Almost half of tuberculosis patients who received prior treatment were resistant to a second-line drug, suggesting the deadly disease may become “virtually untreatable,” according to a new study.
Among 1,278 patients who were resistant to two or more first-line tuberculosis drugs in Estonia, Latvia, Peru, Philippines, Russia, South Africa, South Korea and Thailand, 43.7 percent showed resistance to at least one second-line drug, according to a study led by Tracy Dalton at the U.S. Centers for Disease Control and Prevention. The findings were published in the Lancet medical journal today.
About 1.4 million people died from TB, the second-deadliest infectious disease globally after AIDS, and 650,000 cases were multi-drug resistant in 2010, according to the World Health Organization. Rising infection rates prompted the U.K. to announce in May it will require pre-entry tuberculosis screening for migrants from 67 countries seeking to enter the country for more than 6 months.
“The global emergence of extensively drug-resistant tuberculosis heralds the advent of widespread, virtually untreatable tuberculosis,” the study authors said in the published paper.
Previous treatment with second-line drugs was the strongest risk factor for resistance to these drugs, the authors said.
The prevalence of drug resistance, which ranged from 33 percent in Thailand to 62 percent in Latvia, also correlates with how long second-line drugs have been available in each country.
South Korea and Russia had the longest histories of availability -- more than 20 years -- and the highest rates of resistance. In contrast, Thailand, Philippines and Peru, where second-line drugs were introduced 10 years ago or less, had the lowest resistance rates.
Unemployment, alcohol abuse and smoking were also associated with resistance to second-line injectable treatment across countries.
This is one of the few studies that have followed patients with the multi-drug-resistant form of TB for several years, Justin Denholm, an infectious disease epidemiologist at the Royal Melbourne Hospital, said in a phone interview.
Patients not taking their medicines properly is a major driver for resistance, said Denholm, who is studying TB transmission patterns in Australia’s Victoria state.
The WHO’s current strategy for tackling TB is called Dots, short for “directly observed treatment, short course.” Under Dots, patients are required to show up at a clinic three times a week to be supervised when taking their medicine to be sure they complete the treatment.
“The reality is that this one-size-fits-all approach is a major part of what’s led to this drug resistance issue,” Denholm said. “I think individualized treatment is what we should be aiming for.”
Scientists are also researching new treatments. In a study published last month in the Lancet, researchers from Stellenbosch University in Cape Town said an experimental three-drug combination killed 99 percent of the bacteria within two weeks. As the combination doesn’t contain isoniazid or rifampicin, the two main medicines used against TB, it may also provide a much-needed weapon against drug-resistant strains, the researchers wrote.
India and China, which have the world’s highest numbers of tuberculosis cases, weren’t included in Dalton’s study as they hadn’t begun pilot programs for increasing access to second-line drugs until after the study began.
In a 2007 national survey in China, 27 percent of multi-drug-resistant tuberculosis cases showed resistance to the antibiotic fluoroquinolone, according to the Lancet report. In India, a 2006 population-based survey in the western state of Gujarat reported fluoroquinolone resistance in 24 percent of cases.
The U.K. Border Agency this month began requiring TB screening for Indians applying for a settlement visa and will extend the rule to those obtaining a work visa from Sept. 10. The new requirement replaces screening at airports.
TB is at the highest level in 30 years in the U.K. In London, 84 percent of the 3,302 people infected in 2010 were foreign-born, according to the Health Protection Agency.