scholarly journals The Use of High Resolution Melting (HRM) Method to Detect rs1800629 of Tumor Necrosis Factor-alpha (TNF-alpha) Gene among Tuberculosis Patients

2021 ◽  
Vol 7 (1) ◽  
pp. 66
Author(s):  
Kinasih Prayuni ◽  
Intan Razari ◽  
Silviatun Nihayah ◽  
Rika Yuliwulandari
Keyword(s):  
Low Cost ◽  
Mutation Screening ◽  
Cost Effective ◽  
Multidrug Resistant ◽  
Drug Induced ◽  
Necrosis Factor Alpha ◽  
Tuberculosis Patients ◽  
Direct Dna Sequencing ◽  
Tnf Α ◽  
Mdr Tb

The rs1800629 polymorphism plays a crucial role in the pathogenesis of infectious and autoimmune diseases. Meanwhile, tuberculosis (TB) remains a health primary infectious disease in Indonesia. The purpose of this study is to evaluate the HRM method in detecting the rs1800629 genotype, in the TNF-α gene’s promoter region, within TB patients. The benefit of this study is to accelerate the detection of rs1800629 with a simple, rapid, and cost-effective method for genotyping and mutation screening that does not include the use of a fluorescent probe. In this experimental study, the rs1800629 genotyped in a total of 25 tuberculosis patients using KAPA HRM kit in MyGo Mini PCR, and all amplified PCR products subsequently dispatched for direct DNA sequencing to Macrogen Inc, South Korea. Based on the results, a 100% concordance find in the genotyping of rs1800629 between HRM and sequencing. The authors provided evidence to use HRM in detecting rs1800629 within the TNF-α promotor region. This application as a genotyping assay in tuberculosis patients is a low-cost, rapid, and accurate detection. However, further studies using the HRM method in case-control samples of tuberculosis are required to evaluate the method’s effectiveness and to obtain more information regarding the genotype’s susceptibility to tuberculosis and its adverse effect treatment, including anti-tuberculosis drug, induced liver injury (AT-DILI), and multidrug-resistant TB (MDR-TB), within the Indonesian population.

scholarly journals The epidemiologic impact and cost-effectiveness of new tuberculosis vaccines on multidrug-resistant tuberculosis in India and China

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Chathika K Weerasuriya ◽  
Rebecca C Harris ◽  
C Finn McQuaid ◽  
Fiammetta Bozzani ◽  
Yunzhou Ruan ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Cost Effective ◽  
Multidrug Resistant ◽  
Second Line ◽  
Second Line Therapy ◽  
China And India ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Line Therapy ◽  
Mdr Tb

Abstract Background Despite recent advances through the development pipeline, how novel tuberculosis (TB) vaccines might affect rifampicin-resistant and multidrug-resistant tuberculosis (RR/MDR-TB) is unknown. We investigated the epidemiologic impact, cost-effectiveness, and budget impact of hypothetical novel prophylactic prevention of disease TB vaccines on RR/MDR-TB in China and India. Methods We constructed a deterministic, compartmental, age-, drug-resistance- and treatment history-stratified dynamic transmission model of tuberculosis. We introduced novel vaccines from 2027, with post- (PSI) or both pre- and post-infection (P&PI) efficacy, conferring 10 years of protection, with 50% efficacy. We measured vaccine cost-effectiveness over 2027–2050 as USD/DALY averted-against 1-times GDP/capita, and two healthcare opportunity cost-based (HCOC), thresholds. We carried out scenario analyses. Results By 2050, the P&PI vaccine reduced RR/MDR-TB incidence rate by 71% (UI: 69–72) and 72% (UI: 70–74), and the PSI vaccine by 31% (UI: 30–32) and 44% (UI: 42–47) in China and India, respectively. In India, we found both USD 10 P&PI and PSI vaccines cost-effective at the 1-times GDP and upper HCOC thresholds and P&PI vaccines cost-effective at the lower HCOC threshold. In China, both vaccines were cost-effective at the 1-times GDP threshold. P&PI vaccine remained cost-effective at the lower HCOC threshold with 49% probability and PSI vaccines at the upper HCOC threshold with 21% probability. The P&PI vaccine was predicted to avert 0.9 million (UI: 0.8–1.1) and 1.1 million (UI: 0.9–1.4) second-line therapy regimens in China and India between 2027 and 2050, respectively. Conclusions Novel TB vaccination is likely to substantially reduce the future burden of RR/MDR-TB, while averting the need for second-line therapy. Vaccination may be cost-effective depending on vaccine characteristics and setting.

scholarly journals Genetic characterization of N-acetyltransferase 2 variants in acquired multidrug-resistant tuberculosis in Indonesia

2021 ◽  
Author(s):  
Rika Yuliwulandari ◽  
Kinasih Prayuni ◽  
Intan Razari ◽  
Retno W Susilowati ◽  
Yenni Zulhamidah ◽  
...  
Keyword(s):  
Multidrug Resistant ◽  
Resistance Rate ◽  
Published Data ◽  
Drug Induced ◽  
Tb Treatment ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Appropriate Treatment ◽  
Acetylator Status ◽  
Mdr Tb

Background: Owing to the high resistance rate of tuberculosis (TB) to isoniazid, which is metabolized by N-acetyltransferase 2 (NAT2), we investigated the associations between NAT2 variants and multidrug-resistant (MDR)-TB. Materials & methods: The acetylator status based on NAT2 haplotypes of 128 patients with MDR-TB in Indonesia were compared with our published data from patients with anti-TB drug-induced liver injury (AT-DILI), TB and the general population. Results: NAT2*4 was more frequent in the MDR-TB group than in the AT-DILI group, TB controls and general controls. NAT2*4/*4 was significantly more frequent in patients with MDR-TB than in those with AT-DILI. NAT2*5B/7B, *6A/6A and *7B/*7B were detected at lower frequencies in patients with AT-DILI. Rapid acetylators were significantly more frequent in patients with MDR-TB than in those with AT-DILI. Conclusion: These results provide an initial data for optimizing TB treatment in the Indonesian population, and suggest that NAT2 genotyping may help to select appropriate treatment by predicting TB-treatment effect.

scholarly journals Constraints of Drug Resistance in Mycobacterium tuberculosis - Prospects for Pharmacological Reversion of Susceptibility to Antibiotics

2017 ◽  
Vol 8 (1) ◽  
pp. 33-43 ◽  
Author(s):  
Aleksandr I. Ilin ◽  
Murat E. Kulmanov ◽  
Ilya S. Korotetskiy ◽  
Marina V. Lankina ◽  
Gulshara K. Akhmetova ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Genetic Heterogeneity ◽  
Multidrug Resistant ◽  
Resistance Mutations ◽  
General Increase ◽  
Drug Induced ◽  
Mdr Tb ◽  
Resistant Strains

Emergence of multidrug resistant strains ofMycobacterium tuberculosis(MDR-TB) threatens humanity. This problem was complicated by the crisis in development of new anti-tuberculosis antibiotics. Induced reversion of drug resistance seems promising to overcome the problem. Successful clinical trial of a new anti-tuberculosis nanomolecular complex FS-1 has demonstrated prospectively of this approach in combating MDR-TB. Several clinical MDR-TB cultures were isolated from sputum samples prior and in the process of the clinical trial. Every isolate was tested for susceptibility to antibiotics and then they were sequenced for comparative genomics. It was found that the treatment with FS-1 caused an increase in the number of antibiotic susceptible strains among Mtb isolates that was associated with a general increase of genetic heterogeneity of the isolates. Observed impairing of phthiocerol dimycocerosate biosynthesis by disruptive mutations inppsACDsubunits indicated a possible virulence remission for the sake of persistence. It was hypothesized that the FS-1 treatment eradicated the most drug resistant Mtb variants from the population by aggravating the fitness cost of drug resistance mutations. Analysis of distribution of these mutations in the global Mtb population revealed that many of them were incompatible with each other and dependent on allelic states of many other polymorphic loci. The latter discovery may explain the negative correlation between the genetic heterogeneity of the population and the level of drug tolerance. To the best of our knowledge, this work was the first experimental confirmation of the drug induced antibiotic resistance reversion by the induced synergy mechanism that previously was predicted theoretically.

scholarly journals Early detection of MDR Mycobacterium tuberculosis mutations in Pakistan

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ayma Aftab ◽  
Samia Afzal ◽  
Zahida Qamar ◽  
Muhammad Idrees
Keyword(s):  
Early Detection ◽  
Control Program ◽  
Cost Effective ◽  
Treated Group ◽  
Multidrug Resistant ◽  
Control Group ◽  
Double Mutation ◽  
Treatment Regimens ◽  
Mdr Tb ◽  
Save Energy

AbstractThe result of improper treatment has led to the rise of Multidrug-resistant (MDR) strains. This concern still exists in Pakistan. In order to save energy, time and resources an early detection of resistant cases is imperative. Thus, a treated group of 100 isolates and a control group of 56 untreated isolates were studied. PCR and gene sequencing showed mutations at codon 531 and 513 in the rpoB gene. 12% of cases showed a double mutation in the rpoB gene. katG gene showed mutations at codon 315 and 299. 28.6% of the control group cases were positive for MDR whereas 100% of the treated group were positive for MDR. This study explores the significantly increasing ratio of MDR-TB among Pakistani population. This study provides prevalent MDR mutations among Pakistanis and suggests developing such molecular assays that are time and cost effective. Importance: Pakistan is a developing country and has fourth highest incidence rate of MDR-TB. The treatment of MDR-TB is the use of second line drugs that has severe side effects as well as it requires long time span. One of the strategies to control the spread of MDR-TB is to decipher the aberrations at molecular level in order to formulate potent drugs that can treat the patients within short span of time. Determining the mutation profile of MDR in Pakistani populations will open new horizons for the improvement of drug treatment regimens to make it more effective or for the development of novel potent drugs and vaccines to better treat the drug-resistant TB. Moreover, this study will be help in disease control program.

scholarly journals Analysis of Smear Microscopy and Culture Conversion Results in Multidrug-Resistant Tuberculosis Patients with and without Type 2 Diabetes Mellitus

2020 ◽  
Vol 26 (3) ◽  
Author(s):  
Henny Fauziah ◽  
Aprianti S. ◽  
Handayani I. ◽  
Kadir NA
Keyword(s):  
Diabetes Mellitus ◽  
Multidrug Resistant ◽  
World Health ◽  
Smear Microscopy ◽  
Tuberculosis Patients ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Significant Difference ◽  
Mdr Tb ◽  
Culture Conversion

  The World Health Organization (WHO) recommended microscopic AFB smear examination and culture as follow-ups to the response of MDR TB therapy. Analyzed the results of microscopic AFB smear and culture conversion as well as treatment outcome in Multidrug-Resistant Tuberculosis (MDR-TB) patients with and without Diabetes Mellitus (DM). This is a retrospective study involved 70 MDR-TB patients with (27 patients) with DM and without DM (43 patients) who had microscopic AFB smear and culture results at the start of the follow-up therapy. This research was conducted at Labuang Baji Regional Public Hospital, Makassar, from June to July 2019, used medical records of MDR-TB patients the period of June 2016 to December 2017. The results showed that 52 out of 70 MDR-TB patients had microscopic AFB smear and culture conversion in MDR-TB with DM (21 patients) and without DM (31 patients). The duration of microscopic AFB smear conversion in MDR TB patients with DM (3.33±0.54 months) was longer than patients without DM (2.07±0.05 months), p=0.001. While in culture conversion, there was no significant difference between MDR-TB with DM (1.28±0.64 months) and without DM (1.25±0.59), p=0.648. The recovery outcome between MDR-TB with (48.1%) and without DM (48.8%) was not significantly different. However, the output of treatment failure was greater in DM (11.2%) than without DM (2.3%), although statistically, there was no significant difference (p=0.568). Multidrug-resistant tuberculosis patients with DM experienced slower microscopic AFB smear conversion than MDR-TB patients without DM. However, in culture, there was no significant difference in the conversion period between the two groups. MDR-TB patients, both of with and without DM, had the same chance of recovery.

scholarly journals N-Acetyl Cysteine as an Adjunct in the Treatment of Tuberculosis

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Dawit A. Ejigu ◽  
Solomon M. Abay
Keyword(s):  
Oxidative Stress ◽  
Hearing Loss ◽  
Multidrug Resistant ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Beneficial Effects ◽  
Tb Treatment ◽  
Mdr Tb ◽  
Acetyl Cysteine ◽  
Karnofsky Performance Index

Oxidative stress is a common feature of tuberculosis (TB), and persons with reduced antioxidants are at more risk of TB. TB patients with relatively severe oxidative stress had also more advanced disease as measured by the Karnofsky performance index. Since adverse effects from anti-TB drugs are also mediated by free radicals, TB patients are prone to side effects, such as hearing loss. In previous articles, researchers appealed for clinical trials aiming at evaluating N-acetyl cysteine (NAC) in attenuating the dreaded hearing loss during multidrug-resistant TB (MDR-TB) treatment. However, before embarking on such trials, considerations of NAC’s overall impact on TB treatment are crucial. Unfortunately, such a comprehensive report on NAC is missing in the literature and this manuscript reviews the broader effect of NAC on TB treatment. This paper discusses NAC’s effect on mycobacterial clearance, hearing loss, drug-induced liver injury, and its interaction with anti-TB drugs. Based on the evidence accrued to date, NAC appears to have various beneficial effects on TB treatment. However, despite the favorable interaction between NAC and first-line anti-TB drugs, the interaction between the antioxidant and some of the second-line anti-TB drugs needs further investigations.

scholarly journals Plasma Levels of Cytokines (IL-10, IFN-γ and TNF-α) in Multidrug Resistant Tuberculosis and Drug Responsive Tuberculosis Patients in Ghana

Diseases ◽  
2018 ◽  
Vol 7 (1) ◽  
pp. 2 ◽  
Author(s):  
Anthony Basingnaa ◽  
Samuel Antwi-Baffour ◽  
Dinah Nkansah ◽  
Emmanuel Afutu ◽  
Enid Owusu
Keyword(s):  
Plasma Levels ◽  
Sandwich Elisa ◽  
Plasma Concentrations ◽  
Multidrug Resistant ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Tnf Α ◽  
Mdr Tb ◽  
Ifn Γ ◽  
Socio Economic Factors

The emergence of multidrug-resistant tuberculosis (MDR–TB) and more recently, extensively drug-resistant (XDR) TB has intensified the need for studies aimed at identifying factors associated with TB drug resistance. This study determined the differences in plasma concentrations of pro-inflammatory (IFN-γ and TNF-α) and anti-inflammatory (IL-10) cytokines in MDR-TB and drug-susceptible (DS) TB patients, in addition to some socio-economic factors. Plasma levels of IL-10, IFN-γ and TNF-α were measured in 83 participants (comprising 49 MDR-TB and 34 DS-TB patients) using sandwich ELISA. Levels of the three cytokines were elevated in MDR-TB patients compared to DS-TB patients. The mean level of IL-10 (7.8 ± 3.61 ρg/mL) measured in MDR-TB cases was relatively higher than those of TNF-α and IFN-γ, and statistically significant (p = 0.0022) when compared to the level of IL-10 (4.8 ± 4.94 ρg/mL) in the DS-TB cases. There were statistically significant associations between MDR-TB and factors such as education level (X2 = 9.895, p = 0.043), employment status (X2 = 19.404, p = 0.001) and alcoholism (X2 = 3.971, p = 0.046). This study adds to the knowledge that IFN-γ, TNF-α and IL-10 play a role in the host response to Mycobacterium tuberculosis (MTB). Alcohol intake can be considered as an important MDR-TB risk factor.

scholarly journals An Abundant New Saponin-Polybromophenol Antibiotic (CU1) from Cassia fistula Bark Against Multi-Drug Resistant Bacteria Targeting RNA Polymerase

2020 ◽  
Author(s):  
Asit Kumar Chakraborty ◽  
Sourajit Saha ◽  
Kousik Poria ◽  
Tanmoy Samanta ◽  
Sudhanshu Gautam ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
Low Cost ◽  
Broad Band ◽  
Ethanol Extract ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Cassia Fistula ◽  
Major Band ◽  
Drug Resistant Bacteria ◽  
Mdr Tb

AbstractSpread of multidrug-resistant infections is a threat to human race and need for new drug development is great. Bark ethanol extract of Cassia fistula inhibited MDR bacteria isolated from Ganga River water, human and animal. On TLC, a gray colour major band ran fast (CU1; 6.6% of bark and ~30% of crude extract) which quickly purified on HPLC C18 column at 3 min. Chemical assays suggested a triterpene linked to polyphenol known as saponin. CHN Elements analysis (35.9% C; 5.5% H) did not identified nitrogen suggesting a polyphenol or glycoside. VU-Vis spectra gave high peak at below 200nm with a secondary peak at 275nm with minor hinge at 578nm indicating a fused ring with bromo-polyphenol. CU1 Mass (897 Daltons) with fragments of 515, 325, 269, 180 daltons and six halogen substitutions reflected by 82 molecular mass of DBr deviate six larger fragments. FT-IR suggested broad band at 3500-3000 cm−1 for −OH where as two strong peaks at 1552cm−1 for aromatic C=C and 1408cm−1 for phenol. Proton-NMR confirmed polymeric phenol at δ 4.86-4.91 ppm and tetratet at δ3.57-3.618 ppm with phenolic bromo-substituents. Carbon-NMR identified a strong peak at δ=23.7ppm for many C-Br and at 165ppm for a polybenzoid compound. CU1 inhibited the RNA Polymerase of E. coli (IC50=23μg/ml) and M. tuberculosis (IC50=34μg/ml) but not DNA polymerase. Gel shift assays demonstrated that CU1 drug interacted with enzyme and inhibited its binding to open promoter complex. Thus, CU1 phyto-chemical is an alternative safer and low cost drug against MDR-TB as well as other MDR pathogens.

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