if an individual receives a negative and then a positive tst they will be assessed for full tb treatment beginning with x-ray to confirm tb is not active and proceeding from there. conversely, the uk guidelines acknowledge the potential effect of the bcg vaccination, as it is mandatory and therefore a prevalent concern – though the uk shares the procedure of administering two tests, one week apart, and accepting the second one as the accurate result, they also assume that a second positive is indicative of an old infection (and therefore certainly ltbi) or the bcg itself. in the case of bcg vaccinations confusing the results, interferon-γ (ifn-γ) tests may be used as they will not be affected by the bcg. interpretation 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. 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 with the mantoux test are possible as a result of: (1) having previously had a bcg (even many years ago), or (2) periodical testing with tuberculin skin tests. having regular tsts boosts the immunological response in those people who have previously had bcg, so these people will falsely appear to be tuberculin conversions. this may lead to treating more people than necessary, with the possible risk of those patients developing 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 reflect a desire to err on the side of safety. 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. interferon-γ testing the role of ifn-γ tests is undergoing constant review and various guidelines have been published with the option for revision as new data becomes available.cdc:mmwr health protection agency:uk there are currently two commercially available interferon-γ release assays (igras): quantiferon-tb gold 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: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. drug-resistant strains it is usually assumed by most medical practitioners in the early stages of a diagnosis that a case of latent tuberculosis is the normal or regular strain of tuberculosis. it will therefore be most commonly treated with isoniazid (the most used treatment for latent tuberculosis.) only if the tuberculosis bacteria does not respond to the treatment will the medical practitioner begin to consider more virulent strains, requiring significantly longer and more thorough treatment regimens. there are 4 types of tuberculosis recognized in the world today: tuberculosis (tb) multi-drug-resistant tuberculosis (mdr tb) extensively drug-resistant tuberculosis (xdr tb) totally drug-resistant tuberculosis (tdr tb) treatment main article: tuberculosis treatment 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. terminology 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. specific situations main article: tuberculosis treatment "populations at increased risk of progressing to active infection once exposed: persons with recent tb infection congenital or acquired immunosuppressed patients (in particular, hiv-positive patients) illicit intravenous drug users; alcohol and other chronic substance users children (particularly those younger than 4 years old) persons with comorbid conditions (ie, chronic kidney failure, diabetes, malignancy, hematologic cancers, body weight of at least 10% less than ideal, silicosis, gastrectomy, jejunoileal bypass, asthma, or other disorders requiring long-term use of corticosteroids or other immunosuppressants)." treatment regimens 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: 9h — isoniazid for 9 months is the gold standard (93% effective, in patients with positive test results and fibrotic pulmonary lesions compatible with tuberculosis). 6h — isoniazid for 6 months might be adopted by a local tb program based on cost-effectiveness and patient compliance. this is the regimen currently recommended in the uk for routine use. the u.s. guidance excludes this regimen from use in children or persons with radiographic evidence of prior tuberculosis (old fibrotic lesions) (69% effective). 6 to 9h2 — an intermittent twice-weekly regimen for the above two treatment regimens is an alternative if administered under directly observed therapy (dot). 4r — rifampicin for 4 months is an alternative for those who are unable to take isoniazid or who have had known exposure to isoniazid-resistant tb. 3hr — isoniazid and rifampin may be given daily for three months. 2rz — the two-month regimen of rifampin and pyrazinamide is no longer recommended for treatment of ltbi because of the greatly increased risk of drug-induced hepatitis and death. 3hp – three-month (12-dose) regimen of weekly rifapentine and isoniazid. the 3hp regimen has to be administered under dot. a self-administered therapy (sat) of 3hp is investigated in a large international study. evidence for treatment effectiveness 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. treatment efficacy 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. 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 (in patients with positive ltbi test results and fibrotic pulmonary lesions compatible with tuberculosis) if taken daily for 9 months." 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, "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 in the strictest definition of the word, 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. as such, a person diagnosed with latent tb can safely assume that, even after treatment, they will carry the bacteria – likely for the rest of their lives. furthermore, "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." this means that in areas where tb is endemic treatment may be even less certain to "cure" tb, as reinfection could trigger activation of latent tb already present even in cases where treatment was followed completely. epidemiology tuberculosis exists in all countries in the world, though some countries have a larger number of people infected than others. per 100,000 people, eswatini has the greatest number of tuberculosis cases in the world (627). second is cambodia (560), followed by zambia (445), fourth is djibouti (382), fifth is indonesia (321), mali (295), zimbabwe (291), kenya (291), papua new guinea (283) and gambia (283). the united states, sweden and iceland have some of the lowest rates of tuberculosis at 2 per 100,000. canada, netherlands, jamaica, norway, malta, grenada and antigua and barbuda also have low infection rates, at 3 per 100,000. in north america, countries over 10:100,000 include mexico (14), belize (18), bahamas (19), panama (28), el salvador (36), nicaragua (35), honduras (46), guatemala (48), and the dominican republic (88). most western european countries have less than 10 per 100,000 except spain (14), portugal (16), estonia (27), latvia (43) and lithuania (48), while eastern and southern european countries tend to have a greater number, with romania (94) being the highest. in south america, the countries with the greatest rates of tuberculosis per 100,000