Image credit: NIAID
FIRST PUBLISHED IN NATURE, 2 JANUARY 2013
REPUBLISHED IN NATURE OUTLOOK SPECIAL COLLECTION ON TUBERCULOSIS, 2017
If there was any doubt that tuberculosis (TB) was fighting back, it was dispelled in 2005, at the Church of Scotland Hospital in the village of Tugela Ferry, South Africa. Doctors at the hospital, in a rough, remote corner of KwaZulu-Natal province, were hardened to people dying from gunshots and AIDS. But even they were puzzled and frightened when patients with HIV who were responding well to antiretroviral drugs began dying — rapidly — from TB.
With ordinary TB, patients start to feel better after a few weeks or months on a selection of four mainstay antibiotics. But of the 542 people with TB at the hospital in 2005 and early 2006, 221 (41%) had a multi-drug-resistant (MDR) form, against which these therapies are mostly powerless. Worse, 53 of them did not even respond to the few antibiotics that form a second line of defence. Eventually, doctors had nothing left to try: all but one of the 53 died, half of them within 16 days of diagnosis. It was the first major outbreak of what became known as extensively drug-resistant (XDR) TB — and a wake-up call to the world that TB had taken a turn for the worse1.
In the early 1980s, TB cases had dropped to such low rates that Western policy-makers frequently talked of eradication of the disease. Then came the HIV epidemic, which triggered a resurgence of TB in the late 1990s. But the latest report on TB from the World Health Organization (WHO), published in October, revealed signs of progress against normal — or drug-sensitive — cases of the bacterial disease. New infections have fallen and the mortality rate has dropped by 41% since 1990. But, the report warned, “drug-resistant TB threatens global TB control”. Some 3.7% of new cases and 20% of previously treated cases are MDR-TB. And whereas in 2000 the highest incidence of MDR-TB was 14%, in Estonia; in 2010 that figure had jumped to 35%, in Russia's Arkhangelsk province. An estimated 9% of drug-resistant cases are XDR-TB, which has now been reported in 84 countries.
It is a tale of two TBs. Once detected, drug-sensitive TB is almost always treatable, as long as the appropriate drugs are provided and taken. Simple practices — such as checking that patients take their medicine — can be transformative. But in some countries, particularly in eastern Europe, Asia and Africa, the weakening or collapse of health-care systems over the past two decades has meant that patients do not always finish their drugs, or they take the wrong ones, allowing highly transmissible, drug-resistant strains to emerge and spread.
Drug-resistant TB is harder, more expensive and more time-consuming to treat. New tools are needed — but there have been no new anti-TB drugs in more than 50 years, and the current vaccine is largely ineffective. The most common diagnostic technique — analysing sputum samples under a microscope — can determine that Mycobacterium tuberculosis bacteria are present but not whether they are drug resistant. Meanwhile, researchers have lacked interest in developing drugs and tests, and drug companies have lacked market incentives to do so.
The growth of multi-drug resistance is an “escalating public-health emergency”, says Grania Brigden, TB adviser for Médecins Sans Frontières (Doctors Without Borders) in Geneva, Switzerland: “With barely 1 in 20 TB patients being tested for drug resistance, we're just seeing the tip of the iceberg.”
But scientists are careful to temper their alarm. In the past decade, researchers and policy-makers have fought for and won a reversal in funding and attention for TB. Several new drugs are in development, and progress is being made towards an effective vaccine.
“I do worry when people stand up at conferences and talk about MDR-TB and say it's a big disaster and the whole world is going to collapse. It's not that severe yet,” says Tim McHugh, head of the Centre for Clinical Microbiology at University College London, who leads a team that is trialling one of the two most advanced candidates for new TB drugs. “The big anxiety is that if we don't act now, it will easily run away from us.”