SPECIAL FEATURES: HEALTH POLICY

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1 Public Health Nursing / 2013 Wiley Periodicals, Inc. doi: /phn SPECIAL FEATURES: HEALTH POLICY Cost-effectiveness of Using Quantiferon Gold (QFT-G) versus Tuberculin Skin Test (TST) among U.S. and Foreign Born Populations at a Public Health Department Clinic with a Low Prevalence of Tuberculosis Ayesha Z. Iqbal, M.B.B.S., M.P.H., 1 Jenelle Leighton, R.N., B.S.N., 1 John Anthony, M.T. (A.S.C.P.) C.I.C., 1 Richard C. Knaup, B.S., 1 Eleanor B. Peters, M.S.P.H., M.S., 1 and Thomas C. Bailey, M.D. 2 1 St Louis County Department of Health, Communicable Disease Control Services Division (CDCS), Berkeley, Missouri; and 2 Washington University School of Medicine, St Louis, Missouri Correspondence to: Ayesha Z. Iqbal, St Louis County Department of Health, Division of Communicable Disease Control, 6121 N. Hanley Road, Berkeley, MO aiqbal@stlouisco.com ABSTRACT Objective: The purpose of this study was to determine the cost benefit to routinely using QFT-G versus the standard TST for screening U.S. and foreign born populations at a public health department clinic with a low prevalence of tuberculosis. Design and Sample: A comparative cost analysis of the monetization between QFT-G and TST was conducted: Data from the health departments Chest Clinic patients seen in 2007 were used to model cost predictions. Measures: The net costs of screening, x-rays, the standard 9 months of latent tuberculosis infection treatment, laboratory, and administration for U.S. born patients and foreign born patients were investigated. Results: There are no apparent cost savings for U.S. born individuals, but due to the higher specificity of QFT-G for foreign born BCG-vaccinated individuals, there are unnecessary expenditures associated with the higher number of false positives incurred when using TST compared with QFT-G on 1,000 foreign born individuals (69%, 18%). Conclusion: QFT-G is cost-effective and should be used at local health department clinics that want to achieve savings in screening and treating those suspected of having TB infection, especially for high-risk populations such as foreign born individuals. Key words: tuberculosis, LTBI, screening, TST, Cost-effectiveness. Background Approximately 10% of people with latent tuberculosis infection (LTBI) will progress to active tuberculosis. Early detection of LTBI is important in public health practice because treatment can prevent the much more serious and communicable active form of the disease (Geiter, 2000). Since its development in 1907, the tuberculin skin test (TST) has been used for LTBI screening in the United States (Brock, Weldingh, Lillebaek, Follmann, & Andersen, 2004; Geiter, 2000). The TST is based on delayed-type hypersensitivity immune response h after 0.1 ml of purified TB protein derivative is intradermally introduced into the forearm (Geiter, 2000). There is no gold standard for determining the performance characteristics of tests for LTBI. The sensitivity of these tests is extrapolated from testing patients with confirmed tuberculosis, 1

2 2 Public Health Nursing and specificity is extrapolated from testing healthy individuals who have a low risk of TB exposure. The sensitivity of the TST in non-bcg-vaccinated individuals is estimated at % (Pai, Zwerling, & Menzies, 2008). However, prior Bacillus Calmette-Guerin (BCG) vaccination can cause cross-reactivity with the test, resulting in high false-positive results (Pai et al., 2008) and reducing specificity to % (Pai et al., 2008). Although not standard practice in the United States, BCG vaccination is routinely used in many other countries for tuberculosis prevention (Cohn et al., 2000). Many public health agencies follow the Centers for Disease Control and Prevention guidelines and initiate a standard 9-month prophylactic regimen for any patient with a positive TST or positive immune globulin release assay (Brock et al., 2004; Geiter, 2000). With a high false-positive rate in foreign born individuals who may have been vaccinated with BCG, this approach can lead to unnecessary chest x-rays, patient anxiety about side effects, and high costs for follow-up and treatment (Brock et al., 2004; Geiter, 2000; Pai et al., 2006). Other studies have documented interpreter bias, a waiting period for immune response generation, and two visits per patient from the time of administering the test to reading the results as further disadvantages of using TST (Dewan et al., 2006; Johnson et al., 1999). In contrast, more recently developed screening tests such as Quantiferon Gold (QFT-G) measure gamma interferon released by T-cells when exposed to the specific TB antigenic proteins ESAP-6 and CFP-10 (Mazurek et al., 2010; Mazurek et al., 2005). QFT-G is a simple, one-step blood test with a reported specificity of for BCG-vaccinated persons and for non-bcg-vaccinated persons (Geiter, 2000; Mori & Harada, 2005; Pai et al., 2008). These antigens are not found in the BCG vaccine strain and do not cross-react (Nienhaus, Schablon, Costa, & Diel, 2011). Hence, QFT-G can be used to diagnose LTBI in BCG-vaccinated individuals (Geiter, 2000; Mori & Harada, 2005; Pai et al., 2008). Since the Food and Drug Administration (FDA) approved its use in 2005, QFT-G has been incorporated into various LTBI screening programs across the United States (Bennett et al., 2008; Diel, Nienhaus, & Loddenkemper, 2007; Franken et al., 2007). Researchers have conducted numerous studies on the cost-effectiveness of LTBI screening with QFT-G versus the standard TST. These studies are mostly international and compare different screening methodologies involving a multistep approach. The majority are experimental studies (Khan et al., 2008). There is a distinct need for more studies that are done at the local public health level (Shah et al., 2012). The Saint Louis County Department of Health in St. Louis, Missouri annually manages approximately 20 active TB cases and screens more than 300 individuals who are close contacts of TB cases and health care workers involved in TB patient care. In 2007, the Department of Health managed 20 TB cases and 474 LTBI cases. Like other local health departments across the nation, the Saint Louis County Department of Health has limited resources, and continually aims to achieve prevention at a lower cost to the taxpayer. It was for this reason that we embarked on this modeling exercise using real data to see if our research question could be answered. Research question The research question for this study was to determine if there is a cost benefit to routinely using QFT-G versus the standard TST in United States and foreign born populations at a local health department. Methods Design and sample Data were extracted from the Saint Louis County Department of Health s electronic medical record for its Chest Clinic patients seen in The U.S. born population was defined as those born in the United States of America and foreign born individuals were defined as those born outside the United States of America. The study included patients 18 years old with a positive TST and a normal chest x-ray, who had their first office visit between January 1st and December 31st Patients with symptoms of night sweats, persistent cough, weight loss, children <18 years old, those who were immune-compromised or on chemotherapy, those who needed treatment other than Isoniazid (INH) or Vitamin B6 (B6) or with a negative TST and an abnormal chest x-ray were excluded from the analysis. The demographic characteristics of the patient base that were analyzed included sex, age, occupation,

3 Iqbal et al.: Cost-effectiveness of Using QFT-G 3 and continent of origin. Occupation was categorized into high risk and low risk, based on the relative likelihood of being exposed to individuals with active tuberculosis, or the risk to others if an individual in this occupation were to develop tuberculosis. Highrisk occupations included health care, day care, and correctional workers. Low-risk occupations included students, food handlers, homemakers, those who are retired, and those who are unemployed. Nativity was categorized as U.S. born or foreign born, based on patients reported country of origin (Table 1). TABLE 1. General Characteristics of U.S. and Foreign Born Patients Total n (% total) U.S. born n (% total) Foreign born n (% total) Total 221 (100) 89 (40) 132 (60) Sex Male 105 (48) 37 (42) 68 (52) Female 116 (52) 52 (58) 64 (48) Age (18) 22 (25) 17 (13) * (40) 26 (29) 62 (47) (36) 30 (34) 50 (38) (6) 11 (12) 3 (2) Treatment status Completed 33 (15) 15 (17) 18 (14) * Ongoing 41 (19) 21 (24) 25 (19) Not 26 (12) 12 (13) 14 (11) recommended Declined 28 (13) 3 (3) 20 (15) Patient 93 (42) 38 (43) 55 (42) discontinued Continent of origin Africa 33 (15) 0 (0) 33 (25) * Asia 76 (34) 0 (0) 76 (58) Europe 15 (7) 0 (0) 15 (11) North America 97 (44) 89 (100) 8 (6) Occupation by type Student 44 (20) 16 (18) 28 (21) Health care 39 (18) 16 (18) 23 (17) worker Other 103 (47) 42 (47) 61 (46) Unemployed 17 (8) 9 (10) 8 (6) Unknown 18 (8) 6 (7) 12 (9) Occupation by risk High risk 39 (18) 16 (18) 24 (18) Nonhigh risk 164 (74) 67 (75) 97 (73) Unknown 18 (8) 6 (7) 12 (9) *p <.05. p-value Because of the high prevalence of BCG use in foreign countries, our analysis focused on nativity as a likely indicator of whether TST or QFT-G would be most cost-effective. Patient treatment status was categorized as completed, discontinued, declined, ongoing, or not recommended based on a relevant clinical decision. Treatment was categorized as completed if a patient finished a daily regimen that consisted of 300 mg of Isoniazid (INH) and 50 mg of vitamin B6 (B6) for 9 months. Treatment was categorized as discontinued if a patient chose to not fully and wholly complete the allotted 9-month regimen within a 12-month time frame or was lost to follow-up. Treatment was categorized as declined if a patient declined the treatment when it was first offered. Treatment was categorized as ongoing if a patient was in the process of completing the treatment when the defined study period elapsed. Treatment was categorized as not recommended if the treating physician decided that the patient was not a candidate for treatment at the time of the study period. Based on the standard evaluation of a patient presenting at the Saint Louis County Chest Clinic, costs were grouped into four main categories: (1) Screening, (2) Chest x-ray, (3) Treatment, and (4) Lab and Administrative (combined from Table 2). The screening category included the cost of the test and the average 10 min of staff time (the admitting clerk, the nurse and for QFT-G, the phlebotomist). The category of chest x-ray included the cost of x-ray and also included the average 10 min of the radiologist s time, and average 15 min of the radiology technician s time. The treatment category included the cost of the standard 9 months of INH 300 mg and B6 50 mg. The lab and administrative combined category included the staff time for medication pick up visits comprised of the average 10 min a patient spends with the clerk and the nurse, the average 10 min a patient spends with the physician after the initial positive test, and the cost of liver function tests. The cost summary is as follows: TST ($24), QFT-G ($64), chest x-ray ($67), Isoniazid 300 mg ($38), vitamin B6 50 mg ($1), liver function test ($4), admitting clerk ($3/10 min), nurse ($4/10 min), physician ($18/10 min), x-ray technician ($4/15 min), radiology consult ($11/10 min), phlebotomist ($3/10 min).

4 4 Public Health Nursing TABLE 2. Cost Sheet Item TST QFT-G Difference (QFT-G minus TST) Test $24 $64 $40 Clerk 10 min $6 $3 $3 Nurse 10 min $8 $4 $4 Phlebotomist $0 $3 $3 Screening total $38 $74 $36 X-ray $67 $67 $0 Radiation consult 10 min $11 $11 $0 Tech 15 min $4 $4 $0 X-ray total $82 $82 $0 INH 300 mg 9 9 $342 $342 $0 B6 50 mg 9 9 $9 $9 $0 Rx total $351 $351 $0 Liver function tests 9 9 $36 $36 $0 Phlebotomist 10 min 9 9 $27 $27 $0 Lab total $63 $63 $0 MD 10 min 9 1 $18 $18 $0 Nurse 10 min 9 9 $36 $36 $0 Clerk 10 min 9 9 $27 $27 $0 Administrative total $81 $81 $0 Total of all services combined $615 $651 $36 All administrative costs were assumed at an averaged 10 min and were calculated by dividing the hourly salaries by six. For the cost of x-ray technician, an average of 15 min instead of 10 min was used to calculate the cost. All these calculations were rounded to the nearest dollar. Refer to Table 2 for the cost summary. The total cost for two visits when screening a patient with TST was $38. This included the cost of the one test ($24), and an average 10 min that a patient spends with an admitting clerk ($3), and a nurse ($4) for two visits ($14) (Table 2). The cost for a single visit when screening a patient with QFT-G was $74. This figure included the cost of the one test ($64), the average 10 min a patient spends with an admitting clerk ($3) and a nurse for single visit ($4), and a phlebotomist ($3). The net difference between screening a patient with QFT-G versus TST was $36 ($74 - $38). The x-ray cost was $82 per patient regardless of screening test used. This included the cost of the x-ray ($67), the cost of the radiology consult for an average of 10 min ($11), and the cost of 15 min of the x-ray technician s time ($4). The standard 9-month treatment course was $351. This included the cost of 9 months of daily Isoniazid 300 mg ($342), and daily B6 50 mg ($9). The net combined laboratory and administrative costs for 9 months were $144. This included the cost of monthly liver function tests ($36), and the summed cost of the nine visits with a phlebotomist ($27), the average 10 min a patient spends with the clerk and the nurse at for a total of nine visits ($63), and the cost of seeing the physician on at least 1 visit for an average of 10 min ($18). The cost of x-rays, the standard 9-month treatment course and lab and administration was $577 per patient regardless of the testing method used. Due to the difference in the screening costs, the average cost from screening to follow-up for a single patient was $615 with TST and $651 with QFT- G (Table 2). Measures Two calculators for analyzing cost savings between TST and QFT-G were developed using Microsoft Excel, one each for U.S. and foreign born individuals. These cost calculators allowed for simultaneous analysis of U.S. and foreign born individuals while controlling for various factors such as sensitivity, specificity, LTBI prevalence rates, population, and the average cost per patient. The analysis used a prevalence rate of 2% for the U.S. born population and 19% for the foreign born population (Bennett et al., 2008). For U.S. born patients, a pooled sensitivity of 0.77 for both screening tests and a specificity of 0.97 for TST and 0.99 for QFT-G were included in the analysis (Pai et al., 2008). For foreign born patients, a pooled sensitivity of 0.77 for TST and 0.78 for QFT-G and a specificity of 0.59 for TST, 0.96 for QFT-G were included in the analysis (Pai et al., 2008). The results change proportionately to the number of patients screened, but to avoid rounding errors with small numbers, we used 1,000 patients in our assumption models. Negative and positive predictive values and false-positive values were also determined using these calculators. The calculators were designed to be flexible and easy to use by anyone interested in replicating similar results with their own data. Both calculators can be customized and are instruments that are formulated specifically to be utilized by any public health department wanting to quickly analyze cost savings when deciding on whether to replace TST with QFT-G. The calculators are available at no cost by ing the author (Tables 3 and 4).

5 Iqbal et al.: Cost-effectiveness of Using QFT-G 5 TABLE 3. Values for Cost Calculators U.S. born Foreign born TST QFT-G TST QFT-G Source Number of patients 1,000 1,000 1,000 1,000 User enters own data Prevalence 2% 2% 19% 19% Bennett et al. (2008) Sensitivity Pai et al. (2008) Specificity Pai et al. (2008) PPV a 34% 60% 31% 82% Table 4 NPV b 99% 99% 92% 95% Table 4 False positives 66% 40% 69% 18% Table 4 Total positive Patients c Table 4 Net costs $63,388 $88,425 $313,806 $177,860 Table 5 Percent difference (savings) 39% 43% Table 5 a Positive predictive value. b Negative predictive value. c Truly and falsely positive patients. TABLE 4. Estimated Number of U.S. and Foreign Born Individuals with TB Infection Based on Sensitivity and Specificity of the Two Tests and Prevalence of Latent Tuberculosis Infection (LTBI) Analytic strategy The Statistical Package for the Social Sciences (SPSS), version 19.0 (IBM SPSS, Armonk, NY, USA) and Microsoft Excel version 2007 (Redmond, WA, USA) were used for the analysis. Descriptive statistics were computed for sex, age, occupation, continent of origin, and treatment status. Chi-square analysis was used to evaluate general characteristics in U.S. and foreign born individuals. A model was created to calculate the total cost for all patients screened and average costs per patient from screening to completion of treatment for both U.S. and foreign born persons. For cost comparison analysis, sensitivity and specificity parameters were derived from the meta-analysis done by Pai et al. (2008). Results U.S. born Foreign born LTBI+ LTBI Total LTBI+ LTBI Total TST TST Total , ,000 QFT-G QFT-G Total , ,000 General characteristics of patients screened at our public health department clinic are presented in Table 1. Age, treatment status, and continent of origin were significantly associated with nativity (Chisquare p-value <.05). Screening U.S. born patients Assuming a sample population of 1,000 people with a 2% prevalence rate, if all were tested, screening costs would be nearly two times higher for QFT-G than TST ($74,000 and $38,000). Of the 1,000 people screened, 15 individuals would have received truly positive results and 29 individuals would have received falsely positive results with TST, compared with screening with QFT-G, where 15 individuals would be truly positive and 10 individuals would be falsely positive. The total number of true and false positives for U.S. born individuals with TST would be 44 compared with 25 with QFT-G. See Table 4 for true- and false-positive models for both U.S. and foreign born individuals for TST and QFT-G. Given a 66% false-positive rate with TST compared with 40% with QFT-G, the costs for x-rays on both true and false positives would be 43% lower for QFT-G compared with TST ($2,050 and $3,608). Assuming that all of these patients would be given a standard 9-month treatment, the costs would also be 43% lower if QFT-G is compared with TST ($8,775 and $15,444). The lab and administrative costs were also lower with QFT-G ($3,600 vs. $6,336). However, adding up the total costs of screening, x-ray, treatment, and follow-up for 1,000 patients, the net cost is lower if patients are screened with TST as compared with QFT-G ($63,388 and $88,425). The net difference between

6 6 Public Health Nursing the total cost of QFT-G and TST is $25,037. See Figure 1 and Table 5. Screening foreign born patients Assuming a sample population of 1,000 people with a 19% prevalence rate, 146 individuals would have received truly positive results and 332 individuals would have received falsely positive results with Expense Expense $90,000 $80,000 $70,000 $60,000 $50,000 $40,000 $30,000 $20,000 $10,000 $0 $400,000 $350,000 $300,000 $250,000 $200,000 $150,000 $100,000 $50,000 $0 US TST cost Total costs TST vs. QFT-G: US born US QFT-G cost Number of patients FB TST cost Total costs TST vs. QFT-G: Foreign born FB QFT-G cost Number of patients Figure 1. Cost-effectiveness Comparison: U.S. and Foreign Born Individuals Screened with TST versus QFT-G TST. When screening this same population with QFT-G, 148 individuals would be truly positive and 32 individuals would be falsely positive. The total number of true and false positives for foreign born individuals with TST would be 478 compared with 180 with QFT-G. Given a 69% false-positive rate with TST compared with 18% with QFT-G, the costs for x-rays on both true and false positives would be 62% lower for QFT-G compared with TST ($14,760 and $39,196). Assuming that all of these patients would be given a standard 9-month treatment, the costs would also be 62% lower when QFT-G is compared with TST ($63,180 and $167,778). The lab and administrative costs were also lower with QFT-G ($25,920 vs. $68,832). Adding up the total costs of screening, x-ray, treatment, and follow-up for 1,000 patients, the net cost is lower if patients are screened with QFT-G as compared with TST ($177,860 and $313,806). The net difference between the total cost of QFT-G and TST is -$135,946. See Figure 1 and Table 5. Discussion Our analysis shows that due to negligible difference between the sensitivity and specificity of the two tests for U.S. born individuals, there are no net savings when using QFT-G in U.S. born individuals. However, there are net savings in using QFT-G versus TST if using only one test for foreign born populations. Furthermore, according to Diel et al. (2007), a two test approach where a primary TST is completed and then followed by a QFT-G test on foreign born individuals with an induration the size TABLE 5. Comparison of Costs Incurred for Screening and Subsequent Follow-up for Those Who Are Test Positive on 1,000 Latent Tuberculosis Infection U.S. and Foreign Born Patients a U.S. born Foreign born TST QFT-G Diff b TST QFT-G Diff a Number screened 1,000 1,000 1,000 1,000 Screening cost $38,000 $74,000 $36,000 $38,000 $74,000 $36,000 Number of estimated test positives X-ray cost $3,608 $2,050 $1,558 $39,196 $14,760 $24,436 Rx cost $15,444 $8,775 $6,669 $167,778 $63,180 $104,598 Lab and administrative costs $6,336 $3,600 $2,736 $68,832 $25,920 $42,912 Net $63,388 $88,425 $25,037 $313,806 $177,860 $135,946 a Data synthesized from Tables 2 and 4. b Difference (Cost QFT-G minus Cost TST).

7 Iqbal et al.: Cost-effectiveness of Using QFT-G 7 of 5 mm or greater is cost-effective (Diel et al., 2007; Machado et al., 2007; Mazurek et al., 2005; Pratt, Robison, Navın, Hlavsa, & Pevzner, 2007). Per this methodology, QFT-G should be offered to individuals with a positive TST. When applying two-step methodology, screening the 478 foreign born individuals out of the original 1,000 who would be positive (true and false) with TST, the cost for that second screening with QFT-G ($74) would be $35,372. With a true- and false-positive test, 86 individuals of the 478 would have a positive result from that second screening with QFT-G. The cost of x-ray, treatment, and lab and administration ($577, see Table 2) for those 86 individuals would be $49,622. So, the total cost for screening to treatment of 1,000 foreign born individuals using the two-step methodology of QFT-G after a positive TST ($38,000 for 1,000 tests) at a 19% prevalence rate would be $122,994. Hence, the total cost with this two-step method would be $190,812 lower than the total cost incurred with TST alone ($313,806). This two-step methodology is costeffective among U.S. born individuals as well. The St. Louis County Department of Health is unique in that the majority of the patients referred to the Chest Clinic have already received a TST from an outside source before visiting. As the St. Louis County Department of Health predominantly sees most patients who present with a recent positive TST for follow-up, this two-step approach is automatically applied when high-risk individuals who are positive with TST are given QFT-G upon entry into the Chest Clinic. This two-step method effectively translates into de facto cost savings for the St. Louis County Department of Health. The majority of follow-up cost burden for a health department for TB-related expenditures, other than the costs of screening, is comprised of the burdens of further diagnostic tests such as x-rays, the standard 9-month treatment regimen, the blood tests, and the administrative costs at each patient visit. The better specificity of QFT-G results in cost savings for foreign born individuals by avoiding the unnecessary follow-up that would occur after an individual receives a falsely positive TST (de Perio, Tsevat, Roselle, Kralovic, & Eckman, 2009). Also as with any test, both TST and QFT-G carry a sensitivity of.77 and will miss a certain amount of truly positive individuals. Being a relatively new test in the market, numerous research studies report varied sensitivity and specificity for QFT-G versus TST. Values for sensitivity and specificity in this study were taken from a meta-analysis done by Pai et al. (2008). Due to this variability, the calculators are flexible and can accommodate different values for sensitivity and specificity as well as LTBI prevalence rates. Not included in this study s analysis is the cost burden of the potential and actualized side effects, and additional blood tests needed for treating foreign born patients who received a false-positive result with TST or what cost savings could be achieved by only doing chest x-rays on those who have a positive IGRA. The general characteristics of our population are shown in Table 1. The cumulative costs of screening, x-ray, treatment, and lab and administration of our 221 patients was $47,699 during Of these 221 individuals, 89 were U.S. born and 132 were foreign born. Of that $47,699, the St. Louis County Chest Clinic spent $22,141 on the U.S. born patients and $25,558 on the foreign born patients. With these numbers and the data in the treatment status category of Table 1, it is clear to see that it is harder to incorporate and retain foreign born individuals during the whole course of treatment. The attrition of these individuals is very detrimental to the efforts of local TB control programs; LTBI treatment completion rates are integral for prevention of tuberculosis, and ultimately reduce the direct medical costs incurred for treating the disease (Rajbhandary, Marks, & Bock, 2004). Studies have suggested that approximately 2 5% of those who test positive ( 10 mm) for LTBI will develop TB less than 2 years after acquiring infection (Cohn et al., 2000; Ferebee, 1970; Small & Fujiwara, 2001). Our data demonstrate that foreign born individuals not only decline treatment more often but are also less likely to complete treatment than U.S. born individuals. In this study, 15% of the foreign born patients declined treatment compared with 3% of the U.S. born. Modeling forward, assuming that 150 of 1,000 foreign born patients decline treatment at the Chest Clinic, using our calculators, of those 150, 22 would be truly positive and 5%, or 1.1 individuals, of those truly positive, 22 patients could potentially acquire active TB in less than 2 years (Ferebee, 1970). The cost of treating 1 pan sensitive case could be as much as $4,000 and if the patient had pan-resistant TB, the total cost incurred could increase to anywhere from

8 8 Public Health Nursing $15,000 to $137,000, depending on the duration of hospitalization and side effects (Franken et al., 2007; Taylor et al., 2000). Data on prior BCG vaccination history will help local health departments adjust and improve screening policies in deciding whether to use QFT-G or not. Finally, these analyses can be replicated by any local health department to bring about policy change for screening methods based on demonstrated cost savings. QFT-G is cost-effective and should be used at local health department clinics that want to achieve savings in screening and treating those suspected of having TB infection. It is especially efficacious for high-risk populations such as foreign born individuals. Because of the cost savings demonstrated in this research and because of the higher specificity of IGRAs, the St. Louis County Department of Health implemented the use of screening for TB solely with QFT-G in 2008 and switched to T-SPOT (another gamma interferon release assay) in References Bennett, D. E., Courval, J. M., Onorato, I., Agerton, T., Gibson, J. D., Lambert, L., et al. (2008). Prevalence of tuberculosis infection in the United States population: the national health and nutrition examination survey, American Journal of Respiratory and Critical Care Medicine, 177(3), doi: /rccm oc. Brock, I., Weldingh, K., Lillebaek, T., Follmann, F., & Andersen, P. (2004). Comparison of tuberculin skin test and new specific blood test in tuberculosis contacts. American Journal of Respiratory and Critical Care Medicine, 170 (1), doi: /rccm oc. Cohn, D. L., O Brien, R. J., Geiter, L. J., Gordin, F., Hershfield, E., & Horsburgh, C. (2000). Centers for Disease Control and Prevention (CDC). Targeted tuberculin testing and treatment of latent tuberculosis infection. Morbidity and Mortality Weekly Report, 49(6), Dewan, P. K., Grinsdale, J., Liska, S., Wong, E., Fallstad, R., & Kawamura, L. M. (2006). Feasibility, acceptability, and cost of tuberculosis testing by whole-blood interferon-gamma assay. BMC Infectious Diseases, 6, 47. doi: / Diel, R., Nienhaus, A., & Loddenkemper, R. (2007). Cost-effectiveness of interferon-gamma release assay screening for latent tuberculosis infection treatment in Germany. Chest, 131(5), doi: /chest Ferebee, S. H. (1970). Controlled chemoprophylaxis trials in tuberculosis. A general review. Bibliotheca Tuberculosea, 26, Franken, W. P., Timmermans, J. F., Prins, C., Slootman, E.-J. H., Dreverman, J., Bruins, H., et al. (2007). Comparison of Mantoux and QuantiFERON TB Gold tests for diagnosis of latent tuberculosis infection in Army personnel. Clinical and Vaccine Immunology, 14(4), Geiter, L. e. (2000). Ending Neglect: The Elimination of Tuberculosis in the United States. Washington, D.C: The National Academies Press. Johnson, P., Stuart, R., Grayson, M., Olden, D., Clancy, A., Ravn, P., et al. (1999). Tuberculin-purified protein derivative-, MPT-64-, and ESAT-6-stimulated gamma interferon responses in medical students before and after Mycobacterium bovis BCG vaccination and in patients with tuberculosis. Clinical and Diagnostic Laboratory Immunology, 6 (6), Khan, K., Wang, J., Hu, W., Bierman, A., Li, Y., & Gardam, M. (2008). Tuberculosis infection in the United States: national trends over three decades. American Journal of Respiratory and Critical Care Medicine, 177(4), Machado, A., Szabo, K., Barbosa, T., Arruda, S. M., Reis, M. G., Riley, L. W., et al. (2007). Comparison of whole blood interferon-gamma assay with tuberculin skin testing in household contacts of pulmonary tuberculosis patients in Salvador, Brazil. Chest, 132 (4_MeetingAbstracts), 433a 433. Mazurek, G. H., Jereb, J., LoBue, P., Iademarco, M. F., Metchock, B., & Vernon, A. (2005). Centers for Disease Control and Prevention (CDC). Guidelines for using the QuantiFER- ON-TB Gold test for detecting Mycobacterium tuberculosis infection, United States. MMWR Recommendations and Reports, 54, Mazurek, G., Jereb, J., Vernon, A., LoBue, P., Goldberg, S., Castro, K., et al. (2010). Centers for Disease Control and Prevention (CDC). Updated guidelines for using interferon gamma release assays to detect Mycobacterium tuberculosis infection-united States, MMWR Recommendations and Reports, 59, 1 25.

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