Indian patients with multi-drug-resistant TB are running out of treatment options © AP

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In December 2011, Zarir Udwadia, a tuberculosis expert in Mumbai, announced that he had diagnosed four patients with a new type of tuberculosis that proved resistant to all known medicines. He called the new form of the disease “totally drug-resistant” TB, and since then, he says, he has seen at least eight more cases in India.

Estimates suggest that India also has around 62,000 cases a year of so-called multi-drug-resistant tuberculosis — a form that cannot be cured by the usual first-line treatments but does respond to other drugs. Dr Udwadia considers that figure to be an underestimate, however.

“We have seen a slow but steady rise in the number of patients with the most dreadfully resistant TB strains,” he says. “Some of them are therapeutically destitute — we literally have no drugs left to treat them.”

The rise of drug-resistant TB in India is one instance of a problem that some scientists warn signifies humanity’s return to the dark ages of medicine. Antibiotics could completely lose their efficacy against drug-resistant superbugs, they say, meaning that now-treatable common infections or simple surgical procedures could once again become life-threatening.

Drug-resistant strains of diseases like TB, gonorrhoea and pneumonia are created when patients fail to complete a full course of prescribed drugs. By cutting short a course of medication once they start to feel better, patients allow the remaining bacteria in their bodies to survive and may build up a resistance to the drug.

Scientists and public health workers are increasingly agreeing that vaccines, which curb excessive antibiotic use by reducing incidence of disease, will be a critical weapon in the fight against superbugs.

“Vaccines prevent infections and so reduce the need for antibiotics,” the UK-led Review on Antimicrobial Resistance argued in a February report. “This is true for vaccines that prevent bacterial infections, and it is also true for vaccines that prevent viral infections, such as the flu, which should not be treated with antibiotics, but often are anyway.”

2.2m

Number of new TB cases India has each year, just under a quarter of the world’s total

Widespread overuse of antibiotics — not just for humans, but also in mass agriculture — has even led to the emergence of a separate bacterial gene for antibiotic resistance. But the impact of an advanced pneumococcal vaccine in South Africa has shown that vaccines can help to curb drug resistance.

In 2009, South Africa began vaccinating children for pneumonia, an infection once treatable by penicillin but that was, at the time, showing growing drug resistance. Not only did the vaccination programme sharply reduce the number of pneumonia cases but it also reduced the proportion of drug-resistant strains of the disease. “Infection rates went down, but resistance went down more,” says Seth Berkley, chief executive of Gavi, the global vaccine alliance.

Dr Berkley says that in an environment with limited antibiotic use, the bacteria carrying the gene for resistance — an otherwise inefficient extra gene — lose any advantage over bacteria without the gene. This suggests that bacterial populations can evolve away from drug-resistant strains, if antibiotics are used less. “You take away the incentive for bacteria to have resistance if, over time, you get rid of antibiotic usage,” he says

India has around 2.2m new TB cases a year — just under a quarter of the world’s estimated 9.6m total, and more than any other country. The only vaccine currently available is BCG — named Bacillus Calmette-Guérin after the French scientists who developed it in 1906 — which can protect small children from severe disease, but has limited effect on adults.

Meanwhile, resistance to existing treatments is growing due to weaknesses in the state healthcare system, and incorrect or unsupervised treatment by private practitioners. Some patients have simply run out of medicines to try. “In this setting — when your therapeutic cupboard is bare, immune modulation may be the only strategy left,” Dr Udwadia says. “Vaccines fall into this category.”

Vaccines may be expensive to develop and produce on a large scale, but Dr Berkley believes more investment may be on the horizon. “Gonorrhoea has a huge problem with antimicrobial resistance,” he says. “In the old days, you used penicillin and it was cheap and easy to treat. But with the changes in antimicrobial resistance, vaccines may become more attractive to produce and to pay for.”

Funds are finally trickling into tuberculosis vaccine research, but the investment is still insufficient, according to organisations involved in the research effort, and there are many technical challenges.

“A new and effective vaccine to replace the BCG is desperately needed and in my opinion may be the only way to turn the tide against TB,” says Dr Udwadia. “Sadly, it’s proving fiendishly difficult to design a new vaccine. [It’s] at least a decade away.”

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