Published online 23 June 2010 | Nature | doi:10.1038/news.2010.311

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'Hidden' tuberculosis raises drug-resistance fears

New study doubles known rate of infection at a South African hospital.

Researchers found high rates of TB and HIV, seen here in scanning electron microscope images.Janice Haney Carr-CDC / CDC

Huge and hidden levels of tuberculosis discovered in a South African province devastated by HIV are increasing concerns about the prevalence of drug-resistant tuberculosis in Africa.

As reported in PLoS Medicine1, when researchers examined newly deceased patients at Edendale hospital in the province of KwaZulu-Natal, they discovered that 50% were infected with the bacterium M. tuberculosis, the causal agent of tuberculosis, with 17% of the infected individuals carrying a multi-drug resistant (MDR) strain.

Among those with TB, only 58% had been diagnosed and started on treatment before their death. A previous study had found that only 28% of patients admitted to the same hospital were diagnosed with active tuberculosis.

In the new study, 96% of those positive for M. tuberculosis were also HIV positive, and the alarming prevalence of tuberculosis may reflect the situation in other low-income countries plagued by HIV. With weakened immunity, HIV-positive individuals are extremely vulnerable to other infections.

"This report is extremely serious," says Mario Raviglione, director of the WHO Stop TB Department in Geneva, Switzerland. "It confirms that over the last few years, multidrug-resistant tuberculosis has become rampant in people living with HIV [in Africa]".

According to the World Health Organization, South Africa ranks fifth among countries with the highest tuberculosis burden. Infection rates in KwaZulu-Natal may be especially high as 39% of adults are HIV-positive, according to a 2008 UNAIDS report2.

Douglas Wilson, head of medicine at Edendale and an author on the PLoS Medicine paper, hadn't expected such staggering rates of tuberculosis. "When you drive to my hospital, you see a number of funeral parlours along the road," he says. "At least we now know why they are in business."

The new study looked at 240 adults aged between 20 and 45 who died from any cause excluding trauma or childbirth. Many of these patients might have survived had their tuberculosis been detected earlier, as 42% of them were not being treated for it.

Tuberculosis slips under the radar because many patients admitted to hospitals never get tested. Even if they do, the cheapest and most commonly used diagnostic tests, which involve examining sputum under a microscope, often miss cases. In particular, HIV-positive people typically suffer from forms of tuberculosis that sputum tests don't detect.

By culturing samples drawn from organs and the respiratory tract, this team diagnosed the presence of MDR M. tuberculosis with greater accuracy than less invasive tests can.

Drug-resistant danger

Although too little information exists to tell if MDR tuberculosis is on the rise globally, Peter Cegielski, at the US Center for Disease Control's Division of Tuberculosis Elimination in Atlanta, Georgia, predicts that the epidemic will worsen because of inadequate capability for diagnosis and treatment.

"As drugs are used more and more, they will create new cases of MDR TB as predictably as the sun will rise tomorrow," he says. "That's the nature of evolution. When we put tremendous selective pressure on those bacteria, the drug-resistant mutants are going to survive."

Poor-quality drugs or incomplete drug regimens also give resistant TB bacteria time to arise, multiply, and infect others.

On June 15, the non-profit Center for Global Development in Washington DC warned that drug quality must be more carefully monitored and diagnostic capabilities improved so that drug-resistant tuberculosis can be stopped before it spreads further.

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Rachel Nugent, deputy director of global health at the organization, says long-term savings from such moves will vastly exceed up-front costs, as standard tuberculosis treatments cost US$20 whereas those for the drug-resistant form of the disease start at $3,500.

Yet Wilson says Edendale lacks the expertise and resources required to run faster, more accurate tests on a large scale.

In the meantime he's turned to HIV prevention as a means to slow the tuberculosis epidemic. "You can chose to have safe sex," he says, "but you can't chose not to breathe." 

  • References

    1. Cohen, T. et al. PLoS Med. 7, e1000296 (2010). | Article
    2. 2008 Report on the Global AIDS Epidemic (UNAIDS, 2008).
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