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tuberculin skin test &#40;TST&#41; with induration diameter of at least 5&#8239;mm and&#47;or positive QuantiFERON TB Gold &#40;QFT&#41; with a cut-off of 0&#46;35 IU&#47;mL<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a>&#44; and no evidence of active disease&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Diagnostic strategy</span>&#58; techniques used to diagnose LTBI&#44; according to the sequence established at the discretion of the attending physician&#46; Three options were considered&#58; dual &#40;TST plus QFT combined&#41;&#59; TST alone&#59; or QFT alone&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Direct costs were extracted from the data provided by the Health Service of the Principality of Asturias<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> and the Catalan Public Health Agency<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a>&#44; as shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46; Indirect costs for the treatment and follow-up of active TB cases detected in the contact study were &#1028;10&#44;262 per patient<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a>&#46; Using these data&#44; we performed a cost-effectiveness analysis of the diagnostic strategy and LTBI treatment&#46; Baseline strategies selected for diagnosis and treatment were TST and a 6-month course of isoniazid &#40;6H&#41;&#44; respectively&#44; and the target population consisted of all contacts of the 4832 TB cases diagnosed in Spain in 2018<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a>&#44; estimating that each of them would have an average of 4 contacts&#46; The number of TB cases avoided was used as a measure of efficacy&#44; assuming that 10&#37; of infected contacts will develop TB during their lifetime<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a>&#44; and that LTBI treatment reduces the overall risk by between 56&#37; and 75&#37;&#44; depending on the regimen used<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a>&#46; The incremental cost-effectiveness ratio &#40;ICER&#41; was calculated to compare the different strategies&#46; When a strategy was less expensive and more effective than the baseline strategy&#44; the ICER was not calculated and that strategy was considered dominant&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">Proportions were compared using the Student&#8217;s <span class="elsevierStyleItalic">t</span>-test or its non-parametric equivalent&#44; the Mann-Whitney <span class="elsevierStyleItalic">U</span> test A <span class="elsevierStyleItalic">p</span>-value of less than &#46;05 was considered significant&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">A total of 1035 contacts of 265 index cases with a mean age of 37&#46;96&#8239;&#177;&#8239;20&#46;13 years were identified&#46; The diagnostic strategy was dual in 374 &#40;36&#46;4&#37;&#41;&#44; TST in 537 &#40;51&#46;9&#37;&#41;&#44; and QFT in 124 &#40;11&#46;7&#37;&#41;&#59; the percentage of LTBI in each group was 48&#46;2&#37;&#44; 27&#46;4&#37;&#44; and 40&#46;4&#37;&#44; respectively &#40;<span class="elsevierStyleItalic">P</span>&#8239;&#61;&#8239;&#46;01&#41;&#46; LTBI was diagnosed in 346 &#40;33&#46;4&#37;&#41; contacts and 295 started treatment&#58; 156 &#40;52&#46;9&#37;&#41; received isoniazid plus rifampicin for 3 months &#40;3HR&#41;&#44; 124 &#40;42&#37;&#41; received 6H&#44; 5 &#40;1&#46;9&#37;&#41; received rifampicin for 4 months &#40;4R&#41;&#44; and 10 &#40;3&#46;2&#37;&#41; received isoniazid for 9 months&#59; 91&#46;1&#37;&#44; 89&#46;1&#37;&#44; 80&#37;&#44; and 70&#37; completed treatment&#44; respectively &#40;<span class="elsevierStyleItalic">P</span>&#8239;&#61;&#8239;&#46;1&#41;&#46; Seventeen cases of TB were diagnosed &#40;1&#46;6&#37;&#41;&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">The total cost was &#1028;545&#44;491&#46;80&#58; &#1028;371&#44;037&#46;80 for direct costs&#44; of which 40&#46;8&#37; was for medical consultations&#44; 26&#46;1&#37; for LTBI treament&#44; and 25&#46;1&#37; for diagnostic studies&#46; The average cost per contact studied was &#1028;548&#46;23 &#40;SD 142&#46;97&#41;&#46; Dual and QFT strategies were significantly more expensive than TST but more effective&#44; and the 3HR treatment was dominant over 6H&#46; The costs of diagnosis and LTBI treatment and corresponding ICERs are shown in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">The cost per contact studied was higher than the &#1028;368&#46;23 reported in a German study<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a>&#44; but unlike our series&#44; that study did not include the costs of preventive treatment&#46; In another study conducted in Norway<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a>&#44; the average cost was &#1028;1934&#44; significantly higher than ours&#44; due to differences in the costs charged&#44; especially for medical consultations&#46; If we extrapolate our results to the approximate number of contacts to be evaluated in Spain<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a>&#44; the estimated total cost of contacts study would be &#1028;10&#46;6 million&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">With regard to LTBI treatment&#44; the 3HR regimen was less expensive and more effective&#44; confirming that it would be a better choice than 6H&#46; This was also demonstrated in a cost-effectiveness study<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> in which all short regimens&#44; including 3HR&#44; were more cost-effective than 6H&#44; although the authors&#44; unlike us&#44; found that 4R was slightly better&#59; however&#44; our results should be interpreted with caution due to the low representation of 4R in our series&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">With regard to diagnosis&#44; the dual strategy and QFT were more expensive but more effective than TST&#44; with an ICER of &#1028;8865&#46;61 and &#1028;8463&#46;57 per TB case avoided&#44; respectively&#46; If we bear in mind that health interventions with an ICER of up to &#1028;30&#44;000 are efficient<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a>&#44; both strategies would be cost-effective&#46; To determine the best option&#44; we must analyze the ICER together with the potential health benefit of the intervention&#44; &#8211; in this case&#44; identifying contacts with LTBI and offering them treatment to reduce the risk of developing TB as well the environment in which the strategy is implemented&#46; Given that the percentage of LTBI is higher when the dual strategy is used&#44; we believe that this would be the most appropriate in a country with a low incidence of disease&#44; such as Spain&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Several studies conducted in low-incidence countries have shown that the use of both interferon-&#947; release assays &#40;IGRA&#41; and TST techniques is cost-effective in certain groups such as household contacts<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;15</span></a> and health workers<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a>&#46; Spanish clinical guidelines also recommend this approach in children under the age of 5 and in individuals who are immunocompromised&#44; HIV-positive&#44; or receiving biological drugs&#44; while for the contacts study they recommend that TST be complemented by IGRA in BCG-vaccinated individuals with a positive TST<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;17</span></a>&#46; Our study included regular contacts&#44; with exposure time to the index case greater or less than 6 hours a day&#44; and sporadic&#44; who accounted for 36&#37; of the total&#46; The rate of LTBI in both groups was higher when TST and QFT were used&#44; but the difference among sporadic contacts was particularly striking &#40;54&#46;6&#37; versus 19&#46;1&#37; for TST or 30&#46;2&#37; for QFT alone&#41;&#44; suggesting that the dual strategy may be the best way of initiating the contacts study&#44; regardless of exposure intensity&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">Similarly&#44; Erkens et al&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> in a series of 10&#44;000 contacts&#44; of which 39&#37; were sporadic&#44; found that adding IGRA to TST modified the diagnosis of LTBI in 40&#37; of contacts&#46; They argue that the higher cost would be balanced by a more accurate indication for preventive treatment&#44; and consider this practice to be the most appropriate in low-prevalence countries&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Our study has some limitations&#46; Firstly&#44; its design has an inherent risk of selection bias&#46; However&#44; it should be noted that one of the main strengths of our study is that all researchers were TB experts who participate regularly in the PII-TB&#44; which we believe ensure the quality of data collection and reduces this possibility of selection bias&#46; Secondly&#44; to determine effectiveness&#44; we estimated that 10&#37; of infected contacts might develop TB over their lifetime&#44; while other studies suggest a rate of 15&#37;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a>&#59; however&#44; we do not believe that this difference reduces the validity of our results&#46; Finally&#44; we did not analyze other indirect costs&#44; such as transport or work absenteeism&#44; so the total cost may be underestimated&#44; but we should remember that this study was conducted in a country with high economic resources&#44; so the likely impact of these factors on the final results would&#44; in our opinion&#44; be marginal&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">We conclude that the study of TB contacts generates a significant health expense&#44; derived mainly from diagnostic techniques and the treatment of latent tuberculosis infection&#46; In this respect&#44; we believe that the most appropriate strategy is the sequential use of TST plus QFT in all contacts&#44; and treatment with 3HR&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Funding</span><p id="par0105" class="elsevierStylePara elsevierViewall">This study was funded by the <span class="elsevierStyleGrantSponsor" id="gs0005">Instituto de la Salud Carlos III-Fondos FEDER</span> grant <span class="elsevierStyleGrantNumber" refid="gs0005">PI17&#47;00724</span> and by the <span class="elsevierStyleGrantSponsor" id="gs0010">Spanish Society of Pulmonology and Thoracic Surgery &#40;SEPAR&#41;</span> grant <span class="elsevierStyleGrantNumber" refid="gs0010">378&#47;2017</span>&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Conflict of interests</span><p id="par0110" class="elsevierStylePara elsevierViewall">The authors state that they have no conflicts of interest&#46;</p></span></span>"
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                "apendice" => "<p id="par0120" class="elsevierStylePara elsevierViewall">Fernando &#193;lvarez Navascues &#40;Unidad de Gesti&#243;n Cl&#237;nica Neumolog&#237;a Hospital Universitario San Agust&#237;n&#44; Avil&#233;s&#44; Spain&#41;&#46; Mar&#237;a Somoza-Gonz&#225;lez &#40;Servicio de Neumolog&#237;a Consorcio Sanitario de Terrassa&#44; Terrassa&#44; Spain&#41;&#46; Christian Anchorena &#40;Servicio de Neumolog&#237;a&#44; Complexo Hospitalario de Pontevedra&#44; Pontevedra&#44; Spain&#41;&#46; &#193;ngel Dom&#237;nguez-Castellano &#40;Servicio de Enfermedades Infecciosas&#44; Hospital Universitario Virgen Macarena&#44; Seville&#44; Spain&#41;&#46; Ant&#243;n Penas-Truque &#40;Servicio de Neumolog&#237;a&#44; Hospital Universitario Lucus Augusti&#44; Lugo&#44; Spain&#41;&#46; Silvia Dorronsoro-Quintana &#40;Secci&#243;n de Neumolog&#237;a&#44; Hospital de Zum&#225;rraga&#44; Zum&#225;rraga&#44; Spain&#41;&#46; Juan-Francisco Medina-Gallardo &#40;Servicio de Neumolog&#237;a&#44; Hospital Universitario Virgen del Roc&#237;o&#44; Seville&#44; Spain&#41;&#46; Lander Altube-Urrengoetxea &#40;Servicio de Neumolog&#237;a&#44; Hospital Universitario de Galdakao&#44; Galdakao&#44; Spain&#41;&#46; Mar&#237;a Otero-Santiago &#40;Hospital Universitario de A Coru&#241;a&#44; Corunna&#44; Spain&#41;&#46; Concepci&#243;n Rodr&#237;guez-Garc&#237;a &#40;Unidad de Gesti&#243;n Cl&#237;nica Neumolog&#237;a Hospital Universitario San Agust&#237;n&#44; Avil&#233;s&#44; Spain&#41;&#46; Juan Rodr&#237;guez-L&#243;pez &#40;Secci&#243;n de Neumolog&#237;a Hospital Grande Covi&#225;n&#44; Arriondas&#44; Spain&#41;&#46;</p>"
                "titulo" => "PII-TB Research Group &#40;Integrated Research Program-TB&#41;"
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          "leyenda" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">LTBI&#58; latent tuberculosis infection&#46;</p>"
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                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Variable&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Cost &#40;&#1028;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Medical consultations</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Initial&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">120&#46;30&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Subsequent&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">72&#46;20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Blood tests &#40;blood count&#44; biochemistry with liver function tests&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23&#46;48&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Sputum smear and sputum culture</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">19&#46;66&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Plain chest X-ray</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9&#46;51&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Tuberculin skin test</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">QuantiFERON TB Gold</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">125&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">LTBI treatment</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cost &#40;&#1028;&#41; per patient&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Isoniazid for 6 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">18&#46;72&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Isoniazid plus rifampicin for 3 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">71&#46;52&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Rifampicin for 4 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">83&#46;71&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Isoniazid for 9 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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          "leyenda" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Dx&#58; diagnostic strategy&#59; LTIT&#58; latent tuberculous infection treatment&#46;</p><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Total cost&#58; calculated for 19&#44;328 contacts with an LTBI prevalence of 33&#46;4&#37;&#46; Effectiveness&#58; number of TB cases avoided&#44; assuming that 10&#37; of infected contacts will develop the disease over their lifetime&#46; ICER &#40;incremental cost-effectiveness ratio&#41;&#8239;&#61;&#8239;&#91;total cost of strategy A1-total cost of strategy A2&#93;&#47;&#91;effectiveness of strategy A1-effectiveness of strategy A2&#93;&#59; 6H&#58; isoniazid for 6 months&#59; 3HR&#58; isoniazid and rifampicin for 3 months&#59; 4R&#58; rifampicin for 4 months&#59; 9H&#58; isoniazid for 9 months&#46;</p>"
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">---------&nbsp;\t\t\t\t\t\t\n
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Scientific Letter
Tuberculosis contacts tracing in Spain: Cost analysis
Estudio de contactos de pacientes con tuberculosis en España: analisis de costes
José Antonio Gullón-Blancoa,b,
Corresponding author
josegubl@gmail.com

Corresponding author.
, Teresa Rodrigo-Sanzb, Eva Tabernero-Huguetb,c, Josefina Sabría-Mestresb,d, Luis Anibarrob,e, Manuel-Ángel Villanueva-Montesa,b, Isabel Mir-Viladrichb,f, Juan-Diego Álvarez-Mavarezg, José-María García-Garcíab, Grupo de trabajo del Programa Integrado de Investigación en Tuberculosis (PII-TB) 1
a Unidad de Gestión Clínica Neumología, Hospital Universitario San Agustín, Avilés, Spain
b Programa Integrado de Investigación en Tuberculosis (PII-TB) SEPAR, Barcelona, Spain
c Servicio de Neumología, Hospital Universitario de Cruces, Baracaldo, Spain
d Servicio de Neumología, Hospital Moisés Broggi, Sant Joan Despí, Spain
e Servicio de Medicina Interna, Complexo Hospitalario de Pontevedra, Pontevedra, Spain
f Sección de Neumología, Hospital Son Llatzer, Palma De Mallorca, Spain
g Sección de Neumología, Hospital Carmen y Severo Ochoa, Cangas del Narcea, Spain
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database&#46; Research group members were given a username and password to access the registry&#46; Twelve centers from 6 Spanish autonomous communities participated&#44; and the study was approved by all corresponding Ethics and Research Committees&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">The following definitions were established&#58;</p><p id="par0025" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Index case</span>&#58; case recognized as the source of the infection of other patients and&#47;or infected cases<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a>&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Secondary case</span>&#58; a contact diagnosed with TB&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Contact</span>&#58; person with exposure to the index case<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a>&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Latent tuberculosis infection &#40;LTBI&#41;</span>&#58; tuberculin skin test &#40;TST&#41; with induration diameter of at least 5&#8239;mm and&#47;or positive QuantiFERON TB Gold &#40;QFT&#41; with a cut-off of 0&#46;35 IU&#47;mL<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a>&#44; and no evidence of active disease&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Diagnostic strategy</span>&#58; techniques used to diagnose LTBI&#44; according to the sequence established at the discretion of the attending physician&#46; Three options were considered&#58; dual &#40;TST plus QFT combined&#41;&#59; TST alone&#59; or QFT alone&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Direct costs were extracted from the data provided by the Health Service of the Principality of Asturias<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> and the Catalan Public Health Agency<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a>&#44; 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and that LTBI treatment reduces the overall risk by between 56&#37; and 75&#37;&#44; depending on the regimen used<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a>&#46; The incremental cost-effectiveness ratio &#40;ICER&#41; was calculated to compare the different strategies&#46; When a strategy was less expensive and more effective than the baseline strategy&#44; the ICER was not calculated and that strategy was considered dominant&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">Proportions were compared using the Student&#8217;s <span class="elsevierStyleItalic">t</span>-test or its non-parametric equivalent&#44; the Mann-Whitney <span class="elsevierStyleItalic">U</span> test A <span class="elsevierStyleItalic">p</span>-value of less than &#46;05 was considered significant&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">A total of 1035 contacts of 265 index cases with a mean age of 37&#46;96&#8239;&#177;&#8239;20&#46;13 years were identified&#46; The diagnostic strategy was dual in 374 &#40;36&#46;4&#37;&#41;&#44; TST in 537 &#40;51&#46;9&#37;&#41;&#44; and QFT in 124 &#40;11&#46;7&#37;&#41;&#59; the percentage of LTBI in each group was 48&#46;2&#37;&#44; 27&#46;4&#37;&#44; and 40&#46;4&#37;&#44; respectively &#40;<span class="elsevierStyleItalic">P</span>&#8239;&#61;&#8239;&#46;01&#41;&#46; LTBI was diagnosed in 346 &#40;33&#46;4&#37;&#41; contacts and 295 started treatment&#58; 156 &#40;52&#46;9&#37;&#41; received isoniazid plus rifampicin for 3 months &#40;3HR&#41;&#44; 124 &#40;42&#37;&#41; received 6H&#44; 5 &#40;1&#46;9&#37;&#41; received rifampicin for 4 months &#40;4R&#41;&#44; and 10 &#40;3&#46;2&#37;&#41; received isoniazid for 9 months&#59; 91&#46;1&#37;&#44; 89&#46;1&#37;&#44; 80&#37;&#44; and 70&#37; completed treatment&#44; respectively &#40;<span class="elsevierStyleItalic">P</span>&#8239;&#61;&#8239;&#46;1&#41;&#46; Seventeen cases of TB were diagnosed &#40;1&#46;6&#37;&#41;&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">The total cost was &#1028;545&#44;491&#46;80&#58; &#1028;371&#44;037&#46;80 for direct costs&#44; of which 40&#46;8&#37; was for medical consultations&#44; 26&#46;1&#37; for LTBI treament&#44; and 25&#46;1&#37; for diagnostic studies&#46; The average cost per contact studied was &#1028;548&#46;23 &#40;SD 142&#46;97&#41;&#46; Dual and QFT strategies were significantly more expensive than TST but more effective&#44; and the 3HR treatment was dominant over 6H&#46; The costs of diagnosis and LTBI treatment and corresponding ICERs are shown in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">The cost per contact studied was higher than the &#1028;368&#46;23 reported in a German study<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a>&#44; but unlike our series&#44; that study did not include the costs of preventive treatment&#46; In another study conducted in Norway<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a>&#44; the average cost was &#1028;1934&#44; significantly higher than ours&#44; due to differences in the costs charged&#44; especially for medical consultations&#46; If we extrapolate our results to the approximate number of contacts to be evaluated in Spain<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a>&#44; the estimated total cost of contacts study would be &#1028;10&#46;6 million&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">With regard to LTBI treatment&#44; the 3HR regimen was less expensive and more effective&#44; confirming that it would be a better choice than 6H&#46; This was also demonstrated in a cost-effectiveness study<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> in which all short regimens&#44; including 3HR&#44; were more cost-effective than 6H&#44; although the authors&#44; unlike us&#44; found that 4R was slightly better&#59; however&#44; our results should be interpreted with caution due to the low representation of 4R in our series&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">With regard to diagnosis&#44; the dual strategy and QFT were more expensive but more effective than TST&#44; with an ICER of &#1028;8865&#46;61 and &#1028;8463&#46;57 per TB case avoided&#44; respectively&#46; If we bear in mind that health interventions with an ICER of up to &#1028;30&#44;000 are efficient<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a>&#44; both strategies would be cost-effective&#46; To determine the best option&#44; we must analyze the ICER together with the potential health benefit of the intervention&#44; &#8211; in this case&#44; identifying contacts with LTBI and offering them treatment to reduce the risk of developing TB as well the environment in which the strategy is implemented&#46; Given that the percentage of LTBI is higher when the dual strategy is used&#44; we believe that this would be the most appropriate in a country with a low incidence of disease&#44; such as Spain&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Several studies conducted in low-incidence countries have shown that the use of both interferon-&#947; release assays &#40;IGRA&#41; and TST techniques is cost-effective in certain groups such as household contacts<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;15</span></a> and health workers<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a>&#46; Spanish clinical guidelines also recommend this approach in children under the age of 5 and in individuals who are immunocompromised&#44; HIV-positive&#44; or receiving biological drugs&#44; while for the contacts study they recommend that TST be complemented by IGRA in BCG-vaccinated individuals with a positive TST<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;17</span></a>&#46; Our study included regular contacts&#44; with exposure time to the index case greater or less than 6 hours a day&#44; and sporadic&#44; who accounted for 36&#37; of the total&#46; The rate of LTBI in both groups was higher when TST and QFT were used&#44; but the difference among sporadic contacts was particularly striking &#40;54&#46;6&#37; versus 19&#46;1&#37; for TST or 30&#46;2&#37; for QFT alone&#41;&#44; suggesting that the dual strategy may be the best way of initiating the contacts study&#44; regardless of exposure intensity&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">Similarly&#44; Erkens et al&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> in a series of 10&#44;000 contacts&#44; of which 39&#37; were sporadic&#44; found that adding IGRA to TST modified the diagnosis of LTBI in 40&#37; of contacts&#46; They argue that the higher cost would be balanced by a more accurate indication for preventive treatment&#44; and consider this practice to be the most appropriate in low-prevalence countries&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Our study has some limitations&#46; Firstly&#44; its design has an inherent risk of selection bias&#46; However&#44; it should be noted that one of the main strengths of our study is that all researchers were TB experts who participate regularly in the PII-TB&#44; which we believe ensure the quality of data collection and reduces this possibility of selection bias&#46; Secondly&#44; to determine effectiveness&#44; we estimated that 10&#37; of infected contacts might develop TB over their lifetime&#44; while other studies suggest a rate of 15&#37;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a>&#59; however&#44; we do not believe that this difference reduces the validity of our results&#46; Finally&#44; we did not analyze other indirect costs&#44; such as transport or work absenteeism&#44; so the total cost may be underestimated&#44; but we should remember that this study was conducted in a country with high economic resources&#44; so the likely impact of these factors on the final results would&#44; in our opinion&#44; be marginal&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">We conclude that the study of TB contacts generates a significant health expense&#44; derived mainly from diagnostic techniques and the treatment of latent tuberculosis infection&#46; In this respect&#44; we believe that the most appropriate strategy is the sequential use of TST plus QFT in all contacts&#44; and treatment with 3HR&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Funding</span><p id="par0105" class="elsevierStylePara elsevierViewall">This study was funded by the <span class="elsevierStyleGrantSponsor" id="gs0005">Instituto de la Salud Carlos III-Fondos FEDER</span> grant <span class="elsevierStyleGrantNumber" refid="gs0005">PI17&#47;00724</span> and by the <span class="elsevierStyleGrantSponsor" id="gs0010">Spanish Society of Pulmonology and Thoracic Surgery &#40;SEPAR&#41;</span> grant <span class="elsevierStyleGrantNumber" refid="gs0010">378&#47;2017</span>&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Conflict of interests</span><p id="par0110" class="elsevierStylePara elsevierViewall">The authors state that they have no conflicts of interest&#46;</p></span></span>"
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                "apendice" => "<p id="par0120" class="elsevierStylePara elsevierViewall">Fernando &#193;lvarez Navascues &#40;Unidad de Gesti&#243;n Cl&#237;nica Neumolog&#237;a Hospital Universitario San Agust&#237;n&#44; Avil&#233;s&#44; Spain&#41;&#46; Mar&#237;a Somoza-Gonz&#225;lez &#40;Servicio de Neumolog&#237;a Consorcio Sanitario de Terrassa&#44; Terrassa&#44; Spain&#41;&#46; Christian Anchorena &#40;Servicio de Neumolog&#237;a&#44; Complexo Hospitalario de Pontevedra&#44; Pontevedra&#44; Spain&#41;&#46; &#193;ngel Dom&#237;nguez-Castellano &#40;Servicio de Enfermedades Infecciosas&#44; Hospital Universitario Virgen Macarena&#44; Seville&#44; Spain&#41;&#46; Ant&#243;n Penas-Truque &#40;Servicio de Neumolog&#237;a&#44; Hospital Universitario Lucus Augusti&#44; Lugo&#44; Spain&#41;&#46; Silvia Dorronsoro-Quintana &#40;Secci&#243;n de Neumolog&#237;a&#44; Hospital de Zum&#225;rraga&#44; Zum&#225;rraga&#44; Spain&#41;&#46; Juan-Francisco Medina-Gallardo &#40;Servicio de Neumolog&#237;a&#44; Hospital Universitario Virgen del Roc&#237;o&#44; Seville&#44; Spain&#41;&#46; Lander Altube-Urrengoetxea &#40;Servicio de Neumolog&#237;a&#44; Hospital Universitario de Galdakao&#44; Galdakao&#44; Spain&#41;&#46; Mar&#237;a Otero-Santiago &#40;Hospital Universitario de A Coru&#241;a&#44; Corunna&#44; Spain&#41;&#46; Concepci&#243;n Rodr&#237;guez-Garc&#237;a &#40;Unidad de Gesti&#243;n Cl&#237;nica Neumolog&#237;a Hospital Universitario San Agust&#237;n&#44; Avil&#233;s&#44; Spain&#41;&#46; Juan Rodr&#237;guez-L&#243;pez &#40;Secci&#243;n de Neumolog&#237;a Hospital Grande Covi&#225;n&#44; Arriondas&#44; Spain&#41;&#46;</p>"
                "titulo" => "PII-TB Research Group &#40;Integrated Research Program-TB&#41;"
                "identificador" => "sec0020"
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          "leyenda" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">LTBI&#58; latent tuberculosis infection&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Variable&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Cost &#40;&#1028;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Medical consultations</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Initial&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">120&#46;30&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Subsequent&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">72&#46;20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Blood tests &#40;blood count&#44; biochemistry with liver function tests&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23&#46;48&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Sputum smear and sputum culture</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">19&#46;66&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Plain chest X-ray</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9&#46;51&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Tuberculin skin test</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">QuantiFERON TB Gold</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">125&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">LTBI treatment</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cost &#40;&#1028;&#41; per patient&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Isoniazid for 6 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">18&#46;72&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Isoniazid plus rifampicin for 3 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">71&#46;52&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Rifampicin for 4 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">83&#46;71&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Isoniazid for 9 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">28&#46;08&nbsp;\t\t\t\t\t\t\n
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Indirect costs&#46;</p>"
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          "leyenda" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Dx&#58; diagnostic strategy&#59; LTIT&#58; latent tuberculous infection treatment&#46;</p><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Total cost&#58; calculated for 19&#44;328 contacts with an LTBI prevalence of 33&#46;4&#37;&#46; Effectiveness&#58; number of TB cases avoided&#44; assuming that 10&#37; of infected contacts will develop the disease over their lifetime&#46; ICER &#40;incremental cost-effectiveness ratio&#41;&#8239;&#61;&#8239;&#91;total cost of strategy A1-total cost of strategy A2&#93;&#47;&#91;effectiveness of strategy A1-effectiveness of strategy A2&#93;&#59; 6H&#58; isoniazid for 6 months&#59; 3HR&#58; isoniazid and rifampicin for 3 months&#59; 4R&#58; rifampicin for 4 months&#59; 9H&#58; isoniazid for 9 months&#46;</p>"
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                  \t\t\t\t">---------&nbsp;\t\t\t\t\t\t\n
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ISSN: 03002896
Original language: English
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