Incidence Of Multidrug-resistant Tuberculosis Research Articles

Interdisciplinary Treatment of Patients with Pulmonary Tuberculosis

Today surgical procedures for pulmonary tuberculosis are highly selective but owing to the increasing incidence of multidrug resistant tuberculosis has been becoming more and more relevant. Besides the treatment of tuberculosis foci in multidrug resistance tuberculosis to eliminate the source of relapse, complications as sequelae of tuberculosis are among the most frequent indications for surgery. In patients with cavernous lesions, destroyed lobe or lung, bronchiectasis, pleural empyema or hemoptysis thoracic surgical procedures may be warranted. However, in solitary pulmonary nodules operations with diagnostic purpose are necessary, not only to rule out a potential malignancy, but also to identify a so far unidentified tuberculoma. Considering the heterogenous group of patients with tuberculosis, surgical morbidity and mortality are in the known range for surgical resections in lung cancer patients.

Estimating the future burden of multidrug-resistant and extensively drug-resistant tuberculosis in India, the Philippines, Russia, and South Africa: a mathematical modelling study

Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis are emerging worldwide. The Green Light Committee initiative supported programmatic management of drug-resistant tuberculosis in 90 countries. We used estimates from the Preserving Effective TB Treatment Study to predict MDR and XDR tuberculosis trends in four countries with a high burden of MDR tuberculosis: India, the Philippines, Russia, and South Africa. We calibrated a compartmental model to data from drug resistance surveys and WHO tuberculosis reports to forecast estimates of incident MDR and XDR tuberculosis and the percentage of incident MDR and XDR tuberculosis caused by acquired drug resistance, assuming no fitness cost of resistance from 2000 to 2040 in India, the Philippines, Russia, and South Africa. The model forecasted the percentage of MDR tuberculosis among incident cases of tuberculosis to increase, reaching 12·4% (95% prediction interval 9·4-16·2) in India, 8·9% (4·5-11·7) in the Philippines, 32·5% (27·0-35·8) in Russia, and 5·7% (3·0-7·6) in South Africa in 2040. It also predicted the percentage of XDR tuberculosis among incident MDR tuberculosis to increase, reaching 8·9% (95% prediction interval 5·1-12·9) in India, 9·0% (4·0-14·7) in the Philippines, 9·0% (4·8-14·2) in Russia, and 8·5% (2·5-14·7) in South Africa in 2040. Acquired drug resistance would cause less than 30% of incident MDR tuberculosis during 2000-40. Acquired drug resistance caused 80% of incident XDR tuberculosis in 2000, but this estimate would decrease to less than 50% by 2040. MDR and XDR tuberculosis were forecast to increase in all four countries despite improvements in acquired drug resistance shown by the Green Light Committee-supported programmatic management of drug-resistant tuberculosis. Additional control efforts beyond improving acquired drug resistance rates are needed to stop the spread of MDR and XDR tuberculosis in countries with a high burden of MDR tuberculosis. US Agency for International Development and US Centers for Disease Control and Prevention, Division of Tuberculosis Elimination.

First Insight Into the Fluoroquinolone and Aminoglycoside Resistance of Multidrug-Resistant Mycobacterium tuberculosis in Saudi Arabia.

AbstractIn Saudi Arabia, there were no nationwide screening studies conducted so far to determine the aminoglycoside and fluoroquinolone resistance among multidrug-resistant tuberculosis (MDR-TB) isolates. Therefore, as the first attempt in the country, a retrospective analysis has been conducted on a nationwide collection of 2,956 M. tuberculosis clinical isolates screened with phenotypic drug susceptibility testing to define MDR-TB. Enrolled MDR-TB isolates were subjected to second-line drug susceptibility testing, detection of mutations conferring resistance to aminoglycosides and fluoroquinolone, followed by 24-loci mycobacterial interspersed repetitive unit-variable number of tandem repeat typing and spoligotyping. Overall, 83 isolates were identified as MDR-TB, and 13 (15.7%) isolates showed resistance to second-line drugs. Moxifloxacin (low level) showed higher resistant rates (10.8%) followed by ofloxacin (7.2%), capreomycin (3.6%), kanamycin (3.6%), and amikacin (2.4%). Overall fluoroquinolone resistance was 12%, whereas aminoglycoside resistance was 7.2%. Predominant mutations conferring resistance to fluoroquinolone were found in gyrA A90V and D94G, whereas aminoglycoside resistance was observed only with rrs gene A1401G mutation. The corresponding strain lineages predominated with Indo-Oceanic and East-African Indian origin. Interestingly, none of the isolates with second-line drug resistance was defined as extensively drug-resistant TB (XDR-TB). Surprisingly, many isolates (50.6%) were panresistant to first-line drugs. Saudi Arabia faces considerable burden of fluoroquinolone- and aminoglycoside-resistant MDR-TB. Higher incidence of panresistant MDR-TB reveals a threat for the emergence of XDR-TB strains in the near future.

MDR-TB treatment as prevention: The projected population-level impact of expanded treatment for multidrug-resistant tuberculosis.

BackgroundIn 2013, approximately 480,000 people developed active multidrug-resistant tuberculosis (MDR-TB), while only 97,000 started MDR-TB treatment. We sought to estimate the impact of improving access to MDR-TB diagnosis and treatment, under multiple diagnostic algorithm and treatment regimen scenarios, on ten-year projections of MDR-TB incidence and mortality.MethodsWe constructed a dynamic transmission model of an MDR-TB epidemic in an illustrative East/Southeast Asian setting. Using approximate Bayesian computation, we investigated a wide array of potential epidemic trajectories consistent with current notification data and known TB epidemiology.ResultsDespite an overall projected decline in TB incidence, data-consistent simulations suggested that MDR-TB incidence is likely to rise between 2015 and 2025 under continued 2013 treatment practices, although with considerable uncertainty (median 17% increase, 95% Uncertainty Range [UR] -38% to +137%). But if, by 2017, all identified active TB patients with previously-treated TB could be tested for drug susceptibility, and 85% of those with MDR-TB could initiate MDR-appropriate treatment, then MDR-TB incidence in 2025 could be reduced by 26% (95% UR 4–52%) relative to projections under continued current practice. Also expanding this drug-susceptibility testing and appropriate MDR-TB treatment to treatment-naïve as well as previously-treated TB cases, by 2020, could reduce MDR-TB incidence in 2025 by 29% (95% UR 6–55%) compared to continued current practice. If this diagnosis and treatment of all MDR-TB in known active TB cases by 2020 could be implemented via a novel second-line regimen with similar effectiveness and tolerability as current first-line therapy, a 54% (95% UR 20–74%) reduction in MDR-TB incidence compared to current-practice projections could be achieved by 2025.ConclusionsExpansion of diagnosis and treatment of MDR-TB, even using current sub-optimal second-line regimens, is expected to significantly decrease MDR-TB incidence at the population level. Focusing MDR diagnostic efforts on previously-treated cases is an efficient first-step approach.

Mutations in Streptomycin Resistance Genes and Their Relationship to Streptomycin Resistance and Lineage of Mycobacterium tuberculosis Thai Isolates.

BackgroundStreptomycin (SM) is recommended by the World Health Organization (WHO) as a part of standard regimens for retreating multidrug-resistant tuberculosis (MDR-TB) cases. The incidence of MDR-TB in retreatment cases was 19% in Thailand. To date, information on SM resistance (SMR) gene mutations correlated to the SMR of Mycobacterium tuberculosis Thai isolates is limited. In this study, the mutations in rpsL, rrs, gidB, and whiB7 were investigated and their association to SMR and the lineage of M. tuberculosis were explored.MethodsThe lineages of 287 M. tuberculosis collected from 2007 to 2011 were identified by spoligotyping. Drug susceptibility profiles were evaluated by the absolute concentration method. Mutations in SMR genes of 46 SM-resistant and 55 SM-susceptible isolates were examined by DNA sequencing.ResultsThree rpsL (Lys43Arg, Lys88Arg, and Lys88Thr) and two gidB (Trp45Ter and Gly69Asp) mutations were present exclusively in the SM resistant M. tuberculosis. Lys43Arg rpsL was the most predominant SMR mutations (69.6%) and prevailed among Beijing isolates (p<0.001). No SMR-related mutation in was found rrs. The combination of rpsL and gidB mutations provided 76.1% sensitivity for detecting SMR in M. tuberculosis Thai isolates. whiB7 was not responsible for SMR in SM resistant isolates lacking rpsL and rrs mutations. The significance of the three gidB mutations, 276A>C, 615A>G, and 330G>T, as lineage signatures for Beijing and EAI were underscored. This study identified 423G>A gidB as a novel sub-lineage marker for EAI6-BGD1.ConclusionOur study suggested that the majority of SMR in M. tuberculosis Thai isolates were responsible by rpsL and gidB polymorphisms constantly providing the novel lineage specific makers.

Emergence of drug resistance in patients with tuberculosis cared for by the Indian health-care system: a dynamic modelling study

India has the highest number of patients with tuberculosis and multidrug-resistant tuberculosis in the world. We used a transmission model to project the emergence of drug resistance in India due to incorrect tuberculosis management practices in multiple sectors, including public and private providers, chemists, and non-allopathic practitioners. We constructed a dynamic Markov model to represent India's tuberculosis epidemic, including a probabilistic framework reflecting complex treatment-seeking pathways. Underlying drug resistance and the acquisition of drug resistance during treatment were included. India-specific epidemiological data, including tuberculosis management practices, were obtained from published literature. Outcomes, which included annual risk of infection, incidence of new disease, prevalence of untreated tuberculosis, and tuberculosis-related mortality, were stratified by underlying drug resistance, as well as by health sector to understand how each sector contributes to the emergence of drug resistance. If tuberculosis management practices across sectors in India remain unchanged over the next 20 years, we estimated a 47% increase in the incidence of isoniazid resistance, a 152% increase in multidrug-resistant tuberculosis incidence, a 242% increase in prevalent untreated multidrug-resistant tuberculosis, and a 275% increase in the risk of multidrug-resistant tuberculosis infection. By 2032, an estimated 85% of multidrug-resistant tuberculosis will be primary multidrug-resistant tuberculosis compared with only 15% in 2012. The public sector contributed 87% of acquired multidrug-resistant tuberculosis, related to irregular adherence; the remainder came from the private sector, related to treatment non-completion. Chemists and non-allopathic practitioners do not treat with rifampicin, but because of the high rates of inappropriate isoniazid-containing regimens, and treatment non-adherence, this would generate isoniazid resistance. We predict a gradual transformation from the current epidemic of drug-susceptible tuberculosis to a drug-resistant epidemic. Evidence-based strategies to improve provider practices and patient adherence across health sectors are urgently needed to prevent this. United States Agency for International Development and the Canadian Institutes for Health Research.

Expected effects of adopting a 9 month regimen for multidrug-resistant tuberculosis: a population modelling analysis

SummaryBackgroundIn May, 2016, WHO endorsed a 9 month regimen for multidrug-resistant tuberculosis that is cheaper and potentially more effective than the conventional, longer (20–24 month) therapy. We aimed to investigate the population-level implications of scaling up this new regimen.MethodsIn this population modelling analysis, we developed a dynamic transmission model to simulate the introduction of this short-course regimen as an instantaneous switch in 2016. We projected the corresponding percentage reduction in the incidence of multidrug-resistant tuberculosis by 2024 compared with continued use of longer therapy. In the primary analysis in a representative southeast Asian setting, we assumed that the short-course regimen would double treatment access (through savings in resources or capacity) and achieve long-term efficacy at levels seen in preliminary cohort studies. We then did extensive sensitivity analyses to explore a range of alternative scenarios.FindingsUnder the optimistic assumptions in the primary analysis, the incidence of multidrug-resistant tuberculosis in 2024 would be 3·3 (95% uncertainty range 2·2–5·6) per 100 000 population with the short-course regimen and 4·3 (2·9–7·6) per 100 000 population with continued use of longer therapy—ie, the short-course regimen could reduce incidence by 23% (10–38). Incidence would be reduced by 14% (4–28) if the new regimen affected only treatment effectiveness and by 11% (3–24) if it affected only treatment availability. Under more pessimistic assumptions, the short-course regimen would have minimal effect and even potential for harm—eg, when 30% of patients are ineligible for the new regimen because of second-line drug resistance, we projected a change in incidence of −2% (−20 to +28). The new regimen's effect was greater in settings with more ongoing transmission of multidrug-resistant tuberculosis, but results were otherwise similar across settings with different levels of tuberculosis incidence and prevalence of multidrug resistance.InterpretationThe short-course regimen has potential to substantially lessen the multidrug-resistant tuberculosis epidemic, but this effect depends on its long-term efficacy, its ability to expand treatment access, and the role of second-line drug resistance.FundingUS National Institutes of Health and Bill & Melinda Gates Foundation.

Modelling the effect of short-course multidrug-resistant tuberculosis treatment in Karakalpakstan, Uzbekistan.

BackgroundMultidrug-resistant tuberculosis (MDR-TB) is a major threat to global TB control. MDR-TB treatment regimens typically have a high pill burden, last 20 months or more and often lead to unsatisfactory outcomes. A 9–11 month regimen with seven antibiotics has shown high success rates among selected MDR-TB patients in different settings and is conditionally recommended by the World Health Organization.MethodsWe construct a transmission-dynamic model of TB to estimate the likely impact of a shorter MDR-TB regimen when applied in a low HIV prevalence region of Uzbekistan (Karakalpakstan) with high rates of drug resistance, good access to diagnostics and a well-established community-based MDR-TB treatment programme providing treatment to around 400 patients. The model incorporates acquisition of additional drug resistance and incorrect regimen assignment. It is calibrated to local epidemiology and used to compare the impact of shorter treatment against four alternative programmatic interventions.ResultsBased on empirical outcomes among MDR-TB patients and assuming no improvement in treatment success rates, the shorter regimen reduced MDR-TB incidence from 15.2 to 9.7 cases per 100,000 population per year and MDR-TB mortality from 3.0 to 1.7 deaths per 100,000 per year, achieving comparable or greater gains than the alternative interventions. No significant increase in the burden of higher levels of resistance was predicted. Effects are probably conservative given that the regimen is likely to improve success rates.ConclusionsIn addition to benefits to individual patients, we find that shorter MDR-TB treatment regimens also have the potential to reduce transmission of resistant strains. These findings are in the epidemiological setting of treatment availability being an important bottleneck due to high numbers of patients being eligible for treatment, and may differ in other contexts. The high proportion of MDR-TB with additional antibiotic resistance simulated was not exacerbated by programmatic responses and greater gains may be possible in contexts where the regimen is more widely applicable.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-016-0723-2) contains supplementary material, which is available to authorized users.

Pediatric Extrapulmonary Tuberculosis: Clinical Spectrum, Risk Factors and Diagnostic Challenges in a Low Prevalence Region.

Children are at higher risk of tuberculosis (TB) dissemination and extrapulmonary disease, contributing greatly to TB-associated morbidity and long-term sequelae. However, there are very few studies that assess the impact and clinical spectrum of pediatric extrapulmonary TB (EPTB) in low-prevalence regions. Children <18 years of age diagnosed with TB in Madrid region (2005-2013) were reviewed. We compared the epidemiology, clinical characteristics and the performance of diagnostic tests in childhood extrapulmonary and pulmonary disease. We performed a multivariate logistic regression to identify factors associated with EPTB. During the study period, 93 of 526 pediatric TB cases had EPTB (17.7%). The most common site was lymphatic TB (34.5%). The source case was not identified in most extrapulmonary cases, contrary to pulmonary TB (28% vs. 63.3%; P < 0.001). The tuberculin-skin-test induration was smaller in EPTB cases (<5 mm 22% vs. 5%; P < 0.001), but the sensitivity of interferon-gamma-release-assays was similar (76.9% vs. 79.4%). Children with EPTB presented higher rate of bacteriologic confirmation (66% vs. 49.4%; P < 0.01), and higher incidence of multidrug resistant TB (8.2% vs. 1.6%; P = 0.03). Complications were present in 40.2% extrapulmonary cases. EPTB was associated with the child's foreign origin [odds ratio (OR) 2.3 (1.1-5.3)], immune disorders [OR 5.8 (1.9-17.1)] and drug resistance [OR 2.4 (1.1-5.4)]. In our low-prevalence region, childhood EPTB was linked to immigrant status, immune disorders and drug resistance, and presented high rate of complications. Our study underscores the relevance of improved diagnostic tools and systematic TB screening in high risk populations.

Influential Factors to Prolonged Tuberculosis Treatment Duration and Multidrug-resistant Tuberculosis Incidence

Objectives Tuberculosis (TB) is a very important infectious disease in Korea. Among OECD countries, Korea has been had the highest rate in TB incidence, prevalence and death. In this study, we analyzed influencing factors to prolonged TB treatment and multidrug-resistant TB (MDR-TB) incidence. Methods We collected 2007-2009 TB claim data in the National health insurance data. TB patients who diagnosed TB for the fist time in 2008 were selected. Variables like gender, age, grade of insurance premium, length of stay in inpatient service, number of visits in outpatient services, type of employment, and size of residential of the patients were included to analyse. The prolonged TB treatment duration was defined as more than 9 months for TB treatment. MDR-TB incidence was defined as U88.0 or U88.1 in KCD-5. Provit model was used to find influencing factors to prolonged TB treatment and MDR-TB incidence. And marginal effects were calculated to analyse the influencing intensity of variables. Results 42,347 patients diagnosed and treated TB in 2008. 14,317 patients (33.8%) took treatment more than 9 months. The risk of prolonged TB treatment duration were increased significantly in male (0.6%), young (<20, 14.7%) or old (≥75, 6.0%) age groups, and lower income groups (5.9-2.5%). The risk of MDR-TB incidence were increased in lower income groups. Conclusions Age and income level influenced th prolonged TB treatment and MDR-TB incidence risk. More effective TB managements have to be developed for young (<20) or old (≥75) age group, and low income groups. Key words: Tuberculosis (TB), Prolonged treatment, Multidrug-resistant tuberculosis (MDR-TB)

Audiological Evaluation of Patients Taking Kanamycin for Multidrug Resistant Tuberculosis.

The incidence of multidrug resistant tuberculosis is increasing in developing countries. Aminoglycosides are an integral part of second-line drugs, however ototoxicity is a major limitation for their use. This study aims to determine the extent of hearing loss in patients taking one of the commonly prescribed drugs for Multidrug resistant tuberculosis (MDR-TB), Kanamycin, at a Government Medical College, Patiala, Punjab, India, which is a 1200 bed tertiary care hospital. A total of 100 patients (68 males and 32 females) with confirmed diagnosis of MDR-TB were included in this study conducted between January 2012 and February 2014. Subjects were between 15 to 60 years of age, with a mean age of 37.46 ± 10.1. Pure tone audiometry (PTA) was performed before the start of the therapy, as a baseline, and was repeated after 1 week and 6 weeks of Kanamycin use to assess hearing loss as an effect of therapy. Of the 100 patients examined, ototoxicity was found in 18 subjects post therapy. Incidence of high frequency hearing loss was 2% at week 1, and 12% after 6 weeks of follow up. However, 4% of the cases developed flat loss at week 6. The hearing loss was bilateral in 13 patients and unilateral in 5 patients. Ototoxicity was more common in males (66.67%) compared to females (33.3%). Maximum cases were found in the age group of 36 to 45 years (36.8%), the majority being from a rural background (83.3%). The association with socioeconomic status (P=0.024) and co-morbid conditions like diabetes and hypertension (P=0.001) reached statistical significance. Lack of specific guidelines to monitor patients taking aminoglycosides makes ototoxicity a major adverse effect of their use in MDR-TB. More studies are mandated to study the risk factors associated with the development of ototoxicity and for the development of alternate drugs for the treatment of MDR-TB.

Prospective Study of Moxifloxacin prophylaxis in Patients Suffering with HIV Having Contact History of Multidrug Resistant Tuberculosis (MDR-TB)

Aim and Objectives: To find out the effectiveness of moxifloxacin prophylaxis in HIV patients having contact history of MDR-TB. Materials and Methods: This is an observational prospective cohort study of HIV patients divided in to two groups, moxifloxacin prophylaxis group and non-prophylaxis group. These groups are followed for four years from March 2012 to March 2016 to appraise the incidence of tuberculosis and mortality in these two cohorts. Results: The tuberculosis incidence in more in non-prophylaxis group when compared to prophylaxis group. Crude tuberculosis incidence is 275 per 1000 person/years in non-prophylaxis group when compared to 42 per 1000 person/years in prophylaxis group (p<0.005). Incidence of MDR-TB is more in non-prophylaxis group (26 vs 6; p=0.002) when compared to prophylaxis group. Crude mortality rate is more in non-prophylaxis group (774 vs 103; p=0.003) when compared to the other group which was further confirmed by Cox regression hazards model. Proportional hazards model in which moxifloxacin prophylaxis had a 60% decrease in mortality compared to non-prophylaxis (adjusted relative hazard). Conclusion: Prophylaxis with 6-months moxifloxacin is an effective alternative for HIV patients instead of isoniazid suspected to contact with multidrug resistant tuberculosis.

Meta-analysis on risk factors of multidrug resistant tuberculosis in China

To synthetically evaluate the risk factors of multidrug resistant tuberculosis (MDR-TB) in China. Chinese databases (CNKI, Wanfang, SinoMed and VIP) and English database (PubMed) were used to collect studies on risk factors for MDR-TB from 1990 to 2013. Meanwhile, relevant studies were manually retrieved. According to the inclusion and exclusion criteria, studies were screened, data were extracted and quality assessed. A Meta-analysis was performed by using Stata 11.0 software. Twenty five studies on the risk factors of MDR-TB were synthetically and quantitatively analyzed. The results of Meta-analysis showed that factors as: being Han ethnic group, history of tuberculosis treatment, pulmonary cavity, floating population, TB case contact history, regular medication, living in rural areas, and poor economy were associated with the incidence of MDR-TB, the pooled OR values were 3.12 (95%CI: 1.16-8.40) , 5.27 (95% CI:3.60-7.72) , 1.39 (95%CI:1.03-1.87) , 1.69 (95%CI: 1.07-2.68) , 4.34 (95%CI: 1.91-9.86) , 0.23 (95% CI: 0.16-0.35) , 1.86 (95% CI: 1.59-2.18) and 1.62 (95% CI: 1.34-1.96) , respectively. Factors as: being Han ethnic group, history of tuberculosis treatment, pulmonary cavity, floating population, TB case contact history, living in rural areas and poor economy were considered to be at risk of MDR-TB while regular medication might be a protective factor to MDR-TB.

Tuberculosis control in China: use of modelling to develop targets and policies.

It is unclear if current programmes in China can achieve the post-2015 global targets for tuberculosis – 50% reduction in incidence and a 75% reduction in mortality by 2025. Chinese policy-makers need to maintain the recent decline in the prevalence of tuberculosis, while revising control policies to cope with an epidemic of drug-resistant tuberculosis and the effects of ongoing health reform. Health reforms are expected to shift patients from tuberculosis dispensaries to designated hospitals. We developed a mathematical model of tuberculosis control in China to help set appropriate targets and prioritize interventions that might be implemented in the next 10 years. This model indicates that, even under the most optimistic scenario – improved treatment in tuberculosis dispensaries, introduction of a new effective regimen for the treatment of drug-susceptible tuberculosis and optimal care of cases of multidrug-resistant tuberculosis – the current global targets for tuberculosis are unlikely to be reached. However, reductions in the incidence of multidrug-resistant tuberculosis should be feasible. We conclude that a shift of patients from tuberculosis dispensaries to designated hospitals is likely to hamper efforts at tuberculosis control if cure rates in the designated hospitals cannot be maintained at a high level. Our results can inform the planning of tuberculosis control in China.

Treatment outcomes for HIV and MDR-TB co-infected adults and children: systematic review and meta-analysis.

The incidence of multidrug-resistant tuberculosis (MDR-TB) is increasing in high human immunodeficiency virus (HIV) prevalence settings, with high associated mortality. Treatment outcomes in HIV-co-infected adults and children are poorly documented. To systematically assess treatment outcomes among HIV-MDR-TB co-infected patients. We searched two databases and the proceedings of an annual international conference up to November 2014 for studies reporting on major clinical outcomes among HIV-MDR-TB-co-infected adults and children, and pooled the results using random-effects meta-analysis. Of 4812 abstracts and articles screened, 30 studies providing data on 2578 adults and 147 children were included. Overall pooled treatment success was 56.9% (95% confidence interval [CI] 46.2-67.6), 49.9% (95%CI 38.5-61.2) among adults and 83.4% (95%CI 74.7-92) among children. Mortality was 38% in adults (95%CI 28-48.1) and 11.4% (95%CI 5.8-17.1) in children. Loss to follow-up was higher among adults (16.1%, 95%CI 9-23.2) than among children (3.9%, 95%CI 0.9-6.9). Adverse events were experienced by the majority of patients; however, this was inconsistently documented. The use of fluoroquinolones, aminoglycosides and Group IV drugs appeared to be associated with treatment success. The proportion of HIV-MDR-TB-co-infected patients achieving treatment success was similar to success rates reported among MDR-TB patients in general, regardless of HIV status; however, mortality was higher, particularly among adults, highlighting the need for early diagnosis and more effective treatment regimens.

Mycobacterium Strain and Type of Resistance in Pulmonary Tuberculosis Patients: A Missed Link in Iran’s National Tuberculosis Plan

Background:: The Incidence of multi-drug resistant tuberculosis (MDR-TB) is constantly increasing. Objectives:: This study aimed to clarify an important missed link in Iran’s national TB plan. Patients and Methods:: Through a 9-month period, all pulmonary TB patients diagnosed based on the national TB protocol, in Shiraz TB center, were selected and culture of TB colonies, drug susceptibility testing (DST), polymerase chain reaction (PCR) for detection of IS6110 gene, Isoniazid (INH) and Rifampin (RIF) tuberculosis resistance were done to collect data. Data were analyzed using SPSS. Results:: In 92 included patients, (mean age 45.4 ± 15 years), DST results showed that 16 cases (17.4%) were resistant to INH, 19 (20.7 %) to RIF and 24 (26.1%) to both INH and RIF. Polymerase chain reaction identified IS6110 gene in 71 cases (77.2%) and gene mutations in 3 (3.2%) KatG, 3 (3. 2%) InhA, 9 (9.7%) both KatG and InhA, 17 (18.4%) rpoB and 20 (21.7%) in KatG, InhA and rpoB genes. Patients with INH-resistant tuberculosis were more than those with RIF-resistant (OR = 7.1). Conclusions:: Findings of the present study show that 4 out of five new cases of pulmonary TB patients who were diagnosed based on the national TB protocol (clinical symptoms and acid fast bacilli staining) had IS6110 gene (MTB, Mycobactrium TB) and at least one-fifth of this group had A kind of Drug Resistant TB. Therefore, by using PCR ,as a complementary test, it could be possible to start 1st line anti-TB drugs for only MTB cases (up to 77% of the patients) and 2nd line drugs for MDR cases (15% of cases). This policy aims to achieve safety and better outcome for patients while saving human and financial resources in health care system.

Fluoroquinolone Therapy for the Prevention of Multidrug-Resistant Tuberculosis in Contacts. A Cost-Effectiveness Analysis.

Fluoroquinolone (FQN) therapy of latent tuberculosis infection among contacts of individuals with multidrug-resistant tuberculosis (MDR-TB) is controversial. To determine the potential benefits, risks (including acquired FQN resistance), and cost-effectiveness of FQN therapy to prevent TB in contacts of individuals with MDR-TB. We used decision analysis to estimate costs and outcomes associated with no therapy compared with a 6-month course of daily FQN therapy to treat latent TB infection in contacts of individuals with MDR-TB. Outcomes modeled were the incidence of MDR-TB, MDR-TB with FQN resistance, TB-related death, quality-adjusted life years, and health system costs. FQN preventive therapy resulted in health system savings, lower incidence of MDR-TB, and lower mortality than no treatment. We found the incidence of MDR-TB with acquired FQN resistance would also be lower with FQN therapy of infected contacts. In our model, FQN preventive therapy resulted in substantial health system savings and in reduced mortality, incidence of MDR-TB, and incidence of acquired FQN-resistant disease as well as improved quality of life. FQN therapy remained cost saving with improved outcomes even if the effectiveness of therapy in preventing MDR-TB was as low as 10%.

TO STUDY INCIDENCE OF MULTI DRUG RESISTANT TUBERCULOSIS IN MUMBAI

Ionized and Rifampicin, the two most potent anti-tuberculosis drugs are rendered ineffective in Multidrug-resistant Tuberculosis (MDR-TB). India, China and Russia contribute to more than 62% of MDR-TB globally. In India, endemic areas like Mumbai are “hotspots” for the dissemination of MDR-TB. The aim of the study was to investigate the incidence of MDR-TB in cases of pulmonary tuberculosis in Mumbai. Total hundred and two clinical isolates of.Tuberculosiswas tested in the study. Drug susceptibility testing of these strains were carried by Resistance Ratio method to ant tuberculosis drugs namely Ionized, Streptomycin andEthambutol and by absolute concentration method for Rifampicinand Pyrazinamide. In our study highest resistance (46 %) was observed to INH followed by RF (42.16 %), SM (29.41 %) and EMB (25.49 %). While, resistance to Pyrazinamide (PZ) was least (7.8%). MDR TB cases were found to be 41.18%.There was significant difference between resistance pattern of INH and EMB, INH and SM, PZ and EMB, PZ and SM, EMB and RF, PZ and RF. (chi square with Yates correction =8.5, p<0.01).Detection of MDR TB strain would not only eliminate non-essential use of antibiotics, but would also help in the selection of most effective drug regimen and guide therapy in chronic cases. Article DOI: https://dx.doi.org/10.20319/lijshls.2015.s11.122138 This work is licensed under the Creative Commons Attribution-Non-commercial 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc/4.0/ or send a letter to Creative Commons, PO Box 1866, Mountain View, CA 94042, USA.

Proteins purified from Mycobacterium tuberculosis MDR and Susceptible clinical isolates: Identification by proteomics approach

Aims and objectivesTuberculosis (TB) remains a major global health problem. The incidence of multidrug-resistant tuberculosis (MDR-TB) has increased in recent years. To combat the disease, novel intervention strategies effective against drug-resistant and susceptible subpopulations of Mycobacterium tuberculosis are urgently required as adducts in present treatment regimen. This study has employed a proteomic approach, which is a direct method, to identify proteins from resistant M. tuberculosis isolates compared with sensitive isolates. MethodsThe clinical isolates M.tuberculosis strains were provided by the TB bank of Pasteur Institute of Iran. The bacilli were cultured on 7H9 broth with ADC enrichment at 37°C for 3–4weeks (late log phase). Cells were washed with PBS, suspended in sonication buffer (10mM DTT, 1μg/ml DNAse, 100mM Glycerol, 10mM Triton X100, 20mM EDTA, 50mM Tris-Hcl, 1mM PMSF, 0.02% sodium azide, pH 7.4) and then were subjected to sonication for 1h at 50Hz, in ice, and subsequently centrifuged at 5000rpm for 45min at −4°C. Proteins were precipitated by adding refrigerated ethanol or saturated ammonium sulfate to the supernatant. Pellet resuspended in PBS and then dialyzed for 24h against PBS pH 7.4. IEF was carried out using the Ettan IPGphor 3 isoelecteric focusing system. Immobilized pH gradient IPG strips of pH 4–7 and length 11cm were rehydrated overnight at 20°C with 500μg protein which was mixed with rehydration buffer. Proteins were separated in second dimension on 12% SDS-PAGE in a vertical electrophoretic dual gel. 2D gels were analyzed using Image Master, Melanie 7.0 software. Mass spectrometry was performed using Autoflex II TOF/TOF. Protein sequences were retrieved from Tuberculist server hosted by Pasteur Institute, Paris. ResultsMass spectrometry and bioinformatic characterization of both drug-resistant and sensitive isolates of M. tuberculosis showed that the majority of commonly expressed/upregulated proteins belonged to the cellular metabolism and respiration category (Rv0866, Rv3057c, Rv3248c, Rv1133c, Rv0462, and Rv1876). One hypothetical protein (Rv2744c) and two membrane and cell wall fraction proteins (Rv0379, Rv1886c) were identified. Protein spot 1 was 60kDa chaperonin-2/GroEl-2 (Rv0440). This essential gene prevents misfolding and promotes the refolding and proper assembly of unfolded/misfolded polypeptides generated under stress conditions. Further, another spot Rv2013c (HSP16.3/HSPX) has been shown to be induced under oxygen-deficient conditions. Its role in maintenance of long-term viability during latent, asymptomatic infections and in replication during initial infection has also been proposed. ConclusionSuch information could be helpful for the development of newer therapeutic agents or of diagnostic markers for better treatment or diagnosis of TB. This study extends the list of the potential determinants of differences in virulence between the two isolates (MDR and susceptible TB) and adds to the current understanding of MTB pathogenesis.

The importance of implementation strategy in scaling up Xpert MTB/RIF for diagnosis of tuberculosis in the Indian health-care system: a transmission model.

India has announced a goal of universal access to quality tuberculosis (TB) diagnosis and treatment. A number of novel diagnostics could help meet this important goal. The rollout of one such diagnostic, Xpert MTB/RIF (Xpert) is being considered, but if Xpert is used mainly for people with HIV or high risk of multidrug-resistant TB (MDR-TB) in the public sector, population-level impact may be limited. We developed a model of TB transmission, care-seeking behavior, and diagnostic/treatment practices in India and explored the impact of six different rollout strategies. Providing Xpert to 40% of public-sector patients with HIV or prior TB treatment (similar to current national strategy) reduced TB incidence by 0.2% (95% uncertainty range [UR]: -1.4%, 1.7%) and MDR-TB incidence by 2.4% (95% UR: -5.2%, 9.1%) relative to existing practice but required 2,500 additional MDR-TB treatments and 60 four-module GeneXpert systems at maximum capacity. Further including 20% of unselected symptomatic individuals in the public sector required 700 systems and reduced incidence by 2.1% (95% UR: 0.5%, 3.9%); a similar approach involving qualified private providers (providers who have received at least some training in allopathic or non-allopathic medicine) reduced incidence by 6.0% (95% UR: 3.9%, 7.9%) with similar resource outlay, but only if high treatment success was assured. Engaging 20% of all private-sector providers (qualified and informal [providers with no formal medical training]) had the greatest impact (14.1% reduction, 95% UR: 10.6%, 16.9%), but required >2,200 systems and reliable treatment referral. Improving referrals from informal providers for smear-based diagnosis in the public sector (without Xpert rollout) had substantially greater impact (6.3% reduction) than Xpert scale-up within the public sector. These findings are subject to substantial uncertainty regarding private-sector treatment patterns, patient care-seeking behavior, symptoms, and infectiousness over time; these uncertainties should be addressed by future research. The impact of new diagnostics for TB control in India depends on implementation within the complex, fragmented health-care system. Transformative strategies will require private/informal-sector engagement, adequate referral systems, improved treatment quality, and substantial resources. Please see later in the article for the Editors' Summary.