
made, totalling $2 747 000. HIV research, by comparison, has a budget of
some $400 million. The big jump has come only this year in response to
MDR TB. NIAID planned originally to spend $5.2 million on TB in 1992, but
has shifted money from other research programmes to almost double this figure.
No new money has been provided this year. Next year, says Rosenberg at the
NIAID, funding will probably reach $13.5 million. But a task force estimated
that the required budget for doing the necessary basic research on TB next
year would be $43 million, more than three times as much.

Rosenberg defends the tiny budget for next year on the grounds that
it takes time to build up enough expertise to use the money well. This year,
the NIAID has developed a strategic plan for TB research. It is requesting
research applications in the basic biology of TB vaccines, and is casting
its net very wide to try to attract good scientists from other disciplines.

Why, though, is there so much to do? TB, like many major diseases, remains
largely a mystery to biologists. Certainly we know that M. tuberculosis
causes it, but the rest is largely a mess. This is for several reasons.
First, the bacterium is ‘dauntingly’ difficult to work with, according to
Bloom. It is so infectious that it must be handled only in special laboratories.
It grows extremely slowly, taking about four weeks to produce a colony
of 107 organisms, compared with eight hours for the gut bacterium Escherichia
coli. And the thick waxy coat that is the hallmark of mycobacteria makes
it difficult to manipulate.

At present, most hospitals take at least 4 weeks to confirm a diagnosis
of TB. A simple microscopic examination of sputum from a patient can detect
the presence of waxy-coated bacteria, known as acid-fast bacilli, but there
are others besides M. tuberculosis. To confirm the diagnosis, the hospital
laboratory must culture a colony of bacteria. It takes longer to determine
whether a patient has a drug-resistant strain, and during this time the
patient may be receiving no drugs or the wrong ones. In many cases in the
US, patients with drug-resistant strains have died waiting for results to
come back. Better, more rapid diagnostic tools are obviously a priority.

DIFFICULTIES OF DIAGNOSIS

Laboratories in the US, the Netherlands, Britain and France have recently
applied the technology of the polymerase chain reaction (PCR) to TB diagnosis.
¿ìè¶ÌÊÓƵs can amplify stretches of DNA from the bacterium in sputum to
produce results in hours. Stuart Wilson and his colleagues at the London
School of Hygiene and Tropical Medicine are developing a simplified PCR
system for detecting TB. The system is designed for use in the limited facilities
of developing countries and so far, say the researchers, results have been
encouraging.

Although this particular group had good results, early reports from
a systematic assessment of the method by the WHO are less cheerful. Douglas
Young, chairman of the WHO’s standing committee on the immunology of mycobacteria,
at the Hammersmith Hospital in London, says that most of the laboratories
have found too many false positive results to make the technique efficient.
Even if a few clever hands can make the technique work well, it is not yet
ready for most hospitals.

It is even more difficult to diagnose people who are infected with
M. tuberculosis but not suffering from active disease. The current ‘technology’
consists of injecting purified protein derivative (PPD) from the bacterium
into the skin and waiting for a red swelling. The red mark indicates that
T cells have recognised and responded to the protein, suggesting that a
person is infected. The size of the red mark, measured with a ruler, is
critical: red marks below a certain size are taken to mean a person is
not infected. There are several problems with this crude technique. For
example, not everyone who is infected responds to the skin test, particularly
HIV-positive people whose immune systems are already compromised. Also,
the skin test cannot differentiate between people who are infected and people
who have been immunised against TB with the BCG vaccine.

¿ìè¶ÌÊÓƵs are now looking at other ways to identify infected people.
The obvious targets for future tests would be antigens and antibodies in
the blood of infected people, but these are usually present at very low
levels in people with latent infection, says Douglas Young. Also, in populations
where TB is endemic, they may fail to distinguish between people who have
natural immunity and people who are latently infected.

The BCG vaccine itself is another controversial question . Meanwhile,
no one knows what immune responses to the bacterium might protect against
infection. No one knows, in fact, whether some immune responses to the bacterium
end up damaging the body. M. tuberculosis infects macrophages, a class of
white blood cell that destroy foreign invaders. In healthy people, these
cells seem to be able to deal with the TB bacterium. But in some cases
the bacterium can resist the action of free radicals and other substances
that the macrophage normally uses to destroy invaders.

People whose immune cells make specific messenger proteins or cytokines,
such as tumour necrosis factor (TNF) and interferon gamma, are able to wall
off the bacteria in structures known as granulomas. Yet, while granulomas
may restrict the spread of disease, they may also do damage to lung tissues.
Too much TNF is toxic to the body. Clearly, says Bloom, the body must reach
a delicate balance between fighting the bacterium and doing itself harm.
In HIV-positive people, whose immune systems are compromised, the signs
and symptoms of TB are often different from those of HIV-negative people.
For example, their infections are more likely to spread throughout the lungs
than to be contained within granulomas.

WORSENING HIV INFECTION

The tangled relationship between HIV and TB is still only partly understood.
It has long been known that the virus opens the door to rampant TB. But
now there is some suggestion that the TB bacterium may also encourage HIV.
Preliminary evidence from a team led by Zarah Toossi at Case Western Reserve
University in Ohio shows that, in the laboratory, the bacterium increases
HIV’s rate of replication in cells. If this effect proves to be true in
people – and it is a big ‘if’ – then the implications could be dramatic.
With one-third of the world infected, TB could be an extremely potent cofactor
for HIV. So far, researchers are cautious, although Bloom says it would
almost be surprising if the bacterium did not worsen HIV infection. The
difficulty, he adds, would be in measuring its influence in populations.
In Africa for instance, TB is likely to kill HIV-positive people before
the virus has a chance.

The search for new drugs is an urgent priority. Ideally, scientists
would like to develop drugs that need only a short course or could be delivered
in the form of a slow-release implant. And if scientists understood more
about the genetic mechanisms of resistance to the existing drugs, this might
help them to design drugs that outwit the bacteria. So far, isoniazid (also
known as INH) is the only drug for which scientists have pinpointed a genetic
mechanism of resistance (This Week, 29 August). Some resistant strains of
M. tuberculosis lack a gene encoding an enzyme, catalase, which scientists
believe is involved in activating isoniazid. Without catalase, the drug
fails to work. But this is not the only mechanism that the bacterium uses
to resist the drug: Bloom and his colleagues have identified another gene
implicated in resistance.

The picture might look gloomy, but in one area of study, the technology
has been transformed. William Jacobs, a mathematician turned molecular
geneticist at the Howard Hughes Medical Institute of the Albert Einstein
College in the Bronx, has developed methods to manipulate the genes of
M. tuberculosis. This means that a devilishly difficult bacterium can be
mastered to learn more about its virulence and its mechanisms of drug resistance.
Perhaps even more importantly, the methods should make it possible to design
a genetically engineered BCG vaccine that carries extra antigens.

Jacobs describes his team’s success as ‘winning at lotto’. ‘Bacterial
genetics is like New York,’ he says. ‘Anything that can happen will happen.’
But this modesty belies the rigorous and ingenious work he and his colleagues
have been doing for more than five years on M. tuberculosis and related
mycobacteria. Their techniques have led to an explosion of new studies.

The key problems with mycobacteria are their slow growth, their waxy
coat and their tendency to form clumps. ¿ìè¶ÌÊÓƵs had already begun to
sidestep these problems by taking genes out of mycobacteria and inserting
them into another, fast-growing and laboratory-friendly bacterium, E. coli.
Jacobs, for example, has already made ‘gene libraries’ of the mycobacterium
that causes leprosy, M. leprae, in this way. One set of vectors that scientists
use to get DNA into E. coli are phages, viruses that infect bacteria. Phages
are commonplace in the soil: one of Jacobs’s favourites came from his own
back yard and was christened the Bronx Bomber.

But Jacobs wanted to study the effects of individual manipulated genes
in mycobacteria, which presented a tricky problem: how could he transfer
the DNA back from E. coli into the mycobacterium? With something akin to
molecular wizardry, Jacobs and his team selected an ideal phage and found
a region of its DNA that was not essential to its survival. This region
of the DNA could be manipulated without destroying the phage. Into it, they
introduced a cosmid – a circular piece of DNA containing the genetic components
of E. coli that are essential for its growth.

NAKED DNA

The resultant molecule is a kind of chameleon which can replicate as
a phage in a mycobacterium, but also in E. coli as a self-contained piece
of DNA known as a plasmid. In other words, Jacobs had devised a shuttle
that could be manipulated in E coli and then transferred into mycobacteria.
‘This allowed us to get naked recombinant DNA into the mycobacterium for
the first time,’ he says. The initial shuttle was not ideal, because it
killed the mycobacteria but eventually, the group engineered one that could
integrate its DNA stably into mycobacteria without killing them. Using
this, they were able to identify individual genes, and devise markers
for distinguishing one strain of mycobacterium from another. They went
on to develop a whole arsenal of vectors, some based simply on plasmids,
to manipulate mycobacterial DNA.

From there, Bloom, Jacobs and their colleagues at the University of
Pittsburgh and a company called MedImmune, went on to make a recombinant
form of BCG, the mycobacterium that is used for vaccinating against TB.
The recombinant BCG carries genes from other disease-causing organisms,
such as HIV, so that antigens from the other organisms are carried on the
bacterium’s coat. The aim is to exploit BCG’s convenience as a cheap, safe
vaccine and improve it to make a single vaccine that could immunise against
all the major killer diseases.

In the long term, TB is likely to continue killing millions each year
in the developing world. So far, the US’s response to the new epidemic has
been less than overwhelming. ‘Not a single new dollar has been allocated
to this epidemic by Congress,’ says Bloom. Even if the spread of drug-resistant
strains can be brought under control, sceptics fear that the disease will
disappear from the political agenda again as soon as the threat to the
so-called ‘general population’ is thought to have diminished. If that happens,
then history will repeat itself.

Jane Seymour is a freelance health writer based in London.

* * *

1: The poverty connection

We drive between the burnt-out buildings and dead cars of the south
Bronx, under the network of expressways that whisk affluent New Yorkers
over the top of this third world and out to the north. People wander about
in the traffic trying to sell doormats and dishcloths.

Our first patient is Vincent, a 42-year-old Vietnam veteran who has
been taking TB drugs for a few months. He grew up in the housing projects
of Long Island City, came to the Bronx ‘by mistake’ and started injecting
heroin. Now he lives in a single people’s hostel. He stopped taking heroin,
abruptly, after injecting a batch that was laced, he says, with meat tenderiser.

Vincent is witty, intelligent and sad. He jokes about Ronald Young,
his health visitor and my guide for the morning, not giving him time to
put his make-up on for my visit. Treatment will resolve his TB, but his
life will hardly be any easier as a result.

The same is true of Theresa, a 37-year-old with eight children living
in a two-roomed apartment in Newark, New Jersey. The living room is tiny,
with no direct source of natural light. Theresa is painfully thin but Judy
Thomas, the field nurse from Newark’s University Hospital who is supervising
her therapy, says she is much better than she was. Theresa’s rent bill for
the apartment is $450 a month, and her electricity costs about $130. She
gets $617 in welfare payments, and food stamps. Social workers recently
threatened to take her children into care when she failed to bring them
to clinic for their own TB treatment.

Debra has a strain of TB that is resistant to both isoniazid and rifampin.
She became infected in 1988, she believes, after nursing her sister, who
died of TB. Her mother also died of TB. As a former nursing assistant in
a local hospital, Debra has had to give up work because TB has affected
her back. She gets $483 in welfare benefits; her rent is $500.

In the informal economy, she trades food stamps for dollars with a relative
in order to pay her gas and electricity bills. There is no phone in the
building. Debra is entitled to a disability pension, but is still waiting
for her claim to be processed. She says she has a drug-resistant strain
because she originally failed to take the evening doses of her drugs. ‘I
was a drinker. I would come home from work and sit and drink a pint of
rum.’ She has stopped drinking now because her sons depend on her. She
is bitter about her mother’s death, which she feels could have been avoided
with a more prompt diagnosis.

* * *

2: Questions and answers

What’s the difference between TB infection and TB disease? A third of
the world’s population is infected with TB, and the number of new cases
of disease for 1990 was 8 million. Once infected with the TB bacterium,
you have a 10-per-cent chance of developing the active disease over your
entire lifetime. If you are infected with HIV and TB, the risk of developing
TB disease increases dramatically, to 8 per cent a year. Malnutrition and
immune suppression increase the chances of developing active TB disease
too.

How is TB spread? The bacterium travels in airborne droplets, so it
can be spread by coughing, sneezing and even talking.

Can I get infected in public places? There is no simple answer. Only
a quarter of the household contacts of TB patients are found to be infected,
and provided your immune system is healthy, you have to share the same air
with an infected person for several hundred hours on average before you
get infected.

But if you have AIDS or are on immunosuppressive drugs for cancer therapy,
for example, you can become infected simply by sharing a clinic waiting
room with someone who has TB. People on antibiotic treatment are no longer
infectious, provided that their strain of TB is sensitive to the TB drugs
that they are receiving. Ultraviolet light kills the bacterium, and ventilating
the air sharply reduces the risk of spread.

* * *

3: Fears mount over Britain’s TB figures

Once the scourge of Victorian England and many an artist and poet, tuberculosis
has long since lost any literary cachet. But in recent years, the steady
decline of the disease in Britain, which began with the advent of effective
antibiotics following the Second World War, has come to an abrupt halt.
In 1987, 5086 cases of TB were reported to the Communicable Diseases Surveillance
Centre; the latest figure, for 1991, is 5504.

Why? Much of the recent rise in tuberculosis in the US has been blamed
on HIV, but the situation in Britain is far less clear. John Watson, a consultant
epidemiologist at the CDSC, attributes the bucking of the downward trend
to several factors. One of the most important, he says, is that there are
still people alive today who contracted TB as teenagers during the Second
World War, when the disease was still rife. As they age and their immune
systems weaken, their latent infections are often reactivated.

Researchers estimate that more than 25 per cent of all TB cases reported
in Britain are confined to patients over the age of 65.

Another large TB group comprises people from the Indian subcontinent,
for whom TB is 30 times more prevalent than in the rest of the population.
The CDSC’s annual statistics are not detailed enough to reveal whether the
overall rate is increasing or decreasing in this section of the population,
says Watson, but at least some of the recent increases in TB have occurred
in areas with large Asian communities.

The spread of HIV accounts for some of the increase in TB in Britain,
but Watson describes its contribution as ‘pretty small’. And while he expects
it to rise, he is not predicting the phenomenal increase seen in the US.
The reason, he says, is that there is only a small overlap between the groups
of people who are most at risk from TB and those who are contracting HIV.

To a casual onlooker, Britain’s overall figures for TB might suggest
the disease is simply not disappearing as fast as everyone expected. But
increasingly, health workers with direct experience of TB patients are pinning
the blame for its comeback on the disease’s traditional allies: burgeoning
poverty and homelessness. In the wake of particularly sharp increases in
TB in certain deprived inner city areas, many fear that the health services
needed to keep the disease check are no longer in place.

One problem area is Camberwell in southeast London, where the TB rate
is five times the average for the rest of England and Wales and nearly half
that of Karachi in Pakistan. One in four of Camberwell’s TB patients is
homeless. Homeless patients are a particular challenge because health workers
find it hard to monitor their progress while they are taking antibiotics.
TB patients often need to take drugs for up to nine months, and failing
to complete a course encourages drug-resistant strains to develop. In Britain,
about 2 per cent of reported TB infections are resistant to one or more
major drugs.

Many of the specialist health services which once kept TB in check no
longer exist. Until 1985, for example, Camberwell had a hostel dedicated
to housing TB patients – only if patients took their tablets did they receive
breakfast there. Until recently, Britain had several specialised X-ray
facilities to which doctors could refer patients for diagnosis. The money
saved from its closure was lost to TB services.

In August, researchers at the CDSC reported in the British Medical
Journal that some health authorities have cut childhood vaccination programmes.
Fifteen authorities no longer offer schoolchildren the standard BCG immunisation
and 31 authorities do not offer it to newborn children. Eight of this second
group are in areas where more than 3 per cent of the population comes from
the Indian subcontinent.

‘It looks rather gloomy from the prevention point of view when you realise
that just one person can give 50 contacts,’ says Barry Gray, a consultant
in thoracic medicine at King’s College Hospital in London. ‘We need good
old-fashioned public health measures but that’s going to need money. The
Department of Health needs to target money to provide specialist training.’

Prevention plans need to be based on sound data regarding how TB is
likely to spread and on which strains of the bacterium will predominate.
Fortunately, research into the microbiology of TB, especially rare strains
of the bacterium, has survived marginally better than the public health
measures. Even so, there is only one clinical research unit, based at the
Sefton General Hospital in Liverpool. According to Peter Davies, the chest
specialist who heads the unit, getting money for long-term studies is nigh
impossible: over the past three years Britain has spent less than £30
000 on clinical research into TB.

‘There’s just no interest at the moment. I have tried to get money for
a statistician to do the mathematical modelling but have not got past first
base on that one.’

The consensus is that what are most needed are faster-acting drugs;
According to Davies, however, the pharmaceuticals industry isn’t interested.
‘There are no new drugs being manufactured specifically towards TB,’ he
says. ‘Companies are not interested unless they can recoup millions of dollars.’

‘I’m concerned about the lack of concern. It looks as though we’ll have
to wait until the statistics get more worrying before anything is done.’

* * *

4: Trials of a vaccine

There is no doubt that the BCG vaccine saves millions of children’s
lives by protecting them against TB. This and its cheapness and safety have
made it the most widely used vaccine in the world. In adults, however, the
story is more complicated and scientists are divided as to whether the
vaccine works or not. The vaccine is not widely used in the US. By contrast,
in Britain most schoolchildren receive the vaccine, although some health
authorities have recently stopped giving it.

Bacille Calmette-Guerin is a live mycobacterium from cattle, which has
been weakened in the laboratory by passing it through cultures until it
is incapable of causing disease. There have been 18 controlled trials of
the vaccine in adults. The results are perplexing: some of the trials show
the vaccine to be highly protective, some show it to fail miserably, and
the remainder were inconclusive. What does this mean? So far, no one knows.
It is impossible to try to analyse the old trials further, because they
were designed to answer only one question: Does the vaccine work or not?
No other data were collected, and in any case, it is a dangerous business
to try to interpret clinical trials retrospectively.

But there is one possible explanation. Where the trials failed, such
as in a large study in India, the populations tended to have something in
common. They were all in environments where other, benign, mycobacteria
are endemic. By contrast, such mycobacteria tend to be absent in populations
where the vaccine has worked. It could be, says Barry Bloom of the Albert
Einstein College of Medicine, that the benign mycobacteria had stimulated
some degree of protective immunity in people. If this were so, the vaccine
would have added little and the trials would have failed to detect any
difference in infection rates between the vaccinated and unvaccinated.

One other controversy surrounds the use of BCG. Could this normally
harmless bacterium cause problems in people whose immune systems have been
destroyed by HIV? There are rare, anecdotal accounts of the vaccine causing
‘BCG disease’ in people whose immune systems are suppressed. Some scientists
argue that it might be dangerous to vaccinate all babies in areas where
large numbers of women are infected with HIV and are passing the virus on
to their offspring. Most researchers argue, however, that there is no evidence
of widespread BCG disease in children in populations heavily affected by
HIV and that TB poses a far greater threat. They argue that TB poses a
far greater threat to infants.