Strategies employed to evade the host immune response and the mechanism of drug resistance in Mycobacterium tuberculosis: In search of finding new targets

: The partial effectiveness of the host immune response to M. tuberculosis drives bacteria into a latent state, but it is difficult to eliminate the bacteria completely. Usually, this latent condition of M. tuberculosis is reversible, and reactivation of tuberculosis is the leading cause of the majority of transmission. A number of studies performed on animal models and in humans have not yet provided a detailed understanding of the mechanisms or correlates of immunity of M. tuberculosis infection or why there is a significant immunity failure to remove the pathogen. Moreover, the mechanism of resistance involved in drug-resistant M. tuberculosis leading to the emergence of strains of bacteria that show significant resistance to the majority of anti-tuberculosis drugs. We have also provided the recent findings and trends regarding the development of new drug molecules to treat drug and multidrug-resistant tuberculosis and the advancements in immunotherapy in the treatment of drug-resistant tuberculosis. This article provides an in-depth and critical analysis of various strategies employed by the drug-resistant M. tuberculosis to escape the host immune response, as a result of which this bacterium persists in the host for a longer period of time and leads to the development of tuberculosis infection. Furthermore, we also discussed the new targets for the effective treatment of drug resistant tuberculosis.

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Use of fluorescein diacetate (FDA) staining to detect viable Mycobacterium tuberculosis

Bangladesh Journal of Medical Science ◽

10.3329/bjms.v11i4.12605 ◽

2012 ◽

Vol 11 (4) ◽

pp. 322-330 ◽

Cited By ~ 1

Author(s):

Shamima Islam ◽

Farjana Rahman ◽

Saurab Kisore Munshi ◽

Jewel Ahmed ◽

S M Mostafa Kamal ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Treatment Failure ◽

Medical Science ◽

Multidrug Resistant ◽

Fluorescein Diacetate ◽

Drug Resistant ◽

Drug Resistant Tuberculosis ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Auramine O

Objective: Drug resistant tuberculosis has long been a common problem prevailing in developing countries including Bangladesh. Present study focused on the rapid identification of live Mycobacterium tuberculosis among treatment failure cases.Materials and Methods: Sputum samples from a total of 100 category-I and category-II treatment failure cases, assumed as multidrug resistant tuberculosis, were studied through fluorescein diacetate (FDA) staining under light emitting diode (LED) fluorescence microscope. Considering culture method as gold standard, we also compared the results of FDA staining with that of auramine O staining.Results: A total of 85% acid-fast bacilli were detected by FDA staining, 82% by auramine O staining and a total of 85% isolates were detected in Lowenstein-Jensen (LJ) culture. The sensitivity of FDA staining (96.47%) was estimated to be slightly higher than that of auramine O staining (91.76%). Moreover,76.47% cases were detected as multidrug resistant tuberculosis (MDR-TB). Conclusion: Taken together, FDA staining method has been proposed to be appropriate for the rapid diagnosis of drug resistant tuberculosis. DOI: http://dx.doi.org/10.3329/bjms.v11i4.12605 Bangladesh Journal of Medical Science Vol. 11 No. 04 Oct12

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Development of Extensively Drug-resistant Tuberculosis during Multidrug-resistant Tuberculosis Treatment

American Journal of Respiratory and Critical Care Medicine ◽

10.1164/rccm.200911-1768oc ◽

2010 ◽

Vol 182 (3) ◽

pp. 426-432 ◽

Cited By ~ 41

Author(s):

Sonya S. Shin ◽

Salmaan Keshavjee ◽

Irina Y. Gelmanova ◽

Sidney Atwood ◽

Molly F. Franke ◽

...

Keyword(s):

Multidrug Resistant ◽

Tuberculosis Treatment ◽

Drug Resistant ◽

Drug Resistant Tuberculosis ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Extensively Drug Resistant

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Novel drugs against tuberculosis: a clinician's perspective

European Respiratory Journal ◽

10.1183/09031936.00162314 ◽

2014 ◽

Vol 45 (4) ◽

pp. 1119-1131 ◽

Cited By ~ 39

Author(s):

Ioana Diana Olaru ◽

Florian von Groote-Bidlingmaier ◽

Jan Heyckendorf ◽

Wing Wai Yew ◽

Christoph Lange ◽

...

Keyword(s):

Clinical Trials ◽

Phase Ii ◽

Multidrug Resistant ◽

Drug Resistant ◽

Drug Resistant Tuberculosis ◽

Resistant Tuberculosis ◽

Phase Ii Clinical Trials ◽

Multidrug Resistant Tuberculosis ◽

Novel Drugs ◽

Phase Ii And Iii

The United Nations Millennium Development Goal of reversing the global spread of tuberculosis by 2015 has been offset by the rampant re-emergence of drug-resistant tuberculosis, in particular fluoroquinolone-resistant multidrug-resistant and extensively drug-resistant tuberculosis. After decades of quiescence in the development of antituberculosis medications, bedaquiline and delamanid have been conditionally approved for the treatment of drug-resistant tuberculosis, while several other novel compounds (AZD5847, PA-824, SQ109 and sutezolid) have been evaluated in phase II clinical trials. Before novel drugs can find their place in the battle against drug-resistant tuberculosis, linezolid has been compassionately used with success in the treatment of fluoroquinolone-resistant multidrug-resistant tuberculosis. This review largely discusses six novel drugs that have been evaluated in phase II and III clinical trials, with focus on the clinical evidence for efficacy and safety, potential drug interactions, and prospect for using multiple novel drugs in new regimens.

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Determinants Of Multidrug Resistant Tuberculosis Among Adultsundergoing Treatment For Tuberculosis In Tigray Region, Ethiopia: A Case Control Study

10.21203/rs.2.15772/v2 ◽

2019 ◽

Author(s):

Kidane Zereabruk ◽

Tensay Kahsay ◽

Hiyab Teklemichael ◽

Woldu Aberhe ◽

Abrha Hailay ◽

...

Keyword(s):

Multidrug Resistant ◽

Multi Drug Resistance ◽

P Value ◽

Rural Residence ◽

Drug Resistant ◽

Drug Resistant Tuberculosis ◽

Tigray Region ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Multi Drug Resistant Tuberculosis

Abstract Background Multidrug-resistant tuberculosis is a type of tuberculosis that is resistant to at least the first line anti-tuberculosis drugs namely, Rifampicin and Isoniazid. Multidrug-resistant tuberculosis has continued to be a challenge for tuberculosis control globally. Globally 600,000 people were newly eligible for Multidrug-resistant tuberculosis treatment with an estimated 240,000 deaths annually. There are few numbers of multi drug resistant tuberculosis studies in different regions of Ethiopia. However, most of these studies were restricted only to a single hospital and there is no published information regarding multi drug resistant tuberculosis in Tigray region. Therefore, the aim of this study was to assess the determinants of multidrug resistant tuberculosis among adults undergoing treatment for tuberculosis in Tigray region, Ethiopia.Methods A hospital based unmatched case control study was conducted from April to June, 2019. Simple random sampling method was used to select 85 cases and 169 controls. Primary data was collected by face-to-face interview and secondary data by reviewing patients’ charts using pretested structured questionnaires. The data were entered and cleaned using Epi data manager then exported to SPSS for analysis. Binary Logistic regression model was used to test the association between independent and dependent variables. Model fitness was checked using Hosmer-Lemeshow goodness-of-fit and Variance inflation factor was used to assess multi collinearity between the independent variables. Variables at p-value less than 0.25 in bivariate analysis was entered into a multivariable analysis to identify the determinant factors of multi drug resistant tuberculosis. Finally, level of significance was declared at p-value <0.05.Results A total of 254 participants with 85 cases and 169 controls were included in this study. Of the respondents, 62 (36.7%) among the controls and 48 (56.5%) among the cases were living in rural residence. Rural residence [AOR=2.54;95%CI=1.34,4.83], HIV[AOR=4.5;95%CI=1.4,14.2], relapse [AOR=3.86;95%CI;1.98,7.5], return after lost follow up [AOR=6.29;95% 1.64,24.2], treatment failure [AOR=5.87; CI=1.39,24.8] were among the determinants of Multi drug resistance tuberculosis.Conclusion Rural residence, HIV, relapse, return after lost follow up and treatment failure were the identified determinant factors of Multi drug resistance tuberculosis.

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Status of antituberculosis drug resistance in Saudi Arabia 1979-98

Eastern Mediterranean Health Journal ◽

10.26719/2002.8.4-5.664 ◽

2021 ◽

Vol 8 (4-5) ◽

pp. 664-670

Author(s):

K. K. Abu Amero

Keyword(s):

Saudi Arabia ◽

Drug Sensitivity ◽

National Policy ◽

Multidrug Resistant ◽

Drug Resistant ◽

First Line ◽

Sensitivity Testing ◽

Drug Resistant Tuberculosis ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis

All published material on the prevalence of drug-resistant tuberculosis within Saudi Arabia over the period 1979-98 was reviewed. The prevalence of single-drug-resistant tuberculosis ranged from 3.4% to 41% for isoniazid, 0% to 23.4% for rifampicin, 0.7% to 22.7% for streptomycin and 0% to 6.9% for ethambutol. The prevalence of multidrug-resistant tuberculosis [defined by WHO as resist1qance to two or more first-line antituberculosis drugs] ranged from 1.5% to 44% in different regions. No strong conclusions could be drawn owing to variations in the populations studied, geographical origins, site of Mycobacterium tuberculosis isolation [pulmonary or extrapulmonary] and drug sensitivity testing. However, the need to develop a standardized national policy for surveillance of drug-resistant tuberculosis in Saudi Arabia is clear

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Neuropsychiatric reactions induced by cycloserine in the treatment of multidrug-resistant tuberculosis: what an Indian female patient tells us

BMJ Case Reports ◽

10.1136/bcr-2019-230993 ◽

2019 ◽

Vol 12 (12) ◽

pp. e230993 ◽

Cited By ~ 2

Author(s):

Enrica Intini ◽

Girija Kishore ◽

Luca Richeldi ◽

Zarir F Udwadia

Keyword(s):

Adverse Events ◽

Multidrug Resistant ◽

Drug Resistant ◽

Drug Resistant Tuberculosis ◽

Health Crisis ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Multi Drug Resistant Tuberculosis ◽

Group B

Multidrug-resistant tuberculosis continues to be a public health crisis. Urgent action is required to improve the coverage and quality of diagnosis, treatment and care for people affected by drug-resistant tuberculosis. To implement tuberculosis control, in 2018, WHO recommended cycloserine as one of the Group B drugs. Following this recommendation, cycloserine should be generally included in the starting line-up in the longer regimen for the treatment of multidrug-resistant tuberculosis. However, neurological toxicity associated with this drug concerns clinicians and limits its use. In this paper, we present a case of a 48-year-old woman with a diagnosis of multidrug-resistant tuberculosis treated with cycloserine, who developed psychiatric adverse events after 3 months of administration. This case shows the need for close psychiatric follow-up to promptly detect adverse events in patients receiving regimens for multi-drug resistant tuberculosis.

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Impact of Extensively Drug-Resistant Tuberculosis on Treatment Outcome of Multidrug-Resistant Tuberculosis Patients with Standardized Regimen: Report from Iran

Microbial Drug Resistance ◽

10.1089/mdr.2009.0073 ◽

2010 ◽

Vol 16 (1) ◽

pp. 81-86 ◽

Cited By ~ 15

Author(s):

Payam Tabarsi ◽

Ehsan Chitsaz ◽

Parvaneh Baghaei ◽

Masoud Shamaei ◽

Parisa Farnia ◽

...

Keyword(s):

Treatment Outcome ◽

Multidrug Resistant ◽

Drug Resistant ◽

Drug Resistant Tuberculosis ◽

Tuberculosis Patients ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Extensively Drug Resistant

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Extensively Drug-Resistant Tuberculosis Is Worse than Multidrug-Resistant Tuberculosis: Different Methodology and Settings, Same Results

Clinical Infectious Diseases ◽

10.1086/528875 ◽

2008 ◽

Vol 46 (6) ◽

pp. 958-959 ◽

Cited By ~ 23

Author(s):

G. B. Migliori ◽

C. Lange ◽

E. Girardi ◽

R. Centis ◽

G. Besozzi ◽

...

Keyword(s):

Multidrug Resistant ◽

Drug Resistant ◽

Drug Resistant Tuberculosis ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Extensively Drug Resistant

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Modelling the Role of Diagnosis, Treatment, and Health Education on Multidrug-Resistant Tuberculosis Dynamics

ISRN Biomathematics ◽

10.5402/2012/459829 ◽

2012 ◽

Vol 2012 ◽

pp. 1-20 ◽

Cited By ~ 2

Author(s):

M. Maliyoni ◽

P. M. M. Mwamtobe ◽

S. D. Hove-Musekwa ◽

J. M. Tchuenche

Keyword(s):

Health Education ◽

Deterministic Model ◽

Multidrug Resistant ◽

Sub Saharan Africa ◽

Drug Resistant ◽

Drug Resistant Tuberculosis ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Multi Drug Resistant Tuberculosis ◽

The Impact

Tuberculosis, an airborne disease affecting almost a third of the world’s population remains one of the major public health burdens globally, and the resurgence of multidrug-resistant tuberculosis in some parts of sub-Saharan Africa calls for concern. To gain insight into its qualitative dynamics at the population level, mathematical modeling which require as inputs key demographic and epidemiological information can fill in gaps where field and lab data are not readily available. A deterministic model for the transmission dynamics of multi-drug resistant tuberculosis to assess the impact of diagnosis, treatment, and health education is formulated. The model assumes that exposed individuals develop active tuberculosis due to endogenous activation and exogenous re-infection. Treatment is offered to all infected individuals except those latently infected with multi-drug resistant tuberculosis. Qualitative analysis using the theory of dynamical systems shows that, in addition to the disease-free equilibrium, there exists a unique dominant locally asymptotically stable equilibrium corresponding to each strain. Numerical simulations suggest that, at the current level of control strategies (with Malawi as a case study), the drug-sensitive tuberculosis can be completely eliminated from the population, thereby reducing multi-drug resistant tuberculosis.

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