Search results for: latent tuberculosis

Authors: Jamie R. Chua, Christina Irene D. Mejia, Regina P. Berba

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Disseminated tuberculosis is an infectious disease caused by Mycobacterium tuberculosis involving two or more non-contiguous sites identified through bacteriologic confirmation or clinical diagnosis. Over the five year period included in the study, the UP-PGH TB DOTS clinic had total of 3,967 referrals, and the prevalence of disseminated tuberculosis is 1% (68/3967). The mean age was 33.9 years (range 19-64 years) with a male: female ratio of 1:1. 67% (52 patients) had no predisposing comorbid illness or immune disorder. The most common presenting symptoms were abdominal pain (19%), back pain (13%), abdominal enlargement (11%) and mass (10.2%). Anemia, leukocytosis, hypoalbuminemia, and high-normal serum calcium were common biochemical and hematologic findings. Around 36% (25) of patients were diagnosed clinically with disseminated tuberculosis despite lacking bacteriologic evidence of multi-organ involvement. The lungs (86%) is still the most commonly involved site, followed by intestinal (22%), vertebral/Pott’s (27%), and pelvic/genital (19%). The mean time from presentation to initiation of therapy was 22 days (SD 32.7). Only 18 patients (29.3%) were properly recorded to have been referred to local TB DOTs facilities. Of the 68 patients, only 16% (11 patients) continued follow-up at PGH, and all had documented treatment completion. Treatment outcomes of the remaining were unknown. Due to the variety of involved sites, a high index of suspicion is required. Knowledge on clinical features, common radiographic findings, and histopathologic characteristics of disseminated TB is important as bacteriologic evidence of infection is not always apparent.

Keywords: disseminated tuberculosis, Mycobacterium tuberculosis, miliary tuberculosis, tuberculosis

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Authors: Richa Mardianingrum, Srie R. N. Endah

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In this research, we have designed four isoniazid derivatives i.e., isonicotinohydrazide (1-isonicotinoyl semicarbazide, 1-thiosemi isonicotinoyl carbazide, N '-(1,3-dimethyl-1 h-pyrazole-5-carbonyl) isonicotino hydrazide, and N '-(1,2,3- 4-thiadiazole-carbonyl) isonicotinohydrazide. The docking and molecular dynamic have performed to them in order to study its interaction with Mycobacterium tuberculosis Enoyl-Acyl Carrier Protein Reductase (InhA). Based on this research, all of the compounds were predicted to have a stable interaction with Mycobacterium tuberculosis Enoyl-Acyl Carrier Protein Reductase (INHA) receptor, so they could be used as an anti-tuberculosis drug candidate.

Keywords: anti-tuberculosis, docking, Inhibin alpha subunit, InhA, inhibition, synthesis, isonicotinohydrazide

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Authors: Levent Dumenci, Laura A. Siminoff

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Health literacy has been shown to predict a variety of health outcomes. Reliable identification of persons with limited cancer health literacy (LCHL) has been proved questionable with existing instruments using an arbitrary cut point along a continuum. The CHLT-6, however, uses a latent mixture modeling approach to identify persons with LCHL. The purpose of this study was to estimate two-week and six-month stability of identifying persons with LCHL using the CHLT-6 with a discrete latent variable approach as the underlying measurement structure. Using a test-retest design, the CHLT-6 was administered to cancer patients with two-week (N=98) and six-month (N=51) intervals. The two-week and six-month latent test-retest agreements were 89% and 88%, respectively. The chance-corrected latent agreements estimated from Dumenci’s latent kappa were 0.62 (95% CI: 0.41 – 0.82) and .47 (95% CI: 0.14 – 0.80) for the two-week and six-month intervals, respectively. High levels of latent test-retest agreement between limited and adequate categories of cancer health literacy construct, coupled with moderate to good levels of change-corrected latent agreements indicated that the CHLT-6 classification of limited versus adequate cancer health literacy is relatively stable over time. In conclusion, the measurement structure underlying the instrument allows for estimating classification errors circumventing limitations due to arbitrary approaches adopted by all other instruments. The CHLT-6 can be used to identify persons with LCHL in oncology clinics and intervention studies to accurately estimate treatment effectiveness.

Keywords: limited cancer health literacy, the CHLT-6, discrete latent variable modeling, latent agreement

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Authors: Catalina Sau Man Ng

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Workplace bullying is generally defined as a form of direct and indirect maltreatment at work including harassing, offending, socially isolating someone or negatively affecting someone’s work tasks. Workplace bullying is unfortunately commonplace around the world, which makes it a social phenomenon worth researching. However, the measurements and estimation methods of workplace bullying seem to be diverse in different studies, leading to dubious results. Hence, this paper attempts to examine the prevalence of workplace bullying in Hong Kong using the latent class analysis approach. It is often argued that the traditional classification of workplace bullying into the dichotomous 'victims' and 'non-victims' may not be able to fully represent the complex phenomenon of bullying. By treating workplace bullying as one latent variable and examining the potential categorical distribution within the latent variable, a more thorough understanding of workplace bullying in real-life situations may hence be provided. As a result, this study adopts a latent class analysis method, which was tested to demonstrate higher construct and higher predictive validity previously. In the present study, a representative sample of 2814 employees (Male: 54.7%, Female: 45.3%) in Hong Kong was recruited. The participants were asked to fill in a self-reported questionnaire which included measurements such as Chinese Workplace Bullying Scale (CWBS) and Chinese Version of Depression Anxiety Stress Scale (DASS). It is estimated that four latent classes will emerge: 'non-victims', 'seldom bullied', 'sometimes bullied', and 'victims'. The results of each latent class and implications of the study will also be discussed in this working paper.

Keywords: latent class analysis, prevalence, survey, workplace bullying

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Authors: Xiaochun Huang, Xuejun Zhao, Yun Zou, Feiyu Yang, Wenbin Liu, Nan Deng, Ming Zhang, Nengbin Cai

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A simple device termed infrared radiation (IR) was developed for rapid visualization of sweat fingerprints deposit on paper with blue light (450 nm, 11 W). In this approach, IR serves as the pretreatment device before the sweat fingerprints was illuminated by blue light. An annular blue light source was adopted for visualizing latent sweat fingerprints. Sample fingerprints were examined under various conditions after deposition, and experimental results indicate that the recovery rate of the latent sweat fingerprints is in the range of 50%-100% without chemical treatments. A mechanism for the observed visibility is proposed based on transportation and re-impregnation of fluorescer in paper at the region of water. And further exploratory experimental results gave the full support to the visible mechanism. Therefore, such a method as IR-pretreated in detecting latent fingerprints may be better for examination in the case where biological information of samples is needed for consequent testing.

Keywords: forensic science, visualization, infrared radiation, blue light, latent sweat fingerprints, detection

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Authors: Marina Nosik, Irina Rymanova, Konstantin Ryzhov, Joan Yarovaya, Alexander Sobkin

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Tuberculosis (TB) associated with HIV is one of the top causes of death worldwide. However, early detection and treatment of TB in HIV-infected individuals significantly reduces the risk of developing severe forms of TB and mortality. The goal of the study was to analyze the peculiarities of TB associated with HIV infection. Over the period of 2015-2016 a retrospective cohort study was conducted among 377 patients with TB/HIV co-infection who attended the Moscow Tuberculosis Clinic. The majority of the patients was male (64,5%). The median age was: men 37,9 (24÷62) and women 35,4 (22÷72) years. The most prevalent age group was 30-39 years both for men and women (73,3% and 54,7%, respectively). The ratio of patients in age group 50-59 and senior was 3,9%. Socioeconomic status of patients was rather low: only 2.3% of patients had a university degree; 76,1% was unemployed (of whom 21,7% were disabled). Most patients had disseminated pulmonary tuberculosis in the phase of infiltration/ decay (41,5%). The infiltrative TB was detected in 18,9% of patients; 20,1% patients had tuberculosis of intrathoracic lymph nodes. The occurrence of MDR-TB was 16,8% and XDR-TB – 17,9%. The number of HIV-positive patients with newly diagnosed TB was n=261(69,2%). The active TB-form (MbT+) among new TB/HIV cases was 44,7 %. The severe clinical forms of TB and a high TB incidence rate among HIV-infected individuals alongside with a large number of cases of newly diagnosed tuberculosis, indicate the need for more intense interaction with TB services for timely diagnosis of TB which will optimize treatment outcomes.

Keywords: HIV, tuberculosis (TB), TB associated with HIV, multidrug-resistant TB (MDR-TB)

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Authors: Bienvenu Gael Fouda Mbanga, Zikhona Tywabi-Ngeva, Kriveshini Pillay

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This work highlighted a new method for preparing Nitrogen carbon nanoparticles fused on zinc oxide nanoparticle nanocomposite (N-CNPs/ZnONPsNC) to remove copper ions (Cu²+) from wastewater by sol-gel method and applying the metal-loaded adsorbent in latent fingerprint application. The N-CNPs/ZnONPsNC showed to be an effective sorbent for optimum Cu²+ sorption at pH 8 and 0.05 g dose. The Langmuir isotherm was found to best fit the process, with a maximum adsorption capacity of 285.71 mg/g, which was higher than most values found in other research for Cu²+ removal. Adsorption was spontaneous and endothermic at 25oC. In addition, the Cu²+-N-CNPs/ZnONPsNC was found to be sensitive and selective for latent fingerprint (LFP) recognition on a range of porous surfaces. As a result, in forensic research, it is an effective distinguishing chemical for latent fingerprint detection.

Keywords: latent fingerprint, nanocomposite, adsorption, copper ions, metal loaded adsorption, adsorbent

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Authors: Ratchadaporn Ungcharoen, Lily Ingsrisawang

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Capture-recapture methods are popular techniques for indirect estimation the size of wildlife populations and the completeness of cases in epidemiology and social sciences. The aim of this study was to estimate the completeness of pulmonary tuberculosis cases confirmed by two sources of hospital registrations and surveillance systems in 2013 in Nakhon Pathom province, Thailand. Several estimators of population size were considered: the Lincoln-Petersen estimator, the Chapman estimator, the Chao’s lower bound estimator, the Zelterman’s estimator, etc. We focus on the Chapman and Chao’s lower bound estimators for estimating the completeness of pulmonary tuberculosis from two sources. The retrieved pulmonary tuberculosis data from two sources were analyzed and bootstrapped for 30 samples, with 241 observations from source 1 and 305 observations from source 2 per sample, for additional exploration of the completeness of pulmonary tuberculosis. The results from the original data show that the Chapman’s estimator gave the estimation of a total 360 (95% CI: 349-371) pulmonary tuberculosis cases, resulting in 57% estimated completeness cases. But the Chao’s lower bound estimator estimated the total of 365 (95% CI: 354-376) pulmonary tuberculosis cases and its estimated completeness cases was 55.9%. For the results from bootstrap samples, the Chapman and the Chao’s lower bound estimators gave an estimated 347 (95% CI: 309-385) and 353 (95% CI: 315-390) pulmonary tuberculosis cases, respectively. If for two sources recoding systems are available, record-linkage and capture-recapture analysis can be useful for estimating the completeness of different registration system. Both Chapman and Chao’s lower bound estimator approaches produce very close estimates.

Keywords: capture-recapture, Chao, Chapman, pulmonary tuberculosis

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Authors: T. Hojageldiyev, Y. Bolmammedov, S. Gurbanaliyev

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It is known that drugs used in the treatment of tuberculosis show toxic effect to organism especially to liver besides its therapeutic effect. Because of ineffectiveness of drugs used in the treatment regimen of tuberculosis against multidrug resistance (MDR) and extensively drug-resistance (XDR) tuberculosis requires the development of new treatment methods and new, novel drugs. Considering the usage of Artemisia absinthium in traditional medicine in treatment of wounds which suggests its antibacterial activity it seems that, also it may have significant antimycobacterial activity. The objective of present study was to evaluate antibacterial activity of ethanolic extract of A. absinthium against M. tuberculosis. In this study, the effect of ethanolic extract of A. absinthium was tested against tuberculosis and pharmaco-toxicological properties evaluated on laboratory animals. The 20%, 40%, 70% and 96% ethanolic extracts of A. absinthium prepared then its bacteriostatic and bactericidal activities were evaluated by validated methods. Data were analyzed by GraphPad Prism 7.0 at the level P < 0.05. Results showed that ethanolic extracts of A. absinthium show no toxicological properties with having high LD50. All concentrations of extract show high bacteriostatic activity on M. tuberculosis. 96% ethanolic extract has highest bactericidal effect among other concentrations. By conducting further studies, as a result of our study, antimycobacterial drug can be prepared from A. absinthium.

Keywords: Artemisia absinthium, antimycobacterial, ethanolic extract, Mycobacteria tuberculosis

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Authors: Berrin Şentürk

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In this study, due to the recurrence of bovine tuberculosis, in the same areas, the risk factors for the disease were determined and evaluated at the local level. This study was carried out in 32 farms where the disease was detected in the district and center of Samsun province in 2014. Predetermined risk factors, such as farm, environmental and economic risks, were investigated with the survey method. It was predetermined that risks in the three groups are similar to the risk variables of the disease on the global scale. These risk factors that increase the susceptibility of the infection must be understood by the herd owners. The risk-based contagious disease management system approach should be applied for bovine tuberculosis by farmers, animal health professionals and public and private sector decision makers.

Keywords: bovine tuberculosis, disease management, control, outbreak, risk analysis

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Authors: Shakhawan K. Mawlood, Catriona Pickard, Benjamin Pickard

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In summer 2015 the remains of 800 children are among 1,967 bodies were exhumed by archaeologists at St Peter's Burial Ground in Blackburn, Lancashire. One hundred samples from these 19th century ancient bones were selected for DNA analysis. These comprised samples biased for those which prior osteological evidence indicated a potential for microbial infection by Mycobacterium tuberculosis (causing tuberculosis, TB) or Treponema pallidum (causing Syphilis) species, as well a random selection of other bones for which visual inspection suggested good preservation (and, therefore, likely DNA retrieval).They were subject to polymerase chain reaction (PCR) assays aimed at detecting traces of DNA from infecting mycobacteria, with the purpose both of confirming the palaeopathological diagnosis of tuberculosis and determining in individual cases whether disease and death was due to M. tuberculosis or other reasons. Our secondary goal was to determine sex determination and age prediction. The results demonstrated that extraction of vast majority ancient bones DNA samples succeeded.

Keywords: ancient bone, DNA, tuberculosis, age prediction

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Authors: Manaphol Kulpraneet, Anirut Limtrakul, Surangrat Srisurapanon, Piyatida Tangteerawatana

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Tuberculosis (TB) remains a global health care disease world-wide. Control of the global TB epidemic has been impaired by the lack of an effective vaccine, by the emergence of drug resistant forms of Mycobacterium tuberculosis and by lack of sensitive and rapid diagnostics. Cytokines play a major role in defense against M. tuberculosis infection. Polymorphisms in the genes encoding various cytokines have been associated with tuberculosis susceptibility. Polymorphisms of the regulatory cytokine gene, the interleukin (IL)-10 is associated with the risk of tuberculosis (TB) in different populations. However, IL-10 gene polymorphism and susceptibility to TB in Thai is still unknown. The purpose of this study was to evaluate whether the common IL-10 promoter gene polymorphisms are associated with TB in Thai population. Forty eight patients with newly diagnosed pulmonary tuberculosis were studied. DNA samples were extracted from leukocytes and used to investigate -1087A/G, -819C/T, -252C/A (rs1800896, rs1800871, rs1800872) in IL-10 gene using restriction fragment length polymorphism (PCR-RFLP) methods. In this study, the genotype and allele frequencies of IL-10-1087A/G, -819C/T, -252C/A polymorphism did not significantly different between TB patients and healthy controls ((genotype: p=0.38, p=0.92, p=1; allele: p=0.57, p=0.77, p=0.89, respectively). The lack of association between common IL-10 promoter polymorphisms and TB susceptibility in this study may provide clue for better understanding of IL-10-1087A/G, -819C/T, -252C/A polymorphism and TB susceptibility in Thai population, which might facilitate the rationale design of vaccines. However, further studies in large scales population are required for confirmation.

Keywords: IL-10, cytokines, single nucleotide polymorphism (SNP), tuberculosis

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Authors: Raja Arunprasath, P. Gajalakshmi

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Antimycobacterial activity of C. roseus rosea and piperine was evaluated against ofloxacin resistant M. tuberculosis. Among the 68 suspected sputum samples, 32 were AFB positive belongs to age group of 40-50years. Susceptibility of M. tuberculosis was evaluated against ofloxacin and streptomycin by colorimetric assay. Of these 32 positive samples, 20 isolates were resistant to ofloxacin, 12 were resistant to Streptomycin and none of them were found to be multidrug resistant. The sensitivity pattern of ofloxacin resistant M. tuberculosis against two tested plant extracts showed potent tubercular activity. Antimycobacterial activity of C. roseus was 22 + 2.21mm and piperine was found to be 20 + 1.08 mm. The percentage of relative inhibitory zone of C. roseus was 133 % and piperine was found to be 111 %. The MIC of C. roseus and piperine was found at 50 µg/ml. Based on the FICI value 0.37 confirms that both the tested phytochemicals were synergistically active against M. tuberculosis. The MIC of ofloxacin was reduced from 8 mg to 2 mg/l in the presence of piperine but not by C. roseus. This is the first report on Synergistic bioactivity of C. roseus rosea and piperine fractionation leads development of novel antimycobacterial prophylaxis in future.

Keywords: C. roseus, ofloxacin, piperine, synergistic

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Authors: Nouira Mariem, Ben Rayana Hazem, Ennigrou Samir

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Background and aim: During the past decade, the frequency of extrapulmonary forms of tuberculosis has increased. These forms are under-diagnosed using conventional tests. The aim of this study was to evaluate the performance of the Tuberculin Skin Test (TST) for the diagnosis of tuberculosis, using the ROC curve and Fagan’s Nomogram methodology. Methods: This was a case-control, multicenter study in 11 anti-tuberculosis centers in Tunisia, during the period from June to November2014. The cases were adults aged between 18 and 55 years with confirmed tuberculosis. Controls were free from tuberculosis. A data collection sheet was filled out and a TST was performed for each participant. Diagnostic accuracy measures of TST were estimated using ROC curve and Area Under Curve to estimate sensitivity and specificity of a determined cut-off point. Fagan’s nomogram was used to estimate its predictive values. Results: Overall, 1053 patients were enrolled, composed of 339 cases (sex-ratio (M/F)=0.87) and 714 controls (sex-ratio (M/F)=0.99). The mean age was 38.3±11.8 years for cases and 33.6±11 years for controls. The mean diameter of the TST induration was significantly higher among cases than controls (13.7mm vs.6.2mm;p=10-6). Area Under Curve was 0.789 [95% CI: 0.758-0.819; p=0.01], corresponding to a moderate discriminating power for this test. The most discriminative cut-off value of the TST, which were associated with the best sensitivity (73.7%) and specificity (76.6%) couple was about 11 mm with a Youden index of 0.503. Positive and Negative predictive values were 3.11% and 99.52%, respectively. Conclusion: In view of these results, we can conclude that the TST can be used for tuberculosis diagnosis with a good sensitivity and specificity. However, the skin induration measurement and its interpretation is operator dependent and remains difficult and subjective. The combination of the TST with another test such as the Quantiferon test would be a good alternative.

Keywords: tuberculosis, tuberculin skin test, ROC curve, cut-off

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Authors: Naima Nur, Safa Islam, Saeema Islam, Faridul Alam

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Background: Drug-resistant pulmonary tuberculosis (DR-PTB), particularly multidrug-resistant tuberculosis (MDR-TB) and pre-extensive drug-resistant (pre-XDR), is a major challenge in effectively controlling TB, especially in developing. This study aimed to identify the strains of M. tuberculosis complex (MTC) and drug resistance patterns among the pulmonary tuberculosis patients. Methods: The study used a cross-sectional design, and 815 patients were recruited randomly in three study periods. In the first-period, 210 treated PTB patients, who were completed their treatment, received their diagnoses using light microscopy, fluorescence microscopy and cultured on Lowenstein-Jensen (L-J) slant, and then strains were identified as MTC by biochemical tests, and then sensitivity test in National Institute of Diseases of the Chest and Hospital. In the second-period, 220 re-treated PTB patients, who were completed their treatment, received their diagnoses using culture on L-J slant, line probe assay (LPA), and GeneXpert in the same hospital. In the last-period, during treatment, 385 MDR-PTB patients received their diagnoses using culture on L-J slant and LPA in the same hospital. Results: Among sixty-two (29.5%) PTB patients, 13% were sensitive to all first-line anti-TB drugs, 26% were MDR-TB patients, and 14.2% were pre-XDR-TB among 14 MDR-TB patients. After three years, 31% were MDR-TB among 220 re-treated PTB patients. After five years, 16.4% was pre-XDR-TB among 385 MDR-TB patients. Compared to females, male patients were significantly higher at all times. Conclusion: The current study demonstrated that in three study periods, the proportions of DR-TB, MDR-TB, and pre-XDR patients were an alarming issue and increasing daily.

Keywords: multi-drug resistant, drug-resistant, pre-extensive drug resistant, pulmonary tuberculosis

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Authors: Dwitya Elvira, Raveinal Masri, Rohayat Bilmahdi

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Human Immunodeficiency Virus (HIV) pandemic increased significantly worldwide. The rise in cases of HIV/AIDS was also followed by an increase in the incidence of opportunistic infection, with tuberculosis being the most opportunistic infection found in HIV/AIDS and the main cause of mortality in HIV/AIDS patients. Diagnosis of tuberculosis in HIV/AIDS patients is often difficult because of the uncommon symptom in HIV/AIDS patients compared to those without the disease. Thus, diagnostic tools are required that are more effective and efficient to diagnose tuberculosis in HIV/AIDS. CXCL-10/IP-10 is a chemokine that binds to the CXCR3 receptor found in HIV/AIDS patients with a weakened immune system. Tuberculosis infection in HIV/AIDS activates chemokine IP-10 in urine, which is used as a marker for diagnosis of infection. The aim of this study was to prove whether IP-10 urine can be a biomarker diagnosis of active lung tuberculosis in HIV-AIDS patients. Design of this study is a cross sectional study involving HIV/AIDS patients with lung tuberculosis as the subject of this study. Forty-seven HIV/AIDS patients with tuberculosis based on clinical and biochemical laboratory were asked to collect urine samples and IP-10/CXCL-10 urine being measured using ELISA method with 18 healthy human urine samples as control. Forty-seven patients diagnosed as HIV/AIDS were included as a subject of this study. HIV/AIDS were more common in male than in women with the percentage in male 85.1% vs. 14.5% of women. In this study, most diagnosed patients were aged 31-40 years old, followed by those 21-30 years, and > 40 years old, with one case diagnosed at age less than 20 years of age. From the result of the urine IP-10 using ELISA method, there was significant increase of the mean value of IP-10 urine in patients with TB-HIV/AIDS co-infection compared to the healthy control with mean 61.05 pg/mL ± 78.01 pg/mL vs. mean 17.2 pg/mL. Based on this research, there was significant increase of urine IP-10/CXCL-10 in active lung tuberculosis with HIV/AIDS compared to the healthy control. From this finding, it is necessary to conduct further research into whether urine IP-10/CXCL-10 plays a significant role in TB-HIV/AIDS co-infection, which can also be used as a biomarker in the early diagnosis of TB-HIV.

Keywords: chemokine, HIV/AIDS, IP-10 urine, tuberculosis

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Authors: Anita, Sari Septiani Tangke, Rusdina Bte Ladju, Nasrum Massi

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New diagnostic tools are urgently needed to interrupt the transmission of tuberculosis and multidrug-resistant tuberculosis. The microscopic-observation drug-susceptibility (MODS) assay is a rapid, accurate and simple liquid culture method to detect multidrug-resistant tuberculosis (MDR-TB). MODS were evaluated to determine a lower and same concentration of isoniazid and rifampin for detection of MDR-TB. Direct drug-susceptibility testing was performed with the use of the MODS assay. Drug-sensitive control strains were tested daily. The drug concentrations that used for both isoniazid and rifampin were at the same concentration: 0.16, 0.08 and 0.04μg per milliliter. We tested 56 M. tuberculosis clinical isolates and the control strains M. tuberculosis H37RV. All concentration showed same result. Of 53 M. tuberculosis clinical isolates, 14 were MDR-TB, 38 were susceptible with isoniazid and rifampin, 1 was resistant with isoniazid only. Drug-susceptibility testing was performed with the use of the proportion method using Mycobacteria Growth Indicator Tube (MGIT) system as reference. The result of MODS assay using lower concentration was significance (P<0.001) compare with the reference methods. A lower and same concentration of isoniazid and rifampin can be used to detect MDR-TB. Operational cost and application can be more efficient and easier in resource-limited environments. However, additional studies evaluating the MODS using lower and same concentration of isoniazid and rifampin must be conducted with a larger number of clinical isolates.

Keywords: isoniazid, MODS assay, MDR-TB, rifampin

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Authors: Naima Nur, Safa Islam, Saeema Islam, Md. Faridul Alam

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Background: The worldwide increase in pediatric presumptive tuberculosis (TB) is the most life-threatening challenge in effectively controlling TB. The objective of this study was to determine the proportion of presumptive TB and the factors associated with it. Methods: A cross-sectional study was conducted between March and November 2013 at ICDDR-Bangladesh. Two hundred twelve pulmonary and extra-pulmonary specimens were collected from 84 suspected pediatric patients diagnosed with TB based on their clinical symptoms/radiological findings. Presumptive TB and confirmed TB were considered presumptive TB and non-presumptive TB and were isolated by smear-microscopy, culture, and GeneXpert. Logistic regression was used to analyze associations between outcome and predictor variables. Results: The proportion of presumptive TB was 85.7%, and 14.3% of non-presumptive TB. In presumptive TB, vaccine scars, family TB history, and school-going children were 16.6%, 33.3%, and 56.9%, respectively. In contrast, vaccine scars and family TB history were 8.3%, and school-going children were 58.3% in non-presumptive TB. Significant factors did not appear in the logistic regression analysis. Conclusion: Despite the high proportion of presumptive TB, there was no statistically significant between presumptive TB and non-presumptive TB.

Keywords: presumptive tuberculosis, confirmed tuberculosis, patient's characteristics, diagnosis

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Authors: Christy Rosaline, Rathankar Roa, Waheeta Hopper

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Persistence of tuberculosis, emergence of multidrug-resistance and extensively drug-resistant forms of the disease, has increased the interest in developing new antitubercular drugs. Developing inhibitors for 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase from Mycobacterium tuberculosis (MtbDAH7Ps), an enzyme involved in shikimate pathway, gives a selective target for antitubercular agents. MtbDAH7Ps was screened against ZINC database, and shortlisted compounds were subjected to induce fit docking. Prime/Molecular Mechanics Generalized Born Surface Area calculation was used to validate the binding energy of ligand-protein complex. Molecular Dynamics analysis for of the lead compounds–MtbDAH7Ps complexes showed that the backbone of MtbDAH7Ps in their complexes were stable. These results suggest that the shortlisted lead compounds ZINC04097114, ZINC15163225, ZINC16857013, ZINC06275603, and ZINC05331260 could be developed into novel drug leads to inhibit DAH7Ps in Mycobacterium tuberculosis.

Keywords: MtbDAH7Ps, Mycobacterium tuberculosis, HTVS, molecular dynamics

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Authors: Udaykumar R., M. S. Ganachari

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In order to engage community pharmacies in Tuberculosis care, a survey has been conducted in Belgaum city, Karnataka state, India. After the survey divided into two groups one is control group and another one is intervention group. One is dispensing of anti-tuberculosis drugs, and another one is non-availability of anti-tuberculosis drugs. Those community pharmacists who are voluntarily interesting for becoming DOTS (Directly observed treatment short course) provider and RNTCP (Revised national tuberculosis control programme) objectives. Structured training is conducted for community pharmacist who are dispensing anti-tuberculosis drugs. The training module includes record maintaining, reporting to the RNTCP, Medication adherence etc. In case of non-availability of anti-tuberculosis drugs, the district RNTCP has been given training for community pharmacist by providing free of drugs to the community pharmacies. So, community pharmacies can dispense anti-tuberculosis drugs to the patients. The target of this study is Private community pharmacies. A simple random sampling method is used and 550 private community pharmacy shops has been involved in Belgaum city of Karnataka state, India. Significance of the Study: This study mainly focused on training of DOTS (Directly observed treatment short course) to the private community pharmacist. Indian Govt. Considers Private Providers as Assets for TB Control and Care to Achieve National Strategic Plan for TB Elimination 2017-2025. The Govt. has not fully tapped the Potential of Private Pharmacies to Fight TB. Providing DOTS as per patient’s convenience through community DOT Providers with periodic monitoring may reduce the treatment Default. We explore RNTCP objectives interventions that can have directly managed by private community pharmacy shop. Objectives: Survey of anti-tuberculosis drugs in Community pharmacy shop in Belgaum city. Interested community pharmacist who are willing to become DOTS (Directly observed treatment short course) Provider. Major Findings:Most of the community pharmacist are dispensing anti-tuberculosis drugs without having knowledge of DOTS therapy and RNTCP objectives. No community pharmacist is aware of RNTCP and Tuberculosis burden in India. Most of the Pharmacist agreed to come for RNTCP Training module for the community pharmacist. Some of the community pharmacist not dispensing anti-tuberculosis drugs and they agreed to become official DOTS provider. Concluding Statement: Awareness of role of community pharmacist on tuberculosis control and care has been neglected. More than 50% of tuberculosis patients seeking treatments from privatesector. In this study finds the major gap between government and private sector on tuberculosis treatment.

Keywords: community pharmacist, directly observed treatment short course(DOTS), revised national tuberculosis control programme (RNTCP), private pharmacies, anti-tuberculosis drugs

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Authors: Upvan Chobera

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India bears the highest burden of tuberculosis globally, facing a significant incidence rate. To combat this public health challenge, the Ministry of Health and Family Welfare in India has launched an ambitious national strategic plan with the aim of achieving END TB targets by 2025. Addressing tuberculosis requires a comprehensive, multi-sectoral approach that encompasses factors such as nutritional support, living and working conditions, and improved access to diagnostics and treatment services. This study delves into the burden of tuberculosis in India, examining the government's strategic plan to combat the disease. Additionally, it explores the role of Ni-Kshay Mitra (community support) in this fight, encompassing various entities such as cooperative societies, corporations, elected representatives, individuals, institutions, non-government organizations, and political parties or individual donors. These efforts aim to enhance the response against tuberculosis, complementing the government's initiatives and catering to district-specific requirements, all coordinated with the district administration. It is important to note that the support provided under the Ni-Kshay Mitra initiative is supplementary to the free services offered by the National TB Elimination Program (NTEP) available to all patients.

Keywords: end TB targets, Ni-kshay Mitra, NTEP, tuberculosis burden in India

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Authors: J. J. Mathew

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Pulmonary tuberculosis is highly prevalent in the Indian subcontinent. Most cases of pulmonary tuberculosis are diagnosed with sputum examinations and the vast majority of these are undertaken by the government run establishments. However, mycobacterial cultures are not routinely done, unless drug resistance is detected based on clinical response. Modern diagnostic tests like bronchoscopy and Genexpert are not routinely employed in the government institutions for the diagnosis of pulmonary tuberculosis, but have been accepted widely by good private institutions. The utility of these investigations in the private sector is not yet well recognized. This retrospective study aims to assess the usefulness of bronchoscopy and Genexpert in the diagnosis of pulmonary tuberculosis in quaternary care private hospital in India. 30 patients with respiratory symptoms raising the possibility of tuberculosis based on clinical and radiological features, but without any significant sputum production, were subject to bronchoscopy and BAL samples taken for microbiological studies, including Genexpert. 6 out of the 30 patients were found to be Genexpert positive and none of them showed Rifampicin resistance. All the 6 cases had upper zone predominant disease. One of the 6 cases of tuberculosis had another co-existent bacterial infection according to the routine culture studies. 6 other cases were proven to be due to other bacterial infections alone, 2 had a malignant diagnosis and the remaining cases were thought to be non-infective pathologies. The Genexpert results were made available within 48 hours in the 6 positive cases. All of them were commenced on standard anti-tuberculous regimen with excellent clinical response. The other infective cases were also managed successfully based on the drug susceptibilities. The study has shown the usefulness of these investigations as early intervention enabled diagnosis facilitating treatment and prevention of any clinical deterioration. The study lends support to early bronchoscopy and Genexpert testing in suspected cases of pulmonary tuberculosis without significant sputum production, in a high prevalence country which normally relies on sputum examination for the diagnosis of pulmonary tuberculosis.

Keywords: pulmonary, tuberculosis, bronchoscopy, genexpert

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Authors: Shubhita Mathur, Ritika Kar Bahal, Priyanka Chauhan, Anil K. Tyagi

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Mycobacterium tuberculosis, the causative agent of human tuberculosis, is a major cause of mortality. Bacillus Calmette-Guérin (BCG), the only licensed vaccine available for protection against tuberculosis confers highly variable protection ranging from 0%-80%. Thus, novel vaccine strains need to be evaluated for their potential as a vaccine against tuberculosis. We had previously constructed a triple gene mutant of M. tuberculosis (MtbΔmms), having deletions in genes encoding for phosphatases mptpA, mptpB, and sapM that are involved in host-pathogen interaction. Though vaccination with Mtb∆mms strain induced protection in the lungs of guinea pigs, the mutant strain was not able to control the hematogenous spread of the challenge strain to the spleens. Additionally, inoculation with Mtb∆mms resulted in some pathological damage to the spleens in the early phase of infection. In order to overcome the pathology caused by MtbΔmms in the spleens of guinea pigs and also to control the dissemination of the challenge strain, MtbΔmms was genetically modified by disrupting bioA gene to generate MtbΔmmsb strain. Further, in vivo attenuation of MtbΔmmsb was evaluated, and its protective efficacy was assessed against virulent M. tuberculosis challenge in guinea pigs. Our study demonstrates that Mtb∆mmsb mutant was highly attenuated for growth and virulence in guinea pigs. Vaccination with Mtb∆mmsb mutant generated significant protection in comparison to sham-immunized animals at 4 and 12 weeks post-infection in lungs and spleens of the infected animals. Our findings provide evidence that deletion of genes involved in signal transduction and biotin biosynthesis severely attenuates the pathogen and the single immunization with the auxotroph was able to provide significant protection as compared to sham-immunized animals. The protection imparted by Mtb∆mmsb fell short in comparison to the protection observed in BCG-immunized animals. This study nevertheless indicates the importance of attenuated multiple gene deletion mutants of M. tuberculosis in generating protection against tuberculosis.

Keywords: Mycobacterium tuberculosis, BCG, MtbΔmmsb, bioA, guinea pigs

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Authors: Aswathi Thrivikraman, S. Advaith

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The study is aimed at designing encoders for deciphering intricacies in time series data by redescribing the dynamics operating on a lower-dimensional manifold. A semi-supervised LSTM autoencoder is devised and investigated to see if the latent representation of the time series data can better forecast the data. End-to-end training of the LSTM autoencoder, together with another LSTM network that is connected to the latent space, forces the hidden states of the encoder to represent the most meaningful latent variables relevant for forecasting. Furthermore, the study compares the predictions with those of a traditional seq2seq model.

Keywords: LSTM, autoencoder, forecasting, seq2seq model

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Authors: Jiyoung Bae, Gyoomi Kim

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This study explores a range of linguistic features used in Korean college students’ argumentative writings for the purpose of developing a model that identifies variables which predict writing proficiencies. This study investigated the latent variable structure of L2 linguistic features, including syntactic complexity, the lexical complexity, and fluency. One hundred forty-six university students in Korea participated in this study. The results of the study’s confirmatory factor analysis (CFA) showed that indicators of linguistic features from this study-provided a foundation for re-categorizing indicators found in extant research on L2 Korean writers depending on each latent variable of linguistic features. The CFA models indicated one measurement model of L2 syntactic complexity and L2 learners’ writing proficiency; these two latent factors were correlated with each other. Based on the overall findings of the study, integrated linguistic features of L2 writings suggested some pedagogical implications in L2 writing instructions.

Keywords: linguistic features, syntactic complexity, lexical complexity, fluency

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Authors: E. Tchandao Mangamana, V. Cariou, E. Vigneau, R. Glele Kakai, E. M. Qannari

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A new definition of a latent variable associated with a dataset makes it possible to propose variants of the PLS2 regression and the multi-block PLS (MB-PLS). We shall refer to these variants as Rd-PLS regression and Rd-MB-PLS respectively because they are inspired by both Redundancy analysis and PLS regression. Usually, a latent variable t associated with a dataset Z is defined as a linear combination of the variables of Z with the constraint that the length of the loading weights vector equals 1. Formally, t=Zw with ‖w‖=1. Denoting by Z' the transpose of Z, we define herein, a latent variable by t=ZZ’q with the constraint that the auxiliary variable q has a norm equal to 1. This new definition of a latent variable entails that, as previously, t is a linear combination of the variables in Z and, in addition, the loading vector w=Z’q is constrained to be a linear combination of the rows of Z. More importantly, t could be interpreted as a kind of projection of the auxiliary variable q onto the space generated by the variables in Z, since it is collinear to the first PLS1 component of q onto Z. Consider the situation in which we aim to predict a dataset Y from another dataset X. These two datasets relate to the same individuals and are assumed to be centered. Let us consider a latent variable u=YY’q to which we associate the variable t= XX’YY’q. Rd-PLS consists in seeking q (and therefore u and t) so that the covariance between t and u is maximum. The solution to this problem is straightforward and consists in setting q to the eigenvector of YY’XX’YY’ associated with the largest eigenvalue. For the determination of higher order components, we deflate X and Y with respect to the latent variable t. Extending Rd-PLS to the context of multi-block data is relatively easy. Starting from a latent variable u=YY’q, we consider its ‘projection’ on the space generated by the variables of each block Xk (k=1, ..., K) namely, tk= XkXk'YY’q. Thereafter, Rd-MB-PLS seeks q in order to maximize the average of the covariances of u with tk (k=1, ..., K). The solution to this problem is given by q, eigenvector of YY’XX’YY’, where X is the dataset obtained by horizontally merging datasets Xk (k=1, ..., K). For the determination of latent variables of order higher than 1, we use a deflation of Y and Xk with respect to the variable t= XX’YY’q. In the same vein, extending Rd-MB-PLS to the path modeling setting is straightforward. Methods are illustrated on the basis of case studies and performance of Rd-PLS and Rd-MB-PLS in terms of prediction is compared to that of PLS2 and MB-PLS.

Keywords: multiblock data analysis, partial least squares regression, path modeling, redundancy analysis

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Authors: Yulistiani Yulistiani, Zamrotul Izzah, Lintang Bismantara, Wenny Putri Nilamsari, Arif Bachtiar, Budi Suprapti

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Interferon-gamma (IFN-γ) and interleukin-6 (IL-6) are pro-inflammatory cytokines, which have the protective immune response against Tuberculosis (TB). Indeed, pro-inflammatory cytokines Mycobacterium tuberculosis antigen-specific CD4+ and CD8+ T cells and NK cells increase the level of production of IFN-γ, a cytokine critical for augmenting the microbicidal activity of phagocytes. On the other hand, M. tuberculosis reduces the effects of IFN-γ by inhibiting the transcription of IFN-γ- responsive genes and by inducing the secretion of IL-6, which inhibits IFN-γ signaling. Probiotics Lactobacillus sp. and Bifidobacterium sp. were known to increase IFN-γ production in vivo, while vitamin B1, B6, and B12 worked on macrophages and releasing cytokines. Therefore, the present study was to evaluate the effect of probiotics and vitamin B supplement on changes of plasma cytokine levels in active pulmonary TB. From October to November 2016, twelve M. tuberculosis-infected patients starting anti-TB drugs were recruited, then divided into two groups. Seven patients were given a combination of probiotics and vitamin B, while five patients were in the control group. Plasma IFN-γ and IL-6 levels were measured by the ELISA kit before and a month after treatment. IFN-γ levels raised in four patients receiving the supplement (P = 0.743), while IL-6 increased in three patients in this group until day 30 of treatment (P = 0.298). Taken together, these results show the promising effect of probiotics and vitamin B on stimulation of IFN-γ and IL-6 production during intensive therapy of TB.

Keywords: interferon-gamma, interleukin-6, probiotic, tuberculosis

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Authors: Elena G. Salina, Laurent R. Chiarelli, Maria R. Pasca, Vadim A. Makarov

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Tuberculosis is one of the most challenging threats to human health, confronted by the problem of drug resistance. Evidently, new drugs for tuberculosis are urgently needed. Thienopyrimidine TP053 is one of the most promising new antitubercular prodrugs. Mycothiol-dependent reductase Mrx2, encoded by rv2466c, is known to be a TP053 activator; however, the precise mode of action of this compound remained unclear. Being highly active against both replicating and non-replicating tuberculosis bacilli, TP053 also revealed dose-escalating activity for M. tuberculosis-infected murine macrophages. The chemical structure of TP053 is characterized by the presence of NO₂ group which was suggested to be responsible for the toxic effects of the activated compound. Reduction of a nitroaromatic moiety of TP53 by Mrx2 was hypothesized to result in NO release. Analysis of the products of enzymatic activation of TP053 by Mrx2 by the Greiss reagent clearly demonstrated production of nitric oxide in a time-dependent manner. Mass-spectra of cell lysates of TP-treated M. tuberculosis bacilli demonstrated the transformation of TP053 to its non-active metabolite with Mw=261 that corresponds NO release. The mechanism of NO toxicity for bacteria includes DNA damage and degradation of iron-sulfur centers, especially under oxygen depletion. Thus, TP-053 drug-like scaffold is prospective for further development of novel anti-TB drug. This work was financially supported by the Russian Foundation for Basic Research (Grant 17-04-00342).

Keywords: drug discovery, M. tuberculosis, nitric oxide, NO donors

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Authors: Xinyuan Y. Song, Kai Kang

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Joint models for analyzing longitudinal and survival data are widely used to investigate the relationship between a failure time process and time-variant predictors. A common assumption in conventional joint models in the survival analysis literature is that all predictors are observable. However, this assumption may not always be supported because unobservable traits, namely, latent variables, which are indirectly observable and should be measured through multiple observed variables, are commonly encountered in the medical, behavioral, and financial research settings. In this study, a joint modeling approach to deal with this feature is proposed. The proposed model comprises three parts. The first part is a dynamic factor analysis model for characterizing latent variables through multiple observed indicators over time. The second part is a random coefficient trajectory model for describing the individual trajectories of latent variables. The third part is a proportional hazard model for examining the effects of time-invariant predictors and the longitudinal trajectories of time-variant latent risk factors on hazards of interest. A Bayesian approach coupled with a Markov chain Monte Carlo algorithm to perform statistical inference. An application of the proposed joint model to a study on the Alzheimer's disease neuroimaging Initiative is presented.

Keywords: Bayesian analysis, joint model, longitudinal data, time-to-event data

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Authors: Anna-Mari Kok, Carel B. Oosthuizen, Namrita Lall

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Tuberculosis (TB) is a disease caused by the bacterial pathogen Mycobacterium tuberculosis. It is associated with high mortality rates in both developing and developed countries. Many higher plants are found that are medicinally associated with tuberculosis infection. Plants belonging to thirteen families were selected, based on their traditional usage for tuberculosis and its associated symptoms. Eight plants showed the best antimycobacterial activities (MIC-value ≤ 500.0 µg/ml) against M. tuberculosis H37Rv. LS was found to have a minimum inhibitory concentration (MIC) of 125 µg/ml whereas, Tulbaghia violacea, Heteromorpha arborescens, Sutherlandia frutescens, Eucalyptus deglupta, and Plectranthus neochilus were found to have a MIC value of 250 µg/ml against M. tuberculosis H37Rv. Cytotoxicity values on U937 and HepG2 cells were obtained and the IC50 values ranged between 40 ±4.30 and > 400 µg/ml for the U937 cell line and 72.4 ±1.50 and > 400 µg/ml for the HepG2 cell line. Heteromorpha arborescens had the lowest IC50 value in both cell lines and therefore showed moderate levels of toxicity. Of the 19 samples that underwent the 2, 2- diphenyl- 1- picrylhydrazyl (DPPH) antioxidant assay, Eucalyptus deglupta and Melianthus major showed significant free radical scavenging activities with concentrations of 1.33 and 1.32 µg/ml respectively for the inhibition of DPPH. Hepatotoxicity induced by acetaminophen identified Searsia lancea with hepatoprotective activity of 59.37% at a ¼ IC50 concentration. Out of the 7 samples that were investigated for their immunomodulatory capabilities, Eucalyptus deglupta produced the most IL-12 with Sutherlandia frutescens also showing positive results for IL-12 production. In the present study, Eucalyptus deglupta showed the most promising results with good activity against M. tuberculosis with an MIC-value of 250 µg/ml. It also has potent antioxidant activity with an IC50 value of 1.33 µg/ml. This sample also stimulated high production of the cytokine, IL-12. Searsia lancea showed moderate antimycobacterial acticvity with an MIC-value of 500 µg/ml. The antioxidant potential also showed promising results with an IC50 value of 4.50 µg/ml. The hepatoprotective capability of Searsia lancea was 59.34% at a ¼ IC50 concentration. Another sample Sutherlandia frutescens showed effective antimycobacterial activity with an MIC-value of 250 µg/ml. It also stimulated production of IL-12 with 13.43 pg/ml produced. These three samples can be considered for further studies for the consideration as adjuvants for current tuberculosis treatment.

Keywords: adjuvant, hepatoprotection, immunomodulation, tuberculosis

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