Is it a case of one step forward, two steps back?
The manifestations of tuberculosis (TB) have been recognized since antiquity, with evidence of spinal TB found in Egyptian mummies dating from around 1000 BC. Yet one hundred and thirty years after the German scientist Dr Robert Koch stunned the world by discovering the cause of TB – the TB bacillus (Mycobacterium tuberculosis) – this preventable, treatable and curable infectious disease continues to kill millions of people around the globe. In 2010, there were an estimated 8.8 million cases of TB and nearly 1.5 million deaths from TB worldwide.[1]
TB is partly a disease of poverty. While the greatest disease burden occurs in low and middle-income countries, increased movement of people between countries and deepening economic woes have ensured that TB remains highly relevant to medical practitioners all over the world. In 2011, there were 3,588 new cases of TB in London alone.[2] According to the author of a report on the rising incidence of TB in the UK, “Poor housing, inadequate ventilation and overcrowding – conditions prevalent in Victorian Britain – are causes of the higher tuberculosis incidence rates in certain London boroughs”.[3]
Challenges to effective solutions to controlling TB include the lack of access to diagnosis and treatment, the frequent co-existence of TB and HIV, and the increasing prevalence of multidrug-resistant TB (MDR-TB).[4] Diagnosis of active TB has traditionally required a constellation of clinical, radiographic, microbiological, and histopathologic hallmarks,[5] entailing considerable delay, however this is slowly changing. Among the most exciting developments in the battle against TB is the advent of new rapid diagnostic tests.
The WHO has recently endorsed the roll out of an automated, cartridge-based nucleic amplification assay for the simultaneous detection of TB and rifampicin resistance directly from sputum in under two hours. Other point-of-care tests are in the pipeline. These include a mobile device that detects TB by ‘sniffing’ a person’s breath.[6] But diagnosis alone is not enough in the fight against TB. As the Director of WHO’s Stop TB Programme says, “The promise of testing more people must be matched with the commitment to treat all detected. It would be a scandal to leave diagnosed patients without treatment”.[7]
Adequate treatment of TB poses many difficulties, with even drug-sensitive disease requiring supervised treatment for at least 6 months with four antimicrobial drugs. Adherence is of critical importance and is the major rationale for recommending Directly Observed Therapy (DOT). Perhaps most worryingly, multi drug resistant strains of the disease are at record high levels.[8] The primary cause of MDR-TB is inappropriate treatment, or as Dr Paul Nunn, coordinator of the WHO’s global TB response team puts it more bluntly, “It occurs basically when the health system screws up”.[9]
Though still treatable, second-line treatment options for MDR-TB are limited, more expensive and require even longer durations of treatment. Not surprisingly, only 16% of those with multi drug-resistant forms of the disease are being treated.[8] This in turn exacerbates the spread of MDR-TB and contributes to an even more disturbing phenomena – the advent of extensively drug resistant TB (XDR-TB), a form of multi-drug resistant TB that respond to even fewer available medicines, including the most effective second line anti-TB drugs. Around one in ten resistant cases are XDR-TB.
Shorter treatment regimens for TB are urgently needed. Encouragingly, there are several new or repurposed TB drugs undergoing clinical trials that have the potential to shorten treatment duration and improve the treatment of MDR-TB. Results from multiple Phase III trials of 4-month regimens for drug susceptible TB are expected over the next two years. New vaccine candidates are also in development.
Treatment of TB should be accompanied by robust public health measures. Dr Matteo Zignol, from the Stop TB Department at the WHO and Lead Author of a recent report of the rise in MDR-TB says, “Surveillance of resistance to drugs is the cornerstone of TB control”. This will require significant improvements in data collection. Currently, a third of estimated TB cases worldwide are not notified so it remains unknown as to whether they are diagnosed and properly treated.
Of particular concern have been recent cuts in donor funding to the Global Fund, an organization originally established to tackle the “big three” of HIV, malaria and TB, and a significant player in the fight against all three killer diseases. The United Nations has warned that declining funding could put progress in TB at risk, with Secretary General Ban Ki-moon urging against complacency. His calls are supported by other NGOs, with the President of Medicines San Frontiers, Dr. Unni Karunakara, saying, “Efforts to scale-up detection of MDR-TB are being severely undermined by a retreat in donor funding”.[10]
Today, we have the know-how to treat and prevent this age-old killer. Unfortunately, yet again, economic considerations concerns appear to trump public health concerns.
References
[1] Global tuberculosis control: WHO report. 2011. Retrieved on 02/05/2012 from www.who.int/tb/publications/global_report/en/index.htm
[2] Health Protection Agency. Tuberculosis in the UK: 2011 report. London. 2011. Retrieved on 02/05/2012 from www.hpa.org.uk
[3] Zumla A. The white plague returns to London–with a vengeance. Lancet 2011; 377:10-11.
[4] Lonnroth K., Castro K.G., Chakaya J.M. et al. Tuberculosis control and elimination 2010-50: cure, care, and social development. Lancet 2010; 375:1814-1829.
[5] Sia I.G., Wieland M.L. Current concepts in the management of tuberculosis. Mayo Clin Proc 2011; 86:348-361.
[6] Tran, M. Tuberculosis breakthrough as scientists get funds for ‘electronic nose’. The Guardian. 7-11-2011. Retrieved on 02/05/2012 from www.guardian.co.uk/global-development/2011/nov/07/tuberculosis-electronic-nose-device
[7] Boseley, S. Battle against TB is being won, says World Health Organisation. The Guardian. 11-10-2011. Retrieved on 02/05/2012 from www.guardian.co.uk/world/2011/oct/11/tb-battle-world-health-organisation
[8] Zignol M., van G.W., Falzon D. et al. Surveillance of anti-tuberculosis drug resistance in the world: an updated analysis, 2007-2010. Bull World Health Organ 2012; 90:111-119D.
[9] McVeigh, T. Drug-resistant strains of TB are out of control warn health experts. The Observer. 25-3-2012. Retrieved on 02/05/2012 from www.guardian.co.uk/world/2012/mar/25/drug-resistant-strains-of-tb
[10] Medecins Sans Frontieres. Alarming scale of multidrug-resistant tuberculosis requires rapid response to avert emerging global crisis. 20-3-2012. Retrieved on 02/05/2012 from www.msf.org/msf/articles/2012/03/alarming-scale-of-multidrug-resistant-tuberculosis-requires-rapid-response.cfm