Drug Resistance Pattern in Pulmonary Tuberculosis Patients and Risk Factors Associated with Multi-Drug Resistant Tuberculosis

Introduction: Anti-tuberculosis drug resistance is a major problem in tuberculosis (TB) control programme, particularly multi-drug resistance TB (MDR-TB) in Nepal. Drug resistance is difficult to treat due to its associated cost and side effects. The objective of this study was to assess the drug resistance pattern and assess risk factor associated with MDR-TB among pulmonary tuberculosis patients attending National Tuberculosis Center. Methodology: The comparative cross sectional study was conducted at National Tuberculosis Center during August 2015 to February 2015. Early morning sputum samples were collected from pulmonary tuberculosis suspected patients and subjected to Ziehl-Neelsen staining and fluorochrome staining and culture on Lowenstein-Jensen (LJ) medium. Drug Susceptibility test was performed on culture positive isolates by using proportion method. Univariate and multivariate analysis was computed to assess the risk factors of MDR-TB. Results: Out of 223 sputum samples, 105 were fluorochrome staining positive, 85 were ZN staining positive and 102 were culture positive. Out of 102 culture positive isolates, 37.2% were resistance to any four anti-TB drugs. 11 (28.9%) were initial drug resistance and 28 (43.7%) were acquired drug resistance. The overall prevalence of MDR-TB was 11.7%, of which 2 (5.3%) were initial MDR-TB and 10 (15.6%) were acquired MDR-TB. Univariate and multivariate analysis showed female were significantly associated (P = 0.05) with MDR-TB. Conclusion: Drug resistance TB particularly MDR-TB is high. The most common resistance pattern observed in this study was resistance to both isoniazid and rifampicin. Female were found to be associated with MDR-TB. Thus, early diagnosis of TB and provision of culture and DST are crucial in order to combat the threat of DR-TB.

In Vitro Anti-tuberculosis Activity of Total Crude Extract of Echinops Amplexicaulis against Multi-drug Resistant Mycobacterium Tuberculosis

Background： TB （Tuberculosis） is the second leading killer infectious disease after HIV （human immunodeficiency virus）. Its incidence is worsened by development of multi-drag resistant and extensive drug resistant TB stxains. Available treatment regimens are expensive, toxic and lengtjy resulting to problems of non-adherence and inadequate response. Medicinal plants on the other hand may offer hope for developing alternative medicine for treatment of TB. This study evaluated the anti-tuberculosis activity of Echinops amplexicaulis. Materials and methods： Total crude extracts ofE. amplexicaulis were tested for activity against a wild strain resistant to Rifampicin and Isoniazid （MDR）, a fully susceptible laboratory strain （H37Rv） and Mycobacwrium boris （BCG strain） using disk diffusion method. MIC （minimum inhibitory concentration） was determined using Middlebrook 7H9 broil1. The strains were sub-cultured on Middlebrook 7H10 medium and MBC （minimum bactericidal concentration） determined. Susceptibility was evaluated by measuring zones of inhibition; MIC was obtained as the lowest concentration with no significant growth as shown by clog formation ofMTB （Mycobacwria tuberculosis） cells on the walls of the macro broth tube and MBC was obtained as the lowest concentration that inhibited growth of MTB colonies on Middlebrook 7H10 medium. Results： The extract showed a significant effect at a concentration of 50 mg/mL against all the three test strains F （2, 18） = 437.7, p = 0.00. It exhibited a MIC of 0.0488 mg/mL against MDR-TB and M. boris. Its MBC was the same at 0.0977 mg/mL against both MDR TB and M. boris. The MIC was much lower （0.0122 mg/mL） for the H37Rv strain. Terpenoids, alkaloids and tannins were present in large amount in the extract while saponins were present in small amounts. Flavonoids were not detected in the extract. Conclusion： E. amplexicaulis has the potential to be developed into new anti-TB drug and outcome of tile study supports the folkloric claims of anti-tuberculosis activity of tile plant.

Diabetes and tuberculosis:An emerging dual threat to healthcare

Tuberculosis(TB)remains a huge global healthcare challenge even in the 21^(st) century though the prevalence has dropped in developed countries in recent decades.Diabetes mellitus(DM)is an important risk factor for the development and perpetuation of TB owing to the immune dysfunction in patients with DM.The coexistence of both diseases in the same individual also aggravates disease severity,complications,and chance of treatment failure because of gross immune alterations posed by DM as well as TB.Various complex cellular and humoral immunological factors are involved in the dangerous interaction between TB and DM,some of which remain unknown even today.It is highly important to identify the risk factors for TB in patients with DM,and vice versa,to ensure early diagnosis and management to prevent complications from this ominous coexistence.In their research study published in the recent issue of the World Journal of Diabetes,Shi et al elaborate on the factors associated with the development of TB in a large cohort of DM patients from China.More such research output from different regions of the world is expected to improve our knowledge to fight the health devastation posed by TB in patients with diabetes.

Prevalence and Risk Factors of Primary Drug-Resistant Tuberculosis in China

Objective To investigate the prevalence of primary drug-resistant tuberculosis（TB） and associated risk factors in China. We also explored factors contributing to the transmission of multidrug-resistant tuberculosis（MDR-TB）. Methods A total of 2794 representative, Mycobacterium tuberculosis isolates from treatment-naive patients were subjected to drug susceptibility testing, and risk factors for drug-resistant TB were analyzed. We also analyzed MDR-TB strain sublineages, drug-resistance-conferring mutations, and risk factors associated with clustered primary MDR strains. Results Among 2794 Mycobacterium tuberculosis isolates from treatment-naive patients, the prevalence of any resistance to first-line drugs was 33.2% and the prevalence of MDR-TB was 5.7%. We did not find any risk factors significantly associated with resistance to first-line drugs. The 93 primary MDR-TB isolates were classified into six sublineages, of which, 75（80.6%） isolates were the RD105-deleted Beijing lineage. The largest sublineage included 65（69.9%） isolates with concurrent deletions of RD105, RD207, and RD181. Twenty-nine（31.2%） primary MDR strains grouped in clusters; MDR isolates in clusters were more likely to have S531 L rpoB mutation. Conclusion This study indicates that primary drug-resistant TB and MDR-TB strains are prevalent in China, and multiple measures should be taken to address drug-resistant TB.

Epidemiological characteristics of 369 tuberculosis patients with multidrug resistance inHainan Island: A cross-sectional study

Objective:To investigate the epidemic characteristics of multidrug resistant tuberculosis in Hainan,China,to provide basic information and theories for the prevention and control of multidrug resistant tuberculosis.Methods:A retrospective descriptive epidemiological study was conducted.Data of multidrug resistant tuberculosis in Hainan Island from January 1,2014 to December 31,2019 were collected for statistical analysis.The counting data were described by frequency(percentage),and the measurement data were described by mean±standard deviation.Chi square test was used to compare the differences between different groups.If P<0.05,the difference was statistically significant.Results:From 2014 to 2019,the multidrug resistant rate of tuberculosis in Hainan Island was 24.9%(369/1484),8.0%(63/791)in newly-treated tuberculosis,and 44.2%(306/693)in retreatedmultidrug resistant rate of tuberculosis in Hainan Island was 24.9%(369/1484),8.0%(63/791)in newly-treatedtuberculosis,and 44.2%(306/693)in retreated tuberculosis.The multidrug resistant rate of newly-treated tuberculosis decreased by 0.05%per year,while that of retreated tuberculosis increased by 0.03%per year.multidrug resistant tuberculosis was mainly distributed in the city of Haikou(83 cases),Danzhou(44 cases),Wenchang(42 cases),Wanning(37 cases)and Dongfang(32 cases),accounting for 64.5%of all multidrug resistant tuberculosis.Among 369 multidrug resistant tuberculosis,81.0%were male.The proportion of newly-treated cases was 17.1%(63/369),while the proportion of retreated cases was 82.9%(306/369),which was significantly higher than that of newly-treated cases.The multidrug resistant rate of tuberculosis in different years was different.Conclusion:The drug resistance rate of tuberculosis in Hainan Island is higher than the national average level,which needs attention.The epidemiological characteristics of multidrug resistant tuberculosis with different treatment history were different.

Prevalence of Mycobacterium tuberculosis Strains Isolated from Both Pulmonary and Extra Pulmonary Samples and Their Resistance to Rifampicin: A Study from Kolkata and Surrounding Suburbs

Tuberculosis (TB) is one of the major causes of morbidity and mortality worldwide. In India, nearly 1.8 million new cases of TB are reported annually, which accounts for a fifth of new cases in the world—greater than in any other country. Anti-tubercular drugs (ATDs) have been used for decades, and widespread resistance to them is a very serious public health concern in any part of the world. Aim of this study was to determine the prevalence of Rifampicin (the first line Anti-TB drug) resistance among both pulmonary and extra-pulmonary samples tested positive for Mycobacterium tuberculosis and thereby predict the prevalence of Multi-drug resistant (MDR) tuberculosis in Kolkata and its Suburban regions. All 331 randomly collected clinical samples (both Pulmonary and Extra Pulmonary) were initially screened by Zeihl-Neelsen AFB staining followed by culture on BacT/Alert 3D system and on Lowenstein-Jensen medium and the positive samples were subjected to detection of Mycobacterium tuberculosis complex (MTBC) and simultaneous analysis of Rifampicin resistance by Xpert MTB/RIF assay. Out of the 51 (15.40%) culture positive samples, 13.7% of pulmonary samples and 9.09% of extra-pulmonary samples were Rifampicin resistant. The prevalence of Rifampicin resistant TB in our study is high and the possible reasons can be mixing of new as well as retreatment cases and smaller sample size but, yet it can help Government and public health regulatory bodies to formulate adequate strategies to fight against drug resistant tuberculosis, especially in this part of the world.

The History of Tuberculosis: Past, Present, and Future

Tuberculosis (TB), transmitted by the bacteria Mycobacterium tuberculosis has been a global epidemic for years. The evidence for infection with TB is centuries old. It can have an indolent course, and may remain inactive for years in individuals with the possibility of reactivation at any time, causing widespread systemic symptoms. The treatment and management of TB has become more effective over the years. It is estimated that more than one-third of the world population, especially in poor and developing countries are harboring this bacterium with varying manifestations of the disease from no symptoms to life-threatening infections. This manuscript describes the history of the disease and the discoveries. It also includes the recent advances and challenges facing the world and how governments and organizations are working together to control this disease.

Tuberculosis treatment-new approach to an old problem

Chronic mycobacterium infections are major causes of disease burden of 20%in a tropical country like India. The inflammatory cascade following these bacterial infections often leads to tissue damage and perpetuates necrosis, fibrosis and the disease process.Pulmonary tuberculosis,multi-drug resistant tuberculosis not only affects individuals but society at large.Current remedial measures using various technology platforms singularly did not produce effective and appreciable reduction in global disease burden.On the contrary,the conventional chemotherapeutic chemical moieties have demonstrated variable pharmacogenomic expression,increased drug resistance,non compliance of strict prolonged drug regimens with debilitating side effects and contraindications. Furthermore,secreted inflammatory cytokines results in chronic infection,immune deviation,and immunopathology in the lungs.Hence,identification of immune escape mechanisms leading to chronic mycobacterial infections is crucial for development of new treatments.The review would dwell into the basic pathogenic mechanism and the newer approaches that may need to be considered for developing novel therapeutic strategies.

The Prediction Factors of Pre-XDR and XDR-TB among MDR-TB Patients in Northern Thailand

Background: Molecular diagnosis based on the detection of mutations conferring genetic drug resistance is useful for early diagnosis and treatment of Pre-XDR and XDR-TB patients. However, the study of mutation as a marker to predict Pre-XDR and XDR-TB is rare. Methods: Thirty-four Mycobacterium tuberculosis (MTB) isolates from MDR, Pre-XDR and XDR-TB patients in the upper north of Thailand, who had been identified for drug susceptibility using the indirect agar proportion method from 2005-2012, were examined for genetic site mutations of katG, inhA, and ahpC for isoniazid (INH) drug resistance, rpoB for rifampicin (RIF) drug resistance, gyrA for ofloxacin (OFX), and rrs for kanamycin (KAN). Associations between resistant genes and Pre-XDR and XDR-TB in the MDR patients were performed using exact probability tests. Univariable logistic regression was used to quantify the strength of association between the gene mutation with Mycobacterium tuberculosis and the prevalence of Pre-XDR and XDR-TB in the MDR patients. Results: The mutations in the region of the rpoB gene at codon 445 (C445T) in the Pre-XDR or XDR-TB patients were significantly 20.6 times more prevalent among the MDR-TB patients. The inhA gene mutation at codon 114 (T114G) was also significantly 8.1 times more prevalent. Conclusion: The findings can be used to predict the odds of Pre-XDR and XDR-TB in MDR-TB patients, as a guide for prevention and treatments.

上海市耐多药结核病患者经济负担研究

目的基于上海市近年结核病诊疗费用减免政策,探索耐多药结核病(multidrug resistant tuberculosis,MDR-TB)患者疾病经济负担及其影响因素,为优化MDR-TB诊疗费用减免政策和综合管理模式提供依据。方法收集上海市2017—2019年确诊MDR-TB患者情况和诊疗费用减免情况数据,开展针对疾病经济负担的问卷调查,建立涵盖患者人口和社会经济情况、临床特征、疾病经济负担和诊疗费用减免情况数据库,明确患者疾病经济负担和灾难性卫生支出(catastrophic health expenditure)发生情况。以多元线性回归法分析可能影响患者疾病经济负担的因素,以多因素logistic回归法分析不同比例下灾难性卫生支出发生的影响因素。结果196例纳入研究分析的MDR-TB患者平均年龄为(44±16)岁,男性139例(占70.9%),上海户籍占46.4%,49%的患者为家庭主要劳动力。治疗期间,患者自付诊疗费用中位数为4.0(四分位数区间2.0~6.5)万元。113例患者获得减免诊疗,减免费用中位数为2.6(四分位数区间1.3~4.9)万元。若自付费用占家庭年收入的40%及以上,有47.8%的患者会发生灾难性支出;若不考虑减免政策,有59.8%的患者发生灾难性卫生支出。上海户籍(OR=0.3,95%CI为0.1~1.0)、更低家庭收入水平(P_(trend)=0.002)、医疗保险类型[(农村合作医疗保险/外来人口综合保险(OR=13.3,95%CI为1.0~171.2),无医疗保险(OR=17.5,95%CI为2.7~113.0)]和既往结核病治疗史(OR=3.3,95%CI为1.1~10.0)可能影响灾难性卫生支出的发生。结论上海市MDR-TB患者的自付诊疗费用较高。医疗保障力度较小和家庭经济情况不佳的患者更易发生高额自付费用,导致灾难性卫生支出。上海市MDR-TB诊疗费用减免政策有效降低了患者的经济负担。

Isoniazid and Rifampicin as Therapeutic Regimen in the Current Era: A Review

Tuberculosis represents one of the biggest challenges in the medical field. According to World Health Organization (WHO) Global Tuberculosis Report, 2012, there were estimated 8.7 million new TB cases worldwide while 1.4 million people died of TB. Additionally, 90% of the cases of TB are reported in developing countries, with India having the largest number of incident cases. The current treatment method includes the administration of a cocktail of drugs which includes Isoniazid (INH), Rifampicin (RIF), Ethambutol (EMB) and Pyrazinamide (PZA) which are referred to as the first line of drugs. Isoniazid and Rifampicin are currently the two most powerful anti-TB medications. The occurrences of multi-drug and extensive-drug resistant strains (MDR-TB and XDR-TB, respectively) have become a global concern and pose a serious challenge for public health management. Treatment of these resistant cases involves the usage of the second line of anti-tuberculosis drugs which are less effective than the first line and are known to cause adverse reactions or toxic side-effects. Tuberculosis research should not only focus on treatment methods but also on management of the current cases of resistance and measures to prevent an outbreak of resistant TB infection. This review outlines the mechanism of action of isoniazid and rifampicin and how resistance to these drugs emerges. We also provide a brief insight into the prevalence of HIV in TB patients and the challenges associated with treatment regimens in this co-infection.