Comparing Two Preventive Regimens for Latent Tuberculosis Infection (LTBI)
Comparing Two Preventive Regimens for Latent Tuberculosis Infection (LTBI)
Though still an endemic area, the incidence of tuberculosis (TB) in Taiwan is decreasing in
 recent years. Further reduction in TB incidence, or even elimination should rely on treatment
 for LTBI. However, which is the cost-effective screening method or what is the cost-effective
 regimen in Taiwan is still unclear.

 Therefore, the investigators designed this prospective study to follow up adult household
 contacts with LTBI for 2 years and compare the efficacy of 9-month isoniazid and 4-month
 rifampicin).
In countries with a low incidence of tuberculosis (TB), most new, active cases have occurred
 among persons who were once infected, contained this infection, and then later developed
 active TB. Therefore, identifying persons with latent Mycobacterium tuberculosis infection
 (LTBI) followed by preventive therapy is an important strategy in public health for TB
 elimination. Until this decade, the diagnosis of LTBI had been based on contact investigation
 and tuberculin skin testing (TST). However, false-positive results are not uncommon due to
 its cross-reactivity with the bacille Calmette-Guérin (BCG) vaccine and some species of
 non-tuberculosis mycobacteria (NTM), and false-negative results can occur in at least 20% in
 immunocompromised hosts.

 With the application of M. tuberculosis-specific antigens, current interferon-gamma release
 assays (IGRAs) have been shown to have a better sensitivity and specificity than TST for
 detecting host response to M. tuberculosis. Therefore, current guidelines for the diagnosis
 and management of latent tuberculosis infection recommend using IGRA to replace TST. Reports
 from recent studies comparing the sensitivity, specificity and availability, as well as
 cost-effective analysis for both tests are inconclusive. The best way varies in different
 areas, cultures and facilities. Therefore, collecting local data would be very helpful for
 policy making in public health.

 Several regimens have been used in treating LTBI, including 9-month isoniazid, 4-month
 rifampin, 2-month rifampin plus pyrazinamide, and 3-month isoniazid plus rifampin. Among the
 4 regimens, 2-month rifampin plus pyrazinamide has been reported to associate with
 unacceptable hepatotoxicity and even mortality due to hepatic failure. Therefore, this
 regimen has now been abandoned in treating LTBI. The treatment completion rate, adverse
 events, and reduction in risk of developing active TB are similar in 3-month isoniazid plus
 rifampin as in 6-month Isoniazid. At present, 9-month isoniazid is still the most popular
 regimen for LTBI, because the toxicity is low, the drug interaction is seldom, and isoniazid
 has been used for many years. However, the long treatment duration seriously compromises the
 completion rate. By contrast, rifampin is safe, cheap and more acceptable. Recent studies,
 including cost-effective analysis, favor using 4-month rifampin in treating LTBI. However,
 the outcome in these studies is completion rate of preventive therapy, rather than the event
 of developing active TB. In addition, some use statistic modeling rather conducting a
 clinical trial.

 Though still an endemic area, the incidence of TB in Taiwan is decreasing in recent years.
 Further reduction in TB incidence, or even elimination should rely on treatment for LTBI.
 However, which is the cost-effective screening method or what is the cost-effective regimen
 in Taiwan is still unclear.

 Therefore, the investigators designed this prospective study to follow up adult household
 contacts with LTBI for 2 years and compare the efficacy of 9-month isoniazid and 4-month
 rifampicin).
Inclusion Criteria:

 -  household contact of patients with newly diagnosed, culture-confirmed pulmonary
 tuberculosis

 -  age > 18

 -  tuberculin skin testing-positive or QuantiFERON-positive

 -  hemoglobin > 8 g/dL

 -  neutrophil > 750 /uL

 -  total bilirubin < 2.5 mg/dL

 -  aspartic and alanine transaminases < 2 times of upper limit of normal

 -  willing to receive serology tests for HBV and HCV infection

 -  no history of allergy to isoniazid and rifampin

 -  not currently pregnant or breast-feeding

 Exclusion Criteria:

 -  the M. tuberculosis isolate of the index case were isoniazid- or rifampin-resistant

 -  liver cirrhosis

 -  clinical or radiographical evidence of active tuberculosis

 -  active hepatitis

 -  currently receiving medication that have documented drug interaction with isoniazid or
 rifampin

 -  life expectancy < 3 years