scholarly journals Molecular Mechanisms of Drug Resistance in Mycobacterium tuberculosis: Role of Nanoparticles Against Multi-drug-Resistant Tuberculosis (MDR-TB)

2020 ◽  
pp. 285-314
Author(s):  
Amit Singh ◽  
Anil Kumar Gupta ◽  
Sarman Singh
Author(s):  
Prashant V. Solanke ◽  
Preeti Pawde ◽  
Ajin R. M.

Background: Tuberculosis (TB) is one of the major causes of morbidity and mortality worldwide. Resistance to antitubercular drugs has been noted since the drugs were first introduced, and occasionally outbreaks of drug-resistant tuberculosis have been reported worldwide. WHO emphasizes that good TB control prevents the emergence of drug resistance in the first place and that the proper treatment of multi-drug resistant tuberculosis prevents the emergence of XDR-TB. The objectives of the study were to examine the sputum samples regarding MDR-TB, to study the grading regarding sputum positive and to study the multi-drug resistance tuberculosis in Sree Mookambika Institute of Medical sciences.Methods: Study design was cross-sectional, Study duration was January 2016-March 2017. Study place was Sree Mookambika Institute of Medical Sciences Hospital, Kulasekharam. Sample size was 400. Data entered in MS-Office Word- 2016. Institutional ethical committee clearance was obtained. Results: In present study 54.86% patient had sputum AFB positive, 45.13% had sputum AFB negative smears. 75% of the sputum AFB positive pulmonary TB came under the age group between 20-60 and 25% above 60 yrs. 78.24% males, 21.75% females had sputum AFB smear positive pulmonary tuberculosis and 43.73% patients had positive sputum culture, 56.26% patients had negative sputum culture and the most common strain found was Mycobacterium tuberculosis. Conclusions: So from our study we found that Mycobacterium tuberculosis is the major strain isolated from sputum samples. The resistance is more to Isoniazid and Rifampicin and is more in the rural parts of India. Early screening and drug susceptibility test of culture positive and MTB cases will help in initiating treatment of MDR-TB. 


2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S276-S276
Author(s):  
Emily Weldon ◽  
Naveen Patil ◽  
Jan Voyles ◽  
Sandra Chai ◽  
Marsha Majors ◽  
...  

Abstract Background Multi-drug-resistant tuberculosis (MDR-TB) is a threat to TB elimination strategies worldwide. From 1998 to 2016, six cases of MDR-TB were reported in Arkansas. In 2017 alone, three cases were detected. We sought to describe the characteristics of these cases to inform our MDR-TB prevention strategy in AR. Methods The surveillance database identified three MDR-TB cases in 2017. A detailed review was done to define the demographics, clinical presentation, and laboratory reports relating to drug susceptibility testing (DST), including molecular detection of drug resistance (MDDR). A search was done in the Genotyping database for genotype patterns of the patient isolates. Results All three cases were born outside the United States and developed active disease after arrival in AR. Case 1, age 52, was born in the Marshall Islands, arrived in 2016, and had a history of Type 2 diabetes. He developed MDR-TB in February 2017. Case 2, age 42, was born in Mexico, arrived over 20 years ago, and was HIV positive. He developed TB in July 2016 with a pan-sensitive organism and completed an intermittent treatment regimen. A second TB episode with matching genotype but different drug sensitivities occurred in April 2017, less than 4 months after treatment completion, and was considered treatment failure. Case 3, age 56, was born in the Philippines, arrived in 1990, and was reportedly treated for latent TB infection in 1993 with 6 months of isoniazid. She visited the Philippines April–May 2017 and developed MDR-TB in October 2017. Her isolate was in cluster with a case in Oklahoma who came from Mexico in 2006 and was admitted in an AR hospital with a pan-sensitive organism. There are no epidemiological links between the two cases; only one isolate in each case. Because both isolates were identified in AR State TB laboratory, a complex contamination has been considered with no definite resolution at this time. Conclusion MDR-TB, due to both primary and secondary drug resistance, remains a threat in AR. Cooperation and communication between all levels of healthcare are crucial to avoid delayed diagnosis of MDR-TB. Timely DST via technologies like GeneXpert and MDDR service at CDC is critical. Consultation from Centers of Excellence is vital in the treatment of MDR-TB complicated by diabetes and HIV. Whole-genome sequencing could provide clarity in the cluster with discordant DST patterns. Disclosures All authors: No reported disclosures.


Author(s):  
Chandra Prakash Bhatt ◽  
B KC

Introduction: Treatment of multi drug resistant Mycobacterium tuberculosis (MDR-TB) with second line drugs is associated with adverse drug reactions and toxicity. Aim of this study were to determine side effects associated with drugs used in treatment of multi drug resistant tuberculosis and treatment related factors of MDR-TB patients.Methodology: A prospective study was carried out in National Tuberculosis Centre Bhaktapur Nepal. Questionnaires were used to collect data from patients.Results: Total 101 MDR TB patients were included among them majorities were male (52%) and mean age of the patients was 31.2 years. Majority of patients (87.1%) had previous history of tuberculosis treatment and 54.5% were in intensive phase of treatment. The side effect associated with drugs used in treatment of MDR-TB reported by patients were joint pain (21.2%), nausea (20.3%), hearing disturbances (11%), gastrointestinal disturbance (9.9%), depression (9.6%), itching (8.1%), hypothyroidism (6.4%), dizziness (6.4%), seizures (3.8%) and hepatitis (3.5%). Last month 25.74% patients missed one or more doses of drugs and 3.9% missed drug doses due to side effect of drugs. Majorities of the patients used vehicle to reach health centre (92.07%), time to reach the health center (59.4%) were less than 30 minutes but majorities of patients (57.4%) were not satisfied by the counseling of health care worker.Conclusion: The finding of this study shows that in MDR patients 12.8% were found new cases. Last month 3.9% patients were stopped the drugs due to side effects of drugs. Majority of patients (57.4%) were not satisfied by counseling of health care worker. Treatment of multi drug resistant tuberculosis with second line anti tubercular drugs is associated with side effects, health care worker counseling to MDR- TB patients with full attention is essential to encourage the patient’s moral and complete the treatment. Timely managing the side effects of medication is important in helping people to complete their treatment.SAARC J TUBER LUNG DIS HIV/AIDS, 2017; XIV(1), Page: 1-6


2020 ◽  
Vol 46 (1) ◽  
pp. 22-28
Author(s):  
Shirin Tarafder ◽  
Md Bayzid Bin Monir

Background: To investigate the spread of specific genotypes in a defined geographical area and to determine any relationship of these genotypes with drug resistance the most essential method is molecular typing. It allows a rapid and precise species differentiation. Objective: This study was intended to observe the genotypes of XDR mycobacterium tuberculosis by determining 24 loci MIRU-VNTR analysis. Methods: To gain an insight about molecular typing of MTB and drug resistance-associated mutations in XDR-TB isolates a total of 98 multi drug resistant tuberculosis (MDR-TB) isolates collected through Xpert MTB/RIF assay. They were subjected to 2nd line (Fluoroquinolones, kanamycin, capreomycin and amikacin) drug susceptibility testing through line probe assay (LPA) in a view to detect extensively drug resistant tuberculosis (XDR-TB). Genotyping was done for XDR-TB isolates using 24 loci Mycobacterial Interspersed Repetitive Units-Variable Number of Tandem Repeats (MIRU-VNTR) using the online tool at http://www.MIRU-VNTRplus.org.. Out of 98 MDR-TB isolates 11(11.23%)  XDR-TB isolates were typed and analysed. Results: Twenty four loci MIRU-VNTR genotyping involving similarity searching and phylogenetic tree analysis revealed that six (54.60%) XDR-TB isolates belonged to Beijing strain, Other MTB strain also detected were Delhi/CAS two(18.20%), Haarlem two(18.20%) and New-1, one (9.10%) in number. Minimum spanning tree analysis showed two strain of Beijing family form a clonal complex. Beijing strains were more common among younger age group and within urban population. Beijing strains were also predominant in treatment failure patient. Only one new case of XDR-TB belongs to Delhi/CAS family. Second line mycobacterial drug resistance (MTBDRsl) detected by LPA showed the most prevalent mutations involved in Fluoroquinolones drug resistance (FQ) was Asp94Gly in gyrA gene (54.55%) in quinolone resistance determining region (QRDR) and for Injectable 2nd line Drug resistance (ISL) was A1401G, C1402T in 16S rrs gene (100%)..  All XDR-TB isolates showed resistance to Levofloxacin in 2nd line LPA but Moxifloxacin showed low level resistance to some cases. Conclusion: Molecular typing of XDR- TB isolates and pattern of drug resistance associated mutations in XDR-TB isolates in Bangladesh have not been reported previously. The result of this study highlights the need to reinforce the TB policy in Bangladesh with regard to control the spread and transmission as well as detection and treatment strategies regarding XDR-TB. Bangladesh Med Res Counc Bull 2020; 46(1): 22-28


2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Teklu Molie ◽  
Zelalem Teklemariam ◽  
Eveline Klinkenberg ◽  
Yadeta Dessie ◽  
Andargachew Kumsa ◽  
...  

Abstract Background Multi-drug resistant Tuberculosis (MDR-TB) is a strain of Mycobacterium tuberculosis that is resistant to at least Rifampicin and Isoniazid drugs. The treatment success rate for MDR-TB cases is lower than for drug susceptible TB. Globally only 55% of MDR-TB patients were successfully treated. Monitoring the early treatment outcome and better understanding of the specific reasons for early unfavorable and unknown treatment outcome is crucial for preventing the emergence of further drug-resistant tuberculosis. However, this information is scarce in Ethiopia. Therefore, this study aimed to determine the intensive phase treatment outcome and contributing factors among patients treated for MDR-TB in Ethiopia. Methods A 6 year retrospective cohort record review was conducted in fourteen TICs all over the country. The records of 751 MDR-TB patients were randomly selected using simple random sampling technique. Data were collected using a pre-tested and structured checklist. Multivariable multinomial logistic regression was undertaken to identify the contributing factors. Results At the end of the intensive phase, 17.3% of MDR-TB patients had an unfavorable treatment outcome, while 16.8% had an unknown outcome with the remaining having a favorable outcome. The median duration of the intensive phase was 9.0 months (IQR 8.04–10.54). Having an unfavorable intensive phase treatment outcome was found significantly more common among older age [ARRR = 1.047, 95% CI (1.024, 1.072)] and those with a history of hypokalemia [ARRR = 0.512, 95% CI (0.280, 0.939)]. Having an unknown intensive phase treatment outcome was found to be more common among those treated under the ambulatory care [ARRR = 3.2, 95% CI (1.6, 6.2)], rural dwellers [ARRR = 0.370, 95% CI (0.199, 0.66)], those without a treatment supporter [ARRR = 0.022, 95% CI (0.002, 0.231)], and those with resistance to a limited number of drugs. Conclusion We observed a higher rate of unfavorable and unknown treatment outcome in this study. To improve favorable treatment outcome more emphasis should be given to conducting all scheduled laboratory monitoring tests, assignment of treatment supporters for each patient and ensuring complete recording and reporting which could be enhanced by quarterly cohort review. Older aged and rural patients need special attention. Furthermore, the sample referral network should be strengthened.


2012 ◽  
Vol 8 (4) ◽  
pp. 392-397 ◽  
Author(s):  
S B Marahatta ◽  
J Kaewkungwal ◽  
P Ramasoota ◽  
P Singhasivanon

Introduction Tuberculosis is the most widespread infectious disease in Nepal and poses a serious threat to the health and development of the country. Incidences of drug resistant tuberculosis in Nepal are increasing and this tuberculosisis a major threat to successfully controlling tuberculosis . Objective The general objective of the study was to assess the risk factors of multi-drug resistant tuberculosis among the patients attending the National Tuberculosis Centre, Bhaktpur Nepal. Methods An observational study/ case-control study with a Atotal number of 55 multi-drug resistant tuberculosis cases and 55 controls. The study was conducted among the patient attending in the National Tuberculosis Centre , Bhaktpur Nepal for six months, between May–October 2010. sImulti-drug resistant tuberculosis wasThe collected data was analysed in SPSS 11.5 version. The association between categorical variables were analysed by chi-square tests, OR and their 95% CI were measured. Results The total number of patients used for the study was 110, of which among them 55 were cases and 55 were controls . Our study revealed that there were significant associations between history of prior TB MDR-TB OR =2.799 (95 % CI 1.159 to 6.667) (p=0.020); smoking habit OR =2.350 and (95%CI 1.071 to 5.159) (p=0.032); social stigma social stigma OR 2.655 (95%CI r 1.071 to 5.159) (p=0.013); knowledge on MDR-TB OR =9.643 (95% CI 3.339 to 27.846) (p < 0.001)and knowledge on DOTS Plus OR=16.714 (95% CI is ranging from 4.656 to 60.008) (p< 0.001). However, there was no association found between alcohol drinking habits and ventilation in the room. Conclusion Our study revealed that there were significant associations between history of prior tuberculosis, smoking habit social stigma social stigma, knowledge on multi-drug resistant tuberculosis and knowledge on DOTS Plus with multi-drug resistant tuberculosis However there was no association between alcohol drinking habit and ventilation in room with multi-drug resistant tuberculosis. http://dx.doi.org/10.3126/kumj.v8i4.6238 Kathmandu Univ Med J 2010;8(4):392-7


2017 ◽  
Vol 18 (2) ◽  
pp. 62-67 ◽  
Author(s):  
Ummay Fatema Khatun ◽  
Robed Amin ◽  
Muna Islam ◽  
Abdur Rob ◽  
Abdur Rahim

Background: Drug resistant tuberculosis has been reported in all regions of the world. In this study we address the socio-demographic profile and drug sensitivity pattern as well as prevalence of drug resistance tuberculosis in a tertiary center (regional TB reference laboratory) in Bangladesh.Method: This Study was carried out in R.T.R.L. (Regional TB Reference Laboratory) in 250 bedded Chittagong General Hospital. Patients who were referred to R.T.R.L during the period July 2012 to July 2013 were included in the study. Total 100 patients with suspected drug resistant tuberculosis (TB) who had any one of 9 criteria of NTP (National Tuberculosis Control Programme) were selected consecutively. Gene xpert MTB/RIF (Rifampicin resistance) test for all sputum positive cases were performed. Sputum sample of Patients with positive microscopy for AFB or positive Xpert/MTB was sent for culture. The samples with positive sputum culture were sent for drug sensitivity test for 1st line anti- tubercular drug.Result: Among 100 patients 78 were male and 22 were female, majority of the patients (64) were between 15-45 years with poor socio economic condition (73%) and primarily educated. Analysis of our Study result showed that 18% of patients were mono-drug resistant. Among them 13% showed resistance to isoniazid (INH), 4% to streptomycin and only 2% to rifampicin. No patient was found resistant to pyrazinamide (PNZ) and 38% of patient with suspected drug – resistant TB was found to have no drug resistance. 18% of patient had multidrug resistant tuberculosis (MDR-TB) among which 56% were relapse cases (48% after cat -I, 8% after cat II), 24% were non – converter of cat –I, 12% belonged to failure of cat –I, 3% failure of cat –II, 2% return after default and others. 1% of patient had history of contact with MDR –TB patient.Conclusion: Drug-resistance tuberculosis especially MDR-TB, was higher in patients with previously incomplete anti-tuberculosis treatment. A high level of drug resistance among the re-treatment TB patients poses a threat of transmission of resistant strains to susceptible persons in the community. For this reason proper counseling of patients and attention towards the completion of the anti-TB treatment are needed.J MEDICINE July 2017; 18 (2) : 62-67


2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Shona Horter ◽  
Beverley Stringer ◽  
Nell Gray ◽  
Nargiza Parpieva ◽  
Khasan Safaev ◽  
...  

Abstract Introduction Person-centred care, an internationally recognised priority, describes the involvement of people in their care and treatment decisions, and the consideration of their needs and priorities within service delivery. Clarity is required regarding how it may be implemented in practice within different contexts. The standard multi-drug resistant tuberculosis (MDR-TB) treatment regimen is lengthy, toxic and insufficiently effective. 2019 World Health Organisation guidelines include a shorter (9–11-month) regimen and recommend that people with MDR-TB be involved in the choice of treatment option. We examine the perspectives and experiences of people with MDR-TB and health-care workers (HCW) regarding person-centred care in an MDR-TB programme in Karakalpakstan, Uzbekistan, run by Médecins Sans Frontières and the Ministry of Health. Methods A qualitative study comprising 48 interviews with 24 people with MDR-TB and 20 HCW was conducted in June–July 2019. Participants were recruited purposively to include a range of treatment-taking experiences and professional positions. Interview data were analysed thematically using coding to identify emerging patterns, concepts, and categories relating to person-centred care, with Nvivo12. Results People with MDR-TB were unfamiliar with shared decision-making and felt uncomfortable taking responsibility for their treatment choice. HCW were viewed as having greater knowledge and expertise, and patients trusted HCW to act in their best interests, deferring the choice of appropriate treatment course to them. HCW had concerns about involving people in treatment choices, preferring that doctors made decisions. People with MDR-TB wanted to be involved in discussions about their treatment, and have their preference sought, and were comfortable choosing whether treatment was ambulatory or hospital-based. Participants felt it important that people with MDR-TB had knowledge and understanding about their treatment and disease, to foster their sense of preparedness and ownership for treatment. Involving people in their care was said to motivate sustained treatment-taking, and it appeared important to have evidence of treatment need and effect. Conclusions There is a preference for doctors choosing the treatment regimen, linked to shared decision-making unfamiliarity and practitioner-patient knowledge imbalance. Involving people in their care, through discussions, information, and preference-seeking could foster ownership and self-responsibility, supporting sustained engagement with treatment.


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