Once one of the deadliest diseases in the United States, tuberculosis (TB) has been controlled over the past 50 years by antibiotics. Fewer than 10,000 U.S. cases are diagnosed each year, or almost 3 cases per 100,000. On a global scale, TB remains one of the Top Ten causes of death. If you have a compromised immune system, then the disease poses a genuine health threat. 

At Yale Medicine’s Laboratory Medicine department, scientists work to diagnose latent (inactive) and active tuberculosis as quickly and efficiently as possible so patients can get the best treatment to fight the disease.

Tuberculosis – a bacterial infection that mostly affects the lungs – is transmitted through tiny droplets in the air. When a person with active tuberculosis coughs, sneezes, or speaks, he or she sends these particles flying through the air. The infection gets passed on to another person when he or she breathes in those particles. A person is most likely to contract tuberculosis when working or living with someone who has active symptoms of the disease.

Most people who inhale the bacteria do not have any symptoms and cannot infect other people. This is known as latent tuberculosis. It means a person’s immune system is strong enough to fight off the illness. But tuberculosis bacteria that stay dormant in the body can awaken at any time, especially as people get older, or if they become sick and their immune system weakens, says Yale Medicine's pathologist Sheldon M. Campbell, MD, PhD.

If you’ve been exposed to someone with active tuberculosis (TB), even if you don’t have symptoms, it is crucial to be tested and treated so you can control the infection before it becomes active, Dr. Campbell says. Treating the active disease is tricky and this places more importance on treating latent TB as soon as possible.

“Someone who has latent tuberculosis has about a 10 percent lifetime risk of developing active tuberculosis disease,” says Dr. Campbell. “If we find the bacteria while it’s still in its latent phase, the active disease can be prevented with a simple drug treatment before it ever gets going.”

The simplest way to test for latent tuberculosis (TB) is with a skin test:

A small, harmless sample of TB protein is injected underneath the skin on your arm. Then 48 to 72 hours later, a healthcare worker checks your arm for a reaction.

“If you have latent tuberculosis, then your immune system recognizes the protein, and some of the immune cells react by migrating to the spot, creating a little lump,” Dr. Campbell says. If you have received a vaccine in the past for tuberculosis (many foreign-born people have received the bacille Calmette–Guérin, or BCG, vaccine), you may get a false positive from this test.

A second type of test for latent tuberculosis are interferon gamma release assays (IGRAs). In this test, a technician draws a blood sample and then sends it for lab testing, where it is incubated in a test tube with some tuberculosis proteins. The sample is then tested for the presence of immune cells that produce gamma-interferon in the presence of TB proteins.

Results from this test take about 72 hours. Unlike the skin test, it doesn’t require a follow-up visit and it is not affected by the vaccine, so it may be preferable for some patients.

Whether a person is infected soon after encountering another tuberculosis patient, or it takes years for the dormant disease to activate, tuberculosis can cause severe, life-threatening symptoms.

In addition to causing a bad cough, chest pain, fever, weight loss, and fatigue, the germ can spread to other organs, causing spinal pain, infection of the abdominal cavity, or inflammation of the membranes surrounding the brain.

To test for active tuberculosis, lab scientists examine your sputum – the mucus that comes up from coughing.

There are two main methods used to test the sputum. One technique that can be tried immediately is to examine the mucus on a slide under the microscope. “A recently developed way to test sputum is with a DNA test, called GeneXpert, which can rapidly identify the strain of bacteria and also can test it for susceptibility to a key antituberculosis drug,” Dr. Campbell says.

For the DNA test, a sputum sample must be grown in a culture for four to six weeks before it can be tested. Depending on the patient’s risk factors, symptoms, and chest X-ray results, treatment for the disease can begin before lab results are complete.

Patients with latent tuberculosis receive one or two drugs for four to six months. Active tuberculosis is treated with three or more antibiotics for six to nine months. For some forms of drug-resistant tuberculosis, treatment with both oral and injectable medications are necessary for as long as 30 months.

In addition to having state-of-art testing apparatus, Yale Medicine is also home to important research being done on drug-resistant strains of tuberculosis affecting people across the world, especially in South Africa.