Broadcaster: BBC 4
Reviewed by Emma Sterling
“It’s very difficult to cure XDR because we’re just giving what we have on the table. The reality of XDR is that it’s almost incurable.”
(WARNING: Distressing content): BBC 4’s long-format (90 minute) documentary TB: Return of the Plague, reports on the fight against tuberculosis (TB) in Swaziland, the country with the highest rate of infection in the world.
TB is a highly contagious airborne disease caused by Mycobacterium tuberculosis (Mtb). The bacteria can move from the lungs into the blood and from there to other parts of the body. Symptoms include loss of appetite, a persistent cough, night sweats and fever. Mtb is a slow-growing bacterial species, necessitating treatment with a combination of antibiotics for 6 months or more. Not only do the medicines need to be taken consistently for a long period, some are also toxic; side effects include liver damage, kidney damage and loss of hearing. When patients fail to comply with the drug regime, missing days or not completing the course of antibiotics, the disease is given a window to mutate into the more aggressive strain, known as multi drug resistant TB (MDR-TB). MDR-TB can also be contracted directly from an infected person. In Swaziland, approximately 1 in 25 TB cases are MDR-TB. At the time of this documentary (2014) there had been no new treatments for TB in the last 40-70 years. Unfortunately, MDR-TB has further mutated into a potentially incurable strain, extensively drug resistant TB (XDR-TB), first described in 2006.
In this clip (15 mins) we follow the stories of Bheki and his sister Zandile who have both been diagnosed with MDR-TB as well as Gcinekile, diagnosed with XDR-TB. These case studies illustrate some of the day to day pressures for patients with TB, which can carry as much stigma as HIV in the region. It could be useful as a starting point for an epidemiology case study, although the fact that much of the relevant dialogue requires the reading of subtitles to follow what is going on and this might limit application. Nevertheless, the clip has the potential to offer insight into the dangers of disease mutation and resilience due to antibiotic misuse.
It is estimated that 1 in 3 people have the Mycobacterium tuberculosis bacteria, which can stay dormant in the host’s system for years. In order for it to cause TB disease, the bacteria need to be active. This is more likely in hosts whose immune system is compromised and is unable to fight the growth and spread of the bacteria. For this reason TB is closely associated with HIV/ AIDS. In Swaziland, approximately 1 in 4 adults have HIV and 80% of TB patients are co-infected with HIV.
MDR-TB is diagnosed when the bacteria are resistant to at least rifampicin and isoniazid, two primary anti-TB drugs. The disease is classed as XDR-TB when the bacteria are resistant to second line MDR treatment such as kanamycin and any fluoroquinolone. More recently, there have been cases, first described in India, of totally drug resistant TB (TDR-TB) where the bacteria has developed resistance to all available treatments.
In order to effectively combat these more resistant strains, TB needs to be detected and treated as soon as possible and a tailored combination of the correct drugs for the strain must be employed. Further knowledge is needed about the mechanisms of resistance that the bacteria have to the drugs in order to develop more efficient and targeted treatments.
For further reading on TB drugs and resistance mechanisms:
Drug Resistance Mechanisms in Mycobacterium tuberculosis (Antibiotics, open access)
One of first new anti-TB drug to be available in almost 50 years is bedaquiline. It is part of the diarylquioline family of drugs and has proved effective in treating TB and some cases of MDR-TB/XDR-TB. The WHO guidelines state that it is to be administered in varying doses over 6 months.
Click here for more on the WHO’s implementation plan for Bedaquiline.
There are other drugs in the pipeline for treatment of TB and its more resistant strains, but progress is slow and has its challenges. For example there can be pre-existing resistance to drugs currently in phase II or phase III of clinical trials. Additionally, any new medicines are likely to be expensive ans, as seen in the clip, countries where TB is most prevalent tend to be amongst the poorest. Treatment needs to be not only effective but affordable if real global impact is to be made.
For further reading on some of the challenges facing TB drug development see:
Barriers to new drug development in respiratory disease (European Respiratory Journal, subscription required)