Sandbox:Mydah

Associate Editor(s)-in-Chief: Mydah Sajid, MD[1]

Tuberculosis

Overview

Tuberculosis is caused by inhalation of bacteria named Mycobacterium tuberculosis. It causes pulmonary and disseminated infection. In the lungs, it cause cavitary lesions in the upper and posterior lobe. It can cause disseminated infection in the brain, lymph nodes, and gastrointestinal tract. It presents with chronic productive cough with purulent phlegm which may contain blood. The patient also presents with systemic symptoms like night sweats, low-grade fever, and significant weight loss. As of 2018 one quarter of the world's population is thought to have latent infection with TB. New infections occur in about 1% of the population each year. In 2018, there were more than 10 million cases of active TB which resulted in 1.5 million deaths. Tuberculosis causes second highest number of deaths from an infectious disease.

Historical Prespective

• TB in humans can be traced back to 9,000 years ago in Atlit Yam, a city now under the Mediterranean Sea, off the coast of Israel.
• Mycobacterium tuberculosis was discovered on March 24, 1882 by Dr. Robert Koch.

Classification

• Latent tuberculosis
• Active tuberculosis
  • Pulmonary infection
  • Extrapulmonary infection

Pathophysiology

When people with active pulmonary TB cough, sneeze, speak, sing, or spit, they expel infectious aerosol droplets 0.5 to 5.0 µm in diameter. A single sneeze can release up to 40,000 droplets. Each one of these droplets may transmit the disease, since the infectious dose of tuberculosis is very small (the inhalation of fewer than 10 bacteria may cause an infection). About 90% of those infected with M. tuberculosis have asymptomatic, latent TB infections (sometimes called LTBI), with only a 10% lifetime chance that the latent infection will progress to overt, active tuberculous disease. TB infection begins when the mycobacteria reach the alveolar air sacs of the lungs, where they invade and replicate within endosomes of alveolar macrophages. Macrophages identify the bacterium as foreign and attempt to eliminate it by phagocytosis. The primary site of infection in the lungs, known as the "Ghon focus", is generally located in either the upper part of the lower lobe or the lower part of the upper lobe. Tuberculosis of the lungs may also occur via infection from the bloodstream. This is known as a Simon focus and is typically found in the top of the lung. This hematogenous transmission can also spread the infection to more distant sites, such as peripheral lymph nodes, the kidneys, the brain, and the bones.

Causes

The main cause of TB is Mycobacterium tuberculosis (MTB), a small, aerobic, nonmotile bacillus. The high lipid content of this pathogen accounts for many of its unique clinical characteristics. Mycobacteria stain by acid-fast stain called Ziehl-Neelson stain. Auramine-rhodamine staining and fluorescence microscopy are also used. The M. tuberculosis complex (MTBC) includes four other TB-causing mycobacteria: M. bovis, M. africanum, M. canetti, and M. microti.

Differntiating tuberculosis from other diseases

Pulmonary tuberculosis must be differentiated from other diseases that cause productive cough and systemic symptoms like brucellosis, bronchogenic carcinoma, Hodgkin lymphoma, bacterial pneumonia, sarcoidosis, mycoplasmal pneumonia.

Epidemiology and Demographics

Roughly one-quarter of the world's population has been infected with M. tuberculosis, with new infections occurring in about 1% of the population each year. However, most infections with M. tuberculosis do not cause TB disease, and 90–95% of infections remain asymptomatic. In 2012, an estimated 8.6 million chronic cases were active. In 2010, 8.8 million new cases of TB were diagnosed, and 1.20–1.45 million deaths occurred, most of these occurring in developing countries. Of these 1.45 million deaths, about 0.35 million occur in those also infected with HIV. Tuberculosis is the second-most common cause of death from infectious disease (after those due to HIV/AIDS).

Risk Factors

1. HIV infection
2. Impoverish living conditions: Homeless shelters, prisons
3. Chronic lung diseases i.e. Silicosis
4. Medications: immunosuppressants like corticosteroids and TNF alpha inhibitors

Screening

The primary screening method for TB infection (active or latent) is the Mantoux tuberculin skin test with purified protein derivative (PPD). An in vitro blood test based on interferon-gamma release assay (IGRA) with antigens specific for M tuberculosis can also be used to screen for latent TB infection.

Natural History, Complications and Prognosis

Tuberculosis infection can manifest with pulmonary symptoms and if the infection is disseminated, patient can have symptoms in other systems.

Pulmonary

If a tuberculosis infection does become active, it most commonly involves the lungs (in about 90% of cases) <ref/ Lancet. 2011 Jul 2;378(9785):57-72.> Symptoms may include chest pain and a prolonged cough producing sputum. About 25% of people may not have any symptoms (i.e. they remain "asymptomatic"). Tuberculosis may become a chronic illness and cause extensive scarring in the upper lobes of the lungs. The upper lung lobes are more frequently affected by tuberculosis than the lower ones.

Extrapulmonary

In 15–20% of active cases, the infection spreads outside the lungs, causing other kinds of TB. These are collectively denoted as extrapulmonary tuberculosis. Notable extrapulmonary infection sites include the pleura (in tuberculous pleurisy), the central nervous system (in tuberculous meningitis), the lymphatic system (in scrofula of the neck), the genitourinary system (in urogenital tuberculosis), and the bones and joints (in Pott disease of the spine), among others.

Complications

• Acute
  • Tb-related sepsis
• Chronic
  • Mycetomas developing within residual TB cavities
  • Impaired pulmonary function
  • Focal neurological deficits

Prognosis

The prognosis for drug-sensitive tuberculosis is good if the patient is compliant and complete the treatment protocols. The recurrence rate of TB is low (0%-14%) and some may be due to reinfection. Drug-resistant tuberculosis is more difficult to treat, and the prognosis is not as good.

Treatment

Latent

Latent tuberculosis is treated with either Isoniazid alone or both Isoniazid and Rifampicin given for three to nine months.

Active

Active tuberculosis is treated with two months of four drug regime intensive phase and four to six months of continuation phase with Isoniazid and Rifampicin. The first-line drugs for the treatment of tuberculosis are:

• Isoniazid
• Rifampicin
• Ethambutol
• Pyrazinamide
• Streptomycin

Treatment of multi-drug resistant tuberculosis (MDR Tb) is a challenge. The second-line drug regime is used for MDR Tb. It includes:

• Aminoglycosides
• Fluoroquinolones
• Polypeptides
• Thioamides
• Terizidone
• Cycloserine