Tuberculosis: the return of the great white plague
This essay was written by Jo Colston and was first published in the 1995 Mill Hill Essays.
Everyone over the age of forty-five can remember someone who suffered from tuberculosis. A school friend who “disappeared” from school for many months while being treated in a sanatorium; an ageing aunt, uncle or grandparent who died or had major surgery as a result of developing TB. Even in post World War II Britain it touched many peoples’ lives and was greatly feared. However, the 1950s saw the introduction of drugs which were active against TB and for the first time it became a disease which could be cured. As well as new drugs a large-scale vaccination programme was introduced throughout the UK in the 1950s and 60s; virtually all adolescent schoolchildren eventually received the vaccine. Although TB continued to cause disease in about ten thousand people a year in this country, it was no longer the threat to life which had made it the most feared of diseases for the previous five centuries.
TB, or consumption as it was commonly known because of the weight-loss and wasting that characterises the disease, is shrouded in folk-lore, fear and antiquity. It is known to have occurred in stone-age man, but blossomed into a prolonged and devastating epidemic throughout Europe from the 1500s until the beginning of this century. At the height of the epidemic a staggering one in four deaths were due to TB and it is thought that the entire population of western Europe was infected. So what had happened to trigger this prolonged and devastating epidemic? Urbanisation. Man began to move into centres of ever-enlarging population. Cities expanded, industries boomed and tuberculosis wreaked havoc. The bacteria which cause TB are carried in the air from one infected person to the next; coughs and sneezes spread this disease, and crowded living conditions along with social deprivation created exactly the right conditions for the disease to spread. TB started to decline in Western Europe from the early part of this century, long before the introduction of vaccination or effective drug treatment. It declined as a result of improved living conditions. TB acts as a barometer of social change, it increases when living conditions deteriorate and decreases as they improve. The increase in homelessness and poverty, which many industrialised countries such as Britain and the USA have experienced in recent years, has led to renewed concern of an increase of TB in these countries.
In addition to infection between people living in overcrowded conditions, TB in cattle was also a problem, with the possibility of the disease being transmitted to man through infected dairy products. The widespread testing of herds and treatment of milk has largely eradicated this, but in certain parts of the UK, especially Southwest England, tuberculosis in cattle remains a significant problem. The finding, in the 1970s, of badgers with tuberculosis in this region has led to the suggestion that the cattle are being infected by contact with badgers which have TB, and to the highly controversial policy of culling badgers in an attempt, so far unsuccessful, to reduce the outbreaks of TB in cattle.
As the amount of TB decreased in Western Europe and the USA, and with the introduction of drug treatments and vaccination programmes, it became perceived as a problem that had been solved. This belief ignored what was happening elsewhere in the world. In developing countries with poor living conditions, unable to afford drugs or vaccines and with inadequate health care systems, tuberculosis continued to flourish. TB will kill thirty million people in this decade alone; it will kill more adults than any other infectious agent; one third of the world’s population is currently infected with TB. The figures are staggering, but until recently, they have been ignored; sadly, what happens in the third world is rarely considered to be news-worthy and so we continued to believe that TB was a problem that had been solved. But our complacency has been shattered. The steady decline in TB which developed countries have experienced for several decades began to slow down; by the mid-eighties the decline was over and in the early nineties we have seen a small but significant increase in several industrialised countries. This increase is trivial when compared to the global problem of TB, but at least it has reminded us that TB is still with us. A problem that has been solved? In 1993, the World Health Organisation declared TB to be “a global emergency”, the first disease to receive that dubious accolade!
Statistics such as “a third of the world’s population are infected with TB” are difficult to comprehend; does it mean that all of those people, approximately two billion, will go on to get the disease and require treatment? No. Most people who become infected will never develop disease. The bacteria will remain in their lungs undetected and unnoticed. Some people, however, will start to develop symptoms almost immediately after becoming infected, the bacteria multiplying in their lungs from the word go. Others may develop the disease many years, or decades, later, the bacteria, having been sitting dormant in their lungs for all of that time, suddenly starting to multiply. We don’t know precisely what determines how things will develop after infection has occurred; no disease at all, immediate disease, or disease which develops many years later. What we do know however, is that the state of the person’s immune system is a crucial factor. People whose immune system has been damaged, for example by poor nutrition and living standards or by HIV the virus that causes AIDS, are much more likely to develop the disease. The TB bacterium and the AIDS virus are a deadly combination. The vast majority of TB-infected people are not infected with HIV. However if people are infected with both, the damage done to the immune system by the HIV means that they are much more likely to be unable to control their TB infection. HIV has not, as yet, been a major factor for TB in this country, but in Africa, and increasingly in Asia where HIV infection is spreading rapidly, TB is one of the major causes of death in AIDS patients.
Virtually all adolescents in the UK are given BCG, a vaccine specifically aimed at protecting them against TB. BCG is the most widely used vaccine world-wide. So, if a vaccine against TB is available and widely administered, how come so many people still get the disease? The fact is that the effectiveness of BCG varies widely from place to place. The UK policy of mass vaccination of adolescents is based on a large trial carried out by Dr. Philip D’Arcy Hart and his colleagues working on behalf of the Medical Research Council in the 1950s and 60s. More than fifty thousand school children were involved in the trial, some being vaccinated with BCG, others being unvaccinated, as controls. These schoolchildren were then followed for many years, to see if they developed TB. In fact there was nearly eighty percent more TB in the unvaccinated than the vaccinated group, and it was largely this result which led to the policy of mass vaccination. Unfortunately results with BCG in other parts of the world have been far less impressive. In a number of trials in the USA, it was found to have little or no effect; today BCG is very rarely given in the United States. More recently a large trial in South India, just the sort of area where an effective vaccine is most needed, also gave poor results. So it seems that BCG works in some places but not in others and we don’t really know why.
So vaccination against TB is sometimes unsatisfactory. What about treatment of patients with antibiotics? Effective treatment has been available for many years. The first drugs which were effective against TB were introduced in the early 1950s, and the armoury of effective drugs available has gradually increased. The vast majority of TB cases are curable, so why is there still a problem? Well the first difficulty is that patients have to be diagnosed. An undiagnosed and therefore untreated TB patient can infect many people over the course of a few months. Unlike diseases such as AIDS, where close contact is required for the disease to spread, TB can be spread by quite casual contact. So even if a patient is put onto effective therapy and cured, unless they have been diagnosed quickly they may already have infected several other people before the treatment was started. Secondly, drug treatment of TB takes several months before a patient can be considered cured. Since the vast majority of sufferers live in countries where health-care is inadequate, it is often difficult to maintain drug supplies. It is also difficult to persuade people to continue to take drugs for several months at a time. Even in this country, TB patients are often living at the margins of society and are just the sort of people who are likely to fail to keep up their treatment. Finally the sinister threat of drug-resistance has emerged.
Whenever infections are treated with antibiotics there is the threat that a drug resistant mutant will develop. Drug resistant TB has been known right from the early days of drug-treatment. Usually we know how to deal with drug resistance; by treating patients with several different drugs at once we can virtually eliminate the chances of drug-resistance becoming a problem. Unfortunately many patients do not get treated correctly and that is when they are at risk of developing drug-resistant TB. Until recently, most strains of drug-resistant TB have been resistant to only one of the drugs available so it has not been a major problem. There are several other drugs available to treat such patients. However, at the beginning of this decade a new, and altogether more difficult problem started to emerge; multiple drug-resistance. Some patients in New York City were found to be infected with TB which was resistant to virtually all known drugs. These patients were often put onto experimental drug combinations which were extremely expensive and often ineffective. What is more, these patients could infect other individuals with drug-resistant TB; a number of health-care workers have died after becoming infected with drug-resistant TB. Fortunately, multiple drug resistance is rare and has been localised. But imagine what would happen if it became widespread; with no effective drugs available we would be stepping back into the nineteenth century with the added complication of HIV infection to make matters even worse.
So the TB threat, which we thought was declining, has re-emerged with a vengeance. Not only is the disease spreading rapidly throughout the world, but the tools required to control it, vaccination and effective drug-treatments are under threat. There is no doubt that a great deal could be achieved by improving health care systems and applying the tools that we already have available to the problem. That in itself is a major task, but surely more is needed. We respond to outbreaks of disease and epidemics with a surge of interest which declines when the crisis appears to be over. Unfortunately the microbes that we are fighting are much more resourceful. They continuously find ways to overcome our best efforts, evolving new strategies to defeat our drugs and vaccines. We not only need to apply existing tools, but we need to develop new tools and to anticipate new threats; this can only be achieved by increasing our understanding of the disease at all levels.
The bacterium which causes TB was one of the first to be associated with a human disease, and yet our knowledge of it, and the way it interacts with man, lags far behind that of other microbes. We desperately need to increase that knowledge and to maintain our vigilance. Even when the current epidemic subsides and is no longer headline news TB will have many more surprises in store for us in the future.