Nanomedicine as a Newly Emerging Approach Against Multidrug-Resistant Tuberculosis (MDR-TB)

2017 ◽  
pp. 50-73
Author(s):  
Muthupandian Saravanan ◽  
Kebret Duche ◽  
Tsehaye Asmelash ◽  
Araya Gebreyesus ◽  
Anima Nanda ◽  
...  
Keyword(s):  
Large Scale ◽  
Current Knowledge ◽  
Low Cost ◽  
Multidrug Resistant ◽  
Current Treatment ◽  
Diagnostic Assays ◽  
Resistant Tuberculosis ◽  
Mdr Tb ◽  
Potential Applications ◽  
The Impact

Emergence of MDR-TB is highly associated with morbidity and mortality and it needs high concerns about the possibility of a future TB epidemic as limited therapeutic options are available. The current treatment against TB needs daily administration for at least 6 months. That in turn leads to the development and spread of drug-resistant TB. Plenty of work has been done in nanomedicine that provides hope to encounter TB effectively. In the developing world the development of nanoparticle-based aerosol vaccines for tuberculosis has potential applications using on a large scale at relatively low cost, and particularly attractive for use. This book review examines the current TB diagnostic assays and treatment by nanotechnologies and highlight recent advances in Anti-TB Drug (ATD) delivery systems and anti-TB drug encapsulation. It also discusses the impact of the nanoparticles as an emerging treatment against MDR-TB and discusses the current knowledge and potential nanomedicine to improve MDR-TB therapy.

Nanomedicine as a Newly Emerging Approach Against Multidrug-Resistant Tuberculosis (MDR-TB)

2018 ◽  
pp. 941-960
Author(s):  
Muthupandian Saravanan ◽  
Kebret Duche ◽  
Tsehaye Asmelash ◽  
Araya Gebreyesus ◽  
Anima Nanda ◽  
...  
Keyword(s):  
Large Scale ◽  
Current Knowledge ◽  
Low Cost ◽  
Multidrug Resistant ◽  
Current Treatment ◽  
Diagnostic Assays ◽  
Resistant Tuberculosis ◽  
Mdr Tb ◽  
Potential Applications ◽  
The Impact

Emergence of MDR-TB is highly associated with morbidity and mortality and it needs high concerns about the possibility of a future TB epidemic as limited therapeutic options are available. The current treatment against TB needs daily administration for at least 6 months. That in turn leads to the development and spread of drug-resistant TB. Plenty of work has been done in nanomedicine that provides hope to encounter TB effectively. In the developing world the development of nanoparticle-based aerosol vaccines for tuberculosis has potential applications using on a large scale at relatively low cost, and particularly attractive for use. This book review examines the current TB diagnostic assays and treatment by nanotechnologies and highlight recent advances in Anti-TB Drug (ATD) delivery systems and anti-TB drug encapsulation. It also discusses the impact of the nanoparticles as an emerging treatment against MDR-TB and discusses the current knowledge and potential nanomedicine to improve MDR-TB therapy.

scholarly journals Assessing the impacts of short-course multidrug-resistant tuberculosis treatment in the Southeast Asia Region using a mathematical modeling approach

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0248846
Author(s):  
Win Min Han ◽  
Wiriya Mahikul ◽  
Thomas Pouplin ◽  
Saranath Lawpoolsri ◽  
Lisa J. White ◽  
...  
Keyword(s):  
Southeast Asia ◽  
Treatment Initiation ◽  
Multidrug Resistant ◽  
Treatment Regimens ◽  
Tb Treatment ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Short Course ◽  
Mdr Tb ◽  
The Impact

This study aimed to predict the impacts of shorter duration treatment regimens for multidrug-resistant tuberculosis (MDR-TB) on both MDR-TB percentage among new cases and overall MDR-TB cases in the WHO Southeast Asia Region. A deterministic compartmental model was constructed to describe both the transmission of TB and the MDR-TB situation in the Southeast Asia region. The population-level impacts of short-course treatment regimens were compared with the impacts of conventional regimens. Multi-way analysis was used to evaluate the impact by varying programmatic factors (eligibility for short-course MDR-TB treatment, treatment initiation, and drug susceptibility test (DST) coverage). The model predicted that overall TB incidence will be reduced from 246 (95% credible intervals (CrI), 221–275) per 100,000 population in 2020 to 239 (95% CrI, 215–267) per 100,000 population in 2035, with a modest reduction of 2.8% (95% CrI, 2.7%–2.9%). Despite the slight reduction in overall TB infections, the model predicted that the MDR-TB percentage among newly notified TB infections will remain steady, with 2.4% (95% CrI, 2.1–2.9) in 2020 and 2.5% (95% CrI, 2.3–3.1) in 2035, using conventional MDR-TB treatment. With the introduction of short-course regimens to treat MDR-TB, the development of resistance can be slowed by 38.6% (95% confidence intervals (CI), 35.9–41.3) reduction in MDR-TB case number, and 37.6% (95% CI, 34.9–40.3) reduction in MDR-TB percentage among new TB infections over the 30-year period compared with the baseline using the standard treatment regimen. The multi-way analysis showed eligibility for short-course treatment and treatment initiation greatly influenced the impacts of short-course treatment regimens on reductions in MDR-TB cases and percentage resistance among new infections. Policies which promote the expansion of short-course regimens and early MDR-TB treatment initiation should be considered along with other interventions to tackle antimicrobial resistance in the region.

scholarly journals Impact of multidrug-resistant tuberculosis and its medications on adverse maternal and perinatal outcomes: protocol for a systematic review and meta-analysis

BMJ Open ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. e034821 ◽  
Author(s):  
Kefyalew Addis Alene ◽  
Akilew Awoke Adane ◽  
Alemken Jegnie
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
Perinatal Outcomes ◽  
Public Health Problem ◽  
Multidrug Resistant ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
The Impact

IntroductionMultidrug-resistant tuberculosis (MDR-TB) is a common public health problem affecting pregnant women. However, the impact of MDR-TB and its medication on pregnancy and perinatal outcomes has been poorly understood and inconsistently reported. Therefore, using the available literature, we aim to determine whether MDR-TB and its medications during pregnancy impact maternal and perinatal outcomes.Methods and analysisThis systematic review and meta-analysis will adhere to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Systematic searches will be conducted in PubMed, Scopus and Web of Science on 10 February 2020 for studies that reported adverse maternal and perinatal outcomes due to MDR-TB and/or its medication. The search will be performed without language and time restrictions. Adverse birth outcomes include miscarriage or abortion, stillbirth, preterm birth, low birth weight, small and large for gestational age, and neonatal death. Two independent reviewers will screen search records, extract data and assess the quality of the studies. The Newcastle-Ottawa Quality Assessment Scale will be used to assess the methodological quality of the included studies. In addition to a narrative synthesis, a random-effects meta-analysis will be conducted when sufficient data are available. I2 statistics will be used to assess the heterogeneity between studies.Ethics and disseminationAs it will be a systematic review and meta-analysis based on previously published evidence, there will be no requirement for ethical approval. Findings will be published in a peer-reviewed journal and will be presented at various conferences.

scholarly journals CURRENT STRATEGIES IN THE TREATMENT OF MULTIDRUG-RESISTANT TUBERCULOSIS

2018 ◽  
Vol 11 (7) ◽  
pp. 70
Author(s):  
Neethu Td ◽  
Mebin Alias
Keyword(s):  
Treatment Regimen ◽  
Current Knowledge ◽  
Multidrug Resistant ◽  
Control Measures ◽  
World Health ◽  
Drug Resistant ◽  
Proper Treatment ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb

Objective: The objective of the study was to analyze and review the current knowledge about the principles of treatment of multidrug-resistant tuberculosis (MDR-TB), World Health Organization treatment regimen to treat MDR-TB, mechanism of resistance, and risk factors for emergence of resistance, and novel antitubercular drugs (ATDs) available and control measures to improve treatment outcomes of MDR-TB.Methods: Various articles were reviewed from PubMed and other databases and were analyzed to write the review.Results: Mycobacterium is a largely curable infectious disease if proper treatment should be followed. The success of the treatment depends on the designing of proper treatment regimen and patient adherence to that medication.Conclusion: Mycobacterium tuberculosis is now the most lethal infectious pathogen. Drug resistance has become a major problem in the treatment of TB. In MDR-TB, the bacteria is resistant to at least isoniazid (INH) and rifampicin (RIF), and in extensively drug-resistant TB the bacteria is resistant to INH, RIF, any fluoroquinolone, and at least one of three injectable second-line drugs for TB such as kanamycin, capreomycin, and amikacin. More recently, a more worrying situation has emerged with the description of M. tuberculosis strains that have been found resistant to all antibiotics that were available for testing, a situation labeled as totally drug resistant-TB. Other reasons like poor planning by the authorities and the government may also result in the emergence of resistant strain. Rather than the effective chemotherapy and the moderately protective vaccine, new anti-TB agents, and novel controlled release nanoparticulate system like polymeric nanocarrier systems containing existing ATDs are urgently needed to decrease the global incidence of TB.

scholarly journals Risk of hearing loss among multidrug-resistant tuberculosis patients according to cumulative aminoglycoside dose

2020 ◽  
Vol 24 (1) ◽  
pp. 65-72 ◽  
Author(s):  
H. Hong ◽  
D. W. Dowdy ◽  
K. E. Dooley ◽  
H. W. Francis ◽  
C. Budhathoki ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Dose Group ◽  
Low Dose ◽  
Multidrug Resistant ◽  
Prognostic Impact ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Increased Risk ◽  
Mdr Tb ◽  
The Impact

SETTING: The ototoxic effects of aminoglycosides (AGs) lead to permanent hearing loss, which is one of the devastating consequences of multidrug-resistant tuberculosis (MDR-TB) treatment. As AG ototoxicity is dose-dependent, the impact of a surrogate measure of AG exposure on AG-induced hearing loss warrants close attention for settings with limited therapeutic drug monitoring.OBJECTIVE: To explore the prognostic impact of cumulative AG dose on AG ototoxicity in patients following initiation of AG-containing treatment for MDR-TB.DESIGN: This prospective cohort study was nested within an ongoing cluster-randomized trial of nurse case management intervention across 10 MDR-TB hospitals in South Africa.RESULTS: The adjusted hazard of AG regimen modification due to ototoxicity in the high-dose group (≥75 mg/kg/week) was 1.33 times higher than in the low-dose group (<75 mg/kg/week, 95%CI 1.09–1.64). The adjusted hazard of developing audiometric hearing loss was 1.34 times higher than in the low-dose group (95%CI 1.01–1.77). Pre-existing hearing loss (adjusted hazard ratio [aHR] 1.71, 95%CI 1.29–2.26) and age (aHR 1.16 per 10 years of age, 95%CI 1.01–1.33) were also associated with an increased risk of hearing loss.CONCLUSION: MDR-TB patients with high AG dose, advanced age and pre-existing hearing loss have a significantly higher risk of AG-induced hearing loss. Those at high risk may be candidates for more frequent monitoring or AG-sparing regimens.

Effect of Global Fund financial support for patients with multidrug-resistant tuberculosis

2020 ◽  
Vol 24 (7) ◽  
pp. 686-693 ◽  
Author(s):  
T. Watthananukul ◽  
T. Liabsuetrakul ◽  
P. Pungrassami ◽  
V. Chongsuvivatwong
Keyword(s):  
Financial Support ◽  
Global Fund ◽  
Positive Impact ◽  
Multidrug Resistant ◽  
Drug Adherence ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Significant Difference ◽  
Mdr Tb ◽  
The Impact

SETTING: The Global Fund provides financial support for patients with multidrug-resistant tuberculosis (MDR-TB), patients' families and hospitals providing services for these patients in Thailand, but the impact of this support has not been evaluated.OBJECTIVE: To assess the impact of Global Fund financial support on drug adherence, out-of-pocket (OOP) payments, sputum culture conversion and the perception of the usefulness of this support.DESIGN: A retrospective cohort study was conducted in eight provincial hospitals with and without financial support in four regions of Thailand. MDR-TB patients aged ≥15 years registered in 2015–2016 who received treatment at these hospitals for at least 6 months were included.RESULTS: There was no significant difference in drug adherence rates. The OOP payments during treatment were significantly lower in patients who received financial support (P < 0.001). Although the supported group had higher positive culture rates at the beginning of treatment, sputum converted at a faster rate than for the unsupported group (P = 0.034). More than 80% of both groups perceived financial support as being useful, leading to faster diagnosis and improving follow-up compliance.CONCLUSION: Financial support for MDR-TB patients has a positive impact on treatment and should be continued.

Prevalence of Multi-Drug Resistant Tuberculosis among Tuberculosis Patients Attending Chest Clinics in Osun-State, Nigeria

2020 ◽  
Vol 21 (10) ◽  
pp. 939-947
Author(s):  
Gbadebo J. Oyedeji ◽  
Charles Adeyemo ◽  
Affolabi Dissou ◽  
Tope Abiodun ◽  
Oyebode A.T. Alli ◽  
...  
Keyword(s):  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Drug Susceptibility Testing ◽  
Tuberculosis Control ◽  
First Line ◽  
Tuberculosis Patients ◽  
Resistant Tuberculosis ◽  
Mdr Tb ◽  
Previously Treated ◽  
The Impact

Background: The development of multidrug-resistant tuberculosis (MDR-TB) poses a considerable threat to tuberculosis control programmes in Nigeria. There is an increase in the prevalence of MDR-TB worldwide both among new tuberculosis cases as well as previously-treated ones. There is also a rise in transmission of resistant strains due to an increase in MDR-TB patients largely due to the poor drug compliance and the impact of Human immunodeficiency virus infection. Therefore, we intend to determine the extent of MDR-TB among attendees of chest clinics in Osun-State, Nigeria. Objectives: The objective of this study was to determine the prevalence of MDR-TB among confirmed tuberculosis patients attending chest clinics in Osun-State, Nigeria. Methods: This study was conducted among 207 attendees of chest clinics in Osun-State between June, 2015 and October 15, 2016. Sputum and blood samples of the participants were collected. GeneXpert test was carried out first on the samples for simultaneous identification of MTB and rifampicin resistance. Sputum samples were cultured on Lowenstein-Jensen (L-J) medium using N-acetyl-Lcysteine- sodium hydroxide (NALC-NaOH) decontamination method. Drug susceptibility testing (DST) to three first-line drugs was carried out using the proportion DST method. Results: The prevalence of MTB was found to be 27.5% while the prevalence of MDR-TB from the fifty-seven isolates was 10.5%. Previously treated and new cases had a prevalence of 7.0% and 3.5% MDR-TB, respectively. Seventy (33.8%) participants were positive for HIV infection, out of which twenty-six (12.6%) had co-infection of tuberculosis and HIV. The mono-resistance rates of the three first-line drugs used were: 5.3% and 8.7% for ethambutol (EMB) and isoniazid (INH), respectively. No isolate had mono-resistance (0%) to rifampicin (RIF). Conclusion: This study observed the prevalence of 27.5% MTB and a prevalence of 10.5% MDR-TB among the MTB isolates. The prevalence of TB is high in Osun State. MDR-TB prevalence is higher compared with the national estimate of MDR-TB (5.1%) of 2017. Resistant TB is a threat to national tuberculosis control and it is recommended that all the facilities be equipped to cater to its diagnosis.

scholarly journals Mycobacteriophage Lysis Enzymes: Targeting the Mycobacterial Cell Envelope

Viruses ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 428 ◽  
Author(s):  
Maria Catalão ◽  
Madalena Pimentel
Keyword(s):  
Current Knowledge ◽  
Cell Envelope ◽  
Multidrug Resistant ◽  
Mycolic Acid ◽  
Lytic Enzymes ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mycobacterial Cell ◽  
Host Cell Death ◽  
Potential Applications

Mycobacteriophages are viruses that specifically infect mycobacteria, which ultimately culminate in host cell death. Dedicated enzymes targeting the complex mycobacterial cell envelope arrangement have been identified in mycobacteriophage genomes, thus being potential candidates as antibacterial agents. These comprise lipolytic enzymes that target the mycolic acid-containing outer membrane and peptidoglycan hydrolases responsive to the atypical mycobacterial peptidoglycan layer. In the recent years, a remarkable progress has been made, particularly on the comprehension of the mechanisms of bacteriophage lysis proteins activity and regulation. Notwithstanding, information about mycobacteriophages lysis strategies is limited and is mainly represented by the studies performed with mycobacteriophage Ms6. Since mycobacteriophages target a specific group of bacteria, which include Mycobacterium tuberculosis responsible for one of the leading causes of death worldwide, exploitation of the use of these lytic enzymes demands a special attention, as they may be an alternative to tackle multidrug resistant tuberculosis. This review focuses on the current knowledge of the function of lysis proteins encoded by mycobacteriophages and their potential applications, which may contribute to increasing the effectiveness of antimycobacterial therapy.

scholarly journals Drug exposure and susceptibility of second-line drugs correlate with treatment response in patients with multidrug resistant tuberculosis: a multi-centre prospective cohort study in China

2021 ◽  
pp. 2101925
Author(s):  
Xubin Zheng ◽  
Lina Davies Forsman ◽  
Ziwei Bao ◽  
Yan Xie ◽  
Zhu Ning ◽  
...  
Keyword(s):  
Drug Exposure ◽  
Multidrug Resistant ◽  
Target Attainment ◽  
Cart Analysis ◽  
Tb Treatment ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
The Impact ◽  
Culture Conversion

BackgroundUnderstanding the impact of drug exposure and susceptibility on treatment response of multidrug-resistant tuberculosis (MDR-TB) will help to optimize treatment. This study aimed to investigate the association between drug exposure, susceptibility and response to MDR-TB treatment.MethodsDrug exposure and susceptibility for second-line drugs were measured for patients with MDR-TB. Multivariate analysis was applied to investigate the impact of drug exposure and susceptibility on sputum culture conversion and treatment outcome. Probability of target attainment was evaluated. Random Forest and classification and regression tree (CART) analysis was used to identify key predictors and their clinical targets among patients on WHO-recommended regimens.ResultsDrug exposure and corresponding susceptibility were available for 197 patients with MDR-TB. Target attainment was highly variable ranging from 0% for ethambutol to 97% for linezolid, while patients with fluoroquinolones above targets had higher probability of two-month culture conversion (56.3% versus 28.6%, OR 2.91, 95% CI 1.42–5.94) and favourable outcome (88.8% versus 68.8%, OR 2.89, 95% CI 1.16–7.17). Higher exposure values of fluoroquinolones, linezolid and pyrazinamide were associated with earlier sputum culture conversion. CART analysis selected moxifloxacin AUC/MIC of 231 and linezolid AUC/MIC of 287 as best predictors for six-month culture conversion in patients receiving identical Group A-based regimen. These association were confirmed in multivariate analysis.ConclusionsOur findings indicated that target attainment of TB drugs is associated with response to treatment. The CART-derived thresholds may serve as targets for early dose adjustment in a future randomized controlled study to improve the MDR-TB treatment outcome.

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