Factors contributing to the high prevalence of multidrug-resistance/Rifampicin-resistance in patients with tuberculosis: an epidemiological cross sectional and qualitative study from Khabarovsk krai region of Russia.

BACKGROUND: Growing prevalence of multidrug-resistant/Rifampicin-resistant tuberculosis (MDR/RR-TB; resistance to Isoniazid and Rifampicin/Isolated resistance to Rifampicin) is putting in jeopardy the WHO End TB strategy. This study aimed to identify factors contributing to the high prevalence of MDR/RR-TB in Khabarovsk krai region of Russia. METHODS: A cross-sectional retrospective study was conducted, analyzing clinical, demographic, and drug susceptibility testing data on 1440 patients. As a source of raw data, the national electronic TB surveillance system was used. Anonymous data was collected on every patient diagnosed with TB in all healthcare facilities of the region from January 2018 to December 2019. Only patients with proven excretion of m. tuberculosis were included in the study. Factors associated with MDR/RR-TB were identified through logistic regression analysis, in conjunction with in-depth interviews with eight patients, five healthcare managers and five doctors. FINDINGS: 2661 patients were identified with TB, 1440 were incorporated in the study based on inclusion criteria. Of these, 618 (42.9%) were identified with MDR/RR-TB. Patients with a history of imprisonment were 16.53 times (95% CI 5.37 to 50.88,) more likely to have MDR/RR-TB, whereas re-treatment patients were 2.82 times (95% CI 2.16 to 3.66) more likely to have MDR/RR-TB. Other influencing factors included presence of disability (AOR is 2.32, 95% CI 1.38 to 3.89), cavitary disease (AOR is 1.76, 95% CI 1.37 to 2.25), and retirement status (AOR 0.65, 95% CI 0.43 to 0.98, p = 0.042). Poor patient knowledge and understanding of the disease, progressive weariness of prolonged TB treatment, and inability hospitalize infectious patients without their consent were perceived by the interviewees as major influencing factors. CONCLUSIONS: Incarceration and treatment history, regardless of outcome, were identified as major factors influencing MDR/RR-TB prevalence. It is essential for the TB care system to eliminate legal loopholes, which deprive doctors of means to enforce quarantine procedures and epidemiological surveillance on infected patients, former and current inmates. Increasing people's awareness of TB, early detection and appropriate treatment of patients with TB are needed for successfully combating MDR/RR-TB.

Clinical characteristics of COVID-19 in patients with tuberculosis and factors associated with the disease severity.

BACKGROUND: Data on patients with COVID-19 who have pulmonary tuberculosis (TB) are limited. In this study, we compared the clinical characteristics of patients with COVID-19/TB and patients with COVID-19 only. In addition, we analyzed the links between the severity of COVID-19 disease and the clinical characteristics of patients with COVID-19/TB. METHODS: We conducted a retrospective, anonymized, cross-sectional study of 111 patients who met inclusion criteria for analysis (75 patients with COVID-19/TB and 36 patients with COVID-19). RESULTS: Patients in both groups (COVID-19/TB vs COVID-19) mainly suffered from fever (72.0% vs 100%, p < 0.001), fatigue (76.0% vs 94.4%, p  =  0.018), chest pain (72.0% vs 36.1%, p < 0.001), followed by cough (60.0% vs 97.2%, p < 0.001) and dyspnea (44.0% vs 63.9%, p  =  0.05). In group COVID-19/TB the most frequently reported co-morbidities were chronic liver disease (17 [22.7%]), cardiovascular diseases (25 [33.3%]), and diseases of the nervous system (13 [17.3%]). Female gender, fever, dyspnea, pulmonary bilateral TB lesion, and three or more co-morbidities have a statistically significant positive effect on the severity of the disease among patients with COVID-19/TB. CONCLUSION: It is important to perform rapid molecular testing and computed tomography to correctly distinguish COVID-19 and TB because of the similar clinical characteristics of both diseases. Bilateral pulmonary TB lesion and co-morbidity should be considered risk factors for severe COVID-19.

Human non-CG methylation: are human stem cells plant-like?

Non-CG methylation is well characterized in plants, where it appears to play a role in gene silencing and genomic imprinting. Although strong evidence for the presence of non-CG methylation in animals has been available for some time, both its origin and function remain elusive. In this review we discuss available evidence on non-CG methylation in animals in light of evidence suggesting that the human stem cell methylome contains significant levels of methylation outside the CG site.

Transgene-induced CCWGG methylation does not alter CG methylation patterning in human kidney cells.

Several reports suggest that C(m)CWGG methylation tends not to co-exist with (m)CG methylation in human cells. We have asked whether or not methylation at CCWGG sites can influence CG methylation. DNA from cells expressing an M.EcoRII-GFP fusion was actively methylated at CCWGG sites. CG methylation as measured by R.HpaII/R.MspI ratios was unchanged in cells expressing the transgene. Cloned representatives of C(m)CWGG methylated DNA often contained, or were adjacent to an ALU repeat, suggesting that M.EcoRII-GFP actively methylated gene-rich R-band DNA. The transgenic methyltransferase applied C(m)CWGG methylation to a representative human promoter that was heavily methylated at CG dinucleotides (the SERPINB5 promoter) and to a representative promoter that was essentially unmethylated at CG dinucleotides (the APC promoter). In each case, the CG methylation pattern remained in its original state, unchanged by the presence of neighboring C(m)CWGG sites. Q-PCR measurements showed that RNA expression from the APC gene was not significantly altered by the presence of C(m)CWGG in its promoter. Kinetic studies suggested that an adjacent C(m)CWGG methylation site influences neither the maintenance nor the de novo methylation activities of purified human Dnmt1. We conclude that C(m)CWGG methylation does not exert a significant effect on CG methylation in human kidney cells.