scholarly journals Efficacy of treatment of extensive drug resistant tuberculosis in patients with different genotypes in the biotransformation enzyme genes of CYP2B6 and NAT2

2020 ◽  
Vol 98 (6) ◽  
pp. 40-46
Author(s):  
M. M. Yunusbаevа ◽  
L. Ya. Borodinа ◽  
F. S. Bilаlov ◽  
R. A. Shаripov ◽  
T. R. Nаsibullin ◽  
...  
Keyword(s):  
Molecular Genetic ◽  
Molecular Genetic Analysis ◽  
Patient Treatment ◽  
Control Group ◽  
Drug Resistant ◽  
Blood Leukocytes ◽  
Drug Resistant Tuberculosis ◽  
Polymorphic Loci ◽  
Resistant Tuberculosis ◽  
Efficacy Of Treatment

The objective of the study: to evaluate the efficacy of treatment of extensive drug resistant tuberculosis (XDR-TB) in patients with different genotypes in the biotransformation system NAT2 (rs1041983, rs1799930, rs1799931, rs1801280) and CYP2B6 genes (rs3745274).Subjects and methods. The study involved patients undergoing in-patient treatment at Republican Clinical TB Dispensary in Ufa from 2016 to 2018. XDR TB group included 210 people; the control group included 343 healthy donors. Molecular genetic analysis was performed on DNA samples isolated from peripheral blood leukocytes. Genotyping of polymorphic loci was carried out by kompetitive allele specific PCR (KASP).Results. It was revealed that polymorphic loci rs1799931 of NAT2 gene and rs3745274 of CYP2B6 gene were associated with the risk of developing XDR TB. Regression analysis detected combinations of the predictor genotypes of rs1799931*G/A × rs3745274*G/T and rs1799931*G/G × rs37455274*(G/G+T/T), that significantly reduce efficacy of XDR TB treatment.

scholarly journals Efficacy, safety and tolerability of linezolid for the treatment of XDR-TB: a study in China

2014 ◽  
Vol 45 (1) ◽  
pp. 161-170 ◽  
Author(s):  
Shenjie Tang ◽  
Lan Yao ◽  
Xiaohui Hao ◽  
Xia Zhang ◽  
Gang Liu ◽  
...  
Keyword(s):  
Adverse Events ◽  
Success Rate ◽  
Therapy Group ◽  
Treatment Success ◽  
Control Group ◽  
Drug Resistant ◽  
Drug Resistant Tuberculosis ◽  
Resistant Tuberculosis ◽  
Extensively Drug Resistant ◽  
Linezolid Therapy

Linezolid may be effective in treating multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis. We conducted a prospective, multicentre, randomised study to further evaluate the efficacy, safety and tolerability of linezolid in patients with extensively drug-resistant tuberculosis in China.65 patients who had culture-positive sputum for extensively drug-resistant tuberculosis were randomly assigned to a linezolid therapy group or a control group. Patients in the two groups adopted a 2-year individually based chemotherapy regimen. The linezolid therapy group was given linezolid at a start dose of 1200 mg per day for a period of 4–6 weeks and this was then followed by a dose of 300–600 mg per day.The proportion of sputum culture conversions in the linezolid therapy group was 78.8% by 24 months, significantly higher than that in the control group (37.6%, p<0.001). The treatment success rate in linezolid therapy group was 69.7%, significantly higher than that in the control group (34.4%, p=0.004). 27 (81.8%) patients had clinically significant adverse events in the linezolid group, of whom 25 (93%) patients had events that were possibly or probably related to linezolid. Most adverse events resolved after reducing the dosage of linezolid or temporarily discontinuing linezolid.Linezolid containing chemotherapy for treatment of extensively drug-resistant tuberculosis may significantly promote cavity closure, increase sputum culture-conversion rate and improve treatment success rate.

scholarly journals Safety and efficiency of the port-catheter for intensive intravenous chemotherapy in patients with multi-drug resistant tuberculosis and extensively drug-resistant tuberculosis

2018 ◽  
pp. 19-24
Author(s):  
S. O. Cherenko ◽  
N. A. Lytvynenko ◽  
O. A. Reva ◽  
O. V. Khmel ◽  
R. A. Veremeenenko ◽  
...  
Keyword(s):  
Intravenous Infusion ◽  
Control Group ◽  
Study Group ◽  
Drug Resistant ◽  
Intravenous Therapy ◽  
Port Catheter ◽  
Drug Resistant Tuberculosis ◽  
Resistant Tuberculosis ◽  
Mdr Tb ◽  
Sputum Conversion

PURPOSE. To study the efficacy and tolerability of the port catheter for continuous intravenous infusion in patients with MDR-TB and XDR-TB. MATERIALS AND METHODS. In a controlled study examined the effectiveness of the port catheter during an intensive 7-component anti-TB treatment with intravenous application of 3 anti-TB drugs (moxifloxacin, PAS, linezolid) in 16 patients with MDR-TB and XDR-TB. In the comparison group, which is formed by a pair of matching according to the drug resistance profile of MTB, the same intensive chemotherapy regimens in which the infusion of these drugs was carried out by daily injections of veins. In each group dominated patients with retreatment cases — 14 (87.5 %) patients. The planned duration of intravenous therapy was 2—4 months. RESULTS. Port-catheter for continuous infusion of combination of anti-tuberculosis drugs in comparison to their administration in the usual way ensures high efficiency and safety. In any case, was not observed phlebitis, no complaints of pain at the injection site, only 12.5 % cases were hematoma after setting the port in comparison to 100.0 % of patients with daily venous injections. In the study group was not a single case of interruption of intravenous infusion. In the control group, 56.2 % of patients discontinued intravenous treatment due to inability to penetrate the vein, patient’s complaints pain or phlebitis. At the end of the intensive phase of chemotherapy sputum conversion and disappearance of clinical symptoms were observed in 15 (3.7 %) patients of the study group, that was 26.7 % higher, than in control group (p>0,05). We found significant difference in terms of sputum conversion, which occurred in the study group through (2,2±0,1) months vs (3,7±0,3) months (<0,05) in control group. CONCLUSIONS. Port-catheter for long-term daily infusions of combination of anti-TB drugs compared with their usual daily injections is safe and effective method of intravenous therapy. It is not accompanied by subjective complaints of patients and the development of phlebitis, which leads to early sputum conversion. With daily injections of veins 56.2 % of patients prematurely discontinued treatment through intensive local complications or phlebitis. Application of intensive treatment with the introduction of anti-TB drugs allows for faster time to achieve sputum conversion.

scholarly journals Frequency of Cytokine Gene Polymorphism in Full-Term Newborns with Hypoxic Events

2020 ◽  
Vol 5 (4) ◽  
pp. 21-27
Author(s):  
M. S. Panova ◽  
A. S. Panchenko ◽  
B. S. Pushkarev
Keyword(s):  
Gene Polymorphism ◽  
Brain Damage ◽  
Molecular Genetic ◽  
Molecular Genetic Analysis ◽  
Full Term ◽  
Control Group ◽  
Cytokine Gene ◽  
Cytokine Gene Polymorphism ◽  
Blood Leukocytes ◽  
Intrauterine Hypoxia

Background. An infant brain damage is an extremely urgent problem, this pathology is difficult to prevent, and subsequently it manifests itself with a variety of neurological consequences. Various mechanisms are involved in neurodamage; cytokines, as well as genes that control their activity, are under a great concern today. However, there is little data about their role as predictors of the brain damage among children after hypoxia. Aim of the research. To identify the frequency of cytokine gene polymorphism: interleukin (IL)-1β(C-511T), IL-1β(C3953T), IL-4(C589T), IL-6(C174G), IL-10(C819T), IL-10(G1082A) among newborns with hypoxic events. Materials and methods. The study involved 128 full-term newborn patients with hypoxic events: the first group (n = 48) included newborns who experienced chronic intrauterine hypoxia (CVH), the second group (n = 80) included newborns born in asphyxiation. Control group (52) included babies born without asphyxia and not suffering from CVH. A retrospective analysis of case-records was carried out. The material for molecular genetic analysis was DNA samples isolated from umbilical cord blood leukocytes using DNA Express Blood reagents (Scientific and Production Company LITECH, Moscow). Results. Compared to the control group (p = 0.03) children born in asphyxia had their T allele IL-1β (C-511T) prevailed. The group of newborn who had CVH had their TT genotype (p = 0.04) and the T IL-1β allele (C-511T) (p = 0.01) prevailed compared to the control group. In the same study group while studying the polymorphism of the IL-1β gene, the T allele (p = 0.03) at the point C3953T prevailed, in contrast to the control group. Conclusion. Due to the fact that cytokines are part of a reaction cascade leading to the secondary brain damage, under the action of hypoxia, it was found that among newborns undergoing asphyxia and chronic intrauterine hypoxia the increased frequencies of carriage of IL-1β-511TT and IL-1β-3953TT genotypes, and IL-1β-511T and IL-1β-3953T alleles increase the risk of neurodamage.

New technologies for the diagnosis of drug-resistant tuberculosis

2020 ◽  
Vol 74 (6) ◽  
pp. 413-422
Author(s):  
Atadzhan E. Ergeshov ◽  
Larisa N. Chernousova ◽  
Sofya N. Andreevskaya
Keyword(s):  
New Technologies ◽  
Negative Impact ◽  
Treatment Success ◽  
Molecular Genetic ◽  
Diagnostic Process ◽  
Drug Resistant ◽  
Diagnostic Systems ◽  
Drug Resistant Tuberculosis ◽  
Resistant Tuberculosis ◽  
Microbiological Methods

Widespread drug-resistant tuberculosis is a global challenge that has a potential to have a negative impact on the global TB situation. Rapid TB diagnosis and early initiation of effective treatment based on the individualized chemotherapy regimens underpin efforts in prevention of further spread of tuberculosis. Microbiological methods of TB diagnosis that provide evidence of the TB process etiology and identify drug susceptibility of the pathogen play a very important role. The review covers the current and emerging methods of the microbiological TB diagnosis including conventional microbiological (microscopy of diagnostic material, cultural studies on solid media and culture fluids) and modern molecular genetic tests (DNA strips, biological microchips, multiplex PCR, GeneXpert and diagnostic systems of the new generation and point-of-care tests) and demonstrates the role of the described methods in the diagnostic TB laboratory algorithm. The example of the Microbiology Department of the Central TB Research Institute illustrates the effectiveness of modern developments in the diagnosis of drug-resistant tuberculosis and their impact on improving treatment success in the clinical departments of the CTRI. The review presents further prospects of drug-resistant TB diagnosis in relation to the new technologies such as Next Generation Sequencing. The conclusion summarizes information on the current state of microbiological diagnosis of drug-resistant tuberculosis and emphasizes the importance of developing and introducing new technologies into the diagnostic process.

scholarly journals Budgetary impact of using BPaL for treating extensively drug-resistant tuberculosis

2022 ◽  
Vol 7 (1) ◽  
pp. e007182
Author(s):  
Christiaan Mulder ◽  
Stephan Rupert ◽  
Ery Setiawan ◽  
Elmira Mambetova ◽  
Patience Edo ◽  
...  
Keyword(s):  
Patient Treatment ◽  
Drug Resistant ◽  
Drug Resistant Tuberculosis ◽  
Budgetary Impact ◽  
Tb Treatment ◽  
Resistant Tuberculosis ◽  
Extensively Drug Resistant ◽  
Budget Reduction ◽  
The Status ◽  
Gradual Introduction

IntroductionBedaquiline, pretomanid and linezolid (BPaL) is a new all oral, 6-month regimen comprised of bedaquiline, the new drug pretomanid and linezolid, endorsed by the WHO for use under operational research conditions in patients with extensively drug-resistant tuberculosis (XDR-TB). We quantified per-patient treatment costs and the 5-year budgetary impact of introducing BPaL in Indonesia, Kyrgyzstan and Nigeria.MethodsPer-patient treatment cost of BPaL regimen was compared head-to-head with the conventional XDR-TB treatment regimen for respective countries based on cost estimates primarily assessed using microcosting method and expected frequency of each TB service. The 5-year budget impact of gradual introduction of BPaL against the status quo was assessed using a Markov model that represented patient’s treatment management and outcome pathways.ResultsThe cost per patient completing treatment with BPaL was US$7142 in Indonesia, US$4782 in Kyrgyzstan and US$7152 in Nigeria – 57%, 78% and 68% lower than the conventional regimens in the respective countries. A gradual adoption of the BPaL regimen over 5 years would result in an 5-year average national TB service budget reduction of 17% (US$128 780) in XDR-TB treatment-related expenditure in Indonesia, 15% (US$700 247) in Kyrgyzstan and 32% (US$1 543 047) in Nigeria.ConclusionOur study demonstrates that the BPaL regimen can be highly cost-saving compared with the conventional regimens to treat patients with XDR-TB in high drug-resistant TB burden settings. This supports the rapid adoption of the BPaL regimen to address the significant programmatic and clinical challenges in managing patients with XDR-TB in high DR-TB burden countries.

scholarly journals Safety and efficiency of the port-catheter for intensive intravenous chemotherapy in patients with multi-drug resistant tuberculosis and extensively drug-resistant tuberculosis

2018 ◽  
pp. 19-24
Author(s):  
S. O. Cherenko ◽  
N. A. Lytvynenko ◽  
O. A. Reva ◽  
O. V. Khmel ◽  
R. A. Veremeenenko ◽  
...  
Keyword(s):  
Intravenous Infusion ◽  
Control Group ◽  
Study Group ◽  
Drug Resistant ◽  
Intravenous Therapy ◽  
Port Catheter ◽  
Drug Resistant Tuberculosis ◽  
Resistant Tuberculosis ◽  
Mdr Tb ◽  
Sputum Conversion

PURPOSE. To study the efficacy and tolerability of the port catheter for continuous intravenous infusion in patients with MDR-TB and XDR-TB. MATERIALS AND METHODS. In a controlled study examined the effectiveness of the port catheter during an intensive 7-component anti-TB treatment with intravenous application of 3 anti-TB drugs (moxifloxacin, PAS, linezolid) in 16 patients with MDR-TB and XDR-TB. In the comparison group, which is formed by a pair of matching according to the drug resistance profile of MTB, the same intensive chemotherapy regimens in which the infusion of these drugs was carried out by daily injections of veins. In each group dominated patients with retreatment cases – 14 (87.5 %) patients. The planned duration of intravenous therapy was 2–4 months. RESULTS. Port-catheter for continuous infusion of combination of anti-tuberculosis drugs in comparison to their administration in the usual way ensures high efficiency and safety. In any case, was not observed phlebitis, no complaints of pain at the injection site, only 12.5 % cases were hematoma after setting the port in comparison to 100.0 % of patients with daily venous injections. In the study group was not a single case of interruption of intravenous infusion. In the control group, 56.2 % of patients discontinued intravenous treatment due to inability to penetrate the vein, patient’s complaints pain or phlebitis. At the end of the intensive phase of chemotherapy sputum conversion and disappearance of clinical symptoms were observed in 15 (3.7 %) patients of the study group, that was 26.7 % higher, than in control group (p>0,05). We found significant difference in terms of sputum conversion, which occurred in the study group through (2,2±0,1) months vs (3,7±0,3) months (<0,05) in control group. CONCLUSIONS. Port-catheter for long-term daily infusions of combination of anti-TB drugs compared with their usual daily injections is safe and effective method of intravenous therapy. It is not accompanied by subjective complaints of patients and the development of phlebitis, which leads to early sputum conversion. With daily injections of veins 56.2 % of patients prematurely discontinued treatment through intensive local complications or phlebitis. Application of intensive treatment with the introduction of anti-TB drugs allows for faster time to achieve sputum conversion.

Molecular Characterization and Genetic Diversity Study in F3 Population of Rice

2013 ◽  
Vol 20 (1-2) ◽  
pp. 1-8
Author(s):  
MM Rahman ◽  
L Rahman ◽  
SN Begum ◽  
F Nur
Keyword(s):  
Genetic Distance ◽  
Gene Diversity ◽  
Random Amplified Polymorphic Dna ◽  
Molecular Genetic ◽  
Molecular Genetic Analysis ◽  
Polymorphic Loci ◽  
Rice Genotypes ◽  
High Level ◽  
Genetic Diversity Study ◽  
Diversity Study

Random Amplified Polymorphic DNA (RAPD) assay was initiated for molecular genetic analysis among 13 F3 rice lines and their parents. Four out of 15 decamer random primers were used to amplify genomic DNA and the primers yielded a total of 41 RAPD markers of which 37 were considered as polymorphic with a mean of 9.25 bands per primer. The percentage of polymorphic loci was 90.24. The highest percentage of polymorphic loci (14.63) and gene diversity (0.0714) was observed in 05-6 F3 line and the lowest polymorphic loci (0.00) and gene diversity (0.00) was found in 05-12 and 05-15 F3 lines. So, relatively high level of genetic variation was found in 05-6 F3 line and it was genetically more diverse compared to others. The average co-efficient of gene differentiation (GST) and gene flow (Nm) values across all the loci were 0.8689 and 0.0755, respectively. The UPGMA dendrogram based on the Nei’s genetic distance differentiated the rice genotypes into two main clusters: PNR-519, 05-19, 05-14, 05-12 and 05-17 grouped in cluster 1. On the other hand, Baradhan, 05-9, 05-13, 05-11, 05-5, 05-6, 05-1, 05-4, 05-15 and 05-25 were grouped in cluster 2. The highest genetic distance (0.586) was found between 05-4 and 05-17 F3 lines and they remain in different cluster.DOI: http://dx.doi.org/10.3329/pa.v20i1-2.16839 Progress. Agric. 20(1 & 2): 1 – 8, 2009

Sign in / Sign up

Export Citation Format

Share Document