Not all TB infections lead to disease. The TB organism invades the body, where it attempts to reproduce. In most instances, the body's immune system succeeds in walling off the TB bacteria and killing it. Sometimes the bacteria remains alive, but is not causing disease and cannot be passed to another person. That state is called a latent infection which can become active disease if the host's immune system is compromised. The part of the immune system that is active against TB is called cell-mediated immunity and is moderated and controlled by T-cell lymphocytes. Anything that weakens the controller T-cells weakens the body's resistance to TB. Some of the things that compromise T-cells are: injuries to the lungs (such as silicosis and black lung disease), infectious agents (such as HIV today and measles in the past), malnutrition and low body weight, certain genetic factors, and stress (which cause the body to release corticosteroids, which negatively affects the immune system). Research has shown that those who are 10% underweight are three times as likely to get TB. In overcrowded, unventilated conditions. the body-particularly the lungs-is exposed to many more aerosolized TB bacteria, so there are more infections and more chances for infections to turn into disease. There are some genetic factors that make some people more susceptible to TB disease than others. Cell-mediated immunity is impaired in those more likely to develop disease.
TB epidemics differ from epidemics of other diseases. Other diseases cause epidemics that last months, years, or even decades. TB epidemics last centuries. The number of TB-diseased people steadily rose from the late 1500s to a peak in the late 1800s. The people in Grantville are dropped into the earlier stages of what was called the Great White Plague of Europe. The number of cases gradually dropped off in most of Europe in the late 1800s and early 1900s. This was beforeany effective treatment or vaccination was discovered.
Why did the epidemic wane? To this day, no one knows for sure. Despite the white plague epidemic's centuries old existence, that is still too short a time for natural selection to have any effect. Most experts think that better living conditions and nutrition played a big part. People have a stronger immune system with better nutrition and less crowded living conditions. Also, when people have more breathing room, there is less exposure to the TB bacteria in the air. Some speculate that there was a "helper infection" to TB that adversely affected their T-cells, much like HIV virus does today. The population became resistant to the helper infection to the point it became much less common. Today we know that there are many mycobacteria that do not cause disease. Some speculate that there was a rise in the exposure to another mycobateria that partially immunized a significant part of the population against TB.
Another characteristic of TB epidemics is that they can wax and wane in geographic areas. One village or country may be in the midst of a terrible outbreak where nearly everyone is TB infected and diseased, while their neighbors have much less or even no disease. The neighbors will have infection, but less disease. Then the pattern will reverse in the next year or century. Environmental factors and living conditions alone cannot account for the huge difference in the number of cases. It is another one of the unknowns about TB.
Physicians and scientists have studied TB for millennia trying to understand the disease in order find effective cures, preventatives, or treatments. Ancient Indian and Chinese texts refer to TB. Hippocrates and Galen, famous physicians of antiquity, were familiar with the disease. Hippocrates did not think that TB was passed from person to person. Galen did think TB was a communicable disease. In 1680, Franciscus Sylvius, a Frenchman living in Germany, described pulmonary tubercles and thought the disease might be hereditary. The specific cause of TB remained unknown until Robert Koch, the Prussian doctor, revealed in 1882 that he had isolated and identified the TB mycobacterium from diseased patients and produced TB in laboratory animals with the organism. Koch also produced tuberculin by killing the TB mycobacteria and filtering the solution of dead organisms. He touted tuberculin as a cure for TB-in which role it failed miserably. However, tuberculin is still used today to test for TB in the host.
Before the advent of modern vaccines and antimicrobials, treatment for TB was very hit and miss. Mostly miss. Galen advocated bleeding, among other things. Bleeding TB patients not only doesn't work, it will make them worse.
In Europe, until the early modern era, it was believed that the touch of a ruling monarch could cure scrofula. Any of the old treatments that decrease further exposure to TB bacilli or that strengthens the body's immune system will have some positive effects. Fresh air and sunshine actually work to some degree. Modern research has shown that a person with vitamin D deficiency is more likely to develop TB disease. Exposure to UV light in sunshine increases the body's stores of vitamin D. Proper rest was also prescribed for TB patients. Rest enhances the immune system, as does the absence of stress factors. Various changes of diet were also advocated. Those changes usually eliminated malnutrition.
In our world, it has proven much easier to significantly decrease the incidence of bovine TB affecting people than the human strain. Once it was discovered in the late 1800s that most bovine TB was caused by ingesting infected milk and meat, control measures were quickly implemented in most American and European countries. Boiling or pasteurizing all milk kills TB bacilli. Sale of meat from TB infected livestock was forbidden. Skin-testing livestock using tuberculin was implemented. TB infected herds were quarantined or destroyed with compensation paid by the government to the owners. Extensive education programs aimed at healthcare workers, farmers, and consumers were initiated. In the UK, there was widespread opposition to control measures by farmer's groups and the MP's that they controlled. So the UK fell decades behind in controlling bovine TB. Once bovine TB control measures were put in place, the rate of TB meningitis in infants and small children was cut in half.
Albert Calmette, a bacteriologist, and Camille Guerin, a veterinarian, developed the first effective and safe vaccine for human TB. Working out of the Pasteur Institute in Lille, France, they attenuated (weakened) a strain of TB using multiple subcultures in a glycerin-bile-potato culture medium. Each subsequent culture in the medium was less virulent than the last. They named the attenuated TB strain Bacillus Calmette-Guerin (BCG). Human tests of the BCG live vaccine began in 1921. BCG is still the only vaccine used to combat TB. It is variably effective. It will prevent some forms of TB more effectively than others. It also works better in northern Europe than it does near the equator. A tuberculin skin test should be done on everyone, except newborns, before they get BCG vaccine. A positive tuberculin test indicates prior exposure to TB or another mycobacterium. BCG should not be given to those who have a positive reaction to a tuberculin skin test. In tuberculin reactors there can be a severe local reaction to vaccine with scarring. BCG vaccine will cause a positive reaction on a tuberculin test given later. So it is important to test before the vaccination to differentiate between natural infection and vaccination positives. People should not take antimicrobials for a few weeks after BCG vaccination. The antimicrobial will very likely kill the live vaccine in the body before it can produce immunity.
Detection of TB uses several methods. Chest x-rays can detect typical pulmonary TB lesions in the lungs. Sputum and other body fluids from those suspected to be infected is stained to find the very typical TB bacilli. The tuberculin skin test, made from killed, filtered, and diluted T. bovis bacilli has been the most common test for TB for many years. A tiny amount of tuberculin is injected intradermally. Three days later the skin reaction, if any, is measured. The size of the reaction is used to determine whether the person is positive or negative for TB infection. Tuberculin testing can detect those with active disease, those with latent (currently inactive) infection, and those that were infected in the past but don't have TB bacilli in their systems now.