Comment

Resistance Made Futile

22 August 2017

Singapore, 2012: Kannan, my uncle, dies aged fifty-one. Cause of death: myocardial infarction – heart failure. But the disease that ravaged his lungs and consumed his body goes unmentioned. My uncle’s tuberculosis (TB), contracted on a working-trip to India, went undiagnosed for 10 months.

Five years on, my uncle’s death continues to trouble me. Kannan was unwell for almost two years after returning from India. By the time someone thought to x-ray his chest, his lungs had been consumed and he was beyond help. How did doctors in Singapore’s world class health system overlook TB, despite knowing that Kannan’s work took him frequently to India, a TB hotspot?

Perhaps it was because today, TB is relatively unheard of in developed countries, where it receives little funding and mainstream media attention. This rarity, however, could be about to change. Antibiotic resistance, in addition to increased global mobility and a lack of significant antibiotic development, is once again making TB a significant threat on a global scale.

The 20th Century was the golden age of TB treatment and control thanks to the Bacille Calmette-Guérin (BCG) vaccine and an arsenal of antibiotics. But this era has ended. Today, the BCG vaccine is known to be frequently ineffective and increasingly resistant strains of the bacteria Mycobacterium tuberculosis have emerged, rejuvenating TB.

Antibiotic resistance occurs when bacteria develop immunity against an antibiotic. Within a population of bacteria exposed to an antibiotic, some resistance is always present due to random genetic mutations. Resistant bacteria survive treatment, reproducing until they are the majority. Resistance can itself be passed within and across species of bacteria.

Today, drug-resistant strains of almost every pathogenic bacterium, collectively referred to as ‘superbugs’, are ubiquitous. Increased mobility exacerbates the problem – that anyone could come into contact with resistant bacteria wherever they go and then spread them round the world

The World Health Organisation declared TB a global emergency in 1993. It is the world’s deadliest infectious disease and is becoming progressively resistant to more and more antibiotics. Yet compared to HIV/AIDS, malaria and recent epidemics like Ebola, TB receives little funding and mainstream media attention. Why?

Perhaps because there appear to be no more medical avenues to exploit. The BCG vaccination against TB is mostly ineffective as are many treatment methods. But behind these medical and biological factors lies a web of political and economic issues that have encouraged antibiotic resistance.

Antibiotic resistance stems from antibiotic abuse which is a complex political and economic issue. It is particularly prevalent where governments fail to regulate antibiotic accessibility. This enables the purchase of antibiotics without a prescription, resulting in their incorrect use. In Thailand and the Philippines, for example, the anti-TB drug Rifampin can be brought over the counter and is commonly used ineffectively as protection against sexually transmitted infections.

Powerful pharmaceutical companies exert pressure on general practitioners and hospitals to prescribe more lucrative antibiotics over others, bribing them to win their allegiance. Subsequently, ineffective antibiotics may be employed over more efficient antibiotics, fostering antibiotic resistance.

More than any other industry, pharmaceutical companies spend exorbitant amounts lobbying and encouraging most governments to turn a blind eye to their activities. These profit-oriented companies function as they please, choosing which diseases and medications merit research and development. To date, antimicrobial research has not merited their attention. Why?

Antibiotics are short-course medications and are less profitable than chronic disease and lifestyle drugs. Additionally, infectious diseases like TB are associated with impoverished or developing countries that cannot afford to fund antimicrobial research and development. Consequently, there has been a serious decline in the development of new antibiotics. The last new class of antibiotics was discovered during the ‘80s. The resulting ‘discovery void’ means the medical arsenal cannot properly combat antibiotic resistance.

This lack of new treatments means that TB afflicted populations, concentrated in Asia and Africa, have little access to effective medication. Increasing resistance to front-line antibiotics forces individuals to depend on more expensive and less effective second-line drugs. Patients are more likely to default on treatment, which in turn makes the treatment less effective, as it takes up to two years, is very expensive and uses medication with serious side effects.

Commercial animal husbandry and agriculture is another cause of antibiotic resistance. Filthy, crowded factory farms are breeding grounds for disease. Epidemics are prevented by pumping animals full of antibiotics, encouraging antibiotic resistance that then affects humans. The American Farming Lobby, similar to its pharmaceuticals counterpart, is so powerful that it has repeatedly stymied government attempts to pass laws for new standards in industry practice.

If global action is not taken immediately, a drug-resistant TB pandemic is almost inevitable. The latest Global Plan to stop TB by the Stop TB Partnership, a coalition of NGOs, foundations and other organisations fighting TB, demands a paradigm shift. We can no longer focus on merely controlling or slowing TB – we must aim to end TB. Such a goal requires a change in ambition, and – most importantly – full investment in a strategy for ending TB.

Little has been done to enable such a change. In 2011, Stop TB Partnership estimated that US$9.84 billion was required for TB R&D to bring an end to the global crisis. Actual funding amounted to a mere US$3.29 billion.  Between 2011 and 2015 pharmaceutical industry investments in TB R&D dropped by 40 per cent, putting more pressure on not-for-profit organisations. In that time frame, several studies described cases of totally drug-resistant TB in India.

I do not – and probably never will – know if my uncle had drug-resistant TB. What I do know is that TB should not be a killer anywhere, particularly not in Singapore. Earlier this year, echoing my uncle’s case, a man returned to Sydney from a trip through South-East Asia with what he thought was a flu. Only on his third visit to a doctor was he correctly diagnosed with multi-drug-resistant TB. By then, 10 others had been infected.

Continuous antibiotics abuse, intensified by stagnating antibiotics research and development industry policy and a lack of awareness, have created the perfect environment for a drug-resistant TB pandemic. Non-government organisations alone cannot stop TB. An immediate concerted effort by government organisations and private corporations is necessary. In addition, action is required by all of us – demanding action of our governments, becoming involved in the campaign against TB and becoming better users of antibiotics.