{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:19:27Z","timestamp":1792801167346,"version":"4.5.0"},"reference-count":58,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2018,12,1]],"date-time":"2018-12-01T00:00:00Z","timestamp":1543622400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Wellcome Trust","award":["MR\/M007340\/1"],"award-info":[{"award-number":["MR\/M007340\/1"]}],"id":[{"id":"https:\/\/ror.org\/029chgv08","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Medical Research Council","award":["MR\/M007340\/1"],"award-info":[{"award-number":["MR\/M007340\/1"]}]},{"DOI":"10.13039\/501100000278","name":"Department for International Development","doi-asserted-by":"publisher","award":["MR\/M007340\/1"],"award-info":[{"award-number":["MR\/M007340\/1"]}],"id":[{"id":"10.13039\/501100000278","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001322","name":"South African Medical Research Council","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001322","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Trials"],"published-print":{"date-parts":[[2018,12]]},"DOI":"10.1186\/s13063-018-3070-0","type":"journal-article","created":{"date-parts":[[2018,12,20]],"date-time":"2018-12-20T09:05:54Z","timestamp":1545296754000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["Levofloxacin versus placebo for the prevention of tuberculosis disease in child contacts of multidrug-resistant tuberculosis: study protocol for a phase III cluster randomised controlled trial (TB-CHAMP)"],"prefix":"10.1186","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2296-2302","authenticated-orcid":false,"given":"James A.","family":"Seddon","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony J.","family":"Garcia-Prats","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan E.","family":"Purchase","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Osman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne-Marie","family":"Demers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graeme","family":"Hoddinott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela M.","family":"Crook","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen","family":"Owen-Powell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret J.","family":"Thomason","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Turkova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana M.","family":"Gibb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee","family":"Fairlie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil","family":"Martinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. Simon","family":"Schaaf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anneke C.","family":"Hesseling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,12,20]]},"reference":[{"issue":"1","key":"3070_CR1","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1086\/595012","volume":"48","author":"AC Hesseling","year":"2009","unstructured":"Hesseling AC, Cotton MF, Jennings T, et al. High incidence of tuberculosis among HIV-infected infants: evidence from a South African population-based study highlights the need for improved tuberculosis control strategies. Clin Infect Dis. 2009;48(1):108\u201314.","journal-title":"Clin Infect Dis"},{"issue":"4","key":"3070_CR2","first-page":"392","volume":"8","author":"BJ Marais","year":"2004","unstructured":"Marais BJ, Gie RP, Schaaf HS, et al. The natural history of childhood intra-thoracic tuberculosis: a critical review of literature from the pre-chemotherapy era. Int J Tuberc Lung Dis. 2004;8(4):392\u2013402.","journal-title":"Int J Tuberc Lung Dis"},{"key":"3070_CR3","unstructured":"World Health Organization, Geneva, Switzerland. Global Tuberculosis Report 2018. Available at: \n                    http:\/\/apps.who.int\/iris\/bitstream\/handle\/10665\/274453\/9789241565646-eng.pdf?ua=1\n                    \n                  . Accessed 6 Dec 2018"},{"issue":"10","key":"3070_CR4","doi-asserted-by":"publisher","first-page":"1193","DOI":"10.1016\/S1473-3099(16)30132-3","volume":"16","author":"PJ Dodd","year":"2016","unstructured":"Dodd PJ, Sismanidis C, Seddon JA. Global burden of drug-resistant tuberculosis in children: a mathematical modelling study. Lancet Infect Dis. 2016;16(10):1193\u2013201.","journal-title":"Lancet Infect Dis"},{"key":"3070_CR5","first-page":"28","volume":"26","author":"SH Ferebee","year":"1970","unstructured":"Ferebee SH. Controlled chemoprophylaxis trials in tuberculosis. A general review. Bibl Tuberc. 1970;26:28\u2013106.","journal-title":"Bibl Tuberc"},{"issue":"6","key":"3070_CR6","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1016\/S1473-3099(12)70033-6","volume":"12","author":"D Ettehad","year":"2012","unstructured":"Ettehad D, Schaaf HS, Seddon JA, Cooke GS, Ford N. Treatment outcomes for children with multidrug-resistant tuberculosis: a systematic review and meta-analysis. Lancet Infect Dis. 2012;12(6):449\u201356.","journal-title":"Lancet Infect Dis"},{"issue":"8","key":"3070_CR7","doi-asserted-by":"publisher","first-page":"e1001300","DOI":"10.1371\/journal.pmed.1001300","volume":"9","author":"SD Ahuja","year":"2012","unstructured":"Ahuja SD, Ashkin D, Avendano M, et al. Multidrug resistant pulmonary tuberculosis treatment regimens and patient outcomes: an individual patient data meta-analysis of 9,153 patients. PLoS Med. 2012;9(8):e1001300.","journal-title":"PLoS Med"},{"issue":"9","key":"3070_CR8","doi-asserted-by":"publisher","first-page":"1191","DOI":"10.5588\/ijtld.10.0707","volume":"15","author":"S Thee","year":"2011","unstructured":"Thee S, Zollner EW, Willemse M, Hesseling AC, Magdorf K, Schaaf HS. Abnormal thyroid function tests in children on ethionamide treatement (short communication). Int J Tuberc Lung Dis. 2011;15(9):1191\u20133.","journal-title":"Int J Tuberc Lung Dis"},{"key":"3070_CR9","doi-asserted-by":"publisher","first-page":"458","DOI":"10.1136\/thoraxjnl-2013-203900","volume":"69","author":"JA Seddon","year":"2014","unstructured":"Seddon JA, Hesseling AC, Godfrey-Faussett P, Schaaf HS. High treatment success in children treated for multidrug-resistant tuberculosis: an observational cohort study. Thorax. 2014;69:458\u201364.","journal-title":"Thorax"},{"issue":"4","key":"3070_CR10","first-page":"320","volume":"66","author":"JA Seddon","year":"2013","unstructured":"Seddon JA, Thee S, Jacobs K, Ebrahim A, Hesseling AC, Schaaf HS. Hearing loss in children treated for multidrug-resistant tuberculosis. J Inf Secur. 2013;66(4):320\u20139.","journal-title":"J Inf Secur"},{"issue":"7","key":"3070_CR11","doi-asserted-by":"publisher","first-page":"e241","DOI":"10.1371\/journal.pmed.0030241","volume":"3","author":"SC Resch","year":"2006","unstructured":"Resch SC, Salomon JA, Murray M, Weinstein MC. Cost-effectiveness of treating multidrug-resistant tuberculosis. PLoS Med. 2006;3(7):e241.","journal-title":"PLoS Med"},{"issue":"9","key":"3070_CR12","doi-asserted-by":"publisher","first-page":"e352","DOI":"10.1371\/journal.pmed.0030352","volume":"3","author":"TE Tupasi","year":"2006","unstructured":"Tupasi TE, Gupta R, Quelapio MI, et al. Feasibility and cost-effectiveness of treating multidrug-resistant tuberculosis: a cohort study in the Philippines. PLoS Med. 2006;3(9):e352.","journal-title":"PLoS Med"},{"issue":"RR-11","key":"3070_CR13","first-page":"61","volume":"41","author":"Centres for Disease Control, Atlanta, Georgia, USA","year":"1992","unstructured":"Centres for Disease Control, Atlanta, Georgia, USA. Management of persons exposed to multidrug-resistant tuberculosis. MMWR Recomm Rep. 1992;41(RR-11):61\u201371.","journal-title":"MMWR Recomm Rep"},{"key":"3070_CR14","volume-title":"Management of contacts of MDR TB and XDR TB patients","author":"European Centre for Disease Prevention and Control","year":"2012","unstructured":"European Centre for Disease Prevention and Control. Management of contacts of MDR TB and XDR TB patients. 2012. \n                    http:\/\/ecdc.europa.eu\/en\/publications\/Publications\/201203-Guidance-MDR-TB-contacts.pdf\n                    \n                  . Accessed July 2013."},{"issue":"5","key":"3070_CR15","first-page":"648","volume":"8","author":"SM Graham","year":"2004","unstructured":"Graham SM, Gie RP, Schaaf HS, Coulter JB, Espinal MA, Beyers N. Childhood tuberculosis: clinical research needs. Int J Tuberc Lung Dis. 2004;8(5):648\u201357.","journal-title":"Int J Tuberc Lung Dis"},{"issue":"7","key":"3070_CR16","doi-asserted-by":"publisher","first-page":"e150","DOI":"10.1371\/journal.pmed.0050150","volume":"5","author":"FG Cobelens","year":"2008","unstructured":"Cobelens FG, Heldal E, Kimerling ME, et al. Scaling up programmatic management of drug-resistant tuberculosis: a prioritized research agenda. PLoS Med. 2008;5(7):e150.","journal-title":"PLoS Med"},{"issue":"10","key":"3070_CR17","doi-asserted-by":"publisher","first-page":"1078","DOI":"10.1164\/rccm.200511-1809SO","volume":"173","author":"BJ Marais","year":"2006","unstructured":"Marais BJ, Gie RP, Schaaf HS, Beyers N, Donald PR, Starke JR. Childhood pulmonary tuberculosis: old wisdom and new challenges. Am J Respir Crit Care Med. 2006;173(10):1078\u201390.","journal-title":"Am J Respir Crit Care Med"},{"issue":"12","key":"3070_CR18","first-page":"1370","volume":"12","author":"F Scano","year":"2008","unstructured":"Scano F, Vitoria M, Burman W, Harries AD, Gilks CF, Havlir D. Management of HIV-infected patients with MDR- and XDR-TB in resource-limited settings. Int J Tuberc Lung Dis. 2008;12(12):1370\u20135.","journal-title":"Int J Tuberc Lung Dis"},{"key":"3070_CR19","volume-title":"Report on the RESIST-TB Protocol Workshop, 5\u20136 October","author":"RESIST-TB","year":"2017","unstructured":"RESIST-TB. Report on the RESIST-TB Protocol Workshop, 5\u20136 October. 2017. \n                    http:\/\/www.resisttb.org\/uploads\/RESIST-TB_Protocol_Workshop_summary.pdf\n                    \n                  . Accessed 29 May 2011."},{"key":"3070_CR20","volume-title":"Report of the Technical Consultation on the Programmatic Management of Latent Tuberculosis Infection","author":"World Health Organization","year":"2017","unstructured":"World Health Organization. Report of the Technical Consultation on the Programmatic Management of Latent Tuberculosis Infection. Geneva: WHO; 2017. \n                    http:\/\/apps.who.int\/iris\/bitstream\/10665\/259380\/1\/WHO-HTM-TB-2017.27-eng.pdf\n                    \n                  . Accessed 15 Dec 2017"},{"issue":"7585","key":"3070_CR21","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1136\/bmj.39000.486400.55","volume":"334","author":"HJ Zar","year":"2007","unstructured":"Zar HJ, Cotton MF, Strauss S, et al. Effect of isoniazid prophylaxis on mortality and incidence of tuberculosis in children with HIV: randomised controlled trial. BMJ. 2007;334(7585):136.","journal-title":"BMJ"},{"key":"3070_CR22","first-page":"CD001363","volume":"2","author":"MJ Smieja","year":"2000","unstructured":"Smieja MJ, Marchetti CA, Cook DJ, Smaill FM. Isoniazid for preventing tuberculosis in non-HIV infected persons. Cochrane Database Syst Rev. 2000;2:CD001363.","journal-title":"Cochrane Database Syst Rev"},{"issue":"4 Pt 2","key":"3070_CR23","first-page":"S221","volume":"161","author":"CDC\/ATA\/IDSA","year":"2000","unstructured":"CDC\/ATA\/IDSA. Targeted tuberculin testing and treatment of latent tuberculosis infection. This official statement of the American Thoracic Society was adopted by the ATS Board of Directors, July 1999. This is a Joint Statement of the American Thoracic Society (ATS) and the Centers for Disease Control and Prevention (CDC). This statement was endorsed by the Council of the Infectious Diseases Society of America. (IDSA), September 1999, and the sections of this statement. Am J Respir Crit Care Med. 2000;161(4 Pt 2):S221\u201347.","journal-title":"Am J Respir Crit Care Med"},{"key":"3070_CR24","first-page":"CD006418","volume":"1","author":"DM Gray","year":"2009","unstructured":"Gray DM, Zar H, Cotton M. Impact of tuberculosis preventive therapy on tuberculosis and mortality in HIV-infected children. Cochrane Database Syst Rev. 2009;1:CD006418.","journal-title":"Cochrane Database Syst Rev"},{"key":"3070_CR25","first-page":"CD005435","volume":"2","author":"A Fraser","year":"2006","unstructured":"Fraser A, Paul M, Attamna A, Leibovici L. Drugs for preventing tuberculosis in people at risk of multiple-drug-resistant pulmonary tuberculosis. Cochrane Database Syst Rev. 2006;2:CD005435.","journal-title":"Cochrane Database Syst Rev"},{"issue":"12","key":"3070_CR26","doi-asserted-by":"publisher","first-page":"1670","DOI":"10.1093\/cid\/cix208","volume":"64","author":"SM Marks","year":"2017","unstructured":"Marks SM, Mase SR, Morris SB. Systematic review, meta-analysis, and cost-effectiveness of treatment of latent tuberculosis to reduce progression to multidrug-resistant tuberculosis. Clin Infect Dis. 2017;64(12):1670\u20137.","journal-title":"Clin Infect Dis"},{"issue":"8","key":"3070_CR27","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1097\/00006454-200008000-00005","volume":"19","author":"HS Schaaf","year":"2000","unstructured":"Schaaf HS, Van Rie A, Gie RP, et al. Transmission of multidrug-resistant tuberculosis. Pediatr Infect Dis J. 2000;19(8):695\u20139.","journal-title":"Pediatr Infect Dis J"},{"issue":"3","key":"3070_CR28","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1093\/cid\/cit709","volume":"58","author":"JB Parr","year":"2014","unstructured":"Parr JB, Mitnick CD, Atwood SS, Chalco K, Bayona J, Becerra MC. Concordance of resistance profiles in households of patients with multidrug-resistant tuberculosis. Clin Infect Dis. 2014;58(3):392\u20135.","journal-title":"Clin Infect Dis"},{"issue":"3","key":"3070_CR29","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1093\/cid\/cit643","volume":"58","author":"NS Shah","year":"2014","unstructured":"Shah NS, Yuen CM, Heo M, Tolman AW, Becerra MC. Yield of contact investigations in households of patients with drug-resistant tuberculosis: systematic review and meta-analysis. Clin Infect Dis. 2014;58(3):381\u201391.","journal-title":"Clin Infect Dis"},{"key":"3070_CR30","volume-title":"Guidance for national tuberculosis programme on the management of tuberculosis in children (Second edition)","author":"World Health Organization","year":"2014","unstructured":"World Health Organization. Guidance for national tuberculosis programme on the management of tuberculosis in children (Second edition). Geneva: WHO; 2014. \n                    http:\/\/apps.who.int\/iris\/bitstream\/10665\/112360\/1\/9789241548748_eng.pdf?ua=1\n                    \n                  . Accessed 11 Jun 2018"},{"key":"3070_CR31","unstructured":"World Health Organization. Guidelines on the management of latent tuberculosis infection (WHO\/HTM\/TB\/2015.01). Geneva: WHO; 2015. \n                    http:\/\/apps.who.int\/iris\/bitstream\/handle\/10665\/136471\/9789241548908_eng.pdf?sequence=1\n                    \n                  . Accessed 11 Jun 2018"},{"issue":"10","key":"3070_CR32","doi-asserted-by":"publisher","first-page":"3459","DOI":"10.1128\/JCM.00973-08","volume":"46","author":"M Mphahlele","year":"2008","unstructured":"Mphahlele M, Syre H, Valvatne H, et al. Pyrazinamide resistance among South African multidrug-resistant Mycobacterium tuberculosis isolates. J Clin Microbiol. 2008;46(10):3459\u201364.","journal-title":"J Clin Microbiol"},{"issue":"11","key":"3070_CR33","first-page":"785","volume":"99","author":"KG Hoek","year":"2009","unstructured":"Hoek KG, Schaaf HS, Gey van Pittius NC, van Helden PD, Warren RM. Resistance to pyrazinamide and ethambutol compromises MDR\/XDR-TB treatment. S Afr Med J. 2009;99(11):785\u20137.","journal-title":"S Afr Med J"},{"key":"3070_CR34","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/0378-4274(77)90016-9","volume":"1","author":"B Ingham","year":"1977","unstructured":"Ingham B, Brentnall D, Dale E, McFadzean J. Arthropathy induced by antibacerial fused N-Alkyl-4-pyridone-3-carboxylic acids. Toxicol Lett. 1977;1:21\u20136.","journal-title":"Toxicol Lett"},{"issue":"12","key":"3070_CR35","doi-asserted-by":"publisher","first-page":"1676","DOI":"10.1093\/cid\/cit655","volume":"57","author":"JA Seddon","year":"2013","unstructured":"Seddon JA, Hesseling AC, Finlayson H, et al. Preventive therapy for child contacts of multidrug-resistant tuberculosis: a prospective cohort study. Clin Infect Dis. 2013;57(12):1676\u201384.","journal-title":"Clin Infect Dis"},{"issue":"6","key":"3070_CR36","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1017\/S1481803500015517","volume":"9","author":"CT Forsythe","year":"2007","unstructured":"Forsythe CT, Ernst ME. Do fluoroquinolones commonly cause arthropathy in children? CJEM. 2007;9(6):459\u201362.","journal-title":"CJEM"},{"issue":"5","key":"3070_CR37","doi-asserted-by":"publisher","first-page":"1196","DOI":"10.1086\/516119","volume":"25","author":"JE Burkhardt","year":"1997","unstructured":"Burkhardt JE, Walterspiel JN, Schaad UB. Quinolone arthropathy in animals versus children. Clin Infect Dis. 1997;25(5):1196\u2013204.","journal-title":"Clin Infect Dis"},{"issue":"6","key":"3070_CR38","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1097\/00006454-200206000-00009","volume":"21","author":"CL Yee","year":"2002","unstructured":"Yee CL, Duffy C, Gerbino PG, Stryker S, Noel GJ. Tendon or joint disorders in children after treatment with fluoroquinolones or azithromycin. Pediatr Infect Dis J. 2002;21(6):525\u20139.","journal-title":"Pediatr Infect Dis J"},{"issue":"10","key":"3070_CR39","doi-asserted-by":"publisher","first-page":"2281","DOI":"10.1093\/jac\/dkr281","volume":"66","author":"R Cremades","year":"2011","unstructured":"Cremades R, Rodriguez JC, Garcia-Pachon E, et al. Comparison of the bactericidal activity of various fluoroquinolones against Mycobacterium tuberculosis in an in vitro experimental model. J Antimicrob Chemother. 2011;66(10):2281\u20133.","journal-title":"J Antimicrob Chemother"},{"key":"3070_CR40","volume-title":"World Health Organization Public Assessment Report on Moxifloxacin. Part 3: Patient Information Leaflet","author":"World Health Organization","year":"2017","unstructured":"World Health Organization. World Health Organization Public Assessment Report on Moxifloxacin. Part 3: Patient Information Leaflet. Geneva: WHO; 2017. \n                    https:\/\/extranet.who.int\/prequal\/sites\/default\/files\/TB286part3v1.pdf\n                    \n                  . Accessed 31 Jul 2018"},{"issue":"5","key":"3070_CR41","doi-asserted-by":"publisher","first-page":"2948","DOI":"10.1128\/AAC.02755-13","volume":"58","author":"S Thee","year":"2014","unstructured":"Thee S, Garcia-Prats AJ, McIlleron HM, et al. Pharmacokinetics of ofloxacin and levofloxacin for prevention and treatment of multidrug-resistant tuberculosis in children. Antimicrob Agents Chemother. 2014;58(5):2948\u201351.","journal-title":"Antimicrob Agents Chemother"},{"issue":"1","key":"3070_CR42","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.tube.2011.11.001","volume":"92","author":"JA Seddon","year":"2012","unstructured":"Seddon JA, Hesseling AC, Marais BJ, et al. Paediatric use of second-line anti-tuberculosis agents: A review. Tuberculosis (Edinb). 2012;92(1):9\u201317.","journal-title":"Tuberculosis (Edinb)"},{"issue":"11","key":"3070_CR43","first-page":"1355","volume":"13","author":"HS Schaaf","year":"2009","unstructured":"Schaaf HS, Victor TC, Venter A, et al. Ethionamide cross- and co-resistance in children with isoniazid-resistant tuberculosis. Int J Tuberc Lung Dis. 2009;13(11):1355\u20139.","journal-title":"Int J Tuberc Lung Dis"},{"issue":"3","key":"3070_CR44","doi-asserted-by":"publisher","first-page":"e0119628","DOI":"10.1371\/journal.pone.0119628","volume":"10","author":"M Seifert","year":"2015","unstructured":"Seifert M, Catanzaro D, Catanzaro A, Rodwell TC. Genetic mutations associated with isoniazid resistance in Mycobacterium tuberculosis: a systematic review. PLoS One. 2015;10(3):e0119628.","journal-title":"PLoS One"},{"key":"3070_CR45","volume-title":"The use of delamanid in the treatment of multidrug-resistant tuberculosis in children and adolescents: Interim policy guidance","author":"World Health Organization","year":"2016","unstructured":"World Health Organization. The use of delamanid in the treatment of multidrug-resistant tuberculosis in children and adolescents: Interim policy guidance. Geneva: WHO; 2016. \n                    http:\/\/apps.who.int\/iris\/bitstream\/10665\/250614\/1\/9789241549899-eng.pdf?ua=1\n                    \n                  . Accessed 21 Feb 2017"},{"issue":"5","key":"3070_CR46","doi-asserted-by":"publisher","first-page":"744","DOI":"10.3201\/eid1205.050681","volume":"12","author":"ME Balcells","year":"2006","unstructured":"Balcells ME, Thomas SL, Godfrey-Faussett P, Grant AD. Isoniazid preventive therapy and risk for resistant tuberculosis. Emerg Infect Dis. 2006;12(5):744\u201351.","journal-title":"Emerg Infect Dis"},{"key":"3070_CR47","volume-title":"The 2013 National Antenatal Sentinel HIV Prevalence Survey South Africa","author":"Department of Health","year":"2013","unstructured":"Department of Health. The 2013 National Antenatal Sentinel HIV Prevalence Survey South Africa. Johannesburg: Department of Health; 2013. \n                    https:\/\/www.health-e.org.za\/wp-content\/uploads\/2016\/03\/Dept-Health-HIV-High-Res-7102015.pdf\n                    \n                  . Accessed Aug 2017"},{"issue":"8","key":"3070_CR48","doi-asserted-by":"publisher","first-page":"1033","DOI":"10.5588\/ijtld.12.0027","volume":"16","author":"AM Mandalakas","year":"2012","unstructured":"Mandalakas AM, Kirchner HL, Lombard C, et al. Well-quantified tuberculosis exposure is a reliable surrogate measure of tuberculosis infection. Int J Tuberc Lung Dis. 2012;16(8):1033\u20139.","journal-title":"Int J Tuberc Lung Dis"},{"issue":"2","key":"3070_CR49","doi-asserted-by":"publisher","first-page":"157","DOI":"10.5588\/ijtld.11.0393","volume":"16","author":"SS Wyk Van","year":"2012","unstructured":"Van Wyk SS, Mandalakas AM, Enarson DA, Gie RP, Beyers N, Hesseling AC. Tuberculosis contact investigation in a high-burden setting: house or household? Int J Tuberc Lung Dis. 2012;16(2):157\u201362.","journal-title":"Int J Tuberc Lung Dis"},{"key":"3070_CR50","unstructured":"World Health Organization. Companion handbook to the WHO guidelines for the programmatic management of drug-resistant tuberculosis. Geneva: WHO; 2014. \n                    http:\/\/apps.who.int\/iris\/bitstream\/handle\/10665\/130918\/9789241548809_eng.pdf?sequence=1\n                    \n                  . Accessed 20 Oct 2017"},{"issue":"2","key":"3070_CR51","doi-asserted-by":"publisher","first-page":"e01521","DOI":"10.1128\/AAC.01521-17","volume":"62","author":"P Denti","year":"2018","unstructured":"Denti P, Garcia-Prats AJ, Draper HR, et al. Levofloxacin population pharmacokinetics in South African children treated for multidrug-resistant tuberculosis. Antimicrob Agents Chemother. 2018;62(2):e01521\u201317. \n                    https:\/\/doi.org\/10.1128\/AAC.01521-17\n                    \n                  .","journal-title":"Antimicrob Agents Chemother"},{"key":"3070_CR52","volume-title":"Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events. Version 2.1","author":"Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, US Department of Health and Human Services","year":"2017","unstructured":"Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, US Department of Health and Human Services. Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events. Version 2.1. Washington: National Institutes of Health, US Department of Health and Human Services; 2017. \n                    https:\/\/rsc.tech-res.com\/docs\/default-source\/safety\/daids-ae-grading-table-mar2017.pdf\n                    \n                  . Accessed 11 Jun 2018"},{"key":"3070_CR53","doi-asserted-by":"publisher","first-page":"1777","DOI":"10.1093\/cid\/ciy416","volume":"67","author":"AJ Garcia-Prats","year":"2018","unstructured":"Garcia-Prats AJ, Draper HR, Finlayson H, et al. Clinical and cardiac safety of long-term levofloxacin in children treated for multidrug-resistant tuberculosis. Clin Infect Dis. 2018;67:1777\u201380. \n                    https:\/\/doi.org\/10.1093\/cid\/ciy416\n                    \n                  .","journal-title":"Clin Infect Dis"},{"issue":"5","key":"3070_CR54","doi-asserted-by":"publisher","first-page":"765","DOI":"10.1542\/peds.109.5.765","volume":"109","author":"HS Schaaf","year":"2002","unstructured":"Schaaf HS, Gie RP, Kennedy M, Beyers N, Hesseling PB, Donald PR. Evaluation of young children in contact with adult multidrug-resistant pulmonary tuberculosis: a 30-month follow-up. Pediatrics. 2002;109(5):765\u201371.","journal-title":"Pediatrics"},{"issue":"6","key":"3070_CR55","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1038\/bjc.1976.220","volume":"34","author":"R Peto","year":"1976","unstructured":"Peto R, Pike MC, Armitage P, et al. Design and analysis of randomized clinical trials requiring prolonged observation of each patient. I. Introduction and design. Br J Cancer. 1976;34(6):585\u2013612.","journal-title":"Br J Cancer"},{"issue":"526","key":"3070_CR56","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1259\/0007-1285-44-526-793","volume":"44","author":"JL Haybittle","year":"1971","unstructured":"Haybittle JL. Repeated assessment of results in clinical trials of cancer treatment. Br J Radiol. 1971;44(526):793\u20137.","journal-title":"Br J Radiol"},{"issue":"Suppl 3","key":"3070_CR57","doi-asserted-by":"publisher","first-page":"S179","DOI":"10.1093\/cid\/civ581","volume":"61","author":"SM Graham","year":"2015","unstructured":"Graham SM, Cuevas LE, Jean-Philippe P, et al. Clinical Case Definitions for Classification of Intrathoracic Tuberculosis in Children: An Update. Clin Infect Dis. 2015;61(Suppl 3):S179\u201387.","journal-title":"Clin Infect Dis"},{"issue":"9","key":"3070_CR58","doi-asserted-by":"publisher","first-page":"1249","DOI":"10.5588\/ijtld.15.0051","volume":"20","author":"HS Schaaf","year":"2016","unstructured":"Schaaf HS, Garcia-Prats AJ, du Preez K, Rautenbach C, Hesseling AC. Surveillance provides insight into epidemiology and spectrum of culture-confirmed mycobacterial disease in children. Int J Tuberc Lung Dis. 2016;20(9):1249\u201356.","journal-title":"Int J Tuberc Lung Dis"}],"container-title":["Trials"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13063-018-3070-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s13063-018-3070-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13063-018-3070-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,5,20]],"date-time":"2020-05-20T12:20:35Z","timestamp":1589977235000},"score":1,"resource":{"primary":{"URL":"https:\/\/trialsjournal.biomedcentral.com\/articles\/10.1186\/s13063-018-3070-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,12]]},"references-count":58,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2018,12]]}},"alternative-id":["3070"],"URL":"https:\/\/doi.org\/10.1186\/s13063-018-3070-0","relation":{},"ISSN":["1745-6215"],"issn-type":[{"value":"1745-6215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,12]]},"assertion":[{"value":"20 December 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 November 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 December 2018","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The trial has been approved by the Stellenbosch University Human Research Ethics Committee (M16\/02\/009) and the University of the Witwatersrand Ethics Committee (160409).","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The authors declare that they have no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Publisher\u2019s Note"}}],"article-number":"693"}}