Tuberculosis
Tuberculosis, or TB, is an airborne infectious disease caused by Mycobacterium tuberculosis. It most commonly affects the lungs, but can infect other parts of the body. It is the most common fatal infectious disease in the world: one-third of the world's population is currently infected and more than 1.5 million people die each year due to tuberculosis.[1] This article will discuss pulmonary tuberculosis, for more information on non-pulmonary tuberculosis see Extrapulmonary Tuberculosis.
Other Names
- TB - common abbreviation
- Consumption - old name to describe the disease which wastes away or consumes its victims
- Pthisis (Greek for consumption) used by Hippocrates to describe the disease
Types
Pulmonary tuberculosis is usually classified based on the time between infection and appearance of symptoms of disease:
Latent TB Infection (LTBI)
In most people who breathe in tuberculosis bacteria and become infected, the body is able to fight the bacteria to stop them from growing. The bacteria become inactive, but they remain alive in the body and can become active later. This is called latent tuberculosis infection. People with latent tuberculosis infection:
- Have no symptoms and don't feel sick.
- Cannot spread tuberculosis to others.
- Usually have a positive skin test reaction (PPD) or a positive QuantiFERON-TB Gold test (QFT-G).
- May develop active tuberculosis disease if they do not receive treatment for latent tuberculosis infection.
Many people who have latent tuberculosis infection never develop active tuberculosis disease. In these people, the tuberculosis bacteria remain inactive for a lifetime without causing disease. On the other hand, in other people, especially those who have weak immune systems, the bacteria become active and cause tuberculosis disease.
Active TB disease
Tuberculosis bacteria can become active if the immune system can't stop them from growing, allowing for them to begin to multiply in the body and cause active tuberculosis disease. When this occurs, the bacteria attack the body and destroy different tissues, in the lungs, they can actually create a hole. Some people develop active tuberculosis disease soon after becoming infected, before their immune system can fight the tuberculosis bacteria, like in infants. Others may get sick later, when their immune system becomes weak for another reason, seen in patients with HIV/AIDS.
Signs and Symptoms
Often no symptoms are noticeable until tuberculosis is well advanced and even then the hallmark symptoms — weight loss, fatigue, poor appetite, fever, productive cough, and night sweats — might easily be blamed on another disease.
Tuberculosis in the lungs usually causes symptoms such as:
- A bad cough that lasts 3 weeks or longer.
- Coughing up blood or sputum (phlegm from deep inside the lungs).
- Chest pain
- Weakness or fatigue
- Weight loss
- No appetite
- Chills
- Fever
- Sweating at night.
Causes
Tuberculosis is caused by infection with bacteria from the Mycobacterium tuberculosis complex, which includes: M. Tuberculosis, M. africanum, M. canettii (the later two responsible for a few cases in Africa), and M. bovis. The lungs are the usual route of infection. When someone with tuberculosis infection coughs, sneezes, or talks, tiny droplets of saliva or mucus are expelled into the air, which could be inhaled by another person. Once infectious particles reach the alveoli, small sacs in your lungs, another cell called the macrophage engulfs the tuberculosis bacteria. Then the bacteria can be transmitted to the lymphatic system and bloodstream and spread to other organs. The bacterium M. tuberculosis is a member of the mycobacteria family and is unusual in several respects. It grows slowly, has a unique type of cell wall with a high lipid (or fat) content. These characteristics mean that it generally is resistant to many antibiotics (like penicillins), and also that it can more easily become immune or resistant to antibiotics that usually work against it. These drug resistant tuberculosis bacteria are a growing problem throughout the world.
Exposure to the organism does not always result in infection, and infections do not always cause disease, demonstrating that a complex relationship between the host and the organism ultimately determines the outcome. Several strains of the organism are known to be much more likely to cause disease than others, and certain populations (e.g., Eskimo populations in North America, Yanomami Indians in the Brazilian Amazon, and black populations in the United States) show extreme susceptibility to the disease. This may be because populations from Europe have experienced selection pressures leading to some innate resistance to the organism.[2]
Diagnosis
Latent Tuberculosis Infection
Latent tuberculosis diagnosis in the United States usually consists of a tuberculosis skin test and/or chest X-ray. A new test the QuantiFERON Gold blood test is also used to diagnose latent tuberculosis infection. Many other countries, for example Mexico, do not test for latent tuberculosis infection as much of the population will be positive, either due to high tuberculosis incidence and/or use of the BCG vaccine. The tuberculosis skin test (TST), also called the tuberculin test or Mantoux test, detects an immune response to tuberculosis antigens. The test involves injecting a small amount of tuberculosis bacterial antigens (called PPD for purified protein derivative) under the skin and waiting several days to observe any reaction. The TST test is known to have several problems:
- There are many false positives (that is people who have not been exposed to tuberculosis who test positive). Sometimes this is due to BCG vaccination, which can have cause people to have positive TST tests.
- The test requires trained personnel to evaluate whether it is positive or not.
- It requires two visits by the patient to a healthcare provider. This results in both inconvenience and many lost tests as patients may not return.
The QuantiFERON Gold blood test was approved by the FDA in 2005 and does not suffer from many of the problems of the tuberculosis skin test.
Active pulmonary Tuberculosis disease
Patients suspected of active pulmonary tuberculosis usually have, at a minimum, the following tests performed:
- AFB smear (stain)
- AFB culture
- Chest X-ray
AFB stands for acid-fast bacilli, another name for Mycobacterium. The AFB smear and culture is done on sputum (expectorated lung material) or fluid from examination procedures (broncheolar washes, biopsies, aspirates). For an AFB stain, the material is spread on a microscope slide and killed with heat, then stained with a special stain that only stains mycobacteria. The slide is then observed in a microscope and the number of mycobacteria counted. The AFB smear can be done within hours.
The same material is used in an AFB culture, where mycobacteria are grown in special medium. Because mycobacteria grow so slowly, the culture usually takes weeks or months for results.
Chest x-rays are used to check for lung abnormalities in people who have symptoms of tuberculosis disease, but the chest X-ray cannot confirm that a person has active tuberculosis, especially if the infection is not in the lungs. The chest X-ray also has a poor ability to detect infection in the early stages of disease, the damage to the lungs may not yet have become sufficiently marked to be detectable by chest X-ray and thus people who have active tuberculosis can be missed. Also, scarring in the lungs remains after a previous tuberculosis disease (even if the patient is completely cured) and therefore it is difficult to distinguish past cured tuberculosis from current active disease. Other diseases, like lung cancer and even pneumonia, can sometimes appear similar to tuberculosis on a chest X-ray.
Culture of M. tuberculosis is usually the definitive test for diagnosis of active tuberculosis since positive results of AFB smears and chest X-rays could be other diseases.
Because culture takes up to six weeks, molecular tests, such as polymerase chain reaction (PCR) and transcription-mediated amplification (TMA), are becoming widely used for tuberculosis diagnosis. These tests detect very small amounts of M. tuberculosis and are very rapid; with results available in a few hours.
Even when molecular tests are used in diagnosis, culture is still important both to confirm the molecular tests and to provide live tuberculosis bacteria for drug susceptibility testing. In tuberculosis drug susceptibility testing, tuberculosis bacteria from culture is tested for resistance to the "first-line" of tuberculosis antibiotics. This testing ensures that an appropriate treatment regimen is used, because the drug susceptibility results can take several weeks, treatment is started immediately and changed if necessary.
Treatment
Latent Tuberculosis Infection
A person with a positive TST, but no symptoms and a normal chest x-ray, most likely has only a few tuberculosis bacteria in a dormant state and is not contagious. In the US, Canada, and a few other countries, treatment with an antibiotic is recommended for this person to prevent the tuberculosis from turning into an active infection. The antibiotic used for treatment of latent tuberculosis is isoniazid (INH). If taken for 6 to 12 months, it will prevent the tuberculosis from becoming active in the future. In fact, if a person with a positive skin test does not take INH, there is a 5-10% lifelong risk that the tuberculosis will become active and contagious. Many countries do not consider "latent tuberculosis" as a disease state and do not recommend treatment.
Taking isoniazid can be inadvisable (contraindicated) during pregnancy or for those with impaired liver function. Liver damage from isoniazid is a rare occurrence and typically reverses once the drug is stopped. Very rarely, however, especially in older people, the liver damage (INH hepatitis) can even be fatal. It is important therefore, for the doctor to monitor a patient's liver by periodically ordering blood tests called "liver function tests" during the course of INH therapy. Another side effect of INH is a decreased sensation in the extremities referred to as a peripheral neuropathy. This can be avoided by taking vitamin B6 (pyridoxine), and is often prescribed along with INH.
Active Tuberculosis disease
Tuberculosis (non-drug resistant) is treated using four "first-line" tuberculosis drugs (antibiotics):
- Rifampicin
- Isoniazid
- Pyrazinamide
- Ethambutol
- Streptomycin (occasionally)
At least two of these antibiotics are used together to prevent the emergence of drug resistance.
In a new case of tuberculosis, during the first two months these four drugs are given together followed by just rifampicin and isoniazid for the remaining four months. The treatment regimen and duration differs depending on the severity and the type of the disease. In more severe cases other anti-tuberculosis medicines may be added.
If the proper treatment is not followed it can worsen the patient’s condition and the tuberculosis bacteria may develop resistance to one or more of the tuberculosis drugs prescribed.
Treatment usually lasts for many months or years. Successful treatment of tuberculosis is dependent largely on the compliance of the patient. Indeed, the failure of a patient to take the medications is the most important cause of failure to cure the tuberculosis infection. The health department often directly monitors patient compliance with therapy, this is known as DOTS (Directly Observed Therapy Short-course), it is the main pilar of tuberculosis treatment and is the internationally recommended strategy for tuberculosis control.
The DOTS strategy emphasizes on the completion of treatment and thereby cure of the patient. By doing so, it stops tuberculosis at the source, prevents the spread of the disease, the development of MDR-TB, and complications of tuberculosis, relapse and death.
Surgery on the lungs may be indicated to help cure tuberculosis when medication has failed, but in this day and age, surgery for tuberculosis is unusual.
Without treatment, tuberculosis can be a lethal infection.
Drug resistant Tuberculosis
Although drugs to treat tuberculosis have only been used for the last 50 years, strains of tuberculosis resistant to a single drug are relatively common. Drug-resistant tuberculosis is caused by inconsistent or partial treatment, when patients do not take all their medicines regularly for the required period of time because they start to feel better, because doctors and health workers prescribe the wrong treatment regimens, or because the drug supply is unreliable. A particularly dangerous form of drug-resistant tuberculosis is multidrug-resistant tuberculosis (MDR-TB), which is defined as the disease caused by tuberculosis bacteria resistant to at least isoniazid (INH) and rifampicin, the two most powerful anti-tuberculosis drugs. Rates of MDR-TB are high in some countries, especially in countries of the former Soviet Union, and threaten tuberculosis control efforts.
While drug-resistant tuberculosis is treatable, it requires extensive chemotherapy (up to two years of treatment) with second-line anti-tuberculosis drugs which are more costly than first-line drugs, and which produce adverse drug reactions that are more severe, though manageable.
The emergence of extensively drug-resistant (XDR) tuberculosis, particularly in settings where many tuberculosis patients are also infected with HIV, poses a serious threat to public health. XDR-TB are resistant to INH and rifampicin and also one or more of the second-line tuberculosis drugs.
Prevention
General measures
There are many general measures that can help in the prevention of tuberculosis:
- Promptly identify, diagnose and treat potentially infectious patients with tuberculosis.
- Educate population in mode of spread and methods of control; cover mouth and nose when when coughing and sneezing, and when entering a room with a tuberculosis patient to wear a protective mask.
- Reduce or eliminate the social conditions that increase the risk of infection.
- In countries were BCG immunization is not routinely carried out, selective tuberculin-testing may be considered in high risk groups:
- Health care workers
- Prison inmates
- IV drug users
- Foreign born persons from areas of high tuberculosis prevalence
- Isolation: patients whose sputum-postive pulmonary tuberculosis should be considered for a private room with negative pressure ventilation (if feasible and if home treatment is not optimal).
BCG vaccine
BCG, or bacille Calmette and Guérin, is a vaccine for tuberculosis disease. BCG is a live, attenuated vaccine; this means it is a live organism similar to M. tuberculosis. BCG is used in many countries, in fact, it is one of the most frequently administered vaccines in the world.[3] Unlike other vaccines, it does not prevent the vaccinated from getting tuberculosis. However, it does protect children who contract tuberculosis from developing tuberculous meningitis and other types of extrapulmonary tuberculosis. Some countries use BCG on newborns, others at older ages. The United Kingdom had a universal BCG vaccination for 13 year-olds until it was discontinued in 2005. Although the BCG vaccine is not in general use in the United States, many foreign-born persons have been BCG-vaccinated which may cause a positive reaction to the tuberculin skin test (TST), therefore, may complicate decisions about prescribing treatment.
BCG is not recommended for general use in the United States because of the low risk of infection with M. tuberculosis, the variable effectiveness of the vaccine against adult pulmonary tuberculosis, and the vaccine’s potential interference with tuberculin skin test reactivity. The BCG vaccine should be considered only for very select persons who meet specific criteria.[4]
Chances of Developing Tuberculosis
Risk factors
Risk factors for tuberculosis include the following:
- Latent tuberculosis infection
- HIV infection
- Low socioeconomic status
- Alcoholism
- Homelessness
- Crowded living conditions
- Diseases that weaken the immune system
- Residency or travel in a high-incidence country
- Health care workers
How Tuberculosis is Spread
tuberculosis is spread through the air from one person to another. The bacteria are put into the air when a person with active tuberculosis disease of the lungs or throat coughs or sneezes. People nearby may breathe in these bacteria and become infected, the bacteria settle in the lungs and begin to grow. From there, they can move through the blood to other parts of the body, such as the kidney, spine, and brain.
Tuberculosis in the lungs or throat can be infectious. This means that the bacteria can be spread to other people.People with active tuberculosis disease are most likely to spread it to people they spend time with every day, including family members, friends, and coworkers. Tuberculosis in other parts of the body, such as the kidney or spine, is usually not infectious.
Related Problems
Comorbidity
People who are infected with HIV are especially susceptible to developing active tuberculosis. Tuberculosis is the leading cause of death among people living with HIV/AIDS and one of the most common opportunistic infections they experience. The prevalence of HIV infection among patients in tuberculosis clinical settings is high, up to 80% in some countries. Worldwide, tuberculosis is a leading cause of death among persons infected with HIV.[5] As of 2005, CDC estimated that 9% of all tuberculosis cases and nearly 16% of tuberculosis cases among persons aged 25 to 44 were occurring in HIV-infected persons. Because HIV infection so severely weakens the immune system, persons dually infected with HIV and tuberculosis, compared with persons not infected with HIV, are at very high risk for active tuberculosis disease. Of the tuberculosis patients reported (in 2005) to be infected with HIV, 63% were non-Hispanic blacks.[6] This high level of risk underscores the need for tuberculosis screening and preventive treatment programs for HIV-infected persons and those at greatest risk for HIV infection. Everyone infected with HIV should be tested for tuberculosis, and those infected with tuberculosis should complete preventive therapy as soon as possible to prevent progression to tuberculosis disease.
Related disorders
Several diseases caused by bacteria related to M. tuberculosis can mimic the symptoms of tuberculosis, although they are not transmitted from person-to-person like tuberculosis. The two most commonly seen diseases are atypical tuberculosis and bovine tuberculosis. Atypical tuberculosis is caused by other species of Mycobacteria, especially Mycobacterium avium complex or MAC. Atypical tuberculosis is most commonly seen in the elderly and immunocompromised.
Bovine tuberculosis
Bovine tuberculosis is caused by Mycobacterium bovis, a bacterium related to Mycobacterium tuberculosis that causes tuberculosis-like disease in cows. Before milk was routinely pasteurised cattle infected with ‘’M. bovis’’, the bovine variant of tuberculosis could pass disease to humans who drank infected milk. Transmission by this route gives rise to a gastrointestinal form of tuberculosis. The increased consumption of organic and “natural” foods has resulted in several outbreaks of bovine-tuberculosis in the US in recent years.[7]
Clinical Trials
Open clinical trials in Tuberculosis
Research
Recently, a new way to treat patients with latent tuberculosis, who are infected with tuberculosis but without symptoms, was described. This treatment can effectively cure latent tuberculosis in less than half the time and at a lower cost than the current standard treatment of INH. The results were presented at the American Thoracic Society’s 2008 International Conference in Toronto on Tuesday, May 20. [8]
Expected Outcome
With treatment tuberculosis is a curable disease. Latent tuberculosis is cured by the standard 9 month therapy in more than 96% of cases. Treatment failure is almost always due to patient's not completing the full course of treatment.
MDR-TB is also curable, but antibiotic therapy often continues for two years or more.
History
Mycobacterium tuberculosis, the causative agent of tuberculosis, was first described by Robert Koch in the 1880s. Koch also was the first to produce tuberculin from the bacteria, which is still used in the tuberculin skin test.
Immunizing against tuberculosis was developed from attenuated Mycobacterium bovis by Albert Calmette and Camille Guerin in 1906 called the BCG (Bacillus of Calmette and Guerin) vaccine.
Tuberculosis caused the most widespread public concern in the 19th and early 20th centuries as the endemic disease of the urban poor. In 1815 England one in four deaths were from consumption; by 1918 one in six deaths in France were still caused by tuberculosis. After being established, in the 1880s, that the disease was contagious, tuberculosis was made a notifiable disease in Britain; there were campaigns to stop spitting in public places, and the infected poor were "encouraged" to enter a sanatorium.
In the United States, concern about the spread of tuberculosis played a role in the movement to prohibit public spitting except into spittoons.
Starting in the 1940s, scientists discovered the first of several medicines now used to treat tuberculosis and as a result, tuberculosis slowly began to decrease. But in the 1970s and early 1980s, tuberculosis control efforts were neglected, as a result, between 1985 and 1992, the number of tuberculosis cases increased. However, with increased funding and attention to the tuberculosis problem, there has been a steady decline in the number of persons with tuberculosis since 1992.
Epidemiology
Global impact
Although the incidence in the Unites States and some other developed countries is low, one-third of the world's population, about 2 billion people, are infected with tuberculosis. Most of these are latent tuberculosis, but 200 million will become active in any given year.
In 2005, estimated per capita tuberculosis incidence was stable or falling in all six WHO regions. However, the slow decline in incidence rates per capita is offset by population growth. Consequently, the number of new cases arising each year is still increasing globally and in the WHO regions of Africa, the Eastern Mediterranean and South-East Asia.
Multi-drug resistant tuberculosis is very rare in countries (like the US) at employ DOTS for treatment, but is becoming a serious problem in parts of the world where incomplete treatment and empiric therapy (treatment without drug-susceptibility testing) are common. Although MDR-TB occurs globally, it appears to be rare compared to drug-sensitive tuberculosis. XDR-TB is of particular concern among HIV-infected or other immunocompromised persons.
Interesting Facts
Here are some interesting facts regarding tuberculosis[5]:
- Every second, someone in the world is newly infected with tuberculosis.
- Nearly one percent of the world's population is newly infected with tuberculosis each year.
- 200 million people worldwide, or 10% of those infected, will develop active tuberculosis and be able to infect others for 3 decades.
- 6 - 8 million news cases of tuberculosis are diagnosed each year.
- In the last 100 years, 200 million people have died of tuberculosis.
- Tuberculosis kills 8,000 people a day - that is 2-3 million people each year. It kills more people than either AIDS or malaria. In fact, tuberculosis is the biggest killer of young people and adults in the world today.
- Tuberculosis spreads through the air and is highly contagious. On average, a person with infectious tuberculosis infects 10-15 others every year.
- People infected with tuberculosis do not necessarily become ill - the immune system creates a barrier around the bacilli that can remain dormant for years. 10% of infected people (who do not have HIV/AIDS) develop active tuberculosis at some point during their lifetime.
- Many notable people from the past had tuberculosis and many died of the disease[9]. Some novels like Dumas The Lady of the Camellias that also became the opera La Traviata, were inspired on people with tuberculosis.
Notable experts
National Jewish Medical and Research Center
Francis J. Curry National Tuberculosis Center
New Jersey Medical Center: Global tuberculosis Institute
Public Health
In most countries tuberculosis infection has to be reported to the local health authorities. Usually this report must state if the case is bacteriologically positive or based in clinical and/or x-ray findings. As mentioned under prevention, isolation is considered on a case by case basis; quarantines are not necessary.
Investigation of contacts through PPD testing of all members of the patient's household and other close contacts is recommended. If negative, a repeat skin test should be done 2-3 months after exposure has ended.
References
- ↑ World Health Organization. [http://www.who.int/mediacentre/factsheets/fs104/en/index.html Tuberculosis Fact sheet. March 2006.
- ↑ Schluger NW. The pathogenesis of tuberculosis: the first one hundred (and twenty-three) years. Am J Respir Cell Mol Biol. 2005 Apr;32(4):251-6. Abstract Full Text PDF
- ↑ World Health Organization. Issues Related to the use of BCG in Immunization Programmes. 1999. PDF file.
- ↑ CDC. The Role of BCG vaccine in the prevention and control of tuberculosis in the United States. (ACET and ACIP). MMWR Recomm Rep. 1996;45(RR-4).Full Text.
- ↑ 5.0 5.1 World Health Organization. 2007 Tuberculosis facts. PDF
- ↑ CDC. Reported HIV status of tuberculosis patients—United States, 1993–2005. MMWR 2007;56:1103-1106. Full Text.
- ↑ Santora, M. Tuberculosis Cases Prompt Warning on Raw-Milk Cheese NY Times March 16, 2005.
- ↑ ScienceDaily (May 23, 2008) Latent tuberculosis Treatment Saves Time, Money, And Lives Accessed June26, 2008.
- ↑ State of Delaware, Div. of Public Health
External Links
- World Health Organization: A World Free of TB
TB databases
Tuberculosis diagnosis and testing
- Lab Tests Online: TB Skin Test
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