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Current Pediatrics Reports
Published in: Current Pediatrics Reports 3/2016

01-09-2016 | Infectious Diseases (B Marais, Section Editor)

Multidrug-Resistant Tuberculosis in Children: Recent Developments in Diagnosis, Treatment and Prevention

Authors: H. Simon Schaaf, Anthony J. Garcia-Prats

Published in: Current Pediatrics Reports | Issue 3/2016

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Abstract

Purpose of review

Multidrug-resistant (MDR) tuberculosis (TB) threatens global TB control. Few children with MDR-TB are diagnosed and appropriately treated; this is related to difficulties confirming a diagnosis of TB disease and challenges with current treatment regimens. This review highlights recent developments in the diagnosis, treatment and prevention of MDR-TB in children.

Recent findings

Although phenotypic drug susceptibility testing (DST) remains the gold standard, molecular DST methods are facilitating rapid confirmation of MDR-TB. Increased knowledge about correct paediatric dosing of existing drugs and the addition of new and repurposed drugs is improving treatment. Observational studies support the effectiveness of preventing disease in MDR-TB-exposed contacts.

Summary

Although challenges remain, there have been many exciting developments in the diagnosis and treatment of MDR-TB in children; it is a priority to continue improving MDR-TB care and to improve access for children. Preventive therapy following MDR-TB exposure/infection is a promising strategy under evaluation.
Literature
1.
• Jenkins HE, Tolman AW, Yuen CM, et al. Incidence of multidrug-resistant tuberculosis disease in children: systematic review and global estimates. Lancet. 2014;383(9928):1572–79. doi:10.​1016/​S0140-6736(14)60195-1. Mode-based estimates of the global burden of MDR-TB in children.
2.
World Health Organisation. Global tuberculosis report 2015. WHO, Geneva. WHO/HTM/TB/2015.22.
3.
4.
5.
Prajapati S, Upadhyay K, Mukherjee A, et al. Delhi Pediatric TB Study Group. High prevalence of primary drug resistance in children with intrathoracic tuberculosis in India. Paediatr Int Child Health. 2015 Jun 8:2046905515Y0000000041. [Epub ahead of print].
6.
7.
• Rose PC, Schaaf HS, du Preez K, et al. Completeness and accuracy of electronic recording of paediatric drug-resistant tuberculosis in Cape Town, South Africa. Public Health Action. 2013;3(3):214–19. doi:10.​5588/​pha.​13.​0041. An example of a study showing under-recording of MDR-TB in children, which is common.
8.
Ballif M, Nhandu V, Wood R, et al, for the International epidemiological Databases to Evaluate AIDS (IeDEA). Detection and management of drug-resistant tuberculosis in HIV-infected patients in lower-income countries. Int J Tuberc Lung Dis. 2014;18(11):1327–36. doi: 10.​5588/​ijtld.​14.​0106.
9.
•• Seddon JA, Fred D, Amanullah F, et al. Post-exposure management of multidrug-resistant tuberculosis contacts: evidence-based recommendations. Policy Brief No. 1. Dubai, United Arab Emirates: Harvard Medical School Center for Global Health Delivery–Dubai. 2015. Important overview of existing data and consensus recommendations for approaching the management of child contacts of infectious MDR-TB source cases.
10.
11.
• 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):392–5. doi: 10.​1093/​cid/​cit709. Recent data showing high rates of concordant strains in child contact-adult source case pairs with MDR-TB.
12.
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):381–91. doi:10.​1093/​cid/​cit643.CrossRefPubMed
13.
14.
15.
16.
17.
Zar HJ, Workman L, Isaacs W, Dheda K, Zemanay W, Nicol MP. Rapid diagnosis of pulmonary tuberculosis in African children in a primary care setting by use of Xpert MTB/RIF on respiratory specimens: a prospective study. Lancet Glob Health. 2013;1(2):e97–104. doi:10.​1016/​S2214-109X(13)70036-6.CrossRefPubMed
18.
19.
20.
Rachow A, Clowes P, Saathoff E, et al. Increased and expedited case detection by Xpert MTB/RIF assay in childhood tuberculosis: a prospective cohort study. Clin Infect Dis. 2012;54(10):1388–96. doi:10.​1093/​cid/​cis190.CrossRefPubMed
21.
22.
23.
World Health Organization. Use of liquid TB culture and drug susceptibility testing (DST) in low- and medium-income settings. Geneva: WHO; 2007.
24.
Barnard M, van Pittius GNC, van Helden PD, Bosman M, Coetzee G, Warren RM. The diagnostic performance of the GenoType MTBDRplus version 2 line probe assay is equivalent to that of the Xpert MTB/RIF assay. J Clin Microbiol. 2012;50(11):3712–6. doi:10.​1128/​JCM.​01958-12.CrossRefPubMedPubMedCentral
25.
Matabane MM, Ismail F, Strydom KA, Onwuegbuna O, Omar SV, Ismail N. Performance evaluation of three commercial molecular assays for the detection of Mycobacterium tuberculosis from clinical specimens in a high TB-HIV-burden setting. BMC Infect Dis. 2015;15:508. doi:10.​1186/​s12879-015-1229-9.CrossRefPubMedPubMedCentral
26.
• Rufai SB, Kumar P, Singh A, Prajapati S, Balooni V, Singh S. Comparison of Xpert MTB/RIF with line probe assay for detection of rifampin-monoresistant Mycobacterium tuberculosis. J Clin Microbiol. 2014;52(6):1846–52. doi:10.​1128/​JCM.​03005-13. Important to note differences in test results and how to interpret this.
27.
28.
Schaaf HS, Walters E, Hesseling A, Rautenbach C, Bosch C, Garcia-Prats A. Surveillance of childhood tuberculosis drug resistance in Cape Town, South Africa: increasing rifampicin mono-resistance. Int J Tuberc Lung Dis. 2015;19(Suppl 2):S444.
29.
30.
31.
32.
Mathys V, van de Vyvere M, de Droogh E, Soetaert K, Groenen G. False-positive rifampicin resistance on Xpert MTB/Rif caused by a silent mutation in the rpoB gene. Int J Tuberc Lung Dis. 2014;18(10):1255–7. doi:10.​5588/​ijtld.​14.​0297.CrossRefPubMed
33.
Mao X, Ke Z, Shi X, et al. Diagnosis of drug resistance to fluoroquinolones, amikacin, capreomycin, kanamycin and ethambutol with Genotype MTBDRsl assay: a meta-analysis. Ann Clin Lab Sci. 2015;45(5):533–44.PubMed
34.
Tagliani E, Cabibbe AM, Miotto P, et al. Diagnostic performance of the new version (v2.0) of GenoType MTBDRsl assay for detection of resistance to fluoroquinolones and second-line injectable drugs: a multicenter study. J Clin Microbiol. 2015;53(9):2961–9. doi:10.​1128/​JCM.​01257-15.CrossRefPubMedPubMedCentral
35.
•• Coll F, McNerney R, Preston MD, et al. Rapid determination of anti-tuberculosis drug resistance from whole-genome sequences. Genome Med. 2015;7(1):51. doi:10.​1186/​s13073-015-0164-0. Important to take note of increasing role of genotypic approaches to Mycobacterium tuberculosis drug susceptibility testing.
36.
•• Walker TM, Kohl TA, Omar SV, et al; Modernizing Medical Microbiology (MMM) Informatics Group. Whole-genome sequencing for prediction of Mycobacterium tuberculosis drug susceptibility and resistance: a retrospective cohort study. Lancet Infect Dis. 2015;15(10):1193–1202. doi: 10.​1016/​S1473-3099(15)00062-6. Important to take note of increasing role of genotypic approaches to Mycobacterium tuberculosis drug susceptibility testing.
37.
Outhred AC, Jelfs P, Suliman B, et al. Added value of whole-genome sequencing for management of highly drug-resistant TB. J Antimicrob Chemother. 2015;70(4):1198–202. doi:10.​1093/​jac/​dku508.PubMed
38.
39.
40.
• 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(5):458–64. doi:10.​1136/​thoraxjnl-2013-203900. Large prospective cohort study demonstrating the excellent outcomes possible in children treated for MDR-TB, including a large proportion with non-severe disease treated without or with shortened duration of injectable medications.
41.
42.
•• Nachman S, Ahmed A, Amanullah F, et al. Towards early inclusion of children in tuberculosis drugs trials: a consensus statement. Lancet Infect Dis. 2015; 15(6):711–20. doi:10.​1016/​S1473-3099(15)00007-9. An important article presenting expert consensus on how to evaluate new drugs and/or regimens in children, and calling for earlier inclusion of children and adolescents in trials of novel TB drugs and regimens.
43.
World Health Organization. Guidelines for the programmatic management of drug-resistant tuberculosis—2011 update. WHO, Geneva. WHO/HTM/TB/2011.6.
44.
45.
World Health Organization. Guidance for national tuberculosis programmes on the management of tuberculosis in children. 2nd ed. WHO, Geneva. 2014. WHO/HTM/TB/2014.03.
46.
47.
48.
49.
Thee S, Garcia-Prats AJ, Draper HR, McIlleron HM, Wiesner L, Castel S, Schaaf HS, Hesseling AC. The pharmacokinetics and safety of moxifloxacin in children with multidrug-resistant tuberculosis. Clin Infect Dis. 2015;60(4):549–56. doi:10.​1093/​cid/​ciu868.CrossRefPubMed
50.
Mase SR, Jereb JA, Gonzalez D, et al. Pharmacokinetics and dosing of levofloxacin in children treated for active or latent multidrug-resistant tuberculosis, Federated States of Micronesia and Republic of the Marshall Islands. Pediatr Infect Dis J. 2016;35:414–21. doi:10.​1097/​INF.​0000000000001022​.CrossRefPubMed
51.
• Garcia-Prats AJ, Rose PC, Hesseling AC, Schaaf HS. Linezolid for the treatment of drug-resistant tuberculosis in children: A review and recommendations. Tuberculosis (Edinb). 2014;94(2):93–104. doi:10.​1016/​j.​tube.​2013.​10.​003. A review on linezolid as an antituberculosis agent in children.
52.
Rose PC, Hallbauer U, Seddon JA, Hesseling AC, Schaaf HS. Linezolid-containing regimens for the treatment of drug-resistant tuberculosis in South African children. Int J Tuberc Lung Dis. 2012; 2012;16(12):1588–93. doi:10.​5588/​ijtld.​12.​0322.
53.
54.
55.
56.
57.
Centers for Disease Control and Prevention. Provisional CDC guidelines for the use and safety monitoring of bedaquiline fumarate (Sirturo) for the treatment of multidrug-resistant tuberculosis. MMWR 2013;62(No. RR-9):1–11.
58.
World Health Organization. Introduction of bedaquiline for the treatment of multidrug-resistant tuberculosis at country level. WHO, Geneva. WHO/HTM/TB/2015.10.
59.
60.
61.
Hafkin J, Gler M, Frias M, et al. Long-term safety, tolerability and pharmacokinetics of delamanid in children aged 12–17 years. Abstract EP-115-04. Int J Tuberc Lung Dis. 2015;19(Suppl 2):S91–2.
62.
Hafkin J, Frias M, Hesseling A, et al. Pharmacokinetics and safety of delamanid in pediatric MDR-TB patients, ages 6–17 years. ICAAC 2015; Sep 17–21, in San Diego, California. Poster A-960.
63.
Esposito S, D’Ambrosio L, Tadolini M, et al. ERS/WHO tuberculosis consilium assistance with extensively drug-resistant tuberculosis management in a child: case study of compassionate delamanid use. Eur Respir J. 2014;44(3):811–5. doi:10.​1183/​09031936.​00060414.CrossRef
64.
Dawson R, Diacon AH, Everitt D, et al. Efficiency and safety of the combination of moxifloxacin, pretomanid (PA-824), and pyrazinamide during the first 8 weeks of antituberculosis treatment: a phase 2b, open-label, partly randomised trial in patients with drug-susceptible or drug-resistant pulmonary tuberculosis. Lancet. 2015;385(9979):1738–47. doi:10.​1016/​S0140-6736(14)62002-X.CrossRefPubMed
65.
Aung KJ, Van Deun A, Declercq E, et al. Successful ‘9-month Bangladesh regimen’ for multidrug-resistant tuberculosis among over 500 consecutive patients. Int J Tuberc Lung Dis. 2014;18(10):1180–7. doi:10.​5588/​ijtld.​14.​0100.CrossRefPubMed
66.
Piubello A, Harouna SH, Souleymane MB, et al. High cure rate with standardised short-course multidrug-resistant tuberculosis treatment in Niger: no relapses. Int J Tuberc Lung Dis. 2014;18(10):1188–94. doi:10.​5588/​ijtld.​13.​0075.CrossRefPubMed
67.
68.
69.
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. doi:10.​1002/​14651858.​CD007545.​pub2.PubMed
70.
71.
72.
73.
• Seddon JA, McKenna L, Shah T, Kampmann B. Recent developments and future opportunities in the treatment of tuberculosis in children. Clin Infect Dis. 2015;61(Suppl 3):S188–S99. doi:10.​1093/​cid/​civ582. A broad update on developments in the treatment of childhood tuberculosis.
74.
Moultrie H, McIlleron H, Sawry S, et al. Pharmacokinetics and safety of rifabutin in young HIV-infected children receiving rifabutin and lopinavir/ritonavir. J Antimicrob Chemother. 2015;70(2):543–9. doi:10.​1093/​jac/​dku382.CrossRefPubMed
75.
Garcia-Prats A, Draper HR, Thee S, et al. Emerging data on PK and safety of levofloxacin and amikacin informs care and design of new regimens. Int J Tuberc Lung Dis. 2015;19(Suppl 2):S29–30.
76.
•• Thee S, Garcia-Prats AJ, Donald PR, Hesseling AC, Schaaf HS. Fluoroquinolones for the treatment of tuberculosis in children. Tuberculosis (Edinb). 2015. doi:10.​1016/​j.​tube.​2015.​02.​037. An important review summarizing the literature on fluoroquinolone use in children with tuberculosis.
77.
78.
•• Thee S, Garcia-Prats AJ, Donald PR, Hesseling AC, Schaaf HS. A review of the use of ethionamide and prothionamide in childhood tuberculosis. Tuberculosis (Edinb). 2016;97:126–36. doi:10.​1016/​j.​tube.​2015.​09.​007. A review on the thioamides as antituberculosis drugs in children.
79.
Diacon A, Donald P, Pym A, et al. Randomized pilot trial of eight weeks of bedaquiline (TMC207) treatment for multidrug-resistant tuberculosis: long-term outcome, tolerability, and effect on emergence of drug resistance. Antimicrob Agents Chemother. 2012;56(6):3271–6. doi:10.​1128/​AAC.​06126-11.CrossRefPubMedPubMedCentral
80.
World Health Organization. WHO policy on TB infection control in health-care facilities, congregate settings and households. WHO, Geneva, Switzerland. WHO/HTM/TB/2009.419.
81.
Cruz AT, Medina D, Whaley EM, Ware KM, Koy TH, Starke JR. Tuberculosis among families of children with suspected tuberculosis and employees at a children’s hospital. Infect Control Hosp Epidemiol. 2011;32(2):188–90. doi:10.​1086/​657940.CrossRefPubMed
82.
Zimri K, Hesseling AC, Godfrey-Faussett P, Schaaf HS, Seddon JA. Why do child contacts of multidrug-resistant tuberculosis not come to the assessment clinic? Public Health Action. 2012;2(3):71–5.CrossRefPubMedPubMedCentral
Metadata
Title
Multidrug-Resistant Tuberculosis in Children: Recent Developments in Diagnosis, Treatment and Prevention
Authors
H. Simon Schaaf
Anthony J. Garcia-Prats
Publication date
01-09-2016
Publisher
Springer US
Published in
Current Pediatrics Reports / Issue 3/2016
Electronic ISSN: 2167-4841
DOI
https://doi.org/10.1007/s40124-016-0100-9

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