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|Classification and external resources|
|Classification and external resources|
A diagnosis of Latent tuberculosis (LTB), also called latent tuberculosis infection (LTBI) means a patient is infected with Mycobacterium tuberculosis, but the patient does not have active tuberculosis disease. Active tuberculosis is contagious while latent tuberculosis is not. It is not possible to get TB from someone with latent tuberculosis. The main risk is that approximately 10% of these patients (5% in the first two years after infection and 0.1% per year thereafter but higher risk if immunosuppressed) will go on to develop active tuberculosis at a later stage of their life. This is particularly true, and there is added risk, under any of the following circumstances:
The identification and treatment of people with latent TB is an important part of controlling this disease. It is important that a person that suspects tuberculosis as a diagnosis contact a physician immediately.
Tuberculosis exists in all countries in the world. Some countries have a larger number of people infected with tuberculosis than others. For each 100,000 people, Swaziland has the greatest number (627) of tuberculosis cases in the world. Second is Cambodia (560), followed in third position by Zambia (445), fourth is Diibouti (382), fifth is Indonesia (321), sixth is Mali (295), seventh is Zimbabwe (291), eighth is Kenya (291), ninth is Paupua New Guinea (283) and tenth is Gambia (283).
The United States, Sweden and Iceland have one of the lowest populations of tuberculosis at 2 per 100,000. with Canada, Netherlands, Jamaica, Norway, Malta, Granada and Antiqua and Barbuda with 3 per 100,000. In North America, countries over 10:100,000 are Mexico (14), Belize (18), Bahamas (19), Panama (28), El Salvador (36), Nicaragua (35), Honduras (46), Guatemala (48), and the worst is the Dominican Republic (88). Ibid.
Most Western European countries have less than 10 per 100,000 except Spain (14), Estonia (27), Latvia (43), Lithuania (48), while Eastern and Southern European countries have a greater number with Romania (94) being the highest.
In South America, the greatest number of cases of tuberculosis are in Bolivia (30) with Guyana (18) and Honduras (15) following with the remaining countries having less than 10:100,000.
"One-third of the world’s burden of tuberculosis (TB), or about 4.9 million prevalent cases, is found in the World Health Organization (WHO) South-East Asia Region."
"About one-third of the world's population has latent TB, which means people have been infected by TB bacteria but are not (yet) ill with disease and cannot transmit the disease," and most of those cases are in developing countries. (See map here: http://ethnomed.org/clinical/tuberculosis/firland/latent-tb-faqs)
"In the US, over half of all active TB cases occur in immigrants. The reported cases of active TB in foreign-born persons has remained at 7000-8000 per year, while the number of cases in US-born people has dropped from 17,000 in 1993 to 6,500 in 2005. As a result, the percentage of active TB cases in immigrants has increased steadily (from 29% of all cases in 1993 to 54% in 2005)." and most of those cases are in developing countries. (See map here: http://ethnomed.org/clinical/tuberculosis/firland/latent-tb-faqs)
"TB Bacteria Are Spread Only from a Person with Active TB Disease ... In people who develop active TB of the lungs, also called pulmonary TB, the TB skin test will often be positive. In addition, they will show all the signs and symptoms of TB disease, and can pass the bacteria to others. So, if a person with TB of the lungs sneezes, coughs, talks, sings, or does anything that forces the bacteria into the air, other people nearby may breathe in TB bacteria. Statistics show that approximately one-third of people exposed to pulmonary TB become infected with the bacteria, but only one in ten of these infected people develop active TB disease during their lifetimes."
However, exposure to tuberculosis is very unlikely to happen when one is exposed for a few minutes in a store or in a few minutes social contact. "It usually takes prolonged exposure to someone with active TB disease for someone to become infected. After exposure, it usually takes 8 to 10 weeks before the TB test would show if someone had become infected." "Depending on ventilation and other factors, these tiny droplets [from the person who has active tuberculosis] can remain suspended in the air for several hours. Should another person inhale them, he or she may become infected with TB. The probability of transmission will be related to the infectiousness of the person with TB, the environment where the exposure occurred, the duration of the exposure, and the susceptibility of the host."  In fact, "it isn't easy to catch TB. You need consistent exposure to the contagious person for a long time. For that reason, you're more likely to catch TB from a relative than a stranger." 
If a person has latent tuberculosis, they do not have active/contagious tuberculosis. Once exposed, people very often have latent tuberculosis. To convert to active tuberculosis, the bacteria must become active.
People have medical privacy or "confidentiality" and do not have to reveal their active tuberculosis case to family, friends, or co-workers; therefore, the person who gets latent tuberculosis may never know who had the active case of tuberculosis that caused the latent tuberculosis diagnosis for them. Only by required testing (required in some jobs) or developing symptoms of active tuberculosis and visiting a medical doctor who does testing will a person know they have been exposed. Because tuberculosis is not common in the United States, doctors may not suspect tuberculosis; therefore, they may not test. If a person has symptoms of tuberculosis, it is wise to be tested.
Persons with diabetes may have an 18% chance of converting to active tuberculosis. In fact, death from tuberculosis was greater in diabetic patients. IBID. Persons with HIV and latent tuberculosis have a 10% chance of developing active tuberculosis every year. "HIV infection is the greatest known risk factor for the progression of latent M. tuberculosis infection to active TB. In many African countries, 30-60% of all new TB cases occur in people with HIV, and TB is the leading cause of death globally for HIV-infected people."
Once a person has been diagnosed with Latent Tuberculosis (LTBI) and a medical doctor confirms no active tuberculosis, the person should remain alert to symptoms of active tuberculosis for the remainder of his or her life. Even after completing the full course of medication, there is no guarantee that the tuberculosis bacteria have all been killed.
"When a person develops active TB (disease), the symptoms (cough, fever, night sweats, weight loss etc.) may be mild for many months. This can lead to delays in seeking care, and results in transmission of the bacteria to others." 
Tuberculosis does not always settle in the lungs. If the outbreak of tuberculosis is in the brain, organs, kidneys, joints, or others areas, the patient may have active tuberculosis for an extended period of time before discovering that they are active. "A person with TB disease may feel perfectly healthy or may only have a cough from time to time."  However, these symptoms do not guarantee tuberculosis, and they may not exist at all yet the person still has active tuberculosis! A person with symptoms listed may have active tuberculosis, and the person should immediately see a physician so that tuberculosis is not spread. If a person with the above symptoms does not see a physician, ignoring the symptoms can result in lung damage, eye damage, organ damage and eventually death.
When tuberculosis settles in other organs (rather than lungs) or other parts of the body (such as the skeletal), symptoms may be different from when it settles in the lungs (such as the symptoms listed above). Thus, without the cough or flu-like symptoms, a person can have active tuberculosis. Other symptoms include back pain, flank pain, PID symptoms, confusion, coma, difficulty swallowing, and many other symptoms that would be a part of other diseases. (Please see the reference for more information on symptoms.) Therefore, seeing a physician and asking for a tuberculosis test is absolutely necessary to rule out tuberculosis when a patient has symptoms without a diagnosis of disease.
There are currently two major classes of tests used to identify patients with latent tuberculosis: tuberculin skin tests and IFN-γ (Interferon-gamma) tests. The tuberculin skin tests in use include (but are not limited to)
There are currently three IFN-γ (interferon-gamma release assay - IGRA) tests available.
A description of the tests and their interpretation follows.
The tuberculin skin test has its origins in the late 19th century. Crudely speaking, tuberculin (also called purified protein derivative or PPD) is a standardised killed extract of cultured TB, injected into the skin to measure the person's immune response to TB. Persons who have had the tuberculosis vaccination (not given in the US) also known as the BCG, may have positive results; however, "positive results [after receiving the tuberculosis vaccination] are not due to vaccination exposure because reactions in vaccinated people tend to be less than 10 mm, and an individual's sensitivity to tuberculin steadily declines after vaccination."  Historically, there have been three methods of tuberculin testing: the Mantoux test, the Heaf test, and the Tine test. The Heaf test was discontinued in 2005 because the manufacturer deemed its production to be financially unsustainable. The Heaf test was preferred in the UK because it requires less training to administer and because there is less interobserver variation in its interpretation.
The Mantoux test is now standardised by the WHO. 0.1 ml of tuberculin (100 units/ml) is given by intradermal injection into the volar surface of the forearm (subcutaneous injection results in false negatives). A waterproof ink mark is drawn around the injection site so as to avoid difficulty finding it later if the level of reaction is small. The test is read two to seven days afterwards. The area of induration (NOT of erythema) is measured transversely across the forearm (left to right, not up and down) and recorded to the nearest millimetre. You can go to the website listed in the reference area (Don't read what's red. Feel what's real.) to see how the test is read, but you should have a professional read your test so that you are sure of the results.
The Heaf test was first described in 1951 . The test uses a Heaf gun with disposable single-use heads; each head has six needles arranged in a circle. There are standard heads and pediatric heads: the standard head is used on all patients aged 2 years and older; the pediatric head is for infants under the age of 2. For the standard head, the needles protrude 2 mm when the gun is actuated; for the pediatric heads, the needles protrude 1 mm. Skin is cleaned with alcohol, then tuberculin (100,000 units/ml) is evenly smeared on the skin (about 0.1 ml); the gun is then applied to the skin and fired. The excess solution is then wiped off and a waterproof ink mark is drawn around the injection site. The test is read 2 to 7 days later.
It is not easy to translate between Heaf and Mantoux, but
The tuberculin used for Heaf tests is 1000 times more concentrated than that used for Mantoux tests. In countries where both tests are used, use of the correct concentration avoids false positive and false negative results.
According to the U.S. guidelines, there are multiple size thresholds for declaring a positive result of latent tuberculosis from the Mantoux test: For testees from high risk groups, such as those who are HIV positive, the cutoff is 5 mm of induration; for medium risk groups, 10 mm; for low risk groups, 15 mm. The U.S. guidelines recommend that a history of previous BCG vaccination should be ignored. For details of tuberculin skin test interpretation, please refer to the CDC guidelines (reference given below).
The UK guidelines are formulated according to the Heaf test: In patients who have had BCG previously, latent TB is diagnosed if the Heaf test is grade 3 or 4 and have no signs or symptoms of active TB; if the Heaf test is grade 0 or 1, then the test is repeated and. In patients who have not had BCG previously, latent TB is diagnosed if the Heaf test is grade 2, 3 or 4, and have no signs or symptoms of active TB. Repeat Heaf testing is not done in patients who have had BCG (because of the phenomenon of boosting). For details of tuberculin skin test interpretation, please refer to the BTS guidelines (references given below).
Given that the US recommendation is that prior BCG vaccination be ignored in the interpretation of tuberculin skin tests, false positives are possible as a result of: (1) people who have previously had BCG (even many years ago) may still have a false positive Mantoux test, and (2) serial testing with tuberculin skin tests boosts the immunological response in those people who have previously had BCG, so these people will falsely appear to be tuberculin converters. This may lead to treating more people than necessary, with the possible risk of those patients suffering adverse drug reactions. However, as Bacille Calmette-Guérin vaccine is not 100% effective, and is less protective in adults than pediatric patients, not treating these patients could lead to a possible infection. The current US policy seems to a reflect a desire to err on the side of safety (of the general public).
The U.S. guidelines also allow for tuberculin skin testing in immunosuppressed patients (those with HIV, or who are on immunosuppressive drugs), whereas the UK guidelines recommend that tuberculin skin tests should not be used for such patients because it is unreliable.
There are currently (26 March 2009) three commercially available interferon-γ release assays (IGRAs): QuantiFERON-TB Gold, QuantiFERON-TB Gold In-Tube and T-SPOT.TB. These tests are not affected by prior BCG vaccination, and look for the body's response to specific TB antigens not present in other forms of mycobacteria and BCG (ESAT-6). Whilst these tests are new they are now becoming available globally.
CDC recommends that QFT-G may be used in all circumstances in which the TST is currently used, including contact investigations, evaluation of recent immigrants, and sequential-testing surveillance programs for infection control (e.g., those for health-care workers).
HPA Interim Guidance:
The HPA recommends the use of IGRA testing in health care workers, if available, in view of the importance of detecting latently infected staff who may go on to develop active disease and come into contact with immunocompromised patients and the logistical simplicity of IGRA testing.
A diagnosis of latent tuberculosis (LTBI) does not mean that the patient is ill with tuberculosis. It means that the patient has been exposed to tuberculosis bacteria through a person who has active tuberculosis. Unfortunately, once exposed, a person has a chance of becoming ill with tuberculosis which is called active tuberculosis. Having active tuberculosis is very serious, and tuberculosis can damage lungs, organs and even kill a person if it becomes active.
The purpose of taking Isoniazid for tuberculosis, especially for those patients with LTBI, is to try to kill every single bacterium in a person's system thereby obtaining a "cure" for tuberculosis (i.e. no more M. Tuberculosis bacteria left in the body) so that the patient will never convert to active tuberculosis; however, there is no test to ascertain if each and every one of the bacterium has died in a person's body. Therefore, no "cure" is certain or promised though many in the medical profession refer to Isoniazid as a "cure" for tuberculosis. However, once completed, the patient can be assured that they took the medication and many bacterium died from the medication, and there is a greater likelihood that all the bacteria has died entirely in the person's system. It is unwise to self-treat (as obtaining medications online is accessible) at the risk of the active tuberculosis being treated incorrectly, this could lead to the development of multi-drug resistant tuberculosis, which is much harder to heal.
Without taking Isoniazid or other prescribed treatment by a medical professional, the person who tested positive for tuberculosis will continue to have living cells of tuberculosis bacteria in his or her body for the remainder of his or her life. In 90% of the cases, the person's body will wall up the tuberculosis bacteria, and there will be no activation (which means the patient will never become active, will not die from tuberculosis, and cannot infect others). However, the problem is that some people's systems, compromised by stress, other disease, and other situations, might allow a tuberculosis bacterium or bacteria to become active, and this active bacterium or bacteria will reproduce and create an active case of tuberculosis. In that case, the person can die, infect others (especially family and friends) and can become very ill and need hospitalization. Therefore, taking the preventative dosage of Isoniazid is highly recommended by most physicians. However, when deciding on chemotherapy of any type, one should definitely discuss the decision with a physician because of the health issues.
Tuberculin conversion is said to occur if a patient who has previously had a negative tuberculin skin test develops a positive tuberculin skin test at a later date. This is strong evidence for significant exposure to TB. The UK recommendation is that the two tests be done at least six weeks apart; the U.S. recommendation is that the two tests can be done as little as one week apart.
The phenomenon of boosting is one way of obtaining a false positive test result. Boosting can occur up to two years after the first Mantoux test. Boosting occurs when people who have had remote infection with Mycobacterium tuberculosis and/or previous exposure to Bacille Calmette-Guerin of Mycobacterium bovis (BCG), an attenuated strain of Mycobacterium bovis that is used in some countries as a vaccine against tuberculosis, are given repeated tuberculin skin tests. In these people, the first test revives or primes the immune response so that on repeat testing, the response is much stronger and the patient then looks as if he now has a positive reaction. The second tuberculin skin test result is the correct one.
The UK and U.S. guidelines approach the phenomenon of boosting differently. Under U.S. guidelines, which say to ignore previous immunisation with BCG, a person showing the phenomenon of boosting will be falsely described as a tuberculin converter. On the other hand, UK guidelines advise two tuberculin skin tests one week apart if boosting is suspected, taking the result of the second test as being the true result.
It is assumed by most medical doctors that latent tuberculosis is the normal or regular strain of tuberculosis. Therefore, it is treated as a regular strain with Isoniazid (the regular treatment for latent tuberculosis. Only when the tuberculosis bacteria does not respond to treatment does a medical doctor begin to suspect other types of tuberculosis.
Nearly all tuberculosis is what would be called regular tuberculosis. <Tuberculosis, National Institute of Allergy and Infectious Diseases, updated April 3, 2012,
There are three other types of tuberculosis recognized in the world today:
There is no evidence for any regimen used for persons with known exposure to MDR-TB and no consensus on optimal treatment. A regimen consisting of ethambutol and PAS has been used before. It would appear sensible to choose a combination of antibiotics based on the known sensitivities of the organism. The CDC have recommended a combination of pyrazinamide and ethambutol, with either pyrazinamide or fluoroquinolone. Immunocompetent contacts should be treated for 6 months; immunocompromised contacts should be treated for 12 months. Multi-drug-resistant tuberculosis happens because a patient does not take the medications correctly, takes one here and there, or takes it for a short time, and then stops and starts. Inside the body, some bacteria die, but those that do not live through the lighter dosage of drugs, and they become resistant. MDR is created when medication is not taken correctly or when a person is exposed to an active case of MDR tuberculosis. It means that the patient's tuberculosis will not die from being exposed to Isoniazid or Rifampin.
XDR has come about mainly because people have not taken medications correctly. XDR tuberculosis cannot be killed by most of the medications used to kill tuberculosis including Isoniazid, Rifampin and various injectable drugs. To cure this tuberculosis requires two years of medication. When a person has active tuberculosis, a different protocol is necessary for them to be cured of active tuberculosis. When the protocol is not followed, the patient can become drug resistant. When the tuberculosis bacteria becomes even more resistant, it is called XDR TB. Unfortunately, XDR TB can be spread in the same way that any tuberculosis can be spread. Although it is far more rare, it has become a problem across the world.
"Drug-resistant TB (MDR or XDR) is more common in people who:
In 2013, a man from Nepal tried to cross the border into Texas illegally and was detained. The type of tuberculosis the Nepalese man has may take years to treat, and this type of tuberculosis is extremely dangerous with treatment options often toxic. He traveled through 13 countries to eventually enter the United States. National governments are attempting to find those people who were exposed to him during his various types of transportation to get to the United States. If a person who rode on "Air France flight #385 / Delta flight 8517 on May 12 with the XDR TB patient," they need to get a tuberculosis test.
The treatment of latent tuberculosis infection (LTBI) is essential to controlling and eliminating TB by reducing the risk that TB infection will progress to disease. Latent tuberculosis will convert to active tuberculosis in 10% of cases (or more in cases of immune compromised patients). Taking medication for latent tuberculosis is recommended by many doctors.
In the U.S., the standard treatment is nine months of isoniazid, but this regimen is not widely used outside of the US.
There is no agreement regarding terminology: the terms preventive therapy and chemoprophylaxis have been used for decades, and are preferred in the UK because it involves giving medication to people who have no disease and are currently well: the reason for giving medication is primarily to prevent people from becoming unwell. In the U.S., physicians talk about latent tuberculosis treatment because the medication does not actually prevent infection: the person is already infected and the medication is intended to prevent existing silent infection from becoming active disease. There are no convincing reasons to prefer one term over the other.
"Populations at increased risk of progressing to active infection once exposed:
It is essential that assessment to rule out active TB be carried out before treatment for LTBI is started. To give treatment for latent tuberculosis to someone with active tuberculosis is a serious error: the tuberculosis will not be adequately treated and there is a serious risk of developing drug-resistant strains of TB.
There are several treatment regimens currently in use:
A 2000 Cochrane review containing 11 double-blinded, randomized control trials and 73,375 patients examined six and 12 month courses of isoniazid (INH) for treatment of latent tuberculosis. HIV positive and patients currently or previously treated for tuberculosis were excluded. The main result was a relative risk (RR) of 0.40 (95% confidence interval (CI) 0.31 to 0.52) for development of active tuberculosis over two years or longer for patients treated with INH, with no significant difference between treatment courses of six or 12 months (RR 0.44, 95% CI 0.27 to 0.73 for six months, and 0.38, 95% CI 0.28 to 0.50 for 12 months). A Cochrane systematic review published in 2013 evaluated four different alternatives regimens to INH monotherapy for preventing active TB in HIV-negative people with latent tuberculosis infection. The evidence from this review found no difference between shorter regimens of Rifampicin or weekly, directly observed Rifapentine plus INH compare to INH monotherapy in preventing active TB in HIV-negative people at risk of developing it . However the review found that the shorter Rifampicin regimen for four months and weekly directly observed Rifapentine plus INH for three months “may have additional advantages of higher treatment completion and improved safety." However the overall quality of evidence was low to moderate (as per GRADE criteria )and none of the included trials were conducted in LMIC nations with high TB transmission and hence might not be applicable to nations with high TB transmission.
There is no guaranteed "cure" for latent tuberculosis. "People infected with TB bacteria have a lifetime risk of falling ill with TB..."  with those who have compromised immune systems, those with diabetes and those who use tobacco at greater risk. Ibid. Although many doctors and professionals speak of Isoniazid as a "cure," it is not assuredly a "cure." Isoniazid may "cure" active tuberculosis so that it no longer is active, but Isoniazid has a failure rate of 10-25% to "cure" latent tuberculosis in patients without immune compromised systems and 50% in patients with HIV  This means that 10-25% of the people taking Isoniazid to cure, or rid their bodies of the bacteria M. tuberculosis will continue to have tuberculosis bacteria living in the body. Unfortunately, a person with tuberculosis (or latent tuberculosis) will never know which category they have finished in—cured or not cured completely though active tuberculosis will be stopped by chemotherapy. Active tuberculosis can be cured to the level of latent tuberculosis. At the current state of medicine, nobody knows if a person with latent tuberculosis (LTBI) has removed every bacterium and is unable to become active; therefore, only an exceptional case of LTBI will go from responding to the tuberculosis testing to no response; therefore, a "cure" is unknown in nearly all people who take the chemotherapy for tuberculosis.
A person who has taken the complete course of Isoniazid (or other full course prescription for tuberculosis) on a regular, timely schedule may have been cured. "Current standard therapy is isoniazid (INH) which reduce the risk of active TB by as much as 90 per cent if taken daily for 9 months." [Emphasis added]  However, if a person has not completed the medication exactly as prescribed, the "cure" is less likely, and the "cure" rate is directly proportional to following the prescribed treatment specifically as recommended. Furthermore, "[I]f you don't take the medicine correctly and you become sick with TB a second time, the TB may be harder to treat if it has become drug resistant."  If a patient were to be cured, it would mean that every single bacterium in the system is removed or dead, and that person cannot get tuberculosis (unless re-infected). However, there is no test to assure that every single bacterium has been killed in a patient's system, and this can not be tested at the present state of medicine. Therefore, a "cure" is possible with proper chemotherapy (which is usually Isoniazid in the case of latent tuberculosis). Medical and science persons believe some patients are cured, but it can never be assured that any patient is cured because certainty of the death of every single bacterium can not be proven. Because of studies, Isoniazid therapy has been indicated to not cure 10-25% of the patients who completed the treatment successfully, and those patients who are not "cured" still carry active bacteria in their system. Those active bacteria can activate and become an active case of tuberculosis and will be infectious to others. " It has been estimated that up to one-third of the world's population is infected with M. tuberculosis, and this population is an important reservoir for disease reactivation." 
Once a positive test is shown, a patient's body will always react to the tuberculosis test even after treatment. This happens because the patient's immune system has already recognized the tuberculosis bacteria as an invader. Since there is no test to ascertain if the bacteria has been entirely cleared or killed in the patient's body, there is no guarantee that the patient is "cured" and there is no test to prove a patient is cured. Therefore, once a person has a positive tuberculosis skin test, that person should never allow another skin test to be performed on him/her.
In light of the previous information, although a patient does take the entire treatment, a "cure" is not assured. Studies indicate that 10-25% of the people who take the medication could harbor tuberculosis bacteria after taking a complete course of medication and become active. If they become active (a 10-25% chance), they will very likely expose others to tuberculosis. Therefore, a person who has tested positive to tuberculosis at any time in his or her life should see a doctor when tuberculosis symptoms recur.
There are people who do get a spontaneous cure to tuberculosis. After this, their system may not recognize the tuberculosis bacteria again, and they will not test positive on the tuberculosis test. These people are rare, and therefore a person who has tested positive to tuberculosis on the skin test should never allow the skin test for tuberculosis to be given again. For those who do spontaneously recover, "28 percent reactivate 15 to 25 years later" which indicates that chemotherapy is a decidedly good idea when diagnosed with tuberculosis bacteria in the body.
Although a tuberculosis cure was developed around 1960, TB continues to kill from 2 to 3 million people every year. According to the World Health Organization (WHO), approximately one-third of the world's population are carriers of latent tuberculosis, 8 million people develop active tuberculosis every year, and approximately 36 million people will die of tuberculosis by 2020 if it is not controlled. Approximately 98 percent of those victims are from developing countries.
Because tuberculosis kills millions of people in the world each year, research has continued to the present day. There are new discoveries for tuberculosis "cures" in the news in the last two years. One of the more recent discoveries is a three cocktail treatment that kills nearly all the active tuberculosis within two weeks. Another new discovery is the Fenton's Reaction created with Vitamin C--a very inexpensive treatment protocol. Vitamin C killed 100% of the tuberculosis bacteria in a pitre dish.
Therefore, the scientific community continues its research efforts to learn more from this disease in order to develop more options for possible treatments.
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