Drug resistance and tuberculosis

Sep 21, 2011 | Anna Tomasulo | Outbreak News

 

In a recent press release, Stop TB reports that 15 of the 27 countries with the highest burden of multi-drug resistant tuberculosis are located in Eastern Europe. According to the Stop TB Partnership, three people die of tuberculosis (TB) every minute.

“TB is an old disease that never went away, and now it is evolving with a vengeance,” says Zsuzsanna Jakab, the Regional Director of WHO-Europe.

On September 15 2011, WHO released an action plan to stifle the spread of drug resistant tuberculosis in the WHO defined European Region. This region contains approximately 18% of the world’s multi-drug resistant tuberculosis (MDR-TB) patients.

This plan has three main goals, scheduled to be met by 2015. These include decreasing the proportion of MDR-TB cases among patients previously treated for TB by 20 percent, diagnosing at least 85 percent of all MDR-TB cases and treating at least 75 percent of MDR-TB patients successfully. 

Hans Kluge, the regional director’s special representative on multi and extensively drug resistant TB (XDR-TB) at WHO Europe says, the problem is “a man-made phenomenon resulting from inadequate treatment.”

 

What is TB?

Tuberculosis is a bacterial disease caused by Mycobacterium tuberculosis. It is transmitted via tiny droplets in the air (droplets containing as few as one to three bacilli can cause infection) that are breathed in by others. Symptoms include persistent coughing, fever, night sweats, loss of appetite and weight and coughing up blood. 

A person with untreated active TB will infect between 10 and 15 people each year.

The proper course of treatment for TB depends on whether the patient has a latent TB infection or active TB disease. People with latent infections have immune systems that are capable of containing the bacteria. They will not infect others with the disease, nor will they experience symptoms. Because containing the bacteria is largely dependent on the strength of the immune system, the person must still be treated. Treatment will consist of taking a drug, such as isoniazid, for up to nine months.

Someone with active TB disease has more TB bacteria in the body than the immune system can handle. He or she will take what are called “first line drugs”. Among these are isoniazid, rifampicin, pyrazinamide and ethambutol. The treatment period may last from six to 12 months. 

 

DOT

Clearly, treating TB is a lengthy process. A challenge with TB treatment is guaranteeing that people take the appropriate dosing of medication for the prescribed length of treatment. 

DOT, or “directly observed therapy,” is a way to ensure adherence to treatment regimens.  A trained health care worker is assigned to a patient. The health care worker provides and watches the patient consume the prescribed drugs. Research shows that DOT increases adherence to treatment, helps prevent the transmission of TB and decreases the development of drug resistant TB.

 

What is MDR-TB?

Multi-drug resistant tuberculosis is defined as tuberculosis that is resistant to two of the first line drugs, isoniazid and rifampicin. Resistance to antimicrobial drugs can either occur based on a characteristic of the microbe itself, mutation in the microbe or gene transfer. 

As previously stated, drug resistance to TB drugs is a man-made problem; wild Mycobacterium tuberculosis is susceptible to anti-TB drugs. Problems arise when an individual has poor adherence to a drug regimen (whether it be due to forgetfulness, stigma associated with being sick, lack of access to the drugs etc) and does not take all of the pills. Exposure to the drug regimen will kill the bacteria susceptible to the drug, but if the regimen is not completed, the strongest bacteria may be left behind. Those bacteria are now resistant to the drug.

This variation of tuberculosis can be transmitted. A previously healthy individual could become infected with a drug resistant strain of tuberculosis.

 

A few (of the many) challenges caused by resistance

Our medicine cabinets and pharmacies are teeming with difficult to pronounce drugs.  One would think we could just prescribe a stronger drug to take care of the remaining TB bacteria. 

Unfortunately, we have a limited number of drugs that have an effect on tuberculosis. The more resistant the strain of TB, the more expensive the drugs are to combat the disease. If we return, for a moment, to what causes resistance in the first place, poor adherence to a drug regimen, the expense of second line drugs becomes more significant.  Some patients may not be able to afford all the necessary TB drugs at once. They may begin treatment only to find that the cost of drugs exceeds their budget.

Tuberculosis, like many diseases and health conditions, affects poorer populations more negatively than affluent populations. Compounding the problem is the fact that TB can prevent work. If a person infected with MDR TB cannot work, they cannot earn an income, and they cannot afford treatment. If they cannot be treated, infection persists and the patient may die, which has a myriad of social, emotional and economic effects on a familial and community basis.

Recently, Nature published an article in which the challenges of developing a new TB drug were discussed. The article concludes by staying that any drugs or vaccines developed will fail to successfully combat TB if they are not accompanied by proper support from the health care system and social and economic changes that guarantee access to care for all TB patients, worldwide. 

 

Extensively drug resistant tuberculosis

The problem doesn’t stop with MDR-TB. Tuberculosis bacteria can develop resistance to second line (a set of drugs used as a back up if the “first line” doesn’t work) drugs as well. Once tuberculosis is resistant to at least two (isoniazid and rifampicin) of the best first line drugs, the best second line drugs (fluoroquinolones) and at least one of the three injectable drugs, it is classified as extensively drug resistant tuberculosis (XDR-TB). Like MDR-TB, XDR-TB is extremely serious because treatment options are limited and less effective.  According to the CDC, curing XDR-TB is possible for an estimated 30% of those affected.

 

Antimicrobial Resistance

Antimicrobial resistance is a serious threat: if microbes develop resistance to all the drugs we have, WHO warns we could return to a “pre-antibiotic era”. 

Other diseases have developed strains of resistance. Chloroquine can no longer be used in many malaria endemic countries, ciprofloxacin is the only drug recommended for use in treatment of Shigella organisms, gonorrhea has become increasingly drug resistant all around the world. 

Through the scope of TB, one can understand how serious drug resistance is. Since the development of penicillin in 1929 and the rapid increase in understanding microbes and how they work over the last 50 years, humans have felt pretty invincible. It would be a mistake to become lackadaisical or careless with drug treatments. Many pathogens have the ability to change; they change in order to survive. 

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