In late 2012, a Nepalese man began a three month-journey, on foot, by car and boat, and in an airplane, through South Asia, Brazil and Mexico, and into Texas. He brought with him an infection called XDR-TB, short for extensively drug resistant tuberculosis, a disease still relatively rare in the US, but one that public health officials fear because it is spreading across the world. We have become complacent about TB because it has been successfully treated with antibiotics since the 1950s and because most tuberculosis cases occur in underdeveloped countries where malnourished and sick people with weakened immune systems live in crowded and unsanitary conditions. But with easy global travel and spreading antibiotic resistance, especially on the Eastern border of Europe and in Africa, China and India, more awareness of this ancient disease is needed again in areas of the world where improved living conditions have made TB uncommon and unknown.

A long history

Three-thousand-year-old writings from China and India, passages in the Old Testament, and the writings of Hippocrates all describe the affliction we call tuberculosis. The disease became a scourge as more and more people crowded into urban centers in northern climates in the middle ages.  Between the 1500s and 1800s, hundreds of millions of people in Western Europe, England and the eastern US died of TB, then called consumption and attributed either to a “malignant miasma” in the air or to hereditary constitutional weakness. Squalid living conditions, poor indoor ventilation and malnutrition common during the early industrial revolution facilitated the spread of the disease, which in 1882 was finally proven to be caused by a bacterium, Mycobacterium tuberculosis.  When living conditions began to improve in the early 1800s the death rate began to decline, but a cure awaited the development of antibiotics in the mid-twentieth century. The goal of eradicating TB, however, has not been achieved.

Latent vs active infections? The immune system decides.

Anyone can be infected with the TB bacteria, acquired by inhaling the respiratory droplets of someone who has an active infection in their lungs. Inhaled TB bacteria are captured by cells that scour the airways for invaders. The bacteria reproduce themselves inside those cells, eventually killing them and exciting an immune response that in 90% of people will clean up the infected area, called a “tubercle,” in a process called caseating necrosis because the dead tissue resembles crumbled cheese. The tubercles may leave small scars in the lung, visible on chest X-ray, without ever having caused any symptoms of illness. Infection in these immuno-competent people, the vast majority, is called latent TB, a condition that affects almost a third of the world’s population, including 13 million people in the US.

In 10 % of people who get infected with the TB bacteria, the immune response is insufficient. Active tuberculosis is the result. Caseating tubercles may grow to large size and collapse producing cavities in the lung. Tubercles that erupt into the airways allow surviving bacteria to spread to other people in sputum and respiratory droplets. In addition, bacteria may travel to other parts of the body via the lymphatic system, setting up infectious nodes in almost any tissue.  Typical symptoms of active tuberculosis develop over weeks to months and include chronic cough, night sweats and fever, weight loss, weakness, fatigue, and skin pallor. Tubercles in various organs and lymph nodes give rise to local symptoms from swelling and inflammation.

Latent infections come alive

Latent TB can reactivate and become active TB if the carrier’s immune system weakens – a result of other disease such as HIV, drug treatment that suppresses the immune system, or just deterioration of health that accompanies drug use or poor living conditions. Ten million cases of active infection occur each worldwide year.

Before antibiotics: high altitude and collapsing lungs

In the 1840s a botany student who suffered from TB traveled to the Himalaya mountains and came home to report his cure, setting in motion the sanatorium treatment for which high altitude locations such as Davos Switzerland and Denver, Colorado became renowned. Much later, scientific work showed that the mycobacterium tuberculosis grows poorly at low oxygen pressures, a fact that may well have added to the other health and nutritional benefits of sanatorium life. Attempts to put infected parts of lungs “to rest” by collapsing them with injections of nitrogen into the chest began in the 1880s.  German Author Thomas Mann memorialized this procedure, called an artificial pneumothorax, in his novel The Magic Mountain.  The treatment method continued well into the 1940s, when the development of antibiotics finally offered a cure for TB.

Not the usual antibiotic treatment

Antibiotic treatment of TB is not easy. Patients must take two to four drugs on a strict schedule for 6-9 months and tolerate some unpleasant side effects like nausea. Until their sputum is free of TB bacteria – which can take several weeks – they must be strictly isolated. Caretakers benefit from proper mask wearing because the tuberculosis bacteria is larger than N95 mask pores.  Because drug resistance has been a result of poor compliance with the drug regimens, strict monitoring and observation of patients is necessary. Often drugs must be taken under direct observation. Once drug resistant disease occurs, treatment becomes more complicated and prolonged, requiring trials of different antibiotics, with even more need for isolation of infectious patients and close supervision throughout the entire course of treatment.

Testing and vaccines

A tuberculin skin test, when positive, indicates prior infection with tuberculosis bacteria, and therefore latent disease in someone who has no symptoms. Chest X-ray and chest CT, as well as collection of sputum for microscopic analysis and culture are the mainstays of diagnosis in active disease or if someone with a positive skin test has any suspicious symptoms.

The only vaccine for TB, used since 1921, is made from a weakened bacterium similar to the TB bacterium. Its acronym BCG is short for the virus name (Bacille Calmette Guerin). BCG reliably prevents neonatal disseminated forms of TB such as meningitis, but is much less effective in preventing the adult respiratory form of TB, which is the usual version beyond childhood. It has not been regularly administered in the US because most people handle primary infections easily. However the spread of drug resistant forms of TB may change that recommendation, especially for people regularly exposed to patients. In the meantime, work on new vaccines employing new technologies continues.

Drug resistance is spreading

TB was on the decline in the US until the 1980s, when HIV disease appeared, devastating the immune systems of its sufferers and making them susceptible to active TB.  With better treatment of HIV, TB is on the decline again, but popping up increasingly in the homeless population, particularly where they congregate indoors in crowded shelters. Recently, cases of drug resistant TB have occurred in people who had never been treated, meaning that the drug resistant bacteria are spreading, not just evolving in treated patients. In eastern Europe 30% of new TB cases are now resistant to many of the TB drugs. The traveler who appeared in Texas with XDR-TB was a warning. We need robust public health measures to monitor infectious diseases, improve sanitation and living conditions as much as we need development of new antibiotics.