RU2787924C1 - Method for preventive treatment of tuberculosis with multidrug resistance in children - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely, to therapy and pulmonology, and can be used for preventive treatment of tuberculosis with multidrug resistance (MDR-TB) in children. Oral administration of moxifloxacin 10 mg/kg daily 1 time a day for 9 months is prescribed.

EFFECT: effective and safe preventive therapy in children with family contact with an MDR-TB patient due to the administration of moxifloxacin in the described regiment, preventing the development of severe adverse reactions associated with enhancement of the QT interval and increase in the activity of liver transaminases.

1 cl, 1 tbl

Description

The invention relates to medicine, namely to therapy and pulmonology, and concerns a method for the preventive treatment of multidrug-resistant tuberculosis (MDR-TB) in children, characterized in that moxifloxacin is prescribed as a preventive treatment for MDR-TB.

Approximately 30,000 children develop multidrug-resistant (MDR) tuberculosis (TB) every year, but most of these cases remain undiagnosed, with high associated mortality. Children who are in close family contact with MDR-TB patients are at high risk of developing active MDR-TB and are strongly encouraged to receive preventive treatment.

There are no known preventive treatments for multidrug-resistant TB in children using moxifloxacin as a preventive treatment for MDR-TB.

The objective of the proposed method is to find an effective and safe method of preventive therapy in children from family contact with an MDR-TB patient.

The problem is solved, and the required technical result is achieved by the fact that as an effective and safe method of preventive therapy in children, from family contact with an MDR-TB patient, moxifloxacin is used for 9 months orally 10 mg/kg daily 1 time per day.

In the Arkhangelsk region, the prevalence of MDR-TB is quite high. In 2020, MDR-TB accounted for 31% of new TB cases and 78% of retreatment cases among adults. Children with family contacts of confirmed pulmonary MDR-TB cases (index cases) without resistance to fluoroquinolones were invited to participate in the study between 1 January 2011 and 31 March 2014. Children were followed up for at least 1 year after completion of prophylactic treatment or for 2 years if they did not receive chemoprophylaxis. Latent TB infection (LTBI) was diagnosed based on a positive tuberculin skin test (2 tuberculin units of purified protein derivative; threshold ≥10 mm induration) or a positive diaskintest (Generium; CFP10-ESAT6 from Echerichia coliBL21 (DE3)/pCFP-ESAT; compaction of any size) in the absence of tuberculosis [6]. All children who were in close family contact with patients were offered prophylactic therapy with moxifloxacin, regardless of the presence or absence of LTBI. According to the national guidelines for the fight against tuberculosis, all children who underwent tuberculosis chemoprophylaxis were offered treatment in a sanatorium. Children whose parents refused treatment at the sanatorium were offered outpatient treatment. For young children, powder formulations were prepared individually at the pharmacy for each child using a mg/kg dose and given with food or juice. All children received treatment under direct observation or under video surveillance by medical personnel. Monitoring the safety of prophylactic therapy included 1-4 weekly clinical examinations with a note in the medical history and monthly monitoring of complete blood count, alanine and aspartate aminotransferases, total bilirubin, urinalysis and ECG (with measurement of the QT interval). Adverse reactions to drugs were evaluated and classified according to DAIDS classification tables [7]. Parents of all eligible children were asked to give voluntary informed consent to participate in the study; parents who refused prophylactic treatment agreed to collect routine data. The ethical aspects of this study were approved by the Ethics Committee of the Northern State Medical University, Arkhangelsk (No. 1; January 12, 2011).

Of the 74 children identified as family contacts of MDR-TB patients, 2 were in close contact with MDR-TB patients with established resistance to fluoroquinolones, which did not meet the selection criteria. The study included 72 children with a mean age of 7.4 years (interquartile range [IQR] 4.0–12.3 20 (28%) <5 years). All cases of active MDR-TB in index cases were bacteriologically confirmed by culture or molecular tests (Gene XpertMTB /RIF, GenoTypeMTBDRplus, GenoTypeMTBDRs/). Sixty-three index cases (82.9%) were shedding bacteria diagnosed by sputum smear microscopy. There were a total of 79 index cases, with four children having contact with more than one index case of MDR-TB in the family. LTBI was diagnosed in 51 (71%) children (38 children had both Mantoux and Diaskintest test results, 13 children only Mantoux, and one child only Diaskintest). There were no significant differences among children who received prophylactic treatment and refused chemoprophylaxis at the time of registration in the TB dispensary in age, the size of positive reactions of skin tests for TB and the duration of observation (Table 1). Fifty-five children (81%) received preventive therapy, 49 children (90%) completed the prescribed 9-month course (Table 1). Moxifloxacin was administered at 10 mg/kg, once daily. Six children experienced adverse reactions that were directly related to the study drug. All were mild (grade 1 or 2) and only one adverse reaction led to discontinuation of treatment (allergic reaction with urticaria and dry cough). Fourteen children (19%) did not receive prophylactic therapy due to parental preference. The mean follow-up period was 25.1 months (IQR: 18.5-30.5). Of the 58 children treated, none developed TB during follow-up; Of the 14 children who did not receive prophylactic treatment, one child became ill with tuberculosis with bacterioexcretion diagnosed by culture 18 months after registration in the TB dispensary with the same resistance profile as in the index case.

The study shows that prophylactic treatment of MDR-TB with fluoroquinolones is safe and well tolerated by children, and none of those children who received chemoprophylaxis developed TB. In 2014, the World Health Assembly made TB prevention a key pillar of the End TB Strategy, and MDR-TB preventive treatment is now considered a key element of public health approaches to reducing the incidence of MDR-TB5. The study was commissioned in 2011 and is one of the first pediatric cohorts to study the safety of preventive treatment for MDR-TB among contact children. We have identified a high proportion of children who become infected with LTBI through family contact with MDR-TB and therefore are at high risk of future MDR-TB. The study showed that prophylactic fluoroquinolone therapy for children was effective and safe. More than 80% of parents agreed to prophylactic treatment for their child, and 90% of treated children completed a full course of chemoprophylaxis. Preventive therapy was carried out under the supervision of medical personnel.

References:

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9. World Health Organization. WHO Consolidated Guidelines on Tuberculosis: Module 1: Prevention: preventive treatment of tuberculosis. Geneva, Switzerland: World Health Organization; March 2020. Available at: https://www.who.int/publications/i/item/who-consolidated-guidelines-on-tuberculosis-module-l-prevention-tuberculosis-preventive-treatment. Last accessed April 10, 2021

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Claims (1)

A method for the preventive treatment of multidrug-resistant tuberculosis in children, characterized in that moxifloxacin is administered orally 10 mg/kg daily once a day for 9 months.