Tuberculosis

What is it?

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis. TB may affect many body organs, but it primarily affects the lungs. It is spread through the air from person to person through lung secretions such as sputum (spit or phlegm) or aerosols released by coughing, sneezing, laughing, or breathing. Most of those who become infected with M. tuberculosis manage to confine the mycobacteria to a few cells in their body, where they stay alive in an inactive form. This inactive or latent TB infection does not make the patient sick or infectious and, in most cases, it does not progress to cause active tuberculosis.

However, some patients - especially those with damaged or compromised immune systems - may proceed directly from initial TB infection to active tuberculosis. And in another ~10%-15% of those with latent TB infection, the mycobacteria will later be reactivated and begin to multiply - leading to active progressive tuberculosis disease.

TB has been a leading cause of death worldwide for thousands of years. In the days before the discovery of antibiotics it was called consumption, and those who contracted it were put into long-term hospitals called sanatoriums for the rest of their lives. TB first became a statutorily notifiable disease in the UK in 1913; with almost 120,000 cases in that year. The number of new cases fell progressively until the mid 1980s, however numbers started to rise again in the early 1990s. Overall total numbers of TB cases has declined by 11.6% in the last two years. However, worldwide, TB is still the leading cause of death due to infection - killing more than 3 million people a year.

In developed countries such as the USA or the UK, the majority of these cases were among those living in overcrowded or confined conditions such as prisons, nursing homes, and schools. The most vulnerable were those who had poor health care or had diseases and conditions that weakened their immune systems, such as: the homeless, alcoholics, intravenous drug users, those with HIV or AIDS, and those with chronic kidney or liver diseases. Often these new cases were multi-drug resistant (MDR), making them more difficult to treat. The revised UK immunisation programme on TB is to target infants in areas where the incidence of TB is greater than 40 cases / 100000, or have parents or grandparents who were born in countries with such an incidence.

Signs and Symptoms

Inactive or latent TB infection does not cause any symptoms. Someone may have latent TB infection for years without knowing it. It is usually diagnosed when a patient has a positive TB skin test or antibody screening test, known as a T Spot.

The symptoms of active tuberculosis depend on what part(s) of the body are involved. The classic symptoms tend to be pulmonary (TB in the lungs) and include:

  • Chronic cough, sometimes with bloody sputum
  • Fever
  • Chills
  • Weight loss
  • Weakness
  • Night sweats

If the TB is extrapulmonary (outside of the lungs), it may cause few noticeable symptoms or a wide range including:

  • Back pain and paralysis (spinal TB)
  • Weakness due to anaemia (TB in the bone marrow)
  • Joint pain
  • Pain associated with reproductive system or urinary tract, and possibly, resulting in infertility
  • Abdominal pain
  • Fever and shortness of breath (TB in the lining around the heart, affecting the pericardium, or miliary TB, a large number in the bloodstream)
  • Altered mental state, headache and coma (TB in the brain and/or central nervous system)

All of these symptoms may also be seen in a variety of other conditions. A diagnosis of active tuberculosis depends on the positive identification of Mycobacterium tuberculosis in the body fluids or tissues.

Tests

Laboratory Tests

Latent TB infection
Testing for Mycobacterium tuberculosis begins with a skin or antibody test for latent TB infection. This is not used as a general screen, but is targeted at those who are at a high risk for contracting the disease and at those who work or live with high-risk patients. These tests may also be done as part of a physical examination prior to starting school or a new job. Positive results may indicate a latent TB infection and should be followed by other investigations such as chest X-rays to look for signs of active disease.

Active Tuberculosis
To diagnose TB of the respiratory tract, 3 - 5 sputum specimens are collected first thing in the morning when they are most likely to contain the most TB bacteria. If extrapulmonary TB is suspected, samples are collected based upon where in the body the infection is likely to be. Multiple samples of gastric washings/aspirates or urine may be collected and submitted to the laboratory. Sometimes cerebral spinal fluid (CSF), biopsied tissue, or other body fluids are also collected.

A presumptive diagnosis of TB can be made by examining a smear of the patient's specimen under the microscope after it has been stained with a special stain to detect acid fast bacteria (AFB). Positive AFB smears are likely to indicate a TB infection, since M. tuberculosis is the most common acid-fast bacillus, but the smears cannot distinguish between the different species of "acid-fast" bacilli.

A genetic probe or molecular TB test can add additional information. It amplifies/replicates genetic components of TB and can narrow the identification to a group of mycobacteria (of which M. tuberculosis is the most common). While AFB smears and genetic tests may provide results the same day that the samples are submitted, both positive and negative results must be confirmed by culture, which can take 6-12 weeks dependant on sample type.

AFB cultures are set up using decontaminated, digested, and concentrated body samples. Nutrients and incubation provide a supportive environment for the slow growing mycobacteria. The results of cultures are definitive: They can tell your doctor what organisms are present and what drugs are likely to kill them but they take time - days to several weeks for positive samples, up to six to twelve weeks to confirm negative results.

Once M. tuberculosis has been identified and treatment has begun, AFB smears and cultures are used to monitor the effectiveness of treatment.

Non-Laboratory Tests

X-rays are often used as a follow-up to positive TB skin and antibody tests to look for signs of mycobacteria growth and to help determine whether someone has active tuberculosis or a latent TB infection. Infection with TB can cause a number of characteristic findings on x-rays, including cavities (holes) and calcification in organs such as the lungs and kidneys

Treatment

Prevention
Prevention of TB infection lies primarily in identifying, isolating, and treating those who have it before they pass it on to others.

A vaccine called Bacillus Calmette-Guerin (BCG) is often routinely administered in parts of the world where TB is much more common, although studies have shown that this vaccine will not prevent every case of TB. BCG vaccination is being used to selectively target “at-risk” groups and those in areas with a high incidence of TB.

Early Detection
Early detection depends on identifying those at risk and testing them at regular intervals for latent TB infection. It also depends on recognising, diagnosing, and treating those who progress to active tuberculosis.

Latent
The decision to treat latent TB infection is up to you and your doctor. If follow-up testing reveals no indication of active tuberculosis and you are not considered at a high risk for developing active TB, your doctor may decide to simply monitor your health at regular intervals (since about 90% of those with latent infections never develop active tuberculosis).

If, however, your doctor is of the opinion that you are at risk of developing active TB, you may be treated with a six month course of an antibiotic called isoniazid. It is necessary to take it for the entire treatment period to ensure that all of the latent bacteria have been killed.  Failure to do so can result in treatment failure and development of multi-drug resistant TB which can prove extremely difficult to treat. Your doctor may use lab tests to monitor your liver during this time period, as isoniazid can sometimes affect how the liver functions.

Active Tuberculosis
Active tuberculosis must always be treated. Once M. tuberculosis has been positively identified, your doctor will start you on a treatment program that involves taking several drugs for several months. The length of treatment depends on the results of the AFB smears and cultures used to monitor the effectiveness of treatment.

Although your symptoms will often go away after several weeks it is crucial that you continue to take your drugs for the entire time period. There are a large number of mycobacteria to kill and it takes several months to make sure that all of them have been eradicated. If treatment is not continued, the TB can come back, and this time it may be more difficult to treat. It may now be resistant to the first choice drugs, requiring treatment for several more months with drugs that have more side effects.

Those with active tuberculosis may be encouraged to participate in DOT (directly observed therapy). This involves taking your medication each day, or several days a week, under the supervision of medical personnel. This increases patient compliance with treatment and decreases the number of people that have to be treated again because their TB has returned.