Tuberculosis is a widespread, and in many cases fatal, infectious disease caused by various strains of mycobacteria, usually Mycobacterium tuberculosis. Tuberculosis typically attacks the lungs, but can also affect other parts of the body. It is spread through the air where people who have an active TB infection cough, sneeze, or otherwise transmit respiratory fluids through the air. Most infections do not have symptoms, known as latent tuberculosis. About one in ten latent infections eventually progress to active disease which, if left untreated, kills more than 50% of those so infected.
The classic symptoms of active TB infection are a chronic cough with blood tinged sputum, fever, night sweats, and weight loss. Infection of other organs causes a wide range of symptoms. Diagnosis of active TB relies on radiology (commonly chest x- rays), as well as microscopic examination and microbiological culture of body fluids. Diagnosis of latent TB relies on the tuberculin skin tests / or blood tests. Treatment is difficult and requires administration of multiple antibiotics over a long period of time. Social contacts are also screened and treated if necessary. Antibiotic resistance is a growing problem in multiple drug- resistant tuberculosis (MDR- TB) infections. Prevention relies on screening programs and vaccination with the Bacillus Calmette – Guerin vaccine. One- third of the world’s population is thought to have been infected with M- tuberculosis, with new infections occurring in about 1% of the population each year. More people in the developing world contract tuberculosis because of a poor immune system, largely due to high rates of HIV infections and the corresponding development of AIDS.
Signs and symptoms
Tuberculosis may infect any part of the body, but most commonly occurs in the lungs ( known as pulmonary tuberculosis ). Extra pulmonary TB occurs when tuberculosis develops outside of the lungs, although extra pulmonary TB may coexist with pulmonary TB, as well. General signs and symptoms include fever, chills, night sweats, loss of appetite, weight loss, and fatigue. Significant nail clubbing may also occur.
If a tuberculosis infection does become active, it most commonly involves the lungs ( in about 90% of cases ). 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 ” ). Occasionally, people may cough up blood in small amounts, and in very rare cases, the infection may erode into the pulmonary artery, resulting in massive bleeding. 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. The reason for this difference is not entirely clear. It may be due either to better airflow, or to poor lymph drainage within the upper lungs.
In 15- 20 percent of active cases, the infection spreads outside the lungs, causing other types of TB. These are collectively denoted as “extra pulmonary tuberculosis “. Extra pulmonary TB occurs more commonly in immunosuppressed persons and young children. In those with HIV, this occurs in more than 50% of cases. Notable extra pulmonary infection sites include the pleura ( in tuberculous pleurisy ), the central nervous system ( in tubercular meningitis ), the lymphatic system ( in scrofula of the neck ), the genitourinary system ( in urogenital tuberculosis ), and the bones and joints ( in Pott’s disease of the spine ), among others. When it spreads to the bones, it is also known as “osseous tuberculosis”, a form of osteomyelitis. Sometimes, bursting of a tubercular abscess through skin results in tubercular ulcer. An ulcer originating from nearby infected lymph nodes are painless, slowly enlarging and has the appearance of “wash leather”. A potentially more serious, widespread form of TB is called “disseminated” TB, commonly known as miliary tuberculosis. Miliary TB makes up about 10% of extra pulmonary cases.
The main cause of TB is mycobacterium tuberculosis, a small, aerobic, nonmotile bacillus. MTB can withstand weak disinfectants and survive in a dry state for weeks. In nature, the bacterium can grow only within the cells of a host organism, but M. Tuberculosis can be cultured in the laboratory. Using histological stains on expectorated samples from phlegm (also called “sputum ” ), scientists can identify MTB under a regular (light) microscope.
A number of factors make people more susceptible to TB infections. The most important risk factor globally is HIV; 13%of all people with TB are infected by the virus. Of people without HIV who are infected with tuberculosis, about 5- 10% develop active disease during their lifetimes, in contrast, 30% of those coinfected with HIV develop the active disease.
Tuberculosis is closely linked to both overcrowding and malnutrition, making it one of the principal diseases of poverty. Those at high risk thus include; people who inject illicit drugs, inhabitants and employees of locales where vulnerable people gather ( e.g., prisons and homeless shelters ), medically underprivileged and resource- poor communities, high risk ethnic minorities, children in close contact with high- risk category patients, and health- care providers serving these patients.
Chronic lung disease is another significant risk factor. Silicosis increases the risk about 30-fold. Those who smoke cigarettes have nearly twice the risk of TB compared to nonsmokers. Other disease states can also increase the risk of developing tuberculosis. These include alcoholism and diabetes mellitus (three- fold increase). Certain medications, such as corticosteroids are becoming increasingly important risk factors. Also a genetic susceptibility element exists, for which the overall importance remains undefined.
When people with active pulmonary TB cough, sneeze, sing, or spit, they expel infectios aerosol droplets 0.5 to 5.0 micrometer 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 fever than 10 bacteria may cause an infection).
People with prolonged, frequent, or close contact with people with TB are at particular high risk of becoming infected, with an estimated 22% infection rate. A person with active but untreated tuberculosis may infect 10-15 ( or more ) other people per year. Transmission should occur from only people with active TB- those with latent infection are not thought to be contagious. The probability of transmission from one person to another depends upon several factors, including the number of infectious droplets expelled by the carrier, the effectiveness of vaccination, the duration of exposure, the virulence of the M. tuberculosis strain, the level of immunity in the uninflected person, and others. The cascade of person- to- person spread can be circumvented by effectively segregating those with active (“overt “) TB and putting them on anti- TB drug regimens. After about two weeks of effective treatment, subjects with nonresistant active infections generally do not remain contagious to others. If someone does become infected, it typically takes three to four weeks before the newly infected person becomes infectious enough to transmit the disease to others.
About 90% of those infected with M. tuberculosis have a symptomatic , latent TB infections, with only a 10% lifetime chance that the latent infection will progress to overt, active tuberculous disease. In those with HIV, the risk of developing active TB increases to nearly 10% a year. If effective treatment is not given, the death rate for active TB cases is up to 66%.
The primary site of infection in the lungs, known as the “Goon 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 blood stream. This is known as a Simon focuses and is typically found in the top of the lung. This haematogenous transmission can also spread infection to more distant sites, such as peripheral lymph nodes, the kidneys, the brain, and the bones. All parts of the body can be affected by the disease, though for unknown reasons it rarely affects the heart, skeletal muscles, pancreas, or thyroid.
If TB bacteria gain entry to the blood stream from an area of damaged tissue, they can spread throughout the body and set up many foci of infection, all appearing as tiny, white tubercles in the tissues. This severe form of TB disease, most common in young children and those with HIV, is called miliary tuberculosis. People with this disseminated TB have a high fatality rate even with treatment (about 30%). In many people, the infection waxes and wanes. Tissue destruction and necrosis are often balanced by healing and fibrosis. Affected tissue is replaced by scarring and cavities filled with caseous necrotic material. During active disease, some of these cavities are joined to the air passages bronchi and this material can be coughed up. It contains living bacteria, so can spread the infection. Treatment with appropriate antibiotics kills bacteria and allows healing to take place. Upon care, affected areas are eventually replaced by scar tissue.
Diagnosing active tuberculosis, based merely on signs and symptoms is difficult, as is diagnosis the disease in those who are immunosuppressed. A diagnosis TB should, however, is considered in those with signs of lung disease or constitutional symptoms lasting longer than two weeks. A chest x- ray and multiple sputum cultures for acid fast bacilli are typically part of the initial evaluation. Tuberculin skin test is of little use in the developing world.
A definitive diagnosis of TB is made by identifying M. tuberculosis in a clinical sample (e.g., sputum, pus, or a tissue biopsy). However, the difficult culture process for this slow- growing organism can take two to six weeks for blood or sputum culture. Thus, treatment is often begun before cultures are confirmed.
Nucleic acid amplification tests and adenosine deaminase testing may allow rapid diagnosis of TB. These tests, however, are not routinely recommended, as they rarely alter how a person is treated. Blood tests to detect antibodies are not specific or sensitive, so they are not recommended.
The Mantoux tuberculin skin test is often used to screen people at high risk for TB. Those who have been previously immunized may have a false- positive test result. The test may be falsely negative in those with sarcoidosis, Hodgkin’s lymphoma, malnutrition, or most notably, in those who truly do have active tuberculosis.
Tuberculosis prevention and control efforts primarily rely on the vaccination of infants and the detection and appropriate treatment of active cases. The World Health Organization has achieved some success with improved treatment regimens, and a small decrease in case numbers.
The only available vaccine is bacillus- Calmette- Guerin (BCG). In children, it decreases the risk of getting the infection by 20% and the risk of infection turning into disease by nearly 60%.
It is the most widely used vaccine worldwide, with more than 90% of all children being vaccinated. The immunity it induces decreases after about 10 years.
Treatment of TB uses antibiotics to kill the bacteria. Effective TB treatment is difficult, due to the unusual structure and chemical composition of the mycobacterial cell wall, which hinders the entry of drugs and makes many antibiotics ineffective. The two antibiotics most commonly used are isoniazid and rifampicin, and treatments can be prolonged, taking several months. Latent TB treatment usually employs a single antibiotic, while active TB disease is best treated with combinations of several antibiotics to reduce the risk of the bacteria developing antibiotic resistance. People with latent infections are also treated to prevent them from progressing to active TB disease later in life. Directly observed therapy, I.e., having a health care provider watch the person take their medications, is recommended by the WHO in an effort to reduce the number of people not appropriately taking antibiotics. The evidence to support this practice over people simply taking their medications independently is poor. Methods to remind people of the importance of treatment do, however, appear effective.
The recommended treatment of new- onset pulmonary tuberculosis is six months of a combination of antibiotics containing rifampicin, isoniazid, pyrizinamide, and ethambutol for the first two months, and only rifampicin and isoniazid for the last four months. Where resistance to isoniazid is high, ethambutol may be added for the last four months as an alternative.
If tuberculosis recurs, testing to determine to which antibiotics it is sensitive is important before determining treatment. If multiple drug- resistant TB is detected, treatment with at least four effective antibiotics for 18 to 24 months is recommended.
Primary resistance occurs when a person becomes infected with a resistant strain of TB. A person with fully susceptible TB may develop secondary (acquired) resistance during therapy because of inadequate treatment, not taking the prescribed regimen appropriately (lack of compliance), or using low- quality medication. Drug resistant TB is a serious public health issue in many developing countries, as its treatment is longer and requires more expensive drugs. MDR- TB is defined as resistance to three or more of the six classes of second- line drugs. Totally drug- resistant TB is resistant to all currently used drugs. XDR- TB is a term sometimes used to define extensively resistant TB, and constitutes one in ten cases of MDR- TB.
Progression from TB infection to overt TB disease occurs when the bacilli overcome the immune system defenses and begin to multiply. In primary TB disease (some 1-5% of cases), this occurs soon after the initial infection. However, in the majority of cases, a latent infection occurs with no obvious symptoms. These dormant bacilli produce active tuberculosis in 5-10% of these latent cases often many years after infection.
The risk of reactivation increases with immunosuppression, such as that caused by infection with HIV. In people coinfected with M. tuberculosis and HIV, the risk of reactivation increases to 10% per year. The chance of death from a case of tuberculosis is about 4%.
Roughly one- third 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.
Tuberculosis is the second- most common cause of death from infectious disease (after those due to HIV/AIDS). The absolute number of tuberculosis cases (“prevalence “) has been decreasing, while new cases (” incidence”) have decreased. Tuberculosis is more common in developing countries; about 80% of the population in many Asian countries test positive in tuberculin tests. Hopes of totally controlling the disease have been dramatically dampened because of a number of factors, including the difficulty of developing an effective vaccine, the expensive and time- consuming diagnostic process, the necessity of many months of treatment, the increase in HIV- associated tuberculosis, and the emergence of drug- resistant cases.
The rate of TB varies with age.
Dr. A. K. M. Aminul Hoque
Associate professor of Medicine
Dhaka Medical College & Hospital