午夜福利1000集合

You鈥檝e heard of bird flu, and you probably remember the SARS panic of 2003. Now there is a new bug on the loose, right here in your backyard, and it is one that the World 午夜福利1000集合 Organization is declaring just as big a threat as those two diseases 鈥� although few column inches have been devoted to it so far.

The disease is an old enemy, but it has a deadly new twist. The bacteria that cause TB have mutated to resist most of the weapons we have against it. Dubbed extremely or extensively drug-resistant TB (XDR-TB), the strain is now spreading to every part of the globe, with cases discovered last year in the UK, US and Canada. And New Scientist can reveal that last month, Italy reported a case of TB that was invulnerable to every single drug we have 鈥� the first-ever known incidence of completely drug-resistant TB.

The advent of this 鈥渆xtreme TB鈥� is prompting some radical countermeasures. Because the disease can be passed on through mere coughing, countries such as the US have resorted to locking up patients who violate quarantine. The WHO is holding crisis meetings and doctors are experimenting with drastic surgery for those who have lost all other hope. Bob Swanepoel, a virologist at South Africa鈥檚 National Institute for Communicable Diseases, has battled plagues of Ebola and HIV, and knows a formidable enemy when he sees one. 鈥淴DR,鈥� he says, 鈥渋s a frightening disease.鈥�

TB has been a scourge of humanity for millennia 鈥� even Egyptian mummies have been found with its deadly fingerprints. Four centuries ago, for reasons that are still unclear, the disease seems to have gone on the rampage in Europe, and was responsible for one in five deaths from the 1600s to the 1900s. Sometimes called the 鈥渨hite plague鈥�, in reference to the deathly pallor of those affected and the only slightly deadlier black death, TB spawned the familiar literary character from that period: the 鈥渃onsumptive鈥� 鈥� feeble, coughing up blood and slowly but inexorably wasting away.

Today about a third of the world鈥檚 population are thought to carry the TB bacterium, Mycobacterium tuberculosis, in their lungs. In most it remains dormant, or latent, but one in 10 of those infected develop the active disease at some point, usually after some stress or setback to the immune system. That is when TB kills, and when it can spread.

The disease is most common in poor countries, and poor communities within rich countries, because dirt, malnutrition and overcrowding prompt the switch to active disease and help the infection spread. It typically passes between people in crowded sleeping areas, though it is possible that simply sharing a long-haul flight may be enough.

TB mainly attacks the lungs, killing tissue and creating holes and abscesses. People become gradually weaker, develop fever and night sweats, and usually die from respiratory failure or lung haemorrhage. Untreated, about a third of people with active TB recover, a third die relatively quickly and the rest linger, spreading infection before they die.

The first antibiotics against TB appeared in the 1940s. For a few decades, it seemed as though the white plague would be eradicated, at least among the wealthy, but now TB is on the rise once more.

Initially, it started spiralling among the poor, and the HIV-positive, whose ravaged immune systems cannot suppress active infection. Now the rise in the west is mainly among immigrants, whose latent infections turn active with the stress of emigration and poverty in a new land. It is this group that accounted for the UK鈥檚 record 10 per cent rise in cases between 2004 and 2005, and for most new cases in the US, although the total number of cases there is stable.

What is really frightening doctors, though, is the growing number of infections that are resistant to antibiotics. Resistance develops because TB is a tough bacterium to kill: it has a slow growth rate and a waxy coat that is hard for drugs to penetrate. Added to that is its habit of living inside the immune cells that should destroy it. So people with the infection must take the standard or 鈥渇irst-line鈥� antibiotics for up to nine months, and during this long siege any mutant strains that can withstand the drugs have time to flourish. In an attempt to pre-empt this, treatment begins with four antibiotics and continues with two of them, to ensure that any bacteria resisting one drug will fall prey to the others in the end. However, if patients stop their treatment too soon, either because they feel better, or because the medicines are unavailable or unaffordable, drug-resistant bacteria may remain.

The 1980s saw growing numbers of cases of multi-drug-resistant TB (MDR-TB), defined as bacteria that can withstand the two main first-line drugs. After that, only four antibiotic classes remain. They are much more expensive and must be taken for up to two years. Some have to be given intravenously, and all have nasty side effects, ranging from nausea and diarrhoea to convulsions and kidney failure.

A year ago this month, US doctors highlighted the first cases of XDR-TB, defined as resistance to the two main first-line drugs, and a specific duo of the second-line ones. This combination means the bacteria tend to be left susceptible to fewer than four other kinds of drugs, the minimum needed for a reliable treatment regimen.

Initially XDR-TB was thought to be a limited problem, primarily in countries such as Russia and China where enough people are taking the second-line drugs under less-than-optimal conditions to promote resistance. Then came a report from South Africa, which shocked delegates at the 26th International AIDS Conference in Toronto last August.

Since 2001, 53 people at one clinic had been diagnosed with XDR-TB, and only one had survived, with the rest dying within a few weeks. 鈥淭hat surprised us,鈥� says Mario Raviglione, head of TB at the WHO. 鈥淲e didn鈥檛 think there was much XDR-TB in Africa.鈥�

By October Raviglione had called a crisis meeting at the WHO headquarters in Geneva, Switzerland. The WHO now has response plans in place, and is trying to improve basic treatment overall.

It is also trying to assess the scale of the problem. Early figures seem to show that XDR is present across South Africa. Public-health labs around the world have pooled data on nearly 20,000 samples from people with TB in 49 countries taken between 2000 and 2004. In February these labs announced that nearly 2 per cent of the samples were XDR. The WHO has new figures due to be announced this month showing that in the US, the proportion of MDR cases that were in fact XDR grew from 3 per cent in 2000 to 11 per cent in 2004.

Now New Scientist has learned of the first known case of completely drug-resistant TB, in Italy. Raviglione points out that we are as helpless against this strain as we were before the development of antibiotics. 鈥淲e are back in the 19th century,鈥� he says.

鈥淲e are as helpless against completely drug-resistant TB as we were in the 19th century, before antibiotics鈥�

With XDR-TB, doctors can still attempt to treat people with the remaining drugs, in the hope that they will kill the bacteria before further resistance mutations arise. But for people with HIV in the developing world, XDR-TB is an almost certain death sentence. Even for those who don鈥檛 have HIV and live in the west, the prognosis seems grim; there are few statistics because this disease is so new, but a group of 64 US patients who received treatment had a death rate of one in three. Some US doctors are resorting to an approach reminiscent of the days before antibiotics 鈥� surgically removing infected lung tissue, or in some cases, a whole lung.

Jail wards

Doctors face another difficulty: how to cope with uncooperative patients. Being admitted to an isolation unit is a daunting prospect 鈥� patients must take nasty drugs, often for many months, possibly until their death. Unsurprisingly, some simply discharge themselves and go home, where they infect others. Another group that presents a dilemma are those who have a track record of stopping taking their TB medicines before the course is complete. Even if such patients are theoretically non-infectious, because they are responding to the antibiotics, doctors may strongly suspect that sending them home risks the life of the patient and those around them.

In the US, one such patient in Arizona is in a hospital jail ward, without visiting privileges, a phone or showers, allegedly because he stopped taking the antibiotics and visited food stores without wearing a mask. The patient, 27-year-old Robert Daniels, who contracted XDR-TB while visiting his native Russia, says he was afraid he would be mistaken for a masked robber. Another person with XDR-TB, in Toronto, Canada, was forced to return to hospital under a court order.

Authorities around the world are debating how to treat such cases. The WHO has issued a statement saying that forced quarantine may be needed as a last resort. But Raviglione warns: 鈥淚f people think they are going to be locked up they will not come for treatment. We will drive [TB] underground.鈥�

In the longer term, a key goal is to develop new antibiotics effective against TB. The pharmaceutical industry has long neglected the disease, as it has mainly affected the poor. Progress is being made, however, by the Stop TB consortium, funded by the WHO, donors and governments. It has nine drugs in development with two in clinical trials (New Scientist, 17 February, p 10), although none may be ready for at least another five years.

We also need to be able to diagnose cases of XDR-TB much more quickly than the present time of two months. The bacteria multiply so slowly that a sputum sample must be cultured for several weeks before getting enough bacteria to test for resistance, which is done by adminstering the drugs and seeing if the growth rate of the bacteria slows. By that time the patient could have infected many others 鈥� and patients with HIV could be dead.

The UK 午夜福利1000集合 Protection Agency鈥檚 TB reference lab has developed better tests, which it will use in southern Africa later this year. One uses an improved culturing method to speed the bacteria鈥檚 growth, allowing XDR to be diagnosed within two weeks. Another can identify MDR within two days using DNA analysis to test for the mutations that cause resistance to the first-line drugs. The tests will be made available to the developing world at an affordable price. Researchers are now trying to identify the mutations that cause resistance to the second-line drugs so they can identify XDR-TB in the same way.

The WHO says $650 million a year is needed to treat the estimated 1.5 million with MDR or XDR-TB worldwide 鈥� of which so far it only has $250 million.

Perhaps the first known case of completely drug-resistant TB will help galvanise global concern. There must be others 鈥� perhaps the person sitting next to you on that plane. The Italian case, says Raviglione, 鈥渋s probably just the tip of the iceberg鈥�.