A Case Study of Multi Drug-Resistant Tuberculosis (MDR-TB), HIV and Diabetes Mellitus (Dm) Comorbidity: Triple Pathology;Challenges and Prospects

Tuberculosis (TB), diabetes mellitus and HIV co-morbidity is a rare and interrelated health condition with associated high morbidity and mortality especially in developing countries with high prevalence of TB. It has become an emerging concern to epidemiologists and TB control programs due to complexities in its control and management. Managing MDR-TB, DM and HIV comorbidity is challenging, with risk of unfavorable outcome;consequently, close monitoring is necessary. Individuals with weak immunity resulting from diseases such as uncontrolled Diabetes Mellitus (DM) and HIV have a higher risk of developing TB or progression from latent to active TB. We present a 65-year old known diabetic patient who presented to Royal Cross Hospital Ugwueke Abia State, Nigeria with a one-year history of recurrent productive cough with associated night sweats, low grade fever and marked weight loss. A diagnosis of drug-resistant TB with DM/HIV co-morbidity was made and co-managed by experts from the respective clinics and the State TB control program. The patient was declared cured (7 months consecutive negative cultures each taken 30 days apart) after completing 20 months of conventional MDR-TB treatment. The patient showed remarkable clinical improvement including weight gain, good diabetic control and significant increase in CD4 (700 cells). Managing MDR-TB patients with diabetes and HIV is challenging, however, appropriate treatment, psychosocial support, adequate blood sugar control as well as monthly monitoring of patients with requisite investigations are vital in achieving good treatment outcome.

Identification, Synthesis, Isolation and Spectral Characterization of Multidrug-Resistant Tuberculosis (MDR-TB) Related Substances

Several related substances were detected at trace level in (2R)-2,3-dihydro-2-methyl-6-nitro-2-[[4-[4-[4-(trifluoromethoxy)phenoxy]-1-piperidinyl] phenoxy] methyl]imidazo[2, 1-b]oxazole drug substance by a newly developed high-performance liquid chromatography method. All related substances were characterized rapidly but some impurities were found to be intermediates. Proposed structures were further confirmed by characterization using NMR, FT-IR, and HRMS techniques. Based on the spectroscopic data;unknown related sub-stances were characterized as 1-(Methylsulfonyl)-4-[4-(trifluoromethoxy) phenoxy]piperidine;4-{4-[4-(Tri-fluoromethoxy)-phenoxy]piperidin-1-yl}phenol and 4-{4-[4-(trifluoromethoxy)phenoxy]piperidin-1-yl}phenyl methane sulfonate;4-Bromophenyl methane sulfonate, Ethyl 3,6-dihydro-1(2H)-pyridine carboxylate, (2S)-3-(4-Bromophenoxy)-2-hydroxy-2-methylpropyl methane sulfonate, (2S)-3-(4-Bromophenoxy)-2-methylpropane-1,2-diyldimethane-sulfonate, (2S)-2-Methyl-3-(4-{4-[4-(trifluoromethoxy) phenoxy]-piperidin-1-yl} phenoxy)-propane-1,2-diyldimethane sulfonate, (S)-3-(4-Bromophenoxy)-2-methyl-propane-1,2-diol and corresponding Enantiomer, (2R)-2-[(4-Bromo-phenoxy)methyl]-2-methyloxirane and (2R)-2-[(4-bromophenoxy)methyl]-2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b][1,3]oxazole. A possible mechanism for the formation of these related substances is also proposed.

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.

Natural Remedies against Multi-Drug Resistant <i>Mycobacterium tuberculosis</i>

Tuberculosis (TB), caused by Mycobacterium tuberculosis is an infectious deadly disease and the treatment of which is one of the most severe challenges at the global level. Currently more than 20 chemical medications are described for the treatment of TB. Regardless of availability of several drugs to treat TB, the causative agent, M. tuberculosis is nowadays getting resistant toward the conventional drugs and leading to conditions known as Multidrug-resistant tuberculosis (MDR-TB) and extensively drug resistant tuberculosis (XDR-TB). This situation has terrified the global health community and raised a demand for new anti-tuberculosis drugs. Medicinal plants have been used to cure different common as well as lethal diseases by ancient civilizations due to its virtue of variety of chemical compounds which may have some important remedial properties. The aim of the present review is to focus the anti-tubercular medicinal plants native to India as well as the plants effective against MDR or XDR-TB across the globe. In the present review, we have addressed 25 medicinal plants for TB and 16 plants effective against MDR-TB testified from India and 23 herbal plants described for MDR-TB across the world during 2011-2015. These herbal plants can serve as promising candidates for developing novel medications to combat multidrug resistant M. tuberculosis.

A Comparative Study of Drug Susceptibility Testing Techniques for Identification of Drug Resistant TB in a Tertiary Care Centre, South India

India tops the global list for Drug resistant Tuberculosis, but inadequate and expensive laboratory culture techniques have led to delay in the diagnosis and treatment. We studied the potential of an alternative method which could be cost-effective by combining the drugs in the same tube for identification of drug resistance. Drug Susceptibility Test (DST) results of 1000 sputum samples are got from suspected TB patients against INH (isoniazid) and Rifampicin by two techniques: a) a modified technique with both drugs in the same MGIT tube and b) a standard technique with the antibiotics in separate MGIT tubes for the diagnosis of MDR-TB (Multidrug Resistant). 39 samples were contaminated and were excluded from final analysis. 198 were smear positives by the concentrated Ziehl-Neelsen’s staining method. 219 were found to be culture positive out of which 195 were identified as M. tuberculosis complex. 40 (20.5%) strains were identified as MDR-TB by the conventional method and 39 were picked up by the modified DST. INH and Rifampicin mono-resistance accounted for 32 (16.4%) and 4 (2%) respectively. 99% concordance was observed between the two tests in categorizing MDR-TB. Similarly modified technique with combination of the second line Antibiotics-Ofloxacin, Kanamycin and Capreomycin was applied on the identified MDR strains in a stepwise manner. 6 (15%) were identified as Pre-XDR strains and 2 (5%) were found to be XDR-TB strains. This study implies that combining drugs in the same tube may be an equivalent and possibly a cost-effective alternative which needs to be explored further.

The Introduction of Bedaquiline Regimen for Drug-Resistant Tuberculosis in the Philippines: An Operational Study

Objectives: Bedaquiline (BDQ) is the first new anti-tuberculosis (TB) drug introduced to the market after 45 years. Recent studies have shown the potential benefits of adding bedaquiline to regimens for drug-resistant TB (DR-TB). In search of more effective regimens for DR-TB, bedaquiline was introduced in the TB program in the Philippines under operational research to assess its effectiveness, safety, and tolerability when given with background regimens among patients with multi-or extensively DR-TB (MDR/XDR-TB). Design: A prospective cohort study of patients with MDR/XDR-TB was given with a bedaquiline-containing regimen from June 2016 to May 2017. Demographic data, presence of comorbidities, and microbiologic profile on entry were recorded. Bedaquiline was administered at the recommended dose of 400 mg once daily for 14 days, then 200 mg three times a week for 22 weeks together with World Health Organization (WHO)-compliant background regimen. The time to culture conversion, interim outcomes at the 6th month of treatment, end-of-treatment outcomes, and post-treatment follow-up outcomes after one year was determined. The frequency and severity of adverse events (SAE) were recorded as part of pharmacovigilance. Results: Seventy-five patients were given with bedaquiline-containing regimen during the study period. Forty-two (56.0%) had second-line injectable resistance, 23 (30.7%) had fluoroquinolone-resistance, 6 (8.0%) had MDR-TB, and 4 (5.3%) had XDR-TB. In the 6th month of post-enrolment, 79% were culture-negative. The treatment success rate was 65.3% (37 were cured and 12 completed treatment), 7 (9.3%) died, 17 (22.7%) lost to follow-up, and 2 (2.7%) were withdrawn from treatment. Adverse events included vomiting (80%), dizziness (69%), nausea (52%), cough (44%), and headache (36%). The post-treatment follow-up of 49 patients in the 12th month showed 92% were culture-negative while 8% of TBC were not done. Conclusion: Bedaquiline-containing regimens for patients with MDR/XDR-TB were highly effective with an acceptable safety profile and favorable treatment outcomes, but the proportion of patients who lost to follow-up remains substantial.

Effect of Nano - Titanium Dioxide with Different Antibiotics against Methicillin-Resistant Staphylococcus Aureus

The different investigation has been carried out on the biological activities of titanium dioxide nanoparticle but the effect of this nano product on the antibacterial activity of different antibiotics has not been yet demonstrated. In this study the nano size TiO2 is synthesized using citric acid and alpha dextrose and the enhancement effect of TiO2 nanoparticle on the antibacterial activity of different antibiotics was evaluated against Methicillin-resistant Staphylococcus aureus (MRSA). During the present study, different concentrations of nano-scale TiO2 were tested to find out the best concentration that can have the most effective antibacterial property against the MRSA culture. Disk diffusion method was used to determine the antibacterial activity of these antibiotics in the absence and presence of sub inhibitory concentration of TiO2 nano particle. A clinical isolate of MRSA, isolated from Intensive Care Unit (ICU) was used as test strain. In the presence of sub-inhibitory concentration of TiO2 nanoparticle (20 μg/disc) the antibacterial activities of all antibiotics have been increased against test strain with minimum 2 mm to maximum 10mm. The highest increase in inhibitory zone for MRSA was observed against pencillin G and amikacin (each 10 mm). Conversely, in case of nalidixic acid, TiO2 nanoparticle showed a Synergic effect on the antibacterial activity of this antibiotic against test strain. These results signify that the TiO2 nanoparticle potentate the antimicrobial action of beta lactums, cephalosporins, aminoglycosides, glycopeptides, macrolids and lincosamides, tetracycline a possible utilization of nano compound in combination effect against MRSA.

Clinical Correlates and Drug Resistance in HIV-Infected and -Uninfected Pulmonary Tuberculosis Patients in South India

Objectives: To examine demographics, clinical correlates, sputum AFB (acid fast bacilli) smear grading DOTS (Directly Observed Therapy Short Course) uptake, and drug resistance in a cohort of newly-diagnosed, smear positive pulmonary tuberculosis (TB) patients with respect to HIV status at baseline, and compare smear conversion rates, side effects and mortality after two months. Design: A prospective study among 54 HIV positive and 41 HIV negative pulmonary TB patients. Data were collected via face-to-face interviews, review of medical records, and lab tests. Results: HIVTB co-infected patients, though more symptomatic at baseline, showed more improvement in their symptoms compared to HIV-uninfected TB patients at follow-up. The HIV co-infected group had more prevalent perceived side effects, and sputum smear positivity was marginally higher compared to the HIV negative group at follow-up. Mortality was higher among the HIV-infected group. Both groups had high rates of resistance to first-line anti-tubercular drugs, particularly isoniazid. There was no significant difference in the drug resistance patterns between the groups. Conclusions: Prompt initiation and provision of daily regimens of ATT (Anti-Tubercular treatment) along with ART (Anti-Retroviral treatment) via ART centers is urgently needed in India. As resistance to ART and/or ATT is directly linked to medication non-adherence, the use of counseling, regular reinforcement, early detection and appropriate intervention strategies to tackle this complex issue could help prevent premature mortality and development of resistance in HIV-TB co-infected patients. The high rate of isoniazid resistance might preclude its use in India as prophylaxis for latent TB in HIV infected persons as per the World Health Organization (WHO) guideline.

Association of KRAS Gene and microRNA-124-3p in Sporadic Colorectal Tumours

Aim: To reveal the exonic and 3’UTR sequences of KRAS, TP53, APC, BRAF, PIK3CA genes in sporadic colorectal tumors and to investigate the clinical relevance of 3’UTR variations in miRNA profiles. Methods: In the study, the exonic and 3’UTR sequences of five genes in 12 sporadic colorectal tumors were extracted by next generation sequencing. In tumors with variation in the 3’UTR region, the changes caused by the variation in the miRNA binding profile were detected. The expression profile of these miRNAs in colorectal and other solid tumors compared to normal tissue was determined. Pathway analysis was performed to determine which signaling pathways miRNAs affect. Results: Case-10 in our study was wild type KRAS and received cetuximab treatment and developed drug resistance. In this case, it was concluded that the expression of KRAS increased and tumorigenesis progressed due to miRNAs that do not bind to this region due to variations in the 3’UTR region. Among these miRNAs, hsa-miR-124-3p was found to have decreased expression in colorectal tumors and to be associated with the ECM-receptor interaction pathway. Conclusion: Variations in the 3’UTR regions of genes critical in the process of carsinogenesis are associated with drug resistance and the process of tumorigenesis.

标准化治疗方案治疗MDR-TB 26例近期疗效分析

目的评价全球基金结核病项目标准化耐多药肺结核治疗方案对耐多药肺结核(MDR-TB)的疗效。方法观察26例MDR-TB采用标准化耐多药肺结核治疗方案后1个月、6月、12月的痰菌计数、病灶吸收、体重指数变化。结果在治疗后6个月,痰菌计数、病灶吸收、体重指数均较前改善,统计有差异性(P<0.05)。结论全球基金结核病项目标准化耐多药肺结核治疗方案对MDR-TB的近期疗效好,值得进一步临床观察及病例积累。

MeltPro®TB技术在结核病耐药诊断中的大样本评估

目的评估MeltPro®TB技术在结核病耐药诊断的准确性及与传统药物敏感试验的一致性。方法在国家科技重大专项传染病防治综合示范区所属3个设区市的结核病定点医疗机构,采集患者痰涂片阳性标本进行MeltPro®TB耐药检测,同时开展传统药物敏感试验。以传统药敏试验结果为金标准,计算MeltPro®TB法检测6种抗结核药物及耐多药、准广泛耐药的敏感性、特异性、阳性预测值和阴性预测值,并对2种方法一致性进行Kappa分析。结果2019年1月—2021年4月,采用传统药敏方法有效检测痰涂片阳性患者1892例,纳入1847例结核分枝杆菌对象标本进行分析,耐药率由高到低为链霉素(13.37%)、异烟肼(11.04%)、氧氟沙星(6.95%)、利福平(5.96%)、乙胺丁醇(3.30%)、阿米卡星(1.25%),耐多药率为5.25%,准广泛耐药率为2.11%;同时进行MeltPro®TB检测,耐药率由高到低为链霉素(17.65%)、异烟肼(14.17%)、利福平(8.71%)、氧氟沙星(7.63%)、乙胺丁醇(4.75%)、阿米卡星(1.57%),耐多药率5.86%,准广泛耐药率2.51%。除阿米卡星外,MeltPro®TB法检测其余5种抗结核药物耐药率和耐多药、准广泛耐药率均高于传统药敏试验(P值均<0.05)。和传统药敏试验结果相比,MeltPro®TB检测6种抗结核药物耐药的敏感性为68.42%~92.00%,特异性为93.03%~97.64%,阳性预测值为48.15%~71.11%,阴性预测值为97.92%~99.64%,Kappa值为0.60~0.74;检测耐多药率和准广泛耐药率的敏感性、特异性、阳性预测值、阴性预测值分别为86.05%和83.87%、98.26%和98.99%、71.84%和60.47%、99.27%和99.70%,Kappa值分别为0.77和0.70。结论MeltPro®TB检测异烟肼、利福平、链霉素、氧氟沙星等4种抗结核药物和耐多药、准广泛耐药与传统药敏法一致性较好。

First Nationwide Survey of the Prevalence of TB/HIV Co-Infection in Ghana

Background: To better understand the extent of the magnitude of tuberculosis (TB) and Human Immunodeficiency Virus (HIV) co-infection in Ghana, a baseline study was conducted to establish the national prevalence of the dual infection. The study aimed to determine the most prevalent HIV serotype (HIV-1 or HIV-2) in TB patients (new and old cases);genotype mycobacterial species causing TB/HIV co-infection and determine their drug susceptibility patterns. Methods: Sputum and dried blood samples were collected from 503 TB patients from 67 health facilities nationwide between December 2007 and November 2008. All samples were processed for mycobacterial and HIV testing using conventional and molecular methods. Results: A total of 517 paired sputum samples were received from 517 patients. A total 503 patients [335 (66.6%) males;168 (33.4%) females] had at least one culture positive sample. Majority (93.0%) of the patients were new cases while 7.0% were old cases. All 503 TB isolates were Mycobacterium tuberculosis complex. Of 503 blood samples, 74 were positive for HIV (14.7%), comprising 71 (14.1%) and 3 (0.6%) for HIV-1 and HIV-1 & 2 respectively;none was positive for HIV-2 alone. The seroprevalence of HIV in newly diagnosed TB patients and those already on treatment, was 69/468 (14.7%) and 5/35 (14.3%) respectively (p > 0.05). Differentiation of isolates from TB/HIV co-infected patients showed that 70/74 (94.6%) were Mycobacterium tuberculosis while 4/74 (5.4%) were Mycobacterium africanum. Monoresistance to isoniazid and rifampicin were 4/74 (5.4%) and 1/74 (1.4%) respectively;resistance to both drugs (multi-drug resistant-MDR) was not observed. Sixty nine (93.2%) isolates were susceptible to both drugs. Conclusion: The prevalence of HIV infection in TB patients was 14.7%. TB/HIV was common among the sexually active age group (25 - 34 years). Majority of the TB isolates were M. tuberculosis which were susceptible to both isoniazid and rifampicin. HIV-1 was the common serotype infecting TB patients in Ghana.

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.

血清胱抑素C在MDR-TB患者化疗中的临床应用

目的探讨血清胱抑素C(CysC)在耐多药结核(MDR-TB)患者化学治疗中的临床应用。方法对MDR-TB患者按照化疗时间不同分7组检测血清CysC,来判断患者化疗过程中氨基糖甙类注射剂及高尿酸血症对患者肾功能损伤情况,同时将7个组的血清肌酐(Scr)、尿素(Urea)、尿酸(UA)的浓度作为观察指标来测定。结果七组的血清CysC、Scr、UA的差异有显著性意义(P<0.05),血清Urea的差异无显著性意义(P>0.05),但与治疗前组相比血清CysC的浓度的变化较Scr的浓度变化出现早;在MDR-TB患者化疗过程中血清SCr、Urea无一例异常,血清UA在治疗不同时期大多数患者间或或者持续升高,血清CysC有两例在治疗2个月后出现异常,经调减注射剂剂量后恢复正常。结论血清CysC是监测MDR-TB患者化疗过程中早期肾功能损伤更敏感的指标。

β-内酰胺酶抑制剂治疗耐多药肺结核初步研究

目的评价β-内酰胺酶抑制剂对耐多药肺结核的临床作用。方法将60例复治耐多药肺结核患者随机分为治疗组与对照组(各30例),据痰菌药敏及个体化等原则,均给予强化期2个月/巩固期4个月方案抗痨,治疗组在强化期加用安灭菌口服。观察痰菌、胸部X-ray及药物不良反应等。结果治疗组2个月末痰菌阴转率为21.43%(6/28),优于对照组为6.67%(2/30),P<0.05;而6个月末为42.86%(12/28),与对照组26.67%(8/30)无显著性差异,P>0.05。强化期增加该药未见不良反应叠加。结论β-内酰胺酶抑制剂与抗生素的等摩尔复合剂(安灭菌片)长期应用,安全、低毒,有益于痰菌阴转,但仍需进一步的大样本、足疗程的临床试验证实。

乙肝合并结核分枝杆菌感染患者的结核耐药基因分布情况

目的:探讨结核病(TB)/慢性乙型肝炎病毒(HBV)合并感染患者对一线抗结核药物耐药的频率和分子机制。方法:研究对来自TB/HBV共感染患者的100株结核分枝杆菌菌株进行了回顾性实验室分析,其中Beijing谱系株最为普遍(49%),其次是EAI谱系株(35%),少数菌株包括Haarlem(2.0%)、LAM(1.0%)、MANU(3.0%)、T(4.0%)和U(6.0%)。所有菌株均于2014年至2018年从患者的痰、胸腔积液标本中分离。对所有菌株进行药敏试验、Spoligotyping分型和24个位点穿插重复单元(MIRU-24分型),并对rpoB、katG、inhA和inhA启动子、rpsL、rrs和embB基因进行测序。结果:总共有42株(42.0%,42/100)菌株表现出耐药性;9株(9.0%,9/100)是多重耐药株(MDR)。对异烟肼的耐药率为25.0%(25/100),利福平的耐药率为10.0%(10/100),乙胺丁醇的耐药率为5.0%(5/100),和链霉素的耐药率为40.0%(40/100)。在利福平耐药菌株中,90%(9/10)具有利福平抗性的分离株在RRDR中具有突变(密码子507-533)。在异烟肼耐药菌株中,分别有100%和21%的katG和inhA(包括inhA启动子)发现基因突变;其多药耐药性主要与katG基因中的Ser315Thr突变相关(7/9,77.8%)。59.5%存在耐药性的菌株属于北京谱系,66.7%的MDR菌株属于北京谱系。结论:在TB/HBV合并感染患者的结核分枝杆菌分离株中接近一半(42%)为耐药株,其中以Beijing谱系为主。

以左氧氟沙星为基础的五联抗结核方案治疗异烟肼耐药肺结核的效果与安全性

目的探讨在吡嗪酰胺、乙胺丁醇、利福平和异烟肼四联用药的基础上增加使用左氧氟沙星治疗异烟肼单耐药肺结核的临床效果。方法选取2020年2月~2022年1月我院收治的176例异烟肼耐药肺结核患者进行分组研究,根据病历单双号分组的方法将患者分成试验组92例及对照组84例;对照组行基本治疗,试验组加用左氧氟沙星,比较的预后情况。结果试验组的病灶吸收率、痰菌转阴率和空洞闭合率均高于对照组(P<0.05)。试验组的治疗有效率95.65%,高于对照组的80.95%(P<0.05)。试验组患者治疗后C反应蛋白、单核细胞趋化蛋白-1和降钙素原水平均低于对照组(P<0.05)。两组不良反应率差异不显著(P>0.05)。结论在异烟肼耐单药肺结核患者的治疗中加入左氧氟沙星可取得更好的治疗效果,同时联合治疗方案安全性良好,值得借鉴。

PCR-LDR-核酸试纸条检测法在结核分枝杆菌katG基因315位密码子突变检测中的应用

目的将一项新的分子生物学方法PCR-LDR-核酸检测试纸条法应用于katG基因315位密码子单碱基突变的检测。方法设计与合成用于检测katG基因315位密码子单碱基突变的引物和探针,通过LDR反应,使用核酸检测试纸条检测结果,并与PCR-RFLP法及直接测序法相比较。结果成功区分各突变类型及野生型,与PCR-RFLP法及直接测序法的检测结果呈高度一致性,符合率分别为97.5%和100%。结论将为katG基因315位密码子单碱基突变的检测提供一种快速廉价的分子诊断方法。

肺结核患者白细胞介素-24水平变化及意义

目的:探讨肺结核患者白细胞介素(IL)-24水平变化及其意义。方法:以肺结核患者117例(初治组84例,复治组33例)和健康志愿者40例为研究对象,采用酶联免疫吸附法(ELISA)和逆转录-聚合酶链反应(RT-PCR)检测受试者血浆及外周血单个核细胞(PBMC)中IL-24的水平。结果:与健康对照组比较,结核患者血浆中IL-24水平下降[(4.5.±1.26)vs(9.62±1.33)ng/ml,P<0.01];与初治组比较,复治组IL-24水平下降[(3.35±1.39)vs(4.95±0.85)ng/ml,P<0.01]。PBMC中IL-24mRNA水平显示与上述相同的变化趋势,差异有统计学意义(P<0.01)。结论:IL-24水平与肺结核的发生、发展密切相关,低IL-24水平可能是肺结核初治患者失败或治愈后复发的重要原因。