Tuberculosis: Active, Latent, and Drug-Resistant

Tuberculosis, or TB, is a chronic infection caused by a bacterium called Mycobacterium tuberculosis. It is spread through the air when an infected person coughs, sneezes, or lives closely with others. TB typically infects the lungs, although in some cases it can affect other parts of the body.

In the lungs, TB can cause symptoms such as chronic cough, which sometimes brings up blood or sputum (phlegm from deep inside the lungs), chest pain, weakness or fatigue, weight loss, lack of appetite, chills, fever, and night sweats.

Immigrants are affected disproportionately by TB, which occurs among foreign-born individuals nearly nine times as frequently as among people born in the US. This is partially because they were exposed to M. tuberculosis in their country of origin before moving to the United States. In 2004, a very high percentage of Asians (95%) and Hispanics (75%) who were reported to have TB were born outside the United States.

Linus Santo Tomas, MD, MS, Assistant Professor of Pulmonary/Critical Care Medicine at the Medical College of Wisconsin, practices at the Pulmonary Medicine Clinic at Froedtert & Medical College Clinics. Dr. Santo Tomas acquired much of his TB expertise during his previous practice in the Philippines, where the disease is quite prevalent.

TB infection can be either active or latent. In a case of active TB, symptoms are present, and the infection is contagious.

Active TB
"When a patient comes in with symptoms such as fever, night sweats, weight loss, a chronic cough with sputum production, especially blood-streaked sputum, we test for tuberculosis." Dr. Santo Tomas performs a tuberculin skin test, in which tuberculin is injected under the skin to see if a red welt forms around the injection site, or the QuantiFERON-TBŪ Gold blood test, which uses whole blood to check for TB infection.

People who test positive on the tuberculin tests don't necessarily have active TB; they might have latent TB from a previous exposure to TB or bacteria related to TB. Although not often used in the US, a TB vaccination from another country might also show a positive result on one or both tests.

Other tests can help to show if patients have active TB. Dr. Santo Tomas often performs a chest x-ray to look for abnormalities that might be caused by TB. The sputum can also be tested, in three samples 8 to 24 hours apart. "If the sputum tests are negative," says Dr. Santo Tomas, "we will do a bronchoscopy. In this procedure, we insert a flexible scope through the mouth or nose, to go into the airway and get samples from the lungs."

Latent TB
An estimated 10 to 15 million people in the United States have latent TB. "Latent tuberculosis means that the organisms have infected the person, but the person is not showing symptoms of tuberculosis," Dr. Santo Tomas says. "During the primary infection, the immune system usually controls the infection so it doesn't spread. However, in some people the primary infection, instead of being controlled by the immune system, can progress and cause symptoms of active tuberculosis."

Most people don't develop the active disease after primary infection, Dr. Santo Tomas says. TB can stay latent indefinitely, but those with latent TB are at higher risk for developing the active form. The risk of developing active disease is greatest in the first 2 years after primary infection, but it sometimes does not occur until many years later.

Latent tuberculosis is usually found by screening, says Dr. Santo Tomas, and then investigated for further symptoms. "If there are no symptoms to indicate active tuberculosis, we still need to treat the latent TB. The treatment of choice is nine months with an antibiotic called isoniazid (INH)."

Groups at Risk
While there isn't a "typical" TB patient, Dr. Santo Tomas says, "People at higher risk are people with diabetes, chronic renal disease, certain occupational diseases like silicosis, patients who have had gastric bypass surgery, drug users, HIV patients, patients taking immunosuppressive medications, and patients with certain cancers such as leukemia, Hodgkin's lymphoma, and head and neck cancers." These groups have a lowered immunity to TB and other infectious disease, says Dr. Santo Tomas.

Other groups, such as people who are in prison and people in some health care settings, have higher risk of TB infection because of possible exposure to persons with active infection, and they should also have regular screenings. Of special concern are people who are about to receive certain immunosuppressive medications because of rheumatic disease or Crohn's disease. "Once you start those medications, the risk of developing active tuberculosis is increased, so we want to screen for latent tuberculosis in those people," says Dr. Santo Tomas.

Global TB Epidemic Leveling Off
The World Health Organization recently announced that the global TB epidemic has leveled off for the first time since it declared TB a public health emergency in 1993. "The first drugs came out for tuberculosis in the 1940s, and that led to its control," says Dr. Santo Tomas. "But people became complacent because of the drug treatments and better public health, and in the 1990s, when HIV caused more people to have depressed immune systems; it started to go up again."

Since then, better education for physicians and the public have led to an annual decrease in TB cases. In the US, the US Centers for Disease Control and Prevention (CDC) reported 14,093 cases of active TB and 10 to 15 million cases of latent TB in 2005.

Multiple Drug Resistant TB
About 1.2% of TB cases in the US are resistant to treatment. "In Multiple Drug Resistant Tuberculosis," says Dr. Santo Tomas, "the TB organism is resistant to two of the first-line drugs we use for treatment, isoniazid and rifampin. It's probably less prevalent in the US than other countries with a higher burden of tuberculosis, but it does happen."

Multiple Drug Resistant Tuberculosis (MDR TB) most commonly develops because of poor compliance with medication, says Dr. Santo Tomas. "It's actually a preventable phenomenon. People are either not finishing their medications, or not taking them as directed." There are different regimens for treating active tuberculosis, he notes, but all are quite lengthy and involve several different drugs. "Some medications are taken on a daily basis, and some are taken less frequently but with a higher dose."

The duration of treatment is also an issue, he says. "In treating active TB, there's an intensive phase, which is usually two months, then a continuation phase, which is at least four months. Patients have to be compliant in terms of what to take daily, as well as how long they need to be taken."

In addition, the bacteria can evolve, or mutate, in order to outwit the medications, says Dr. Santo Tomas. "But by using the different drugs as directed, you significantly reduce the chance that any of these mutations will survive and develop a resistance."

Unfortunately, MDR TB requires treatment for 18 to 24 months with second-line drugs that are much less effective, often poorly tolerated by the patient, and far more costly.

Treatment is Effective
Overall, Dr. Santo Tomas says, TB is a very treatable disease. "The first-line drugs used to treat TB have remained the same over the past 20 years," he says. "They are very effective when taken properly."

P. J. Early
HealthLink Contributing Writer

This article includes information from the National Institute of Allergy and Infectious Diseases, the World Health Organization, the US Centers for Disease Control and Prevention, and the US Department of State.