tuberculosis ( tb ) is well known as an airborne infectious disease that is preventable and curable . people who are recently in contact with active tb patient are more likely to have latent tuberculosis infection ( ltbi ) . the mycobacterium tuberculosis bacilli can remain dormant in the host body for a long period . in general , people with ltbi usually remain asymptomatic , with only 5% to 10% of cases progress to overt tb disease . moreover , the risk of ltbi progressing to active tb is the highest risk during the first 6 to 18 months of infection . during the dormant period , thus , administering drugs to treat ltbi during this period can effectively minimize the risk of subsequent disease development . isoniazid is the main drug for treating ltbi , and it is the only ltbi treatment drug approved by the united states food and drug administration ( fda ) . after continually taking this prophylactic drug for 9 months , people with ltbi can reduce the likelihood of disease development by 60% to 90% ; hence , isoniazid is an economically viable prophylactic drug . however , asymptomatic patients who are prescribed isoniazid tend to have low adherence due to the extensive treatment period and undesirable side effects . consequently , patients discontinue taking the drug without the consent of clinicians , resulting in medical problems . therefore , how to effectively administer prophylaxis in a manner that is convenient for people is a concern among medical personnel and studies in this area are ongoing . to ensure adherence to treatment by tuberculosis patients , the direct observation of treatment ( dots ) by a trained supervisor cdc has approved treating ltbi by administering a high dosage of combined isoniazid ( 900  mg ) and rifapentine ( 900  mg ) once a week for 12 weeks under directly observed treatment , short course ( dots ) . researchers from the united states , united kingdom , and canada have successively compared the ltbi treatment regimens in terms of economic influence , drug efficacy , immunity duration , and side effects . in taiwan the need of taking daily tb prophylactic drug under dots for 9 months and the potential side effects makes the new regimen look attractive to be implemented in taiwan . no studies related to the high rifapentine / isoniazid regimen have been conducted in taiwan , thus this study aims to investigate the effects , costs , and adherence of the 9-month isoniazid regimen ( 9h ) and the 3-month rifapentine / isoniazid regimen ( 3hp ) and compare the differences between the 2 treatments . the active tuberculosis patients referred to the changhua hospital and had been diagnosed with the need to undertake ltbi treatment were enrolled in the study group , from february to july 2014 . participation criteria were : recent contact with patients who have newly developed tb disease and are not resistant to isoniazid or rifampin . positive tuberculin skin test result ( ppd - rt23 + tween80 2  tu/ 0.1 ml mantoux ) with an in duration 10  mm within 72  hours of undergoing a skin test , or purified protein derivative ( ppd )  < 10  mm , but measured 10  mm after 3 months . no clinical tb symptoms , such as coughing , fever , and weight loss . a chest x - ray image presents no sign of disease development or bacteriological evidence ( e.g. , negative sputum culture ) . the exclusion criteria were : pregnant women or women who plan to be pregnant . children younger than abnormal liver and kidney function indices , and cirrhosis or uremia diagnosed by a hepatobiliary , gastroenterology , or liver specialist . consent forms were given and signed by participants following a full explanation of the importance of ltbi treatment , the treatment course , and potential side effects of the treatment . in the study group , 12-dose combined regimen of weekly rifapentine ( 900  mg ) plus isoniazid ( 900  mg ) was administered via dots . the control group ( 9h group ) comprised tb contacts who were required to receive ltbi treatment after being referred for assessment by the changhua county public health bureau . the treatment drug was administered once daily for 270 doses ( 9 months ) and was also administered via dots . we estimated the direct costs ( medications and visits ) of 3hp and 9h in contacts . the risk of developing tb of all contacts with ltbi without treatment during the 5 years following the diagnosis of ltbi was estimated according to the method of vynnycky and fine . thus , the total cost was assessed according to the number of cases of tb avoided as cost - effectiveness . this study was approved by the institutional review board of chung - shan medical university hospital ( csmuh no : cs12161 ) , and informed written consent to participate in the study was obtained from each participant . basic demographic data ( such as sex , age , medical history ) of the participants were collected and the relationships between the participants and the index cases were investigated . each month , the participants underwent a follow - up examination to monitor and record any medication side effects , symptoms as well as their severity . results of the examination were compared to determine the differences between the 2 treatment groups . blood samples were collected before administrate the drug ( baseline ) , 1 month after the drug treatment and at the completion of treatment to monitor the liver function of the participants . while administering the drug , participants who experienced side effects underwent a blood test immediately . asymptomatic participants with an aminotransferase ( ast ) level equal to or higher than 5 times the normal level were required to discontinue any medication . symptomatic participants with an ast level equal to or higher than 3 times the normal level were also required to discontinue their medication . patients with a baseline liver function exceeding the upper limit of normal , patients with liver disease , patients who were hiv - positive , or alcoholic ( high - risk groups for hepatitis ) were carefully monitored and underwent monthly liver function tests . all continuous variables were expressed as the median and range , and the number ( n ) was expressed as percentages for categorical variables . the  test and fisher exact test were used to analyze the difference in medication adherence , types , and severity of side effects from the treatment . statistical analyses were conducted using spss 15.0 statistical software ( spss , chicago , il ) . the active tuberculosis patients referred to the changhua hospital and had been diagnosed with the need to undertake ltbi treatment were enrolled in the study group , from february to july 2014 . participation criteria were : recent contact with patients who have newly developed tb disease and are not resistant to isoniazid or rifampin . positive tuberculin skin test result ( ppd - rt23 + tween80 2  tu/ 0.1 ml mantoux ) with an in duration 10  mm within 72  hours of undergoing a skin test , or purified protein derivative ( ppd )  < 10  mm , but measured 10  mm after 3 months . no clinical tb symptoms , such as coughing , fever , and weight loss . a chest x - ray image presents no sign of disease development or bacteriological evidence ( e.g. , negative sputum culture ) . the exclusion criteria were : pregnant women or women who plan to be pregnant . children younger than abnormal liver and kidney function indices , and cirrhosis or uremia diagnosed by a hepatobiliary , gastroenterology , or liver specialist . consent forms were given and signed by participants following a full explanation of the importance of ltbi treatment , the treatment course , and potential side effects of the treatment . in the study group , 12-dose combined regimen of weekly rifapentine ( 900  mg ) plus isoniazid ( 900  mg ) was administered via dots . the control group ( 9h group ) comprised tb contacts who were required to receive ltbi treatment after being referred for assessment by the changhua county public health bureau . the treatment drug was administered once daily for 270 doses ( 9 months ) and was also administered via dots . we estimated the direct costs ( medications and visits ) of 3hp and 9h in contacts . the risk of developing tb of all contacts with ltbi without treatment during the 5 years following the diagnosis of ltbi was estimated according to the method of vynnycky and fine . thus , the total cost was assessed according to the number of cases of tb avoided as cost - effectiveness . this study was approved by the institutional review board of chung - shan medical university hospital ( csmuh no : cs12161 ) , and informed written consent to participate in the study was obtained from each participant . basic demographic data ( such as sex , age , medical history ) of the participants were collected and the relationships between the participants and the index cases were investigated . each month , the participants underwent a follow - up examination to monitor and record any medication side effects , symptoms as well as their severity . results of the examination were compared to determine the differences between the 2 treatment groups . blood samples were collected before administrate the drug ( baseline ) , 1 month after the drug treatment and at the completion of treatment to monitor the liver function of the participants . the results were also compared to determine the different effects on the liver function . while administering the drug , participants who experienced side effects underwent a blood test immediately . asymptomatic participants with an aminotransferase ( ast ) level equal to or higher than 5 times the normal level were required to discontinue any medication . symptomatic participants with an ast level equal to or higher than 3 times the normal level were also required to discontinue their medication . patients with a baseline liver function exceeding the upper limit of normal , patients with liver disease , patients who were hiv - positive , or alcoholic ( high - risk groups for hepatitis ) were carefully monitored and underwent monthly liver function tests . all continuous variables were expressed as the median and range , and the number ( n ) was expressed as percentages for categorical variables . the  test and fisher exact test were used to analyze the difference in medication adherence , types , and severity of side effects from the treatment . statistical analyses were conducted using spss 15.0 statistical software ( spss , chicago , il ) . among the 104 contacts who provided informed consent to participate in the study , 1 participant was excluded due to the potential interaction of the concurrent medications , and 2 were excluded and their medication was discontinued due to the exclusion of the index cases . the final research sample comprised 44 men and 57 women ( mean age , 34.94 years ; age range , 1375 years ) . sixteen participants had other chronic diseases , including diabetes , heart disease , and hypertension ( table 1 ) . the participants underwent monthly follow - up examinations , during which they were prescribed for 4 doses of medication and requested to describe any side effect they experienced . their blood biochemistry values were examined before drug administration , 1 month after drug administration and again after completing the treatment ( table 2 ) . data from 101 contacts was collected ; however , 3 of them discontinued their medication because of side effects . moreover , in the control group , a total of 590 contacts received the 9-month isoniazid treatment ( mean age , 34.49 years ; age range , 088 years ) , 515 of whom completed the treatment ( table 3 ) . regarding the remaining 75 contacts who discontinued the treatment in the control group , the main reasons for discontinuing the medication were the extensive treatment period and the severity of the side effects from taking the medication . the difference in the completion rate between the control group ( 515/590 : 87.29% ) and experimental group ( 98/101 : 97.03% ) was statistically significant ( p  < 0.001 ) , indicating that patients who were administered the short - term high - dosage rifapentine and isoniazid regimen had a high treatment completion rate . in addition , the discontinuation rate was lower in the experimental group ( 2.97% , 3/101 cases ) than in the control group ( 4.75% , 28/590 cases ) ( table 3 ) . characteristics of the 3-month rifapentine / isoniazid regimen ( 3hp ) population and 9-month isoniazid regimen ( 9h ) . treatment results of the 9h and 3hp regimen . during the follow - up examinations in the experimental group , elevation of got is noted in only 2 cases ( 2/101  =  1.98% ) after the treatment . got level of these 2 cases iu / l , respectively , while this phenomenon was not observed in the rest of patients . in addition , although not considered significant clinically , a noticeable decrease in averaged wbc count , from 7900 ( median ) before the treatment to 6850 after the treatment , was seen in our study ( table 2 ) . moreover , 37 participants reported experiencing uncomfortable side effects , including fever , headache , skin itchiness , and vomiting ( table 4 ) . furthermore , the side effects of the 3 participants discontinued their medications was listed in table 5 . these 3 patients who discontinued their medication presented a fever higher than 38.5c and grade 2 or 3 toxicity . however , in the control group , 28 participants discontinued their medications due to the side effects ( table 5 ) . the uncomfortable side effects included fatigue ( 21 cases ) , headache ( 3 cases ) , skin rashes ( 2 cases ) , diarrhea ( 1 case ) , and chest distress ( 1 case ) . furthermore , elevation of got / gpt was noted in 21 cases with fatigue event ( 21/590  =  3.56% ) . side effects and severity ( who toxicity grading ) caused discontinue medication in 9h and 3hp groups . regarding the cost of treatment , according to taiwanese labor law , minimum hourly wages is us$3.5 per hour and normally dots spend an hour for 1 patient approximately . thus , the medication and labor fee of the 3hp treatment program were approximately us$219.24 and us$42.00 respectively ( table 6 ) . on the other hand , the medication and manual costs for the 9h group were approximately us$24.3 and us$693.00 , respectively . furthermore , the cost - effectiveness ratio with isoniazid for 9 months was us$ 15392/avoided 1 case of tuberculosis and us$ 5225/avoided 1 case of tuberculosis with 3hp ( table 7 ) . therefore , 3hp was dominant in the sensitivity analysis . therefore , the 3hp treatment was substantially cheaper than 9h . the cost - effectiveness ratio to avoided 1 case of tuberculosis in 3hp group and 9h group . this study verified that in taiwan , the administration of a short - term high - dosage rifapentine and isoniazid regimen was significantly more favorable than the standard 9-month isoniazid treatment in terms of medication compliance , treatment completion rate , and economic benefit . the national tuberculosis control program should focus on achieving adequate tb diagnosis and treatment outcomes first , and then prioritize ltbi treatments . taiwan has a moderately high incidence rate of tb , where the diagnosis rate and treatment outcomes remain undesirable ; hence , selective ltbi treatment can serve as a supporting strategy for tb control . however , according to the fda , only an average of 60% patients who have received prophylactic treatment ( or less ) completed the treatment in accordance with their doctors instructions . among the 101 patients who participated in this study , 98 of them completed ltbi treatment ( completion rate , 97.03% ) , which was significantly higher than the completion rate of the control group ( 87.29% ) . this is similar to a large - scale study by sterling et al , who reported an 82.1% completion rate for the 3-month treatment program and a 69% completion rate for the 9-month treatment program . we do not know the contribution of dots and the shorter regimen both probably contributed to the higher completion rate . therefore , dots seems to be the effective method to monitor ltbi closely as well as to decrease default rate . medication side effect was another factor causing patients to discontinue the ltbi treatment course , hepatitis is one of the toxic effects of isoniazid . in the control group , among the 590 patients who underwent the 9-month treatment program , 28 of them did not complete their treatment because of side effects . of the 28 subjects , 21 patients who discontinued their medication presented with elevated got / gpt grade 1 to 4 . the proportion of subjects with elevated got / gpt for the 9-month treatment program ( 21/28  =  75% ) was substantially higher than that for the 3-month treatment program . moreover , the discontinuation rate for the 9-month treatment program ( 4.75% ) was also higher than that for the 3-month treatment program ( 2.97% ) . sterling et al showed that the side - effects ratio of grade 1 , grade 2 , and other side effects observed with the combination therapy was lower than that of the group treated with isoniazid . in the 3hp group , 3 patients who discontinued their medication presented a fever higher than 38.5c and grade 2 or 3 toxicity . however , the control group data in our study was obtained from the cdc central area control center , and the data consisted of only basic patient information and the side effect ratio of the treatment . indeed , the liver function indices of patients receiving ltbi treatment are important and require continuous monitoring and consideration . further analysis of the side effects related to the control group and the ratio of each side effect requires additional data to be collected . in addition to the completion rate and side effects , the lower cost of the treatment course is also a crucial consideration with implementation of ltbi treatment . several large - scale studies have indicated that the efficacy of 3-month rifapentine / isoniazid regimen was similar to that of 9-month isoniazid or 4-month rifampin regimen . therefore , despite those studies might be accurate in stating that the 9-month isoniazid treatment method is the most economical regimen , they fail to consider the labor costs of dots . in taiwan , dots visit ltbi patients 5 days a week for 9 months and spend approximately an hour with each patient . on the other hand , dots only need to visit ltbi patients once a week for 12 weeks for 3hp group . in this study , the medication costs of the 3-month and 9-month treatment programs were approximately us$219.24 and us$24.30 , respectively . although the 9h medication fee appears less than the 3hp , the labor costs of the 3-month and 9-month programs were approximately us$42 and us$693 , respectively ( table 6 ) . the cost - effectiveness ratio with isoniazid for 9 months was us$ 15392/avoided 1 case of tuberculosis and us$ 5225/avoided 1 case of tuberculosis with 3hp . therefore , the 3-month treatment was substantially more beneficial ( table 7 ) . compared with the previous studies in the united states , united kingdom , and canada , our study in taiwan found the similar results that the short - term high - dosage ltbi treatment was cost - effective and associated with higher treatment completion rate . however , we failed to provide data regarding side effects in our control group , which should be collected and analyzed in the future . overall , we determined that the 3-month program was substantially more economically viable than the 9-month program . in conclusion , this project is the first study to investigate and compare 2 dissimilar ltbi treatment regimens in the taiwan area in terms of treatment adherence and the cost . our results showed that the short - term high - dosage ltbi treatment via dot improved the treatment completion rate among the tb contacts in this study . compared with the conventional 9-month ltbi treatment via dot , the short - term high - dosage treatment method improved patient adherence to the treatment , thereby reducing the chance of disease development . moreover , this new prophylactic medication could save a considerable amount of labor cost in preventing tb . a large - scale follow - up study will confirm whether this treatment regimen is appropriate for the general population in taiwan , thereby reducing the disease development rate among tb contacts .