Run! Yes, run, do not walk . . . to the nearest doctor's office and demand that they write a prescription for a twelve-month supply of isoniazid for every member of your family.

Unfortunately, even if the pharmacy has any of the drug, he is going to tell you "Hell, no." He knows just as well as you do that in 1631 you have been dropped in the middle of an epidemic that will last another 250 years. No, it's not the black plague. It's not smallpox, and it's not any of the sexy, fast-burning epidemics.

It is the white plague—tuberculosis.

Every person in Grantville is very likely to be infected with tuberculosis mycobacterium within the first year. One-third of them will get sick. Without modern medical treatment, probably half of those who get sick will die in the next five years. About one-fifth will be chronically sick and eventually die from the disease, and one-third will recover.

How do "they" prevent that from happening? I'm sorry, but "they" includes you and you have an important role to play. How? First you have to learn everything you can about tuberculosis.

Mycobacterium tuberculosis and Mycobacterium bovis, the main two causative agents of tuberculosis(TB), have preyed on their human and animal hosts for thousands of years. Tuberculi and tubercular lesions were found in mummies from Egypt that are thousands of years old. They were found in pre-Columbian mummies and skeletons in Peru. On most continents, there is evidence of TB as soon as people gathered in agricultural communities. M. tuberculosis causes most human TB. M. bovis, which also infects cattle, sheep and goats, is responsible for 5-25% of human infections depending on time period, geographic area, and control measures.

The common names for tuberculosis disease include TB, consumption, scrofula, phthisis, Pott's disease, and white plague. Phthisis is the ancient Greek and Roman name for TB and was the name used by doctors until the 1800s. Consumption, the common name for TB for centuries, was so ubiquitous in the 1800s that the pale skin and wasted appearance of its upper-class victims became fashionable. That fashion has persisted to this day. Think of the heroin addict appearance of many top models or the pale-skinned, razor-thin vampires of contemporary fiction. Consumption was associated with vampirism in some superstitious cultures of the Early Modern Era.

The fashionable consumptive appearance of TB is not the only aspect of the disease that has persisted into the present. Up to one-third of the world's population today is or has been infected with TB. One-tenth of those infected with TB develop disease. Of those that develop disease, over half die within five years if not treated. Between one and two million people die each year from tuberculosis. It is the most common infectious disease on Earth . . . just as it has been since antiquity. Most of today's TB infections and disease occur in Asia and Africa, where the same poor living conditions that were common in 1600-1900 Europe predominate. The sub-optimal living conditions include overcrowding (even in rural villages), poor workplace and home ventilation, malnutrition, poor hygiene, other common diseases, and lack of basic healthcare.

TB can affect nearly all of the body's organs. The most common and well known symptoms are related to the respiratory system. Small and large pulmonary granulomatous (cheesy) abscesses, known as tubercles, form and destroy normal lung tissue and rupture blood vessels in the lung. The disease can spread to other organs from the lungs.

The bovine strain of TB is usually acquired by ingesting infected milk (especially) and meat. It most commonly attacks the digestive system forming tubercles in the lining of the intestines. Tubercular meningitis is common in infants exposed to the bacteria. Scrofula refers to the form of the disease in which the lymph nodes of the throat are visibly swollen. In Pott's disease, the bacteria attacks the bones and connective tissue. The skin form of TB is known as lupus vulgaris. It causes terrible ulcerous disfigurations of the face that resemble leprosy.

Most forms of TB are chronic diseases. They take years to kill their victim. The forms that act quickly usually affect the very young or the very old. Infants and young children are very likely to develop TB disease if exposed to the bacteria. School-age children seem to be more resistant to the disease, but, the age group that TB disease affects the most is people in the prime of their life—the 15-50 year-olds.

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.

The first antimicrobials that were effective against TB were developed in the 1940s in the US, Sweden, and Germany. Streptomycin was developed in the US, PAS in Sweden, and thioacetazone was developed in Germany. At first they were considered miracle drugs because they were so effective in treating all forms of TB. Within a couple of years many patients treated with the drugs were relapsing with TB. Even worse, the TB bacteria in the relapses were now resistant to the drug first used to treat the TB.

In their race to find better drugs, three competing drug companies nearly simultaneously discovered that isoniazid had very strong ant-TB effects. Isoniazid is ...