Newer Drugs for Tuberculosis Prevention and Treatment in Children
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Children suffer a huge and often an unrecognized burden of tuberculosis (TB) in endemic countries like India. Better data have improved the visibility of childhood TB, but the establishment of functional TB prevention and treatment programs for children remains challenging. Barriers to TB prevention include: 1) non-implementation of existing guidelines, 2) perceived inability to rule out active TB with fear of creating drug resistance and 3) limited local guidance on the use of preventive therapy after close contact with drug resistant TB. Barriers to TB treatment include: 1) diagnostic challenges in resource-limited settings, 2) presentation to maternal and child health (MCH) services with poor linkage to the TB control program and 3) limited local guidance on the treatment of children with likely drug resistant TB. The authors provide an overview of newer drugs used for TB prevention and treatment in children. They discuss new options for the treatment of latent TB infection (LTBI) and new or repurposed drugs used in the treatment of children with multidrug resistant (MDR)-TB. The background information provided describes the benefits, risks and feasibility of various treatment options, which should assist treatment decisions until updated World Health Organization (WHO) guidance becomes available.
KeywordsTuberculosis Latent tuberculosis infection Treatment Prevention Therapy
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- 1.Global tuberculosis report 2017. World Health Organization, Geneva, Switzerland. Available at: www.who.int/tb/publications/global_report/en/. Accessed 6th September 2018.
- 2.Jenkins HE, Yuen CM, Rodriguez CA, et al. Mortality in children diagnosed with tuberculosis: a systematic review and meta-analysis. Lancet Infect Dis. 2017;17:285–95.Google Scholar
- 5.Jenkins HE, Tolman AW, Yuen CM, et al. Incidence of multidrug-resistant tuberculosis disease in children: systematic review and global estimates. Lancet. 2014;383:1572–9.Google Scholar
- 7.Harausz EP, Garcia-Prats AJ, Law S, et al. Treatment and outcomes in children with multidrug-resistant tuberculosis: a systematic review and individual patient data meta-analysis. PLoS Med. 2018;15:e1002591.Google Scholar
- 13.Latent TB Infection: Updated and consolidated guidelines for programmatic management 2018. World Health Organization, Geneva, Switzerland Available at: www.whoint/tb/publications/2018/latent-tuberculosis-infection/en/. Accessed 6th September 2018.
- 14.Hong Kong Chest Service. A double-blind placebo-controlled clinical trial of three antituberculosis chemoprophylaxis regimens in patients with silicosis in Hong Kong. Hong Kong chest service/tuberculosis research Centre, Madras/British Medical Research Council. Am Rev Respir Dis. 1992;145:36–41.CrossRefGoogle Scholar
- 15.Menzies D, Long R, Trajman A, et al. Adverse events with 4 months of rifampin therapy or 9 months of isoniazid therapy for latent tuberculosis infection: a randomized trial. Ann Intern Med. 2008;149:689–97.Google Scholar
- 16.Sharma SK, Sharma A, Kadhiravan T, Tharyan P. Rifamycins (rifampicin, rifabutin and rifapentine) compared to isoniazid for preventing tuberculosis in HIV-negative people at risk of active TB. Cochrane Database Syst Rev. 2013;7:CD007545.Google Scholar
- 17.Menzies D, Adjobimey M, Ruslami R, et al. Four months of rifampin or nine months of isoniazid for latent tuberculosis in adults. N Engl J Med. 2018;379:440–53.Google Scholar
- 18.Diallo T, Adjobimey M, Ruslami R, et al. Safety and side effects of rifampin versus isoniazid in children. N Engl J Med. 2018;379:454–63.Google Scholar
- 20.Spyridis NP, Spyridis PG, Gelesme A, et al. The effectiveness of a 9-month regimen of isoniazid alone versus 3- and 4-month regimens of isoniazid plus rifampin for treatment of latent tuberculosis infection in children: results of an 11-year randomized study. Clin Infect Dis. 2007;45:715–22.Google Scholar
- 21.Sterling TR, Villarino ME, Borisov AS, et al. Three months of rifapentine and isoniazid for latent tuberculosis infection. N Engl J Med. 2011;365:2155–66.Google Scholar
- 22.Sterling TR, Scott NA, Miro JM, et al. Three months of weekly rifapentine and isoniazid for treatment of Mycobacterium tuberculosis infection in HIV-coinfected persons. AIDS. 2016;30:1607–15.Google Scholar
- 23.Villarino ME, Scott NA, Weis SE, et al; International maternal pediatric and adolescents AIDS Clinical Trials Group; tuberculosis trials consortium. Treatment for preventing tuberculosis in children and adolescents: a randomized clinical trial of a 3-month, 12-dose regimen of a combination of rifapentine and isoniazid. JAMA Pediatr. 2015;169:247–55.Google Scholar
- 24.Pease C, Hutton B, Yazdi F, et al. Efficacy and completion rates of rifapentine and isoniazid (3HP) compared to other treatment regimens for latent tuberculosis infection: a systematic review with network meta-analyses. BMC Infect Dis. 2017;17:265.Google Scholar
- 26.Jindani A, Harrison TS, Nunn AJ, et al. RIFAQUIN trial Team.High-dose rifapentine with moxifloxacin for pulmonary tuberculosis. N Engl J Med. 2014;371:1599–608.Google Scholar
- 29.Bamrah S, Brostrom R, Dorina F, et al. Treatment for LTBI in contacts of MDR-TB patients, Federated States of Micronesia, 2009-2012. Tuberc Lung Dis. 2014;18:912–8.Google Scholar
- 31.Harausz EP, Garcia-Prats AJ, Seddon JA, et al. Sentinel project on pediatric drug-resistant tuberculosis. New and repurposed drugs for pediatric multidrug-resistant tuberculosis. Practice-based recommendations. Am J Respir Crit Care Med. 2017;195:1300–10.Google Scholar
- 32.Diacon AH, Pym A, Grobusch MP, et al; TMC207-C208 study group. Multidrug-resistant tuberculosis and culture conversion with bedaquiline. N Engl J Med. 2014;371:723–32.Google Scholar
- 33.Rapid Communication: Key changes to treatment of multidrug- and rifampicin-resistant tuberculosis (MDR/RR-TB).WHO, Geneva, Switzerland. Available at: www.who.int/tb/publications/2018/rapid_communications_MDR/en. Accessed 6th September 2018.
- 34.Seddon JA, Schaaf HS, Marais BJ, et al. Time to act on injectable-free regimens for children with multidrug-resistant tuberculosis: time to act. Lancet Respir Med. 2018;6:662–6.Google Scholar
- 35.Lewis JM, Hine P, Walker J, et al. First experience of effectiveness and safety of bedaquiline for 18 months within an optimised regimen for XDR-TB. Eur Respir J. 2016;47:1581–4.Google Scholar
- 37.Pandie M, Wiesner L, McIlleron H, et al. Drug-drug interactions between bedaquiline and the antiretrovirals lopinavir/ritonavir and nevirapine in HIV-infected patients with drug-resistant TB. J Antimicrob Chemother. 2016;71:1037–40.Google Scholar
- 38.Liu Y, Matsumoto M, Ishida H, et al. Delamanid: from discovery to its use for pulmonary multidrug-resistant tuberculosis (MDR-TB). Tuberculosis. 2018;111:20–30.Google Scholar
- 39.The use of delamanid in the treatment of multidrug-resistant tuberculosis in children and adolescents: Interim policy guidance. WHO, Geneva,Switzerland. Available at: www.apps.who.int/iris/bitstream/10665/250614/1/9789241549899-eng.pdf. Accessed 6th September 2018.
- 40.Lachâtre M, Rioux C, Dû DL, et al. Bedaquiline plus delamanid for XDR tuberculosis. Lancet Infect Dis. 2016;16:294.Google Scholar
- 41.Tadolini M, Lingtsang RD, Tiberi S, et al. Cardiac safety of extensively drug-resistant tuberculosis regimens including bedaquiline, delamanid and clofazimine. Eur Respir J. 2016;48:1527–9.Google Scholar
- 42.Lee M, Lee J, Carroll MW, et al. Linezolid for treatment of chronic extensively drug-resistant tuberculosis. N Engl J Med. 2012;367:1508–18.Google Scholar
- 44.Tang S, Yao L, Hao X, et al. Clofazimine for the treatment of multidrug-resistant tuberculosis: prospective, multicenter, randomized control study in China. Clin Infect Dis. 2015;60:1361–7.Google Scholar
- 45.Kroger A, Pannikar V, Htoon MT, et al. International open trial of uniform multi-drug therapy regimen for 6 months for all types of leprosy patients: rationale, design and preliminary results. Tropical Med Int Health. 2008;13:594–602.Google Scholar