What Is Tuberculosis?
Tuberculosis, commonly known as TB,it is a bacterial infection that can spread through the lymph nodes and bloodstream to any organ in your body. It is most often found in the lungs. Most people who are exposed to TB never develop symptoms because the bacteria can live in an inactive form in the body. But if the immune system weakens, such as in people with HIV or elderly adults, TB bacteria can become active. In their active state, TB bacteria cause death of tissue in the organs they infect. Active TB disease can be fatal if left untreated.
Because the bacteria that cause tuberculosis are transmitted through the air, the disease can be contagious. Infection is most likely to occur if you are exposed to someone with TB on a day-to-day basis, such as by living or working in close quarters with someone who has the active disease. Even then, because the bacteria generally stay latent (inactive) after they invade the body, only a small number of people infected with TB will ever have the active disease. The remaining will have what's called latent TB infection -- they show no signs of infection and won't be able to spread the disease to others, unless their disease becomes active.
Because these latent infections can eventually become active, even people without symptoms should receive medical treatment.Medication can help get rid of the inactive bacteria before they become active.
TB was once a widespread disease. It was virtually wiped out with the help of antibiotics developed in the 1950s, but the disease has resurfaced in potent new forms -- multidrug-resistant TB and extensively drug-resistant TB. Today, these new and dangerous forms of the disease -- resistant to some of the commonly used drug treatments -- have created a public health crisis in many large cities worldwide. If you have TB -- in its active or latent state -- you must seek medical treatment.
Symptoms:
The symptoms of active TB are very variable and depend on which part of the body has been infected, that is which type of TB it is. It is very difficult to diagnose TB just from the symptoms, because the symptoms are not usually exclusive to TB. This means that the symptoms can usually also be the symptoms of another disease as well. So to diagnose TB it is always necessary to do at least one TB test.
General symptoms of active TB disease include weakness or feeling very tired, losing weight without trying, lack of appetite, chills, fever (a high temperature of 38C or above) and night sweats.1
Symptoms of pulmonary TB
Pulmonary TB is TB in the lungs. The specific symptoms of pulmonary TB are having a bad cough that lasts longer than three weeks, having pain in the chest, and coughing up blood or phlegm from deep inside the lungs.2
Symptoms of extrapulmonary TB
Extrapulmonary TB, which is also known as disseminated or miliary TB, refers to all the different types of TB other than pulmonary TB.3 Generally it is the types of TB that do not affect the lungs, the main exception to this being the type of extrapulmonary TB known as Pleural TB.
The general symptoms of extrapulmonary TB are the same as for pulmonary TB, but there can then be specific symptoms relating to the particular site or sites in the body that are infected.
Symptoms of lymph node TB
Lymphadenitis is the inflammation and/or enlargement of a lymph node and is a common response to a variety of infections particularly in children.4 The only symptoms of TB lymphadenitis may be painless slowly enlarging lymph nodes, as there are often no general TB symptoms. The swollen lymph nodes are often in the neck area, although they can be in the groin.
TB infection of the lymph nodes in the neck is sometimes referred to by the name Scrofula, or as TB adenitis.5
Symptoms of skeletal (bone and joint) TB
The most common initial symptom of bone TB is pain, but it depends on the bone or joint that is affected. There may also be curving of the affected bone or joint, as well as loss of movement in the affected bone or joint. The affected bone may also be weakened and may fracture easily.6
Spinal TB is also known as TB Spondylitis or Pott Disease. The symptoms of Pott disease depend on the stage of disease, and the affected site, but back pain is the earliest and most common symptom.7
Symptoms of TB meningitis
TB meningitis does not start with classic meningitis symptoms. It begins with vague, general symptoms of aches and pains, a fever, and generally feeling unwell. This lasts for anywhere from about 2 to 8 weeks. Only then do the more obvious symptoms like vomiting, severe headache, a dislike of lights, neck stiffness and seizures occur.8
Gastrointestinal or Abdominal TB & its symptoms
The symptoms of abdominal TB can be abdominal pain, diarrhea, and bleeding from the anus or rectum. As with a number of the other types of TB, the symptoms will depend on the exact area that is affected
· Latent TB. In this condition, you have a TB infection, but the bacteria remain in your body in an inactive state and cause no symptoms. Latent TB, also called inactive TB or TB infection, isn't contagious. It can turn into active TB, so treatment is important for the person with latent TB and to help control the spread of TB in general. An estimated 2 billion people have latent TB.
What causes tuberculosis?
The Mycobacterium tuberculosis bacterium causes TB. It is spread through the air from person to person, when people with TB affecting the lungs cough, sneeze, spit, laugh or talk.
TB is contagious, but it is not easy to catch. The chances of catching TB from someone you live or work with are much higher than from a stranger. Most people with active TB who have received appropriate treatment for at least two weeks are no longer contagious.
Since antibiotics began to be used to fight TB, some strains have become resistant to drugs. Multidrug-resistant TB (MDR-TB) arises when an antibiotic fails to kill all of the bacteria that it targets, with the surviving bacteria developing resistance to that antibiotic and often others at the same time.
MDR-TB is treatable and curable only with the use of very specific anti-TB drugs, which are often limited or not readily available. In 2012, around 450,000 people developed MDR-TB.
Who is at risk?
People with compromised immune systems are most at risk of developing active TB.
HIV suppresses the immune system, making it harder for the body to control TB bacteria. People who are infected with both HIV and TB are around 20-30% more likely to develop active TB than those who do not have HIV.
Tobacco use has also been found to increase the risk of developing active TB. Over 20% of TB cases worldwide are related to smoking.
Tuberculosis (TB): Types
Types of TB
This uncommon type of TB presents as pneumonia and is very infectious. Patients have a high fever and productive cough. It occurs most often in extremely young children and the elderly. It is also seen in patients with immunosuppression, such as people with HIV/AIDS, and in patients on long term corticosteroid therapy.
This usually develops soon after initial infection. A granuloma located at the edge of the lung ruptures into the pleural space, the space between the lungs and the chest wall. Usually, a couple of tablespoons of fluid can be found in the pleural space.
Once the bacteria invade the space, the amount of fluid increases dramatically and compresses the lung, causing shortness of breath (dyspnea) and sharp chest pain that worsens with a deep breath (pleurisy). A chest x-ray shows significant amounts of fluid. Mild- or low-grade fever commonly is present. Tuberculosis pleurisy generally resolves without treatment; however, two-thirds of patients with tuberculosis pleurisy develop active pulmonary TB within 5 years.
Cavitary TB involves the upper lobes of the lung. The bacteria cause progressive lung destruction by forming cavities, or enlarged air spaces. This type of TB occurs in reactivation disease. The upper lobes of the lung are affected because they are highly oxygenated (an environment in which M. tuberculosis thrives). Cavitary TB can, rarely, occur soon after primary infection.
Symptoms include productive cough, night sweats, fever, weight loss, and weakness. There may be hemoptysis (coughing up blood). Patients with cavitary TB are highly contagious. Occasionally, disease spreads into the pleural space and causes TB empyema (pus in the pleural fluid).
Miliary TB is disseminated TB. "Miliary" describes the appearance on chest x-ray of very small nodules throughout the lungs that look like millet seeds. Miliary TB can occur shortly after primary infection. The patient becomes acutely with high fever and is in danger of dying. The disease also may lead to chronic illness and slow decline.
Symptoms may include fever, night sweats, and weight loss. It can be difficult to diagnose because the initial chest x-ray may be normal. Patients who are immunosuppressed and children who have been exposed to the bacteria are at high risk for developing miliary TB.
TB can infect the larynx, or the vocal chord area. It is extremely infectious.
This type of tuberculosis occurs primarily in immunocompromised patients.
Lymph nodes contain macrophages that capture the bacteria. Any lymph node can harbor uncontrolled replication of bacteria, causing the lymph node to become enlarged. The infection can develop a fistula (passageway) from the lymph node to the skin.
Tuberculosis Peritonitis:
M. tuberculosis can involve the outer linings of the intestines and the linings inside the abdominal wall, producing increased fluid, as in tuberculosis pleuritis. Increased fluid leads to abdominal distention and pain. Patients are moderately ill and have fever.
The membrane surrounding the heart (the pericardium) is affected in this condition. This causes the space between the pericardium and the heart to fill with fluid, impeding the heart's ability to fill with blood and beat efficiently.
Infection of any bone can occur, but one of the most common sites is the spine. Spinal infection can lead to compression fractures and deformity of the back.
This can cause asymptomatic pyuria (white blood cells in the urine) and can spread to the reproductive organs and affect reproduction. In men, epididymitis (inflammation of the epididymis) may occur.
TB of the adrenal glands can lead to adrenal insufficiency. Adrenal insufficiency is the inability to increase steroid production in times of stress, causing weakness and collapse.
M. tuberculosis can infect the meninges (the main membrane surrounding the brain and spinal cord). This can be devastating, leading to permanent impairment and death. TB can be difficult to discern from a brain tumor because it may present as a focal mass in the brain with focal neurological signs.
Headache, sleepiness, and coma are typical symptoms. The patient may appear to have had a stroke.
Pathophysiology
Infection with TB requires inhalation of droplet nuclei. Following deposition in the alveoli, M tuberculosis is engulfed by alveolar macrophages, but survives and multiplies within the macrophages. Proliferating bacilli kill macrophages and are released; this event produces a response from the immune system. Exposure may lead to clearance of M tuberculosis, persistent latent infection, or progression to primary disease.
Successful containment of TB is dependent on the cellular immune system, mediated primarily through T-helper cells (TH1 response). T cells and macrophages form a granuloma with a centre that contains necrotic material (caseous centre), M tuberculosis, and peripheral granulation tissue consisting primarily of macrophages and lymphocytes; the granuloma serves to prevent further growth and spread of M tuberculosis. These individuals are non-infectious and have latent TB infection; the majority of these patients will have a normal CXR and be tuberculin skin test (TST)-positive.
Active TB typically occurs through a process of re-activation. Approximately 10% of individuals with latent infection will progress to active disease over their lifetime. The risk is greatest within the 2 years following initial acquisition of M tuberculosis. A number of conditions can alter this risk, particularly HIV infection, in which the annual risk of developing active TB is 8% to 10%. Immunocompromised conditions and treatment with immunosuppressing medicines, including systemic corticosteroids and TNF-alpha antagonists, also contribute to re-activation.
How Do You Evaluate Persons Suspected of Having TB Disease?
A complete medical evaluation for TB includes the following:
1. Medical History
Clinicians should ask about the patient’s history of TB exposure, infection, or disease. It is also important to consider demographic factors (e.g., country of origin, age, ethnic or racial group, occupation) that may increase the patient’s risk for exposure to TB or to drug-resistant TB. Also, clinicians should determine whether the patient has medical conditions, especially HIV infection, that increase the risk of latent TB infection progressing to TB disease.
2. Physical Examination
A physical exam can provide valuable information about the patient’s overall condition and other factors that may affect how TB is treated, such as HIV infection or other illnesses.
3. Test for TB Infection
The Mantoux tuberculin skin test (TST) or the TB blood test can be used to test for M. tuberculosis infection. Additional tests are required to confirm TB disease. The Mantoux tuberculin skin test is performed by injecting a small amount of fluid called tuberculin into the skin in the lower part of the arm. The test is read within 48 to 72 hours by a trained health care worker, who looks for a reaction (induration) on the arm.
The TB blood test measures the patient’s immune system reaction to M. tuberculosis.
4. Chest Radiograph
A posterior-anterior chest radiograph is used to detect chest abnormalities. Lesions may appear anywhere in the lungs and may differ in size, shape, density, and cavitation. These abnormalities may suggest TB, but cannot be used to definitively diagnose TB. However, a chest radiograph may be used to rule out the possibility of pulmonary TB in a person who has had a positive reaction to a TST or TB blood test and no symptoms of disease.
5. Diagnostic Microbiology
The presence of acid-fast-bacilli (AFB) on a sputum smear or other specimen often indicates TB disease. Acid-fast microscopy is easy and quick, but it does not confirm a diagnosis of TB because some acid-fast-bacilli are not M. tuberculosis. Therefore, a culture is done on all initial samples to confirm the diagnosis. (However, a positive culture is not always necessary to begin or continue treatment for TB.) A positive culture for M. tuberculosis confirms the diagnosis of TB disease. Culture examinations should be completed on all specimens, regardless of AFB smear results. Laboratories should report positive results on smears and cultures within 24 hours by telephone or fax to the primary health care provider and to the state or local TB control program, as required by law.
6. Drug Resistance
For all patients, the initial M. tuberculosis isolate should be tested for drug resistance. It is crucial to identify drug resistance as early as possible to ensure effective treatment. Drug susceptibility patterns reported to the primary health care provider and the state or local TB control program.should be repeated for patients who do not respond adequately to treatment or who have positive culture results despite 3 months of therapy. Susceptibility results from laboratories should be promptly
7. PCR
Other mycobacteria are also acid-fast. If the smear is positive, PCR or gene probe tests can distinguish M. tuberculosis from other mycobacteria. Even if sputum smear is negative, tuberculosis must be considered and is only excluded after negative
There are several TB tests available to diagnosis TB, and there are also TB tests to find out whether someone has TB bacteria that are susceptible to TB drug treatment or are drug resistant. TB tests to find out if someone has drug resistant TB, are known as drug susceptibility tests.
TB diagnostic tests
These are TB tests which can be used to determine is someone has latent TB, which means that they are infected with TB bacteria. There are also TB tests, which when considered alongside other factors, such as whether someone has symptoms of TB, can confirm a diagnosis of active TB or TB disease.
Even if a person has symptoms, TB is often difficult to diagnose, and is particularly difficult to diagnose rapidly, which is what is needed to provide effective TB treatment for drug resistant TB.
Evidence of TB bacteria
TB tests look for evidence of these TB bacteria, Mycobacterium tuberculosis, © NIAID
The development of TB disease is a two stage process. In the first stage, known as latent TB, a person is infected with TB bacteria. In the second stage, known as active TB or TB disease, the bacteria have reproduced sufficiently to usually cause the person to have become sick.
A diagnosis of active TB can only be confirmed when there is definite evidence of TB bacteria in the person's body. Some of the TB diagnostic tests look directly for TB bacteria. Others such as the chest X-ray look for the effect of the bacteria on the person suspected of having TB.
Current TB tests - some problems
Some of the current TB tests take a long time to obtain a result, and some are not very accurate. The TB tests either have low sensitivity (the ability to correctly detect people with TB) and/or low specificity (the ability to correctly detect people who haven't got TB).
If a TB test has low sensitivity, it means that there will be a significant number of "false negatives", meaning that the test result is suggesting that a person has not got TB when they actually have. Similarly, a low specificity means that there will be a significant number of "false positives" suggesting that a person has TB when they actually haven't.
Chest X-ray as a TB test:
Acute pulmonary TB can be easily seen on an X-ray. However, the picture it presents is not specific and a normal chest X-ray cannot exclude extra pulmonary TB. Also, in countries where resources are more limited, there is often a lack of X-ray facilities.
The TB skin test:
The TB skin test is a widely used diagnostic TB test, and in countries with low rates of TB it is often used to test for latent TB infection. The problem with using it in countries with high rates of TB infection is that the majority of people may have latent TB.
A health care worker measures the size of the reaction to the tuberculin skin test © CDC
The TB skin test involves injecting a small amount of fluid (called tuberculin) into the skin in the lower part of the arm. Then the person must return after 48 to 72 hours to have a trained health care worker look at their arm. The health care worker will look for a raised hard area or swelling, and if there is one then they will measure its size. They will not include any general area of redness.1The TB skin test result depends on the size of the raised hard area or swelling, and the larger the size of the affected area the greater the likelihood that the person has been infected with TB bacteria at some time in the past. But interpreting the TB skin test result, that is whether it is a positive result, may also involve considering the lifestyle factors of the person being tested for TB.2The TB skin test also cannot tell if the person has latent TB or active TB disease.The Mantoux TB test is the type of TB test most often used, although the Heaf and Tine tests are still used in some countries. None of these TB tests though will guarantee a correct result. False positive results happen with the TB skin test because the person has been infected with a different type of bacteria, rather than the one that causes TB. It can also happen because the person has been vaccinated with the BCG vaccine, and this vaccine is widely used in countries with high rates of TB infection. False negative results particularly happen with children, older people and people with HIV.
TB Interferon gamma release assays (IGRAs):
The Interferon Gamma Release Assays (IGRAs), are a new type of more accurate TB test. In this context referring to an assay is simply a way of referring to a test or procedure.
IGRAs are blood tests that measure a person's immune response to the bacteria that cause TB. The immune system mounts a complex response to TB bacteria, and produces some special molecules called cytokines. These assays work by detecting a cytokine called the interferon gamma cytokine. They are performed in practice by taking a blood sample and mixing it with special substances to identify if the cytokine is present.
Two IGRAs that have been approved by the U.S. Food and Drug Administration (FDA), and are commercially available in the U.S., are the QuantiFERON® TB Gold test, and the T-SPOT® TB test.
The advantages of an IGRA TB test includes the fact that it only requires a single patient visit to conduct the TB test, results can be available within 24 hours, and prior BCG vaccination does not cause a false positive result. Disadvantages include the fact that the blood sample must be processed fairly quickly, laboratory facilities are required, and the test is for latent TB. It is also thought that the IGRAs may not be as accurate in people who have HIV.3 In low prevalence resource rich settings, IGRAs are beginning to be used in place of the TB skin test.
Serological tests for TB:
Serological tests for TB are tests carried out on samples of blood, and they claim to be able to diagnose TB by detecting antibodies in the blood. However, testing for TB by looking for antibodies in the blood is very difficult.
As a result serological tests, sometimes called serodiagnostic tests, for TB are inaccurate and unreliable, and the World Health Organisation has warned that these tests should not be used to try and diagnose active TB. Some countries have banned the use of serological or serodiagnostic tests for TB.
Serological tests for TB are very different from the IGRA tests described above.
Sputum smear microscopy as a test for TB:
A sputum smear stained using fluorescent acid fast stain and being used as a test for TB © CDC/R W Smithwick
Smear microscopy of sputum is often the first TB test to be used in countries with a high rate of TB infection. Sputum is a thick fluid that is produced in the lungs and the airways leading to the lungs, and a sample of sputum is usually collected by the person coughing.
For the diagnosis of TB several samples of sputum will normally be collected. Historically it has been recommended that three sputum specimens are collected on two consecutive days, but in 2007 the World Health Organisation (WHO) recommended that just two specimens could be examined from consecutive days. Now it has been suggested that two specimens can be collected on the same day without any loss of accuracy.
To do the TB test a very thin layer of the sample is placed on a glass slide, and this is called a smear. A series of special stains are then applied to the sample, and the stained slide is examined under a microscope for signs of the TB bacteria.
Sputum smear microscopy is inexpensive and simple, and people can be trained to do it relatively quickly and easily. In addition the results are available within hours. The sensitivity though is only about 50-60%. In countries with a high prevalence of both pulmonary TB and HIV infection, the detection rate can be even lower, as many people with HIV and TB co-infection have very low levels of TB bacteria in their sputum, and are therefore recorded as sputum negative.
Fluorescent microscopy:
The use of fluorescent microscopy is a way of making sputum TB tests more accurate. With a fluorescent microscope the smear is illuminated with a quartz halogen or high pressure mercury vapour lamp, allowing a much larger area of the smear to be seen and resulting in more rapid examination of the specimen.
One disadvantage though is that a mercury vapour lamp is expensive and lasts a very short time. Such lamps also take a while to warm up, they burn significant amounts of electricity, and electricity supply problems can significantly shorten their life span. One way of overcoming these problems is the use of light emitting diodes (LEDs). These switch on extremely quickly, have an extremely long life, and they don't explode.
In 2011 the World Health Organisation issued a policy statement recommending that conventional fluorescence microscopy should be replaced by LED microscopy. It also recommended that in a phased way, that LED microscopy should replace conventional Ziehl-Neelsen light microscopy.
Using culture to test for TB:
Colonies of Mycobacterium tuberculosis growth on a culture plate © CDC/Dr George Kubica
Culturing is a method of studying bacteria by growing them on media containing nutrients. Media can be either solid media on culture plates or bottles of liquid media (culture broths). Different media are used to make it as easy as possible for the suspected microorganisms to grow.
To isolate a single bacterial species from a mixture of different bacteria, solid media are normally used. Individual cells dividing on the surface do not move away from each other as they would do in liquid, and after many replications they form visible colonies composed of tens of millions of cells all derived from a single cell.
Culturing and identification of M. tuberculosis provides a definitive diagnosis of TB and can significantly increase the number of cases found. Culture can also provide drug susceptibility testing, showing which TB drugs a person's bacteria is resistant to. I.e. Has the person got MDR or XDR TB. However, culture is much more complex and expensive than microscopy to perform as it requires specific equipment and enhanced laboratory facilities.
Diagnosing TB using culture can also take weeks because of the slow growth of TB bacilli.12 It averages 4 weeks to get a conclusive test result using the most common methods of solid media, with another 4-6 weeks to produce drug susceptibility results.
TB drug susceptibility tests:
Drug susceptibility testing means testing to find out which drugs the TB bacteria in a patient are susceptible to, and can therefore determine whether the person has got drug resistant TB. Some drug susceptibility tests, such as the Xpert TB test can be used to diagnose TB, as well as testing for some types of TB drug resistance.
The skin test result depends on the size of the raised, hard area or swelling. It also depends on the person’s risk of being infected with TB bacteria and the progression to TB disease if infected.
· Positive skin test:
This means the person’s body was infected with TB bacteria. Additional tests are needed to determine if the person has latent TB infection or TB disease. A health care worker will then provide treatment as needed.
- Negative skin test: This means the person’s body did not react to the test, and that latent TB infection or TB disease is not likely.
· TB blood tests: TB blood tests (also called interferon-gamma release assays or IGRAs) measure how the immune system reacts to the bacteria that cause TB. An IGRA measures how strong a person’s immune system reacts to TB bacteria by testing the person’s blood in a laboratory Two IGRAs are approved by the U.S. Food and Drug Administration (FDA) and are available in the United States:
1. QuantiFERON–TB Gold In-Tube test (QFT-GIT)
2. T-SPOT®.TB test (T-Spot)
· Positive IGRA: This means that the person has been infected with TB bacteria. Additional tests are needed to determine if the person has latent TB infection or TB disease. A health care worker will then provide treatment as needed.
· Negative IGRA: This means that the person’s blood did not react to the test and that latent TB infection or TB disease is not likely.
IGRAs are the preferred method of TB infection testing for the following:
· People who have a difficult time returning for a second appointment to look for a reaction to the TST
TREATMENT:
TB disease can be treated by taking several drugs for 6 to 9 months. It is very important that people who have TB disease finish the medicine, taking the drugs exactly as prescribed. If they stop taking the drugs too soon, they can become sick again; if they do not take the drugs correctly, the bacteria that are still alive may become resistant to those drugs. TB that is resistant to drugs is harder and more expensive to treat.
Recommended Regimens:
There are 10 drugs currently approved by the U.S. Food and Drug Administration (FDA) for treating TB. Of the approved drugs, the first-line anti-TB agents that form the core of treatment regimens include:
isoniazid (INH)
rifampin (RIF)
ethambutol (EMB)
pyrazinamide (PZA)
Listed below are the basic regimens; refer to Treatment of Tuberculosis Adobe PDF file for all options for the treatment of drug-susceptible TB disease.
Table 1. Basic TB Disease Treatment Regimens
Preferred Regimen Alternative Regimen Alternative Regimen
Initial Phase
Daily INH, RIF, PZA, and EMB* for 56 doses (8 weeks)
Initial Phase
Daily INH, RIF, PZA, and EMB* for 14 doses (2 weeks), then twice weekly for 12 doses (6 weeks)
Initial Phase
Thrice-weekly INH, RIF, PZA, and EMB* for 24 doses (8 weeks)
Continuation Phase
Daily INH and RIF for 126 doses (18 weeks)
or
Twice-weekly INH and RIF for 36 doses (18 weeks)
Continuation Phase
Twice-weekly INH and RIF for 36 doses (18 weeks)
Continuation Phase
Thrice-weekly INH and RIF for 54 doses (18 weeks)
*EMB can be discontinued if drug susceptibility studies demonstrate susceptibility to first-line drugs.
Note: A continuation phase of once-weekly INH/rifapentine can be used for HIV negative patients who do not have cavities on the chest film and who have negative acid-fast bacilli (AFB) smears at the completion of the initial phase of treatment.
Continuation Phase of Treatment
The continuation phase of treatment is given for either 4 or 7 months. The 4-month continuation phase should be used in the large majority of patients. The 7-month continuation phase is recommended only for three groups: patients with cavitary pulmonary tuberculosis caused by drug-susceptible organisms and whose sputum culture obtained at the time of completion of 2 months of treatment is positive; patients whose initial phase of treatment did not include PZA; and patients being treated with once weekly INH and rifapentine and whose sputum culture obtained at the time of completion of the initial phase is positive.
Treatment Completion:
Treatment completion is determined by the number of doses ingested over a given period of time. Although basic TB regimens are broadly applicable, there are modifications that should be made under special circumstances (e.g., HIV infection, drug resistance, pregnancy, or treatment of children).
Treatment for Drug-resistant Tuberculosis:
Drug-resistant TB is caused by TB bacteria that are resistant to at least one first-line anti-TB drug. Multidrug-resistant TB (MDR TB) is resistant to more than one anti-TB drug and at least isoniazid (INH) and rifampin (RIF).
Treating and curing drug-resistant TB is complicated. Inappropriate management can have life-threatening results. Drug-resistant TB should be managed by or in close consultation with an expert in the disease.
Drug resistance is proven by drug-susceptibility testing. However, since this testing can take weeks, treatment should be started with an empirical treatment regimen based on expert advice as soon as drug-resistant TB disease is suspected. When the testing results are known, the treatment regimen should be adjusted according to the results. Patients should be monitored closely throughout treatment. Directly observed therapy (DOT)always should be used in the treatment of drug-resistant TB to ensure adherence.
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