In S. Africa, a frightening resurgence

TUGELA FERRY, South Africa — TUGELA FERRY, South Africa -- The nurses now wear masks in the crowded tuberculosis ward at the Church of Scotland Hospital in this small town ringed by rocky hills. The windows stay open, even when it's chilly, to improve the flow of fresh air.

And every patient who arrives at this government hospital with a cough that has lasted at least two weeks is tested for a frightening strain of tuberculosis that has defied all known drug regimens, with deadly results.


Of 63 people known to have developed this mutant TB disease here in rural KwaZulu-Natal Province, 60 have died - most within a month of going to the hospital. With new tests indicating the strain has cropped up at 27 other hospitals in the province, health experts here and abroad are scrambling to figure out whether this could spin into a far-reaching epidemic.

"It could be we have the same problem everywhere. If that's the case, we have a big problem," said Willem Sturm, a medical microbiologist and dean of the University of KwaZulu-Natal's Nelson R. Mandela Medical School in Durban.


Without major action, including scaled-up infection control, "we will have that worst-case scenario of the numbers just getting bigger and bigger, and more and more deaths," said Dr. Tony Moll, chief physician at the missionary-founded Church of Scotland Hospital. "Who knows how fast it can grow and spread?"

Although this type of TB - called Extensive (or Extreme) Drug Resistant TB (XDR for short) - has been found in most regions of the world, including the United States, the numbers have been relatively small: Just 347 cases worldwide were identified by late 2004, and no other place has recorded Tugela Ferry's concentration.

The outbreak has raised such concern that officials of the World Health Organization and U.S. Centers for Disease Control and Prevention converged on Johannesburg this month for two days of urgent meetings.

"TB is a disease without borders," said Dr. Kenneth G. Castro, director of the CDC's Division of Tuberculosis Elimination. The outbreak should reinforce the need for vigilance in the public health sector, he said. "XDR TB anywhere in the world poses a threat to everywhere in the world, including the U.S."

The South African government placed an order this month for two TB drugs long ago discontinued in that country, in the hope that they might provide a cure in combination with other drugs. But Moll and others say they are weak drugs and might not work.

Ignored disease

Medicine's seeming inability to treat XDR stems partly from the fact that the world has largely ignored tuberculosis for years, say experts. Once the No. 1 killer in the United States, according to the CDC, TB was brought under control starting in the 1940s by the development of drugs. No new drugs have been developed in more than 40 years.

Meanwhile, across sub-Saharan Africa, the HIV epidemic continues to fuel a parallel TB epidemic because tuberculosis poses great risk to those with weak immune systems. South Africa has more people with HIV, about 5.5 million, than any country but India. Globally, the WHO estimates TB kills 1.7 million people a year, 590,000 in Africa. Everyone who developed XDR TB here tested positive for HIV or was suspected of having the virus, which causes AIDS.


Since the mid-1980s, the number of active TB cases at Moll's hospital has increased tenfold, from 200 a year to more than 2,000. Nationwide, more than 270,000 people had TB in 2004, the government says.

Even ordinary tuberculosis kills thousands here. Moll said 8,000 people die every year of treatable TB across the province of 9.3 million; perhaps they don't or can't seek treatment, or are so ravaged by it and HIV that they cannot be saved. Without treatment, normal TB will kill otherwise healthy people half of the time, Sturm said.

On top of that, drug-resistant TB, which resists some but not all available drug combinations, is a growing worry that claims 1,500 lives a year in the province, Moll said. It costs $3,250 to treat, compared with $50 for normal TB.

And now there is essentially untreatable XDR, which might have mutated from multidrug-resistant TB. Resistant strains can emerge when patients fail to finish the standard four-drug, six-month treatment, a problem compounded by lack of health care workers to monitor adherence.

Experts have tried to allay growing public alarm by saying healthy people are not at great risk of having a latent infection turn into TB of any sort. Yet news of XDR's emergence in town and the lack of hard information are raising fears.

"I'm afraid. I want to know a lot about that kind of TB," said Mthunzi Makhunga, a store clerk walking along Tugela Ferry's main street Thursday. "Maybe one day it will affect me."


Word that a Johannesburg woman with XDR was unaccounted for in South Africa's biggest city prompted banner headlines. Hers is the 64th confirmed case and the only outside KwaZulu-Natal. By Thursday, she had been located. Health officials said her relatives seem fine, but details of her condition weren't released.

Causes of TB

Tuberculosis is caused by bacteria that usually attack the lungs. It is spread when an afflicted person coughs or sneezes, and someone nearby breathes in the bacteria. Poverty worsens it because the poor often live in cramped, unhealthy conditions.

The WHO estimates a third of the world's population is infected with latent TB. Most people do not develop active TB. The disease arises when weak immune systems are unable to keep the bacteria from multiplying. Symptoms often include a bad cough, phlegm in the lungs, fatigue, weight loss and lack of appetite.

The virulent strain's emergence in Tugela Ferry comes at a cruel time: just as progress is being made on HIV, thanks to antiretroviral drugs rolled out belatedly by the national government in March 2004.

In late 2004, Moll and a Yale University researcher were studying patients with HIV and TB. They saw "amazing turnarounds" because of antiretrovirals. "But we noticed a small group of people who were not getting better," Moll said. "Their TB was rapidly progressing in spite of being on TB drugs" and, often, on antiretrovirals.


In spring 2005 they sent sputum samples from 45 patients to a Durban lab. In May that year, Moll got a call from the lab. Ten of the samples were XDR, meaning the TB was resistant to all so-called first-line drugs and all tested second-line drugs.

"We really were not expecting that," he recalled. "It was not something we'd come up against. That was a big red flashing light that there was something wrong."

Moll alerted the provincial Department of Health. Without any publicity, the Church of Scotland Hospital stepped up surveillance, taking samples of everyone with lingering coughs. The province added hospital staff, including two teams to track down everyone who came in contact with a multidrug-resistant patient.

Moll said the province still should conduct an epidemiological study to understand where this XDR strain came from and just how it is transmitted. He wants better ventilation in TB wards to aid prevention. And while he does not want to sow panic, he wonders why provincial health officials do not seem more worried.

"I talk to provincial people - they say, 'Gee, sorry about that, keep on with the good job, let's hope it doesn't get worse,' " he said. By contrast, at last month's Toronto AIDS conference, people told him, "Wow, this is something really terrible you've got; something needs to be done about it."

The chief spokesman for South Africa's Ministry of Health said provincial authorities have done a fine job managing the problem. "We are really concerned about TB in general, but also about this particular strain," said the spokesman, Sibani Mngadi. On Friday, the ministry, criticized after Health Minister Manto Tshabalala-Msimang skipped this month's Johannesburg meetings with global experts, gathered health officials from all nine provinces to discuss the threat.


Next steps

A presentation in Toronto helped spread the word and led to the Johannesburg meetings with the WHO, CDC and South Africa's Medical Research Council. In response, experts renewed calls for drug development and faster identification of XDR TB than the current six-week period.

Moll said new cases might be spreading in his TB ward during the six weeks when all patients are together. "It's a long time. That's a very dangerous situation." The CDC's Castro said existing methods used in the U.S. halve that to three weeks, and new methods in final-stage development could cut it to one day.

A key next step, Sturm said, will be to do in-depth studies at several hospitals in the province to better understand the scope and gauge whether initial results from the 27 hospitals indicate a wider danger.

XDR's toll may yet grow. Buzaboni Phungula, 42, died Sept. 7, three weeks after falling ill with TB, his family said. "He just became suddenly sick and then died," said his sister, Bongeni. Moll said he is awaiting test results, but "it might be XDR."

Two of the three survivors from the group of 63 are not out of the woods, nor is the Johannesburg woman who is No. 64. But the third survivor in Tugela Ferry is home, doing "amazingly well," Moll said. He cannot explain it, except that the man had been on antiretrovirals for a couple of months.


"He's not coughing XDR germs out anymore, and he's gaining weight and looking strong. Here's one guy who has gone against the grain and [is] doing well and giving us some hope."