UDC 616.24-002.5-036.22-085.28.015.8-085.37-039.71-053.2

Aim – to study the feasibility of using the natural immunomodulator BIVEL (BI-V) as a non-specific immunoprevention of tuberculosis (TB) among contact children from focies of multidrug-resistant tuberculosis infection (FsMDR-TBI) on the basis of clinical and immunological studies.
Materials and methods. The object of study: 120 contacted from FsMDR-TBI (75 children and 45 adolescents). The Group 1 – 95 children/adolescents who did not receive BI-V and the Group 2 – 25 patients who received BI-V. The state of phagocytic reactivity of immunity; cellular and humoral immunity; interleukins and specific immunity were determined. Statistical analysis of the obtained results was performed based on a software package Excel.
Results. In infected children/adolescents with FsMDR-TBI, insignificant functional disorders of the cellular response were revealed (decrease by 1.3 times IRI CD3+CD4+/CD3+CD8+), a shift in the balance in the regulatory system towards pro-inflammatory cytokines (increase by 2.0 times TNF-α/IL-10). The existing deviations in the regulatory and cellular response systems disappeared after the completion of the autumn-spring BI-V course. Preventive administration of immunomodulator BI-V to infected children/adolescents with FsMDR-TBI reduced the frequency of acute respiratory viral infections and exacerbations of bronchopulmonary diseases by 2.0 times, the development of latent tuberculosis infection into an active process by 2.6 times. Among children of the Group 2 – 8% of people fell ill with various forms of primary pulmonary TB, among children of the Group 1 – 22.1%. In both groups, the maximum level of TB occurred in the first two years of observation.
Conclusions. The introduction of the algorithm of preventive measures with appointment of BI-V confirmed feasibility of using this immunomodulator for contact children/adolescents with FsMDR-TBI.
The study was carried out in accordance with the principles of the Declaration of Helsinki. The study protocol was approved by the Local Ethical 
Committee of the participating institution. The informed consent of patient was obtained for conducting the studies.
No conflict of interests was declared by the authors.
Keywords: immunoprevention, contact children and adolescents, focies of multidrug-resistant tuberculosis.

УДК: 616.24-002.5:615.015.8]-085.281-078.73-036.8-053.2/6

BACKGROUND. The feasibility of combining antimycobacterial therapy (AMBT) with bedaquiline (Bdq) and delamanid 
(Dlm) with non-specific immunomodulator BI-V in children and adolescents with multidrug-resistant and rifampicin-resistant pulmonary tuberculosis (MDR/Rif-TBP) needs to be studied.
OBJECTIVE. To find out the effectiveness of the use of complex AMBT with Bdq and Dlm with non-specific immunomodulator BI-V in children and adolescents with MDR/Rif-TBP.
MATERIALS AND METHODS. Children and adolescents with MDR/Rif-TBP at the initial stage of AMBT were given BI-V 
(BIVEL, Slovenia) as a non-specific immunomodulator. The patients were divided into two groups: 1st – 20 patients who received Bdq + Dlm + levofloxacin (Lfx) + linezolid (Lzd) + clofazimine (Cfz); 2nd ‒ 28 patients whose complex treatment included BI-V (Вdq + Dlm + Lfx + Lzd + Cfz + BI-V). BI-V was prescribed from the age of 3 years at 5 ml suspension once a day during 24 days.
RESULTS. The use of BI-V against the background of individualized regimens of AMBT in children and adolescents with  MDR/Rif-TBP increased the effectiveness of treatment, contributed to the disappearance of symptoms of intoxication, the resolution of infiltration foci and the healing of decay cavities in system of immune protection, which contributed to the shortening of the inpatient stage of treatment, while maintaining a high therapeutic effectiveness (“cured” ‒ 92.8 %)  and the formation of small residual changes in the lungs in the majority (89.3 %).
CONCLUSIONS. When using combined complex AMBT with Bdq, Dlm and BI-V, high therapeutic efficiency was observed  in most patients (92.8 %).
KEY WORDS: multiple drug-resistant pulmonary tuberculosis, treatment, bedaquiline, delamanid, BI-V, children, adolescents

UDC: 616.24-002.5:615.015.8]-022.16-085.281-039.71-053.2/.

Summary. 
120 exposed children/adolescents (75 children and 45 adolescents) from the multi-drug resistant tuberculosis sites underwent the complex clinical radiological and immunological examination. Insignificant functional disorders of cellular response (immunoregulatory processes) caused by the prevalence of suppressor and cytotoxic reactions by 1.3 times and by the prevalence of pro-inflammatory cytokines in the regulatory 
system (2.0 times above the norm, TNF-α/IL 10.0. р<0.01) were revealed in the infected children/adolescents from the multi-drug resistant tuberculosis sites, while their СD3+. СD3+СD4+. СD3+СD8+ were within norm. The evident disorders of the regulatory system and cell immune system were eliminated after the completion of the autumn-spring BI-V course. The non-specific immune regulator BI-V is efficient for the prevention of multi-drug resistant tuberculosis for the exposed children/adolescents from the multi-drug tuberculosis sites. Consequently, the latent TB infection grew into the active form by 2.8 times less often in the children that took BI-V as compared to the infected children who did not take the drug.
Key words: BIVEL immunomodulator, pulmonary tuberculosis in children, cellular immunity, tuberculosis.

UDC 616.24-002.5:615.015.8]-085.281-036.8-053.2/.6

Introduction. Against the backdrop of multiple and widespread drug resistance of Mycobacterium tuberculosis (MDR-TB), there has been 
a significant decline in the effectiveness of treatment of tuberculosis (TB) patients in Ukraine and globally. Therefore, in recent years, new 
antimycobacterial drugs, such as bedaquiline (Bdq), delamanid (Dlm) and pretomanid, have been introduced to improve treatment efficacy 
 in adults, children and adolescents.
Purpose. To study the effectiveness of complex treatment with bedaquiline (Bdq) and delamanid (Dlm) in children under 18 years old with 
multiple and extensively drug-resistant pulmonary TB (MDR/XDR-TB).
Materials and methods. To study the clinical efficacy of chemotherapy with Bdq and Dlm, a retrospective cohort analysis of medical 
records was conducted. The main group consisted of 40 children with MDR/XDR-TB who received comprehensive antimycobacterial therapy 
with Bdq and Dlm; and the control group consisted of 27 patients who received treatment without Bdq and Dlm.
Results. It was found that during the first three months of treatment, there was a decrease in bacilli in all patients treated with Bdq and Dlm and in the group of patients without these new drugs (control), but in the control group, the decrease was significantly slower, p<0.05. According to the immune system parameters, after the intensive phase was completed, the activity of a specific process was 1.7 times more frequent in patients of the control group than in the main group. After completion of the course of treatment, all patients in the main group showed resorption of infiltration, compaction of foci, and formation of fibrosis in the lungs according to the results of X-ray tomographic examination. However, in 14.8% of patients in the control group, treatment failure was noted with the resumption of bacterial release and destruction in the lung tissue, and in the main group, all patients had healing of the decay cavities. In the majority (77.5%) of patients in the main group, treatment resulted in the formation of small residual changes, but large residual changes were 2.3 times more common in the control group in the form of multiple dense foci, fibrosis and residual decay cavities.
Conclusions. Studies have shown the high efficacy of complex treatment with Bdq and Dlm in children and adolescents. In particular, in MDR/XDR-TB patients treated with Bdq and Dlm, treatment results were 2 times more likely to be considered «cured» than in the control group, and 1.5 times less likely to be considered «complete». The treatment success rate in the main group was 100.0%, and in the control group — 85.2%. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies.
No conflict of interests was declared by the authors.
Keywords: children, tuberculosis, adolescents, multidrug resistance, extensive drug resistance, treatment, bedaquiline, delamanid

УДК 616.24-002.5-085.8-053.2/.6

Мета роботи — вивчити клінічну ефективність режимів хіміотерапії із застосуванням бедаквіліну (Bdq) і деламаніду (Dlm) у дітей і підлітків, хворих на множинну або широку лікарсько-стійку (МЛС/ШЛС) форму туберкульозу (ТБ) легень.
Матеріали та методи. Проведено ретроспективний когортний аналіз даних медичної документації 40 хворих на ТБ легень з МЛС/ШЛС мікобактерій туберкульозу (МБТ), з них 25 (62,5 %) дітей до 14 років і 15 (37,5 %) підлітків віком від 15 до 17 років. Хлопчиків було 18 (47,5 %), дівчаток — 22 (52,5 %). Мікробіологічне дослідження передбачало виявлення МБТ у мокротинні методом мікроскопії мазка, посіву матеріалу на середовище Левенштейна—Єнсена, типування виділених мікобактерій на BACTEC MGIT 960, проведення тесту медикаментозної чутливості штамів МБТ до антимікобактеріальних препаратів (АМБП) першого та другого ряду, а також молекулярно-генетичне дослідження мокротиння, зокрема методом GeneXpert MTB/RIF/Ultra і лінійного зонд-аналізу. Усі діти і підлітки отримували індивідуальний режим лікування залежно від резистентності МБТ до АМБП або резистентності МБТ у джерела інфекції.
Результати та обговорення. Серед обстежених дітей 44,0 % були віком до 4 років, 12,0 % — віком від 5 до 8 років, 44,0 % — віком від 9 до14 років. Серед підлітків переважали пацієнти віком 17 (46,7 %) років. Резистентність до рифампіцину і МЛС констатували у 10 (40,0 %) дітей, яким призначали нову схему лікування з Bdq і Dlm, ШЛС-ТБ — у 3 (12,0 %), ризик мультирезистентного ТБ — у 12 (48,0 %).
У підлітків у 1,7 разу частіше, ніж у дітей, відзначено наявність МЛС-ТБ, у 2,8 разу — ШЛС-ТБ, у 3,3 разу рідше — мультирезистентного ТБ. Первинний туберкульозний комплекс діагностували у 12 (48,0 %) дітей, ТБ з ураженням легень і кісток — у 4 (16,0 %), ТБ внутрішньогрудних лімфатичних вузлів — у 3 (12,0 %), ТБ легень і ЦНС — у 2 (8,0 %), інфільтративний ТБ легень — у 3 (12,0 % ). У підлітків у 7,5 разу частіше, ніж у дітей, спостерігали інфільтративну форму туберкульозу легень і в 3,3 разу — дисеміновану форму. Протягом перших 2 міс лікування Bdq і Dlm констатовано знебацилення в усіх дітей. Однак припинення бактеріовиділення в усіх підлітків досягнуто за 3 міс хіміотерапії. Через 9 міс хіміотерапії зафіксовано значну позитивну рентгенологічну динаміку у 23 (92,0 %) дітей і 12 (80,0 %) підлітків. Через 9 міс лікування зміни в легенях зберігалися у 2 (8,0 %) дітей та 3 (20,0 %) підлітків, але по закінченні курсу лікування як у дітей, так і у підлітків рентгенологічно констатовано розсмоктування інфільтрації, ущільнення вогнищ, формування фіброзу в легенях.
Висновки. Після курсу комплексного лікування із застосуванням Bdq і Dlm вилікування констатовано у 21 (84,0 %) дитини та 10 (66,7 %) підлітків. Лікування вважали завершеним удвічі частіше у підлітків порівняно з дітьми (33,3 проти 16,0 %; р < 0,05). Успішність лікування при застосуванні нових АМБП констатовано в усіх дітей і підлітків. По закінченні лікування у дітей та підлітків переважно виявляли формування малих залишкових змін (у 84,0 і 73,3 % відповідно).