Tuberculosis (TB) is a disease caused by a bacterial infection and is mainly transmitted through the air when someone who is infectious with the disease coughs or sneezes. TB is both preventable and treatable with special antibiotics, yet every year it still kills more people than any other infectious disease. In fact, in 2018 more people died from TB than HIV and malaria combined.
Treating this disease is not just complicated because the mycobacteria possess an unusually thick, waxy cell wall which isn’t easy for drugs to penetrate but also because it has the ability to survive in multiple locations in the body as well. Of huge significant, it also has the unusual capacity to ‘hideout’ in the body for years following the first infection – a condition which is called ‘latent infection’.
Because the bacteria are so hardy it means that even straightforward treatment of standard ‘drug-susceptible’ TB needs a combination of four different drugs taken for at least six months. With drug-resistant strains, it needs six drugs with pernicious and often permanent side-effects for between 9 and 24 months with very poor treatment outcomes indeed.
TB bacteria also have certain attributes which make them able to develop resistance to antibiotics. When such resistance exists to the two strongest standard TB drugs, Rifampicin and Isoniazid, ‘first line’ drug therapy becomes ineffective, and so it’s called ‘multidrug-resistant’ or MDR-TB. In such instances weaker and more toxic second-line drugs have to be used, normally six drugs for 24 months including daily injections for the first six months all with poor treatment outcomes and pernicious and often permanent side-effects. New shorter regimens are emerging which appear to have less problematic side-effects, although they are still far from optimal in terms of successful outcomes and largely unaffordable.
Tuberculosis is the world’s first (and so far only) major airborne drug-resistant epidemic and its toll is increasing year on year. A quarter of a million people are estimated to have died from multi-drug resistant TB (MDR-TB) in 2017 (and it may well be more) amounting to one-third of all deaths from drug-resistant or 'AMR' disease.
The map above shows where the highest rates of mortality exist for tuberculosis today. This doesn’t just relate to drug-resistance (though it must play a significant part) – it also relates to co-infection rates with HIV/AIDS and also poor health infrastructures.
The threats that have been estimated to be posed by MDR-TB, both human and economic, are potentially catastrophic:
1. Loss of life – It’s estimated that by 2050 MDR-TB alone will be responsible for 2.5 million deaths every year. This adds up to an estimated 75 million people dying from MDR-TB over the next 33 years, or one person every 12 seconds throughout that period.
2. Economic Impact – MDR-TB’s potential cost to the global economy is estimated as totaling US$16.7 trillion by 2050, equating to 0.63% of global GDP. The lowest income countries, however, are predicted to be hit worst, losing 2.45% of their GDP by 2050 due to the disease.
Unfortunately, strains of TB that are even more resistant to TB drugs are also now circulating and are also on the rise. These strains are termed ‘extensively drug-resistant TB’ or XDR-TB. This is defined as MDR-TB which is also resistant to the two strongest groups of second-line TB drugs but possibly to others as well. Treating XDR-TB is extremely difficult with less than one-in-three cases making successful recoveries. Thankfully rates of XDR-TB are still low, but this is no reason for complacency simply because exactly the same was the case with MDR-TB twenty years ago.
LATENT (or 'sub-clinical') INFECTION
This is a really important component of the global pandemic which has unfortunately been terribly neglected to date and is unquestionably one of the reasons why the numbers of new cases each year are still so huge. It’s been recently re-estimated that roughly one-in-four human beings worldwide are latently infected with tuberculosis amounting to nearly 2 billion people, each of whom could develop the active form of the disease at any time. Thankfully not all will - in fact the likelihood of disease progression is normally calculated as between 5% and 15%, but this likelihood is heavily dependant on the state of the host's immune system, itself dependant on nutrition, on other concomitant health issues (particularly HIV and diabetes), on living and working conditions and also on some lifestyle factors.
The key factor is that somehow (and no-one yet knows exactly how) these ‘latent’ bacteria sense when the immune system is weak, and then break out of their latent or sub-clinical state creating active infectious and life-threatening disease.
If someone is known to be latently infected they can normally be successfully treated with a nine-month course of isoniazid (one of the key first-line TB drugs). Of course, if their latent infection is resistant to this drug, then the treatment can be reasonably predicted to fail, something which is sadly becoming more and more likely. In any case, it is also well known that any long-term course of antibiotics can have a deleterious effect on host immunity anyway, leaving the recovered patient at risk of further infection (which unfortunately can quite easily include a further infection of tuberculosis in high-incidence communities).
The logical question, of course, is whether these host immune systems can be effectively strengthened, because this could help solve the major part of this immense pandemic. One way of doing this is through immunotherapy.