Development Of Multidrug-resistant Tuberculosis Research Articles

SHINE trial of shorter course tuberculosis treatment

Journal of Paediatrics and Child HealthVolume 58, Issue 5 p. 935-935 Heads UpFree Access SHINE trial of shorter course tuberculosis treatment First published: 02 April 2022 https://doi.org/10.1111/jpc.15957 edited by Craig Mellis (craig.mellis@sydney.edu.au) [Correction added on 12 April 2022, after first online publication: Figure 1 has been removed from the article.] AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat The World Health Organization (WHO) estimates that 1.1 million children worldwide became ill with tuberculosis (TB) in 2020. Treatment adherence is a possible issue in the development of multidrug-resistant TB. The SHINE trial randomised 1204 African and Indian children (median age 3.5 years, range 2 months to 15 years) diagnosed with respiratory sample smear-negative, ‘non-severe’ TB to either 4 or 6 months of anti-tuberculous treatment using child-friendly fixed dose combinations (8 weeks of isoniazid, rifampicin and pyrazinamide ± ethambutol followed by 8 or 16 weeks of isoniazid and rifampicin).1 Of these, 52% were male, 11% had human immunodeficiency virus (HIV) infection, and 14% had bacteriologically confirmed TB. Retention (95% at 72 weeks) and treatment adherence (94%) were very high. The primary endpoint, unfavourable outcome (treatment failure or death), occurred in 16 participants (3%) in the 4-month group compared with 18 (3%) in the 6-month group (adjusted difference, −0.4%; 95% CI, −2.2 to 1.5). Adverse events mainly occurred in the first 8 weeks of treatment and were equally common (8%) in both groups. As a result of the SHINE trial, new WHO guidelines recommend that children with non-severe TB can now receive 4 months of anti-TB treatment. The challenges are accurate classification of ‘non-severe’ disease in resource-limited settings where disease burdens are highest, and whether clinicians in developed countries will feel comfortable treating for 4 months before more clinical experience accumulates. Reference 1Turkova A, Wills GH, Wobudeya E et al. Shorter treatment for nonsevere tuberculosis in African and Indian children. N. Engl J Med 2022; 399: 911– 22. CrossrefWeb of Science®Google Scholar Reviewers: David Isaacs (david.isaacs@health.nsw.gov.au) and Ben Marais (ben.marais@health.nsw.gov.au), Children's Hospital at Westmead and University of Sydney Volume58, Issue5May 2022Pages 935-935 ReferencesRelatedInformation

Genome-wide analysis to detect multi-drug resistance genes in Mycobacterium tuberculosis strains SWLPK and MNPK resourced from Pakistan

Development of multidrug-resistant tuberculosis is the after effect of various mutational occasions, which leads to the development of protection from hostile to multiple tuberculosis drugs. In this study, we identified drug resistance genes, their evolutionary analysis, mutational variation, and docking to characterize the drug target potentials of two Mycobacterium tuberculosis strains SWLPK and MNPK resourced from Pakistan. For this purpose, we used different bioinformatics tools including the RAST server for annotation, and UniProt, NCBI, BLAST and MUSCLE for data retrieval and analysis. Evolutionary relationships were drawn using MEGA 7. A 3D structure was modelled by I-TASSER, while refinement and minimizations were performed using the UCSF Chimera 1.14.1. Moreover, the Ramachandran plot was used to check the quality of the proteins, while PatchDock was used for the docking analysis. Based on the comparison with the reference genome (M. tuberculosis H37RV), the SWLPK and MNPK strains encoded 24 multi-drug resistance genes. The drug resistance genes of nearby strains had developmental relatedness and comparable useful attributes imperative to their ecological specialties. The docking analysis revealed that the proteins accurately bound at their binding region just like the reference protein H37Rv (NuoG). We identified 24 multi-drug resistance genes in the SWLPK and MNPK strains. Moreover, there were a few missing drug resistance genes found in H37Rv, which were not present in the MNPK and SWLPK strains. The 24 genes reported in the MNPK and SWLPK strains might have a major contribution in drug resistance.

The Neglected Contribution of Streptomycin to the Tuberculosis Drug Resistance Problem.

The airborne pathogen Mycobacterium tuberculosis is responsible for a present major public health problem worsened by the emergence of drug resistance. M. tuberculosis has acquired and developed streptomycin (STR) resistance mechanisms that have been maintained and transmitted in the population over the last decades. Indeed, STR resistant mutations are frequently identified across the main M. tuberculosis lineages that cause tuberculosis outbreaks worldwide. The spread of STR resistance is likely related to the low impact of the most frequent underlying mutations on the fitness of the bacteria. The withdrawal of STR from the first-line treatment of tuberculosis potentially lowered the importance of studying STR resistance. However, the prevalence of STR resistance remains very high, could be underestimated by current genotypic methods, and was found in outbreaks of multi-drug (MDR) and extensively drug (XDR) strains in different geographic regions. Therefore, the contribution of STR resistance to the problem of tuberculosis drug resistance should not be neglected. Here, we review the impact of STR resistance and detail well-known and novel candidate STR resistance mechanisms, genes, and mutations. In addition, we aim to provide insights into the possible role of STR resistance in the development of multi-drug resistant tuberculosis.

A cross-sectional study to correlate demographic and clinical profile of multi-drug resistant tuberculosis patients in a tertiary hospital

One of the major hurdles in eradication of Tuberculosis is the development of Multi-drug resistant Tuberculosis, which needs timely identification and treatment to avoid its spread in the community. The present study is an attempt to correlate demographic and clinical profile of multi drug-resistant tuberculosis cases coming to the facility A Hospital-based Cross-sectional Observational Study in Department of Respiratory Medicine, Smt. B.K. Shah Medical Institute and Research Center and Dhiraj Hospital, Vadodara, Gujarat. Among subjects diagnosed as Multi-drug Resistant Tuberculosis over a period of one and a half years from May 2016 to November 2017. A detailed clinical profile physical examination and laboratory investigations were done and correlated with demographic profile. Data was analyzed in Open source software OpenEpi. P value was considered to be significant at P<0.05. Arithmetic Mean was used wherever deemed necessary. Majority of patients were aged between 40 to 50 years with Male to female ratio was 1.5:1. Most patients were farmers, home makers (unemployed), and labourers and had a low education with lower socioeconomic status. The symptom profile indicated weight loss, loss of appetite, cough with expectoration, dyspnoea and fever. 70% of the patients had haemoglobin levels < or = 10 g/dl. A high proportion of patients had normal TLC (Total Leucocyte Count) levels (n=21; 70%), thus indicating the absence of an inflammatory condition. A major proportion of patients (n=24; 80%) had lymphocyte count > 20. The patients had high prevalence of co-morbidities.Most of patients of multidrug resistant tuberculosis (MDR-TB)were 40 to 50 years of age with male predominance from lower socio-economic strata, had a low annual income and a positive history of tuberculosis. Multidisciplinary approach for the management of MDR-TB is needed.

Factors Influencing Adherence to Tuberculosis Treatment in the Ketu North District of the Volta Region, Ghana.

Annually, ten million cases of tuberculosis (TB) and about 1.8 million mortalities are recorded. Adherence to TB treatment not only reduces death outcomes but prevents prolonged sickness, transmission to others, and the development of multidrug-resistant TB. This study is aimed at determining the rate of treatment adherence, knowledge of TB infection, and the possible factors influencing adherence to TB treatment in the Ketu North District in the Volta Region of Ghana. A cross-sectional study design was employed. A semistructured questionnaire was used to obtain data from respondents. Adherence to TB treatment and knowledge level about TB infection were assessed. A Chi-square test analysis was used to determine the variables that were associated with treatment adherence. Logistic regression analysis was used to determine potential factors that contribute to treatment adherence. A total of 125 TB registrants were enrolled in the study. The majority (102 (81.6%)) adhered to the TB treatment regimen. However, the level of knowledge about night sweat being a symptom of TB infection was relatively low (78 (62.4%)). Logistic regression analysis revealed that the male gender was about three times more likely (OR = 2.978, 95%CI = 1.173‐7.561; p = 0.022) to be associated with adherence to TB treatment. However, food availability (OR = 2.208, 95% CI (0.848-5.753); p = 0.10) and household size (OR = 0.538, 95% CI (0.195-1.483); p = 0.23) were not significantly associated with treatment adherence. In this study, adherence to TB treatment and the knowledge level of TB infection were high. However, the knowledge level of night sweat being a symptom of TB infection was relatively low. Being a male was significantly associated with treatment adherence. An intensified health education on the symptoms of TB infection is therefore recommended.

English

Multi Drug Resistant Tuberculosis (MDR-TB) is a public health challenge, which itself remains a global public health problem. Its impact is worsened by co-infection with Human immunodeficiency virus (HIV). In order to institute successful TB control strategies, factors for development of MDR-TB must be understood. This study aimed to identify and describe clinical and demographic determinants for development of MDR-TB among TB patients. This was a cross sectional, hospital-based study conducted between April 2017 and December 2019 involving 428 presumptive MDR-TB patients. Specimens were subjected to GeneXpert MTB/RIF assay, microscopy and Line probe assay for diagnosis of MDR-TB. A questionnaire was used to collect demographic information from patients. The odds of having MDR-TB among patients who were cigarette smokers were four-times compared to non-smoking patients (aOR=3.94; 95%CI: 1.845-8.428, p<0.001). Alcohol abuse increased the chances of having MDR-TB by ten times (aOR=9.98: 95%CI; 2.414-41.267, p=0.001). Being HIV positive strongly increased the likelihood of having MDR-TB (aOR=2266.0: 95% CI; 407.5-2599.8, p<0.001). Compared to treatment failure, relapse and non-adherence were found to be strong predictors for MDR-TB (aOR=64.22: (95% CI; 12.786-322.507) p=0.001), and (aOR=37.44: (95% CI; 3.895-359.836, p=0.002), respectively. HIV infection, TB relapse, history of irregular treatment, cigarette smoking, alcohol abuse, and treatment failure (return) is factors development of MDR-TB. Integrated TB/HIV control programs that will include the establishment of strong diagnostic and drug delivery systems, patient management, and TB resistance surveillance systems are recommended. Key words: Tuberculosis, multi drug resistant tuberculosis (MDR-TB), HIV, M. tuberculosis, adherence; relapse.

Prevalence of Multi-Drug Resistant Tuberculosis among Tuberculosis Patients Attending Chest Clinics in Osun-State, Nigeria.

The development of multidrug-resistant tuberculosis (MDR-TB) poses a considerable threat to tuberculosis control programmes in Nigeria. There is an increase in the prevalence of MDR-TB worldwide both among new tuberculosis cases as well as previously-treated ones. There is also a rise in transmission of resistant strains due to an increase in MDR-TB patients largely due to the poor drug compliance and the impact of Human immunodeficiency virus infection. Therefore, we intend to determine the extent of MDR-TB among attendees of chest clinics in Osun-State, Nigeria. The objective of this study was to determine the prevalence of MDR-TB among confirmed tuberculosis patients attending chest clinics in Osun-State, Nigeria. This study was conducted among 207 attendees of chest clinics in Osun-State between June, 2015 and October 15, 2016. Sputum and blood samples of the participants were collected. GeneXpert test was carried out first on the samples for simultaneous identification of MTB and rifampicin resistance. Sputum samples were cultured on Lowenstein-Jensen (L-J) medium using N-acetyl-Lcysteine- sodium hydroxide (NALC-NaOH) decontamination method. Drug susceptibility testing (DST) to three first-line drugs was carried out using the proportion DST method. The prevalence of MTB was found to be 27.5% while the prevalence of MDR-TB from the fifty-seven isolates was 10.5%. Previously treated and new cases had a prevalence of 7.0% and 3.5% MDR-TB, respectively. Seventy (33.8%) participants were positive for HIV infection, out of which twenty-six (12.6%) had co-infection of tuberculosis and HIV. The mono-resistance rates of the three first-line drugs used were: 5.3% and 8.7% for ethambutol (EMB) and isoniazid (INH), respectively. No isolate had mono-resistance (0%) to rifampicin (RIF). This study observed the prevalence of 27.5% MTB and a prevalence of 10.5% MDR-TB among the MTB isolates. The prevalence of TB is high in Osun State. MDR-TB prevalence is higher compared with the national estimate of MDR-TB (5.1%) of 2017. Resistant TB is a threat to national tuberculosis control and it is recommended that all the facilities be equipped to cater to its diagnosis.

Increasing Burden of Multidrug Resistant Tuberculosis in HIV Infected Individuals: A Systematic Review and Meta-Analysis

Background: The increasing burden of multidrug-resistant tuberculosis (MDR-TB) in HIV infected individuals is a serious threat to global tuberculosis control programs. The study aimed to summarize the available evidences on the association of HIV infection and the development of MDR-TB and, finally, to provide an up-to-datepooled estimate of risks. Methods: We searched on PubMed, Google Scholar, and ScienceDirect databases to select eligible studies for our systematic review and meta-analysis, published between January 1, 2010, and July 30,2019. Two sets of reviewers independently extracted data and assessed the methodological quality of the studies using the Newcastle-Ottawa Scale. Subgroup analysis was pre-specified to perform according to the continent, country, income level, study design, mean/median age, and type of MDR-TB. The random-effects model was used to obtain the pooled odds ratio of the crude association between HIV infection and MDR-TB with a 95% confidence interval. We investigated the potential publication bias by checking funnel plot asymmetry and using the Egger’s test. Moreover, we assessed the heterogeneity using Cochran’s Q test and the I2 statistic. Findings: We identified 1496 studies through a database search, and after subsequent elimination based on our eligibility criteria, we selected 47 articles, including 60,754 participants. The pooled odds ratio was 1.47 (95% CI= 1.19-1.81) with substantial heterogeneity (I2=80.49%), and there was no evidence of publication bias (p=0.13). Subgroup analysis revealed that the estimated pooled odds ratio for European countries (OR=2.31, 95% CI= 1.80-2.96, I2=32.26%) was higher than the other three continents (South American, Asia, and Africa). Further analysis showed that the effect estimate was higher for primary MDR-TB (OR=3.13, 95% CI= 1.59-6.13, I2=13.13%) with no heterogeneity among the studies. There was also a trend towards increased risk of MDR-TB for HIV patients of 40 years and older (OR=1.96, 95% CI= 1.41-2.73, I2=69.11%) and women HIV patients (OR=1.97, 95% CI 1.03-3.78, I2=80.35%). The MDR-TB is found to be significant in high burden of TB/HIV countries (OR=1.51, 95% CI= 1.18-1.92, I2=78.1%) and in high-income countries (OR=2.64, 95% CI= 2.01-3.48, I2=15.01%). Interpretation:The risk of MDR-TB increases significantly among HIV infected individuals from the last decade. The most considerable burden of MDR-TB in HIV individuals was found in Europe and the women HIV patients with age 40 years and older are most in the risk of MDR-TB. Funding Statement: The authors stated: There was a student seed fund for this study. The corresponding author had full access to all study data and the authorized person for the final submission of the paper for publication. Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: The protocol was registered with PROSPERO-CRD42019132752.

Finding New Ways to Combat Multidrug-Resistant Tuberculosis

Tuberculosis (TB) is a major issue in global health and affects millions of people each year. Multidrug-resistant tuberculosis (MDR-TB) annually causes many deaths worldwide. Development of a way to diagnose and treat patients with MDR-TB can potentially reduce the incidence of the disease. The current study reviews the risk factors, pattern of progression, mechanism of resistance, and interaction between bacteria and the host immune system, which disrupts the immune response. It also targets the components of Mycobacterium tuberculosis (Mtb) and diagnosis and treatment options that could be available for clinical use in the near future. Mutations play an important role in development of MDR-TB and the selection of appropriate mutations can help to understand the type of resistance in patients to anti-TB drugs. In this way, they can be initially treated with proper and effective therapeutic choices, which can accelerate the course of treatment and improve patient health. Targeting the components and enzymes of Mtb is necessary for understanding bacterial survival and finding a way to destroy the pathogen and allow patients to recover faster and prevent the spread of disease, especially resistant strains.

Use of nanotechnology for infectious disease diagnostics: application in drug resistant tuberculosis

BackgroundThe increased transmission of multidrug-resistant (MDR) tuberculosis (TB) poses a challenge to tuberculosis prevention and control in Sri Lanka. Isoniazid (INH) is a key element of the first line anti tuberculosis treatment regimen. Resistance to INH may lead to development of MDR TB. Therefore, early detection of INH resistance is important to curb spread of resistance. Due to the limited availability of rapid molecular methods for detection of drug resistance in Sri Lanka, this study was aimed at developing a simple and rapid gold nanoparticle (AuNP) based lateral flow strip for the simultaneous detection of the most common INH resistance mutation (katG S315 T, 78.6%) and Mycobacterium tuberculosis (MTb).MethodsLateral flow strip was designed on an inert plastic backing layer containing a sample pad, nitrocellulose membrane and an absorption pad. Biotin labeled 4 capture probes which separately conjugated with streptavidin were immobilized on the nitrocellulose. The test sample was prepared by multiplex PCR using primers to amplify codon 315 region of the katG gene and MTb specific IS6110 region. The two detection probes complementary to the 5′ end of each amplified fragment was conjugated with gold nanoparticles (20 nm) and coupled with the above amplified PCR products were applied on the sample pad. The hybridization of the amplified target regions to the respective capture probes takes place when the sample moves towards the absorption pad. Positive hybridization is indicated by red colour lines.ResultsThe three immobilized capture probes on the strip (for the detection of TB, katG wild type and mutation) were 100 and 96.6% specific and 100 and 92.1% sensitive respectively.ConclusionThe AuNP based lateral flow assay was capable of differentiating the specific mutation and the wild type along with MTb identification within 3 h.

RISK FACTORS FOR DEVELOPMENT OF MULTIDRUG-RESISTANT TUBERCULOSIS AMONG RELAPSED PATIENTS IN WEST PAPUA, INDONESIA: A DESCRIPTIVE AND ANALYTICAL STUDY

Objective: Indonesia has one of the highest burdens of multidrug-resistant tuberculosis (MDR-TB), with 6800 new cases of MDR-TB annually and a previously reported cure rate of 51%. This study aimed to identify the risk factors that affect the development of MDR-TB in the diverse population of West Papua.&#x0D; Methods: A case–control study was conducted in Sorong Regency Regional Hospital, a referral center for MDR-TB in West Papua. Data were obtained from medical records of patients with relapsed TB between January 2014 and September 2017. Extracted data included demographic characteristics, family history, medication history (type of medication and duration), smoking history, supporting examinations (sputum test for acid-fast bacilli [AFB] and radiologist interpretation of thoracic X-ray), and comorbidities (HIV and diabetes mellitus).&#x0D; Results: Among 549 patients with suspected MDR-TB, 45 were confirmed to have MDR-TB. These 45 patients were defined as the case group and compared with a control group of 45 relapsed patients who had drug-sensitive TB. A great number of subjects in both case and control groups (44.4% and 57.8%) were categorized as previously lost to follow-up. Bivariate analysis using the chi-squared test found that an AFB result of+3 (odds ratio [OR]: 5.33, 95% confidence interval [CI] 1.76–16.09), diabetes mellitus (OR: 6.14, 95% CI 1.26–29.89), and completion of intensive-phase category I anti-TB therapy (OR: 3.25, 95% CI 1.04–10.07) were associated with MDR-TB.&#x0D; Conclusion: These clinical variables provide initial information about MDR-TB in West Papua and will assist clinicians to manage patients in related populations who have these risk factors.

Factors contributing to development of multidrug resistant tuberculosis

Background: Several factors have been identified in the causation of multidrug-resistant tuberculosis (MDR-TB). The most important is previous inadequate treatment. Other factors include coinfection with HIV, diabetes mellitus, socioeconomically deprived groups, intravenous drug abusers, and other immunocompromised states. This study was planned to find out contributing/associated factors for the development of MDR-TB, specifically patients related factors. Aims and Objectives: The present study was conducted among MDR-TB patients to get the information regarding sociodemographic profile, present and history of TB, problems faced during treatment, and drug resistance pattern. Materials and Methods: A prospective, cross-sectional study was undertaken in a tertiary care teaching hospital. A total of 50 cases were included in the study who fulfilled inclusion criteria. All information was collected by studying the patients’ treatment record and by personal interview of each of the study participants using case record form. Results: Middle age groups (21–30 years and 31–40 years) were most commonly affected with MDR-TB. It was found that 44% of patients were smoker, 34% of patients were alcoholic, and 36% of patients were addicted to tobacco chewing, and 96% of patients have a body mass index below the normal range. Most of the patients were from lower socioeconomic status - Class V followed by class. Most of the patients (44) are of secondary MDR-TB and while only 6 patients are of primary MDR-TB.. Out of 44 secondary cases of MDR-TB total, 16 cases are due to not completion of the treatment, the reasons were poor adherence, adverse drug reactions, and substance abuse, etc., four patients were living with HIV/AIDS, and 3 patients were suffering from diabetes mellitus. Conclusion: There are causative factors and several risk factors associated with the development of MDR-TB has been found in the study. The strategy must be planned for incorporation of these factors in deciding treatment of MDR-TB.

Evaluation of Multi-Drug Resistant Tuberculosis Predictor Index in Surakarta, Central Java

Background : Tuberculosis (TB) remains a global public health problem. New cases of lung Tuberculosis in 2015 were 10.4 million worldwide. One of the challenging in TB control to be addressed is the development of Multi-Drug Resistant Tuberculosis (MDR-TB). There were an estimated 15,380 TB cases in Indonesia by 2015 with 1,860 positive TB cases and 1,566 cases successfully treated. This study aimed to determine the predictor index for MDR-TB. Subjects and Method : This was an analytic observational study with a case-control design. The study was conducted at Dr. Moewardi Hospital, Surakarta, Central Java, from August to November 2017. The study subjects were selected by fixed disease sampling including 75 MDR-TB patients and 75 TB patients. The dependent variable was MDR-TB. The independent variables were medical history, co-morbidity (Diabetes Mellitus), drug side effect, drug-taking supervisor, and regularity of treatment. The data were collected by questionnaire and medical record. The data were analyzed by a multiple logistic regression. Results : MDR-TB Occurrence Index increased with drug-taking supervisor (b = 2.33; 95% CI= 3.83 to 27.91; p<0.001), drug-side effect (b = 0.73; 95% CI= 0.58 to 7.45; p=0.026), medical history (b = 2.35; 95% CI= 3.80 to 29.38; p<0.001). MDR-TB Occurrence Index decreased by absence of type 2 Diabetes Mellitus (b = -0.56; 95% CI= 0.18 to 1.78; p= 0.033), regular treatment (b = -1.73; 95% CI= 0.06 to 0.46; p<0.001). Conclusion : MDR-TB Occurrence Index is determined by the drug-taking supervisor, drug side effect, medical history, Type 2 Diabetes Mellitus, and regular treatment. Keywords : MDR-TB Occurrence Index, medical history, drug-taking supervisor, drug side effect, Type 2 Diabetes Mellitus, regular treatment Correspondence:Â Putri Pamungkas. Masters Program in Public Health, Universitas Sebelas Maret. Jl. Ir. Sutami No. 36 A, 57126, Surakarta, Central Java. Email: pamungkasputri95@gmail.com. Journal of Epidemiology and Public Health (2018), 3(2): 263-276 https://doi.org/10.26911/jepublichealth.2018.03.02.06 Â

Genomic analysis of globally diverse Mycobacterium tuberculosis strains provides insights into the emergence and spread of multidrug resistance.

Multidrug-resistant tuberculosis (MDR-TB), caused by drug resistant strains of Mycobacterium tuberculosis, is an increasingly serious problem worldwide. In this study, we examined a dataset of 5,310 M. tuberculosis whole genome sequences from five continents. Despite great diversity with respect to geographic point of isolation, genetic background and drug resistance, patterns of drug resistance emergence were conserved globally. We have identified harbinger mutations that often precede MDR. In particular, the katG S315T mutation, conferring resistance to isoniazid, overwhelmingly arose before rifampicin resistance across all lineages, geographic regions, and time periods. Molecular diagnostics that include markers for rifampicin resistance alone will be insufficient to identify pre-MDR strains. Incorporating knowledge of pre-MDR polymorphisms, particularly katG S315, into molecular diagnostics will enable targeted treatment of patients with pre-MDR-TB to prevent further development of MDR-TB.

Risk Factors for the Development of multidrug-resistant tuberculosis in Colombia 2008 A 2011

Determining the risk factors associated with developing multidrug-resistant tuberculosis in people aged over 18 years affiliated to 3 Colombian health insurance companies between 2008 and 2011. The study involved a matched case-control design (1 case to 4 controls). Patients were identified from 3 health insurance companies' tuberculosis program database; this gave 45 cases and 180 controls. Demographic, socioeconomic and clinical variables were evaluated. The median age for cases was 43 years (39.5 years for controls); males predominated in cases (73.3 %) while women predominated in controls (51.1 %). A statistically significant association was found between multidrug-resistant tuberculosis and being male (4.47 adjusted OR; 1.01-19.75 95 %CI), having subsidized social security cover (57.6 adjusted OR; 4.6-71.28 95 %CI) and having had prior treatment for tuberculosis (56.2 adjusted OR; 10.03-314.79 95 % CI]. Prior treatment for tuberculosis and being male were risk factors for developing multidrug resistance. Further studies are needed with the Colombian health system to clarify the findings with respect to being affiliated to a subsidized health system and the development of multidrug resistant tuberculosis.

Double Trouble: Prevalence and Factors Associated with Tuberculosis and Diabetes Comorbidity in Bangladesh.

BackgroundDiabetes among tuberculosis patients increases the risk of tuberculosis treatment failure, death, and development of multidrug-resistant tuberculosis. Yet, there is no data is available in Bangladesh on the prevalence of diabetes among tuberculosis patients. The objective of the current study was to estimate prevalence and identify factors associated with tuberculosis-diabetes co-morbidity among TB patients enrolled in the Directly Observed Treatment, Short course program.MethodsA community based cross-sectional quantitative study was conducted among 1910 tuberculosis patients living in six urban and eleven rural areas among whom Oral Glucose Tolerance Test (those who fasted) and Random Blood Sugar test (those who did not fast) were performed. Besides glucose levels, data on socio-demographic information, family history of diabetes and anthropometric measurements (height and weight) were also collected.ResultAmong the 1910 TB patients who participated in screening for diabetes, 245 (12.8%) were found to have diabetes and 296 (15.5%) to have pre-diabetes. Out of those who had diabetes, 34.7% were newly diagnosed through the current study and 65.3% already knew their status. Among those who were found to have prediabetes, 27 (9.1%) had impaired Fasting Blood Glucose (FBG), 230 (77.7%) had Impaired Glucose Tolerance (IGT), and 39 (13.2%) had both Impaired FBG and IGT. Older age, higher BMI, higher education (secondary level and above), being married, participation in less active work, and family history of diabetes are associated with higher prevalence of diabetes.ConclusionWe observed a higher prevalence of diabetes and pre-diabetes in TB patients than reported previously in Bangladesh among the general population which may challenge TB and diabetes control in Bangladesh. Diabetes diagnosis, treatment and care should be integrated in the National TB Program.

More than half of presumptive multidrug-resistant cases referred to a tuberculosis referral laboratory in the Tigray region of Ethiopia are multidrug resistant

Objective/background: Generating epidemiological data on multidrug-resistant tuberculosis (MDR-TB) is essential to assess the magnitude and trends of anti-TB drug resistance. This study determined the prevalence of MDR-TB among presumptive MDR cases referred to a TB referral laboratory in the Tigray region of Ethiopia. Methods: A retrospective cross-sectional study was conducted on 262 culture-positive presumptive MDR-TB samples submitted to the Tigray Regional Research Laboratory for MDR testing between January 2013 and August 2014. Relevant data were recorded using a structured recording format. Results: Out of 262 Mycobacterium tuberculosis isolates, 143 (54.6%) were MDR, 28 (10.7%) were resistant to rifampicin only, and 19 (7.3%) were resistant to isoniazid only. The prevalence of MDR-TB among newly infected cases was 66.7% (8/12) and that among previously treated cases was 54.1% (97/179). Of the variables tested, being a male was found to be associated with the development of MDR-TB (p=.003). Conclusion: More than half of the presumptive MDR cases referred to the Tigray Regional Research Laboratory were MDR. The prevalence was high in both newly infected and previously treated cases. Hence, re-enforcing the TB prevention methods, and strengthening the directly observed treatment short-course (DOTS) strategy and the capacity of laboratories to undertake drug susceptibility testing (DST) in the region are imperative in order to curb the emergence and transmission of MDR-TB.

Multidrug resistant tuberculosis: Understanding the past for the better future

Introduction: Multidrug-resistant tuberculosis (MDR-TB) is an emerging public health problem. The study was done to evaluate the clinical profile of MDR TB patients and to study the diagnostic parameters in a cohort. Materials and Methods: All MDR-PTB patients admitted in a tertiary level TB institute for initiation of treatment for study period were enrolled. Various clinical parameters such as symptomatology profile, past treatment details, details of diagnosis, and methods of diagnosis were studied retrospectively in these patients. Results: A total of 125 patients were enrolled. An average age was 29.5 ± 12.2 years. The average duration of chest symptoms was 2.4 ± 0.6 years; cough and expectoration were the most common symptoms present in all (100%) the patients. Two patients were treatment naοve, and 123 were retreatment cases, in which, 63 were relapse, 42 were treatment after default, and 18 were failure cases, just prior to being diagnosed as MDR-TB. Forty-three patients have received at least one of the reserve line drugs as part of anti-TB treatment in past. The average courses of treatment taken prior to been labeled as MDR-TB were 3.15 times. Majority of patients (99) had been diagnosed by using molecular-based tests. Conclusion: Use of reserve line drugs is common for treatment of TB, even without being diagnosed as MDR-TB. Both physicians- and patient-related factors responsible for the development of MDR-TB may be prevented by improving understanding of the disease and by early and proper treatment of both drugs susceptible and drug resistant TB.

The association between sterilizing activity and drug distribution into tuberculosis lesions.

Finding new treatment-shortening antibiotics to improve cure rates and curb the alarming emergence of drug resistance is the major objective of tuberculosis (TB) drug development. Using a MALDI mass spectrometry imaging suite in a biosafety containment facility, we show that the key sterilizing drugs rifampicin and pyrazinamide efficiently penetrate the sites of TB infection in lung lesions. Rifampicin even accumulates in necrotic caseum, a critical lesion site where persisting tubercle bacilli reside1. In contrast, moxifloxacin which is active in vitro against persisters, a sub-population of Mycobacterium tuberculosis that persists in specific niches under drug pressure, and achieved treatment shortening in mice2, does not diffuse well in caseum, concordant with its failure to shorten therapy in recent clinical trials. We also suggest that such differential spatial distribution and kinetics of accumulation in lesions may create temporal and spatial windows of monotherapy in specific niches, allowing the gradual development of multidrug resistant TB. We propose an alternative working model to prioritize new antibiotic regimens based on quantitative and spatial distribution of TB drugs in the major lesion types found in human lungs. The finding that lesion penetration contributes to treatment outcome has wide implications for TB.

Association between Multidrug-Resistant Tuberculosis and Risk Factors in China: Applying Partial Least Squares Path Modeling.

BackgroundMultidrug-resistant tuberculosis (MDR-TB) resulting from various factors has raised serious public health concerns worldwide. Identifying the ecological risk factors associated with MDR-TB is critical to its prevention and control. This study aimed to explore the association between the development of MDR-TB and the risk factors at the group-level (ecological risk factors) in China.MethodsData on MDR-TB in 120 counties were obtained from the National Tuberculosis Information Management System, and data on risk-factor variables were extracted from the Health Statistical Yearbook, provincial databases, and the meteorological bureau of each province (municipality). Partial Least Square Path Modeling was used to detect the associations.ResultsThe median proportion of MDR-TB in new TB cases was 3.96% (range, 0–39.39%). Six latent factors were extracted from the ecological risk factors, which explained 27.60% of the total variance overall in the prevalence of MDR-TB. Based on the results of PLS-PM, TB prevention, health resources, health services, TB treatment, TB detection, geography and climate factors were all associated with the risk of MDR-TB, but socioeconomic factors were not significant.ConclusionsThe development of MDR-TB was influenced by TB prevention, health resources, health services, TB treatment, TB detection, geography and climate factors. Such information may help us to establish appropriate public health intervention strategies to prevent and control MDR-TB and yield benefits to the entire public health system in China.