Emergence Of Multidrug-resistant Tuberculosis Research Articles

Predictors of treatment outcome among adult patients with multi-drug resistant tuberculosis in Kano, Nigeria

Background: Emergence of multidrug-resistant tuberculosis (MDR-TB) continues to threaten global tuberculosis (TB) treatment, care, and prevention, and it remains a major global health problem in many low- and middle-income countries with high morbidity and mortality. Objectives: The present study assessed MDR-TB treatment outcome and its predictors among adult patients in Kano, Nigeria. Methods: We conducted a secondary data analysis involving 283 adult patients treated for MDR-TB using routine data for MDR-TB programme in Kano State between August 2014 and September 2018. Results: The mean age (±standard deviation) of the respondents was 33.4 ± 11.6 years and up to 40% of them were within the age group of 25–34 years. About three-quarters of the participants 72.4% (205) were males; up to 63.6% (180) of the patients live in the urban areas, and mean duration of treatment initiation was 21 days after the diagnosis. Up to 66.8% (95% confidence interval [CI] = 61.1–72.4), patients had successful treatment, (cured) while 33.2% (95% CI = 27.6–38.9) died. After adjusting for confounding, gender and HIV status were found to be independent predictors of MDR-TB treatment outcome among MDR-TB patients in Kano. Male patients (adjusted odds ratio aOR = 0.38, 95% CI = 0.22–0.66, P = 0.001) and HIV-negative patients (aOR = 0.49, 95% CI = 0.28–0.87, P = 0.015) were less likely to die from MDR-TB. Conclusion: The study found a moderate treatment success rate for MDR-TB in Kano. Early initiation of treatment, control of HIV epidemic, and enhanced treatment supervision would likely improve treatment outcome.

Uncovering the Resistance Mechanism of Mycobacterium tuberculosis to Rifampicin Due to RNA Polymerase H451D/Y/R Mutations From Computational Perspective.

Tuberculosis is still one of the top 10 causes of deaths worldwide, especially with the emergence of multidrug-resistant tuberculosis. Rifampicin, as the most effective first-line antituberculosis drug, also develops resistance due to the mutation on Mycobacterium tuberculosis (Mtb) RNA polymerase. Among these mutations, three mutations at position 451 (H451D, H451Y, H451R) are associated with high-level resistance to rifampicin. However, the resistance mechanism of Mtb to rifampicin is still unclear. In this work, to explore the resistance mechanism of Mtb to rifampicin due to H451D/Y/R mutations, we combined the molecular dynamics simulation, molecular mechanics generalized-Born surface area calculation, dynamic network analysis, and residue interactions network analysis to compare the interaction change of rifampicin with wild-type RNA polymerase and three mutants. The results of molecular mechanics generalized-Born surface area calculations indicate that the binding free energy of rifampicin with three mutants decreases. In addition, the dynamic network analysis and residue interaction network analysis show that when H451 was mutated, the interactions of residue 451 with its adjacent residues such as Q438, F439, M440, D441, and S447 disappeared or weakened, increasing the flexibility of binding pocket. At the same time, the disappearance of hydrogen bonds between R613 and rifampicin caused by the flipping of R613 is another important reason for the reduction of binding ability of rifampicin in H451D/Y mutants. In H451R mutant, the mutation causes the binding pocket change too much so that the position of rifampicin has a large movement in the binding pocket. In this study, the resistance mechanism of rifampicin at the atomic level is proposed. The proposed drug-resistance mechanism will provide the valuable guidance for the design of antituberculosis drugs.

Evaluation of Nitrate Reductase Assay For Rapid Detection of Drug Resistant Tuberculosis

Emergence of multidrug-resistant tuberculosis (MDR-TB) urgently demands for simple, rapid and inexpensive methods of its detection for the effective treatment of drug resistant tuberculosis, particularly in low-income countries. This prospective study was carried out at National Tuberculosis Reference Laboratory and South Asian Association of Regional Cooperation (SAARC) Tuberculosis and HIV/AIDS Centre, Thimi, Bhaktapur, Nepal, from November 2009 to May 2010 to evaluate nitrate reductase assay (NRA) efficacy for rapid determination of streptomycin, isoniazid, rifampicin and ethambutol susceptibility of Mycobacterium tuberculosis strains. A total of 113 clinical isolates of M. tuberculosis were tested for four first line antitubercular drugs by nitrate reductase assay and were compared with standard proportion method. Results were available in 7-14 days by NRA as compared to proportion method which generally takes 4-6 weeks. The sensitivity and specificity of NRA were 98.1% and 100% for isoniazid, 95.1% and 98.6% for rifampicin, 91.4% and 94.9% for streptomycin, and 78.6% and 97.9% for ethambutol respectively. Agreement between NRA and proportion method were 99.1%, 97.3%, 93.8%, 95.6% for isoniazid, rifampicin, streptomycin and ethambutol, respectively. NRA is easier, inexpensive and reliable method for susceptibility testing of Mycobacterum tuberculosis for isoniazid and rifampicin, the two most important drugs for the treatment of tuberculosis. The reduction in susceptibility testing time, and higher sensitivity and specificity of NRA method is of fundamental importance in detecting MDR-TB.
 Key words: Drug susceptibility, MDR-TB, NRA, proportion method

Prevalence of multi-drug resistant (MDR) pulmonary tuberculosis in a tertiary care rural hospital in Western Maharashtra, India

Prevalence of multi-drug resistant (MDR) pulmonary tuberculosis in a tertiary care rural hospital in Western Maharashtra, India - IJMR- Print ISSN No: - 2394-546X Online ISSN No:- 2394-5478 Article DOI No:- 10.18231/j.ijmr.2019.052, Indian Journal of Microbiology Research-Indian J Microbiol Res

Nano-antimicrobials: A New Paradigm for Combating Mycobacterial Resistance.

Mycobacterium group contains several pathogenic bacteria including M. tuberculosis where the emergence of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) is alarming for human and animal health around the world. The condition has further aggravated due to the speed of discovery of the newer drugs has been outpaced by the rate of resistance developed in microorganisms, thus requiring alternative combat strategies. For this purpose, nano-antimicrobials have emerged as a potential option. The current review is focused on providing a detailed account of nanocarriers like liposome, micelles, dendrimers, solid lipid NPs, niosomes, polymeric nanoparticles, nano-suspensions, nano-emulsion, mesoporous silica and alginate-based drug delivery systems along with the recent updates on developments regarding nanoparticle-based therapeutics, vaccines and diagnostic methods developed or under pipeline with their potential benefits and limitations to combat mycobacterial diseases for their successful eradication from the world in future. Distinct morphology and the underlying mechanism of pathogenesis and resistance development in this group of organisms urge improved and novel methods for the early and efficient diagnosis, treatment and vaccination to eradicate the disease. Recent developments in nanotechnology have the potential to meet both the aspects: nano-materials are proven components of several efficient targeted drug delivery systems and the typical physicochemical properties of several nano-formulations have shown to possess distinct bacteriocidal properties. Along with the therapeutic aspects, nano-vaccines and theranostic applications of nano-formulations have grown in popularity in recent times as an effective alternative means to combat different microbial superbugs. Nanomedicine holds a bright prospect to perform a key role in global tuberculosis elimination program.

Management of patients with multidrug-resistant tuberculosis.

The emergence of multidrug-resistant tuberculosis (MDR-TB; defined as resistance to at least rifampicin and isoniazid) represents a growing threat to public health and economic growth. Never before in the history of mankind have more patients been affected by MDR-TB than is the case today. The World Health Organization reports that MDR-TB outcomes are poor despite staggeringly high management costs. Moreover, treatment is prolonged, adverse events are common, and the majority of affected patients do not receive adequate treatment. As MDR-TB strains are often resistant to one or more second-line anti-TB drugs, in-depth genotypic and phenotypic drug susceptibility testing is needed to construct personalised treatment regimens to improve treatment outcomes. For the first time in decades, the availability of novel drugs such as bedaquiline allow us to design potent and well-tolerated personalised MDR-TB treatment regimens based solely on oral drugs. In this article, we present management guidance to optimise the diagnosis, algorithm-based treatment, drug dosing and therapeutic drug monitoring, and the management of adverse events and comorbidities, associated with MDR-TB. We also discuss the role of surgery, physiotherapy, rehabilitation, palliative care and smoking cessation in patients with MDR-TB. We hope that incorporating these recommendations into patient care will be helpful in optimising treatment outcomes, and lead to more MDR-TB patients achieving a relapse-free cure.

Diversified lineages and drug-resistance profiles of clinical isolates of Mycobacterium tuberculosis complex in Malaysia.

Tuberculosis (TB) is still a major health problem in Malaysia with thousands of cases reported yearly. This is further burdened with the emergence of multidrug-resistant TB (MDR-TB). Whole-genome sequencing (WGS) provides high-resolution molecular epidemiological data for the accurate determination of Mycobacterium tuberculosis complex (MTBC) lineages and prediction of the drug-resistance patterns. This study aimed to investigate the diversity of MTBC in Malaysia in terms of lineage and drug-resistance patterns of the clinical MTBC isolates using WGS approach. The genomes of 24 MTBC isolated from sputum and pus samples were sequenced. The phenotypic drug susceptibility testing (DST) of the isolates was determined for ten anti-TB drugs. Bioinformatic analysis comprising genome assembly and annotation and single-nucleotide polymorphism (SNP) analysis in genes associated with resistance to the ten anti-TB drugs were done on each sequenced genome. The draft assemblies covered an average of 97% of the expected genome size. Eleven isolates were aligned to the Indo-Oceanic lineage, eight were East-Asian lineage, three were East African-Indian lineage, and one was of Euro-American and Bovis lineages, respectively. Twelve of the 24 MTBC isolates were phenotypically MDR M. tuberculosis: one is polyresistance and another one is monoresistance. Twenty-six SNPs across nine genes associated with resistance toward ten anti-TB drugs were detected where some of the mutations were found in isolates that were previously reported as pan-susceptible using DST. A haplotype consisting of 65 variants was also found among the MTBC isolates with drug-resistance traits. This study is the first effort done in Malaysia to utilize 24 genomes of the local clinical MTBC isolates. The high-resolution molecular epidemiological data obtained provide valuable insights into the mechanistic and epidemiological qualities of TB within the vicinity of Southeast Asia.

Plasma Levels of Cytokines (IL-10, IFN-γ and TNF-α) in Multidrug Resistant Tuberculosis and Drug Responsive Tuberculosis Patients in Ghana.

The emergence of multidrug-resistant tuberculosis (MDR–TB) and more recently, extensively drug-resistant (XDR) TB has intensified the need for studies aimed at identifying factors associated with TB drug resistance. This study determined the differences in plasma concentrations of pro-inflammatory (IFN-γ and TNF-α) and anti-inflammatory (IL-10) cytokines in MDR-TB and drug-susceptible (DS) TB patients, in addition to some socio-economic factors. Plasma levels of IL-10, IFN-γ and TNF-α were measured in 83 participants (comprising 49 MDR-TB and 34 DS-TB patients) using sandwich ELISA. Levels of the three cytokines were elevated in MDR-TB patients compared to DS-TB patients. The mean level of IL-10 (7.8 ± 3.61 ρg/mL) measured in MDR-TB cases was relatively higher than those of TNF-α and IFN-γ, and statistically significant (p = 0.0022) when compared to the level of IL-10 (4.8 ± 4.94 ρg/mL) in the DS-TB cases. There were statistically significant associations between MDR-TB and factors such as education level (X2 = 9.895, p = 0.043), employment status (X2 = 19.404, p = 0.001) and alcoholism (X2 = 3.971, p = 0.046). This study adds to the knowledge that IFN-γ, TNF-α and IL-10 play a role in the host response to Mycobacterium tuberculosis (MTB). Alcohol intake can be considered as an important MDR-TB risk factor.

801. Emergence of Multi-Drug Resistance Tuberculosis During the Treatment Course of Pan-Susceptible TB: A Case Series

BackgroundSuccessful treatment of tuberculosis (TB) requires monitoring for clinical, radiographic, and microbiologic improvement. Even after negative cultures are obtained, there should be continued monitoring of sputa. If cultures become positive during treatment of drug susceptible TB (DS-TB), there should be concern for multi-drug-resistant tuberculosis (MDR-TB). We present two cases diagnosed with DS-TB who developed MDR-TB during treatment. Case Report: Case 1 is a 33-year-old male who was incarcerated in Peru. During incarceration in 2008, three of his cellmates had MDR-TB and he was diagnosed with DS-TB and treated with directly observed therapy (DOT) for 7 months. In Texas in 2015 he was diagnosed with DS-TB and was initiated on rifampin, isoniazid, pyrazinamide, and ethambutol (RIPE). Five months into DOT, his sputa became culture positive with molecular detection of drug resistance (MDDR) and drug susceptibility testing (DST) revealing resistance to all of RIPE. Repeat MDDR and DST of the 2015 isolate showed no resistance. Genotyping of the two isolates were identical by mycobacterial interspersed repetitive units (MIRU) and spoligotyping. However, whole genome sequencing showed two different isolates. Case 2 is a 63-year-old female diagnosed with DS-TB in Saipan and started on RIPE in April 2017. She was on DOT until July when she moved to Texas and was lost to follow-up until September. She claims adherence with rifampin and isoniazid during this time. All sputa collected between diagnosis and September were smear and culture negative. Six months into therapy, she had sputa that was culture positive with MDDR and DST showing MDR-TB. Her isolates from Saipan and Texas were sent for genotyping. The MIRU and spoligotyping showed two different isolates.ConclusionThese cases show the importance of following cultures throughout treatment. Traditionally, MDR-TB is thought to be due to poor adherence. However, in high prevalence areas, heterogeneous infection with two different strains is an important consideration for the cause of MDR-TB. Concomitant infection of DS and MDR-TB can occur with MDR-TB not being detected until far into therapy. These cases represent heterogeneous exogenous infection of DS and MDR-TB—only discovered after meticulous culture monitoring.Disclosures All authors: No reported disclosures.

A rapid identification technique for drug-resistant Mycobacterium tuberculosis isolates using mismatch specific cleavage enzyme.

The emergence of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) strains is a major health problem for high Tuberculosis (TB) incidence countries. Therefore, it is of interest to identify antibiotic resistant bacteria by mismatch detection using DNA hybridization. We generated PCR products for five genes (rpoB, inhA, katG, gyrA and rrs) associated with drug resistance TB from MDR and XDR Mycobacterium tuberculosis (MTB) DNA samples. These were hybridized to PCR products from MTB H37Rv (pansusceptible laboratory strain) to generate DNA hetero-duplex products, which was digested by Detection Enzyme (GeneArt Genomic Cleavage Detection Kit) and visualized by agarose gel electrophoresis. Results show different bands with sizes of 400 bp and 288 bp (rpoB), 280 bp (inhA), 310 bp (katG), 461 bp (gyrA) and 427 bp (rrs) suggesting mutations in DNA heteroduplex for each gene. Detection Enzyme specifically cleaves DNA hetero-duplex with mismatch. The technique helps in the improved detection of MDR (mutations in rpoB, inhA and katG) and XDR (mutations in rpoB, inhA katG, gyrA and rrs) MTB strains. Moreover, the technique is customized without expensive specialized equipment to detect mutations. It is also fast, efficient and easy to implement in standard molecular biology laboratories.

Pediatric Multidrug Resistant Tuberculosis

Background: Tuberculosis (TB) is consider a difficult infectious disease to treat all over world. The emergence of multi-drug resistant TB (MDR-TB) has become a significant public-health issue and an obstacle to effective TB-control. Argentina's cases were 10,312 in 2016. Cases younger than 20 years-old account for 17,5% of the TB-cases. Methods & Materials: A retrospective study was conducted through the revision of records at TB service of a children's hospital of Buenos Aires, from Jan 2005-Sept 2017. We defined MDR-TB: strains of Mycobacterium tuberculosis resistant, at least, to Rifampicin (R) and Isoniazid (H). The recommended baseline laboratory investigations were carried out in all patients. Statistical analyses: EpiInfo 7®. Results: 1265 TB-cases were admitted; 14 patients (1,1%) had MDR-TB in the same period. Median age: 7.4 years (range: 1-17years), female 57%. Without comorbidities (except one Down Syndrome). TB-source was found in 78%, mostly households. Tuberculine-test was initially positive in 57%. TB-localization was pulmonary in 11 cases, with radiology-pattern: cavitary uni (4) or bilateral (2), nodular (2), pneumonic consolidation (3). Extra-pulmonary TB included 2 cervical lymphadenitis, 1 pleural and 1 Pott. Out of 50% smear positive cases Mycobacterium tuberculosis grow in culture, that after a mean of the end of 4 months (range: 3-5) were all negative. Resistance profiles plus HR were Streptomicine 57%, Ethambutol 28,5%, Quinolone 21%, Pirazinamide 21%, 2° line injectable drugs 14% and p-Aminosalicylic acid 7%. Two patients were classified as pre-XDR-TB and one XDR-TB. 79% had primary drug resistance; 7% acquired drug resistance. Seven patients started treatment with first-line drugs and shifted 1-2 months later. Six patients experienced adverse effects. Seven cases (50%) concluded treatment after a mean of 19 months (range: 13-21), half of them had pulmonary sequelae. Two patients were transferred out for supervised treatment and five are still on follow up. Conclusion: Contact with MDR source, previous default or failure to treatment must be on consideration. Early diagnosis, proper counselling to parents, improved prolonged therapy compliance are the key factors for improved clinical outcome in MDR-patients. Children with suspicious or active TB caused by a drug-resistant strain of Mt should always be referred to a specialized center because of the complexity of patient management and the high frequency of adverse events.

Evaluation of six months sputum culture conversion as a surrogate endpoint in a multidrug resistant-tuberculosis trial

The emergence of multidrug resistant-tuberculosis (MDR-TB), defined as Mycobacterium tuberculosis strains with in vitro resistance to at least isoniazid and rifampicin, has necessitated evaluation and validation of appropriate surrogate endpoints for treatment response in drug trials for MDR-TB. The trial that has demonstrated efficacy of bedaquiline, a diarylquinoline that inhibits mycobacterial ATP synthase, possesses the requisite features to conduct this evaluation. Approval of bedaquiline for use in MDR-TB was based primarily on the results of the controlled C208 Stage II study (ClinicalTrials.gov number, NCT00449644) including 160 patients randomized 1:1 to receive bedaquiline or placebo for 24 weeks when added to an 18–24-month preferred five-drug background regimen. Since randomization in C208 Stage II was preserved until study end, the trial results allow for the investigation of the complex relationship between sustained durable outcome with either Week 8 or Week 24 culture conversion as putative surrogate endpoints. The relationship between Week 120 outcome with Week 8 or Week 24 culture conversion was investigated using a descriptive analysis and with a recently developed statistical methodology for surrogate endpoint evaluation using methods of causal inference.The results demonstrate that sputum culture conversion at 24 weeks is more reliable than sputum culture conversion at 8 weeks when assessing the outcome of adding one new drug to a MDR-TB regimen.

Computational discovery of potent drugs to improve the treatment of pyrazinamide resistant Mycobacterium tuberculosis mutants.

Emergence of multi-drug resistance tuberculosis has become a serious health problem globally. Accumulation of mutations in the drug target led to the development of multi-drug resistant mycobacterial strains that have made most of the conventional drugs ineffective. Hence, there is desperate need for the development of new therapeutic strategies. Here, we focused on the analysis of mutations in Mycobacterium tuberculosis (Mtb) PncA (pyrazinamidase) that is responsible for resistance against first-line anti-tuberculosis pyrazinamide (PZA) drug. First, PZA and its two isoforms were analyzed for their binding affinity toward ligand binding cavity of Mtb wild-type and mutant PncA proteins. The observations suggested that some drug resistant mutations cause strong binding of PncA with the active form of PZA and impair its release, which is required to inhibit the growth of Mtb. To improve the treatment of PZA resistant Mtb, high throughput virtual drug screening was performed to identify potent drug molecules from a library of compounds derived from ChEMBL database. From this library, we predicted a lead molecule (terta-butyl(2S,4S)-4-amino-2-cyclopropyl-6-(trifluoromethyl)-3,4-dihydro-2H-quinoline-1-carboxylate) to be more effective against PZA resistant Mtb strains in comparison to PZA. The lead molecule showed better drug-like properties such as high affinity and atomic interactions with wild-type and drug-resistant mutations in Mtb PncA proteins. Further, molecular dynamic simulation studies showed that this lead molecule has better conformational stability and compatibility with drug-resistant PncA proteins in comparison to PZA drug. We hypothesized that the predicted lead compound could be more effective, and thus may improve the treatment of PZA resistant tuberculosis.

Epidemiological Correlates and Treatment Outcomes among Patients with MDR Tuberculosis in Northern India

Introduction: Multi drug resistant-TB (MDR-TB) threatens global TB control and is a major public health concern in several countries. The present study was undertaken to detect the epidemiological correlates and treatment outcomes among patients with MDR-TB previously or currently admitted in Department of Respiratory Medicine and Pulmonary and Critical Medicine, KGMU, Lucknow. Material & Methods: This retrospective study included 2370 TB patients admitted in the Department of Respiratory Medicine and Pulmonary and Critical Medicine, KGMU, Lucknow between years 2012 to 2015. Treatment outcomes were observed. SPSS software was used for data analysis. Results: The total number of MDR-TB cases enrolled were 2370. There were 772 (32.6%) males (95% CI: 30.7 % -34.5%) and 1598 (67.4%) females (95% CI: 65.5% -69.3%) registered for MDR-TB treatment. The treatment outcomes were as follows: majority (77.1%) were under treatment, 279 (11.8%) patients were declared cured, 10 (0.4%) were failure cases, while 64 (2.7%) were defaulters, 149 (6.3%) had died and 41(1.7%) were transferred out. Conclusion: Emergence of MDR-TB has the potential to be a serious public health problem in Northern India and this necessitates strengthening of TB control and improved continuous monitoring of therapy.

Trend Analysis of Knowledge and Practice of National Tuberculosis Guidelines Among Medical Students: A Two-Year Interventional Study in Shiraz, Iran

Background: Tuberculosis (TB) is the second leading cause of death from infectious diseases. Delayed diagnosis of TB and emergence of multidrug-resistant TB are among the most important issues related to physician performance. Objectives: This study aimed to assess the level of knowledge and practice of TB among medical students. Methods: In this longitudinal, interventional study, 60 final-year medical students, who were referred to the Tuberculosis Research Center, affiliated to Shiraz University of Medical Sciences, were assessed regarding the knowledge and practice of national TB guidelines before education, 1 month after education, and 2 years after education. Data were collected using a valid and reliable questionnaire (Cronbach’s alpha, 0.62). The questionnaire consisted of 10 and 8 questions about knowledge and practice, respectively. The collected data were analyzed using SPSS. Results: Overall, 33 women and 27 men were recruited in this study. The mean age of the participants was 24 ± 1.5 years. The mean time from the internship period was 7.1 ± 4.4 months, and 53.3% of the participants had attended the infection ward during their clinical course. The median score of both knowledge and practice increased by about 50% after 1 month of education, while only practice showed a 25% increase after 2 years of education. No significant difference was found regarding knowledge and practice between genders. In addition, there was no significant difference among individuals who attended the infection ward and those who did not. Similarly, there was no significant difference among individuals who participated in continued medical programs after graduation and those who did not participate in such programs; also, students who visited patients with suspected TB were not significantly different from those who did not. However, a higher frequency of acceptable knowledge (≥ 50%) was reported in students who visited patients with suspected TB; also, a higher sum score of knowledge and practice was found in male students. Conclusions: This study showed that the level of TB knowledge and practice was not optimal among medical students. Therefore, for achieving a higher level of knowledge and practice, a regular patient-centered educational approach is needed, especially for postgraduates.

Assessment of Anti-TB Drug Nonadherence and Associated Factors among TB Patients Attending TB Clinics in Arba Minch Governmental Health Institutions, Southern Ethiopia.

Background Tuberculosis (TB) is an infectious disease caused by the bacillus Mycobacterium tuberculosis. Nonadherence to anti-TB treatment may result in the emergence of multidrug-resistant TB, prolonged infectiousness, and poor tuberculosis treatment outcomes. Ethiopia is one of the seven countries that reported lower rates of treatment success (84%). This study assessed anti-TB drug nonadherence and associated factors among TB patients in Arba Minch governmental health institutions. Methods An institution based cross-sectional study design was conducted from April 15 to May 30, 2017. A systematic sampling technique was employed to select the study subjects. Data was collected using a semistructured questionnaire with Morisky Medication Adherence Scale-8 (MMAS-8) and was entered, cleaned, and analyzed in SPSS version 20. Results The study included 271 TB patients with a response rate of 96.4%; 58.3% were males and 64.9% were Gamo by ethnicity. The overall nonadherence was 67 (24.7%) (CI = 20.0–30.4). Nonadherence was high if the patients experienced side effects (AOR = 13.332; 95% CI = 2.282–77.905), were far from the health facility (AOR = 21.830; 95% CI = 0.054–77.500), and experienced prolonged waiting time to get medical services (AOR = 14.260; 95% CI = 2.135–95.241). Conclusions The proportion of TB patients that did not adhere to anti-TB drugs was high in Arba Minch governmental health institutions.

The ethanolic extract of ashitaba stem (Angelica keskei [Miq.] Koidz) as future antituberculosis.

Considering the easy contagion of tuberculosis (TB) disease spread and the emergence of multidrug-resistant TB, which directly impacts the failure of therapeutic goals and mortality rates increasing, TB disease control remains to be the main concern of continuous health development effort. Therefore, the discovery of new TB drug is needed. This research assessed the new natural anti-TB drug from the ethanolic extract of Angelica keiskei stem obtained from Lombok, Indonesia. The objectives of this study were to evaluate the sensitivity of Mycobacterium tuberculosis (Mtb) H37Rv strain to A. keiskei stem extract and to determine its minimum inhibitory concentration (MIC). The extraction methods of A. keiskei stem were done using a maceration method. In addition to phytochemical screening and water content analysis using standard method, the phytochemical parameters were analyzed by thin-layer chromatography. Ethanolic extract of A. keiskei stem was assayed for their Mtb inhibitory activity using the proportion method. The phytochemical analysis result showed that the secondary metabolites contain in the extract were flavonoid, polyphenol, tannin, monoterpenoid and sesquiterpen, quinon, and saponin. The anti-TB test result showed the active activity of ethanolic extract of A. keiskei against Mtb H37Rv strain with MIC ranging from 6% to 8% w/v. In conclusion, ethanolic extract of A. keiskei is a prospective natural anti-TB for the future.

Psychiatric disorders in patients with multidrug resistant tuberculosis (MDR-TB) in Sardjito Hospital, Yogyakarta, Indonesia

Introduction: Tuberculosis has become a chronic debilitating disease in developing countries, particularly after the emergence of multidrug resistant tuberculosis (MDR-TB). Second line treatments for the disease which were subsequently developed were associated with psychiatric disorders among patients. Psychiatric disorder can either be induced by treatment regiments or psychosocial factors. Cycloserine administration is frequently reported to be associated with psychiatric disorders. In this study, we examined the prevalence and characteristics of psychiatric disorders among MDR-TB patients in Sardjito Hospital, Yogyakarta, Indonesia. Methods: In this descriptive study, we studied medical records of MDR-TB patients admitted for MDR-TB treatments to Sardjito Hospital from January 2014 to July 2016 and screened for psychiatric disorders. Results: We found that 32.8% of the patients had psychiatric disorders, some of which had multiple psychiatric diagnoses (14.1%). The diagnoses were medication induced delirium, substance/medication induced psychotic disorder, substance/medication use depressive disorder, depressive type schizoaffective disorder, bipolar I disorder current episode severe manic with psychotic features, mild depression, moderate depression, major depression without psychotic features, major depression with psychotic features, adjustment disorders with mixed anxiety and depressed mood, adjustment disorder with anxiety, acute stress disorder, and insomnia. Psychiatric disorders were significantly associated with cycloserine dose and sex. Psychotic symptoms were significantly associated with sex and level of education. Conclusion: The presence of psychiatric disorders might disturb MDR-TB treatment resulting in poor outcomes. Precaution and prompt managements are required for psychiatric disorders in patients receiving MDR-TB treatment regiments.

Applying optimization algorithms to tuberculosis antibiotic treatment regimens.

Tuberculosis (TB), one of the most common infectious diseases, requires treatment with multiple antibiotics taken over at least 6 months. This long treatment often results in poor patient-adherence, which can lead to the emergence of multi-drug resistant TB. New antibiotic treatment strategies are sorely needed. New antibiotics are being developed or repurposed to treat TB, but as there are numerous potential antibiotics, dosing sizes and potential schedules, the regimen design space for new treatments is too large to search exhaustively. Here we propose a method that combines an agent-based multi-scale model capturing TB granuloma formation with algorithms for mathematical optimization to identify optimal TB treatment regimens. We define two different single-antibiotic treatments to compare the efficiency and accuracy in predicting optimal treatment regimens of two optimization algorithms: genetic algorithms (GA) and surrogate-assisted optimization through radial basis function (RBF) networks. We also illustrate the use of RBF networks to optimize double-antibiotic treatments. We found that while GAs can locate optimal treatment regimens more accurately, RBF networks provide a more practical strategy to TB treatment optimization with fewer simulations, and successfully estimated optimal double-antibiotic treatment regimens. Our results indicate surrogate-assisted optimization can locate optimal TB treatment regimens from a larger set of antibiotics, doses and schedules, and could be applied to solve optimization problems in other areas of research using systems biology approaches. Our findings have important implications for the treatment of diseases like TB that have lengthy protocols or for any disease that requires multiple drugs.

In vitro Antitubercular Activity of 3-Deoxysappanchalcone Isolated From the Heartwood of Caesalpinia sappan Linn.

Responsible for nearly 1.5 million deaths every year, the infectious disease tuberculosis remains one of the most serious challenges to global health. The emergence of multidrug-resistant tuberculosis and, more recently, extensively drug-resistant tuberculosis poses a significant threat in our effort to control this epidemic. New drugs are urgently needed to combat the growing threat of antimicrobial resistance. To achieve this goal, we screened approximately 500 species of medicinal plant methanol extracts and their solvent partitioned fractions for potential inhibitors of Mycobacterium tuberculosis growth. Using microdilution screening, the ethyl acetate solvent partitioned fraction from the heartwood of Caesalpinia sappan exhibited strong antitubercular activity. We isolated the active compound and identified it as 3-deoxysappanchalcone. The extracted 3-deoxysappanchalcone possessed activity against both drug-susceptible and drug-resistant strains of M.tuberculosis at MIC50 s of 3.125-12.5μg/mL in culture broth and MIC50 s of 6.25-12.5μg/mL inside macrophages and pneumocytes. 3-Deoxysappanchalcone was also found to act in partial synergy with streptomycin/ethambutol against M.tuberculosis H37Rv. 3-Deoxysappanchalcone had no cytotoxicity against the A549 cell line up to a concentration of 100μg/mL (selectivity index>8-32). Further studies are warranted to establish the in vivo effect and therapeutic potential of 3-deoxysappanchalcone. Copyright © 2017 John Wiley & Sons, Ltd.