Preventive chemotherapy in children exposed to multiple drug resistant tuberculosis
https://doi.org/10.21292/2075-1230-2019-97-6-36-43
Abstract
The objective of the study: to assess the safety and efficacy of preventive anti-tuberculosis treatment of children exposed to multiple drug resistant tuberculosis (MDR TB) using different combinations of anti-tuberculosis drugs.
Subjects and methods. 150 children at the age from 1 to 17 years old inclusive were enrolled in the study, they all had a high risk of being infected with MDR M. tuberculosis. All children had been exposed to MDR TB and had no clinical or X-ray signs of active disease. The average age of children made 9.5 ± 4.1 (median 10) years old, girls and boys made 46.6% and 53.4% respectively. Children were divided into two groups of observation: the main one included 100 children who were prescribed with preventive anti-tuberculosis treatment, while the control group consisted of 50 children who did not receive any preventive treatment for various reasons. In the main group, children received various regimens of preventive chemotherapy: pyrazinamide and ethambutol (ZE) – 30 people; pyrazinamide and prothionamide (ZPt) – 40 patients; three drugs – pyrazinamide, ethambutol, and prothionamide (ZEPt) – 30 children. The combination of drugs was based on the drug resistance of the intended source of infection. Treatment was prescribed for 3-4 months.
Results: the use of a combination of first line (pyrazinamide and ethambutol) and second line (prothionamide) drugs demonstrated lower toxicity of the regimen consisting of pyrazinamide and ethambutol compared to pyrazinamide and prothionamide regimen: OR = 0.3; 95% CI – 0.2-0.6.
In Z + Pt and Z + E + Pt regimens, adverse events occurred in 22.5 and 20% of cases, respectively, and in Z + E regimen – only in 6.6% of cases (p < 0.05).
About the Authors
V. A. АksenovaRussian Federation
Valentina A. Аksenova - Doctor of Medical Sciences, Professor, Head of Children and Adolescents Department.
N. I. Klevno
Russian Federation
Nadezhda I. Klevno - Doctor of Medical Sciences, Leading Researcher of Children and Adolescents Department.
Build. 2, 4, Dostoevskiy St., Moscow, 127473, Phone: +7 (495) 681-92-36.
A. V. Kazakov
Russian Federation
Aleksey V. Kazakov - Candidate of Medical Sciences, Senior Researcher of Children and Adolescents Department.
Build. 2, 4, Dostoevskiy St., Moscow, 127473, Phone: +7 (495) 681-92-36.
A. V. Gordina
Russian Federation
Aleksandra V. Gordina - Candidate of Biological Sciences, Chief Specialist of RF Federal TB Control and Monitoring Center.
12, Vucheticha St., Moscow, 127206.
R. Kh. Fatykhova
Russian Federation
Ramzia Kh. Fatykhova - Deputy Director for Pediatrics.
20, Shalyapina St., Kazan, 420049.
References
1. Аksenova V.А., Baryshnikova L.А., Dolzhenko E.N., Kudlay D.А. Topical issues of mass screening in children for tuberculosis under current conditions. Doktor. ru, 2012, vol. 76, no. 8, pp. 27-29. (In Russ.)
2. Аksenova V.А., Klevno N.I., Baryshnikova L.А., Kudlay D.А., Nikolenko N. Yu., Kurilla А.А. Metodicheskie rekomendatsii: Vyavleniye tuberkuleza i taktika dispansernogo nabludeniya za litsami iz grupp riska s ispolzovaniyem rekombinantnogo tuberkuleznogo allergena - Diaskintest®. [Guidelines. Detection of tuberculosis and tactics for dispensary follow-up over risk groups with the use of the recombinant tuberculous allergen – Diaskintest®]. Moscow, Pervy MGMU im. I.M. Sechenova Publ., 2011, 12 p.
3. Аksenova V.А., Klevno N.I., Kavtarashvili S.M., Kazakov А.V., Pakhlavonova А.D. The nidus of tuberculous infection as a risk factor of multiple drug resistant tuberculosis in children. Tuberculosis and Lung Diseases, 2018, no. 1, pp. 11-17. (In Russ.)
4. Lebedeva L.V. Khimioprofilaktika tuberkuleza u detey i podrostkov (pokazaniya, metodika, effektivnost). Diss. dokt. med. nauk. [Preventive chemotherapy of tuberculosis in children and adolescents (indications, methods, efficacy. Doct. Diss.]. Moscow, 1971,
5. Skrytaya tuberkuleznaya infektsiya: obnovlennye i konsolidirovannye rukovodstva po programmnomu upravleniyu. [Latent tuberculous infection: updated and consolidated guidelines on the program management]. Available at: https://apps.who.int/iris/bitstream/handle/10665/312059/9789245550235-rus.pdf?ua=1
6. Slogotskaya L.V., Bogorodskaya E.M., Senchikhina O.Yu., Nikitina G.V., Kudlay D.А. Formation of risk groups among children facing an advanced risk to develop tuberculosis who should undergo various immunological examinations. Rossiyskiy Pediatricheskiy Journal, 2017, vol. 20, no. 4, pp. 207-213. (In Russ.)
7. Federalnye klinicheskie rekomendatsii po diagnostike i lecheniyu latentnoy tuberkuleznoy infektsii u detey. [Federal clinical recommendations on diagnostics and treatment of latent tuberculous infection in children]. Moscow, 2015, 45 p.
8. Bamrah S., Brostrom R., Dorina F., Setik L., Song R., Kawamura L.M. et al. Treatment for LTBI in contacts of MDR-TB patients, Federated States of Micronesia, 2009-2012. Internat. J. Tuberc. Lung Dis., 2014, vol. 18, no. 8, pp. 912-918.
9. Cruz Andrea T., Garcia-Prats Anthony J., Furin J., Seddon James A. Treatment of multidrug-resistant tuberculosis infection in children. Pediatr. Infect. Dis. J., 2018, vol. 37, no. 8, pp. 831.
10. Denti P., Garcia-Prats A.J., Draper H.R., Wiesner L., Winckler J., Thee S., Dooley K.E., Savic R.M., McIlleron H.M., Schaaf H.S., Hesseling A.C. Levofloxacin population pharmacokinetics in South African children treated for multidrug-resistant tuberculosis. Antimicrob. Agents Chemother., 2018, vol. 62, no. 2.
11. Harausz E.P., Garcia-Prats A.J., Law S., Schaaf H.S., Kredo T., Seddon J.A. et al. Treatment and outcomes in cildren with multidrug-resistant tuberculosis: A systematic review and individual patient data metaanalysis. PLoSMed., 2018, vol. 15, no. 7, https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1002591
12. Lobue P., Menzies D. Treatment of latent tuberculosis infection: an update. Respirology, 2010, vol. 15, pp. 603-622.
13. Seddon et al. 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). Trials, 2018, vol. 19, pp. 693 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6302301/
14. Younossian A.B., Rochat T., Ketterer J.P., Wacker J., Janssens J.P. High hepatotoxicity of pyrazinamide and ethambutol for treatment of latent tuberculosis. Eur. Respir. J., 2005, vol. 26, pp. 462-464.
Review
For citations:
Аksenova V.A., Klevno N.I., Kazakov A.V., Gordina A.V., Fatykhova R.Kh. Preventive chemotherapy in children exposed to multiple drug resistant tuberculosis. Tuberculosis and Lung Diseases. 2019;97(6):36-43. (In Russ.) https://doi.org/10.21292/2075-1230-2019-97-6-36-43