World Tuberculosis Day Part III – Treatment & Drug Resistance

March 8, 2016 Maria Wilson Leave a Comment

The World Health Organization (WHO) has declared March 24, 2016 as World Tuberculosis (TB) Day [1]. Over the month of March, the Global Health Office will be publishing a series of blog posts about TB in hopes of raising awareness of its worldwide impact. WHO’s “End TB Strategy” has a goal of ending the TB epidemic by 2030, by targeting poverty, improving testing and treatment, ending stigma and discrimination, and driving research and innovation. Put simply, TB is not yet a disease of the past, but if we unite and focus our efforts, we can make TB history.

Last week we talked about diagnosing TB, and the importance of determining an appropriate treatment course along with that diagnosis. But how is TB treated, and why is drug resistance an issue with TB in particular?

Although those with latent TB infection do not present symptoms, and cannot spread TB bacteria to others, treatment can still be provided to stop them from developing TB disease. This step is important in eliminating and controlling TB around the world, but should only be initiated once the possibility of TB disease has been excluded. In the United States, four treatment regimens are approved, using combinations of isoniazid, rifampicin and rifapentine. Treatment for latent TB can last anywhere from 3 months to 9 months, necessitating between 12 and 270 doses (minimum) of anti-TB drugs [2].

Treating those with active TB disease is a much more pressing matter, as they have the potential to spread the disease to others. Treatment regimens for active TB disease can last between 6 and 30 months depending on resistance, a process which burdens patients and treatment providers alike [3]. With a treatment course this long, some patients inevitably fail to complete the full regimen, for many reasons including finances, social pressures and inadequate access to proper treatment. To provide a glimpse at the financial burden of TB, each case in Canada cost the healthcare system $47,290 [4]. This can lead to acquired drug resistance, which can then be passed on to others when the infected person, coughs, sneezes or spits, releasing TB bacteria into the air [5].

There are two types of drug-resistant TB: multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB). MDR-TB bacteria does not respond to (at least) the two most widely used and powerful first line TB drugs: isoniazid and rifampicin [6]. XDR-TB involves resistance to isoniazid and rifampicin, in addition to resistance to any of the fluoroquinolones (ofloxacin, etc.), and to at least one of three injectable second-line drugs (amikacin, capreomycin or kanamycin) [7]. Both MDR-TB and XDR-TB take longer than regular TB to treat (at least 18 months) and have lower treatment success rates. Furthermore, patients often experience more harsh side effects from treatment, leading to increased hospitalization [8]. In order to maximize the potential for positive treatment outcomes, it is important that further tests are undertaken after initial diagnosis to determine whether bacteria is drug-resistant, and provide appropriate treatment [7].

According to the WHO Global TB Report, in 2014 an estimated 3.3% of new TB cases and 20% of previously treated cases had MDR-TB. More than half of these cases occur in India, China and the Russian Federation. Additionally, an estimated 190,000 people died of MDR-TB in 2014. As of 2015, XDR-TB had been reported in 105 countries. The map below shows the number of patients in these countries with laboratory-confirmed XDR-TB who started treatment in 2014 [9].

Map of the world, showing the number of laboratory-confirmed cases of XDR-TB receiving treatment by country, 2014. (Source: World Health Organization).

In response to treatment non-adherence, and to combat the spread of drug-resistant TB, the directly observed therapy, short-course (DOTS) strategy was developed by WHO in 1994. Health workers meet with patients regularly to help with treatment, adherence, and to provide support and education. This strategy also advocates for increased allocation of domestic and international funding and resources to combat TB [10]. Tuberculosis is also highlighted in two recent worldwide strategies, the WHO End TB Strategy, and the UN Sustainable Development Goals (SDGs), which will be discussed in our next post.

World Tuberculosis Day Part II – Tuberculosis Testing and Diagnosis

March 2, 2016 Maria Wilson Leave a Comment

Mycobacterium tuberculosis scanning electron micrograph. Mag 15549X. Source: CDC.

Now that you have an idea of how TB is spread, its symptoms and its worldwide burden, let’s talk about how TB is diagnosed.

When a patient presents with the symptoms discussed in the last blog post (coughing up blood, cough lasting longer than 3 weeks, unexplained weight loss, etc.), a medical history is taken to determine whether TB infection is probable. Questions that are asked include whether they have been in close contact with someone with TB, if they have a previous history of TB infection, and whether they have an immunocompromising condition (such as HIV) that could increase the risk of latent TB infection progressing to TB disease [2].

There are two primary types of tests that are used to determine if a patient has been infected with TB bacteria: the tuberculin skin test and TB blood tests. The tuberculin skin test (also called the Mantoux tuberculin skin test) involves injecting a small amount of fluid (tuberculin) into the skin of the lower arm. After 48-72 hours have passed, a trained health care worker will look for a raised, hard area or swelling, to determine whether infection is present. TB blood tests (interferon-gamma release assays or IGRAs) measure how a person’s immune system reacts to TB bacteria by testing a blood sample in the laboratory. Blood tests are preferred for those who have had a TB disease vaccine, or who would have difficulty returning for a second appointment. Testing positive on either of these tests does not differentiate between latent TB infection and TB disease, it simply means the person’s body is infected with TB bacteria [3].

Diagnosing active TB involves a series of other tests. Chest X-rays can be used to check for lung abnormalities, but X-rays alone cannot provide a definitive TB disease diagnosis. Sputum Smear Microscopy (SSM) is one of the techniques used to diagnose active TB. Sputum is examined under a microscope for Mycobacterium tuberculosis. SSM can provide results in 24 hours, but it cannot always distinguish between TB and other infections. Polymerase Chain Reaction (PCR) testing can be used to detect genetic material specific to TB in bacteria; however, this test is complicated and can be much more expensive than SSM. Diagnosing TB outside of the lungs can include tests such as a biopsy, lumbar puncture, urine culture or CT scan [4].

Culture techniques, where TB bacteria can be grown in a laboratory from a variety of specimens, are also used to diagnose active TB, though it can take 1-6 weeks to obtain results. Culture techniques are particularly useful in determining an antibiotic treatment course, an important step in combatting TB. One of the largest issues in TB treatment is properly identifying and targeting drug resistance in order to provide appropriate treatment, a topic that will be discussed in our next post [5].

World Tuberculosis Day Part I – What is TB?

March 1, 2016 Maria Wilson Leave a Comment

Tuberculosis (TB), caused by the bacillus Mycobacterium tuberculosis, is an airborne disease that primarily affects the lungs (pulmonary TB) [2]. This means that when people with pulmonary TB cough, sneeze or spit, TB bacteria are propelled into the air, giving them the potential to spread from person to person via inhalation. TB can affect other sites as well, including the brain, the kidneys and the bones [3]. An ancient disease, TB has affected humans for over 4,000 years [2].

In many cases, the immune system will fight off the TB bacteria, and no infection occurs. If the immune system is not able to completely fight off the bacteria, some inactive bacteria may stay in the body, leading to latent TB infection (no symptoms). If the immune system does not respond sufficiently, active TB infection occurs (TB disease), and symptoms begin to manifest [4]. People with latent TB infection cannot spread TB bacteria to others, but can go on to develop active TB over time. WHO estimates that about one-third of the world’s population is infected with latent TB [5]. Symptoms of TB disease include a persistent cough of 3 weeks or longer, pain in the chest, coughing up blood or sputum, weakness or fatigue, weight loss, loss of appetite, chills, fever and night sweats [6].

The burden of TB is mainly concentrated in low and middle income countries, where 95% of TB deaths occur. In 2014, there were 1.5 million TB deaths, and 9.6 million people developed TB disease [5]. TB is one of the leading causes of deaths from infectious diseases worldwide [7]. The map below, produced by WHO, shows estimated TB incidence rates, by country, in 2014.

Map of the world showing estimated TB incidence rates, by country, in 2014 (Source: World Health Organization).

This map provides a visual representation of the worldwide burden of TB, with the lowest rates in Western Europe, Canada, the United States of America, Australia and New Zealand. This has led to a common misperception in higher income countries that TB is a disease of the past. However, in many countries, including Lesotho, South Africa, Swaziland and Mozambique, rates are still above 500 cases per 100,000 population [7].

Keep reading our series of blog posts on TB to learn more about risk factors, diagnosis, treatment and much more.

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