Tuberculosis prevention may speed drug resistance





A study published today in Science Translational Medicine illustrates the perverse choice that public health experts sometimes must make between preventing a disease and preserving the effectiveness of a treatment. When it comes to tuberculosis, the report finds that prophylaxis comes with a higher cost than previously recognized.

The main ingredient in the drug cocktail to cure tuberculosis, isoniazid, can also protect people from contracting the disease in the first place. This second function is particularly important for those with fragile immune systems who frequently acquire and die from tuberculosis. In sub-Saharan Africa, tuberculosis  is the leading cause of death among HIV-infected individuals. To curb this fate, the World Health Organization (WHO) recommends isoniazid as a preventative therapy for HIV-positive patients that don’t already show signs of active tuberculosis.

However, according to new study, led by Harriet Mills at the University of Bristol, in communities that implement isoniazid preventative therapy (IPT) the incidence of new isoniazid-resistant cases per year will double in the next 40 years.

The typical TB treatment that includes isoniazid lasts six months. But when isoniazid cannot be used, a patient has to endure a longer treatment, which includes injections and swallowing a dozen tablets daily for two years. These drugs have side effects such as seizures and permanent hearing loss.

Treatments for drug-resistant tuberculosis cost more too. “South Africa spends half of their tuberculosis budget on multidrug-resistant tuberculosis, even though just 3% of tuberculosis cases are” resistant to drugs, says Ramanan Laxminarayan, the director of the Center for Disease Dynamics, Economics & Policy based in Washington DC.

“From a policy standpoint, this is an extremely important paper,” says Laxminarayan, who is not an author on the report. When deciding whether to follow the WHO’s recommendations, he says the many countries that have not yet implemented IPT should keep this caution in mind.

However, Karin Weyer, a coordinator in the WHO’s Stop TB Department, says, “We do not need to panic.” She says that the study is “interesting” but points out that it is based on mathematical modeling as opposed to observations on real people. “From the WHO’s perspective, we look to field evidence when we write policies.”

Resistance was known to arise when people with active tuberculosis took only isoniazid without the other chemicals present in first-line tuberculosis therapy. This study adds that the preventative treatments may also help resistant strains spread among people on IPT and those in their community. According to mathematical models, drug-resistant strains would rise relative to normal ones because they would have more human hosts to reside in when some community members are given IPT.

Within a decade, an increase in isoniazid-resistant cases might not be catastrophic if new first-line drug cocktails currently in the pipeline make it to the clinic. At least two regimens now in clinical trials do not include isoniazid. And despite fears of resistance, the authors of the study remain in favor of IPT as long as doctors monitor drug resistance.

But few countries burdened with tuberculosis have the funds to diagnose resistance efficiently. For that reason, Laxminarayan says that for the moment, IPT might make sense in South Africa, which has the necessary resources, but not in India. He warns, “You always want to be careful to not cause more damage than you prevent.”