When it comes to diseases that have shaped world history you cannot go past Tuberculosis (TB). Its footprint lingers in literature, it is found in ancient Neolithic remains and Egyptian mummies and we can even link the development of Kellogg’s Cornflakes with the health crazes that it triggered over the previous two centuries.
TB is caused by the bacterium Mycobacterium tuberculosis, in the same genus as the bacteria that cause leprosy, another scourge of the ancient world. M. tuberculosis bacteria invade the body then concentrate in tubercles otherwise known as granulomatous lesions, cysts which are formed around infected tissue by the immune system. While these halt the immediate invasion and minimise tissue damage they do prevent the immune system or certain antibiotics from destroying the bacteria within allowing it to maintain chronic infection. Its slow growth and aberrant cell wall structure allow the bacteria to be further resistant to treatment. Antibiotics find the cell wall, a cross between gram negative and positive structures, difficult to permeate, and many, including penicillin, target the cell replication process. Treatment required a mix of multiple hard hitting antibiotics over at least six months, a schedule that is often not maintained by patients.
M. tuberculosis shows a preference for the lungs but can invade any body tissue including the brain. Military Tuberculosis is when it gets into the blood stream to cause a systemic infection and is often rapidly fatal. Once a rare complication of Tuberculosis, seen mostly in young children, co-morbidity (infection of two or more pathogens) with AIDS results in a 3-6 fold increase in the risk of developing Military Tuberculosis if infected with the bacteria. More commonly the chronic infection causes scarring of the lungs, leading to a slow death from lung failure.
By the start of the 1800s, it was estimated one in four deaths in England was caused by Tuberculosis. The Victorian’s love of tragedy introduced the consumptive beauty into literature, the heroine who slowly succumbed to a disease that made her pale, thin and ethereally lovely. Diseases were considered the result of miasma (bad air) and health resorts became the rage across Europe and America. In Germany and Switzerland health spa tourism was born. In England, it was Bath and the seaside resorts of Brighton and Hampton that benefited. In America, Dr Kellogg’s health sanatorium focused on nutrition, exercise and strangely enemas. The breakfast cereal he developed was wildly successful. His enema treatments not so much.
By the end of this century, the microscope had revealed the cause of infectious disease. This was the age of Koch and Pasteur, the fathers of microbiology and two of the most bitter rivals in scientific history. It was German Robert Koch who identified the M. tuberculosis, a discovery that won him the Nobel prize in medicine in 1905 and lead to M. tuberculosis being commonly called Koch’s bacillus. Public health campaigns started up to prevent the spread the results of that we can still see today. Laws prohibiting public spitting can be traced to anti-tuberculosis campaigns and the signs from the 1920’s campaign prohibiting spitting are still in place at Melbourne’s famous Flinders St train station. Frenchman Louis Pasteur put his own mark on the history of tuberculosis by developing the method of pasteurisation by which milk could be sterilised prior to sale. Pasteurisation stopped the transmission of the closely related bacteria M. bovis from cows to humans, a common cause of TB in the 1900s.
Arrival of Antibiotics
By the 1940s to 1950s antibiotics had come onto the scene and were successful in causing a rapid decrease in the rates of TB. However, M. tuberculosis was quick to fight back and due to its unique cellular quirks was one of the first bacteria in which antibiotic resistance was seen. The emergence of antibiotic resistant TB strains coincided with the sexual revolution and the explosion of AIDS onto the world, first in Africa in between 1950-1970 then into Asia and the western world.
The Link Between HIV and TB
So why should AIDS and TB be linked? After all of the 1.45 million deaths caused by TB in 2013 (second only to AIDS as the leading cause of infectious disease-related deaths worldwide) only 0.34 million were HIV positive. Yet HIV is listed as a risk factor for TB.
Shared Risk Factors
Firstly there are the shared risk factors. Poverty and drug use, which are risk factors for contracting HIV, are also risk factors for many other diseases including TB. TB, like most respiratory diseases, is spread through close personal contact and kissing during sex, like a cold. Secondly, bacteria are primarily opportunistic pathogens. They cause disease for the most part in sick people where the immune system is not so strong and you can’t get all that much more immunocompromised than AIDS. People with compromised immune systems are also more likely to have asymptomatic TB and so spread the disease more readily as they will not take measures to protect their partner. Then there are the drugs, medical drugs I mean. I spoke in an earlier blog piece about how the recent development of one pill HIV PEP combination therapy for HIV was a godsend for doctors as it make people far more likely to take their medication. The same is true for TB.
The Cocktail of Confusion
Imagine that you have AIDS. You are taking three drugs for the HIV, another two to counter side effects, one for the thrush in your mouth, one that you are not sure what it does but your doctor says you have to take it. Then you are told, “Oh and by the way, you have TB. You need to take isoniazid for six months so here are some vitamin B tablets as well and I will also put you on rifampicin. Two months on pyrazinamide, it may cause some joint pain, and ethambutol, now that may cause red-green colour blindness, unlikely, but let me know if you have any trouble with your eyes, ok. Here are some tablets for the diarrhoea this is likely to cause and now I should let you know all of these can cause your liver to shut down, only sometimes, but I will need to you come in for a liver test next month. These need to be taken with food, this one can’t be taken with food, this one twice a day, only take that one in the evening” and so on. I suspect like me you would have trouble keeping them all in order let alone taking them all.
The Problem With Non-compliance
The problem is that non-compliance with the treatment is what causes resistance. There are some superbug strains of M. tuberculosis which nothing will cure, and with a fatality rate of around 50%, that is a scary thought. Compliance programs, where a nurse comes to your house and watches over you while you take your drugs, have been very effective. However, such programs are very expensive and when the highest incidence of TB is in the third world, such programs are just not feasible. You can see why combination therapy for HIV is a wonder. Reducing that list by two drugs makes everything seem far more manageable.
A Problem That Affects Everyone
HIV and TB are both diseases of poverty. They occur most often in the marginalised and those who court risk. But their impacts are felt by all. The AIDS 2031 Cost and Financing Working Group, as part of the Joint United Nations Programme on HIV/AIDS (UNAIDS) Global Resource Needs, estimates that by 2031 HIV may be costing the global economy $35 billion dollars US. TB while less in incidence has not had the global research on reducing costs and is estimated to cost $1-3 trillion a year and can rob a country of up to 7% of its GDP. For both diseases are seen primarily in people of working age, resulting in not only direct costs to the health care services but in the reduction of effective workforce.
The good news is that as they are both seen in the same demographic, resources can be targeted to that demographic for both diseases and share the costs. The chronic condition of TB makes it economically viable for drug companies to research and manufacture combination therapies for TB, whereas they are not for other bacteria diseases. Less arduous treatment options mean that compliance going forward is less costly and more likely without a nurse to hover over the patient’s shoulder.
A vaccine, the bacille Calmette-Guerin (BCG), exists, however causes the patient to give a false positive for blood tests for TB. For this reason, the vaccine was not introduced into the childhood immunisation programs in the USA, though it has been used and still is used in many countries including Singapore and Australia. Australia discontinued immunisation against TB in the 1980s except for children less than six months who would be living in or travelling through a country with high TB incidence. TB incidence has been on the rise in Australia since 2007 as with many first world countries, thought to be a result of increased global migration.
Singapore discontinued the second vaccination for BCG in 2001 following a highly successful campaign with the Singapore TB Elimination Programme (STEP) which saw a 15% reduction in new cases of TB in three years. Infants are still vaccinated and this protects them during the most vulnerable years and the second vaccination is deemed unnecessary save in specific high-risk circumstances. Vaccination of children under six months of age does not cause them to show a false positive in TB tests, leaving the current TB detection tests effective. Research is ongoing for a workable adult vaccine.
Co-morbidity is rare for infectious disease except in STDs. Unfortunately if you have one STD it is likely you also have another, and that list is not just limited to STDs. Singapore is fortunate to have a relatively low incidence of both AIDS and TB. If you are travelling be aware that other countries are not so fortunate and activities that may be fairly low risk in Singapore or Australia may be high risk in China or Africa. Make your doctor aware of any other symptoms you may have as well as regions you have recently visited. These things can be treated if you catch them early. Don’t become a statistic.