Multidrug-resistant tuberculosis (MDR-TB), caused by drug resistant strains of Mycobacterium tuberculosis, is an increasingly serious problem worldwide. In this study, we examined a dataset of 5,310 M. tuberculosis whole genome sequences from five continents. Despite great diversity with respect to geographic point of isolation, genetic background and drug resistance, patterns of drug resistance emergence were conserved globally. We have identified harbinger mutations that often precede MDR. In particular, the katG S315T mutation, conferring resistance to isoniazid, overwhelmingly arose before rifampicin resistance across all lineages, geographic regions, and time periods. Molecular diagnostics that include markers for rifampicin resistance alone will be insufficient to identify pre-MDR strains. Incorporating knowledge of pre-MDR polymorphisms, particularly katG S315, into molecular diagnostics will enable targeted treatment of patients with pre-MDR-TB to prevent further development of MDR-TB.

Introduction: This study aimed to determine first-line anti-tuberculosis drug resistance rates in new and previously treated cases and to identify risk factors associated with multidrug resistant tuberculosis (MDR-TB) at the National Reference Tuberculosis Laboratory of Iran. Methodology: This was a retrospective analysis of all confirmed TB patients from December 2000 to June 2005. Drug susceptibility testing to isoniazid, rifampicin, streptomycin, ethambutol and pyrazinamide was performed on Löwenstein-Jensen (LJ) medium according to the proportion method. Results: Mycobacterium tuberculosis strains were isolated from 1,742 patients with TB, of whom 935 (53.7%) were male. The mean age of patients was 44.2 ± 17.4 years (SD). A total of 1,074 patients were native Iranians while 668 (38.3%) were immigrant patients. Out of 1,139 (65.4%) new cases, 340 (29.9%) had at least one drug resistance. Of 603 (34.6%) previously treated cases, 416 (69.0%) had resistant strains. There were 263 patients (15.1%) with MDR-TB, 72 of whom were new (6.3% of all new cases) and 191 were previously treated (31.7% of all previously treated cases). Factors associated with MDR-TB included age under 45 years, male sex, previous TB treatment, immigration, poor living conditions, and unemployment. Conclusions: The high rate of initial resistance in MDR-TB cases and the high rate of MDR-TB in a young age group were indicators of recent transmission. Therefore, closer monitoring of transmission trends of drug resistant strains should be considered as priority, to ensure a successful TB control programme.

Non-coding RNAs are responsible for the regulation of many cell signaling pathways. These molecules include long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and microRNAs (miR-NAs), which are involved in several biological processes such as apoptosis, mitochondrial dysfunction, and innate immunity. [6][7][8][9][10] lncRNAs are transcripts containing more than 200 nt, whose mechanisms of formation and function have been recently investigated. 11,12 According to some experimental studies, the differential expression of some lncRNAs has been found in cardiomyocytes, monocytes, and human tubular epithelial cells, when subjected to the addition of plasma obtained from septic patients, or, alternatively, the addition of pure lipopolysaccharide (LPS). [13][14][15] However, the function of these lncRNAs in sepsis still remains unclear. Human umbilical vein endothelial cells were screened for lncRNAs, and the results showed 28-to 70-fold increases in the expression of these non-coding RNAs after LPS exposure. 16 These changes could be involved in the modulation of inflammatory responses. For example, the lncRNA called lnc-IL7R

Introduction: Several species of non-tuberculosis mycobacteria (NTM) can affect humans and can cause either symptomatic or asymptomatic infection. This study aimed to determine the clinical and radiological manifestation, as well as the treatment, of M. simiae in patients in Masih Daneshvari Hospital, a TB referral hospital in Iran. Methodology: This retrospective study involved all patients presenting to our referral center from 2002 to 2009, with confirmation of M. simiae pulmonary infection. For all patients, sputum smear and culture for identification was performed, as was drug susceptibility testing. Additionally, PCR identification methods for NTM, and high-resolution CT scan were conducted. All patients were treated according to American Thoracic Society recommendations. Results: In total, 26 cases of M. simiae were identified in our center. The mean age of the patients was 58.23 ± 16.9years. Only one patient was HIV positive, and all but one were Iranian. The most frequent symptom was coughing (92.3%), and 100% of the patients had nodular lesions. In addition, bronchiectasis and cavitation were present in 84.6% and 88.5% respectively. All the patients were resistant to every firstline drug. Two patients failed the treatment, and twenty-four were cured, after which no recurrence of the disease was observed. Conclusion: M. simiae may present with clinical and radiological manifestations consistent with tuberculosis, and be resistant to anti-TB agents. A more efficient treatment for NTMs such as M. simiae is needed, to shorten the period of treatment and proved fewer adverse effects than current therapies.

The novel coronavirus 2019 (2019-nCoV), formally named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a novel human infectious coronavirus. The disease caused by SARS-CoV-2 is named COVID-19. Development and manufacturing of specific therapeutics and vaccines to treat COVID-19 are time-consuming processes. At this time, using available conventional therapeutics along with other treatment options may be useful to fight COVID-19. In different clinical trials, efficacy of remdesivir (GS-5734) against Ebola virus has been demonstrated. Moreover, remdesivir may be an effective therapy in vitro and in animal models infected by SARS and MERS coronaviruses. Hence, the drug may be theoretically effective against SARS-CoV-2. Remdesivir is a phosphoramidate prodrug of an adenosine C-nucleoside. By entrance into respiratory epithelial cells in human, the prodrug is metabolized to a nucleoside triphosphate as the active form. The nucleoside analog inhibits the viral RNA-dependent RNA polymerase (RdRp) by competing with the usual counterpart adenosine triphosphate (ATP). The nucleoside analog is incorporated into the generating RNA strand and causes a delayed stop in the viral replication process. Knowledge about the potential efficacy of remdesivir against coronaviruses has been restricted to in vitro studies and animal models. However, information related to COVID-19 is rapidly growing. Several clinical trials are ongoing for the management of COVID-19 using remdesivir. In this study, characteristics of remdesivir and its usage for treatment of COVID-19 are reviewed based on an electronic search using PubMed and Google Scholar.

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Even in the 21st century, we are losing the battle against eradication of tuberculosis (TB). In 2015, 9.6 million people were estimated to have fallen ill with TB, of which 1.5 million people died. This is the real situation despite the well-structured treatment programs and availability of effective treatment options since the 1950s. The high mortality rate has been associated with other risk factors, such as the HIV epidemic, underlying diseases, and decline of socioeconomic standards. Furthermore, the problem of drug resistance that was recognized in the early days of the chemotherapeutic era raises serious concerns. Although resistance to a single agent is the most common type, resistance to multiple agents is less frequent but of greater concern. The World Health Organization estimated approximately 5% of all new TB cases involved multidrug-resistant (MDR)-TB. The estimation for MDR-TB is 3.3% for new cases, and 20.5% for previously treated cases. Failure to identify and appropriately treat MDR-TB patients has led to more dangerous forms of resistant TB. Based on World Health Organization reports, 5% of global TB cases are now considered to be extensively drug resistant (XDR), defined as MDR with additional resistance to both fluoroquinolones and at least one second-line injectable drug. XDR-TB had been reported by 105 countries by 2015. An estimated 9.7% of people with MDR-TB have XDR-TB. More recently, another dangerous form of TB bacillus was identified, which was named totally drug resistant (TDR-TB) or extremely drug resistant TB. These strains were resistant to all first- and second-line anti-TB drugs. Collectively, it is accepted that 2% of MDR-TB strains turn to be TDR-TB. This number, however, may not reflect the real situation, as many laboratories in endemic TB countries do not have proper facilities and updated protocols to detect the XDR or TDR-TB strains. Nevertheless, existing data emphasize the need for additional control measures, such as new diagnostic methods, better drugs, and more effective vaccines to prevent the spread of these strains around the world.

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