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      Prevalence and molecular characteristics of drug-resistant Mycobacterium tuberculosis in Hainan, China: from 2014 to 2019

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          Abstract

          Background

          The emergence of antimicrobial resistance against Mycobacterium tuberculosis ( M. tuberculosis) has become the major concern in global tuberculosis control due to its limited therapy options and high mortality. However, the clinical and molecular characteristics of drug-resistant strains vary in different geographical areas. Hainan Island located in southern China, is a high drug-resistant tuberculosis burden area. This study aimed to determine the dynamic changes of drug-resistance patterns and drug-related gene mutation types of M. tuberculosis in Hainan from 2014 to 2019.

          Results

          A total of 1484 culture-confirmed M. tuberculosis were included in this study. It was found that the proportions of drug resistance to isoniazid and rifampin were 31.3 and 31.1% respectively. Overall the proportion of multidrug resistant M. tuberculosis was 24.9%. Multivariate logistic regression analysis showed that age and the treatment history were independent influencing factors of drug resistant tuberculosis. The proportions of drug-resistant tuberculosis in retreatment patients were considerably higher than those in new patients. The most common mutation types of isoniazid were Ser315 → Thr (66.3%), and the most common mutation types of rifampin were Ser531 → Leu (41.5%).

          Conclusions

          Our data suggests that the prevalence of drug resistant TB remains high in Hainan, and the risks for developing drug resistance with diversified mutation types increased significantly in retreatment patients. These results contribute to the knowledge of the prevalence of drug resistance in Hainan Province and expand the molecular characteristics of drug resistance in China simultaneously.

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          Most cited references31

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          Risk factors for multidrug resistant tuberculosis in Europe: a systematic review.

          The resurgence of tuberculosis (TB) in western countries has been attributed to the HIV epidemic, immigration, and drug resistance. Multidrug resistant tuberculosis (MDR-TB) is caused by the transmission of multidrug resistant Mycobacterium tuberculosis strains in new cases, or by the selection of single drug resistant strains induced by previous treatment. The aim of this report is to determine risk factors for MDR-TB in Europe. A systematic review was conducted of published reports of risk factors associated with MDR-TB in Europe. Meta-analysis, meta-regression, and sub-grouping were used to pool risk estimates of MDR-TB and to analyse associations with age, sex, immigrant status, HIV status, occurrence year, study design, and area of Europe. Twenty nine papers were eligible for the review from 123 identified in the search. The pooled risk of MDR-TB was 10.23 times higher in previously treated than in never treated cases, with wide heterogeneity between studies. Study design and geographical area were associated with MDR-TB risk estimates in previously treated patients; the risk estimates were higher in cohort studies carried out in western Europe (RR 12.63; 95% CI 8.20 to 19.45) than in eastern Europe (RR 8.53; 95% CI 6.57 to 11.06). National estimates were possible for six countries. MDR-TB cases were more likely to be foreign born (odds ratio (OR) 2.46; 95% CI 1.86 to 3.24), younger than 65 years (OR 2.53; 95% CI 1.74 to 4.83), male (OR 1.38; 95% CI 1.16 to 1.65), and HIV positive (OR 3.52; 95% CI 2.48 to 5.01). Previous treatment was the strongest determinant of MDR-TB in Europe. Detailed study of the reasons for inadequate treatment could improve control strategies. The risk of MDR-TB in foreign born people needs to be re-evaluated, taking into account any previous treatment.
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            Antibiotic resistance mechanisms in M. tuberculosis: an update.

            Treatment of tuberculosis (TB) has been a therapeutic challenge because of not only the naturally high resistance level of Mycobacterium tuberculosis to antibiotics but also the newly acquired mutations that confer further resistance. Currently standardized regimens require patients to daily ingest up to four drugs under direct observation of a healthcare worker for a period of 6-9 months. Although they are quite effective in treating drug susceptible TB, these lengthy treatments often lead to patient non-adherence, which catalyzes for the emergence of M. tuberculosis strains that are increasingly resistant to the few available anti-TB drugs. The rapid evolution of M. tuberculosis, from mono-drug-resistant to multiple drug-resistant, extensively drug-resistant and most recently totally drug-resistant strains, is threatening to make TB once again an untreatable disease if new therapeutic options do not soon become available. Here, I discuss the molecular mechanisms by which M. tuberculosis confers its profound resistance to antibiotics. This knowledge may help in developing novel strategies for weakening drug resistance, thus enhancing the potency of available antibiotics against both drug susceptible and resistant M. tuberculosis strains.
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              Factors influencing adherence to tuberculosis treatment in Asmara, Eritrea: a qualitative study

              Background Non-adherence to tuberculosis (TB) treatment is an important barrier for TB prevention and control. Poor adherence may result in prolonged disease infectiousness, drug resistance, relapse and death. The aim of this study was to assess factors influencing adherence to tuberculosis treatment in selected health facilities in Asmara, Eritrea. Methods A qualitative study which included in-depth interviews with 12 TB patients, three focus group discussions in selected health facilities in which one group comprised eight patients and key informant interviews with three health workers. Data analysis was done by translating and transcribing the verbatim of the interviews and focus group discussions. Transcribed data was then analysed using thematic framework procedure. Results This study found that patients lacked knowledge about the cause, transmission and duration of treatment of TB. The most common reason mentioned for discontinuing treatment was the patient “felt cured”. Almost half of the respondents did not know the standard treatment duration and the consequences they face if they halt treatment. Patients reported losing their job when their diagnosis was known, were too ill to continue working or unable to find daily work due to time-consuming treatment arrangements. With few exceptions, the majority of patients reported that the short distance to the clinic encouraged them to attend regular treatment follow-up. Most of the respondents were unable to get enough food, leading to stress and feelings of hopelessness. Lack of social support for most of the patients was a critical factor for adherence as were stigma, medication side effects and long treatment duration. Recognized as an enabler to treatment adherence, health workers had good communication and positive attitude towards their patients. Conclusion Lack of knowledge, loss of income, stigma and lack of social support, drug side effects and long treatment duration emerged as important barriers for treatment adherence. Short distances to health facilities, good communication and accepting attitude of health care providers emerged as enablers for treatment adherence. For better treatment adherence, comprehensive health education at treatment sites, patient’s family members and the community at large and strengthening of social support structures need to be addressed.
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                Author and article information

                Contributors
                phzmh61@aliyun.com
                xiaqianfeng@hainmc.edu.cn
                Journal
                BMC Microbiol
                BMC Microbiol
                BMC Microbiology
                BioMed Central (London )
                1471-2180
                19 June 2021
                19 June 2021
                2021
                : 21
                : 185
                Affiliations
                [1 ]GRID grid.443397.e, ISNI 0000 0004 0368 7493, NHC Key Laboratory of Control of Tropical diseases, Key Laboratory of Tropical Translational Medicine of Ministry of Education, School of Tropical Medicine and Laboratory Medicine, , Hainan Medical University, ; Haikou, 571199 China
                [2 ]GRID grid.443397.e, ISNI 0000 0004 0368 7493, Public Health School, , Hainan Medical University, ; Haikou, 571199 Hainan China
                [3 ]Hainan Province cadre sanatorium, Hainan Province Geriatric Hospital, Haikou, 571100 China
                [4 ]GRID grid.443397.e, ISNI 0000 0004 0368 7493, Department of Clinical Laboratory, The Second Affiliated Hospital, , Hainan Medical University, ; Haikou, 570311 China
                Article
                2246
                10.1186/s12866-021-02246-7
                8214299
                34147065
                58051d05-eccf-40fd-9428-f59549f36a90
                © The Author(s) 2021

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 8 January 2021
                : 2 June 2021
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100013072, Major Science and Technology Project of Hainan Province;
                Award ID: ZDKJ202003
                Award Recipient :
                Funded by: The National Science and Technology Major Project
                Award ID: 2018ZX10101003-001-009
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 81960002 and 81860002
                Award Recipient :
                Funded by: School of Tropical Medicine and Laboratory Medicine, Hainan medical University/Research Cultivation fund
                Award ID: 1021/XPY180017
                Award Recipient :
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2021

                Microbiology & Virology
                mycobacterium tuberculosis,dna microarray,drug sensitivity test,molecular-characteristics,drug-resistant rate

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