Risk Of Multidrug-resistant Tuberculosis Research Articles

High incidence of drug-resistant Mycobacterium tuberculosis in Hainan Island, China.

To assess the proportion of drug-resistant tuberculosis (TB) cases and to identify independent risk factors associated with drug-resistant TB in Hainan. Descriptive analysis of demographic and clinical data of culture-positive TB patients to assess the trends in drug-resistant TB at the Provincial Clinical Center on Tuberculosis of Hainan between 2014 and 2017. 994 patients were recruited into the study. Overall, the proportion of patients resistant to at least one TB drug tested was 36.1% (359/994). The most frequent resistance was to isoniazid (INH, 29.8%), followed by rifampin (RIF, 29.3%), streptomycin (19.3%), ofloxacin (OFX, 17.4%), ethambutol (9.5%) and kanamycin (KAN, 3.2%). Of 291 RIF-resistant isolates, 228 (78.4%) were also resistant to INH, while the remaining 63 (21.6%) were susceptible to INH. Among those with multidrug-resistant tuberculosis (MDR-TB), 41.2% had additional resistance to OFX and 3.9% to KAN. 8.8% of MDR-TB patients were affected by extensively drug-resistant (XDR-TB). Females were more likely to infected with MDR-TB than males, and young people (<20years old) were more likely to have MDR-TB; patients exhibited decreasing MDR-TB risk with increasing age. Our data provide the first primary understanding of the drug-resistant TB epidemic in Hainan. The high incidence of drug resistance, especially RIF and FQ resistance, highlight the importance of interventions for preventing epidemics of drug-resistant TB. Younger age is an independent predictor of MDR-TB, reflecting the potential transmission in this population.

Plasma indoleamine 2,3-dioxygenase activity as a potential biomarker for early diagnosis of multidrug-resistant tuberculosis in tuberculosis patients.

Purpose: Multidrug-resistant tuberculosis (MDR-TB) remains a challenge of global TB control, with difficulty in early detection of drug-sensitive tuberculosis (DS-TB). We investigate the diagnostic significance of IDO as a potential biomarker to discriminate MDR patients among the TB patients.Patients and methods: Plasma indoleamine 2,3-dioxygenase (IDO) was measured by the ratio of kynurenine (Kyn) to tryptophan (Trp) concentrations, using high performance liquid chromatography-mass spectrometry (LC-MS/MS). Chest computed tomography (CT) imaging signs from TB patients were collected and analyzed in 18 DS-TB patients, 16 MDR-TB patients, 6 lung cancer (LC) patients, and 11 healthy individuals. Lung imaging signs from TB patients were collected and analyzed.Results: We found that plasma IDO activity was significantly higher in the MDR-TB patients than in the DS-TB patients (p=0.012) and in the LC patients (p=0.003). We evaluated the diagnostic significance of plasma IDO activity in discriminating the MDR-TB group from the DS-TB group using a receiver operating characteristic (ROC) curve. With a cutoff level of 46.58 uM/mM, the diagnostic sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for IDO activity were 87.50%, 72.22%, 73.68%, and 86.67%, respectively. Plasma IDO activity was higher in cavity cases than in non-cavity cases (p=0.042), proving a positive correlation between lung cavity number and cavity size (p<0.05, separately) among all the TB patients studied.Conclusion: Our findings confirmed that plasma IDO activity might have an auxiliary diagnosis value for early discrimination of MDR-TB patients from DS-TB patients. Among the TB patients with cavitary lung lesions, higher plasma IDO activity can indicate a higher risk of MDR-TB.

Respiratory tuberculosis incidence and mortality in Estonia: 30-year trends and sociodemographic determinants.

To explore time trends in the incidence and mortality of respiratory tuberculosis (TB) over a 30-year period in Estonia, and to evaluate disease disparities according to sex, age, ethnicity and education. Data from the TB Register and the Causes of Death Register were used to assess time trends in age-standardised incidence and mortality rates. The effect of sociodemographic characteristics on TB risk was modelled using Poisson regression around three population censuses. Respiratory TB incidence and mortality decreased in males and were stable in females in 1987-1991, after which the rates increased sharply in both sexes until 1998 and decreased steadily afterwards. Multidrug-resistant TB (MDR-TB) incidence rose in males until 1998 and in females until 2002, and then started to fall. The incidence of TB and human immunodeficiency virus (HIV) coinfection in males increased until 2007 and decreased thereafter. Less educated people and non-Estonians had a significantly higher relative risk of respiratory TB. Estonia, one of the countries most affected by TB in the World Health Organization European Region, has made considerable progress in reducing the risk of respiratory TB, TB-HIV and MDR-TB. Continuing education- and ethnicity-related disparities in TB risk remain a concern.

Investigating spillover of multidrug-resistant tuberculosis from a prison: a spatial and molecular epidemiological analysis

BackgroundCongregate settings may serve as institutional amplifiers of tuberculosis (TB) and multidrug-resistant tuberculosis (MDR-TB). We analyze spatial, epidemiological, and pathogen genetic data prospectively collected from neighborhoods surrounding a prison in Lima, Peru, where inmates experience a high risk of MDR-TB, to investigate the risk of spillover into the surrounding community.MethodsUsing hierarchical Bayesian statistical modeling, we address three questions regarding the MDR-TB risk: (i) Does the excess risk observed among prisoners also extend outside the prison? (ii) If so, what is the magnitude, shape, and spatial range of this spillover effect? (iii) Is there evidence of additional transmission across the region?ResultsThe region of spillover risk extends for 5.47 km outside of the prison (95% credible interval: 1.38, 9.63 km). Within this spillover region, we find that nine of the 467 non-inmate patients (35 with MDR-TB) have MDR-TB strains that are genetic matches to strains collected from current inmates with MDR-TB, compared to seven out of 1080 patients (89 with MDR-TB) outside the spillover region (p values: 0.022 and 0.008). We also identify eight spatially aggregated genetic clusters of MDR-TB, four within the spillover region, consistent with local transmission among individuals living close to the prison.ConclusionsWe demonstrate a clear prison spillover effect in this population, which suggests that interventions in the prison may have benefits that extend to the surrounding community.

Identification of Risk Factors of Multidrug-Resistant Tuberculosis by using Classification Tree Method

Multidrug-resistant tuberculosis (MDR-TB) has become a major public health problem. We tried to apply the classification tree model in building and evaluating a risk prediction model for MDR-TB. In this case-control study, 74 newly diagnosed MDR-TB patients served as the case group, and 95 patients without TB from the same medical institution served as the control group. The classification tree model was built using Chi-square Automatic Interaction Detectormethod and evaluated by income diagram, index map, risk statistic, and the area under receiver operating characteristic (ROC) curve. Four explanatory variables (history of exposure to TB patients, family with financial difficulties, history of other chronic respiratory diseases, and history of smoking) were included in the prediction model. The risk statistic of misclassification probability of the model was 0.160, and the area under ROC curve was 0.838 (P < 0.01). These suggest that the classification tree model works well for predicting MDR-TB. Classification tree model can not only predict the risk of MDR-TB effectively but also can reveal the interactions among variables.

Multidrug-resistant Tuberculosis Burden among the New Tuberculosis Patients in Zhejiang Province: An Observational Study, 2009-2013.

Background:Screening on multidrug-resistant tuberculosis (MDR-TB) has been limited to the serious TB subpopulations excluding the new TB patients. This study aimed to examine MDR-TB burden among the new TB patients.Methods:We conducted a study in Zhejiang Province during 2009–2013 to screen for MDR-TB patients among the low MDR-TB risk patients and five subpopulations of high MDR-TB risk patients. The number, prevalence, and trend of MDR-TB were compared while the logistic regression model was used to examine risk factors related to MDR-TB.Results:A total of 200 and 791 MDR-TB cases were, respectively, identified from the 9830 new TB cases and 2372 high-risk suspects who took MDR-TB screening from 2009 to 2013. The MDR-TB rates went down in both of the new TB patients and five MDR-TB high-risk groups over the study time, but the percentage of MDR-TB patients identified from the new TB patients in all diagnosed MDR-TB cases kept stable from 28.3% in 2011 to 27.0% in 2012 to 26.0% in 2013.Conclusions:The study indicated that MDR-TB burden among new TB patients was high, thus screening for MDR-TB among the new TB patients should be recommended in China as well as in the similar situation worldwide.

Neural network models for supporting drug and multidrug resistant tuberculosis screening diagnosis

Tuberculosis (TB) is the leading cause of global mortality among communicable diseases. The diagnosis of Drug-Resistant Tuberculosis (DR-TB) demands even more attention, leading to longer treatments and higher deceased rates. All diagnostic methods available have deficiencies in their detection rates, time release results, or have a higher cost and need a complex infrastructure to setup. New molecular diagnostics, such as the Xpert MTB/RIF assay, have great potential for revolutionizing the diagnosis of Rifampicin Resistance (RR). But, a positive RR result with this test should be carefully interpreted and take into consideration the risk of Multidrug-Resistant TB (MDR-TB) according to its prevalence, locally. Therefore, the development of screening approaches for DR/MDR-TB suspects would help to identify those should be tested by Xpert MTB/RIF. This work develops Artificial Neural Network (ANN) models considering data from presumed DR/MDR-TB subjects according to the National Guidelines at Rio de Janeiro/Brazil, attended in reference centers in Rio de Janeiro, from Feb 2011 and May 2013. Subjects aged 18 years or older, and results were compared with models based on Classification And Regression Trees (CART). Practical operation at different epidemiological scenarios are considered by constructing models using different variable selection criteria, so that environments with low resource conditions can be assisted. Among 280 presumed DR-TB cases included, 38 were DR-TB, 48-MDR, 32-Drug-Sensitive and 162 with no TB. Between DR-TB and non DR-TB, the sensitivity and specificity reached 95.1%(±5.0) and 85.0%(±4.9), respectively. The promising results of clinical score for DR/MDR-TB diagnosis indicate that this approach may be used in the evaluation of presumed DR/MDR-TB.

Health Belief Model and PRECEDE PROCEED on the Risk Factors of Multidrug Resistant Tuberculosis in Surakarta, Central Java

Background : Tuberculosis (TB) is one of the lethal infectious diseases in the world. One of the current biggest challenges of Tuberculosis control is the widespread emergence of Multidrug Resistant Tuberculosis (MDR-TB). There are several potential risk factors of MDR-TB that can be explained by Health Belief Model and PRECEDE PROCEED model framework. This study aimed to analyzed factors associated with MDR-TB using Health Belief Model and PRECEDE PROCEED. Subjects and Method : This was an analytic observational study with case control design. The study was conducted at Dr. Moewardi Hospital and BBKPM, Surakarta, from September to November 2017. The study subjects were selected using fixed disease sampling, consisting of 76 MDR-TB patients and 228 TB patients. The dependent variable was MDR-TB. The independent variables were educational level, self-efficacy, drug-taking adherence, smoking, nutritional status, perceived of susceptibility, perceived barrier, perceived severity, perceived benefit, and drug-taking supervisor. The data were collected using questionnaire and analyzed by path analysis. Results : The risk of MDR-TB was increased by lack of drug-taking adherence (b= -1.69; 95% CI= -2.28 to -1.09; p <0.001), poor nutritional status (b= 1.32; 95% CI= 0.72 to 1.92; p<0.001), and smoking (b= 1.32; 95% CI= 0.72 to 1.92; p <0.001). Drug-taking adherence was increased by perceived susceptibility  (b= 0.91; 95% CI= 0.18 to 1.63; p=0.015), perceived severity  (b= 1.01; 95% CI=  0.28 to 1.74; p=0.007), perceived benefit (b= 1.69; 95% CI= 0.97 to 2.41; p<0.001), drug-taking advisor (b= 2.16; 95% CI= 1.44 to 2.88; p<0.001), self efficacy (b= 1.58; 95% CI= 0.86 to 2.31; p<0.001), and low perceived barrier (b= -1.10; 95% CI= -1.82 to -0.38; p=0.003). Conclusion : The risk of MDR-TB is increased by the lack of drug-taking adherence, poor nutritional status, and smoking. Keyword : Health belief model, PRECEDE-PROCEED, MDR-TB Correspondence: Vera. Masters Program in Public Health, Sebelas Maret University, Jl. Ir. Sutami 36 A, Surakarta 57126, Central Java. Email: vera21210@gmail.com Journal of Epidemiology and Public Health (2017), 2(3): 241-254 https://doi.org/10.26911/jepublichealth.2017.02.03.06

Sputum bacterial load predicts multidrug-resistant tuberculosis in retreatment patients: a case-control study.

Rapid and effective diagnosis of multidrug-resistant tuberculosis (MDR-TB) is an essential component of global tuberculosis (TB) control, but most MDR-TB cases are still not diagnosed. To assess whether patient sputum bacterial load can be used to identify patients at increased risk of MDR-TB. We used a case-control study and multivariable logistic regression models to investigate associations between MDR-TB and sputum bacterial load, as measured by semi-quantitative microscopy and automated time to detection (TTD) of liquid culture. We assessed data from retreatment TB patients with MDR-TB (cases) and from those without MDR-TB (controls) at a reference laboratory in Cameroon. MDR-TB was associated with a smear microscopy grade of 3+ (OR 21.9, 95%CI 6.2-76.8) or 2+ (OR 10.8, 95%CI 2.9-40.7), compared to a result of 1+, scanty or smear-negative among 80 MDR-TB cases and 521 controls. MDR-TB was associated with automated TTD of ⩿160 h (OR 2.2, 95%CI 1.1-4.7) compared to >160 h among a subpopulation of 47 cases and 350 controls. A higher sputum bacterial load is associated with MDR-TB in retreatment patients in Cameroon.

Diabetes Reduces the Rate of Sputum Culture Conversion in Patients With Newly Diagnosed Multidrug-Resistant Tuberculosis.

Background. Diabetes is a risk factor for active tuberculosis (TB), but little is known about the relationship between diabetes and multidrug-resistant (MDR) TB. We aimed to assess risk factors for primary MDR TB, including diabetes, and determine whether diabetes reduced the rate of sputum culture conversion among patients with MDR TB. Methods. From 2011 to 2014, we conducted a cohort study at the National Center for Tuberculosis and Lung Diseases in Tbilisi, Georgia. Adult (≥35 years) patients with primary TB were eligible. Multidrug-resistant TB was defined as resistance to at least rifampicin and isoniazid. Patients with capillary glycosylated hemoglobin (HbA1c) ≥ 6.5% or previous diagnosis were defined to have diabetes. Polytomous regression was used to estimate the association of patient characteristics with drug resistance. Cox regression was used to compare rates of sputum culture conversion in patients with and without diabetes. Results. Among 318 patients with TB, 268 had drug-susceptibility test (DST) results. Among patients with DST results, 19.4% (52 of 268) had primary MDR TB and 13.4% (36 of 268) had diabetes. In multivariable analyses, diabetes (adjusted odds ratio [aOR], 2.51; 95% confidence interval [CI], 1.00-6.31) and lower socioeconomic status (aOR, 3.51; 95% CI, 1.56-8.20) were associated with primary MDR TB. Among patients with primary MDR TB, 44 (84.6%) converted sputum cultures to negative. The rate of sputum culture conversion was lower among patients with diabetes (adjusted hazard ratio [aHR], 0.34; 95% CI, .13-.87) and among smokers (aHR, 0.16; 95% CI, .04-.61). Conclusions. We found diabetes was associated with an increased risk of primary MDR TB; both diabetes and smoking were associated with a longer time to sputum culture conversion.

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

ObjectiveTo investigate the prevalence of primary drug-resistant tuberculosis (TB) and associated risk factors in China. We also explored factors contributing to the transmission of multidrug-resistant tuberculosis (MDR-TB). MethodsA total of 2794 representative, Mycobacterium tuberculosis isolates from treatment-naive patients were subjected to drug susceptibility testing, and risk factors for drug-resistant TB were analyzed. We also analyzed MDR-TB strain sublineages, drug-resistance-conferring mutations, and risk factors associated with clustered primary MDR strains. ResultsAmong 2794 Mycobacterium tuberculosis isolates from treatment-naive patients, the prevalence of any resistance to first-line drugs was 33.2% and the prevalence of MDR-TB was 5.7%. We did not find any risk factors significantly associated with resistance to first-line drugs. The 93 primary MDR-TB isolates were classified into six sublineages, of which, 75 (80.6%) isolates were the RD105-deleted Beijing lineage. The largest sublineage included 65 (69.9%) isolates with concurrent deletions of RD105, RD207, and RD181. Twenty-nine (31.2%) primary MDR strains grouped in clusters; MDR isolates in clusters were more likely to have S531L rpoB mutation. ConclusionThis study indicates that primary drug-resistant TB and MDR-TB strains are prevalent in China, and multiple measures should be taken to address drug-resistant TB.

Pathways to multidrug-resistant tuberculosis diagnosis and treatment initiation: a qualitative comparison of patients' experiences in the era of rapid molecular diagnostic tests.

BackgroundAlthough new molecular diagnostic tests such as GenoType MTBDRplus and Xpert® MTB/RIF have reduced multidrug-resistant tuberculosis (MDR-TB) treatment initiation times, patients’ experiences of diagnosis and treatment initiation are not known. This study aimed to explore and compare MDR-TB patients’ experiences of their diagnostic and treatment initiation pathway in GenoType MTBDRplus and Xpert® MTB/RIF-based diagnostic algorithms.MethodsThe study was undertaken in Cape Town, South Africa where primary health-care services provided free TB diagnosis and treatment. A smear, culture and GenoType MTBDRplus diagnostic algorithm was used in 2010, with Xpert® MTB/RIF phased in from 2011–2013. Participants diagnosed in each algorithm at four facilities were purposively sampled, stratifying by age, gender and MDR-TB risk profiles. We conducted in-depth qualitative interviews using a semi-structured interview guide. Through constant comparative analysis we induced common and divergent themes related to symptom recognition, health-care access, testing for MDR-TB and treatment initiation within and between groups. Data were triangulated with clinical information and health visit data from a structured questionnaire.ResultsWe identified both enablers and barriers to early MDR-TB diagnosis and treatment. Half the patients had previously been treated for TB; most recognised recurring symptoms and reported early health-seeking. Those who attributed symptoms to other causes delayed health-seeking. Perceptions of poor public sector services were prevalent and may have contributed both to deferred health-seeking and to patient’s use of the private sector, contributing to delays. However, once on treatment, most patients expressed satisfaction with public sector care. Two patients in the Xpert® MTB/RIF-based algorithm exemplified its potential to reduce delays, commencing MDR-TB treatment within a week of their first health contact. However, most patients in both algorithms experienced substantial delays. Avoidable health system delays resulted from providers not testing for TB at initial health contact, non-adherence to testing algorithms, results not being available and failure to promptly recall patients with positive results.ConclusionWhilst the introduction of rapid tests such as Xpert® MTB/RIF can expedite MDR-TB diagnosis and treatment initiation, the full benefits are unlikely to be realised without reducing delays in health-seeking and addressing the structural barriers present in the health-care system.

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.

The impact of isoniazid resistant Mycobacterium tuberculosis on the epidemic of multi-drug resistant tuberculosis

Objective To investigate the impact of isoniazid (INH)-resistant Mycobacterium tuberculosis (Mtb) on the prevalence and dissemination of multi-drug resistant tuberculosis (MDR-TB). Methods A total of 251 patients diagnosed with tuberculosis in designated hospitals of Guanyun, Jiangsu and Deqing, Zhejiang from 2010 to 2011 were included in the study. The drug susceptibility tests (DST) were performed on all the Mtb isolates available from the sputum cultures. Mycobacteral interspersed repetitive units-variable number tandem repeats (MIRU-VNTR) was conducted for genotyping for all available Mtb isolates. Chi-square test, Fisher exact test, ANOVA and non-conditional Logistic regression modelling were applied for data analysis. Results Among 251 patients with Mtb isolates and DST results available, 72(28.7%) were resistant to INH, including 13 were INH mono-drug resistant. Of the remaining 59 INH-resistant Mtb, 34(13.5%) were resistant to rifampin TB and 25 were resistant to streptomycin and/or ethambutol. The clustering analysis based on MIRU-VNTR genotyping revealed 29 clustered genotypes (including 105 isolates) and 146 unique genotypes (including 119 isolates). Twenty-five clusters contained drug resistant Mtb and 16 clusters of them comprised by 37 INH-resistant isolates and 20 MDR-TB isolates, which accounted for 51.4% of the INH-resistant isolates and 58.8% of the MDR-TB isolates. Single factor analysis showed that sex, age, previous tuberculosis treatment history and sputum smear results were all related to INH-resistant tuberculosis and MDR-TB (all P<0.05). Multiple factors analysis showed that previous tuberculosis treatment history was risk factor of MDR-TB (OR=8.40, 95%CI: 3.342-21.105), while the risk factors of INH-resistant tuberculosis were previous tuberculosis treatment history (OR=3.52, 95%CI: 1.570-7.910), pulmonary caviry (OR=2.27, 95%CI: 1.075-4.799) and sputum smear results (OR=0.50, 95%CI: 0.275-0.892). Conclusions That INH-resistant strain may evolve to the MDR-TB after recent transmission is a possible trend. Patients with previous treatment history and advanced age are at high risk of INH-resistant tuberculosis and MDR-TB. Key words: Mycobacterium tuberculosis; Isoniazid; Tuberculosis, multidrug-resistant

Experiences in anti-tuberculosis treatment in patients with multiple previous treatments and its impact on drug resistant tuberculosis epidemics

BackgroundTuberculosis (TB) patients with a history of multiple anti-TB treatments are the ‘neglected’ group to the free anti-TB treatment policy in China.ObjectiveTo understand the experiences of TB patients with multiple previous treatments with regard to bacteriological diagnosis and treatment regimens, especially for second-line anti-TB drugs, and how this might influence the risks of multidrug and extensively drug-resistant TB (M/XDR-TB).DesignA cross-sectional study was conducted in 10 county/district TB clinics in five provinces of China. The study participants were TB patients that had at least two previous treatment episodes that lasted longer than 1 month each. Face-to-face interviews and drug susceptibility testing (DST) were conducted with the consenting participants.ResultsA total of 328 TB patients were recruited. The proportion of multidrug-resistant tuberculosis (MDR-TB) was 58.2% in the 287 DST-confirmed patients. Forty-two percent of the patients did not complete their first treatment course. About 23.8% of the participants had a history of taking second-line drugs, and more than 77.8% of them were treated in county TB dispensaries where only sputum microscopy was applied. Multivariate analysis found that the use of second-line drugs was significantly associated with frequency of previous treatments (p<0.01), but not with drug resistance profiles of patients.ConclusionsPatients with multiple previous treatments are at extremely high risk of MDR-TB in China. The unregulated use of second-line drugs bring about the threat of XDR-TB epidemic. DST-guided treatment and strict regulations of anti-TB treatment should be assured for the high-risk TB patients for the prevention and control of M/XDR-TB.

Reducing communication delays and improving quality of care with a tuberculosis laboratory information system in resource poor environments: a cluster randomized controlled trial.

BackgroundLost, delayed or incorrect laboratory results are associated with delays in initiating treatment. Delays in treatment for Multi-Drug Resistant Tuberculosis (MDR-TB) can worsen patient outcomes and increase transmission. The objective of this study was to evaluate the impact of a laboratory information system in reducing delays and the time for MDR-TB patients to culture convert (stop transmitting).MethodsSetting: 78 primary Health Centers (HCs) in Lima, Peru. Participants lived within the catchment area of participating HCs and had at least one MDR-TB risk factor. The study design was a cluster randomized controlled trial with baseline data. The intervention was the e-Chasqui web-based laboratory information system. Main outcome measures were: times to communicate a result; to start or change a patient's treatment; and for that patient to culture convert.Results1671 patients were enrolled. Intervention HCs took significantly less time to receive drug susceptibility test (DST) (median 11 vs. 17 days, Hazard Ratio 0.67 [0.62–0.72]) and culture (5 vs. 8 days, 0.68 [0.65–0.72]) results. The time to treatment was not significantly different, but patients in intervention HCs took 16 days (20%) less time to culture convert (p = 0.047).ConclusionsThe eChasqui system reduced the time to communicate results between laboratories and HCs and time to culture conversion. It is now used in over 259 HCs covering 4.1 million people. This is the first randomized controlled trial of a laboratory information system in a developing country for any disease and the only study worldwide to show clinical impact of such a system.Trial RegistrationClinicalTrials.gov NCT01201941

The development of dimple-shaped chitosan carrier for ethambutol dihydrochloride dry powder inhaler

Objective: In this study, a dimple-shaped chitosan carrier was developed for delivering the antituberculosis drug ethambutol dihydrochloride (EDH) from a dry powder inhaler (DPI) to the lungs.Materials and methods: Nanosized drug particles were prepared using nanospray drying. The microsized carrier was developed from a chitosan solution by spray drying. Five formulations were prepared by physically mixing the drug and carrier in different ratios. The physico-chemical properties of the formulations were analyzed using scanning electron microscopy, differential scanning calorimetry, Fourier transform infrared spectroscopy, ultracentrifugation and a cascade impactor.Result and discussion: The EDH size was 222 nm and the chitosan carrier size was 1.2 µm. Five formulations, i.e. 1:2, 1:2.5, 1:3.3, 1:5 and 1:10 w/w of the EDH to chitosan carrier were prepared by physical mixing. The chitosan carrier was spherical in shape with a dimpled surface and this provided shallow cavities to which the drug was bound, both within its grooves as well as on its surface. The median adhesion force (50% of drug detachment) for formulations #1 to #5 was between 122 and 993 µN. The mass median aerodynamic diameter of the EDH was between 2.3 and 2.7 μm, with the fine particle fractions (aerosolized particles less than 4.4 μm) of 32–42% of the nominal dose.Conclusion: We suggest that ethambutol dihydrochloride mixed with a chitosan carrier was suitable for use in a dry powder inhaler for controlling tuberculosis especially in minimizing the risk of multidrug resistant tuberculosis and the possible side effects from EDH.

High risk and rapid appearance of multidrug resistance during tuberculosis treatment in Moldova.

Multidrug-resistant tuberculosis (MDR-TB) is a serious problem in the former Soviet Union and may appear during TB treatment. We aimed to estimate the prevalence of, timing of and factors associated with MDR-TB diagnosis during TB treatment in Moldova, which was part of the former Soviet Union. We analysed data on 3 754 confirmed non-MDR-TB cases (between January 1, 2007 and December 31, 2010) in the Moldovan TB surveillance database, where patients provided sputum specimens for drug-susceptibility testing, multiple times, during treatment. We estimated the percentage of individuals with confirmed baseline non-MDR-TB that were diagnosed with MDR-TB during treatment, documented the time at which MDR-TB was diagnosed, and used a failure-time model to identify factors associated with MDR-TB diagnosis. Between 7.2% and 9.2% of initially non-MDR-TB cases were diagnosed with MDR-TB during treatment. Half of these MDR-TB diagnoses occurred with 3 months of the initial diagnosis. An increased MDR-TB risk during treatment was associated with baseline resistance to first-line TB drugs (linear increase in risk per additional drug), previous incarceration and HIV co-infection. MDR can appear rapidly during TB treatment. Policy considerations should emphasise management during early treatment by increasing ambulatory TB treatment to prevent nosocomial transmission, and ensuring universal rapid diagnostics access to prevent acquisition and transmission of drug resistance.

Association between HIV/AIDS and multi-drug resistance tuberculosis: a systematic review and meta-analysis.

BackgroundHuman immunodeficiency virus (HIV), multi-drug resistant tuberculosis (MDR) is emerging as major challenge facing tuberculosis control programs worldwide particularly in Asia and Africa. Findings from different studies on associations of HIV co-infection and drug resistance among patients with TB have been contradictory (discordant). Some institution based studies found strongly increased risks for multi-drug resistant TB (MDR TB) among patients co-infected with TB and HIV, whereas other studies found no increased risk (it remains less clear in community based studies. The aim was to conduct a systematic review and meta-analysis of the association between multi-drug resistant tuberculosis and HIV infection.Methods and findingsSystematic review of the published literature of observational studies was conducted. Original studies were identified using databases of Medline/Pubmed, Google Scholar and HINARI. The descriptions of original studies were made using frequency and forest plot. Publication bias was assessed using Funnel plot graphically and Egger weighted and Begg rank regression tests statistically. Heterogeneity across studies was checked using Cochrane Q test statistic and I2. Pool risk estimates of MDR-TB and sub-grouping analysis were computed to analyze associations with HIV. Random effects of the meta-analysis of all 24 observational studies showed that HIV is associated with a marginal increased risk of multi-drug resistant tuberculosis (estimated Pooled OR 1.24; 95%, 1.04–1.43). Subgroup analyses showed that effect estimates were higher (Pooled OR 2.28; 95%, 1.52–3.04) for primary multi-drug resistance tuberculosis and moderate association between HIV/AIDS and MDR-TB among population based studies and no significant association in institution settings.ConclusionsThis study demonstrated that there is association between MDR-TB and HIV. Capacity for diagnosis of MDR-TB and initiating and scale up of antiretroviral treatment, and collaborations between HIV and TB control programs need to be considered and strengthened.

Assessing spatial heterogeneity of multidrug-resistant tuberculosis in a high-burden country

Multidrug-resistant tuberculosis (MDR-TB) is a major concern in countries of the former Soviet Union. The reported risk of resistance among tuberculosis (TB) cases in the Republic of Moldova is among the highest in the world. We aimed to produce high-resolution spatial maps of MDR-TB risk and burden in this setting. We analysed national TB surveillance data collected between 2007 and 2010 in Moldova. High drug susceptibility testing coverage and detailed location data permitted identification of subregional areas of higher MDR-TB risk. We investigated whether the distribution of cases with MDR-TB risk factors could explain this observed spatial variation in MDR-TB. 3447 MDR-TB cases were notified during this period; 24% of new and 62% of previously treated patients had MDR-TB. Nationally, the estimated annual MDR-TB incidence was 54 cases per 100 000 persons and >1000 cases per 100 000 persons within penitentiaries. We identified substantial geographical variation in MDR-TB burden and hotspots of MDR-TB. Locations with a higher percentage of previously incarcerated TB cases were at greater risk of being MDR-TB hotspots. Spatial analyses revealed striking geographical heterogeneity of MDR-TB. Methods to identify locations of high MDR-TB risk and burden should allow for better resource allocation and more appropriate targeting of studies to understand local mechanisms driving resistance.