20 Stem Cells in Infectious Diseases

Insight and Control of Infectious Disease in Global Scenario, 2012

International journal of mycobacteriology, 2016

We urgently need novel treatments for multidrug-resistant tuberculosis (MDR-TB). Autologous mesenchymal stromal cell (MSC) infusion is one such possibility due to its potential to repair damaged lung tissue and boost immune responses. We aimed to assess the safety and effectiveness of MSC to improve treatment outcomes among MDR-TB patients. We analyzed treatment outcomes for 108 Belarusian MDR-TB patients receiving chemotherapy. Thirty-six patients (cases) also had MSCs collected, extracted, cultured, and reinfused (average time from chemotherapy start to infusion was 49days) in optimal dose; another 36 patients (without MSC treatment) were "study controls". We identified another control group: 36 patients from the Belarusian national surveillance database (surveillance controls) 1:1 matched to cases. Successful outcomes were observed in 81% of cases, 42% of surveillance controls, and 39% of study controls. After adjusting for age, odds of a successful outcome were 6.5 (95...

PLoS Medicine, 2007

Journal of Stem Cell Research & Therapeutics

Tuberculosis is a global health issue and a major cause of death worldwide. Emerging infectious disease as multidrug resistance and extensively drug resistance tuberculosis triggers the importance to improve the current therapy or else develop an innovative approach. Currently stem cell transplantation emerged as new therapeutic to overcome tuberculosis. Recent studies provide an opportunity to explore stem cell in treatment of drug resistant tuberculosis. This review is in concern with the regime, future effect and challenges of stem cell therapy in drug resistant patients.

American Journal of Respiratory and Critical Care Medicine, 2010

Rationale: Extensively drug-resistant (XDR) tuberculosis (TB) may arise in individuals on treatment for multidrug-resistant (MDR) TB. Preventing this amplification of resistance will likely improve clinical outcomes and delay the secondary spread of XDR-TB. Objectives: To measure the proportion of individuals that develops XDR-TB during the course of MDR-TB treatment, and to identify those factors associated with the development of XDR. Methods: We performed a retrospective analysis of 608 consecutive patients with documented MDR-TB who were started on MDR-TB treatment between September 10, 2000 and November 1, 2004 in the Tomsk Oblast TB Treatment Services in Western Siberia, Russian Federation. Measurements and Main Results: A total of 6% of patients were observed to develop XDR-TB while on MDR-TB treatment. These patients were significantly less likely to be cured or to complete treatment. Using Cox proportional hazard models, we found that the presence of bilateral and cavitary lesions was associated with a greater than threefold increase in hazard (adjusted hazard ratio [HR], 3.47; 95% confidence interval [CI], 1.32-9.14). Prior exposure to a secondline injectable antibiotic was associated with a greater than threefold increase in hazard (adjusted HR, 3.65; 95% CI, 1.81-7.37), and each additional month in which a patient failed to take at least 80% of their prescribed drugs was associated with nearly an additional 20% hazard of developing XDR-TB (adjusted HR, 1.17; 95% CI, 1.01-1.35). Conclusions: Early and rapid diagnosis, timely initiation of appropriate therapy, and programmatic efforts to optimize treatment adherence during MDR-TB therapy are crucial to avoiding the generation of excess XDR-TB in MDR-TB treatment programs.

Understanding Tuberculosis - New Approaches to Fighting Against Drug Resistance, 2012

Chemotherapeutic cure for about 40,000 years old lethal disease-TB (Callaway, 2008), was started mere ~65 years ago, with the discovery of antibiotic-streptomycin. A few effective drugs against TB have been developed since then and have been classified mainly as firstline (viz. rifampicin, isoniazid, pyrazinamide and ethambutol) and second-line drugs (e.g. ciprofloxacin, levofloxacin, cycloserine, clofazimine etc.). Drugs like rifambutin, clarithromycin and linezolid may be considered as "third line" drugs. The current course of therapy with the first-line TB drugs is more than 40 years old and is slowly becoming outdated due to emergence of multidrug-resistant tuberculosis (MDR-TB, resistant to the two first line drugs) and extensively drug-resistant tuberculosis (XDR-TB, an MDR-TB that is resistant to fluoroquinolones and also to any one of the three injectable second-line drugs: amikacin, capreomycin or kanamycin) (World Health Organisation, [WHO], 2011). Treatment with the second line drugs is limited due to the associated toxicity which halts therapy prior to cure in more than half of the patients suffering from serious side effects. The "third line" drugs have issues of proven efficacy/effectiveness and impractical cost. Longer duration of treatment, usually for six months, with complex regimens leads to poor compliance. Although poor compliance can be managed to great extent by Directly Observed Treatment, Short course (DOTS) launched by World Health Organization (WHO); but that is possible practically in developed countries only where manpower along with financial needs are met adequately. Apart from these problems, during this long treatment period, the patient and one's family suffer from socioeconomic problems, whereby psychological issues such as risk of depression come in picture. Side effect(s) of drugs, due to long treatment, is another major concern. Researchers have been trying to find out the answer for why the TB treatment is so long and complex. McCune et al found considerable difference in the efficacy of drugs against Mycobacterium tuberculosis (Mtb) in vitro and in vivo (McCune & Tompsett, 1956; McCune et al 1956). However, other researchers (Barclay et al. 1953; Clark, 1985) showed that bioavailability is not a concern. It was proposed that this persistence of Mtb might be due to physiologic heterogeneity of bacteria in the tissues (Mitchison, 1979; Handwerger & Tomasz, 1985).

EUROPEAN JOURNAL OF PHARMACEUTICAL AND MEDICAL RESEARCH, 2021

Tuberculosis (TB) may be a global infectious threat that's intense by associate degree increasing incidence of extremely drug-resistant disease. A complete of 1.5 million folks died from TB in 2018 occurred worldwide; 3.3% of those cases resulted from multidrug-resistant infectious disease (MDR-TB) and extensively drug-resistant infectious disease (XDR-TB) strains. Prevalence of multidrug-resistant TB (MDR TB) cases is on the rise in India, and proportions of new cases of MDR. Treatment of drug-susceptible TB conducted under strong national TB programs (NTPs) using standard four-drug therapy and directly observed therapy (DOT) has led to relapse-free cure rates over 95% and dramatic national declines in TB incidence. The current proposal of DOTS and by the World Health Organization highlights the great management strategy to manage MDR-TB. MDR-TB may be an unreal downside and its emergence may be prevented by prompt designation and effective treatment of all TB cases along with the recent emergence of covid-19 that may reverse the latest progress in reducing the worldwide load of TB.

International Journal of Infectious Diseases, 2015

Journal of Clinical Investigation