scholarly journals A recombinant selective drug-resistant M. bovis BCG enhances the bactericidal activity of a second-line tuberculosis regimen

2021 ◽  
Author(s):  
Gift Chiwala ◽  
Zhiyong Liu ◽  
Julius N. Mugweru ◽  
Bangxing Wang ◽  
Shahzad Akbar Khan ◽  
...  

AbstractDrug-resistant tuberculosis (DR-TB) results from infection by Mycobacterium tuberculosis strains resistant to at least rifampin or isoniazid. To improve the treatment outcome in DR-TB, therapeutic vaccines are considered an ideal choice as they can enhance pathogen clearance and minimize disease sequelae. To date, there is no therapeutic vaccine reported to be effective when combined with a chemotherapy regimen against DR-TB. The only available TB vaccine, the M. bovis BCG (BCG) is susceptible to several anti-TB drugs hence not a perfect option for therapeutic vaccination. Herein, we developed a recombinant BCG (RdrBCG) overexpressing Ag85B and Rv2628 with resistance to selected anti-TB drugs. When administered three times adjunct to a second-line anti-TB regimen in a classical murine model of DR-TB, the RdrBCG lowered lung M. tuberculosis colony-forming units by 1 log10. Furthermore, vaccination with the RdrBCG adjunct to TB chemotherapy minimized lung tissue pathology in mice. Most importantly, the RdrBCG maintained the exogenously inserted genes and showed almost the same virulence as its parent BCG Tice strain in severe combined immune-deficient mice. All these suggested that the RdrBCG was stable, safe and effective. Hence, the “recombinant” plus “drug-resistant” BCG strategy could be a useful concept for developing therapeutic vaccines against DR-TB.

2013 ◽  
Vol 108 (2) ◽  
pp. 160-166 ◽  
Author(s):  
Pola Becerril-Montes ◽  
Salvador Said-Fernández ◽  
Julieta Luna-Herrera ◽  
Guillermo Caballero-Olín ◽  
José Antonio Enciso-Moreno ◽  
...  

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


Author(s):  
Rajendra Prasad ◽  
Harsh Saxena ◽  
Nikhil Gupta ◽  
Mohammad Tanzeem ◽  
Ronal Naorem

AbstractDrug-resistant tuberculosis (DR-TB) has been an area of growing concern and posing threat to human health worldwide. The treatment has been defined for all types of DR-TB with or without newer anti-TB drugs. multi-DR-TB (MDR-TB) patients have now choice of two types of regimen, shorter and longer regimens. Shorter regimen for treatment of subset of MDR-TB patients who have not been previously treated with second line drugs and in whom resistance to fluoroquinolones and second-line injectable agents has been excluded is given for 9 to 11 months. A longer regimen of at least five effective anti-TB drugs (ATDs) during the intensive phase is recommended, including pyrazinamide and four core second-line ATDs. Intensive phase, including injectables, should be given for at least 8 months. The total duration of treatment is at least 20 months, which can be prolonged up to 24 months depending on the response of the patient. World Health Organization (WHO) has recently revised the grouping of ATD for use in DR-TB patients in 2018 into three groups based on individual patient data meta-analysis depending on their individual efficacy, risk of relapse, treatment failure, and death. Recently, an all oral longer regimen comprising bedaquiline, pretomanid, and linezolid (BPal regime) for 6 to 9 months for extensive-DR-TB (XDR-TB) patients and those MDR-TB patients who cannot tolerate or do not respond to conventional MDR-TB regimen. These new developments will be a step forward toward establishing universal regimen to treat all types of DR-TB. This article has summarized the current evidence from literature search to date, including prevalence of DR-TB, types of regimen used and the advancement in the regimens for effective treatment of DR-TB patients.


PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0241065
Author(s):  
Florence O. Bada ◽  
Nick Blok ◽  
Evaezi Okpokoro ◽  
Saswata Dutt ◽  
Christopher Akolo ◽  
...  

Background Globally, drug resistant tuberculosis (DR-TB) continues to be a public health threat. Nigeria, which accounts for a significant proportion of the global burden of rifampicin/multi-drug resistant-TB (RR/MDR-TB) had a funding gap of $168 million dollars for TB treatment in 2018. Since 2010, Nigeria has utilized five different models of care for RR/MDR-TB (Models A-E); Models A, B and C based on a standardized WHO-approved treatment regimen of 20–24 months, were phased out between 2015 and 2019 and replaced by Models D and E. Model D is a fully ambulatory model of 9–12 months during which a shorter treatment regimen including a second-line injectable agent is utilized. Model E is identical to Model D but has patients hospitalized for the first four months of care while Model F which is to be introduced in 2020, is a fully ambulatory, oral bedaquiline-containing shorter treatment regimen of 9–12 months. Treatment models for RR/MDR-TB of 20–24 months duration have had treatment success rates of 52–66% while shorter treatment regimens have reported success rates of 85% and above. In addition, replacing the second-line injectable agent in a shorter treatment regimen with bedaquiline has been found to further improve treatment success in patients with fluoroquinolone-susceptible RR/MDR-TB. Reliable cost data for RR/MDR-TB care are limited, specifically costs of models that utilize shorter treatment regimens and which are vital to guide Nigeria through the provision of RR/MDR-TB care at scale. We therefore conducted a cost analysis of shorter treatment regimens in use and to be used in Nigeria (Models D, E and F) and compared them to three models of longer duration utilized previously in Nigeria (Models A, B and C) to identify any changes in cost from transitioning from Models A-C to Models D-F and opportunities for cost savings. Methods We obtained costs for TB diagnostic and monitoring tests, in-patient and out-patient care from a previous study, inflated these costs to 2019 NGN and then converted to 2020 USD. We obtained other costs from the average of six health facilities and drug costs from the global drug facility. We modeled treatment on strict adherence to two Nigerian National guidelines for programmatic and clinical management of drug-resistant tuberculosis. Results We estimated that the total costs of care from the health sector perspective for Models D, E and F were $4,334, $7,705 and $3,420 respectively. This is significantly lower than the costs of Models A, B and C which were $14,781, $12, 113, $7,572 respectively. Conclusion Replacing Models A–C with Models D and E reduced the costs of RR/MDR-TB care in Nigeria by approximately $5,470 (48%) per patient treated and transitioning from Models D and E to Model F would result in further cost savings of $914 to $4,285 (21 to 56%) for every patient placed on Model F. If the improved outcomes of patients managed using bedaquiline-containing shorter treatment regimens in other countries can be attained in Nigeria, Model F would be the recommended model for the scale up of RR/MDR-TB care in Nigeria.


2018 ◽  
Vol 22 (2) ◽  
pp. 168-174
Author(s):  
Pranita Tuladhar ◽  
Dhruba Kumar Khadka ◽  
Megha Raj Banjara ◽  
Reshma Tuladhar

With an increase in Multi-drug resistant tuberculosis (MDR-TB), there is a need of second line drug susceptibility test that helps in early diagnosis and minimize the risk of other powerful drug resistant Mycobacterium tuberculosis. The aim of this study was to determine second line drugs (ofloxacin, kanamycin, capreomycin) resistance pattern in MDR-TB isolates and to determine the prevalence of pre-Extensively drug resistant tuberculosis (pre-XDR-TB) and XDR-TB in MDR-TB patients. The study was conducted from February to September 2015 at National Tuberculosis Centre, Thimi, Bhaktapur. MDR-TB (resistant to isoniazid and rifampicin) patients’ sputum samples were processed by Modified Petroff’s method. Out of 92 samples, 57 were found culture positive. Following the species identification of culture positive MDR-TB isolates, second line drug susceptibility test was performed by conventional proportion method. Of 57 MDR-TB isolates, 22 (38.59%) showed resistance to ofloxacin (Ofx), 9 (15.79%) to capreomycin (Cm) and 9 (15.79%) to kanamycin (Km). One XDR-TB (1.8%) resistant to all drugs was detected. Of the remaining, 21(36.8%) were resistant to ofloxacin only and 8(15.4%) were resistant to two drugs i.e.29 (50.9%) were pre-XDR-TB. The prevalence of pre-XDR-TB and XDR-TB was found to be 50.88% and 1.75% respectively. The resistance pattern of second line anti-tuberculosis drugs showed higher ofloxacin resistance in MDR-TB patients. In a nutshell, MDR-TB cases need urgent and timely susceptibility report for second line anti-tuberculosis drugs to help the clinicians start proper drug combinations to treat MDR-TB patients. Journal of Institute of Science and Technology Volume 22, Issue 2, January 2018, page: 168-174


2015 ◽  
Vol 59 (11) ◽  
pp. 7104-7108 ◽  
Author(s):  
Scott K. Heysell ◽  
Suporn Pholwat ◽  
Stellah G. Mpagama ◽  
Saumu J. Pazia ◽  
Happy Kumburu ◽  
...  

ABSTRACTMIC testing forMycobacterium tuberculosisis now commercially available. Drug susceptibility testing by the MycoTB MIC plate has not been directly compared to that by the Bactec MGIT 960. We describe a case of extensively drug-resistant tuberculosis (XDR-TB) in Tanzania where initial MIC testing may have prevented acquired resistance. From testing on archived isolates, the accuracy with the MycoTB plate was >90% for important first- and second-line drugs compared to that with the MGIT 960, and clinically useful quantitative interpretation was also provided.


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